bluuebunny/crossref_metadata_2025 huggingface dataset:
Synthesis, Structure, and Optical Properties of a Molecular Cluster Cd4(p-MBT)10
Authors: Xu Cheng , Zhou Zheng , Han Haixiang
Published: September 2022

The creation of atomically precise nanoclusters has become an important research direction in nanoscience, because such nanomaterials can demonstrate unique chemo-physical properties that are significantly different from their corresponding bulk materials. The cause of such disparities lies in their different construction pattern for the atomic structures, in which the bulk materials display a highly symmetric, extended atomic lattice, while the ultrasmall nanoclusters feature low symmetric molecular structures. In this work, we report a new [HNEt3]2[Cd4(SC7H7)10] (denoted as Cd4(p-MBT)10, p-MBT = p-methylbenzene thiolate) nanocluster obtained through a one-pot synthetic pathway, and its atomic structure was revealed by single crystal X-ray diffraction technique. It shows that the molecular structure for Cd4(p-MBT)10 demonstrates the embryonic features of the corresponding bulk CdS. That is, the whole structure is built from four [CdS4] units which are connected to each other by shared corner S atoms. Due to the molecular nature, the structure of Cd4(p-MBT)10 is distorted, which yields two enantiomeric isomers with chiral Cd-S frameworks that co-crystallize into a non-chiral space group. In addition, the electronic structure was characterized by photoluminescence spectroscopy and calculated by density functional theory.
Evaluation of the Skin Permeation-Enhancing Abilities of Newly Developed Water-Soluble Self-Assembled Liquid Crystal Formulations Based on Hexosomes
Authors: Kadhum Wesam R. , See Gerard Lee , Alhijjaj Muqdad , Kadhim Mustafa M. , Arce Florencio Jr. , Al-Janabi Ahmed S. , Al-Rashidi Reyadh R. , Khadom Anees A.
Published: September 2022

The present study aimed to develop polyethylene glycol–liquid crystals (PEG-LC) ointment formulations, assess their formulation characteristics, and establish their biocompatibility and impact on transdermal drug administration. PEG-LC formulations were prepared using a hydrophilic molecule, p-aminobenzoic acid (PAB). Formulation characterizations such as small-angle X-ray scattering, viscosity, pH, zeta potential, and the particle sizes of the formulations were examined to determine the physicochemical properties of the prepared formulations. The drug release profile of PEG-LC ointment formulations was assessed with a dialysis membrane. In vitro skin permeation testing was performed to establish whether the PEG-LC formulations improved drug skin penetration. The MTT and comet assays were performed to assess the biocompatibility of the formulations. Our data showed that the method is effective in forming hexosome-type PEG-LC formulations and that they were biocompatible. Furthermore, the PEG-LC formulations significantly improved PAB skin penetration when compared with commercial PEG. The PEG-LC formulation is a promising carrier for the delivery of hydrophilic drugs.
Design of Virtual Reality-Based Hippotherapy Simulator Exergaming Software and Its Controller for Rehabilitation of Children with Cerebral Palsy in Indonesia: An Engineering Concept
Authors: Satriawan Ardianto , Trusaji Wildan , Hasanuddin Muhammad Ogin , Rahadini Septia Susanti , Selekta Mayang Cendikia , Sungkar Ellyana
Published: September 2022

Horse riding exercise, also known as hippotherapy is a popular treatment for children with cerebral palsy (CP). However, the need for trained therapist, massive land use, and expensive maintenance of the horse ranch makes hippotherapy not affordable or even available for most patients in Indonesia. This problem motivates us to consider mechanical horse riding simulator machines to replace actual horse hippotherapy. However, most patients are children and are easily bored when asked to do monotonous activities for an extended period. The room setting also does not give the patient visual inputs that usually help motivates the children in real-horse hippotherapy activities. To solve this problem, we designed an exercise game (exergaming) software which we named Sirkus Apel, providing the patients with fun activities while doing the therapy. We also design an inertial sensor-based controller that lets the patients control the in-game horse by their back movements, which also benefits CP patients. To make the visual input enjoyable to the user while also considering the user’s safety, we built a convex mirror-based dome virtual reality to provide an immersive 3-D experience. We then project the game content to the dome to provide an immersive experience to the patients making it as if they are riding a real horse inside the game.
Comparison of Adverse Events of Different Endoscopic Ultrasound-Guided Tissue Acquisition Methods: A Single-Center Retrospective Analysis
Authors: Lin Yen-Chih , Yen Hsu-Heng , Huang Siou-Ping , Shih Kai-Lun , Chen Yang-Yuan
Published: September 2022

The efficacy of new generation endoscopic ultrasound-guided biopsy needles has been promising in recent years. Yet, comparing these needles’ diagnostic yield and safety to conventional needles is not well-known. Our study aims to compare the adverse events of endoscopic ultrasound-guided tissue acquisition (EUS-TA) with different types of needles, including FNA needles, FNB needles with a Franseen tip and FNB needles with a reverse bevel. Furthermore, we will analyze the risk factors, including tumor vascularity, different needle types, and the underlying disease, which may impact the safety of the procedures. From May 2014 to December 2021, 192 consecutive EUS-TAs were performed on pancreatic and peripancreatic lesions in our hospital using different types of FNA and FNB needles. We retrospectively reviewed the data and identified the risk factors for EUS-TA-related complications. As a result, the hypervascular tumor is a significant risk factor for adverse events in our multivariate analysis, with an odds ratio of 4.96 (95% CI 1.33–18.47), while liver cirrhosis is one of the risk factors for adverse events during EUS-TA, with an odds ratio of 5.3 (95% CI 1.1–25.6). However, the risk of adverse events did not increase using Franseen-tip needles, compared to conventional FNA or FNB needles with a reverse bevel. In conclusion, we must be more cautious in patients with liver cirrhosis and hypervascular tumors, such as pancreatic neuroendocrine tumors, when performing EUS-guided tissue acquisition.
Do the Causes of Spontaneous Preterm Delivery Affect Placental Inflammatory Pathology and Neonatal Outcomes?
Authors: Jang Il-Yeo , Jung Hye-Ji , Sung Ji-Hee , Choi Suk-Joo , Oh Soo-Young , Kim Jung-Sun , Roh Cheong-Rae
Published: September 2022

Objective: To investigate the severity of histologic chorioamnionitis /funisitis according to the indication for preterm delivery and their corresponding neonatal outcomes. Method: This study included 411 singleton women who delivered between 21+0 and 31+6 week of gestation due to preterm labor (PTL, n = 165), preterm premature rupture of membranes (PPROM, n = 202), or incompetent internal os of the cervix (IIOC, n = 44). The primary outcome measure was the rate of severe histological chorioamnionitis/funisitis. Secondary outcome measure was neonatal outcomes including neonatal and infant death, and neonatal composite morbidity. Results: The PPROM group demonstrated a higher rate of severe histological chorioamnionitis/funisitis compared to the PTL group (severe histological chorioamnionitis; PPROM, 66.3% vs. PTL, 49.1%, p = 0.001, severe funisitis; PPROM, 44.1% vs. PTL, 23.6%, p < 0.001) and this remained significant after multivariable analysis (severe histologic chorioamnionitis, OR 2.367, 95% CI 1.517–3.693; severe funisitis, OR 2.668, 95% CI 1.684–4.226). For neonatal outcomes only, a higher rate of patent ductus arteriosus was observed in the IIOC group compared to the PTL and PPROM groups (IIOC, 77.3% vs. PTL, 54.0% vs. PPROM, 54.0%, p = 0.043) and this remained significant after multivariable analysis. Conclusion: Indication of spontaneous preterm delivery might affect the placental inflammatory pathology and neonatal morbidity.
Guessing PINs, One Partial PIN at a Time
Authors: Sheil Ashley , Malone David
Published: September 2022

Entering digits of a personal identification number (PIN) is a common form of authentication. One variant of this scheme is to request the digits from a random subset of positions, which is sometimes called a partial PIN. In this paper we consider strategies for guessing the PIN when a partial PIN scheme is in use, which allows the quantification of the strength of this mechanism. We suggest several strategies for guessing the PIN under the assumption that the organisation assigns PINs randomly and requests random positions from the PIN at each login. We present analytic and simulation results from the different strategies and explore their performance when guessing different sizes of PIN and requested subset. We find that the most effective strategies have a reasonable chance of recovering a PIN in tens to hundreds of guesses.
Uniqueness of Solutions in Thermopiezoelectricity of Nonsimple Materials
Authors: Passarella Francesca , Tibullo Vincenzo
Published: September 2022

This article presents the theory of thermopiezoelectricity in which the second displacement gradient and the second electric potential gradient are included in the set of independent constitutive variables. This is achieved by using the entropy production inequality proposed by Green and Laws. At first, appropriate thermodynamic restrictions and constitutive equations are obtained, using the well-established Coleman and Noll procedure. Then, the balance equations and the constitutive equations of linear theory are derived, and the mixed initial-boundary value problem is set. For this problem a uniqueness result is established. Next, the basic equations for the isotropic case are derived. Finally, a set of inequalities is obtained for the constant constitutive coefficients of the isotropic case that, on the basis on the previous theorem, ensure the uniqueness of the solution of the mixed initial-boundary value problem.
Effects of Eight-Week Circuit Training with Core Exercises on Performance in Adult Male Soccer Players
Authors: Belli Guido , Marini Sofia , Mauro Mario , Maietta Latessa Pasqualino , Toselli Stefania
Published: September 2022

Core exercises have been widely promoted in the last 25 years. However, the scientific debate about its efficacy for improving individual and team sports performance is still open. Thus, the present study aims to investigate the effects of circuit training with a core exercise program on physical performance in competitive amateur soccer players. The training was conducted during the off-season period, two times per week for 8 weeks. Pre- and post-evaluations were conducted using the following tests: Y-Balance Test (YB), standing long jump (SLJ), medicine ball chest press (MBC), curl-up (CU), and Illinois Agility Test (IAT). A total of 19 adults were divided into an experimental group (EG, n = 11, age 22 years, weight 71.2 ± 4.8 kg, height 174 ± 5.8 cm) and a control group (CG, n = 8, age 22 years, weight 73.2 ± 4.1 Kg, height 176 ± 6.3 cm). The EG showed significant improvements in lower and upper body strength, core endurance and balance, whereas the CG did not report significant changes in the pre- and post-test comparison. Despite study limitations, our positive results show that circuit training with core exercises appears to be a good strategy for performance improvement in adult soccer players.
Tumblr Facts: Antecedents of Self-Disclosure across Different Social Networking Sites
Authors: Bianchi Marcella , Fabbricatore Rosa , Caso Daniela
Published: September 2022

Previous research investigating antecedents of online self-disclosure pointed out two perspectives: social compensation and enhancement hypotheses, showing controversial findings. Furthermore, most contributions have focused on social networking sites (SNSs) considered mainstream, like Facebook and Instagram, and such results are often considered universally valid for all SNSs. Tumblr is a less-studied SNS with peculiar features—such as anonymity, higher control over the presentation of personal aspects, supportive communities—that could particularly lead individuals to self-disclose. As prior contributions highlighted that the features and affordances could define how a medium will be used, this paper aims to investigate the antecedents of online self-disclosure on Tumblr and other mainstream SNSs. We run a survey on 559 Tumblr users (aged 13–70; M = 28.86; SD = 12.34). T-test showed that Tumblr users have a higher willingness to self-disclose on Tumblr compared to another SNSs (t = 22.44, p < 0.001). A path analysis model confirmed the predictive role of some psychological variables on self-disclosure on Tumblr but not on mainstream SNSs. In particular, self-disclosure on Tumblr was predicted by self-esteem, negative emotionality, and preference for online social interactions, which was in turn predicted by social anxiety. These findings partially supported both social compensation and enhancement hypotheses, indicating that the phenomenon is more complex than expected.
Traffic Management: Multi-Scale Vehicle Detection in Varying Weather Conditions Using YOLOv4 and Spatial Pyramid Pooling Network
Authors: Humayun Mamoona , Ashfaq Farzeen , Jhanjhi Noor Zaman , Alsadun Marwah Khalid
Published: September 2022

Detecting and counting on road vehicles is a key task in intelligent transport management and surveillance systems. The applicability lies both in urban and highway traffic monitoring and control, particularly in difficult weather and traffic conditions. In the past, the task has been performed through data acquired from sensors and conventional image processing toolbox. However, with the advent of emerging deep learning based smart computer vision systems the task has become computationally efficient and reliable. The data acquired from road mounted surveillance cameras can be used to train models which can detect and track on road vehicles for smart traffic analysis and handling problems such as traffic congestion particularly in harsh weather conditions where there are poor visibility issues because of low illumination and blurring. Different vehicle detection algorithms focusing the same issue deal only with on or two specific conditions. In this research, we address detecting vehicles in a scene in multiple weather scenarios including haze, dust and sandstorms, snowy and rainy weather both in day and nighttime. The proposed architecture uses CSPDarknet53 as baseline architecture modified with spatial pyramid pooling (SPP-NET) layer and reduced Batch Normalization layers. We also augment the DAWN Dataset with different techniques including Hue, Saturation, Exposure, Brightness, Darkness, Blur and Noise. This not only increases the size of the dataset but also make the detection more challenging. The model obtained mean average precision of 81% during training and detected smallest vehicle present in the image
Fully Automated Regional Analysis of Myocardial T2* Values for Iron Quantification Using Deep Learning
Authors: Martini Nicola , Meloni Antonella , Positano Vincenzo , Latta Daniele Della , Keilberg Petra , Pistoia Laura , Spasiano Anna , Casini Tommaso , Barone Angelica , Massa Antonella , Ripoli Andrea , Cademartiri Filippo
Published: September 2022

Cardiovascular magnetic resonance (CMR) T2* mapping is the gold standard technique for the assessment of iron overload in the heart. The quantitative analysis of T2* values requires the manual segmentation of T2* images, which is a time-consuming and operator-dependent procedure. This study describes a fully-automated method for the regional analysis of myocardial T2* distribution using a deep convolutional neural network (CNN). A CNN with U-Net architecture was trained to segment multi-echo T2*-weighted images in 16 sectors in accordance with the American Heart Association (AHA) model. We used images from 210 patients (three slices, 10 multi-echo images) with iron overload diseases to train and test the CNN. The performance of the proposed method was quantitatively evaluated on an independent holdout test set by comparing the segmentation accuracy of the CNN and the T2* values obtained by the automated method against ground-truth labels provided by two experts. Segmentation metrics and global and regional T2* values assessed by the proposed DL method closely matched those obtained by experts with excellent intraclass correlation in all myocardial sectors of the AHA model (ICC range [0.944, 0.996]). This method could be effectively adopted in the clinical setting for fast and accurate analysis of myocardial T2*.
An Effective Negotiation Strategy for Quantitative and Qualitative Issues in Multi-Agent Systems
Authors: Mansour Khalid , Al-Lahham Yaser , Tawil Safeyah , Kowalczyk Ryszard , Al-Qerem Ahmad
Published: September 2022

Automated negotiation is an efficient approach for interaction in multi-agent systems in which agents exchange offers and counteroffers to conclude an agreement. This paper addresses the problem of offer formulation during the interaction between buyer and seller software agents for the purpose of reaching an agreement over quantitative and qualitative issues at once. In order to improve the outcome of the negotiation process, a hybrid negotiation method is presented and verified. Offer formulation is based on fuzzy similarity and preference-based methods. The preference-based mechanism is used for quantitative issues, while the fuzzy similarity technique is used for qualitative issues. The preference-based mechanism takes into account the preferences of the opponent when generating offers; the agent makes greater concessions on the issues which the opponent prefers more. The fuzzy-similarity method formulates an offer that considers offering a deal that is more similar to the one received by the opponent during the last round of negotiation. The experiments consists of two parts. The first part compares the hybrid strategy with the basic one. The findings reveal that the hybrid strategy is better in all performance measures, namely, utility rate, agreement rate, and Nash product rate. The second part of the experimental work compares four mechanisms of offer generating mechanisms: basic, preference-based, fuzzy similarity, and hybrid. The results show that the hybrid negotiation strategy performs equal or better that other negotiation strategies. More details can be found in the paper.
Local-Partial Signal Combining Schemes for Cell-Free Large-Scale MU-MIMO Systems with Limited Fronthaul Capacity and Spatial Correlation Channels
Authors: Alammari Amr A. , Sharique Mohd , Moinuddin Athar Ali , Ansari Mohammad Samar
Published: September 2022

Cell-free large-scale multi-user MIMO is a promising technology for the 5G-and-beyond mobile communication networks. Scalable signal processing is the key challenge in achieving the benefits of cell-free systems. This study examines a distributed approach for cell-free deployment with user-centric configuration and finite fronthaul capacity. Moreover, the impact of scaling the pilot length, the number of access points (APs), and the number of antennas per AP on the achievable average spectral efficiency are investigated. Using the dynamic cooperative clustering (DCC) technique and large-scale fading decoding process, we derive an approximation of the signal-to-interference-plus-noise ratio in the criteria of two local combining schemes: Local-Partial Regularized Zero Forcing (RZF) and Local Maximum Ratio (MR). The results indicate that distributed approaches in the cell-free system have the advantage of decreasing the fronthaul signaling and the computing complexity. The results also show that the Local-Partial RZF provides the highest average spectral efficiency among all the distributed combining schemes because the computational complexity of the Local-Partial RZF is independent of the UTs. Therefore, it does not grow as the number of user terminals (UTs) increases.
Defect Synthesis Using Latent Mapping Adversarial Network for Automated Visual Inspection
Authors: Song Seunghwan , Chang Kyuchang , Yun Kio , Jun Changdong , Baek Jun-Geol
Published: September 2022

In Industry 4.0, internet of things (IoT) technologies are expanding and advanced smart factories are currently being developed. To build an automated visual inspection (AVI) and achieve smartization of steel manufacturing, detecting defects in products in real-time and accurately diagnosing the quality of products are essential elements. As in various manufacturing industries, the steel manufacturing process presents a class imbalance problem for products. For example, fewer defect images are available than normal images. This study developed a new image synthesis methodology for the steel manufacturing industry called a latent mapping adversarial network. Inspired by the style-based generative adversarial network (StyleGAN) structure, we constructed a mapping network for the latent space, which made it possible to compose defect images of various sizes. We discovered the most suitable loss function, and optimized the proposed method in terms of convergence and computational cost. The experimental results demonstrate the competitive performance of the proposed model compared to the traditional models in terms of classification accuracy of 92.42% and F-score of 93.15%. Consequently, the problem of data imbalance is solved, and higher productivity in steel products is expected.
A Two-Stage DC/DC Isolated High-Voltage Converter with Zero-Voltage Switching and Zero-Current Switching Applied in Electronic Power Conditioners
Authors: Zheng Wei , Hu Cong , Zhao Bin , Su Xiao-Bao , Wang Gang , Hou Xiao-Wan , Gu Bruce
Published: September 2022

This paper presents a two-stage DC/DC converter with high efficiency utilized in an electronic power conditioner (EPC), which is widely applicable in satellite communications, etc. The galvanically isolated converter contains two cascaded converters: a buck converter, which is a pre-regulator operating under a closed-loop condition, and a push–pull converter, which is intended to boost the input voltage, operating under an open-loop condition. In the push–pull converter, the power switches, including the main switches and the rectifier diodes, operate under zero-voltage switching (ZVS) and zero-current switching (ZCS) at both switch off and switch on, which minimizes the switching loss. Furthermore, all of the parasitic parameters, such as the parasitic capacitance, leakage inductance, and magnetizing inductance of the main transformer, are fully utilized. Therefore, the presented topology benefits from fewer semiconductors but higher efficiency. The proposed topology produces less EMI noise because of ZVS and ZCS processes whose fundamental switching frequency interference is relatively low. The presented converter achieves a wide bus voltage regulation range in a satellite because of the pre-regulation of the buck cell. The theoretical analysis is validated by a prototype and its experimental results. The maximum efficiency of the converter can be up to 94.5%, and the high-voltage output is 7000 V.
Smart Logistics—Sustainable Technological Innovations in Customer Service at the Last-Mile Stage: The Polish Perspective
Authors: Kolasińska-Morawska Katarzyna , Sułkowski Łukasz , Buła Piotr , Brzozowska Marta , Morawski Paweł
Published: September 2022

The present day is marked by the economic expansiveness of societies and the adoption and adaptation of intelligent technologies. In this hyper-world, customers expect a personalized offer enhanced with customized service, which results in the introduction of sustainable and intelligent solutions—among other services. What becomes important is not so much the “Primum non nocere” of creation as much as the “go smart to the future” in creating. The smart logistics concept is a representation of this trend. The subject of the article is an analysis of the impact of the application of the smart idea in the field of sustainable development on changes in logistics in customer service at the last-mile stage. The source of this article is exploratory research of secondary sources, including books, articles, and reports, which has been subjected to a critical content analysis. The obtained results made it possible to design and implement an explanatory study of online-buying habits of people based on the CAWI (Computer Assisted Web Interview) methodology. The collected material has become the basis for the authors to indicate the applicability of smart logistics in the field of last-mile logistics, which can be used by researchers and training institutions in the field of professionalization of management of intelligent logistics processes in customer service at the last-mile stage. The last-mile service in logistics involves reaching the largest possible number of recipients, however, it has a negative impact on the natural environment, which, of course, contradicts the concept of sustainable development, including trends that are noticeable in the logistics market, customers, and in the law. Hence, it is important to look for solutions that allow us to achieve the appropriate level of customer service in the last mile, but at the same time, take care of the natural environment. The study was narrowed down to the Polish perspective due to the growing demand for last-mile logistics services. Moreover, Poland is still a country where the concept of sustainable development is not fully understood and used. The research allowed us to indicate the directions of development of the last-mile service processes by considering the technological innovations that may support the application of the concept of sustainable development.
Development of a Single-Piece Sperm Counting Chamber (SSCC) for Aquatic Species
Authors: Belgodere Jorge A. , Liu Yue , Reich Elizabeth L. , Eades Jason , Tiersch Terrence R. , Monroe William Todd
Published: September 2022

Accurate determination of sperm concentration in aquatic species is important for assisted reproduction and cryopreservation, yet is challenging as current counting methods are costly or not suitable for many species. The goal of this work was to develop a simple (single-piece and single-layer photolithography) sperm counting chamber (SSCC) for aquatic species. Goldfish (Carassius auratus) and zebrafish (Danio rerio) sperm were used for evaluation in the device, which was created with soft lithography. Four designs with different geometries were evaluated for counting accuracy. Open-corner and open-midpoint designs were the most accurate with no significant differences (P > 0.05) for most of the target sperm concentrations (0.5–1.0 × 108 cells/mL). The open-corner design was not significantly different from the Makler® counting chamber intended for human sperm cells (P = 0.6) but was significantly different from a hemocytometer (P < 0.001) intended for other cell sizes. Material cost of device production was USD 16 per unit, including photolithography supplies, glass slide and coverslip, and polydimethylsiloxane. The cost can be reduced to USD 2 per unit with repeated wafer casts. This device could be further refined for resin 3-D printing and sharing via open-hardware approaches and modified to best suit species specific applications.
Carbon Capture from CO2-Rich Natural Gas via Gas-Liquid Membrane Contactors with Aqueous-Amine Solvents: A Review
Authors: da Cunha Guilherme , de Medeiros José , Araújo Ofélia
Published: September 2022

Gas–liquid membrane contactor is a promising process intensification technology for offshore natural gas conditioning in which weight and footprint constraints impose severe limitations. Thanks to its potential for substituting conventional packed/trayed columns for acid-gas absorption and acid-gas solvent regeneration, gas-liquid membrane contactors have been investigated experimentally and theoretically in the past two decades, wherein aqueous-amine solvents and their blends are the most employed solvents for carbon dioxide removal from natural gas in gas-liquid membrane contactors. These efforts are extensively and critically reviewed in the present work. Experimentally, there are a remarkable lack of literature data in the context of gas–liquid membrane contactors regarding the following topics: water mass transfer; outlet stream temperatures; head-loss; and light hydrocarbons (e.g., ethane, propane, and heavier) mass transfer. Theoretically, there is a lack of complete models to predict gas-liquid membrane contactor operation, considering multicomponent mass balances, energy balances, and momentum balances, with an adequate thermodynamic framework for correct reactive vapor–liquid equilibrium calculation and thermodynamic and transport property prediction. Among the few works covering modeling of gas-liquid membrane contactors and implementation in professional process simulators, none of them implemented all the above aspects in a completely successful way.
Mitochondrial DNA Together with miR-142-3p in Plasma Can Predict Unfavorable Outcomes in Patients after Acute Myocardial Infarction
Authors: Barbalata Teodora , Scarlatescu Alina I. , Sanda Gabriela M. , Toma Laura , Stancu Camelia S. , Dorobantu Maria , Micheu Miruna M. , Sima Anca V. , Niculescu Loredan S.
Published: September 2022

Myocardial infarction is one of the leading causes of death worldwide, despite numerous efforts to find efficient prognostic biomarkers and treatment targets. In the present study, we aimed to assess the potential of six microRNAs known to be involved in cardiovascular diseases, cell-free DNA (cfDNA), and mitochondrial DNA (mtDNA) circulating in plasma to be used as prognostic tools for the occurrence of unfavorable outcomes such as major adverse cardiovascular events (MACE) after acute ST-segment elevation myocardial infarction (STEMI). Fifty STEMI patients were enrolled and monitored for 6 months for the occurrence of MACE. Plasma was collected at three time points: upon admission to hospital (T0), at discharge from hospital (T1), and 6 months post-STEMI (T6). Plasma levels of miR-223-3p, miR-142-3p, miR-155-5p, miR-486-5p, miR-125a-5p, and miR-146a-5p, as well as of cfDNA and mtDNA, were measured by RT-qPCR. Results showed that the levels of all measured miRNAs, as well as of cfDNA and mtDNA, were the most increased at T1, compared to the other two time points. In the plasma of STEMI patients with MACE compared to those without MACE, we determined increased levels of miRNAs, cfDNA, and mtDNA at T1. Hence, we used the levels of all measured parameters at T1 for further statistical analysis. Statistical analysis demonstrated that all six miRNAs and cfDNA plus mtDNA levels, respectively, were associated with MACE. The minimal statistical model that could predict MACE in STEMI patients was the combination of mtDNA and miR-142-3p levels, as evidenced by ROC analysis (AUC = 0.97, p < 0.001). In conclusion, the increased plasma levels of mtDNA, along with miR-142-3p, could be used to predict unfavorable outcomes in STEMI patients.
Therapeutics That Can Potentially Replicate or Augment the Anti-Aging Effects of Physical Exercise
Authors: De Sousa Lages Adriana , Lopes Valentim , Horta João , Espregueira-Mendes João , Andrade Renato , Rebelo-Marques Alexandre
Published: September 2022

Globally, better health care access and social conditions ensured a significant increase in the life expectancy of the population. There is, however, a clear increase in the incidence of age-related diseases which, besides affecting the social and economic sustainability of countries and regions around the globe, leads to a decrease in the individual’s quality of life. There is an urgent need for interventions that can reverse, or at least prevent and delay, the age-associated pathological deterioration. Within this line, this narrative review aims to assess updated evidence that explores the potential therapeutic targets that can mimic or complement the recognized anti-aging effects of physical exercise. We considered pertinent to review the anti-aging effects of the following drugs and supplements: Rapamycin and Rapamycin analogues (Rapalogs); Metformin; 2-deoxy-D-glucose; Somatostatin analogues; Pegvisomant; Trametinib; Spermidine; Fisetin; Quercetin; Navitoclax; TA-65; Resveratrol; Melatonin; Curcumin; Rhodiola rosea and Caffeine. The current scientific evidence on the anti-aging effect of these drugs and supplements is still scarce and no recommendation of their generalized use can be made at this stage. Further studies are warranted to determine which therapies display a geroprotective effect and are capable of emulating the benefits of physical exercise.
Overexpression of Sweet Potato Carotenoid Cleavage Dioxygenase 4 (IbCCD4) Decreased Salt Tolerance in Arabidopsis thaliana
Authors: Zhang Jie , He Liheng , Dong Jingjing , Zhao Cailiang , Tang Ruimin , Jia Xiaoyun
Published: September 2022

Salt stress has a serious impact on normal plant growth and yield. Carotenoid cleavage dioxygenase (CCD) degrades carotenoids to produce apocarotenoids, which are involved in plant responses to biotic and abiotic stresses. This study shows that the expression of sweet potato IbCCD4 was significantly induced by salt and dehydration stress. The heterologous expression of IbCCD4 in Arabidopsis was induced to confirm its salt tolerance. Under 200 mM NaCl treatment, compared to wild-type plants, the rosette leaves of IbCCD4-overexpressing Arabidopsis showed increased anthocyanins and carotenoid contents, an increased expression of most genes in the carotenoid metabolic pathway, and increased malondialdehyde (MDA) levels. IbCCD4-overexpressing lines also showed a decreased expression of resistance-related genes and a lower activity of three antioxidant enzymes: peroxidase (POD), superoxide dismutase (SOD), and catalase (CAT). These results indicate that IbCCD4 reduced salt tolerance in Arabidopsis, which contributes to the understanding of the role of IbCCD4 in salt stress.
The Oncolytic Adenovirus XVir-N-31, in Combination with the Blockade of the PD-1/PD-L1 Axis, Conveys Abscopal Effects in a Humanized Glioblastoma Mouse Model
Authors: Klawitter Moritz , El-Ayoubi Ali , Buch Jasmin , Rüttinger Jakob , Ehrenfeld Maximilian , Lichtenegger Eva , Krüger Marcel A. , Mantwill Klaus , Koll Florestan J. , Kowarik Markus C. , Holm Per Sonne , Naumann Ulrike
Published: September 2022

Glioblastoma (GBM) is an obligatory lethal brain tumor with a median survival, even with the best standard of care therapy, of less than 20 months. In light of this fact, the evaluation of new GBM treatment approaches such as oncolytic virotherapy (OVT) is urgently needed. Based on our preliminary preclinical data, the YB-1 dependent oncolytic adenovirus (OAV) XVir-N-31 represents a promising therapeutic agent to treat, in particular, therapy resistant GBM. Preclinical studies have shown that XVir-N-31 prolonged the survival of GBM bearing mice. Now using an immunohumanized mouse model, we examined the immunostimulatory effects of XVir-N-31 in comparison to the wildtype adenovirus (Ad-WT). Additionally, we combined OVT with the inhibition of immune checkpoint proteins by using XVir-N-31 in combination with nivolumab, or by using a derivate of XVir-N-31 that expresses a PD-L1 neutralizing antibody. Although in vitro cell killing was higher for Ad-WT, XVir-N-31 induced a much stronger immunogenic cell death that was further elevated by blocking PD-1 or PD-L1. In vivo, an intratumoral injection of XVir-N-31 increased tumor infiltrating lymphocytes (TILs) and NK cells significantly more than Ad-WT not only in the virus-injected tumors, but also in the untreated tumors growing in the contralateral hemisphere. This suggests that for an effective treatment of GBM, immune activating properties by OAVs seem to be of greater importance than their oncolytic capacity. Furthermore, the addition of immune checkpoint inhibition (ICI) to OVT further induced lymphocyte infiltration. Consequently, a significant reduction in contralateral non-virus-injected tumors was only visible if OVT was combined with ICI. This strongly indicates that for an effective eradication of GBM cells that cannot be directly targeted by an intratumoral OV injection, additional ICI therapy is required.
Implication of Irisin in Different Types of Cancer: A Systematic Review and Meta-Analysis
Authors: Vliora Maria , Nintou Eleni , Karligiotou Eleni , Ioannou Leonidas G. , Grillo Elisabetta , Mitola Stefania , Flouris Andreas D.
Published: September 2022

Cancer is a set of diseases characterized by several hallmark properties, such as increased angiogenesis, proliferation, invasion, and metastasis. The increased angiogenic activity constantly supplies the tumors with nutrients and a plethora of cytokines to ensure cell survival. Along these cytokines is a newly discovered protein, called irisin, which is released into the circulation after physical exercise. Irisin is the product of fibronectin type III domain-containing protein 5 (FNDC5) proteolytic cleavage. Recently it has been the topic of investigation in several types of cancer. In this study, we conducted a systematic review and meta-analysis to investigate its implication in different types of cancer. Our results suggest that irisin expression is decreased in cancer patients, thus it can be used as a valid biomarker for the diagnosis of several types of cancer. In addition, our results indicate that irisin may have an important role in tumor progression and metastasis since it is involved in multiple signaling pathways that promote cell proliferation and migration.
The Mechanism of Lipopolysaccharide’s Effect on Secretion of Endometrial Mucins in Female Mice during Pregnancy
Authors: Lu Dezhang , Hu Wenxiang , Tian Tian , Wang Mengran , Zhou Mengru , Wu Chenchen
Published: September 2022

The main toxic component of endotoxins released from the death or dissolution of Gram-negative bacteria is lipopolysaccharide (LPS), which exists widely in the natural environment, and a large amount of endotoxin can significantly inhibit the reproductive performance of animals. A previous study showed that endotoxins mainly damaged the physiological function of mucins in the endometrium, but the mechanism is not clear. In this study, the PI3K/Akt signaling pathway was not activated, and the NF-κB signaling pathway was inhibited by LPS treatment; the expression of occludin and E-cadherin proteins were decreased and ZO-1 protein expression was increased, because LPS can lead to the mucous layer becoming thinner, so that the embryonic survival rate is significantly reduced in early pregnancy. In middle and late pregnancy, LPS translocated to the epithelial cells of the uterus and the expression of claudin-1, JAMA, and E-cadherin proteins were decreased; at this time, a large number of glycosaminoglycan particles were secreted by endometrial gland cells through the PI3K/Akt/NF-κB signaling pathway that was activated after LPS treatment, However, there was no significant difference between the survival rates of fetal mice in the LPS (+) and LPS (-) groups. Glycosaminoglycan particles and mucins are secreted by gland cells, which can protect and maintain the pregnancy in the middle and late gestational periods.
Cane Vinasses Contain Bioactive Concentrations of Auxin and Abscisic Acid in Their Composition
Authors: Zamarreño Angel Mª , Valduga Giancarlo , Garcia-Mina Jose Mª
Published: September 2022

Currently, high doses of vinasse are employed for the fertigation of sugarcane with positive results on yield. Usually, this effect is related to the presence of mineral nutrients in its composition as well as to its action on soil properties. Consequently, the concentrations of minerals, organic acids, and other metabolites in vinasse are very well characterized. However, considering that cane vinasses are obtained from the treatment of vegetal tissues, it is also possible that they might contain significant concentrations of phytoregulators that could have a relevant role in their beneficial action on yield. To investigate this hypothesis, we analyzed the main plant hormones in 22 samples of vinasse collected in different production sites of Brazil using HPLC–mass spectrometry. The results show that both ABA and IAA present concentrations in vinasse within the micromolar range, thus being potential active ingredients affecting plant development. In conclusion, the beneficial action of cane vinasses on sugarcane yield might involve, among other factors, the action of IAA and ABA on plant growth.
Pretreatment with Zonisamide Mitigates Oxaliplatin-Induced Toxicity in Rat DRG Neurons and DRG Neuron–Schwann Cell Co-Cultures
Authors: Takaku Shizuka , Sango Kazunori
Published: September 2022

Oxaliplatin (OHP) is a platinum-based agent that can cause peripheral neuropathy, an adverse effect in which the dorsal root ganglion (DRG) neurons are targeted. Zonisamide has exhibited neuroprotective activities toward adult rat DRG neurons in vitro and therefore, we aimed to assess its potential efficacy against OHP-induced neurotoxicity. Pretreatment with zonisamide (100 μM) alleviated the DRG neuronal death caused by OHP (75 μM) and the protective effects were attenuated by a co-incubation with 25 μM of the mitogen-activated protein kinase (MAPK; MEK/ERK) inhibitor, U0126, or the phosphatidyl inositol-3′-phosphate-kinase (PI3K) inhibitor, LY294002. Pretreatment with zonisamide also suppressed the OHP-induced p38 MAPK phosphorylation in lined DRG neurons, ND7/23, while the OHP-induced DRG neuronal death was alleviated by pretreatment with the p38 MAPK inhibitor, SB239063 (25 μM). Although zonisamide failed to protect the immortalized rat Schwann cells IFRS1 from OHP-induced cell death, it prevented neurite degeneration and demyelination-like changes, as well as the reduction of the serine/threonine-specific protein kinase (AKT) phosphorylation in DRG neuron–IFRS1 co-cultures exposed to OHP. Zonisamide’s neuroprotection against the OHP-induced peripheral sensory neuropathy is possibly mediated by a stimulation of the MEK/ERK and PI3K/AKT signaling pathways and suppression of the p38 MAPK pathway in DRG neurons. Future studies will allow us to solidify zonisamide as a promising remedy against the neurotoxic adverse effects of OHP.
Silibinin Suppresses the Hyperlipidemic Effects of the ALK-Tyrosine Kinase Inhibitor Lorlatinib in Hepatic Cells
Authors: Verdura Sara , Encinar José Antonio , Fernández-Arroyo Salvador , Joven Jorge , Cuyàs Elisabet , Bosch-Barrera Joaquim , Menendez Javier A.
Published: September 2022

The third-generation anaplastic lymphoma tyrosine kinase inhibitor (ALK-TKI) lorlatinib has a unique side effect profile that includes hypercholesteremia and hypertriglyceridemia in >80% of lung cancer patients. Here, we tested the hypothesis that lorlatinib might directly promote the accumulation of cholesterol and/or triglycerides in human hepatic cells. We investigated the capacity of the hepatoprotectant silibinin to modify the lipid-modifying activity of lorlatinib. To predict clinically relevant drug–drug interactions if silibinin were used to clinically manage lorlatinib-induced hyperlipidemic effects in hepatic cells, we also explored the capacity of silibinin to interact with and block CYP3A4 activity using in silico computational descriptions and in vitro biochemical assays. A semi-targeted ultrahigh pressure liquid chromatography accurate mass quadrupole time-of-flight mass spectrometry with electrospray ionization (UHPLC-ESI-QTOF-MS/MS)-based lipidomic approach revealed that short-term treatment of hepatic cells with lorlatinib promotes the accumulation of numerous molecular species of cholesteryl esters and triglycerides. Silibinin treatment significantly protected the steady-state lipidome of hepatocytes against the hyperlipidemic actions of lorlatinib. Lipid staining confirmed the ability of lorlatinib to promote neutral lipid overload in hepatocytes upon long-term exposure, which was prevented by co-treatment with silibinin. Computational analyses and cell-free biochemical assays predicted a weak to moderate inhibitory activity of clinically relevant concentrations of silibinin against CYP3A4 when compared with recommended (rosuvastatin) and non-recommended (simvastatin) statins for lorlatinib-associated dyslipidemia. The elevated plasma cholesterol and triglyceride levels in lorlatinib-treated lung cancer patients might involve primary alterations in the hepatic accumulation of lipid intermediates. Silibinin could be clinically explored to reduce the undesirable hyperlipidemic activity of lorlatinib in lung cancer patients.
Novel Triterpenic Acid—Benzotriazole Esters Act as Pro-Apoptotic Antimelanoma Agents
Authors: Mioc Marius , Mioc Alexandra , Prodea Alexandra , Milan Andreea , Balan-Porcarasu Mihaela , Racoviceanu Roxana , Ghiulai Roxana , Iovanescu Gheorghe , Macasoi Ioana , Draghici George , Dehelean Cristina , Soica Codruta
Published: September 2022

Pentacyclic triterpenes, such as betulinic, ursolic, and oleanolic acids are efficient and selective anticancer agents whose underlying mechanisms of action have been widely investigated. The introduction of N-bearing heterocycles (e.g., triazoles) into the structures of natural compounds (particularly pentacyclic triterpenes) has yielded semisynthetic derivatives with increased antiproliferative potential as opposed to unmodified starting compounds. In this work, we report the synthesis and biological assessment of benzotriazole esters of betulinic acid (BA), oleanolic acid (OA), and ursolic acid (UA) (compounds 1–3). The esters were obtained in moderate yields (28–42%). All three compounds showed dose-dependent reductions in cell viability against A375 melanoma cells and no cytotoxic effects against healthy human keratinocytes. The morphology analysis of treated cells showed characteristic apoptotic changes consisting of nuclear shrinkage, condensation, fragmentation, and cellular membrane disruption. rtPCR analysis reinforced the proapoptotic evidence, showing a reduction in anti-apoptotic Bcl-2 expression and upregulation of the pro-apoptotic Bax. High-resolution respirometry studies showed that all three compounds were able to significantly inhibit mitochondrial function. Molecular docking showed that compounds 1–3 showed an increase in binding affinity against Bcl-2 as opposed to BA, OA, and UA and similar binding patterns compared to known Bcl-2 inhibitors.
Dynamic and Static Switching in ITO/SnOx/ITO and Its Synaptic Application
Authors: Park Jongmin , Park Hyunwoong , Chung Daewon , Kim Sungjun
Published: September 2022

The attempts to devise networks that resemble human minds are steadily progressing through the development and diversification of neural networks (NN), such as artificial NN (ANN), convolution NN (CNN), and recurrent NN (RNN). Meanwhile, memory devices applied on the networks are also being studied together, and RRAM is the one of the most promising candidates. The fabricated ITO/SnOX/TaN device showed two forms of current–voltage (I-V) curves, classified as dynamic and static. It was triggered from the forming process, and the difference between the two curves resulted from the data retention measured at room temperature for 103 s. The dynamic curve shows a time-dependent change in the data, and the cause of the data preservation period was considered through X-ray photoelectron spectroscopy (XPS) and linear fitting in conduction mechanisms. To confirm whether the memory performance of the device may be implemented on the synapse, the change in the plasticity was confirmed using a rectangular-shaped pulse. Paired-pulse facilitation (PPF) was implemented, and the change from short-term potentiation (STP) to long-term potentiation (LTP) was achieved.