bluuebunny/crossref_metadata_2025 huggingface dataset:
Nutritional Factors Associated with Dental Caries across the Lifespan: A Review
Authors: Dimopoulou Maria , Antoniadou Maria , Amargianitakis Markos , Gortzi Olga , Androutsos Odysseas , Varzakas Theodoros
Published: December 2023

Nutrition and dietetic care span various life stages, addressing nutritional needs and exploring factors that shape dietary habits. Globally, an alarming disproportion in food resource distribution, coupled with substandard nutritional intake, underscores profound implications for oral health. This is evident in the facilitation of dental caries development and its repercussions on oral soft tissue integrity. While modern markets offer advanced edible products, their effects on oral health, especially in relation to dental caries, remain uncharted. This narrative literature review pursues a four-fold objective: (a) scrutinizing the repercussions of inadequate nutrition on dental caries, (b) exploring psychological determinants influencing dietary habits contributing to caries development, (c) investigating potential implications of newly devised food products on caries formation, and (d) elucidating the role of dentists as facilitators in promoting oral health practices. A comprehensive search spanning PubMed, Web of Science, and Cochrane Library yielded 46 cohort, cross-sectional research articles and systematic reviews adhering to standardized diagnostic criteria for dental caries evaluation. The results highlight contemporary lifestyles as potent contributors to heightened risk of caries due to suboptimal nutritional quality and nutrient insufficiency. Additionally, concerns have arisen with the advent of synthetically engineered food products, warranting exploration of potential implications for future caries development and global oral health status. This review emphasizes the pivotal role of dietitians–nutritionists and dental professionals in advocating sound nutritional practices specifically geared towards preventing dental caries. Ultimately, this review contributes to the understanding of the intricate interplay between nutrition, oral health, and the imperative role of healthcare professionals in fostering preventive measures.
A Multi-View Integrated Ensemble for the Background Discrimination of Semi-Supervised Semantic Segmentation
Authors: Gwak Hyunmin , Jeong Yongho , Kim Chanyeong , Lee Yonghak , Yang Seongmin , Kim Sunghwan
Published: December 2023

The key to semi-supervised semantic segmentation is to assign the appropriate pseudo-label to the pixels of unlabeled images. Recently, various approaches to consistency-based training and the filtering of reliable pseudo-labels have shown remarkable results. Nonetheless, there are still issues to be addressed. We find that recent approaches have specific problems in common. In pseudo-labels for training unlabeled images, we confirm that false foreground class pseudo-labels are mostly caused by background class confusion, not confusion between different foreground classes. To solve this problem, we propose a foreground and background discrimination model for semi-supervised semantic segmentation. Our proposed model is trained using a novel approach called multi-view integrated ensemble (MVIE) via output perturbation. Experimental results in various partition protocols show that our approach outperforms the existing state of the art (SOTA) in binary prediction on unlabeled data, and the segmentation model trained with the help of our model outperforms existing models.
Pneumatic Bellows Actuated Parallel Platform Control with Adjustable Stiffness Using a Hybrid Feed-Forward and Variable Gain Integral Controller
Authors: Varga Martin , Virgala Ivan , Kelemen Michal , Miková L’ubica , Bobovský Zdenko , Sincak Peter Jan , Merva Tomáš
Published: December 2023

Redundant cascade manipulators actuated by pneumatic bellows actuators are passively compliant, rugged and dexterous, making them exceptionally well suited for application in agriculture. Unfortunately, the bellows are notoriously difficult to precisely position. This paper presents a novel control algorithm for the control of a parallel platform actuated by pneumatic bellows, which serves as a module of a cascade manipulator. The algorithm combines a feed-forward controller and a variable-gain I-controller. The mathematical model of the module, which serves as the feed-forward controller, was created by applying two simple regression steps on experimentally acquired data. The gain of the I-controller is linearly dependent on the total reference error, thereby addressing the prevalent problem of “a slow response or excessive overshoot”, which, in the described case, the simple combination of a feed-forward and constant-gain I-controller tends to suffer from. The proposed algorithm was experimentally verified and its performance was compared with two controllers: an ANFIS controller and a constant gain PID controller. The proposed controller has outperformed the PID controller in the three calculated criteria: IAE, ISE and ITAE by more than 40%. The controller was also tested under dynamic loading conditions, showing promising results.
Singular and Multimodal Techniques of 3D Object Detection: Constraints, Advancements and Research Direction
Authors: Karim Tajbia , Mahayuddin Zainal Rasyid , Hasan Mohammad Kamrul
Published: December 2023

Two-dimensional object detection techniques can detect multiscale objects in images. However, they lack depth information. Three-dimensional object detection provides the location of the object in the image along with depth information. To provide depth information, 3D object detection involves the application of depth-perceiving sensors such as LiDAR, stereo cameras, RGB-D, RADAR, etc. The existing review articles on 3D object detection techniques are found to be focusing on either a singular modality (e.g., only LiDAR point cloud-based) or a singular application field (e.g., autonomous vehicle navigation). However, to the best of our knowledge, there is no review paper that discusses the applicability of 3D object detection techniques in other fields such as agriculture, robot vision or human activity detection. This study analyzes both singular and multimodal techniques of 3D object detection techniques applied in different fields. A critical analysis comprising strengths and weaknesses of the 3D object detection techniques is presented. The aim of this study is to facilitate future researchers and practitioners to provide a holistic view of 3D object detection techniques. The critical analysis of the singular and multimodal techniques is expected to help the practitioners find the appropriate techniques based on their requirement.
The Moderating Effects of Online Streaming Content Service Characteristics on Online Word-of-Mouth for Service Performance
Authors: Lee Sangjae
Published: December 2023

Online streaming contents are creating greater service uncertainty, as consumers need to experience such contents before making a decision to continue to purchase them. Few studies have investigated the interaction between eWOM (online word-of-mouth) and online streaming content service characteristics with regard to the performance of online streaming contents and explained how this interaction can promote the role of service characteristics in service performance outcomes or remedy service uncertainty attributable to these characteristics. Thus, in order to test the interaction effects, this paper examines the moderating effects of service (webtoon) characteristics (i.e., author experience, genre (drama or fantasy), completion, transfer to paid service, and publication time (Wednesday)) on the relationship between eWOM and certain online streaming contents’ service performance measures; in this case, the publication period and content gamification. Based on scrawled data from 154 webtoons published on Naver Webtoon, a multivariate regression analysis with interaction terms showed that author experience and genre interact with the number of reviews to affect gamification. The transfer to a paid service interacts crucially with review ratings and the number of reviews to influence both the publication period and gamification. Online streaming content completion and publication times are factors that interact with review ratings and thus affect the publication period. Service providers need to cope with service uncertainties when attempting to further their online streaming content service by considering the service characteristics as well as customers’ responses through eWOM.
Acute Effects of Padel Match Play on Circulating Substrates, Metabolites, Energy Balance Enzymes, and Muscle Damage Biomarkers: Sex Differences
Authors: Pradas de la Fuente Francisco , Cádiz María Pía , Moreno-Azze Alejandro , Martínez-Díaz Inmaculada C. , Carrasco Luis
Published: December 2023

This study aimed to analyze the effects of padel match play on circulating substrates, metabolites, energy balance enzymes, and muscle damage biomarkers and evaluate possible sex-related differences. Twenty-two trained padel players (13 female and 9 male young-adult players) were recruited for this study in which simulated padel matches were analyzed. Circulating levels of substrates (glucose -BG- and triglycerides -TGs-), metabolites (creatinine -Cr- and urea), energy balance enzymes (lipoprotein lipase -LPL-), and muscle damage biomarkers (creatine kinase -CK-, lactate dehydrogenase -LDH-, and fatty acid-binding protein 3 -FABP-3-) were assessed both pre- and post-padel competition. Time analysis of padel matches reported a real time–total time ratio of 0.4. Moreover, players’ mean heart rate during padel matches represented around 75% of their individual maximum value. Unaltered BG levels and a slight decrease in TGs were observed post-exercise. Cr, urea, LPL, CK, LDH, and FABP-3 levels increased after padel matches when total group was considered. Moreover, sex-related differences in Cr, CK, and LDH blood concentrations were found in both pre- and post-padel competition. According to our results, the padel competition could be defined as a low- or moderate-impact sport in which aerobic energy system contribution is prevalent although anaerobic metabolism also plays a key role in performing padel shots and other explosive actions. Considering that male and female players exercised at the same relative intensity during padel matches, sex differences found in muscle damage biomarkers could be due to the greater muscle mass in males.
Few-Shot Image Classification via Mutual Distillation
Authors: Zhang Tianshu , Dai Wenwen , Chen Zhiyu , Yang Sai , Liu Fan , Zheng Hao
Published: December 2023

Due to their compelling performance and appealing simplicity, metric-based meta-learning approaches are gaining increasing attention for addressing the challenges of few-shot image classification. However, many similar methods employ intricate network architectures, which can potentially lead to overfitting when trained with limited samples. To tackle this concern, we propose using mutual distillation to enhance metric-based meta-learning, effectively bolstering model generalization. Specifically, our approach involves two individual metric-based networks, such as prototypical networks and relational networks, mutually supplying each other with a regularization term. This method seamlessly integrates with any metric-based meta-learning approach. We undertake comprehensive experiments on two prevalent few-shot classification benchmarks, namely miniImageNet and Caltech-UCSD Birds-200-2011 (CUB), to demonstrate the effectiveness of our proposed algorithm. The results demonstrate that our method efficiently enhances each metric-based model through mutual distillation.
Collaborative Allocation Method of En-Route Network Resources Based on Stackelberg Game Model
Authors: Tian Wen , Zhou Xuefang , Zhang Ying , Fang Qin , Yang Mingjian
Published: December 2023

To further enhance fairness in the allocation of en-route space–time resources in the collaborative trajectory selection program, a study on the plan preferences between air traffic control (ATC) and airlines in the selection process of the final plan is conducted based on the initial resource allocation plans, considering the roles of airlines in resources allocation decisions. By using Stackelberg game theory, a game model is established for the roles played by ATC and airlines in the process of selecting plans. Then, combining the overall consideration of ATC for all affected flights, the preferences of airlines for initial allocation plans are obtained, and the option range of selectable plans is narrowed down to determine the optimal allocation plan. The results of the example analysis show that the proposed model and method can effectively select the optimal allocation plan from the six initial allocation plans, select the trajectories and entry slots in the congestion areas for airlines that better meet the operation demand, and provide the decision basis with more preferences for ATC to select the final allocation plan. When ATC prefers the lowest overall delay cost, the delay cost of the selected optimal allocation plan is 267.7 min, which is 23.84% lower than the traditional RBS algorithm; when considering the preferences of the main base airline in East China, the delay cost of the selected optimal allocation plan is 287.7 min, which is 18.15% lower than the traditional RBS algorithm.
Recent Advances in the Targeting of Head and Neck Cancer Stem Cells
Authors: Vukovic Đerfi Kristina , Vasiljevic Tea , Matijevic Glavan Tanja
Published: December 2023

Head and neck squamous cell carcinoma (HNSCC) is a very heterogeneous cancer with a poor overall response to therapy. One of the reasons for this therapy resistance could be cancer stem cells (CSCs), a small population of cancer cells with self-renewal and tumor-initiating abilities. Tumor cell heterogeneity represents hurdles for therapeutic elimination of CSCs. Different signaling pathway activations, such as Wnt, Notch, and Sonic-Hedgehog (SHh) pathways, lead to the expression of several cancer stem factors that enable the maintenance of CSC features. Identification and isolation of CSCs are based either on markers (CD133, CD44, and aldehyde dehydrogenase (ALDH)), side populations, or their sphere-forming ability. A key challenge in cancer therapy targeting CSCs is overcoming chemotherapy and radiotherapy resistance. However, in novel therapies, various approaches are being employed to address this hurdle such as targeting cell surface markers, other stem cell markers, and different signaling or metabolic pathways, but also, introducing checkpoint inhibitors and natural compounds into the therapy can be beneficial.
Vector-Valued Shepard Processes: Approximation with Summability
Authors: Duman Oktay , Vecchia Biancamaria Della
Published: December 2023

In this work, vector-valued continuous functions are approximated uniformly on the unit hypercube by Shepard operators. If λ denotes the usual parameter of the Shepard operators and m is the dimension of the hypercube, then our results show that it is possible to obtain a uniform approximation of a continuous vector-valued function by these operators when λ≥m+1. By using three-dimensional parametric plots, we illustrate this uniform approximation for some vector-valued functions. Finally, the influence in approximation by regular summability processes is studied, and their motivation is shown.
Spectral Analysis of the Adjacency Matrices for Alternating Quotients of Hyperbolic Triangle Group ▵*(3,q,r) for q < r Primes
Authors: Younas Sajida , Kousar Sajida , Albaity Majed , Mahmood Tahir
Published: December 2023

Hyperbolic triangle groups are found within the category of finitely generated groups. These are topological groups formed by the reflections along the sides of a hyperbolic triangle and acting properly discontinuously on the hyperbolic plane. Higman raised a question about the simplicity of finitely generated groups. The best known example of a simple group is the alternating group An, where n≥5. This article establishes a relation between the hyperbolic triangle group denoted as ▵*(3,7,r) and the alternating group. The approach involves employing coset diagrams to establish this connection. The construction of adjacency matrices for these coset diagrams is performed, followed by a detailed examination of their spectral characteristics.
Finite-Time Stability of Impulsive Fractional Differential Equations with Pure Delays
Authors: Xie Tingting , Li Mengmeng
Published: December 2023

This paper introduces a novel concept of the impulsive delayed Mittag–Leffler-type vector function, an extension of the Mittag–Leffler matrix function. It is essential to seek explicit formulas for the solutions to linear impulsive fractional differential delay equations. Based on explicit formulas of the solutions, the finite-time stability results of impulsive fractional differential delay equations are presented. Finally, we present four examples to illustrate the validity of our theoretical results.
DSE-NN: Deeply Supervised Efficient Neural Network for Real-Time Remote Photoplethysmography
Authors: Lee Seongbeen , Lee Minseon , Sim Joo Yong
Published: December 2023

Non-contact remote photoplethysmography can be used in a variety of medical and healthcare fields by measuring vital signs continuously and unobtrusively. Recently, end-to-end deep learning methods have been proposed to replace the existing handcrafted features. However, since the existing deep learning methods are known as black box models, the problem of interpretability has been raised, and the same problem exists in the remote photoplethysmography (rPPG) network. In this study, we propose a method to visualize temporal and spectral representations for hidden layers, deeply supervise the spectral representation of intermediate layers through the depth of networks and optimize it for a lightweight model. The optimized network improves performance and enables fast training and inference times. The proposed spectral deep supervision helps to achieve not only high performance but also fast convergence speed through the regularization of the intermediate layers. The effect of the proposed methods was confirmed through a thorough ablation study on public datasets. As a result, similar or outperforming results were obtained in comparison to state-of-the-art models. In particular, our model achieved an RMSE of 1 bpm on the PURE dataset, demonstrating its high accuracy. Moreover, it excelled on the V4V dataset with an impressive RMSE of 6.65 bpm, outperforming other methods. We observe that our model began converging from the very first epoch, a significant improvement over other models in terms of learning efficiency. Our approach is expected to be generally applicable to models that learn spectral domain information as well as to the applications of regression that require the representations of periodicity.
An Investigation on the Effects of Dietary Vitamin E on Juvenile Sea Urchin (Strongylocentrotus intermedius): Growth, Intestinal Microbiota, Immune Response, and Related Gene Expression
Authors: Li Min , Gou Dan , Gong Panke , Di Weixiao , Wang Lina , Ding Jun , Chang Yaqing , Zuo Rantao
Published: December 2023

A 90 d feeding experiment was conducted to investigate the effects of vitamin E (VE) on growth, intestinal microbiota, immune response, and related gene expression of juvenile sea urchin (Strongylocentrotus intermedius). Six dry feeds were made to contain graded levels of VE (78, 105, 152, 235, 302, and 390 mg/kg); these were named E78, E105, E152, E235, E302, and E390, respectively. Dry feed E50 and fresh kelp (HD) were used as the control diets. There were six replicates of cages in each dietary group, and each cage held 20 sea urchins with an initial body weight of approximately 1.50 g. Results exhibited that weight gain rate and gonadosomatic index (GSI) of the sea urchins were not significantly affected by dietary VE ranging from 78 to 390 mg/kg. Sea urchins in the dry feed groups showed poorer growth performance, but significantly higher GSI than those in the fresh kelp groups. The pepsin and lipase activities were not significantly promoted by low or moderate VE, but were inhibited by a high level of VE (302–390 mg/kg), while amylase and cellulase activities were significantly increased by low or moderate VE, with the highest values observed in the E105 and E235 groups, respectively. VE addition at a low dosage (105–152 mg/kg) showed inhibitory effects on immune and antioxidant enzyme activities and expression of inflammation-related genes, but showed no beneficial effects at moderate or high dosage (235–390 mg/kg), while a moderate or relatively higher level of VE (235–302 mg/kg) significantly increased the expression of several immune-related genes. The relative abundance of Proteobacteria, Actinobacteria, Ruegeria, and Maliponia in the intestine of the sea urchins increased with the increase in VE in the dry feeds. On the contrary, the relative abundance of the Firmicutes, Bacteroidetes, Escherichia-Shigella, Bacteroides, and Clostridium sensu stricto 1 gradually decreased as VE content increased. These results indicated that a moderate level of VE (172.5–262.4) can achieve ideal digestive enzyme activities and growth performance, but a relatively higher level of VE (235–302 mg/kg) was beneficial for maintaining the immune and antioxidant capacity of juvenile S. intermedius by regulating the expression of inflammation- and immune-related genes and abundance of some bacteria to a healthy state.
A Method to Locally Irradiate Specific Organ in Model Organisms Using a Focused Heavy-Ion Microbeam
Authors: Funayama Tomoo , Suzuki Michiyo , Miyawaki Nobumasa , Kashiwagi Hirotsugu
Published: December 2023

The functions of organisms are performed by various tissues composed of different cell types. Localized irradiation with heavy-ion microbeams, which inactivate only a portion of the constituent cells without destroying the physical intercellular connections of the tissue, is a practical approach for elucidating tissue functions. However, conventional collimated microbeams are limited in the shape of the area that can be irradiated. Therefore, using a focused heavy-ion microbeam that generates a highly precise beam spot, we developed a technology to uniformly irradiate specific tissues of an organism with a defined dose, which conventional methods cannot achieve. The performance of the developed paint irradiation technology was evaluated. By irradiating the CR-39 ion track detector, we confirmed that the new method, in which each ion hit position is placed uniformly in the irradiated area, makes it possible to uniformly paint the area at a specified dose. The targeted irradiation of the pharynx and gonads of living Caenorhabditis elegans demonstrated that the irradiated ions were distributed in the same shape as the targeted tissue observed under a microscope. This technology will elucidate biological mechanisms that are difficult to analyze with conventional collimated microbeam irradiation.
Assessment of Drought and Zinc Stress Tolerance of Novel Miscanthus Hybrids and Arundo donax Clones Using Physiological, Biochemical, and Morphological Traits
Authors: Islam Monirul , Ferrarini Andrea , Ali Amjad , Kam Jason , Trindade Luisa M. , Clifton-Brown John , Amaducci Stefano
Published: December 2023

High-yield potential perennial crops, such as Miscanthus spp. and Arundo donax are amongst the most promising sources of sustainable biomass for bioproducts and bioenergy. Although several studies assessed the agronomic performance of these species on diverse marginal lands, research to date on drought and zinc (Zn) resistance is scarce. Thus, the objective of this study was to investigate the drought and Zn stress tolerance of seven novel Miscanthus hybrids and seven Arundo clones originating from different parts of Italy. We subjected both species to severe drought (less than 30%), and Zn stress (400 mg/kg−1 of ZnSO4) separately, after one month of growth. All plants were harvested after 28 days of stress, and the relative drought and Zn stress tolerance were determined by using a set of morpho-physio-biochemical and biomass attributes in relation to stress tolerance indices (STI). Principal component analysis (PCA), hierarchical clustering analysis (HCA) and stress tolerance indices (STI) were performed for each morpho-physio-biochemical and biomass parameters and showed significant relative differences among the seven genotypes of both crops. Heatmaps of these indices showed how the different genotypes clustered into four groups. Considering PCA ranking value, Miscanthus hybrid GRC10 (8.11) and Arundo clone PC1 (11.34) had the highest-ranking value under both stresses indicating these hybrids and clones are the most tolerant to drought and Zn stress. In contrast, hybrid GRC3 (−3.33 lowest ranking value) and clone CT2 (−5.84) were found to be the most sensitive to both drought and Zn stress.
The Impact of Genetic Polymorphisms on Anterior Cruciate Ligament Injuries in Athletes: A Meta-Analytical Approach
Authors: Bulbul Alpay , Ari Erdal , Apaydin Necdet , Ipekoglu Gokhan
Published: December 2023

This meta-analysis aimed to investigate the association between genetic polymorphisms in Collagen type 1 alpha-1 (COL1A1), Collagen type 3 alpha-1 (COL3A1), Collagen type 5 alpha-1 (COL5A1), and Collagen type 12 alpha-1 (COL12A1) genes and anterior cruciate ligament (ACL) injuries in athletes. A systematic search was diligently conducted on the PubMed and Web of Science databases to identify relevant studies on 5–9 September 2023. Only case–control studies were included in the meta-analysis. A total of 19 studies were reviewed, involving the analysis of 3522 cases and 6399 control subjects. Data relevant to the study objectives were extracted from these chosen studies and subsequently analyzed using either a random-effects or fixed-effects model. It indicates that individuals carrying the G allele in the COL1A1 (rs1107946) gene have a decreased risk of anterior cruciate ligament injuries (OR: −0.27, 95% CI: −0.42 to −0.12, p < 0.001). A similar relationship was observed in the dominant model, but this relationship was reversed in the recessive model (OR: 0.69, 95% CI: 0.33 to 1.05, p < 0.001). However, no significant associations were found in the COL3A1 (rs1800255) and COL5A1 (rs12722) genes. In the COL12A1 (rs970547) gene, the A allele was associated with an increased risk of anterior cruciate ligament injuries (OR: 0.18, 95% CI: 0.01 to 0.36, p = 0.041). This meta-analysis suggests that genetic variants in COL1A1 (rs1107946) and COL12A1 (rs970547) may be associated with ACL injuries in athletes. However, COL3A1 rs1800255 and COL5A1 rs12722 gene variants do not appear to have a significant association with these injuries.
The Molecular Evolution, Structure, and Function of Coproporphyrinogen Oxidase and Protoporphyrinogen Oxidase in Prokaryotes
Authors: Zámocký Marcel , Hofbauer Stefan , Gabler Thomas , Furtmüller Paul G.
Published: December 2023

Coproporphyrinogen oxidase (CgoX) and protoporphyrinogen oxidase (PgoX) catalyze the oxidation of the flexible cyclic tetrapyrrole of porphyrinogen compounds into fully conjugated, planar macrocyclic porphyrin compounds during heme biosynthesis. These enzymes are activated via different pathways. CgoX oxidizes coproporphyrinogen III to coproporphyrin III in the coproporphyrin-dependent pathway, whereas PgoX oxidizes protoporphyrinogen IX to protoporphyrin IX in the penultimate step of the protoporphyrin-dependent pathway. The phylogenetic analysis presented herein demonstrates a clear differentiation between the two enzyme classes, as evidenced by the clustering of sequences in distinct clades, and it shows that, at the origin of porphyrinogen-type oxidase evolution, PgoXs from cyanobacteria were found, which were noticeably separated from descendant PgoX representatives of Deltaproteobacteria and all later PgoX variants, leading to many eukaryotic clades. CgoX sequences originating from the monoderm Actinomycetota and Bacillota were well separated from the predecessor clades containing PgoX types and represent a peculiar type of gene speciation. The structural similarities and differences between these two oxidases are discussed based on their protein sequence alignment and a structural comparison.
The Impact of Apolipoprotein E (APOE) Epigenetics on Aging and Sporadic Alzheimer’s Disease
Authors: Lozupone Madia , Dibello Vittorio , Sardone Rodolfo , Castellana Fabio , Zupo Roberta , Lampignano Luisa , Bortone Ilaria , Daniele Antonio , Bellomo Antonello , Solfrizzi Vincenzo , Panza Francesco
Published: December 2023

Sporadic Alzheimer’s disease (AD) derives from an interplay among environmental factors and genetic variants, while epigenetic modifications have been expected to affect the onset and progression of its complex etiopathology. Carriers of one copy of the apolipoprotein E gene (APOE) ε4 allele have a 4-fold increased AD risk, while APOE ε4/ε4-carriers have a 12-fold increased risk of developing AD in comparison with the APOE ε3-carriers. The main longevity factor is the homozygous APOE ε3/ε3 genotype. In the present narrative review article, we summarized and described the role of APOE epigenetics in aging and AD pathophysiology. It is not fully understood how APOE variants may increase or decrease AD risk, but this gene may affect tau- and amyloid-mediated neurodegeneration directly or indirectly, also by affecting lipid metabolism and inflammation. For sporadic AD, epigenetic regulatory mechanisms may control and influence APOE expression in response to external insults. Diet, a major environmental factor, has been significantly associated with physical exercise, cognitive function, and the methylation level of several cytosine-phosphate-guanine (CpG) dinucleotide sites of APOE.
Influence of Breast Cancer Extracellular Vesicles on Immune Cell Activation: A Pilot Study
Authors: Santoro Jessie , Carrese Barbara , Peluso Maria Sara , Coppola Luigi , D’Aiuto Massimiliano , Mossetti Gennaro , Salvatore Marco , Smaldone Giovanni
Published: December 2023

Breast cancer is the leading cause of cancer-related death in women worldwide. It is well known that breast cancer shows significant alterations in the tumor microenvironment (TME), which is composed of a variety of immune cells, including natural killer (NK) cells, that have a key role in tumor development or anti-tumor responses in breast cancer patients. Luminal B (BT474) and triple-negative breast cancer (HS578T) cell lines were cultured in 2D and 3D model systems. PMBCs from healthy donors were isolated and treated with extracellular vesicles (EVs) from monolayer and spheroids of BT474 and HS578T and analyzed using cytofluorimetric approaches. We observed that EVs can alter the activation and presence of CD335+/CD11b+ NK cells. EVs derived from BT474 and HS578T cells trigger the activation and, simultaneously, a reduction in the percentage of CD335+/CD11b+ NK cells. In addition, EVs derived from BT474 also significantly reduce CD39+ T-regulatory (T-reg) cells. Our preliminary data suggest that using EVs to treat tumors could potentially alter components of the immune system, which causes hyperactivation of specific cell types and can lead to aggressive growth. These data will guide the designing of new personalized diagnostic approaches based on in-depth study of the TME.
Spermine Oxidase–Substrate Electrostatic Interactions: The Modulation of Enzyme Function by Neighboring Colloidal ɣ-Fe2O3
Authors: Rilievo Graziano , Magro Massimiliano , Tonolo Federica , Cecconello Alessandro , Rutigliano Lavinia , Cencini Aura , Molinari Simone , Di Paolo Maria Luisa , Fiorucci Cristian , Rossi Marianna Nicoletta , Cervelli Manuela , Vianello Fabio
Published: December 2023

Protein–nanoparticle hybridization can ideally lead to novel biological entities characterized by emerging properties that can sensibly differ from those of the parent components. Herein, the effect of ionic strength on the biological functions of recombinant His-tagged spermine oxidase (i.e., SMOX) was studied for the first time. Moreover, SMOX was integrated into colloidal surface active maghemite nanoparticles (SAMNs) via direct self-assembly, leading to a biologically active nano-enzyme (i.e., SAMN@SMOX). The hybrid was subjected to an in-depth chemical–physical characterization, highlighting the fact that the protein structure was perfectly preserved. The catalytic activity of the nanostructured hybrid (SAMN@SMOX) was assessed by extracting the kinetics parameters using spermine as a substrate and compared to the soluble enzyme as a function of ionic strength. The results revealed that the catalytic function was dominated by electrostatic interactions and that they were drastically modified upon hybridization with colloidal ɣ-Fe2O3. The fact that the affinity of SMOX toward spermine was significantly higher for the nanohybrid at low salinity is noteworthy. The present study supports the vision of using protein–nanoparticle conjugation as a means to modulate biological functions.
Cervical Sagittal Balance: Impact on Clinical Outcomes and Subsidence in Anterior Cervical Discectomy and Fusion
Authors: Bębenek Adam , Dominiak Maciej , Godlewski Bartosz
Published: December 2023

Degenerative disease of the cervical spine leads to sagittal imbalance, which may affect treatment results. The purpose of this study was to evaluate changes in selected cervical sagittal balance parameters and their effects on subsidence and clinical outcomes of the procedure. This study encompassed a total of 95 evaluated patients who underwent anterior cervical discectomy and fusion (ACDF). Selected cervical sagittal balance parameters were assessed using lateral projection X-rays: C2–C7 spinal vertical axis (C2–C7 SVA), spinocranial angle (SCA), C7 slope, C2–C7 lordosis, and the segmental Cobb angle. Measurements were collected the day before, the day after, and 12 months after surgery. Changes in clinical parameters was assessed using the VAS and NDI scales. Subsidence was defined as a loss of intervertebral height of more than 30% of the baseline value. Among all the assessed parameters, only the C2–C7 SVA demonstrated a statistically significant difference between the groups with and without subsidence: 26.03 vs. 21.79 [mm], with p = 0.0182, preoperatively and 27.80 vs. 24.94 [mm], with p = 0.0449, on the day after surgery, respectively. We conclude that higher preoperative and postoperative C2–C7 SVA values might contribute to an elevated risk of implant subsidence. Furthermore, both the SCA and C7 slope could conceivably influence the clinical outcome, respectively impacting pain, as assessed by the VAS and the disability, as evaluated through the NDI scale.
Improvement of Symptoms and Cardiac Magnetic Resonance Abnormalities in Patients with Post-Acute Sequelae of SARS-CoV-2 Cardiovascular Syndrome (PASC-CVS) after Guideline-Oriented Therapy
Authors: Gyöngyösi Mariann , Hasimbegovic Ena , Han Emilie , Zlabinger Katrin , Spannbauer Andreas , Riesenhuber Martin , Hamzaraj Kevin , Bergler-Klein Jutta , Hengstenberg Christian , Kammerlander Andreas , Kastl Stefan , Loewe Christian , Beitzke Dietrich
Published: December 2023

Cardiac magnetic resonance (CMR) studies reported CMR abnormalities in patients with mild–moderate SARS-CoV-2 infection, suggesting ongoing myocardial inflammation. Patients (n = 278, 43 ± 13 years, 70.5% female) with post-acute sequelae of SARS-CoV-2 cardiovascular syndrome (PASC-CVS) were included prospectively into the Vienna POSTCOV Registry between March 2021 and March 2023 (clinicaltrials.gov NCT05398952). Clinical, laboratory, and CMR findings were recorded. Patients with abnormal CMR results were classified into isolated chronic pericardial (with/without pleural) effusion, isolated cardiac function impairment, or both (myopericarditis) groups. Medical treatment included a nonsteroidal anti-inflammatory agent (NSAID) for pericardial effusion and a condition-adapted maximal dose of heart failure (HF) treatment. Three months after medical therapy, clinical assessment and CMR were repeated in 82 patients. Laboratory analyses revealed normal hematological, inflammatory, coagulation, and cardiac biomarkers. CMR abnormalities were found in 155 patients (55.8%). Condition-adapted HF treatment led to a significant increase in the left ventricular ejection fraction (LVEF) in patients with initially reduced LVEF (from 49 ± 5% to 56 ± 4%, p = 0.009, n = 25). Low–moderate doses of NSAIDs for 3 months significantly reduced pericardial effusion (from 4/3;5.75/mm to 2/0;3/mm, median/interquartile ranges/p < 0.001, n = 51). Clinical symptoms improved markedly with a decrease in CMR abnormalities, which might be attributed to the maintenance of NSAID and HF medical treatment for PASC-CVS.
Generation and Characterization of a Human-Derived and Induced Pluripotent Stem Cell (iPSC) Line from an Alzheimer’s Disease Patient with Neuropsychiatric Symptoms
Authors: Sagar Ram , Zivko Cristina , Xydia Ariadni , Weisman David C. , Lyketsos Constantine G. , Mahairaki Vasiliki
Published: December 2023

Agitation is one of the most eminent characteristics of neuropsychiatric symptoms (NPS) affecting people living with Alzheimer’s and Dementia and has serious consequences for patients and caregivers. The current consensus is that agitation results, in part, from the disruption of ascending monoamine regulators of cortical circuits, especially the loss of serotonergic activity. It is believed that the first line of treatment for these conditions is selective serotonin reuptake inhibitors (SSRIs), but these are effective in only about 40% of patients. Person-specific biomarkers, for example, ones based on in vitro iPSC-derived models of serotonin activity, which predict who with Agitation responds to an SSRI, are a major clinical priority. Here, we report the generation of human-induced pluripotent stem cells (iPSCs) from a 74-year-old AD patient, the homozygous APOE ε4/ε4 carrier, who developed Agitation. His iPSCs were reprogrammed from peripheral blood mononuclear cells (PBMCs) using the transient expression of pluripotency genes. These display typical iPSC characteristics that are karyotypically normal and attain the capacity to differentiate into three germ layers. The newly patient-derived iPSC line offers a unique resource to investigate the underlying mechanisms associated with neuropsychiatric symptom progression in AD.
Impacts of Building Environment and Urban Green Space Features on Urban Air Quality: Focusing on Interaction Effects and Nonlinearity
Authors: Wu Binsheng , Liu Chunqing
Published: December 2023

Air pollution is a rising environmental concern that has detrimental effects on human health and the environment. Building environment and urban green space features play a crucial role in the dispersion and accumulation of air pollutants. This study examines the impacts of building environment and urban green space on air pollution levels in the highly urbanized city of Hong Kong, focusing on their interaction effects and potential nonlinearity. For the analysis, this paper investigates how building density, building height, building types, urban green space size, and number of urban green space clusters, as well as their interplays, impact PM2.5 concentrations using high-resolution, satellite-based PM2.5 grids coupled with spatial analysis techniques. The findings reveal that a unit increase in the size of urban green space and the standard deviation of building height contribute to a 0.0004 and a 0.0154 reduction in PM levels, respectively. In contrast, air pollution levels are found to be positively associated with building density (0.1117), scatteredness of urban green space (0.0003), and share of commercial buildings (1.0158). Moreover, it has been found that building height presents a U-shape relationship with PM2.5 concentrations. Finally, the negative association between the size of urban green space and air pollution levels tends to be enlarged in districts with more low-rise buildings. This study conveys important building environment and urban green space planning implications.
Carbon Footprint Reduction and Climate Change Mitigation: A Review of the Approaches, Technologies, and Implementation Challenges
Authors: Lobus Nikolay V. , Knyazeva Maria A. , Popova Anna F. , Kulikovskiy Maxim S.
Published: December 2023

Since the Industrial Revolution, human economic activity and the global development of society in general have been heavily dependent on the exploitation of natural resources. The use of fossil fuels, deforestation, the drainage of wetlands, the transformation of coastal marine ecosystems, unsustainable land use, and many other unbalanced processes of human activity have led to an increase both in the anthropogenic emissions of climate-active gases and in their concentration in the atmosphere. It is believed that over the past ~150 years these phenomena have contributed to an increase in the global average temperature in the near-surface layer of the atmosphere by ~1 °C. Currently, the most pressing tasks facing states and scientific and civil societies are to reduce anthropogenic CO2 emissions and to limit the global air temperature increase. In this regard, there is an urgent need to change existing production systems in order to reduce greenhouse gas emissions and to sequester them. In this review, we consider up-to-date scientific approaches and innovative technologies, which may help in developing roadmaps to reduce the emissions of climate-active gases, control rising temperatures, decarbonize economies, and promote the sustainable development of society in general.
Comparison of Multiparametric MRI, [68Ga]Ga-PSMA-11 PET-CT, and Clinical Nomograms for Primary T and N Staging of Intermediate-to-High-Risk Prostate Cancer
Authors: Tayara Omar Marek , Pełka Kacper , Kunikowska Jolanta , Malewski Wojciech , Sklinda Katarzyna , Kamecki Hubert , Poletajew Sławomir , Kryst Piotr , Nyk Łukasz
Published: December 2023

Purpose of the Report: Although multiparametric magnetic resonance imaging (mpMRI) is commonly used for the primary staging of prostate cancer, it may miss non-enlarged metastatic lymph nodes. Positron emission tomography-computed tomography targeting the prostate-specific membrane antigen (PSMA PET-CT) is a promising method to detect non-enlarged metastatic lymph nodes, but more data are needed. Materials and Methods: In this single-center, prospective study, we enrolled patients with intermediate-to-high-risk prostate cancer scheduled for radical prostatectomy with pelvic node dissection. Before surgery, prostate imaging with mpMRI and PSMA PET-CT was used to assess lymph node involvement (LNI), extra-prostatic extension (EPE), and seminal vesicle involvement (SVI). Additionally, we used clinical nomograms to estimate the risk of these three outcomes. Results: Of the 74 patients included, 61 (82%) had high-risk prostate cancer, and the rest had intermediate-risk cancer. Histopathology revealed LNI in 20 (27%) patients, SVI in 26 (35%), and EPE in 52 (70%). PSMA PET-CT performed better than mpMRI at detecting LNI (area under the curve (AUC, 95% confidence interval): 0.779 (0.665–0.893) vs. 0.655 (0.529–0.780)), but mpMRI was better at detecting SVI (AUC: 0.775 (0.672–0.878) vs. 0.585 (0.473–0.698)). The MSKCC nomogram performed well at detecting both LNI (AUC: 0.799 (0.680–0.918)) and SVI (0.772 (0.659–0.885)). However, when the nomogram was used to derive binary diagnoses, decision curve analyses showed that the MSKCC nomogram provided less net benefit than mpMRI and PSMA PET-CT for detecting SVI and LNI, respectively. Conclusions: mpMRI and [68Ga]Ga-PSMA-11 PET-CT are complementary techniques to be used in conjunction for the primary T and N staging of prostate cancer.
Challenges and Future Directions in the Management of Tumor Mutational Burden-High (TMB-H) Advanced Solid Malignancies
Authors: Ahmed Jibran , Das Biswajit , Shin Sarah , Chen Alice
Published: December 2023

A standardized assessment of Tumor Mutational Burden (TMB) poses challenges across diverse tumor histologies, treatment modalities, and testing platforms, requiring careful consideration to ensure consistency and reproducibility. Despite clinical trials demonstrating favorable responses to immune checkpoint inhibitors (ICIs), not all patients with elevated TMB exhibit benefits, and certain tumors with a normal TMB may respond to ICIs. Therefore, a comprehensive understanding of the intricate interplay between TMB and the tumor microenvironment, as well as genomic features, is crucial to refine its predictive value. Bioinformatics advancements hold potential to improve the precision and cost-effectiveness of TMB assessments, addressing existing challenges. Similarly, integrating TMB with other biomarkers and employing comprehensive, multiomics approaches could further enhance its predictive value. Ongoing collaborative endeavors in research, standardization, and clinical validation are pivotal in harnessing the full potential of TMB as a biomarker in the clinic settings.
The Role of Geriatric Assessment in the Management of Diffuse Large B-Cell Lymphoma
Authors: Merli Francesco , Pozzi Stefano , Catellani Hillary , Barbieri Emiliano , Luminari Stefano
Published: December 2023

The treatment choice for an older patient with diffuse large B-cell lymphoma (DLBCL) depends on many other factors in addition to age, which alone does not reflect the complexity of the aging process. Functional features and comorbidity incidence differ not only between younger and older patients but also among older patients themselves. The comprehensive geriatric assessment (CGA) quickly evaluates fitness status by investigating the patient’s different functional areas, degree of autonomy, and presence of comorbidities. Various tools are available to evaluate frailty; which assessment tool to use should be based on the clinical aim. The simplified geriatric assessment (sGA) from the elderly project by the Fondazione Italiana Linfomi, prospectively tested on the largest number of patients, categorizes patients as fit, unfit, or frail, with a decreasing rate of overall survival. The elderly prognostic index (EPI), which combines sGA and IPI scores and hemoglobin level, is the first prognostic score for older patients, with three risk groups for survival. Future GAs should consider new parameters, including sarcopenia, which appears to be inversely related to survival. New tools based on prospective studies can help physicians choose the best treatment in light of the individual patient’s characteristics.
Multi-Scale and Multi-Physics Models of the Transport of Therapeutic/Diagnostic Cancer Agents
Authors: Moradi Kashkooli Farshad , Kolios Michael C.
Published: December 2023

The effectiveness of tumor treatment heavily relies on the successful delivery of anticancer drugs [...]
Splenic Hilar Involvement and Sinistral Portal Hypertension in Unresectable Pancreatic Tail Cancer
Authors: Okamoto Takeshi , Takeda Tsuyoshi , Mie Takafumi , Hirai Tatsuki , Ishitsuka Takahiro , Yamada Manabu , Nakagawa Hiroki , Furukawa Takaaki , Kasuga Akiyoshi , Sasaki Takashi , Ozaka Masato , Sasahira Naoki
Published: December 2023

Background: Pancreatic tail cancer (PTC) frequently displays splenic hilar involvement (SHI), but its impact on clinical outcomes remains unclear. We investigated the clinical impact of SHI in patients with unresectable PTC. Methods: We retrospectively reviewed all patients with unresectable PTC who received first-line therapy at our institution from 2016 to 2020. Results: Of the 111 included patients, 48 had SHI at diagnosis. SHI was significantly associated with younger age, liver metastasis, peritoneal dissemination, larger tumor size, modified Glasgow prognostic score of 1 or more, splenic artery involvement, gastric varices, and splenomegaly. Shorter median overall survival (OS; 9.3 vs. 11.6 months, p = 0.003) and progression-free survival (PFS; 4.3 vs. 6.3 months, p = 0.013) were observed in SHI patients. Poor performance status of 1 or 2, tumor size > 50 mm, hepatic metastasis, mGPS of 1 or 2, and SHI (hazard ratio: 1.65, 95% confidence interval: 1.08–2.52, p = 0.020) were independent predictors of shorter OS. Splenic artery pseudoaneurysm rupture and variceal rupture were rare and only observed in cases with SHI. Conclusions: Splenic hilar involvement is associated with worse outcomes in pancreatic tail cancer.