bluuebunny/crossref_metadata_2025 huggingface dataset:
Using System Reliability Concepts to Derive Partial Safety Factors for Punching Shear with Shear Reinforcement: An Explorative Analysis
Authors: Feiri Tânia , Schulze-Ardey Jan Philip , Ricker Marcus , Hegger Josef
Published: January 2023

Punching shear-reinforced flat slabs can fail in three modes: (1) inside the shear-reinforced zone, (2) outside the shear-reinforced zone, or (3) at the maximum punching shear capacity. By using the theory of structural systems reliability, this study investigates how these failure modes combined affect the safety level of reinforced concrete flat slabs with punching shear reinforcement, and ultimately, the variation of partial factors. Based on DIN EN 1992-1-1 together with the German National Annex DIN EN 1992-1-1+NA(D), and by using distinct reliability-based methods (i.e., levels II and III), the variation in the system failure probabilities and, consequently, partial factors were analysed. The results indicated that partial factors can fluctuate significantly depending on the governing ultimate limit state function and the scatter of basic variables. Furthermore, they indicated that the chosen reliability-based method had a significant influence on the resulting safety level. The sensitivity analysis confirmed the premise that partial factors can be reduced without compromising socially accepted safety levels (e.g., recommended in DIN EN 1990). Ultimate benefits include material and cost savings and CO2 emission reductions. Finally, the approach addressed in this paper offers a new perspective on the derivation of partial factors that can be considered by engineering practitioners.
Critical State and the Loosest Jammed State of Granular Materials
Authors: He Xuzhen
Published: January 2023

Solid-state (i.e., jammed) granular soils can be prepared into different densities characterised by the mean pressure p and the solid fraction ϕ (i.e., different p-ϕ combinations). The limits for jammed states (i.e., the range of possible p-ϕ) are studied theoretically in the literature or through isotropic compression simulations with the discrete element method (DEM). Shearing also causes unjamming and the critical state is an important reference state for shear deformation. How the jamming limits from isotropic compression tests are related to the critical state is examined in this paper by DEM simulations. Two methods are used to generate isotropic samples. One is the isotropic compression method, which is mainly used for studying jamming in the literature. Possible jammed states from this method lie between two compression lines. The varying-friction methods can generate samples with a larger range of p-ϕ. Isochoric shear tests are conducted on isotropic specimens prepared with both methods. Some specimens reach liquefaction (p′≈ 0) and the others reach the critical state. The obtained critical state p-ϕ line is found to be the same as the loosest jammed state line from the isotropic compression method. Additionally, the critical state stress state is also well described by a Coulomb-type equation in the octahedral profile.
Algorithm for Cycle-To-Cycle Firing TDC Identification Based on Wasted Spark Duration Measurements in Small Engines
Authors: Irimescu Adrian , Merola Simona Silvia , Vaglieco Bianca Maria
Published: January 2023

Spark ignition (SI) engines are often used as distributed power generation applications. They ensure quick deployment, cost effective electricity, and are a valid choice for back-up power. An essential aspect for small size engines is to improve control margins without increasing the number of sensors. It is not uncommon to employ fixed ignition timing for such power units, with so called wasted spark systems. These feature two spark events per cycle, one during compression and one during the exhaust stroke. On the other hand, ever more complex control systems are applied for this engine category in the search for better efficiency and lower emissions. Control of actuators that is phased with the working cycle could represent a significant advantage in this context. A method previously developed for identifying top dead center (TDC) phasing offline was applied as an algorithm capable of performing the required task while the engine is running. It is based on current measurements in the secondary ignition circuit of systems that feature wasted spark operation. Validation was performed on a 50 cm3 SI unit connected to a 1 kW power generator. Statistical distribution during sequences of 1000 cycles recorded at five different levels of load was used for testing TDC identification capabilities. Results were also compared to evaluations based on engine speed measurements. The overall TDC identification success rate of the proposed algorithm was found to be over 99.8%.
Real-Time Eye Diagram Monitoring for Optical Signals Based on Optical Sampling
Authors: Huang Tao , Fan Zhiqiang , Su Jun , Qiu Qi
Published: January 2023

A real-time eye diagram monitoring method for optical signals is proposed and experimentally demonstrated based on optical sampling. In the system, the optical signals under test are directly sampled by an optical sampling pulse train with a narrow pulse width and a high repetition frequency. The sampling pulse train is achieved in a Mach-Zehnder modulator (MZM), gated on-off by an electrical pulse. The sampled optical signals are then broadened and detected by a photodetector (PD). A low-speed electrical analog-to-digital converter (ADC) will then quantify the detected electrical signals. Combining with an algorithm based on the infinitesimal calculus, the quantified data is then used to achieve the eye diagram, according to which more time-domain parameters, such as period, time jitter, Q value, and bit error rate (BER) for the optical signals under test, are obtained. Thanks to the high repetition rate of the optical sampling pulse train, the eye diagram and the time-domain parameters of the optical signals are observed in real time. Experimental results show that a real time of about 350-μs eye diagram monitoring for a 2.5-Gb/s optical signal with a dynamic range from −10 to −22 dBm is achieved. In addition, time jitters are measured to range from 4.3 to 49.8 ps. Q values are estimated to range from 20.4 to 4.3, corresponding to BERs ranging from 2.3 × 10−92 to 8.5 × 10−6. The results are also verified by a commercial real-time oscilloscope.
Handball Offensive Analysis: Comparative Evolution of Linear Tendency Lines between Finalist Teams in the EHF CL
Authors: Vaz Vasco , Ferrari Willian , Sarmento Hugo , Couceiro Micael , Sousa Tiago , Dias Gonçalo
Published: January 2023

(1) Background: This study aims to analyze the evolution of the finalist teams in five years of the EHF Champions League and compare winning teams with defeated teams, presenting their evolution along the competition from the quarterfinals to the final; (2) Methods: A total of 35 games were analyzed, corresponding to four games per team over five seasons. Tendency lines were created according to the 13 offensive indicators of winning teams, divided into three macro categories: game actions, goals, and effectiveness of shots; (3) Results: The results indicated 21 linear tendency lines valid for the study. Winning teams presented five increasing lines (ascending line) and 16 decreasing lines (negative slope) during the competition. Assists, goals from the 6 m, and effectiveness at 6 m shots presented an increasing tendency line for winning teams, and the effectiveness of shots, the effectiveness of the organized attack, and the effectiveness of shots from 9–6 m presented a decreasing tendency line; (4) Conclusions: winning teams have more constancy during the competition. Due to the expected increased difficulty in successive matches, tendency lines tend to present decreasing slopes as teams advance toward the final. Nevertheless, winning teams need to adapt to the increasing challenge, describing growth in some key indicators, and being more regular than other teams.
A Novel Multi-Factor Authentication Algorithm Based on Image Recognition and User Established Relations
Authors: Carrillo-Torres Diego , Pérez-Díaz Jesús Arturo , Cantoral-Ceballos Jose Antonio , Vargas-Rosales Cesar
Published: January 2023

Conventional authentication methods, like simple text-based passwords, have shown vulnerabilities to different types of security attacks. Indeed, 61% of all breaches involve credentials, whether stolen via social engineering or hacked using brute force. Therefore, a robust user authentication mechanism is crucial to have secure systems. Combining textual passwords with graphical passwords in a multi-factor approach can be an effective strategy. Advanced authentication systems, such as biometrics, are secure, but require additional infrastructure for efficient implementation. This paper proposes a Multi-Factor Authentication (MFA) based on a non-biometric mechanism that does not require additional hardware. The novelty of the proposed mechanism lies in a two-factor authentication algorithm which requires a user to identify specific images out of a set of randomly selected images, then the user is required to establish a self-pre-configured relation between two given images to complete authentication. A functional prototype of the proposed system was developed and deployed. The proposed system was tested by users of different backgrounds achieving 100% accuracy in identifying and authenticating users, if authentication elements and credentials were not forgotten. It was also found to be accepted by the users as being easy to use and preferable over common MFA mechanisms.
Reduction in Ground Times in Passenger Air Transport: A First Approach to Evaluate Mechanisms and Challenges
Authors: Hutter Florina G. , Pfennig Anja
Published: January 2023

Rising air travel demand, airport capacity issues, and schedule disruptions form part of the challenges that aviation stakeholders have to face in the upcoming decades. Minimizing ground times is one of their recent objectives as extended ground times induce operational, economic, and environmental risks. The flow of ground operations has a high impact on the overall air transportation system. Therefore, the impact and risks of extended ground times in passenger air transport were thoroughly compared, weighed, and compared based on pre-selected individual literature sources. Several studies deliver solution approaches to reduce ground times. The turnaround especially is a key element of any flight operation and impacts the competitive advantage of airlines and airports. Next to infrastructural changes, technological advancements, and operational performance improvements, the cooperation of stakeholders is a measure to shorten ground times. Special focus lies on the improvement of boarding procedures. They are essential for passenger air transport and reducing ground times.
Field Inspection of High-Density Polyethylene (HDPE) Storage Tanks Using Infrared Thermography and Ultrasonic Methods
Authors: Behravan Amir , Tran Thien Q. , Li Yuhao , Davis Mitchell , Shaikh Mohammad Shadab , DeJong Matthew M. , Hernandez Alan , Brand Alexander S.
Published: January 2023

High-density polyethylene (HDPE) is widely used for above-ground storage tanks (ASTs). However, there are currently no guidelines for the non-destructive testing (NDT) and evaluation (NDE) of HDPE ASTs. Moreover, the feasibility, limitations, and challenges of using NDT techniques for the field inspection of HDPE ASTs have not been well established. This study used both infrared thermography (IRT) and ultrasonic testing (UT) for the field inspection of HDPE ASTs. Highlighting the implementation challenges in the field, this study determined that: (1) ambient environmental parameters can affect IRT accuracy; (2) there is an ideal time during the day to perform IRT; (3) the heating source and infrared camera orientation can affect IRT accuracy; and (4) with proper measures taken, IRT is a promising method for flaw detection in HDPE ASTs. Additionally, UT can be used following IRT for detailed investigation to quantify the size and depth of defects. The manuscript concludes with a discussion of the limitations and best practices for the implementing of IRT and UT for HDPE AST inspections in the field.
Crime as Pop: Gangsta Rap as Popular Staging of Norm Violations
Authors: Dollinger Bernd , Rieger Julia
Published: January 2023

Crime is quantified extensively, mostly in order to prevent it, therefore assuming it as something purely negative. With the concept “Crime as Pop” we argue that such a view is one-sided, since crime is often staged as something that can be attractive and that can be used constructively for different purposes. We investigate this perspective by studying gangsta rap, which we consider a pop-cultural phenomenon that young people relate to in the context of interactive practices of identity construction. The stories told in gangsta rap are used by the youth recipients in a situation- and location-specific manner to present themselves in a certain way. Young people reproduce motifs of success that often characterize gangsta rap. They portray themselves as agentive and stage forms of resistance against people and institutions to which they might otherwise appear passive and powerless. Young people’s engagement with gangsta rap thus shows how the pop-cultural phenomena can be appropriated in many different ways. “Crime as Pop” illustrates the contingent connections of cultural phenomena and their appropriation that require detailed empirical reconstruction.
First Detection of Global Ionospheric Disturbances Associated with the Most Powerful Gamma Ray Burst GRB221009A
Authors: Pal Sujay , Hobara Yasuhide , Shvets Alexander , Schnoor Peter Wilhelm , Hayakawa Masashi , Koloskov Oleksandr
Published: January 2023

We present the first report of global ionospheric disturbances due to the most powerful Gamma Ray Burst GRB221009A occurred on 9 October 2022. Very Low Frequency (VLF) and Low Frequency (LF) sub-ionospheric radio signals are used to diagnose the effect of the GRB on the lower ionosphere. Both daytime and nighttime effects are analyzed in VLF and LF bands. The magnitude of VLF signal perturbations varied with the propagation condition (day/night), path length, and frequency of the signal. The recovery times for the VLF/LF signals to get back to their pre-GRB levels varied from 2–60 min. Radio signals reflected from the E-region ionosphere for nighttime VLF signals and daytime LF signals showed greater effects compared to the daytime VLF signals reflected from the lower parts of the D-region.
Binary Encounter Electrons in Fast Dressed-Ion–H2 Collisions: Distorted Wave Theories and Experiment
Authors: Esponda Nicolás J. , Nanos Stefanos , Quinto Michele A. , Zouros Theo J. M. , Rivarola Roberto D. , Benis Emmanouil P. , Monti Juan M.
Published: January 2023

We report measurements of double differential cross section for zero-degree binary encounter electrons emitted in collisions of 4.9 MeV and 13 MeV B(2−5)+ ions with H2 targets. The corresponding calculations based on continuum distorted-wave (CDW) theories are critically compared to the measurements. CDW in its post form exhibits a very good agreement with the measurements in all cases. The CDW theories utilized along with the well-known eikonal-initial-state (CDW-EIS) approximation are also examined and their results are compared to both the measurements and the CDW calculations. In particular, CDW-EIS using a recently proposed dynamic effective charge for the final channel projectile distortion exhibits a substantial improvement in comparison with an effective net-charge approximation.
Rapid Morphological Measurement Method of Aortic Dissection Stent Based on Spatial Observation Point Set
Authors: Bai Mateng , Li Da , Xu Kaiyao , Ouyang Shuyu , Yuan Ding , Zheng Tinghui
Published: January 2023

Objectives: Post-operative stent morphology of aortic dissection patients is important for performing clinical diagnosis and prognostic assessment. However, stent morphologies still need to be manually measured, which is a process prone to errors, high time consumption and difficulty in exploiting inter-data associations. Herein, we propose a method based on the stepwise combination of basic, non-divisible data sets to quickly obtain morphological parameters with high accuracy. Methods: We performed the 3D reconstruction of 109 post-operative follow-up CT image data from 26 patients using mimics software. By extracting the spatial locations of the basic morphological observation points on the stent, we defined a basic and non-reducible set of observation points. Further, we implemented a fully automatic stent segmentation and an observation point extraction algorithm. We analyzed the stability and accuracy of the algorithms on a test set containing 8 cases and 408 points. Based on this dataset, we calculated three morphological parameters of different complexity for the different spatial structural features exhibited by the stent. Finally, we compared the two measurement schemes in four aspects: data variability, data stability, statistical process complexity and algorithmic error. Results: The statistical results of the two methods on two low-complexity morphological parameters (spatial position of stent end and vascular stent end-slip volume) show good agreement (n = 26, P1, P2 < 0.001, r1 = 0.992, r2 = 0.988). The statistics of the proposed method for the morphological parameters of medium complexity (proximal support ring feature diameter and distal support ring feature diameter) avoid the errors caused by manual extraction, and the magnitude of this correction to the traditional method does not exceed 4 mm with an average correction of 1.38 mm. Meanwhile, our proposed automatic observation point extraction method has only 2.2% error rate on the test set, and the average spatial distance from the manually marked observation points is 0.73 mm. Thus, the proposed method is able to rapidly and accurately measure the stent circumferential deflection angle, which is highly complex and cannot be measured using traditional methods. Conclusions: The proposed method can significantly reduce the statistical observation time and information processing cost compared to the traditional morphological observation methods. Moreover, when new morphological parameters are required, one can quickly and accurately obtain the target parameters by new “combinatorial functions.” Iterative modification of the data set itself is avoided.
Fast Blue and Cholera Toxin-B Survival Guide for Alpha-Motoneurons Labeling: Less Is Better in Young B6SJL Mice, but More Is Better in Aged C57Bl/J Mice
Authors: Farid Hasan , Gelford Weston , Goss Lori , Garrett Teresa , Elbasiouny Sherif
Published: January 2023

Fast Blue (FB) and Cholera Toxin-B (CTB) are two retrograde tracers extensively used to label alpha-motoneurons (α-MNs). The overall goals of the present study were to (1) assess the effectiveness of different FB and CTB protocols in labeling α-MNs, (2) compare the labeling quality of these tracers at standard concentrations reported in the literature (FB 2% and CTB 0.1%) versus lower concentrations to overcome tracer leakage, and (3) determine an optimal protocol for labeling α-MNs in young B6SJL and aged C57Bl/J mice (when axonal transport is disrupted by aging). Hindlimb muscles of young B6SJL and aged C57Bl/J mice were intramuscularly injected with different FB or CTB concentrations and then euthanized at either 3 or 5 days after injection. Measurements were performed to assess labeling quality via seven different parameters. Our results show that tracer protocols of lower concentration and shorter labeling durations were generally better in labeling young α-MNs, whereas tracer protocols of higher tracer concentration and longer labeling durations were generally better in labeling aged α-MNs. A 0.2%, 3-day FB protocol provided optimal labeling of young α-MNs without tracer leakage, whereas a 2%, 5-day FB protocol or 0.1% CTB protocol provided optimal labeling of aged α-MNs. These results inform future studies on the selection of optimal FB and CTB protocols for α-MNs labeling in normal, aging, and neurodegenerative disease conditions.
Design of an Automatically Controlled Multi-Axis Stretching Device for Mechanical Evaluations of the Anterior Eye Segment
Authors: Wang Kehao , Qiu Ziyan , Xie Yiping , Cai Shuo , Zhao Yang , Pierscionek Barbara K. , Guo Jiangzhen , Fan Yubo
Published: January 2023

The young eye has an accommodative ability involving lens shape changes to focus over different distances. This function gradually decreases with age, resulting in presbyopia. Greater insights into the mechanical properties of anterior eye structures can improve understanding of the causes of presbyopia. The present study aims to develop a multi-axis stretching device for evaluating the mechanical properties of the intact eye lens. A stretching device integrating the mechanical stretcher, motor, torque sensor and data transmission mechanism was designed and developed by 3D printing. The mechanical stretcher can convert rotation into radial movement, both at constant speeds, according to the spiral of Archimedes. The loading unit equipped with eight jaws can hold the eye sample tightly. The developed device was validated with a spring of known constant and was further tested with anterior porcine eye segments. The validation experiment using the spring resulted in stiffness values close to the theoretical spring constant. Findings from measurements with porcine eye samples indicated that the measured forces are within the ranges reported in the literature. The developed multi-axis stretching device has good repeatability during experiments with similar settings and can be reliably used for mechanical evaluations of the intact eye lens.
Nutraceuticals as Supportive Therapeutic Agents in Diabetes and Pancreatic Ductal Adenocarcinoma: A Systematic Review
Authors: Mikolaskova Iveta , Crnogorac-Jurcevic Tatjana , Smolkova Bozena , Hunakova Luba
Published: January 2023

The correlation between pancreatic ductal adenocarcinoma (PDAC) and diabetes-related mechanisms support the hypothesis that early therapeutic strategies targeting diabetes can contribute to PDAC risk reduction and treatment improvement. A systematic review was conducted, using PubMed, Embase and Cochrane Library databases, to evaluate the current evidence from clinical studies qualitatively examining the efficacy of four natural products: Curcumin—Curcuma longa L.; Thymoquinone—Nigella sativa L.; Genistein—Glycine max L.; Ginkgo biloba L.; and a low-carbohydrate ketogenic diet in type 2 diabetes (T2D) and PDAC treatment. A total of 28 clinical studies were included, showing strong evidence of inter-study heterogeneity. Used as a monotherapy or in combination with chemo-radiotherapy, the studied substances did not significantly improve the treatment response of PDAC patients. However, pronounced therapeutic efficacy was confirmed in T2D. The natural products and low-carbohydrate ketogenic diet, combined with the standard drugs, have the potential to improve T2D treatment and thus potentially reduce the risk of cancer development and improve multiple biological parameters in PDAC patients.
The Ratio of von Willebrand Factor Antigen to ADAMTS13 Activity: Usefulness as a Prognostic Biomarker in Acute-on-Chronic Liver Failure
Authors: Takaya Hiroaki , Namisaki Tadashi , Enomoto Masahide , Kubo Takahiro , Tsuji Yuki , Fujinaga Yukihisa , Nishimura Norihisa , Kaji Kosuke , Kawaratani Hideto , Moriya Kei , Akahane Takemi , Matsumoto Masanori , Yoshiji Hitoshi
Published: January 2023

Acute-on-chronic liver failure (ACLF) has a high risk of short-term mortality. A disintegrin-like and metalloproteinase with thrombospondin type-1 motifs 13 (ADAMTS13) is a metalloproteinase that specifically cleaves multimeric von Willebrand factor (VWF). Imbalance between ADAMTS13 and VWF is associated with portal hypertension, which induces ACLF development. A previous study reported that ADAMTS13 activity (ADAMTS13:AC) and VWF antigen (VWF:Ag) are predictive biomarkers of ACLF development in patients with cirrhosis. This study investigated the changes in ADAMTS13:AC and VWF:Ag levels from before to after the development of ACLF to determine their usefulness as a prognostic biomarker in patients with ACLF. In total, 101 patients with cirrhosis were enrolled in this study. The level of ADAMTS13:AC and VWF:Ag was determined by an enzyme-linked immunosorbent assay. Cox proportional hazard regression analysis was conducted to determine independent prognostic factors for patients with liver cirrhosis in the post-ACLF group. ADAMTS13:AC levels gradually decreased in the order of non-ACLF group, pre-ACLF group, and finally post-ACLF group. VWF:Ag and the ratio of VWF:Ag to ADAMTS13:AC (VWF:Ag/ADAMTS13:AC) levels gradually increased in the order of non-ACLF group, pre-ACLF group, followed by post-ACLF group. VWF:Ag/ADAMTS13:AC and CLIF-C ACLF scores were associated with prognosis in the post-ACLF group in multivariate analysis. The cumulative survival of the post-ACLF group was significantly lower for patients with high VWF:Ag/ADAMTS13:AC (>9) compared with those with low VWF:Ag/ADAMTS13:AC (≤9) (HR: 10.72, 95% confidence interval: 1.39–82.78, p < 0.05). The VWF:Ag/ADAMTS13:AC increased according to the progression of ACLF in patients with cirrhosis and predicted prognosis in patients with cirrhosis with ACLF.
Extremely Rare Pulmonary Metastases of Skin Basal Cell Carcinoma: Report of Two Cases with Clinicopathological Features
Authors: Wojtyś Małgorzata Edyta , Kiełbowski Kajetan , Kunc Michał , Skrzyniarz Seweryn Adam , Lisowski Piotr , Becht Rafał , Żukowska Paulina , Ptaszyński Konrad , Wójcik Janusz
Published: January 2023

Basal cell carcinoma (BCC) is the most frequent human skin cancer, but metastasizing BCC (MBCC) is extremely rare, developing in approximately 0.0028% to 0.55% of BCC patients. Herein, we report two cases of pulmonary MBCC. The first one developed in a 72-year-old male who underwent surgical resection due to multiple recurrences and adjuvant radiotherapy. Immunohistochemistry showed that neoplastic cells expressed Ber-EP4, CK5/6, p63, EMA (focally), BCL-2, and CD10, but were negative for CK7, CK20, S100, estrogen and progesterone receptors, and TTF-1. The second case is a 64-year-old female treated with vismodegib. Clinicopathological features and differential diagnoses are described.
Biological Calorimetry: Old Friend, New Insights
Authors: Abian Olga , Vega Sonia , Velazquez-Campoy Adrian
Published: January 2023

Calorimetry is an old experimental technique (first instrument developed in S. XVIII), but it is broadly used and still provides key information for understanding biological processes at the molecular level, particularly, cooperative phenomena in protein interactions. Here, we review and highlight some key aspects of biological calorimetry. Several biological systems will be described in which calorimetry was instrumental for modeling the behavior of the protein and obtaining further biological insight.
Conjugated Aggregation-Induced Fluorescent Materials for Biofluorescent Probes: A Review
Authors: Wang Zheng , Ma Ji , Li Changlin , Zhang Haichang
Published: January 2023

The common fluorescent conjugated materials present weak or quenching luminescent phenomena in the solid or aggregate state (ACQ), which limits their applications in medicine and biology. In the last two decades, certain materials, named aggregation-induced emission (AIE) fluorescent materials, have exhibited strong luminescent properties in the aggregate state, which can overcome the ACQ phenomenon. Due to their intrinsic properties, the AIE materials have been successfully used in biolabeling, where they can not only detect the species of ions and their concentrations in organisms, but can also monitor the organisms’ physiological activity. In addition, these kinds of materials often present non-biological toxicity. Thus, AIE materials have become some of the most popular biofluorescent probe materials and are attracting more and more attention. This field is still in its early infancy, and several open challenges urgently need to be addressed, such as the materials’ biocompatibility, metabolism, and so on. Designing a high-performance AIE material for biofluorescent probes is still challenging. In this review, based on the molecular design concept, various AIE materials with functional groups in the biofluorescent probes are introduced, including tetrastyrene materials, distilbene anthracene materials, triphenylamine materials, and hexaphenylsilole materials. In addition, according to the molecular system design strategy, the donor–acceptor (D-A) system and hydrogen-bonding AIE materials used as biofluorescent probes are reviewed. Finally, the biofluorescent probe design concept and potential evolution trends are discussed. The final goal is to outline a theoretical scaffold for the design of high-performance AIE biofluorescent probes that can at the same time further the development of the applications of AIE-based biofluorescent probes.
Enzyme-Assisted Nucleic Acid Amplification in Molecular Diagnosis: A Review
Authors: Wang Meiling , Liu Hongna , Ren Jie , Huang Yunqi , Deng Yan , Liu Yuan , Chen Zhu , Chow Franklin Wang-Ngai , Leung Polly Hang-Mei , Li Song
Published: January 2023

Infectious diseases and tumors have become the biggest medical challenges in the 21st century. They are driven by multiple factors such as population growth, aging, climate change, genetic predispositions and more. Nucleic acid amplification technologies (NAATs) are used for rapid and accurate diagnostic testing, providing critical information in order to facilitate better follow-up treatment and prognosis. NAATs are widely used due their high sensitivity, specificity, rapid amplification and detection. It should be noted that different NAATs can be selected according to different environments and research fields; for example, isothermal amplification with a simple operation can be preferred in developing countries or resource-poor areas. In the field of translational medicine, CRISPR has shown great prospects. The core component of NAAT lies in the activity of different enzymes. As the most critical material of nucleic acid amplification, the key role of the enzyme is self-evident, playing the upmost important role in molecular diagnosis. In this review, several common enzymes used in NAATs are compared and described in detail. Furthermore, we summarize both the advances and common issues of NAATs in clinical application.
Improved Tool for Predicting Skin Irritation on Reconstructed Human Epidermis Models Based on Electrochemical Impedance Spectroscopy
Authors: Chacón Manuel , Vázquez Natalia , Alonso-Alonso Sergio , Persinal-Medina Mairobi , Llames Sara , Pevida Marta , Alcalde Ignacio , Merayo-Lloves Jesús , Meana Álvaro
Published: January 2023

The rabbit skin irritation test has been the standard for evaluating the irritation potential of chemicals; however, alternative methods that do not use animal testing are actively encouraged. Reconstructed human epidermis (RhE) models mimic the biochemical and physiological properties of the human epidermis and can be used as an alternative method. On RhE methods, the metabolic activity of RhE models is used to predict skin irritation, with a reduction in metabolic activity indicating a reduced number of viable cells and linking cell death to skin irritation processes. However, new challenges have emerged as the use of RhE models increases, including the need for non-invasive and marker-free methodologies to assess cellular states. Electrochemical impedance spectroscopy (EIS) is one such methodology that can meet these requirements. In this study, our results showed that EIS can differentiate between irritant and non-irritant chemicals, with a significant increase in the capacitance values observed in the irritant samples. A ROC curve analysis showed that the prediction method based on EIS met OECD TG 439 requirements at all time points and had 95% within-laboratory reproducibility. Comparison with the MTT viability assay showed that prediction using EIS achieved higher sensitivity, specificity, and accuracy. These results suggest that EIS could potentially replace animal testing in the evaluation of irritation potential and could be a valuable addition to in vitro testing strategies.
A Schematic Colorimetric Assay for Sialic Acid Assay Based on PEG-Mediated Interparticle Crosslinking Aggregation of Gold Nanoparticles
Authors: Tang Shixing , Li Lin , Wang Rui , Regmi Sagar , Zhang Xinyu , Yang Guoqiang , Ju Jian
Published: January 2023

Sialic acid (SA) is a well-known component of glycoproteins, which have applications in various functional processes on the cell’s surface. The colorimetric is a simpler and more convenient method for measuring SA due to its low-cost apparatus and visual signal changes. This work focused on the unpredictable interparticle crosslinking aggregation of the functionalized gold nanoparticles (AuNPs) in complex media. We proposed a balance of the Derjaguin–Landau–Verwey–Overbeek (DLVO)-type aggregation and molecule-based interaction method to solve this problem. Here, we report a novel colorimetric assay for the determination of SA using 4-mercaptophenyl boronic acid (4-MPBA) as an analyte’s recognition molecule, and negative charge PEG400 was used to repulsive the interparticle crosslinking. The proposed sensing platform shows a linear relationship between the ratio of the absorbance intensity (A525/A660) and concentration of SA from 0.05 to 8 mM (R2 = 0.997) and a detection limit of 48 μM was observed. The novel gold-based colorimetric sensor is easy to fabricate, reproducible in its test performance and has been successfully applied for the detection of SA in biological and healthcare product samples.
Point-of-Care Diagnostic Biosensors to Monitor Anti-SARS-CoV-2 Neutralizing IgG/sIgA Antibodies and Antioxidant Activity in Saliva
Authors: Tamiya Eiichi , Osaki Shuto , Tsuchihashi Tomoko , Ushijima Hiromi , Tsukinoki Keiichi
Published: January 2023

Monitoring biomarkers is a great way to assess daily physical condition, and using saliva instead of blood samples is more advantageous as the process is simple and allows individuals to test themselves. In the present study, we analyzed the titers of neutralizing antibodies, IgG and secretory IgA (sIgA), in response to the SARS-CoV-2 vaccine, in saliva. A total of 19 saliva and serum samples were collected over a 10-month period 3 weeks after the first vaccine, 8 months after the second vaccine, and 1 month after the third vaccine. The ranges of antibody concentrations post-vaccination were: serum IgG: 81–15,000 U/mL, salivary IgG: 3.4–330 U/mL, and salivary IgA: 58–870 ng/mL. A sharp increase in salivary IgG levels was observed after the second vaccination. sIgA levels also showed an increasing trend. A correlation with trends in serum IgG levels was observed, indicating the possibility of using saliva to routinely assess vaccine efficacy. The electrochemical immunosensor assay developed in this study based on the gold-linked electrochemical immunoassay, and the antioxidant activity measurement based on luminol electrochemiluminescence (ECL), can be performed using portable devices, which would prove useful for individual-based diagnosis using saliva samples.
Hotel Employees’ Burnout and Intention to Quit: The Role of Psychological Distress and Financial Well-Being in a Moderation Mediation Model
Authors: Baquero Asier
Published: January 2023

Continuous changes, such as pandemics and increasing competition, as well as high workload, affect the workplace behavior of hotel organizations today, resulting in employee burnout and intention to quit. The purpose of this research was to investigate the effect of burnout on intention to quit among male hotel employees, integrating the mediating effect of psychological distress and moderating effect of financial well-being. Male employees in four- and five-star hotels in the UAE completed a total of 304 questionnaires. All direct relationships were positive and statistically significant, there was a partial mediating relationship, and only one of the moderating effects was statistically significant. This study found that burnout predicts the intention to quit as well as psychological distress. Psychological distress partially mediates the relationship between burnout and the intention to quit. Financial well-being moderates the relationship between burnout and psychological distress—making this relationship stronger for employees with high-income prospects—but not the relationship between burnout and intention to quit; regardless of the financial well-being of the employee, burnout will lead to the intention to quit their job. Hotel organizations must be aware of the consequences of employee burnout and concentrate on identifying and treating its causes.
Risk Factors in Specialists and Generalists of Child-to-Parent Violence: Gender Differences and Predictors of Reactive and Proactive Reasons
Authors: Navas-Martínez María J. , Cano-Lozano M. Carmen
Published: January 2023

Recent research on child-to-parent violence (CPV) is advancing in the analysis of the specialist profile (aggressors who show only CPV) and the generalist profile (aggressors who show peer violence in addition to CPV). However, although differences have been found between girls and boys in the risk factors for CPV, there are no studies that analyze these differences according to the type of aggressor. Likewise, the importance of identifying the factors that differentially predict reactive and proactive CPV has been noted but has not been examined in different types of aggressors. The aims of this study were to examine gender differences in CPV patterns, emotional intelligence, parental victimization, and parental permissiveness and to analyze whether these variables predict reactive and proactive CPV, both according to aggressor type. A total of 1559 Spanish CPV aggressors (54.6% females) aged between 12 and 18 years from educational centers participated in the study (22.4% exercised only CPV (specialists) and 77.6% exercised peer violence in addition to CPV (generalists)). In general, no differences were found between girls and boys in the specialist profile, but differences were found in the generalist profile. Specifically, generalist girls exercised more psychological and control/domain violence toward mothers, while boys exercised more physical violence toward fathers and had more parental permissiveness. In specialists, parental victimization predicted reactive CPV, while parental permissiveness predicted proactive CPV. In contrast, in generalists, both parental victimization and parental permissiveness predicted both reactive and proactive CPV. Low emotional regulation was a significant predictor in both cases. This study identifies differences among girls and boys in CPV risk factors and among variables that predict reactive and proactive CPV and that these results differ between specialist and generalist aggressors. Implications for research and professional practice are discussed, highlighting the need to design and implement prevention and intervention programs specialized in the type of aggressor, paying special attention to gender differences and to the factors that motivate one or the other type of CPV.
Applying Explainable Machine Learning Models for Detection of Breast Cancer Lymph Node Metastasis in Patients Eligible for Neoadjuvant Treatment
Authors: Vrdoljak Josip , Boban Zvonimir , Barić Domjan , Šegvić Darko , Kumrić Marko , Avirović Manuela , Perić Balja Melita , Periša Marija Milković , Tomasović Čedna , Tomić Snježana , Vrdoljak Eduard , Božić Joško
Published: January 2023

Background: Due to recent changes in breast cancer treatment strategy, significantly more patients are treated with neoadjuvant systemic therapy (NST). Radiological methods do not precisely determine axillary lymph node status, with up to 30% of patients being misdiagnosed. Hence, supplementary methods for lymph node status assessment are needed. This study aimed to apply and evaluate machine learning models on clinicopathological data, with a focus on patients meeting NST criteria, for lymph node metastasis prediction. Methods: From the total breast cancer patient data (n = 8381), 719 patients were identified as eligible for NST. Machine learning models were applied for the NST-criteria group and the total study population. Model explainability was obtained by calculating Shapley values. Results: In the NST-criteria group, random forest achieved the highest performance (AUC: 0.793 [0.713, 0.865]), while in the total study population, XGBoost performed the best (AUC: 0.762 [0.726, 0.795]). Shapley values identified tumor size, Ki-67, and patient age as the most important predictors. Conclusion: Tree-based models achieve a good performance in assessing lymph node status. Such models can lead to more accurate disease stage prediction and consecutively better treatment selection, especially for NST patients where radiological and clinical findings are often the only way of lymph node assessment.
Organ-on-a-Chip and Microfluidic Platforms for Oncology in the UK
Authors: Nolan Joanne , Pearce Oliver M. T. , Screen Hazel R. C. , Knight Martin M. , Verbruggen Stefaan W.
Published: January 2023

Organ-on-chip systems are capable of replicating complex tissue structures and physiological phenomena. The fine control of biochemical and biomechanical cues within these microphysiological systems provides opportunities for cancer researchers to build complex models of the tumour microenvironment. Interest in applying organ chips to investigate mechanisms such as metastatsis and to test therapeutics has grown rapidly, and this review draws together the published research using these microfluidic platforms to study cancer. We focus on both in-house systems and commercial platforms being used in the UK for fundamental discovery science and therapeutics testing. We cover the wide variety of cancers being investigated, ranging from common carcinomas to rare sarcomas, as well as secondary cancers. We also cover the broad sweep of different matrix microenvironments, physiological mechanical stimuli and immunological effects being replicated in these models. We examine microfluidic models specifically, rather than organoids or complex tissue or cell co-cultures, which have been reviewed elsewhere. However, there is increasing interest in incorporating organoids, spheroids and other tissue cultures into microfluidic organ chips and this overlap is included. Our review includes a commentary on cancer organ-chip models being developed and used in the UK, including work conducted by members of the UK Organ-on-a-Chip Technologies Network. We conclude with a reflection on the likely future of this rapidly expanding field of oncological research.
The Relationship between Cancer and Dementia: An Updated Review
Authors: Kao Yung-Shuo , Yeh Cheng-Chang , Chen Yi-Fang
Published: January 2023

The risk of cancer and dementia increases with age, raising complex questions about whether it is appropriate to continue cancer treatment in older patients. There is emerging research suggesting the association between cancer and dementia. However, the mechanistic underpinnings are still under investigation. Progress has already been made toward understanding the cognitive effects associated with cancer therapy. Such associations raise awareness about the need to establish better prevention methods and early screening in clinical practice. Additionally, recent studies have suggested possible therapeutic strategies for better preserving cognitive function and reducing the risk for dementia before patients start cancer treatment. We review the current literature and summarize the incidence and mechanisms of cognitive impairment in patients with lung cancer, breast cancer, head and neck cancer, gastric cancer, prostate cancer, colorectal cancer, and brain tumor/brain metastasis following different kinds of therapies. Possible risk factors are suggested to identify the early onset of cognitive changes in cancer patients and provide more insight into the pathophysiological process of dementia.
Profiling of G-Protein Coupled Receptors in Adipose Tissue and Differentiating Adipocytes Offers a Translational Resource for Obesity/Metabolic Research
Authors: Al Mahri Saeed , Okla Meshail , Rashid Mamoon , Malik Shuja Shafi , Iqbal Jahangir , Al Ibrahim Maria , Dairi Ghida , Mahmood Amer , Muthurangan Manikandan , Yaqinuddin Ahmed , Mohammad Sameer
Published: January 2023

G protein-coupled receptors (GPCRs) are expressed essentially on all cells, facilitating cellular responses to external stimuli, and are involved in nearly every biological process. Several members of this family play significant roles in the regulation of adipogenesis and adipose metabolism. However, the expression and functional significance of a vast number of GPCRs in adipose tissue are unknown. We used a high-throughput RT-PCR panel to determine the expression of the entire repertoire of non-sensory GPCRs in mouse white, and brown adipose tissue and assess changes in their expression during adipogenic differentiation of murine adipocyte cell line, 3T3-L1. In addition, the expression of GPCRs in subcutaneous adipose tissues from lean, obese, and diabetic human subjects and in adipocytes isolated from regular chow and high-fat fed mice were evaluated by re-analyzing RNA-sequencing data. We detected a total of 292 and 271 GPCRs in mouse white and brown adipose tissue, respectively. There is a significant overlap in the expression of GPCRs between the two adipose tissue depots, but several GPCRs are specifically expressed in one of the two tissue types. Adipogenic differentiation of 3T3-L1 cells had a profound impact on the expression of several GPCRs. RNA sequencing of subcutaneous adipose from healthy human subjects detected 255 GPCRs and obesity significantly changed the expression of several GPCRs in adipose tissue. High-fat diet had a significant impact on adipocyte GPCR expression that was similar to human obesity. Finally, we report several highly expressed GPCRs with no known role in adipose biology whose expression was significantly altered during adipogenic differentiation, and/or in the diseased human subjects. These GPCRs could play an important role in adipose metabolism and serve as a valuable translational resource for obesity and metabolic research.
Antithymocyte Globulin Inhibits CD8+ T Cell Effector Functions via the Paracrine Induction of PDL-1 on Monocytes
Authors: Copic Dragan , Direder Martin , Klas Katharina , Bormann Daniel , Laggner Maria , Ankersmit Hendrik Jan , Mildner Michael
Published: January 2023

Background: Antithymocyte globulins (ATG) are T cell-depleting antibodies used in solid organ transplantation for induction therapy in sensitized patients with a high risk of graft rejection. Previously described effects besides the depletion of T cells have suggested additional modes of action and identified further cellular targets. Methods: We examined the transcriptional changes arising in immune cells from human blood after ex vivo stimulation with ATG at the single-cell level to uncover additional mechanisms by which ATG regulates T cell activity and effector functions. Findings: Analysis of the paracrine factors present in the plasma of ATG-treated whole blood revealed high levels of chemokines and cytokines, including interferon-γ (IFN-γ). Furthermore, we identified an increase in the surface expression of the programmed death ligand 1 (PDL-1) on monocytes mediated by the released paracrine factors. In addition, we showed that this induction is dependent on the activation of JAK/STAT signaling via the binding of IFN-γ to interferon-γ receptor 1 (IFN-γR1). Lastly, we demonstrated that the modulation of the immune regulatory axis of programmed cell death protein 1 (PD1) on activated CD8+ T cells with PDL-1 found on monocytes mediated by ATG potently inhibits effector functions including the proliferation and granzyme B release of activated T cells. Interpretation: Together, our findings represent a novel mode of action by which ATG exerts its immunosuppressive effects.