bluuebunny/crossref_metadata_2025 huggingface dataset:
Sustainability Research in the Wine Industry: A Bibliometric Approach
Authors: Montalvo-Falcón Johnny Vicente , Sánchez-García Eduardo , Marco-Lajara Bartolomé , Martínez-Falcó Javier
Published: March 2023

Currently, the wine industry has gained great relevance worldwide. At the same time, the sustainability of the business activity has positioned itself as one of the main challenges to be achieved in the coming years. Due to the great impact that agricultural processes can have on the environment, vine and wine production is particularly susceptible to the application of new technologies and processes that improve its sustainability in the medium and long term, while allowing the improvement of product quality. The main objective of this paper is to analyze the academic literature in the field of wine industry sustainability, to determine the main contributions carried out, as well as the most prominent authors, universities, and countries in this field of study. The methodology used is bibliometric analysis, specifically the Bibliometrix® R package, in its version 4.1.1. The results reveal that research in the field of sustainability in the wine industry has increased considerably in the last three years by several leading researchers, mainly from universities located in wine-producing regions. It is concluded that research shows a trend towards collaboration among stakeholders, especially in terms of innovation, which is postulated as the main tool to improve the sustainability of the sector in the coming years.
Presumed Presence of Extensor Indicis et Digiti Medii Communis Muscle in a 70-Year-Old White Male Donor
Authors: Penkwitz Isabella , Wind Gary , Maynes Elizabeth , Leighton Maria Ximena , Granite Guinevere
Published: March 2023

Forearm extensor muscle variations can be diverse and, in some instances, rare. During a routine anatomical dissection of human cadaveric donors during the 2021 first-year medical gross anatomy course and 2021 graduate nursing advanced anatomy course at the Uniformed Services University of the Health Sciences, bilateral agenesis of the extensor carpi ulnaris muscle was noted in one 70-year-old white male donor. This variation is described as extremely rare in the literature. The presence of an extensor indicis et digiti medii tendon, a variant of the extensor indicis tendon, appeared to be evident in post-dissection photographs on the left hand. The presence of a duplicated extensor indicis proprious tendon appears to be evident on the right hand. However, further inspection of this region was impeded as the body was sent for cremation prior to the variation being identified. The presence of various juncturae tendinum was also noted bilaterally. Reported prevalence of extensor indicis muscle variants ranges from 0.75% to 13%, depending on the specific type or grouping of variations observed. Knowledge of variations in the extensor compartment of the forearm and wrist is crucial for orthopedic surgeons and specialists. Alteration of surgical approaches may be necessary if such a variation is present. Such variations can be options for grafts, resulting in minimal functional change to the grafted area due to the continued existence of other muscles performing similar functions. Knowledge of such variations, and alternative, synonymous names for them, is also important for anatomy instructors, who may need to assist students in identifying these rare variations during anatomical dissection.
The Power of Discourse: Associations between Trainers’ Speech and the Responses of Socialized Wolves and Dogs to Training
Authors: Fonseca Melissa Gabriela Bravo , Hilário Heron Oliveira , Kotrschal Kurt , Range Friederike , Virányi Zsófia , Duarte Marina Henriques Lage , Pereira Laryssa Cristina Gomes , Vasconcellos Angélica da Silva
Published: March 2023

In a previous study, we found that Positive Reinforcement Training reduced cortisol of wolves and dogs; however, this effect varied across trainer–animal dyads. Here we investigate whether and how the trainers’ use of speech may contribute to this effect. Dogs’ great interest in high-pitched, intense speech (also known as Dog Directed Speech) has already been reported, but whether and how wolves respond similarly/differently to voice characteristics has never been studied before. We analyzed 270 training sessions, conducted by five trainers, with nine mixed-breed dogs and nine wolves, all human-socialized. Through Generalized Linear Mixed Models, we analyzed the effects of (a) three speech categories (nice, neutral, reprehensive) and laugh; and (b) acoustic characteristics of trainers’ voices on animals’ responses (correct responses, latency, orientation, time at less than 1 m, non-training behaviors, tail position/movements, cortisol variation). In both subspecies, tail wagging occurred more often in sessions with longer durations of nice speech, and less often in sessions with reprehensive speech. For dogs, the duration of reprehensive speech within a session was also negatively related to correct responses. For wolves, retreat time was associated with more reprehensive speech, whereas duration of nice speech was positively associated with time spent within one meter from the trainer. In addition, most dog behavioral responses were associated with higher average intonations within sessions, while wolf responses were correlated with lower intonations within sessions. We did not find any effects of the variables considered on cortisol variation. Our study highlights the relevance of voice tone and speech in a training context on animals’ performances and emotional reactions.
Perchlozone Resistance in Clinical Isolates of Mycobacterium tuberculosis
Authors: Ushtanit Anastasia , Mikhailova Yulia , Krylova Ludmila , Grigorash Dmitry , Makarova Marina , Safonova Svetlana , Zimenkov Danila
Published: March 2023

The emergence of drug-resistant tuberculosis forced the development of new drugs and the screening of more effective or less toxic analogues. Mycolic acid biosynthesis is targeted by several antituberculosis drugs, isoniazid being one of the most important in tuberculosis therapy. Recently, perchlozone, acting on another step in the FAS-II cycle, was officially approved for tuberculosis treatment in the Russian Federation and was included in the Russian national clinical guidelines. Using the serial dilution method on 7H10 agar plates for perchlozone and a Sensititre MYCOTB microdilution plate, we analyzed the phenotypic properties of primary clinical isolates of M. tuberculosis and analyzed the molecular determinants of resistance to isoniazid, ethionamide, and perchlozone. We found a wide variation in the MIC of perchlozone from 2 to 64 mg/L, correlating with the overall resistance profile: the MIC was higher for MDR and pre-XDR isolates. The cross-resistance between ethionamide and perchlozone was driven by mutations in the ethA gene encoding monooxygenase responsible for the activation of both drugs. The presumably susceptible to perchlozone and wild-type strains had MICs ranging from 2 to 4 mg/L, and the breakpoint was estimated to be 4 or 8 mg/L. In conclusion, susceptibility to perchlozone is retained for a part of the MDR strains, as is susceptibility to ethionamide, providing the possibility of therapy for such cases based on phenotypic or molecular analysis.
The 2022 Seismic Sequence in the Northern Adriatic Sea and Its Long-Term Simulation
Authors: Console Rodolfo , Vannoli Paola , Carluccio Roberto
Published: March 2023

We studied the long-term features of earthquakes caused by a fault system in the northern Adriatic sea that experienced a series of quakes beginning with two main shocks of magnitude 5.5 and 5.2 on 9 November 2022 at 06:07 and 06:08 UTC, respectively. This offshore fault system, identified through seismic reflection profiles, has a low slip rate of 0.2–0.5 mm/yr. As the historical record spanning a millennium does not extend beyond the inter-event time for the largest expected earthquakes (M≃6.5), we used an earthquake simulator to generate a 100,000-year catalogue with 121 events of Mw≥5.5. The simulation results showed a recurrence time (Tr) increasing from 800 yrs to 1700 yrs as the magnitude threshold increased from 5.5 to 6.5. However, the standard deviation σ of inter-event times remained at a stable value of 700 yrs regardless of the magnitude threshold. This means that the coefficient of variation (Cv=σ/Tr) decreased from 0.9 to 0.4 as the threshold magnitude increased from 5.5 to 6.5, making earthquakes more predictable over time for larger magnitudes. Our study supports the use of a renewal model for seismic hazard assessment in regions of moderate seismicity, especially when historical catalogues are not available.
Seismotectonics, Geomorphology and Paleoseismology of the Doroud Fault, a Source of Seismic Hazard in Zagros
Authors: Kamali Zahra , Nazari Hamid , Rashidi Ahmad , Heyhat Mahmoud Reza , Khatib Mohammad Mahdi , Derakhshani Reza
Published: March 2023

In this study, the active tectonics, paleoseismicity, and seismic hazards of the Doroud Fault are examined through high-resolution satellite image interpretations, field investigations, outcrop and trench excavations, and the dating of geochronology samples. The Doroud Fault (DF), one of the essential segments of the Main Recent Fault in the northern margin of the Zagros mountain range, has a historical and instrumental background of high seismicity. We present the first constraints from tectonic geomorphology and paleoseismology along the Doroud Fault near the capital city of Dorud. Detailed observations from satellite imagery, field investigations, real-time kinematic (RTK) measurements, paleoseismological trenching, the radiocarbon (C14), and optically stimulated luminescence (OSL) as ages allowed us to map the fault in detail, describe and characterize its kinematics, and document its recent activity and seismic behavior (cumulative displacements, paleoseismicity, and magnitude, as well as recurrence interval) relevant to the recent seismic activity of the Doroud Fault during the late Holocene as one of the most important seismogenic faults in Zagros. Modern alluvial terraces of gullies and loess accumulations are systematically deflected and/or offset with co-seismic rupture, landslides, and scarps, indicating that the Doroud Fault has been active in the late Quaternary and is characterized by dextral strike–slip movements with a normal component. In addition, our findings provide a comprehensive analysis of the fault displacement, the timing of paleoearthquakes, and the right-lateral slip rate of the Doroud Fault. The late Holocene slip rate of the Doroud Fault using the OSL dating the gully is as follows: the minimum and maximum horizontal slip rates are estimated to be 1.82 and 2.71 mm/yr, and vertical slip rates of 1.03 and 1.53 mm/yr are calculated for the past 4600 ± 900 years in the middle segment of the fault. This study focused on a paleoseismological trench within the archeological sites of Darbe-Astaneh. The central portion of the fault has historically hosted more than nine earthquakes in the last 66 ka years, according to the study’s findings. According to paleoseismology studies, the Doroud Fault has the seismic capability to cause earthquakes with a magnitude of more than 7.4 and a total slip rate of about 3.83 ± 0.1 m. The average recurrence interval for the identified paleoearthquakes is approximately 104 ± 7 years.
A Study of Wind Shear Influences on the Aerodynamic Performances of a UAV Airfoil
Authors: Yang Yin , Liu Dawei , Lu Lianshan
Published: March 2023

In order to study the flight strategies of birds in shear wind and realize the long-range flight of an unmanned aerial vehicle (UAV), the aerodynamic performances of a UAV’s airfoil under different shear wind are studied using numerical methods. The results are calculated using the RANS method in shear wind with a linear and logarithmic distribution of velocity. The results show that the slope of the lift curve, the maximum lift coefficient and the stall angle decrease when the velocity gradient is positive or increasing, conversely, they increase at a negative gradient compared to gradient-free wind fields. A positive gradient of wind significantly increased the maximum lift-drag ratio and the effective angle of attack. Compared with linear distributed shear wind with the same velocity at both the lowest and highest points of the flow field, logarithmic distribution decreases the slope of the lift curve, the maximum lift coefficient and the maximum lift-drag ratio and the effective angle of attack. Therefore, a shear wind with a positive gradient is beneficial to the increase of lift-drag ratio and more conducive to cruise flight, and a negative gradient is beneficial for increased lift and more conducive to take-off and landing of UAVs. The velocity distributions influence the aerodynamic performances of the airfoil which is related to the speed and gradient distribution of shear wind.
A Methodology for Continuous Monitoring of Rail Corrugation on Subway Lines Based on Axlebox Acceleration Measurements
Authors: Faccini Leonardo , Karaki Jihad , Di Gialleonardo Egidio , Somaschini Claudio , Bocciolone Marco , Collina Andrea
Published: March 2023

Rail corrugation is a degradation phenomenon that manifests as a quasi-periodic irregularity on the running surface of the rail. It is a critical problem for urban railway lines because it induces ground-borne vibrations transmitted to the buildings near the infrastructure, causing complaints from the inhabitants. A typical treatment to mitigate the rail corrugation problem is the periodic grinding of the rails, performed by dedicated vehicles. The scheduling of rail maintenance is particularly critical because it can be performed only when the service is interrupted. A procedure for the continuous monitoring of rail corrugation is proposed, based on axlebox acceleration measurements. The rail irregularity is estimated from the measured acceleration by means of a frequency domain model of vertical dynamics of the wheel–rail interaction. The results obtained by using two different methods (a state-of-the-art method and a new one) are compared. Finally, the study of the evolution of the power content of the rail irregularity enables the identification of the track sections where corrugation is developing and rail grinding is necessary.
Advanced CT Imaging, Radiomics, and Artificial Intelligence to Evaluate Immune Checkpoint Inhibitors’ Effects on Metastatic Renal Cell Carcinoma
Authors: Greco Federico , Beomonte Zobel Bruno , Di Gennaro Gianfranco , Mallio Carlo Augusto
Published: March 2023

Advances in the knowledge of renal cell carcinoma (RCC)’s oncogenesis have led to the development of new therapeutic approaches, such as immune checkpoint inhibitors (ICIs), which have improved the clinical outcomes of metastatic RCC (mRCC) patients. Our literature search led to a series of studies that were divided into four subcategories: RECIST criteria, radiomics and artificial intelligence, atypical response patterns, and body composition. These studies provide novel and promising data aimed at improving patient management and clinical outcomes, further strengthening the concept of precision medicine. Radiomics and artificial intelligence allow us to obtain—in a non-invasive fashion—a multitude of data that cannot be detected with the naked eye, offering potential advantages that might help to predict the response to treatments and possibly improve patients’ outcomes through a personalized therapeutic approach. The purpose of this literature review is to describe the available evidence on the role of computed tomography (CT) in evaluating and predicting ICIs’ effects on mRCC patients by applying radiomics and artificial intelligence.
Applied Radiation Chemistry: Theory, Methods and Applications
Authors: Swiatla-Wojcik Dorota , Katsumura Yosuke , Wach Radoslaw A.
Published: March 2023

Radiation chemistry deals with chemical processes initiated by the interaction of high-energy photons (X-rays) or charged particles (electrons, protons, alpha or heavy ions) with matter [...]
URANS Simulations of Vehicle Exhaust Plumes with Insight on Remote Emission Sensing
Authors: Plogmann Justin , Stauffer Christian , Dimopoulos Eggenschwiler Panayotis , Jenny Patrick
Published: March 2023

Remote Emission Sensing (RES) is a measurement method based on absorption spectroscopy for the determination of pollutant concentrations. The absorption of the exhaust plume of a vehicle is measured from the roadside without intervention by means of a light/laser barrier during a short measurement (∼0.5 s) and concentration ratios of pollutants (e.g., NOx to CO2) are estimated. Unsteady Reynolds-Averaged Navier-Stokes (URANS) simulations of exhaust plumes in vehicle wakes are performed using the k-ω SST turbulence model with focus on pollutant dispersion. The simulation setup has been validated by a comparison with experimentally obtained drag coefficients. The resulting concentration fields represent the pollutants available for measurements by a RES device. The influence of the characteristics of the RES device on the measurement is assessed. In addition, investigations involve several environmental and vehicle related parameters. The results demonstrate that due to strong turbulence, mixing is enhanced and the exhaust plumes rapidly disperse in the near vehicle wakes. Results show that emission characteristics of a vehicle are contained downstream for approximately half the vehicle length, regardless of different vehicle configurations, driving and ambient parameters. Further downstream dispersion of pollutants results in concentrations that are less than 1/100 of the pollutant concentration in the vehicle’s exhaust tailpipe implying that RES devices have to measure at a high sampling frequency. Therefore, reliable determination of the concentration ratios of pollutant at high vehicle velocities requires the RES device to operate in the order of 1000 Hz sampling frequency. Ultimately, the numerical simulations not only help to understand exhaust plume dispersion, but provide a very useful tool to minimize RES uncertainties.
Thermodynamics of Evaporation from the Ocean Surface
Authors: Feistel Rainer , Hellmuth Olaf
Published: March 2023

Adopted by the Intergovernmental Oceanographic Commission (IOC) of UNESCO in 2010 and the International Union of Geodesy and Geophysics (IUGG) in 2011, the Thermodynamic Equation of Seawater 2010 (TEOS-10) is the current geophysical standard for the thermodynamic properties of humid air, seawater and ice. TEOS-10 equations for evaporation and sublimation enthalpies are derived mathematically from the thermodynamic potential of a »sea air« model, denoting a multi-phase equilibrium composite of the geophysical aqueous mixtures. To estimating evaporation rates from the ocean, Dalton equations in various versions are implemented in numerical climate models. Some of those equations appear to be biased on climatic time scales if compared with proper thermodynamic driving forces. Such equations may lead to a spurious amplification of the hydrological cycle and an implied effect of cooling oceans. As an unbiased alternative, Dalton equations are proposed in terms of TEOS-10 relative fugacity (RF) or its conventional relative humidity (RH) approximations. With respect to RH uncertainties or trends, the substantial sensitivity of the evaporation flux may be estimated to be as much as 5 W m−2 per 1 %rh. Within a maximum error of only 0.04 %rh, sea-surface RF may be approximated in terms of dew-point or frost-point temperatures using a simple formula.
Evaluation of Respiratory, Genotoxic and Cytotoxic Effects from Occupational Exposure to Typography Activities
Authors: Linhares Diana , Rocha Joana , Rodrigues Armindo , Camarinho Ricardo , Garcia Patrícia
Published: March 2023

This cross-sectional study was structured to allow the evaluation of the respiratory, genotoxic, and cytotoxic effects of occupational exposure to products resulting from the activity of printers in typographies and, to determine the risk of genotoxicity associated with such exposure. This study comprised 69 subjects, 25 individuals occupationally exposed to the products of typographies (study group), and 44 individuals non-exposed to the environment studied (reference group). The frequency of micronucleated cells and other nuclear anomalies (binucleated, karyolitic, pyknotic, and karyorrhectic cells) in the oral epithelia of each subject were analyzed. The frequency of micronucleated cells was significantly higher in the study group when compared to the reference one (12.96 MN/2000 cells vs. 4MN/2000 cells, respectively). Occupational exposure to products of typography is a risk factor for the occurrence of micronucleated cells in the study group (RR = 3.2; 95% CI, 2.7–3.9; p < 0.001). The results of the spirometry test did not reveal significant respiratory effects between the reference and study groups.
Analysis of ℝ=P[Y<X<Z] Using Ranked Set Sampling for a Generalized Inverse Exponential Model
Authors: Hassan Amal S. , Alsadat Najwan , Elgarhy Mohammed , Chesneau Christophe , Nagy Heba F.
Published: March 2023

In many real-world situations, systems frequently fail due to demanding operating conditions. In particular, when systems reach their lowest, highest, or both extremes operating conditions, they usually fail to accomplish their intended functions. This study considers estimating the stress–strength reliability, for a component with a strength (X) that is independent of the opposing lower bound stress (Y) and upper bound stress (Z). We assumed that the strength and stress random variables followed a generalized inverse exponential distribution with different shape parameters. Under ranked set sampling (RSS) and simple random sampling (SRS) designs, we obtained four reliability estimators using the maximum likelihood method. The first and second reliability estimators were deduced when the sample data of the strength and stress distributions used the sample design (RSS/SRS). The third reliability estimator was determined when the sample data for Y and Z were received from the RSS and the sample data for X were taken from the SRS. The fourth reliability estimator was derived when the sample data of Y and Z were selected from the SRS, while the sample data of X were taken from the RSS. The accuracy of the suggested estimators was compared using a comprehensive computer simulation. Lastly, three real data sets were used to determine the reliability.
Immediate Effects of Whole-Body versus Local Dynamic Electrostimulation of the Abdominal Muscles in Healthy People Assessed by Ultrasound: A Randomized Controlled Trial
Authors: Álvarez-Barrio Lorena , Rodríguez-Pérez Vicente , Calvo-Lobo César , Leirós-Rodríguez Raquel , Alba-Pérez Eduardo , López-Rodríguez Ana Felicitas
Published: March 2023

Dynamic electrostimulation consists of the application of local or global electrostimulation together with physical exercise. This study aimed to investigate the immediate effects of a dynamic electrostimulation session on the thickness of the abdominal musculature, inter-rectus distance, heart rate, blood pressure, and body temperature, and to identify possible differences in its form of application. A total of 120 healthy participants were divided into three groups: the whole-body electrostimulation group, the local electrostimulation group, and the control group without electrical stimulation. All groups performed a single session with the same dynamic exercise protocol. Muscle thickness and inter-rectus distance were evaluated ultrasonographically using the Rehabilitative Ultrasound Imaging technique both at rest and in muscle contraction (the active straight leg raise test) to find the post-intervention differences. The results showed significant differences in immediate post-intervention heart rate, with a smaller increase in the local electrostimulation group compared to the control and whole-body electrostimulation groups. No significant differences were identified between the groups after the interventions in the rest of the variables analyzed. Therefore, a local application, with the same effects as a global application on the abdominal musculature, has fewer contraindications, which makes its use more advisable, especially in populations with cardiorespiratory disorders, for which more research is needed.
Biomarker Detection in Early Diagnosis of Cancer: Recent Achievements in Point-of-Care Devices Based on Paper Microfluidics
Authors: Asci Erkocyigit Bilge , Ozufuklar Ozge , Yardim Aysenur , Guler Celik Emine , Timur Suna
Published: March 2023

Microfluidics is very crucial in lab-on-a-chip systems for carrying out operations in a large-scale laboratory environment on a single chip. Microfluidic systems are miniaturized devices in which the fluid behavior and control can be manipulated on a small platform, with surface forces on the platform being greater than volumetric forces depending on the test method used. In recent years, paper-based microfluidic analytical devices (μPADs) have been developed to be used in point-of-care (POC) technologies. μPADs have numerous advantages, including ease of use, low cost, capillary action liquid transfer without the need for power, the ability to store reagents in active form in the fiber network, and the capability to perform multiple tests using various measurement techniques. These benefits are critical in the advancement of paper-based microfluidics in the fields of disease diagnosis, drug application, and environment and food safety. Cancer is one of the most critical diseases for early detection all around the world. Detecting cancer-specific biomarkers provides significant data for both early diagnosis and controlling the disease progression. μPADs for cancer biomarker detection hold great promise for improving cure rates, quality of life, and minimizing treatment costs. Although various types of bioanalytical platforms are available for the detection of cancer biomarkers, there are limited studies and critical reviews on paper-based microfluidic platforms in the literature. Hence, this article aims to draw attention to these gaps in the literature as well as the features that future platforms should have.
The Synergy between Deep Learning and Organs-on-Chips for High-Throughput Drug Screening: A Review
Authors: Dai Manna , Xiao Gao , Shao Ming , Zhang Yu Shrike
Published: March 2023

Organs-on-chips (OoCs) are miniature microfluidic systems that have arguably become a class of advanced in vitro models. Deep learning, as an emerging topic in machine learning, has the ability to extract a hidden statistical relationship from the input data. Recently, these two areas have become integrated to achieve synergy for accelerating drug screening. This review provides a brief description of the basic concepts of deep learning used in OoCs and exemplifies the successful use cases for different types of OoCs. These microfluidic chips are of potential to be assembled as highly potent human-on-chips with complex physiological or pathological functions. Finally, we discuss the future supply with perspectives and potential challenges in terms of combining OoCs and deep learning for image processing and automation designs.
Standardization of Strategies to Perform a Parafascicular Tubular Approach for the Resection of Brain Tumors in Eloquent Areas
Authors: Abdala-Vargas Nadin J. , Umana Giuseppe E. , Patiño-Gomez Javier G. , Ordoñez-Rubiano Edgar , Cifuentes-Lobelo Hernando A. , Palmisciano Paolo , Ferini Gianluca , Viola Anna , Zagardo Valentina , Casanova-Martínez Daniel , Tomasi Ottavio S. , Campero Alvaro , Baldoncini Matias
Published: March 2023

Objective: The aim of this work is to define a methodological strategy for the minimally invasive tubular retractor (MITR) parafascicular transulcal approach (PTA) for the management of brain tumors sited in eloquent areas. Methods: An observational prospective study was designed to evaluate the benefits of PTA associated with MITRs, tractography and intraoperative cortical stimulation. They study was conducted from June 2018 to June 2021. Information regarding white matter tracts was processed, preventing a potential damage during the approach and/or resection. All patients older than 18 years who had a single brain tumor lesion were included in the study. Patients with a preoperative Karnofsky Performance Scale (KPS) score greater than 70% and a Glasgow Coma Scale (GCS) score > 14 points were included. Results: 72 patients were included in the study, the mean age was 49.6, the most affected gender was male, 12.5% presented aphasia, 11.1% presented paraphasia, 41.6% had motor deficit, 9.7% had an affection in the optic pathway, the most frequently affected region was the frontal lobe (26.3%), the most frequent lesions were high-grade gliomas (34.7%) and the measurement of the incisions was on average 5.58 cm. Of the patients, 94.4% underwent a total macroscopic resection and 90.2% did not present new postoperative neurological deficits. In all cases, a PTA was used. Conclusion: Tubular minimally invasive approaches (MIAs) allow one to perform maximal safe resection of brain tumors in eloquent areas, through small surgical corridors. Future comparative studies between traditional and minimally invasive techniques are required to further investigate the potential of these surgical nuances.
Factors Influencing Adoption of Digital Twin Advanced Technologies for Smart City Development: Evidence from Malaysia
Authors: Waqar Ahsan , Othman Idris , Almujibah Hamad , Khan Muhammad Basit , Alotaibi Saleh , Elhassan Adil A. M.
Published: March 2023

Digital Twin Technology (DTT) has gained significant attention as a vital technology for the efficient management of smart cities. However, its successful implementation in developing countries is often hindered by several barriers. Despite limited research available on smart city development in Malaysia, there is a need to investigate the possible challenges that could affect the effective implementation of DTT in the country. This study employs a mixed methodology research design, comprising an interview, a pilot survey, and the main survey. Firstly, we identified barriers reported in the literature and excluded insignificant factors through interviews. Next, we conducted an Exploratory Factor Analysis (EFA) on the pilot survey results to further refine the factors. Finally, we performed a Structural Equation Modeling (SEM) analysis on the main survey data to develop a model that identifies barriers to DTT implementation in smart city development in Malaysia. Our findings suggest the presence of 13 highly significant barriers, which are divided into four formative constructs. We found that personalization barriers are highly crucial, while operational barriers were less important for DTT implementation in smart city development in Malaysia.
The Vault Complex Is Significantly Involved in Therapeutic Responsiveness of Endocrine Tumors and Linked to Autophagy under Chemotherapeutic Conditions
Authors: Bornstein Stefan , Shapiro Igor , Mazumdar Alekhya , Zitzmann Kathrin , Nölting Svenja , Luca Edlira , Beuschlein Felix , Sharma Ashish , Hantel Constanze
Published: March 2023

Cancers display dynamic interactions with their complex microenvironments that influence tumor growth, invasiveness, and immune evasion, thereby also influencing potential resistance to therapeutic treatments. The tumor microenvironment (TME) includes cells of the immune system, the extracellular matrix, blood vessels, and other cell types, such as fibroblasts or adipocytes. Various cell types forming this TME secrete exosomes, and molecules thereby released into the TME have been shown to be important mediators of cellular communication and interplay. Specific stressors in the TME, such as hypoxia, starvation, inflammation, and damage, can furthermore induce autophagy, a fundamental cellular process that degrades and recycles molecules and subcellular components, and recently it has been demonstrated that the small non-coding vault RNA1-1 plays a role as a regulator of autophagy and the coordinated lysosomal expression and regulation (CLEAR) network. Here, we demonstrate for the first time that intra-tumoral damage following effective therapeutic treatment is linked to specific intracellular synthesis and subsequent exosomal release of vault RNAs in endocrine tumors in vitro and in vivo. While we observed a subsequent upregulation of autophagic markers under classical chemotherapeutic conditions, a downregulation of autophagy could be detected under conditions strongly involving inflammatory cascades.
Exercise Intervention for Bone Metastasis: Safety, Efficacy and Method of Delivery
Authors: Duong Huong , Walker Meegan , Maugham-Macan Michelle
Published: March 2023

Background: The benefits of exercise for patients with cancer are well-established, however, for patients with bone metastases, exercise as adjuvant therapy is underutilised due to concerns for safety, efficacy and other barriers such as the method of delivery. This scoping review explores these barriers by reviewing the results of clinical trials conducted on participants with bone metastases. Methods: A thorough literature search was undertaken using PubMed, Scopus, NIH Clinical Trials and Google Scholar databases. Articles that involved an exercise intervention and patients with bone metastases were included. Data were pooled, charted, analysed and reported according to PRISMA-ScR standards. Results: A total of 26 trials were reviewed with interventions that included aerobic and resistance training. Only three serious adverse events occurred, not likely related to bone metastases. Nine trials (34.6%) involved unsupervised exercise sessions. Remote exercise delivery had an average of 80.3% compliance, rivalling in-person and mixed supervision. The results of this review reaffirm that exercise helps improve functional capacity, muscle strength, lean mass and cardiovascular function, and is safe in patients with bone metastases irrespective of in-person or remote delivery. Conclusions: Exercise therapy, whether delivered in person or remotely, is safe and efficacious for patients with bone metastases.
Re-Whole Brain Radiotherapy for Brain Metastases: How to Evaluate an Outcome of Repeat Treatment When Its First Use Is Debatable
Authors: Kępka Lucyna
Published: March 2023

Recently, a review on a pertinent issue of repeat whole-brain radiotherapy (re-WBRT) for recurring brain metastases was published [...]
Deregulated Gene Expression Profiles and Regulatory Networks in Adult and Pediatric RUNX1/RUNX1T1-Positive AML Patients
Authors: Kanellou Peggy , Georgakopoulos-Soares Ilias , Zaravinos Apostolos
Published: March 2023

Acute myeloid leukemia (AML) is a heterogeneous and complex disease concerning molecular aberrations and prognosis. RUNX1/RUNX1T1 is a fusion oncogene that results from the chromosomal translocation t(8;21) and plays a crucial role in AML. However, its impact on the transcriptomic profile of different age groups of AML patients is not completely understood. Here, we investigated the deregulated gene expression (DEG) profiles in adult and pediatric RUNX1/RUNX1T1-positive AML patients, and compared their functions and regulatory networks. We retrospectively analyzed gene expression data from two independent Gene Expression Omnibus (GEO) datasets (GSE37642 and GSE75461) and computed their differentially expressed genes and upstream regulators, using limma, GEO2Enrichr, and X2K. For validation purposes, we used the TCGA-LAML (adult) and TARGET-AML (pediatric) patient cohorts. We also analyzed the protein–protein interaction (PPI) networks, as well as those composed of transcription factors (TF), intermediate proteins, and kinases foreseen to regulate the top deregulated genes in each group. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways enrichment analyses were further performed for the DEGs in each dataset. We found that the top upregulated genes in (both adult and pediatric) RUNX1/RUNX1T1-positive AML patients are enriched in extracellular matrix organization, the cell projection membrane, filopodium membrane, and supramolecular fiber. Our data corroborate that RUNX1/RUNX1T1 reprograms a large transcriptional network to establish and maintain leukemia via intricate PPI interactions and kinase-driven phosphorylation events.
Multidisciplinary Approach to Spinal Metastases and Metastatic Spinal Cord Compression—A New Integrative Flowchart for Patient Management
Authors: Esperança-Martins Miguel , Roque Diogo , Barroso Tiago , Abrunhosa-Branquinho André , Belo Diogo , Simas Nuno , Costa Luis
Published: March 2023

Metastatic spine disease (MSD) and metastatic spinal cord compression (MSCC) are major causes of permanent neurological damage and long-term disability for cancer patients. The development of MSD is pathophysiologically framed by a cooperative interaction between general mechanisms of bone growth and specific mechanisms of spinal metastases (SM) expansion. SM most commonly affects the thoracic spine, even though multiple segments may be affected concomitantly. The great majority of SM are extradural, while intradural-extramedullary and intramedullary metastases are less frequently seen. The management of patients with SM is particularly complex and challenging, with multiple factors—such as the spinal stability status, primary tumor radio and chemosensitivity, cancer biological burden, patient performance status and comorbidities, and patient’s oncological prognosis—influencing the clinical decision-making process. Different frameworks were developed in order to systematize and support this process. A multidisciplinary, personalized approach, enriched by the expertise of each involved specialty, is crucial. We reviewed the most recent evidence and proposed an updated algorithmic approach to patients with MSD according to the clinical scenario of each patient. A flowchart-based approach offers an evidence-based management of MSD, providing a valuable clinical decision tool in a context of high uncertainty and quick-acting need.
Chemoresistive Nanosensors Employed to Detect Blood Tumor Markers in Patients Affected by Colorectal Cancer in a One-Year Follow Up
Authors: Astolfi Michele , Rispoli Giorgio , Anania Gabriele , Zonta Giulia , Malagù Cesare
Published: March 2023

Colorectal cancer (CRC) represents 10% of the annual tumor diagnosis and deaths occurring worldwide. Given the lack of specific symptoms, which could determine a late diagnosis, the research for specific CRC biomarkers and for innovative low-invasive methods to detect them is crucial. Therefore, on the basis of previously published results, some volatile organic compounds (VOCs), detectable through gas sensors, resulted in particularly promising CRC biomarkers, making these sensors suitable candidates to be employed in CRC screening devices. A new device was employed here to analyze the exhalations of blood samples collected from CRC-affected patients at different stages of their pre- and post-surgery therapeutic path, in order to assess the sensor’s capability for discriminating among these samples. The stages considered were: the same day of the surgical treatment (T1); before the hospital discharge (T2); after one month and after 10–12 months from surgery (T3 and T4, respectively). This device, equipped with four different sensors based on different metal–oxide mixtures, enabled a distinction between T1 and T4 with a sensitivity and specificity of 93% and 82%, respectively, making it suitable for clinical follow-up protocols, patient health status monitoring and to detect possible post-treatment relapses.
Correlation between Key Steps and Hydricity in CO2 Hydrogenation Catalysed by Non-Noble Metal PNP-Pincer Complexes
Authors: Moni Snehasis , Mondal Bhaskar
Published: March 2023

Transition metal-catalysed homogeneous hydrogenation of CO2 to formate or formic acid has emerged as an appealing strategy for the reduction of CO2 into value-added chemicals. Since the state-of-the-art catalysts in this realm are primarily based on expensive precious metals and require demanding reaction conditions, the design and development of economically viable non-noble metal catalysts are in great demand. Herein, we exploit the thermodynamic correlation between the crucial reaction steps of CO2 hydrogenation, that is, base-promoted H2-splitting and hydride transfer to CO2 as a guide to estimate the catalytic efficiency of non-noble metal complexes possessing a ligand backbone containing a secondary amine as an “internal base”. A set of three non-noble metal complexes, one bearing tri-coordinated PNP-pincer (1Mn) and the other two based on tetra-coordinated PNPN-pincer (2Mn and 3Fe), have been investigated in this study. The computational mechanistic investigation establishes the role of the “internal” amine base in heterolytically splitting the metal-bound H2, a critical step for CO2 hydrogenation. Furthermore, the thermodynamic correlation between the hydricity (ΔGH−°) of the in situ generated metal-hydride species and the free energy barrier of the two crucial steps could provide an optimal hydricity value for efficient catalytic activity. Based on the computational estimation of the optimal hydricity value, the tri-coordinated PNP-pincer complex 1Mn appears to be the most efficient among the three, with the other two tetra-coordinated PNPN-pincer complexes, 2Mn and 3Fe, showing promising hydricity values. Overall, this study demonstrates how the crucial thermodynamic and kinetic parameters for pincer-based complexes possessing an “internal base” can be correlated for the prediction of novel non-noble metal-based catalysts for CO2 hydrogenation.
JNK Activation Correlates with Cognitive Impairment and Alteration of the Post-Synaptic Element in the 5xFAD AD Mouse Model
Authors: Priori Erica Cecilia , Musi Clara Alice , Giani Arianna , Colnaghi Luca , Milic Ivana , Devitt Andrew , Borsello Tiziana , Repici Mariaelena
Published: March 2023

The c-Jun N-terminal kinases (JNKs) are a family of proteins that, once activated by stress stimuli, can alter neuronal functions and survival. The JNK cascade plays a crucial role in the post-synaptic neuronal compartment by altering its structural organization and leading, at worst, to an overall impairment of neuronal communication. Increasing evidence suggests that synaptic impairment is the first neurodegenerative event in Alzheimer’s disease (AD). To better elucidate this mechanism, we longitudinally studied 5xFAD mice at three selected time points representative of human AD symptom progression. We tested the mice cognitive performance by using the radial arm water maze (RAWM) in parallel with biochemical evaluations of post-synaptic enriched protein fraction and total cortical parenchyma. We found that 5xFAD mice presented a strong JNK activation at 3.5 months of age in the post-synaptic enriched protein fraction. This JNK activation correlates with a structural alteration of the post-synaptic density area and with memory impairment at this early stage of the disease that progressively declines to cause cell death. These findings pave the way for future studies on JNK as a key player in early neurodegeneration and as an important therapeutic target for the development of new compounds able to tackle synaptic impairment in the early phase of AD pathology.
Neurofilament Levels in Dendritic Spines Associate with Synaptic Status
Authors: Gürth Clara-Marie , do Rego Barros Fernandes Lima Maria Augusta , Macarrón Palacios Victor , Cereceda Delgado Angel Rafael , Hubrich Jasmine , D’Este Elisa
Published: March 2023

Neurofilaments are one of the main cytoskeletal components in neurons; they can be found in the form of oligomers at pre- and postsynapses. How their presence is regulated at the postsynapse remains largely unclear. Here we systematically quantified, by immunolabeling, the occurrence of the neurofilament isoform triplet neurofilament light (NFL), medium (NFM), and heavy (NFH) at the postsynapse using STED nanoscopy together with markers of synaptic strength and activity. Our data show that, within dendritic spines, neurofilament isoforms rarely colocalize with each other and that they are present to different extents, with NFL being the most abundant isoform. The amount of the three isoforms correlates with markers of postsynaptic strength and presynaptic activity to varying degrees: NFL shows the highest correlation to both synaptic traits, suggesting its involvement in synaptic response, while NFM exhibits the lowest correlations. By quantifying the presence of neurofilaments at the postsynapse within the context of the synaptic status, this work sheds new light on the regulation of synaptic neurofilaments and their possible contribution to synaptopathies.
The Heparan Sulfate Proteoglycan Syndecan-1 Triggers Breast Cancer Cell-Induced Coagulability by Induced Expression of Tissue Factor
Authors: Hassan Nourhan , Bückreiß Nico , Efing Janes , Schulz-Fincke Marie , König Philipp , Greve Burkhard , Bendas Gerd , Götte Martin
Published: March 2023

Syndecan-1 (Sdc-1) upregulation is associated with poor prognosis in breast cancer. Sdc-1 knockdown results in reduced angiogenesis and the dysregulation of tissue factor (TF) pathway constituents. Here, we evaluate the regulatory mechanisms and functional consequences of the Sdc-1/TF-axis using Sdc-1 knockdown and overexpression approaches in MCF-7 and MDA-MB-231 breast cancer cells. Gene expression was analyzed by means of qPCR. Thrombin generation and cell migration were detected. Cell-cycle progression and apoptosis were investigated using flow cytometry. In MDA-MB-231 cells, IL6, IL8, VEGF, and IGFR-dependent signaling affected TF pathway expression depending on Sdc-1. Notably, Sdc-1 depletion and TF pathway inhibitor (TFPI) synergistically affected PTEN, MAPK, and STAT3 signaling. At the functional level, the antiproliferative and pro-apoptotic effects of TFPI depended on Sdc-1, whereas Sdc-1’s modulation of cell motility was not affected by TFPI. Sdc-1 overexpression in MCF-7 and MDA-MB-231 cells led to increased TF expression, inducing a procoagulative phenotype, as indicated by the activation of human platelets and increased thrombin formation. A novel understanding of the functional interplay between Sdc-1 and the TF pathway may be compatible with the classical co-receptor role of Sdc-1 in cytokine signaling. This opens up the possibility of a new functional understanding, with Sdc-1 fostering coagulation and platelet communication as the key to the hematogenous metastatic spread of breast cancer cells.
Increased Yield of Extracellular Vesicles after Cytochalasin B Treatment and Vortexing
Authors: Kurbangaleeva Sirina V. , Syromiatnikova Valeriia Y. , Prokopeva Angelina E. , Rogov Aleksey M. , Khannanov Artur A. , Rizvanov Albert A. , Gomzikova Marina O.
Published: March 2023

Extracellular vesicles (EVs) are promising therapeutic instruments and vectors for therapeutics delivery. In order to increase the yield of EVs, a method of inducing EVs release using cytochalasin B is being actively developed. In this work, we compared the yield of naturally occurring extracellular vesicles and cytochalasin B-induced membrane vesicles (CIMVs) from mesenchymal stem cells (MSCs). In order to maintain accuracy in the comparative analysis, the same culture was used for the isolation of EVs and CIMVs: conditioned medium was used for EVs isolation and cells were harvested for CIMVs production. The pellets obtained after centrifugation 2300× g, 10,000× g and 100,000× g were analyzed using scanning electron microscopy analysis (SEM), flow cytometry, the bicinchoninic acid assay, dynamic light scattering (DLS), and nanoparticle tracking analysis (NTA). We found that the use of cytochalasin B treatment and vortexing resulted in the production of a more homogeneous population of membrane vesicles with a median diameter greater than that of EVs. We found that EVs-like particles remained in the FBS, despite overnight ultracentrifugation, which introduced a significant inaccuracy in the calculation of the EVs yield. Therefore, we cultivated cells in a serum-free medium for the subsequent isolation of EVs. We observed that the number of CIMVs significantly exceeded the number of EVs after each step of centrifugation (2300× g, 10,000× g and 100,000× g) by up to 5, 9, and 20 times, respectively.