bluuebunny/crossref_metadata_2025 huggingface dataset:
Social Inclusion: A Factor That Influences the Sustainable Entrepreneurial Behavior of Generation Z
Authors: Burlea-Schiopoiu Adriana , Popovici Norina
Published: March 2024

Young people from Generation Z are a subject of analysis for researchers because they will prevail in the labor market as successors of the Millennial generation. Taking into account the imprint that digitization has left on the behavior of Generation Z, our research aims to analyze how young people manifest their entrepreneurial intention and, mainly, how the “Me generation” perceives entrepreneurship both as a means by which they manifest their desire to control their behavior and as a factor that contributes to their social inclusion. Therefore, based on the bottom-up spillover theory, we propose to analyze the moderating effect of gender and the mediating effect of self-efficacy on the relationship between social inclusion and entrepreneurial intention. Using a quantitative research approach and a sample of 781 representatives of Generation Z, we demonstrate that social inclusion is an essential factor for Generation Z. The findings prove that Generation Z manifests a strong desire for social inclusion, which influences entrepreneurial intention, and that gender moderates this relationship. Finally, the originality of our research consists of the empirical identification of the synergy between entrepreneurial intention, self-efficacy, and the desire for social inclusion of Generation Z.
Applied Hedgehog Conservation Research
Authors: Reeve Nigel , Berger Anne , Rasmussen Sophie Lund
Published: March 2024

Hedgehogs (Order Eulipotyphla, Family Erinaceidae, Subfamily Erinaceinae) are familiar and popular spiny mammals, but they face many challenges in modern human-dominated environments [...]
Antimicrobial and Diagnostic Stewardship of the Novel β-Lactam/β-Lactamase Inhibitors for Infections Due to Carbapenem-Resistant Enterobacterales Species and Pseudomonas aeruginosa
Authors: Ferous Stefanos , Anastassopoulou Cleo , Pitiriga Vassiliki , Vrioni Georgia , Tsakris Athanasios
Published: March 2024

Carbapenem-resistant Gram-negative bacterial infections are a major public health threat due to the limited therapeutic options available. The introduction of the new β-lactam/β-lactamase inhibitors (BL/BLIs) has, however, altered the treatment options for such pathogens. Thus, four new BL/BLI combinations—namely, ceftazidime/avibactam, meropenem/vaborbactam, imipenem/relebactam, and ceftolozane/tazobactam—have been approved for infections attributed to carbapenem-resistant Enterobacterales species and Pseudomonas aeruginosa. Nevertheless, although these antimicrobials are increasingly being used in place of other drugs such as polymyxins, their optimal clinical use is still challenging. Furthermore, there is evidence that resistance to these agents might be increasing, so urgent measures should be taken to ensure their continued effectiveness. Therefore, clinical laboratories play an important role in the judicious use of these new antimicrobial combinations by detecting and characterizing carbapenem resistance, resolving the presence and type of carbapenemase production, and accurately determining the minimum inhibitor concentrations (MICs) for BL/BLIs. These three targets must be met to ensure optimal BL/BLIs use and prevent unnecessary exposure that could lead to the development of resistance. At the same time, laboratories must ensure that results are interpreted in a timely manner to avoid delays in appropriate treatment that might be detrimental to patient safety. Thus, we herein present an overview of the indications and current applications of the new antimicrobial combinations and explore the diagnostic limitations regarding both carbapenem resistance detection and the interpretation of MIC results. Moreover, we suggest the use of alternative narrower-spectrum antibiotics based on susceptibility testing and present data regarding the effect of synergies between BL/BLIs and other antimicrobials. Finally, in order to address the absence of a standardized approach to using the novel BL/BLIs, we propose a diagnostic and therapeutic algorithm, which can be modified based on local epidemiological criteria. This framework could also be expanded to incorporate other new antimicrobials, such as cefiderocol, or currently unavailable BL/BLIs such as aztreonam/avibactam and cefepime/taniborbactam.
Cyanide Insensitive Oxidase Confers Hydrogen Sulfide and Nitric Oxide Tolerance to Pseudomonas aeruginosa Aerobic Respiration
Authors: Nastasi Martina R. , Caruso Lorenzo , Giordano Francesca , Mellini Marta , Rampioni Giordano , Giuffrè Alessandro , Forte Elena
Published: March 2024

Hydrogen sulfide (H2S) and nitric oxide (NO) are long-known inhibitors of terminal oxidases in the respiratory chain. Yet, they exert pivotal signaling roles in physiological processes, and in several bacterial pathogens have been reported to confer resistance against oxidative stress, host immune responses, and antibiotics. Pseudomonas aeruginosa, an opportunistic pathogen causing life-threatening infections that are difficult to eradicate, has a highly branched respiratory chain including four terminal oxidases of the haem-copper type (aa3, cbb3-1, cbb3-2, and bo3) and one oxidase of the bd-type (cyanide-insensitive oxidase, CIO). As Escherichia coli bd-type oxidases have been shown to be H2S-insensitive and to readily recover their activity from NO inhibition, here we tested the effect of H2S and NO on CIO by performing oxygraphic measurements on membrane preparations from P. aeruginosa PAO1 and isogenic mutants depleted of CIO only or all other terminal oxidases except CIO. We show that O2 consumption by CIO is unaltered even in the presence of high levels of H2S, and that CIO expression is enhanced and supports bacterial growth under such stressful conditions. In addition, we report that CIO is reversibly inhibited by NO, while activity recovery after NO exhaustion is full and fast, suggesting a protective role of CIO under NO stress conditions. As P. aeruginosa is exposed to H2S and NO during infection, the tolerance of CIO towards these stressors agrees with the proposed role of CIO in P. aeruginosa virulence.
Performance of Fly-Ash- and Cement-Bound Granular Mixtures with Dispersed Fiber Reinforcement—A Case Study
Authors: Chomicz-Kowalska Anna , Maciejewski Krzysztof
Published: March 2024

This paper investigates the effects of incorporating dispersed fibrous reinforcement in hydraulically bound granular 0/16-mm mixtures. The evaluated fibrous reinforcement comprised a mixture of polypropylene and alkali-resistant glass fibers in a 1:2 weight ratio. The fibrous reinforcement was added to the mixtures in amounts of 0.05% and 0.10% by weight. The prepared mixtures utilized 1% of CEM II/B-V 32.5 R Portland cement together with 3.5%, 7%, and 14% of fly ash, characterized by a high content of reactive calcium oxide. It was found that the fibrous additives had only a small effect on the maximum dry densities and virtually none on the optimum moisture contents of the mixtures. The use of the fiber mix significantly improved the compressive strength of the reinforced samples resulting after 42 days of curing, with a performance comparable to a reference mixture bound with 8% of Portland cement. The addition of fibrous reinforcement increased the indirect tensile strength of the mixtures by up to 300%, resulting in a performance similar to that of a reference mixture with 5% of Portland cement. It was found that the use of this particular fibrous reinforcement significantly improved the performance of predominantly fly-ash-bound granular mixtures, allowing the reduction in cement content used in this type of material.
Camouflaged Object Detection That Does Not Require Additional Priors
Authors: Dong Yuchen , Zhou Heng , Li Chengyang , Xie Junjie , Xie Yongqiang , Li Zhongbo
Published: March 2024

Camouflaged object detection (COD) is an arduous challenge due to the striking resemblance of camouflaged objects to their surroundings. The abundance of similar background information can significantly impede the efficiency of camouflaged object detection algorithms. Prior research in this domain has often relied on supplementary prior knowledge to guide model training. However, acquiring such prior knowledge is resource-intensive. Furthermore, the additional provided prior information is typically already embedded in the original image, but this information is underutilized. To address these issues, in this paper, we introduce a novel Camouflage Cues Guidance Network (CCGNet) for camouflaged object detection that does not rely on additional prior knowledge. Specifically, we use an adaptive approach to track the learning state of the model with respect to the camouflaged object and dynamically extract the cues of the camouflaged object from the original image. In addition, we introduce a foreground separation module and an edge refinement module to effectively utilize these camouflage cues, assisting the model in fully separating camouflaged objects and enabling precise edge prediction. Extensive experimental results demonstrate that our proposed methods can achieve superior performance compared with state-of-the-art approaches.
Real-Time Batch Optimization for the Stochastic Container Relocation Problem
Authors: Zhou Sifang , Zhang Qingnian
Published: March 2024

The container relocation problem (CRP) is an important factor affecting the operation efficiency of container terminal yards, and it has attracted much attention for decades. The CRP during the pickup operations of import containers is still an intractable problem for two reasons: the first is that the solution efficiency of the algorithms developed in the existing literature cannot meet the real-time operation requirements; the second is that the pre-optimized operation plan cannot cope with the changes in the real-time operation scenarios caused by the uncertainty of the arrival time of external trucks. This paper proposes an optimization method for the real-time operation scenario which aims to solve the most reasonable operation plan quickly according to the arrivals of external trucks, in which a dynamic upper bound of the optimal solution is derived based on the dynamic programming model of the import containers’ CRP, and an approximate optimal solution can be obtained by minimizing this dynamic upper bound. A heuristic algorithm based on three relocation rules is developed to implement this method, considering the adjustment of the pickup sequence of the target containers. Numerical experiments show that (1) when the number of a batch of target containers is less than 10 (excluding target containers that can be directly picked up), the method proposed in this paper can solve the problem quickly to meet the demand of optimizing real-time pickup operations; (2) compared with other outstanding algorithms, the quality of the solutions obtained by this method is also improved; and (3) this method can be applied to the most container terminals for optimizing real-time pickup operations.
Migration Behaviour of the Combined Pollutants of Cadmium and 2,2′,4,4′,5,5′-Hexabrominated Diphenyl Ether (BDE-153) in Amaranthus mangostanus L. and Their Toxicity to A. mangostanus
Authors: Pan Weijie , Wang Jicheng , Cui Shengyan , Wu Sai , Wang Cuiping
Published: March 2024

The effects of different concentrations of cadmium and 2,2′,4,4′,5,5′-hexabrominated diphenyl ether (BDE-153) on the growth and related physiological and biochemical indexes of Amaranthus mangostanus L. (amaranth) were studied. The results showed that the presence of BDE-153 promoted the absorption of Cd by the amaranth and inhibited the migration of Cd from the roots to the shoots. At the same time, 0.1 mg/L of Cd had a synergistic effect on the migration of BDE-153, but 5 mg/L Cd inhibited the accumulation of BDE-153 in the aboveground part of the amaranth. In addition, the kinetics of the uptake of pollutants by the amaranth showed that both Cd and BDE-153 could be transported by amaranth, but Cd and BDE-153 were mainly enriched in the roots, and the presence of Cd may cause a lag in the uptake of BDE-153 in the shoots. Compared with the control group, the biomass of the amaranth affected by BDE-153 and a high concentration of Cd (5 mg/L) decreased by 30.2–49.5%, the chlorophyll content decreased by 43.0–60.3%, the Evans blue increased, and the MDA content was higher. The activities of superoxide dismutase (SOD) and catalase (CAT) also decreased with an increase in the BDE-153 concentration. This indicates that the interaction between BDE-153 and a high concentration of Cd (5 mg/L) is more toxic to amaranth than single Cd pollution. This paper provides the necessary data support for phytoremediation of heavy metal and organic compound pollution.
Modeling and Analysis of a Radiative Thermal Memristor
Authors: Odebowale Ambali Alade , Berhe Andergachew Mekonnen , Hattori Haroldo T. , Miroshnichenko Andrey E.
Published: March 2024

This study presents a theoretical framework for a radiative thermal memristor (RTM), utilizing Tungsten-doped vanadium dioxide (WVO) as the phase-change material (PCM) and silicon carbide (SiC) in the far-field regime. The behavior of the RTM is depicted through a Lissajous curve, illustrating the relationship between net flux (Q) and a periodically modulated temperature difference ΔT(t). It is established that temperature variations in the memristance (M) of the RTM form a closed loop, governed by PCM hysteresis. The analysis explores the impact of thermal conductivity contrast (r) and periodic thermal input amplitude (θ) on the Q–ΔT curve and the M–ΔT curve and negative differential thermal resistance (NDTR), revealing notable effects on the curve shapes and the emergence of NDTR. An increasing r leads to changes in the Lissajous curve’s shape and enhances the NDTR influence, while variations in both r and (θ) significantly affect the Q values and Lissajous curve amplitudes. In the M–ΔT curve, the height is linked to thermal conductivity contrast (r), with increasing r resulting in higher curve heights.
Diagnostic Accuracy of Digital Solutions for Screening for Cognitive Impairment: A Systematic Review and Meta-Analysis
Authors: Magno Marisa , Martins Ana Isabel , Pais Joana , Silva Anabela G. , Rocha Nelson Pacheco
Published: March 2024

The early detection of cognitive impairment is essential in order to initiate interventions and guarantee access to healthcare services. Digital solutions are emerging in the literature as an alternative approach to cognitive screening. Our primary goal is to synthesize the evidence on digital solutions’ diagnostic ability to screen for cognitive impairment and their accuracy. A secondary goal is to distinguish whether the ability to screen for cognitive impairment varies as a function of the type of digital solution: paper-based or innovative digital solutions. A systematic review and meta-analysis of digital solutions’ diagnostic accuracy were conducted, including 25 studies. Digital solutions presented a variable diagnostic accuracy range. Innovative digital solutions offered at least 0.78 of sensitivity but showed lower specificity levels than the other subgroup. Paper-based digital solutions revealed at least 0.72 of specificity, but sensitivity started at 0.49. Most digital solutions do not demand the presence of a trained professional and include an automatic digital screening system and scoring, which can enhance cognitive screening and monitoring. Digital solutions can potentially be used for cognitive screening in the community and clinical practice, but more investigation is needed for an evidence-based decision. A careful assessment of the accuracy levels and quality of evidence of each digital solution is recommended.
GIS-Based Spatial Analysis Model for Assessing Impact and Cumulative Risk in Road Traffic Accidents via Analytic Hierarchy Process (AHP)—Case Study: Romania
Authors: Bilașco Ștefan , Man Titus-Cristian
Published: March 2024

On a global scale, traffic incidents are a leading cause of mortality and material damage. Romania exhibits the highest rate of road traffic fatalities both in the European Union and worldwide, requiring a comprehensive examination of its overall influence on a national level. The current study uses an extensive approach centering on a spatial analysis model based on the Analytic Hierarchy Process (AHP). Employing a series of spatial databases, this model delineates the geographical distribution and characteristics of road accidents to establish both their cumulative national impact and the identification of high-risk areas. The spatial database, containing traffic incident data, is constructed using geolocation techniques and integrated through network analysis to evaluate the impact in relation to distance. The AHP framework is applied in analyzing the impact across five key dimensions: accident severity, occurrence mode, prevailing weather conditions, traffic restrictions, and road markings. This multi-level AHP analysis not only identifies high-risk hotspots but also confirms the effectiveness of the proposed spatial model.
The Influence of Arabinoxylan on the Properties of Sourdough Wheat Bread
Authors: Bieniek Angelika , Buksa Krzysztof
Published: March 2024

Sourdough bread is a traditional product made using lactic acid bacteria (LAB) and yeast. The influence of rye arabinoxylans (AXs) of different molar masses on sourdough wheat bread has not been studied to date. The aim of this study was to research the influence of arabinoxylans of different molar masses on the properties of sourdough wheat bread. The breads were baked using the sourdough method with wheat flour without and with 1% or 2% rye AX with different molar masses, which were unmodified, partially enzymatically hydrolyzed and cross-linked. The addition of all the AX preparations significantly increased the water absorption of the wheat flour. In particular, the addition of the preparation of cross-linked arabinoxylans at an amount of 2% caused the highest increase (by 9.8%) in the addition of water to the wheat flour dough. It was shown that a 2% addition of partially hydrolyzed AXs, with a low molar mass (190,440 g/mol), had the highest influence on increasing (by 23.7%) the volume of the bread and decreasing (by 41%) the crumb hardness of the sourdough bread, determined on the day of baking. The addition of the cross-linked AXs at an amount of 2% had the strongest influence on increasing the moisture content of the crumbs on the day of baking, both in the central (by 2.6%) and peripheral (by 5.1%) parts of the bread compared to the bread without the addition of AXs. The breads with all the AX preparations after the first and third days of storage had a higher crumb moisture content compared to the bread without the AXs.
A Unified Visual and Linguistic Semantics Method for Enhanced Image Captioning
Authors: Peng Jiajia , Tang Tianbing
Published: March 2024

Image captioning, also recognized as the challenge of transforming visual data into coherent natural language descriptions, has persisted as a complex problem. Traditional approaches often suffer from semantic gaps, wherein the generated textual descriptions lack depth, context, or the nuanced relationships contained within the images. In an effort to overcome these limitations, we introduce a novel encoder–decoder framework called A Unified Visual and Linguistic Semantics Method. Our method comprises three key components: an encoder, a mapping network, and a decoder. The encoder employs a fusion of CLIP (Contrastive Language–Image Pre-training) and SegmentCLIP to process and extract salient image features. SegmentCLIP builds upon CLIP’s foundational architecture by employing a clustering mechanism, thereby enhancing the semantic relationships between textual and visual elements in the image. The extracted features are then transformed by a mapping network into a fixed-length prefix. A GPT-2-based decoder subsequently generates a corresponding Chinese language description for the image. This framework aims to harmonize feature extraction and semantic enrichment, thereby producing more contextually accurate and comprehensive image descriptions. Our quantitative assessment reveals that our model exhibits notable enhancements across the intricate AIC-ICC, Flickr8k-CN, and COCO-CN datasets, evidenced by a 2% improvement in BLEU@4 and a 10% uplift in CIDEr scores. Additionally, it demonstrates acceptable efficiency in terms of simplicity, speed, and reduction in computational burden.
High-Resolution Temperature Evolution Maps of Bangladesh via Data-Driven Learning
Authors: Wu Yichen , Yang Jiaxin , Zhang Zhihua , Das Lipon Chandra , Crabbe M. James C.
Published: March 2024

As a developing country with an agricultural economy as a pillar, Bangladesh is highly vulnerable to adverse effects of climate change, so the generation of high-resolution temperature maps is of great value for Bangladesh to achieve agricultural sustainable development. However, Bangladesh’s weak economy and sparse meteorological stations make it difficult to obtain such maps. In this study, by mining internal features and links inside observed data, we developed an efficient data-driven downscaling technique to generate high spatial-resolution temperature distribution maps of Bangladesh directly from observed temperature data at 34 meteorological stations with irregular distribution. Based on these high-resolution historical temperature maps, we further explored a data-driven forecast technique to generate high-resolution temperature maps of Bangladesh for the period 2025–2035. Since the proposed techniques are very low-cost and fully mine internal links inside irregular-distributed observations, they can support relevant departments of Bangladesh to formulate policies to mitigate and adapt to climate change in a timely manner.
Dissecting the Roles of the Cytokinin Signaling Network: The Case of De Novo Shoot Apical Meristem Formation
Authors: Pokimica Nina , Ćosić Tatjana , Uzelac Branka , Ninković Slavica , Raspor Martin
Published: March 2024

Numerous biotechnological applications require a fast and efficient clonal propagation of whole plants under controlled laboratory conditions. For most plant species, the de novo regeneration of shoots from the cuttings of various plant organs can be obtained on nutrient media supplemented with plant hormones, auxin and cytokinin. While auxin is needed during the early stages of the process that include the establishment of pluripotent primordia and the subsequent acquisition of organogenic competence, cytokinin-supplemented media are required to induce these primordia to differentiate into developing shoots. The perception of cytokinin through the receptor ARABIDOPSIS HISTIDINE KINASE4 (AHK4) is crucial for the activation of the two main regulators of the establishment and maintenance of shoot apical meristems (SAMs): SHOOTMERISTEMLESS (STM) and the WUSCHEL-CLAVATA3 (WUS-CLV3) regulatory circuit. In this review, we summarize the current knowledge of the roles of the cytokinin signaling cascade in the perception and transduction of signals that are crucial for the de novo establishment of SAMs and lead to the desired biotechnological output—adventitious shoot multiplication. We highlight the functional differences between individual members of the multigene families involved in cytokinin signal transduction, and demonstrate how complex genetic regulation can be achieved through functional specialization of individual gene family members.
Molecular Profiling of Axial Spondyloarthritis Patients Reveals an Association between Innate and Adaptive Cell Populations and Therapeutic Response to Tumor Necrosis Factor Inhibitors
Authors: Sobral Daniel , Fernandes Ana Filipa , Bernardes Miguel , Pinto Patrícia , Santos Helena , Lagoas-Gomes João , Tavares-Costa José , Silva José A. P. , Dias João Madruga , Bernardo Alexandra , Gaillard Jean-Charles , Armengaud Jean , Benes Vladimir , Domingues Lúcia , Maia Sara , Branco Jaime C. , Coelho Ana Varela , Pimentel-Santos Fernando M.
Published: March 2024

This study aims at identifying molecular biomarkers differentiating responders and non-responders to treatment with Tumor Necrosis Factor inhibitors (TNFi) among patients with axial spondyloarthritis (axSpA). Whole blood mRNA and plasma proteins were measured in a cohort of biologic-naïve axSpA patients (n = 35), pre and post (14 weeks) TNFi treatment with adalimumab. Differential expression analysis was used to identify the most enriched pathways and in predictive models to distinguish responses to TNFi. A treatment-associated signature suggests a reduction in inflammatory activity. We found transcripts and proteins robustly differentially expressed between baseline and week 14 in responders. C-reactive protein (CRP) and Haptoglobin (HP) proteins showed strong and early decrease in the plasma of axSpA patients, while a cluster of apolipoproteins (APOD, APOA2, APOA1) showed increased expression at week 14. Responders to TNFi treatment present higher levels of markers of innate immunity at baseline, and lower levels of adaptive immunity markers, particularly B-cells. A logistic regression model incorporating ASDAS-CRP, gender, and AFF3, the top differentially expressed gene at baseline, enabled an accurate prediction of response to adalimumab in our cohort (AUC = 0.97). In conclusion, innate and adaptive immune cell type composition at baseline may be a major contributor to response to adalimumab in axSpA patients. A model including clinical and gene expression variables should also be considered.
Exploring the Landscape of Anti-Inflammatory Trials: A Comprehensive Review of Strategies for Targeting Inflammation in Acute Myocardial Infraction
Authors: Mitsis Andreas , Kyriakou Michaela , Sokratous Stefanos , Karmioti Georgia , Drakomathioulakis Michail , Myrianthefs Michael , Ziakas Antonios , Tzikas Stergios , Kassimis George
Published: March 2024

The role of inflammation in the pathophysiology of acute myocardial infarction (AMI) is well established. In recognizing inflammation’s pivotal role in AMI, this manuscript systematically traces the historical studies spanning from early attempts to the present landscape. Several anti-inflammatory trials targeting inflammation in post-AMI have been performed, and this review includes the key trials, as well as examines their designs, patient demographics, and primary outcomes. Efficacies and challenges are analyzed, thereby shedding light on the translational implications of trial outcomes. This article also discusses emerging trends, ongoing research, and potential future directions in the field. Practical applications and implications for clinical practice are considered by providing a holistic view of the evolving landscape of anti-inflammatory interventions in the context of AMI.
Comparing the Efficacy of Two Generations of EGFR-TKIs: An Integrated Drug–Disease Mechanistic Model Approach in EGFR-Mutated Lung Adenocarcinoma
Authors: Darré Hippolyte , Masson Perrine , Nativel Arnaud , Villain Laura , Lefaudeux Diane , Couty Claire , Martin Bastien , Jacob Evgueni , Duruisseaux Michaël , Palgen Jean-Louis , Monteiro Claudio , L’Hostis Adèle
Published: March 2024

Mutationsin epidermal growth factor receptor (EGFR) are found in approximately 48% of Asian and 19% of Western patients with lung adenocarcinoma (LUAD), leading to aggressive tumor growth. While tyrosine kinase inhibitors (TKIs) like gefitinib and osimertinib target this mutation, treatments often face challenges such as metastasis and resistance. To address this, we developed physiologically based pharmacokinetic (PBPK) models for both drugs, simulating their distribution within the primary tumor and metastases following oral administration. These models, combined with a mechanistic knowledge-based disease model of EGFR-mutated LUAD, allow us to predict the tumor’s behavior under treatment considering the diversity within the tumor cells due to different mutations. The combined model reproduces the drugs’ distribution within the body, as well as the effects of both gefitinib and osimertinib on EGFR-activation-induced signaling pathways. In addition, the disease model encapsulates the heterogeneity within the tumor through the representation of various subclones. Each subclone is characterized by unique mutation profiles, allowing the model to accurately reproduce clinical outcomes, including patients’ progression, aligning with RECIST criteria guidelines (version 1.1). Datasets used for calibration came from NEJ002 and FLAURA clinical trials. The quality of the fit was ensured with rigorous visual predictive checks and statistical tests (comparison metrics computed from bootstrapped, weighted log-rank tests: 98.4% (NEJ002) and 99.9% (FLAURA) similarity). In addition, the model was able to predict outcomes from an independent retrospective study comparing gefitinib and osimertinib which had not been used within the model development phase. This output validation underscores mechanistic models’ potential in guiding future clinical trials by comparing treatment efficacies and identifying patients who would benefit most from specific TKIs. Our work is a step towards the design of a powerful tool enhancing personalized treatment in LUAD. It could support treatment strategy evaluations and potentially reduce trial sizes, promising more efficient and targeted therapeutic approaches. Following its consecutive prospective validations with the FLAURA2 and MARIPOSA trials (validation metrics computed from bootstrapped, weighted log-rank tests: 94.0% and 98.1%, respectively), the model could be used to generate a synthetic control arm.
Integrating an Image-Generative Tool on Creative Design Brainstorming Process of a Safavid Mosque Architecture Conceptual Form
Authors: Maksoud Aref , Elshabshiri Aya , Saeed Hilal Humaid Alzaabi Amani , Hussien Aseel
Published: March 2024

The study aims to understand to what extent employing A.I. image-generative tools in architectural concept brainstorming demonstrates effectiveness, accuracy, and adherence to text and image inputs, and evaluate the utilization of A.I. image-generative tools in the architectural ideation phase, considering factors such as speed, creativity, and accuracy. Thus, this study will investigate using an A.I. image-generative tool, Midjourney, in the creative brainstorming stage for a Safavid mosque architectural form design process. The study will quantitatively evaluate the form proportions of mosques generated by Midjourney based on certain criteria as they pertain to the Shah Mosque as the inspiration for the design as it encompasses many of the Safavid Mosque’s typical elements and characteristics. The most matching form will then be found. The findings are that Midjourney is reliable in terms of its speed and creativity; however, it lacks accuracy and adherence to inputs. This study is essential as limited literature exists on A.I. image-generative tools in the brainstorming process of architectural projects, particularly mosque architecture. It also provides architects and designers with a framework and the pros and cons of the use of A.I. generative tools, such as Midjourney, in the ideation process for an architectural project.
Correction: Zwergel et al. Novel Quinoline Compounds Active in Cancer Cells through Coupled DNA Methyltransferase Inhibition and Degradation. Cancers 2020, 12, 447
Authors: Zwergel Clemens , Fioravanti Rossella , Stazi Giulia , Sarno Federica , Battistelli Cecilia , Romanelli Annalisa , Nebbioso Angela , Mendes Eduarda , Paulo Alexandra , Strippoli Raffaele , Tripodi Marco , Pechalrieu Dany , Arimondo Paola B. , De Luca Teresa , Del Bufalo Donatella , Trisciuoglio Daniela , Altucci Lucia , Valente Sergio , Mai Antonello
Published: March 2024

In the original publication [...]
Enhancing Whole-Brain Magnetic Field Homogeneity for 3D-Magnetic Resonance Spectroscopic Imaging with a Novel Unified Coil: A Preliminary Study
Authors: Malagi Archana Vadiraj , Li Xinqi , Zhang Na , Liu Yucen , Huang Yuheng , Serry Fardad Michael , Long Ziyang , Yang Chia-Chi , Shan Yujie , Cai Yubin , Zepeda Jeremy , Binesh Nader , Li Debiao , Yang Hsin-Jung , Han Hui
Published: March 2024

The spectral quality of magnetic resonance spectroscopic imaging (MRSI) can be affected by strong magnetic field inhomogeneities, posing a challenge for 3D-MRSI’s widespread clinical use with standard scanner-equipped 2nd-order shim coils. To overcome this, we designed an empirical unified shim–RF head coil (32-ch RF receive and 51-ch shim) for 3D-MRSI improvement. We compared its shimming performance and 3D-MRSI brain coverages against the standard scanner shim (2nd-order spherical harmonic (SH) shim coils) and integrated parallel reception, excitation, and shimming (iPRES) 32-ch AC/DC head coil. We also simulated a theoretical 3rd-, 4th-, and 5th-order SH shim as a benchmark to assess the UNIfied shim–RF coil (UNIC) improvements. In this preliminary study, the whole-brain coverage was simulated by using B0 field maps of twenty-four healthy human subjects (n = 24). Our results demonstrated that UNIC substantially improves brain field homogeneity, reducing whole-brain frequency standard deviations by 27% compared to the standard 2nd-order scanner shim and 17% compared to the iPRES shim. Moreover, UNIC enhances whole-brain coverage of 3D-MRSI by up to 34% compared to the standard 2nd-order scanner shim and up to 13% compared to the iPRES shim. UNIC markedly increases coverage in the prefrontal cortex by 147% and 47% and in the medial temporal lobe and temporal pole by 29% and 13%, respectively, at voxel resolutions of 1.4 cc and 0.09 cc for 3D-MRSI. Furthermore, UNIC effectively reduces variations in shim quality and brain coverage among different subjects compared to scanner shim and iPRES shim. Anticipated advancements in higher-order shimming (beyond 6th order) are expected via optimized designs using dimensionality reduction methods.
Pros and Cons of Cryopreserving Allogeneic Stem Cell Products
Authors: Valentini Caterina Giovanna , Pellegrino Claudio , Teofili Luciana
Published: March 2024

The COVID-19 pandemic has precipitously changed the practice of transplanting fresh allografts. The safety measures adopted during the pandemic prompted the near-universal graft cryopreservation. However, the influence of cryopreserving allogeneic grafts on long-term transplant outcomes has emerged only in the most recent literature. In this review, the basic principles of cell cryopreservation are revised and the effects of cryopreservation on the different graft components are carefully reexamined. Finally, a literature revision on studies comparing transplant outcomes in patients receiving cryopreserved and fresh grafts is illustrated.
Assessment of Psychotic Risk in a Sample of Children and Adolescents with Autism Spectrum Disorder Compared to a Group of “Clinical High Risk” Patients: A Preliminary Study
Authors: Mammarella Valeria , Monducci Elena , Maffucci Alessia , Terenzi Letizia , Ferrara Mauro , Sogos Carla
Published: March 2024

1. Background: Autism spectrum disorder and psychotic risk show several overlapping symptoms, so differential diagnosis is often difficult. In addition, there is a high rate of comorbidity between the two conditions, which further complicates the work of clinicians. We evaluated the presence of subthreshold psychotic symptoms and/or defined psychotic risk syndromes in autistic children and adolescents; we compared the prevalence, type, and severity of psychotic risk symptoms with those of a group of non-autistic patients at clinical high risk for psychosis (CHR-P). 2. Methods: In total, 23 autistic patients and 14 CHR-P patients without autism (aged 8–17) were enrolled in the study. The main assessment was made through clinical interviews for autism (Autism Diagnostic Observation Schedule, Second Edition—ADOS-2, Autism Diagnostic Interview, Revised—ADI-R) and psychotic risk (Schizophrenia Proneness Instrument, Child and Youth version—SPI-CY, Structured Interview for Psychosis Risk Syndromes—SIPS). 3. Results: No above-threshold psychotic risk symptoms were detected in our autistic patients, but subthreshold psychotic symptoms were identified in all areas. Specific items from all four dimensions of SIPS appear to be more specific for psychotic risk than autism without comorbidity. 4. Conclusions: An a priori screening of psychotic risk in neurodiverse populations is fundamental to prevent more severe conditions. Research should clarify the effective specificity of the available tools to modify them to improve their detection capability.
Editorial for the Special Issue “New Research in Childhood Nutrition” of the Journal Children
Authors: Muros Jose Joaquín
Published: March 2024

Nutrition is much more than food [...]
Current Uses of Bromelain in Children: A Narrative Review
Authors: Locci Cristian , Chicconi Elena , Antonucci Roberto
Published: March 2024

Bromelain is a complex natural mixture of sulfhydryl-containing proteolytic enzymes that can be extracted from the stem or fruit of the pineapple. This compound is considered a safe nutraceutical, has been used to treat various health problems, and is also popular as a health-promoting dietary supplement. There is continued interest in bromelain due to its remarkable therapeutic properties. The mechanism of action of bromelain appears to extend beyond its proteolytic activity as a digestive enzyme, encompassing a range of effects (mucolytic, anti-inflammatory, anticoagulant, and antiedematous effects). Little is known about the clinical use of bromelain in pediatrics, as most of the available data come from in vitro and animal studies, as well as a few RCTs in adults. This narrative review was aimed at highlighting the main aspects of the use of bromelain in children, which still appears to be limited compared to its potential. Relevant articles were identified through searches in MEDLINE, PubMed, and EMBASE. There is no conclusive evidence to support the use of bromelain in children, but the limited literature data suggest that its addition to standard therapy may be beneficial in treating conditions such as upper respiratory tract infections, specific dental conditions, and burns. Further studies, including RCTs in pediatric settings, are needed to better elucidate the mechanism of action and properties of bromelain in various therapeutic areas.
Microstructural Analysis on Grain Boundary of Boron– and Zirconium–Containing Wrought Nickel-Based Superalloys
Authors: Kang Byungil , Lee Youngki , Kim Jongmin , Ha Taekyu , Kim Youngjig
Published: March 2024

Trace elements such as boron (B) and zirconium (Zr) can increase creep resistance in nickel-based superalloys. This study investigates the change of microstructures on the grain boundary (GB) in phase-controlled nickel-based superalloys through the addition of trace elements. The basis alloy without B and Zr has distributed micrometer-sized (Nb, Ti)C and Cr23C6 carbides at the GBs. Zr is detected alongside Nb and Ti within certain (Nb, Ti)C carbides and its addition increases the fraction of (Nb, Ti)C or (Nb, Ti, Zr)C carbides. B affects the formation of precipitates constructed by nanometer-sized precipitates, which are Cr23C6 carbides, Cr23(C, B)6 boro-carbides, and Cr-rich borides, surrounded by γ’ phases. This film structure, which includes nanometer-sized precipitates surrounded by γ’ phases, forms more continuously with the addition of B and Zr. It is constructed with precipitates of (Nb, Ti)C carbides and Cr23(C, B)6 boro-carbides surrounded by γ’ phases. Numerous nanometer-sized precipitates (i.e., (Nb, Ti)C and Cr23(C, B)6) are distributed alternately within the film structure. The effect of the addition of B and Zr is such that nucleation sites of each precipitate are formed simultaneously and alternately along the GBs. The experimental results were discussed by correlating them with the predicted fraction of stable phases depending on the temperatures of these alloys, using the JMatPro program.
Comparative Review of the Current and Future Strategies to Evaluate Bone Marrow Infiltration at Diffuse Large B-Cell Lymphoma Diagnosis
Authors: Martin-Moro Fernando , Lopez-Jimenez Javier , Garcia-Marco Jose A. , Garcia-Vela Jose A.
Published: March 2024

Diffuse large B-cell lymphoma (DLBCL) requires a complete staging at diagnosis that may have prognostic and therapeutic implications. The role of bone marrow (BM) biopsy (BMB) is controversial in the era of nuclear imaging techniques. We performed a comparative review of 25 studies focused on BM evaluation at DLBCL diagnosis, including at least two of the following techniques: BMB, flow cytometry, and positron emission tomography (PET-FDG). The report about BM involvement (BMi), diagnostic accuracy, and prognostic significance was collected and compared among techniques. A concordance analysis between BMB, FCM, and PET was also performed, and we deeply evaluated the implications of the different types of BMi: concordant by LBCL or discordant by low-grade B-cell lymphoma for both BMB and FCM, and focal or diffuse uptake pattern for PET. As a main conclusion, BMB, FCM, and PET are complementary tools that provide different and clinically relevant information in the assessment of BMi in newly diagnosed DLBCL.
Identification and Validation of T-Cell Exhaustion Signature for Predicting Prognosis and Immune Response in Pancreatic Cancer by Integrated Analysis of Single-Cell and Bulk RNA Sequencing Data
Authors: Zhu Yaowu , Tan Li , Luo Danju , Wang Xiong
Published: March 2024

Purpose: Pancreatic cancer (PACA) is one of the most fatal malignancies worldwide. Immunotherapy is largely ineffective in patients with PACA. T-cell exhaustion contributes to immunotherapy resistance. We investigated the prognostic potential of T-cell exhaustion-related genes (TEXGs). Methods: A single-cell RNA (scRNA) sequencing dataset from Tumor Immune Single-Cell Hub (TISCH) and bulk sequencing datasets from the Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) were used to screen differentially expressed TEXGs. Kaplan–Meier survival, LASSO regression, and univariate/multivariate Cox regression analyses were performed to construct a TEXG risk model. This model was used to predict the prognosis, tumor immune microenvironment, and immunotherapy response. The PACA cohorts from the ICGC and GSE71729 datasets were used to validate the risk model. Pan-cancer expression of SPOCK2 was determined using the TISCH database. Results: A six-gene (SPOCK2, MT1X, LIPH, RARRES3, EMP1, and MEG3) risk model was constructed. Patients with low risk had prolonged survival times in both the training (TCGA-PAAD, n = 178) and validation (ICGC-PACA-CA, ICGC-PAAD-US, and GSE71729, n = 412) datasets. Multivariate Cox regression analysis demonstrated that the risk score was an independent prognostic variable for PACA. High-risk patients correlated with their immunosuppressive status. Immunohistochemical staining confirmed the changes in TEXGs in clinical samples. Moreover, pan-cancer scRNA sequencing datasets from TISCH analysis indicated that SPOCK2 may be a novel marker of exhausted CD8+ T-cells. Conclusion: We established and validated a T-cell exhaustion-related prognostic signature for patients with PACA. Moreover, our study suggests that SPOCK2 is a novel marker of exhausted CD8+ T cells.
Autonomic Nervous System Activity and Dental Anxiety in the Northern Finland Birth Cohort (NFBC1966) Population
Authors: Somero Atte , Suominen Auli , Pohjola Vesa , Ogawa Mika , Sipilä Kirsi , Kakko Niklas , Tulppo Mikko , Lahti Satu
Published: March 2024

Autonomic nervous system (ANS) activity may be associated with dental anxiety; however, no studies exist on the topic. The aim of this study was to assess if ANS activity and dental anxiety are associated. Data were collected as part of a Northern Finland Birth Cohort Study, NFBC1966, at the age of 46 years with eligible data on 1905 participants. Dental anxiety was measured using the Modified Dental Anxiety Scale (MDAS) categorized as follows: 19–25 = high, 10–18 = moderate, 5–9 = no to low dental anxiety. Heart rate variability (HRV) data were collected using an HR monitor and a standard lead-II electrocardiogram (ECG). Baroreflex sensitivity (BRS) was calculated from continuous ECG and blood pressure signals. Participants were categorized into three groups as follows: Low = the lowest 20th percentile, Mid = medium 21–79th percentile, and High = the highest 20th percentile according to their ANS variables. The associations between the MDAS and ANS activity parameters were evaluated using unordered multinomial logit models adjusted for comorbidities, β-blockers, BMI, smoking, and education. High heart rate, reduced HRV, low cardiac vagal modulation, and poor BRS were associated with moderate dental anxiety, and high cardiac vagal modulation and good BRS were associated with no to low dental anxiety. Poorer ANS activity might predispose some to dental anxiety, and better ANS activity might protect from dental anxiety.
Texture Analysis of Temporomandibular Joint Disc Changes Associated with Effusion Using Magnetic Resonance Images
Authors: Girondi Camila Miorelli , de Castro Lopes Sérgio Lúcio Pereira , Ogawa Celso Massahiro , Braz-Silva Paulo Henrique , Costa Andre Luiz Ferreira
Published: March 2024

The purpose of this study was to identify changes in the temporomandibular joint disc affected by effusion by using texture analysis of magnetic resonance images (MRIs). Methods: A total of 223 images of the TMJ, 42 with joint effusion and 181 without, were analyzed. Three consecutive slices were then exported to MaZda software, in which two oval ROIs (one in the anterior band and another in the intermediate zone of the joint disc) were determined in each slice and eleven texture parameters were calculated by using a gray-level co-occurrence matrix. Spearman’s correlation coefficient test was used to assess the correlation between texture variables and to select variables for analysis. The Mann–Whitney test was used to compare the groups. Results: The significance level was set at 5%, with the results demonstrating that there was no high correlation between the parameter directions. It was possible to observe a trend between the average parameters, in which the group with effusion always had smaller values than the group without effusion, except for the parameter measuring the difference in entropy. Conclusion: The trend towards lower overall values for the texture parameters suggested a different behavior between TMJ discs affected by effusion and those not affected, indicating that there may be intrinsic changes.
Augmented Reality in Industry 4.0 Assistance and Training Areas: A Systematic Literature Review and Bibliometric Analysis
Authors: Morales Méndez Ginés , del Cerro Velázquez Francisco
Published: March 2024

Augmented reality (AR) technology is making a strong appearance on the industrial landscape, driven by significant advances in technological tools and developments. Its application in areas such as training and assistance has attracted the attention of the research community, which sees AR as an opportunity to provide operators with a more visual, immersive and interactive environment. This article deals with an analysis of the integration of AR in the context of the fourth industrial revolution, commonly referred to as Industry 4.0. Starting with a systematic review, 60 relevant studies were identified from the Scopus and Web of Science databases. These findings were used to build bibliometric networks, providing a broad perspective on AR applications in training and assistance in the context of Industry 4.0. The article presents the current landscape, existing challenges and future directions of AR research applied to industrial training and assistance based on a systematic literature review and citation network analysis. The findings highlight a growing trend in AR research, with a particular focus on addressing and overcoming the challenges associated with its implementation in complex industrial environments.