bluuebunny/crossref_metadata_2025 huggingface dataset:
Putative Molecular Mechanisms Underpinning the Inverse Roles of Mitochondrial Respiration and Heme Function in Lung Cancer and Alzheimer’s Disease
Authors: Afsar Atefeh , Zhang Li
Published: March 2024

Mitochondria are the powerhouse of the cell. Mitochondria serve as the major source of oxidative stress. Impaired mitochondria produce less adenosine triphosphate (ATP) but generate more reactive oxygen species (ROS), which could be a major factor in the oxidative imbalance observed in Alzheimer’s disease (AD). Well-balanced mitochondrial respiration is important for the proper functioning of cells and human health. Indeed, recent research has shown that elevated mitochondrial respiration underlies the development and therapy resistance of many types of cancer, whereas diminished mitochondrial respiration is linked to the pathogenesis of AD. Mitochondria govern several activities that are known to be changed in lung cancer, the largest cause of cancer-related mortality worldwide. Because of the significant dependence of lung cancer cells on mitochondrial respiration, numerous studies demonstrated that blocking mitochondrial activity is a potent strategy to treat lung cancer. Heme is a central factor in mitochondrial respiration/oxidative phosphorylation (OXPHOS), and its association with cancer is the subject of increased research in recent years. In neural cells, heme is a key component in mitochondrial respiration and the production of ATP. Here, we review the role of impaired heme metabolism in the etiology of AD. We discuss the numerous mitochondrial effects that may contribute to AD and cancer. In addition to emphasizing the significance of heme in the development of both AD and cancer, this review also identifies some possible biological connections between the development of the two diseases. This review explores shared biological mechanisms (Pin1, Wnt, and p53 signaling) in cancer and AD. In cancer, these mechanisms drive cell proliferation and tumorigenic functions, while in AD, they lead to cell death. Understanding these mechanisms may help advance treatments for both conditions. This review discusses precise information regarding common risk factors, such as aging, obesity, diabetes, and tobacco usage.
Artificial Feeding Systems for Vector-Borne Disease Studies
Authors: Olajiga Olayinka M. , Jameson Samuel B. , Carter Brendan H. , Wesson Dawn M. , Mitzel Dana , Londono-Renteria Berlin
Published: March 2024

This review examines the advancements and methodologies of artificial feeding systems for the study of vector-borne diseases, offering a critical assessment of their development, advantages, and limitations relative to traditional live host models. It underscores the ethical considerations and practical benefits of such systems, including minimizing the use of live animals and enhancing experimental consistency. Various artificial feeding techniques are detailed, including membrane feeding, capillary feeding, and the utilization of engineered biocompatible materials, with their respective applications, efficacy, and the challenges encountered with their use also being outlined. This review also forecasts the integration of cutting-edge technologies like biomimicry, microfluidics, nanotechnology, and artificial intelligence to refine and expand the capabilities of artificial feeding systems. These innovations aim to more accurately simulate natural feeding conditions, thereby improving the reliability of studies on the transmission dynamics of vector-borne diseases. This comprehensive review serves as a foundational reference for researchers in the field, proposing a forward-looking perspective on the potential of artificial feeding systems to revolutionize vector-borne disease research.
Heart Rate and Acceleration Dynamics during Swim-Fitness and Stress Challenge Tests in Yellowtail Kingfish (Seriola lalandi)
Authors: Palstra Arjan P. , Abbink Wout , Agbeti Wisdom E. K. , Kruijt Leo , Jéhannet Pauline , Lankheet Martin J.
Published: March 2024

The yellowtail kingfish is a highly active and fast-growing marine fish with promising potential for aquaculture. In this study, essential insights were gained into the energy economy of this species by heart rate and acceleration logging during a swim-fitness test and a subsequent stress challenge test. Oxygen consumption values of the 600–800 g fish, when swimming in the range of 0.2 up to 1 m·s−1, were high—between 550 and 800 mg·kg−1·h−1—and the heart rate values—up to 228 bpm—were even among the highest ever measured for fishes. When swimming at these increasing speeds, their heart rate increased from 126 up to 162 bpm, and acceleration increased from 11 up to 26 milli-g. When exposed to four sequential steps of increasing stress load, the decreasing peaks of acceleration (baseline values of 12 to peaks of 26, 19 and 15 milli-g) indicated anticipatory behavior, but the heart rate increases (110 up to 138–144 bpm) remained similar. During the fourth step, when fish were also chased, peaking values of 186 bpm and 44 milli-g were measured. Oxygen consumption and heart rate increased with swimming speed and was well reflected by increases in tail beat and head width frequencies. Only when swimming steadily near the optimal swimming speed were these parameters strongly correlated.
Exploration of the Binding Mechanism of Cyclic Dinucleotide Analogs to Stimulating Factor Proteins and the Implications for Subsequent Analog Drug Design
Authors: Yuan Shu-Wei , Shi Hong-Ling , Fu Mu-Ran , Zhang Xi-Chuan , Xi Xiao-Qi , Wang Yao , Shen Tai-Song , Ma Jin-Liang , Tang Cun-Duo
Published: March 2024

Cyclic dinucleotides (CDNs) are cyclic molecules consisting of two nucleoside monophosphates linked by two phosphodiester bonds, which act as a second messenger and bind to the interferon gene stimulating factor (STING) to activate the downstream signaling pathway and ultimately induce interferon secretion, initiating an anti-infective immune response. Cyclic dinucleotides and their analogs are lead compounds in the immunotherapy of infectious diseases and tumors, as well as immune adjuvants with promising applications. Many agonists of pathogen recognition receptors have been developed as effective adjuvants to optimize vaccine immunogenicity and efficacy. In this work, the binding mechanism of human-derived interferon gene-stimulating protein and its isoforms with cyclic dinucleotides and their analogs was theoretically investigated using computer simulations and combined with experimental results in the hope of providing guidance for the subsequent synthesis of cyclic dinucleotide analogs.
The Possible Role of Pathogens and Chronic Immune Stimulation in the Development of Diffuse Large B-Cell Lymphoma
Authors: Gergely Lajos , Udvardy Miklos , Illes Arpad
Published: March 2024

Diffuse large B-cell lymphoma (DLBCL) is the most common type of non-Hodgkin lymphoma. The disease is very heterogeneous, with distinct genetic alterations in subtypes. The WHO 2022 5th edition classification identifies several minor groups of large B-cell lymphoma where the pathogenetic role of viruses (like EBV and HHV-8) is identified. Still, most cases fall into the group of DLBCL not otherwise specified (NOS). No review focuses only on this specific lymphoma type in the literature. The pathogenesis of this entity is still not fully understood, but several viruses and bacteria may have a role in the development of the disease. The authors review critical pathogenetic events in the development of DLBCL (NOS) and summarize the data available on several pathogenetic viruses and bacteria that have a proven or may have a potential role in the development of this lymphoma type. The possible role of B-cell receptor signaling in the microenvironment is also discussed. The causative role of the Epstein–Barr virus (EBV), human herpesvirus-8 (HHV-8), Hepatitis C virus (HCV), human immunodeficiency virus (HIV), Hepatitis B virus (HBV), and other viruses are explored. Bacterial infections, such as Helicobacter pylori, Campylobacter jejuni, Chlamydia psittaci, Borrelia burgdorferi, and other bacteria, are also reviewed.
The hTERT and iCasp9 Transgenes Affect EOMES and T-BET Levels in NK Cells and the Introduction of Both Genes Improves NK Cell Proliferation in Response to IL2 and IL15 Stimulation
Authors: Palamarchuk Anastasia I. , Kovalenko Elena I. , Streltsova Maria A.
Published: March 2024

The NK cell exhaustion state evolving during extensive and prolonged cultivation is still one of the limitations of NK cell approaches. In this research, we transduced NK cells with the hTERT and iCasp9 genes. hTERT overexpression can prevent the functional exhaustion of NK cells during long-term cultivation, but, still, the therapeutic use of such cells is unsafe without irradiation. To overcome this obstacle, we additionally transduced NK cells with the iCasp9 transgene that enables the rapid elimination of modified cells. We compared the proliferative and functional activities of the hTERT- and/or iCasp9-modified NK cells, determined their exhaustion state and monitored the levels of EOMES and T-BET, the main NK cell transcription factors. The hTERT and iCasp9 genes were shown to affect the EOMES and T-BET levels differently in the NK cells. The EOMES+T-BET+ phenotype characterized the functionally active NK cells during two months of culture upon stimulation with IL2 and K562-mbIL21 feeder cells, which induced the greatest expansion rates of the NK cells, independently of the transgene type. On the other hand, under cytokine stimulation, the hTERT-iCasp9-NK cells displayed improved proliferation over NK cells modified with iCasp9 alone and showed an increased proliferation rate compared to the untransduced NK cells under stimulation with IL2 and IL15, which was accompanied by reduced immune checkpoint molecule expression. The individual changes in the EOMES and T-BET levels strictly corresponded to the NK cell functional activity, the surface levels of activating and inhibitory receptors along with the expansion rate and expression levels of pro-survival and pro-apoptotic genes.
TAFRO Syndrome: A Syndrome or a Subtype of Multicentric Castleman Disease?
Authors: Takai Kazue
Published: March 2024

TAFRO (thrombocytopenia, anasarca, fever, reticulin fibrosis of bone marrow/renal dysfunction, organomegaly) syndrome is a systemic inflammatory disorder of unknown etiology. It has been recognized as a subtype of idiopathic multicentric Castleman disease (iMCD), and the international diagnostic criteria for iMCD-TAFRO require a lymph node histopathology consistent with iMCD. Furthermore, TAFRO syndrome is defined as a heterogeneous clinical entity caused by underlying diseases such as malignancy, autoimmune diseases, or infections. However, the cases that led to the proposal of TAFRO syndrome lacked recognizable lymphadenopathy and were inconsistent with any other diseases, despite vigorous efforts in differential diagnosis. Irrespective of the presence or absence of Castleman disease (CD)-like histology, TAFRO syndrome exhibits homogeneous clinical, laboratory, and prognostic features, setting it apart from iMCD without TAFRO syndrome. Defining iMCD-TAFRO apart from TAFRO syndrome is deemed meaningless and confusing. MCD is a heterogeneous lymphoproliferative disorder consisting of several subtypes with different pathogenesis, clinical manifestations, and histological features. Typical MCD in Japan, characterized by the histology of plasma cell type and marked polyclonal hypergammaglobulinemia, is identical to idiopathic plasmacytic lymphadenopathy with polyclonal hyperimmunoglobulinemia (IPL). Although IPL is classified into iMCD-NOS (not otherwise specified), it should be recognized as a distinct clinicopathological entity. Furthermore, we propose to separate TAFRO syndrome from the MCD category as a defined disorder.
Incretin Hormone Secretion in Women with Polycystic Ovary Syndrome: Roles of Obesity, Insulin Sensitivity and Treatment with Metformin and GLP-1s
Authors: Etrusco Andrea , Mikuš Mislav , D’Amato Antonio , Barra Fabio , Planinić Petar , Goluža Trpimir , Buzzaccarini Giovanni , Marušić Jelena , Tešanović Mara , Laganà Antonio Simone
Published: March 2024

Background: The purpose of this narrative review is to describe the mechanisms that are responsible for the development of infertility and PCOS, with a focus on the role of obesity, insulin sensitivity and treatment with metformin and GLP-1s. Methods: The relevant publications were identified after systematic queries of the following sources: PubMed, Google Scholar, Web of Science, and publishers’ databases, complemented by a cross-check of the reference lists. We used a combination of the search terms “polycystic ovary syndrome”, “obesity” and “insulin resistance” with “metformin”, “exenatide”, “liraglutide”, “semaglutide”, “orlistat” and terms relevant to the topic of each paragraph (e.g., “pathophysiology”, “metabolism”, “infertility”, “treatment”). Results: All articles describing the mechanisms responsible for the development of infertility and PCOS, with a focus on the role of obesity, insulin sensitivity and treatment with metformin and GLP-1s, were considered for this review. Conclusions: The existing research on GLP-1 receptor agonists (GLP-1RAs) has not conclusively established a specific therapeutic use for these drugs. Additionally, the efficacy of the newer generation of GLP-1RAs, particularly in terms of dosage and duration of exposure, warrants more extensive research. Understanding the optimal dosing and treatment duration could significantly enhance the therapeutic use of GLP-1RAs in managing PCOS and its associated conditions.
Eosinophilic Myocarditis: From Bench to Bedside
Authors: Piccirillo Francesco , Mastroberardino Sara , Nafisio Vincenzo , Fiorentino Matteo , Segreti Andrea , Nusca Annunziata , Ussia Gian Paolo , Grigioni Francesco
Published: March 2024

Myocarditis is a polymorphic and potentially life-threatening disease characterized by a large variability in clinical presentation and prognosis. Within the broad spectrum of etiology, eosinophilic myocarditis represents a rare condition characterized by eosinophilic infiltration of the myocardium, usually associated with peripheral eosinophilia. Albeit uncommon, eosinophilic myocarditis could be potentially life-threatening, ranging from mild asymptomatic disease to multifocal widespread infiltrates associated with myocardial necrosis, thrombotic complications, and endomyocardial fibrosis. Moreover, it could progress to dilated cardiomyopathy, resulting in a poor prognosis. The leading causes of eosinophilic myocarditis are hypersensitivity reactions, eosinophilic granulomatosis with polyangiitis, cancer, hyper-eosinophilic syndrome variants, and infections. A thorough evaluation and accurate diagnosis are crucial to identifying the underlying cause and defining the appropriate therapeutic strategy. On these bases, this comprehensive review aims to summarize the current knowledge on eosinophilic myocarditis, providing a schematic and practical approach to diagnosing, evaluating, and treating eosinophilic myocarditis.
Transforming Diabetes Care: The Molecular Pathways through Which GLP1-RAs Impact the Kidneys in Diabetic Kidney Disease
Authors: Rroji Merita , Spasovski Goce
Published: March 2024

Diabetic kidney disease (DKD) is a substantial complication of type 2 diabetes (T2D), presenting challenges in chronic kidney disease (CKD) management. In addition to traditional and recent therapies, including angiotensin, converting enzyme (ACE) inhibitors, angiotensin receptor blockers, sodium-glucose cotransporter 2 (SGLT2) inhibitors, and mineralocorticoid receptor antagonists, the evolution of antihyperglycemic treatments has introduced a promising agent, glucagon-like peptide-1 receptor agonist (GLP-1RA) for the management of DKD. GLP-1RAs enhance insulin release and reduce glucagon release, offering a novel approach to DKD management. This review analyzes the molecular pathways through which GLP1-RAs confer renal protection in T2D and DKD, which are complex and multifaceted. They include modulation of renal hemodynamics, antioxidative and anti-inflammatory actions, metabolic regulation, and direct cellular effects. These mechanisms highlight GLP1-RA’s potential as a therapeutic option for glycemic control and direct or indirect renal function protection in diabetic patients, emphasizing the potentiality of GLP-1RAs for dual therapy, with cardiovascular and renal protection as a holistic approach. Clinical evidence supports GLP-1RAs in reducing albuminuria and enhancing kidney outcomes, highlighting their value in a comprehensive DKD management strategy.
Ceruloplasmin, Catalase and Creatinine Concentrations Are Independently Associated with All-Cause Mortality in Patients with Advanced Heart Failure
Authors: Smyła-Gruca Wiktoria , Szczurek-Wasilewicz Wioletta , Skrzypek Michał , Karmański Andrzej , Romuk Ewa , Jurkiewicz Michał , Gąsior Mariusz , Szyguła-Jurkiewicz Bożena
Published: March 2024

The role of oxidative/antioxidative system imbalances in advanced heart failure (HF) has not been fully investigated. The aim of this study was to identify factors associated with one-year mortality in patients with advanced HF, with particular emphasis on oxidative/antioxidative balance parameters. We analyzed 85 heart transplant candidates who were hospitalized at our institution for right heart catheterization. Ten milliliters of coronary sinus blood was collected to measure oxidative/antioxidative markers. The median age was 58 (50–62) years, and 90.6% of them were male. The one-year mortality rate was 40%. Multivariable logistic regression analysis revealed that ceruloplasmin (OR = 1.342 [1.019–1.770], p = 0.0363; per unit decrease), catalase (OR = 1.053 [1.014–1.093], p = 0.0076; per unit decrease), and creatinine (OR = 1.071 [1.002–1.144], p = 0.0422; per unit increase) were independently associated with one-year mortality. Ceruloplasmin, catalase, and creatinine had areas under the curve of 0.9296 [0.8738–0.9855], 0.9666 [0.9360–0.9971], and 0.7682 [0.6607–0.8756], respectively. Lower ceruloplasmin and catalase in the coronary sinus, as well as higher creatinine in peripheral blood, are independently associated with one-year mortality in patients with advanced HF. Catalase and ceruloplasmin have excellent prognostic power, and creatinine has acceptable prognostic power, allowing the distinction of one-year survivors from nonsurvivors.
High Hopes for the Biofabrication of Articular Cartilage—What Lies beyond the Horizon of Tissue Engineering and 3D Bioprinting?
Authors: Sbirkov Yordan , Redzheb Murad , Forraz Nico , McGuckin Colin , Sarafian Victoria
Published: March 2024

Technologies and biomaterials for 3D bioprinting have been developing extremely quickly in the past decade as they hold great potential in tissue engineering. This, together with the possibility to differentiate stem cells of different origin into any cell type, raises the hopes in regenerative medicine once again after the initial breakthrough with stem cells in the 1980s. Nevertheless, three decades of 3D bioprinting experiments have shown that the production of functional tissues would take a longer time than anticipated. Cartilage, one of the simplest tissues in the body, consists of only one cell type. It is not vascularised and innervated and does not have lymphatic vessels either, which makes it a perfect target tissue for successful implantation. The tremendous amount of work since the beginning of this century, combining the efforts of bioengineers, material scientists, biologists, and physicians, has culminated in multiple proof-of-concept constructs that have been implanted in animals. However, there is no single reproducible, standardised, widely accessible and accepted strategy that can be readily applied in the clinic. In this review, we focus on the current progress in the field of the 3D biofabrication of articular cartilage and critically assess failures and future challenges.
Systematic Assessment of Human CCR7 Signalling Using NanoBRET Biosensors Points towards the Importance of the Cellular Context
Authors: Vanalken Nathan , Boon Katrijn , Szpakowska Martyna , Chevigné Andy , Schols Dominique , Van Loy Tom
Published: March 2024

The human CC chemokine receptor 7 (CCR7) is activated by two natural ligands, CC chemokine ligand 19 (CCL19) and 21 (CCL21). The CCL19-CCL21-CCR7 axis has been extensively studied in vitro, but there is still debate over whether CCL21 is an overall weaker agonist or if the axis displays biased signalling. In this study, we performed a systematic analysis at the transducer level using NanoBRET-based methodologies in three commonly used cellular backgrounds to evaluate pathway and ligand preferences, as well as ligand bias and the influence of the cellular system thereon. We found that both CCL19 and CCL21 activated all cognate G proteins and some non-cognate couplings in a cell-type-dependent manner. Both ligands recruited β-arrestin1 and 2, but the potency was strongly dependent on the cellular system. Overall, CCL19 and CCL21 showed largely conserved pathway preferences, but small differences were detected. However, these differences only consolidated in a weak ligand bias. Together, these data suggest that CCL19 and CCL21 share mostly overlapping, weakly biased, transducer profiles, which can be influenced by the cellular context.
Effects of Various Caffeine Doses on Cognitive Abilities in Female Athletes with Low Caffeine Consumption
Authors: Bougrine Houda , Ammar Achraf , Salem Atef , Trabelsi Khaled , Jahrami Haitham , Chtourou Hamdi , Souissi Nizar
Published: March 2024

Caffeine (CAF), a prevalent psychoactive stimulant, is believed to potentially enhance cognitive ability. However, studies on the effects of various doses are limited and yield inconsistent results, particularly in female athletes. Therefore, we aimed to assess the association between three different dosages of CAF intake (low, moderate, and high) and cognitive skills in female athletes with low CAF consumption. This study had a randomized, crossover, double-blind design in which each athlete performed four experimental sessions after ingesting either a placebo (PLAC), 3 mg·kg−1 of CAF (3 mg of CAF), 6 mg·kg−1 of CAF (6 mg of CAF), or 9 mg·kg−1 of CAF (9 mg of CAF) with an in-between washout period of at least 72 h. Following a 60 min window post-capsule consumption, fourteen female athletes (age: 17.4 ± 0.8 years) were assessed through various cognitive tests, namely, simple reaction time (SRT), choice reaction time (CRT), and attentional task (AT) tests, along with the mental rotation test (MRT). Additionally, they were required to complete a questionnaire about the undesirable side effects of CAF. Our results indicated that, compared to those of PLAC, the SRT, CRT, and AT performance were significantly improved following the administration of both 3 mg of CAF and 6 mg of CAF. While the greatest enhancement was observed after consuming 3 mg of CAF, no significant differences were found between the effects of 3 mg and 6 mg of CAF. Interestingly, MRT performance did not improve with any of the CAF dosages. Moreover, the ingestion of 9 mg of CAF did not enhance cognitive skills and was linked to the highest occurrence of CAF-related side effects. In conclusion, our results highlight the recommendation for a low CAF dosage of 3 mg·kg−1, in contrast to a higher dose of 6 mg·kg−1 or 9 mg·kg−1 of CAF, to enhance various aspects of cognitive performance in female athletes with low CAF consumption without adverse side effects.
Bimodal Transformer with Regional EEG Data for Accurate Gameplay Regularity Classification
Authors: Lee Jinui , Han Jae-Ho
Published: March 2024

As games have been applied across various fields, including education and healthcare, numerous new games tailored to each field have emerged. Therefore, understanding user behavior has become crucial in securing the right players for each type of game. This study provides valuable insights for improving game development by measuring the electroencephalography (EEG) of game users and classifying the frequency of game usage. The multimodal mobile brain-body imaging (MOBI) dataset was employed for this study, and the frequency of game usage was categorized into ”often” and ”sometimes”. To achieve decent classification accuracy, a novel bimodal Transformer architecture featuring dedicated channels for the frontal (AF) and temporal (TP) lobes is introduced, wherein convolutional layers, self-attention mechanisms, and cross-attention mechanisms are integrated into a unified model. The model, designed to differentiate between AF and TP channels, exhibits functional differences between brain regions, allowing for a detailed analysis of inter-channel correlations. Evaluated through five-fold cross-validation (CV) and leave-one-subject-out cross-validation (LOSO CV), the proposed model demonstrates classification accuracies of 88.86% and 85.11%, respectively. By effectively classifying gameplay frequency, this methodology provides valuable insights for targeted game participation and contributes to strategic efforts to develop and design customized games for player acquisition.
Performance Pressure and Employee Presenteeism: The Joint Effects of Authoritarian Leadership and Independent Self-Construal
Authors: Zhang Siyi , Wang Haijia , He Qi
Published: March 2024

Due to the increasing competition in the market and the limited availability of high-quality employment opportunities, an increasing number of employees struggle to maintain a balance between their physical conditions and performance demands, resulting in a more widespread occurrence of “working while ill”. However, little is known about the controlled motivation behind the phenomenon under pressure. Drawing on self-determination theory, this study utilized 281 questionnaire data to examine the positive effect of performance pressure on employee presenteeism, and to explore the moderating role of authoritarian leadership and its joint moderation function effect with independent self-construal. The results indicated that performance pressure had a significant positive effect on employee presenteeism. Authoritarian leadership imposed an enhanced moderating effect between performance pressure and employee presenteeism, while independent self-construal diminished the augmentative moderating role played by authoritarian leadership in the relationship between performance pressure and employee presenteeism. This study reveals the controlled motivation of employee presenteeism under performance pressure, taking into account the cultural background and organizational context of China. Moreover, it also offers novel perspectives for effectively managing this phenomenon.
A Study on Seismic Dynamic Response of Pile-Supported Tunnels in Deep Backfill Area of Soil–Rock Mixture Based on a Model Test
Authors: Li Hanlin , Jin Xiaoguang , Sun Guodong , He Jie
Published: March 2024

Aiming to address the problem of construction and environmental risks in tunnel construction through the soil–rock mixture backfill area, this paper carried out a seismic dynamic response model test of a pile-supported tunnel based on practical projects. Firstly, the stress–strain curves and failure characteristics of the soil–rock mixture in the study area were obtained through triaxial tests, and based on this, similar materials for the model test were developed. Then, a vibration table model test was devised to investigate the seismic dynamic response of the pile–tunnel structure. The findings revealed the following: when subjected to seismic waves, the soil–rock mixture stratum displayed a “skin effect” in its acceleration response, indicating that closer proximity to the surface led to heightened horizontal acceleration responses; the horizontal peak acceleration of the grouting mixture stratum in the vertical direction exhibited a “Zigzag” pattern; the peak values of strain response and bending moment in the tunnel lining cross-section exhibited an “X” shape and inverted “V” shape, respectively. The bending moment at the pile crown increased alongside the peak value of the input seismic wave acceleration. The maximum surface settlement in the model ranged from 0.5 to 1 cm, with the tunnel–pile structure effectively mitigating surface settlement.
Study of the Impact of Varying Inclination Angles of Arch Ribs on the Seismic Behavior of Half-Through Steel Basket-Handle Arch Bridge
Authors: Sun Jubo , Chen Siyao , Wang Zhanfei , Sui Weining , Zhang Qiang
Published: March 2024

In the present study, multiscale finite element (FE) models of half-through steel basket-handle arch bridges were established. The eigenvalue analyses were conducted to explore the dynamic characteristics of the arch bridges based on the FE models. In addition, a parametric analysis was carried out to investigate the impact of the inclination angle of the arch rib (0°, 4°, and 7°) on the longitudinal and transverse seismic performances of arch bridges. The results show that with the increase in inclination angle, the out-of-plane stiffness of half-through steel basket-handle arch bridges increases, resulting in the natural period of the structure becoming shorter from 3.09 s to 2.93 s. Adjusting the inclination angle appropriately has a beneficial impact on the overall seismic performance of the structures, affecting both displacement and internal forces, in which the most significant improvements include a 42.8% decrease in displacement and a 62.6% reduction in internal forces. Adjusting the inclination angle can cause the arch springing and transverse brace to undergo larger plastic deformation. It is advisable to judiciously enlarge the sectional dimensions and enhance the material strength of both the arch springing and the transverse bracing in seismic designs.
Study on Early Age Concrete’s Compressive Strengths in Unmanaged Curing Condition Using IoT-Based Maturity Monitoring
Authors: Kim Sanghee , Jung Donghyuk , Kim Ju-Yong , Mun Ju-Hyun
Published: March 2024

Although accurately estimating the early age compressive strength of concrete is essential for the timely removal of formwork and the advancement of construction processes, it is challenging to estimate it in cool, cold, hot, or unmanaged conditions. Various nondestructive testing methods, including recent IoT-based techniques, have been proposed to determine the compressive strength of concrete. This study evaluates the maturity method using the wireless thermocouple sensor in assessing the early age compressive strength of concrete slabs, particularly those not subjected to watering and protection in a cool environment below 20 °C. For this purpose, wire and wireless thermocouple sensors were installed in reinforced concrete (RC) slabs, whereas wire thermocouple sensors were installed in concrete cylinders. In addition, the compressive strengths of standard-cured cylinders, field-cured cylinders, and core samples extracted from the RC slab were measured. On day 7, the maturity index (M) values for the field-cured cylinders were 7% lower than those of the standard-cured cylinders, and the M values for the RC slabs with wire and wireless sensors were 6% lower. The compressive strengths of the field-cured cylinders and core samples extracted from the RC slabs were 19% and 14% lower than those of the standard-cured cylinders, respectively. Thus, while the difference in M values was 6–7%, the difference in compressive strength was significantly higher, at 14–19%. In a cool environment without watering or protection, the difference in strength can be even greater. Consequently, a commercial IoT-based thermocouple sensor can replace conventional wire sensors and adopt to estimate early age compressive strength of concrete in unmanaged curing condition.
Assessment of Contact Laws Accounting for Softening in 3D Rigid Concrete Particle Models
Authors: Azevedo Nuno Monteiro , Farinha Maria Luísa Braga , Oliveira Sérgio
Published: March 2024

To obtain predictions closer to concrete behaviour, it is necessary to employ a particle model (PM) that considers contact softening. A bilinear softening contact model (BL) has been adopted in PM studies. Several limitations in PM predictions have been identified that may be due to BL assumptions. For this reason, this paper compares BL predictions with those obtained with more complex models to assess if PM predictions can be improved. As shown, it is possible to calibrate each contact model to reproduce the complex behaviour observed in concrete in uniaxial and biaxial loading. The predicted responses are similar, and the known PM limitations still occur independently of the adopted model. Under biaxial loading, it is shown that a response closer to that observed in concrete can be obtained (higher normal-to-stiffness ratio of ≈0.50, maximum contact compressive strength of ≈60 MPa, and 30% reduction in the number of working contacts). The BL contact model for PM concrete DEM-based simulations is shown to have (i) lower associated computational costs (15% to 50% lower); (ii) a reduced number of contact strength parameters; and (iii) similar responses to those predicted with more complex models. This paper highlights that the BL contact model can be used with confidence in PM fracture studies.
PAX5 Alterations in a Consecutive Childhood B-Cell Acute Lymphoblastic Leukemia Cohort Treated Using the ALL IC-BFM 2009 Protocol
Authors: Črepinšek Klementina , Klobučar Nika , Tesovnik Tine , Šket Robert , Jenko Bizjan Barbara , Kovač Jernej , Kavčič Marko , Prelog Tomaž , Kitanovski Lidija , Jazbec Janez , Debeljak Maruša
Published: March 2024

In this study, we aimed to identify patients within our B-ALL cohort with altered PAX5. Our objective was to use a comprehensive analysis approach to characterize the types of genetic changes, determine their origin (somatic/germline), and analyze the clinical outcomes associated with them. A consecutive cohort of 99 patients with B-ALL treated at the Children’s Hospital of the UMC Ljubljana according to the ALL IC-BFM 2009 protocol was included in our study. We used RNA sequencing data for gene expression analysis, fusion gene detection and single nucleotide variant identification, multiplex-ligation dependent probe amplification for copy number variation assessment, and Sanger sequencing for germline variant detection. PAX5 was impacted in 33.3% of our patients, with the genetic alterations ranging from CNVs and rearrangements to SNVs. The most common were CNVs, which were found in more than a third of patients, followed by point mutations in 5.2%, and gene rearrangements in 4.1%. We identified eight patients with a PAX5-associated genetic subtype that were previously classified as “B-other”, and they showed intermediate outcomes. We showed higher minimal residual disease values at the end of induction and poorer event-free survival in hyperdiploid cases carrying duplications in PAX5 compared to other hyperdiploid cases. We also report an interesting case of a patient with PAX5::FKBP15 and a pathogenic variant in PTPN11 who underwent an early relapse with a monocytic switch. In conclusion, this study provides valuable insights into the presence, frequency, and prognostic significance of diverse PAX5 alterations in B-ALL patients, highlighting the complexity of genetic factors and their impact on patient outcomes.
Insights into Disease Progression of Translational Preclinical Rat Model of Interstitial Pulmonary Fibrosis through Endpoint Analysis
Authors: Kadam Anil H. , Schnitzer Jan E.
Published: March 2024

Idiopathic pulmonary fibrosis (IPF) is a devastating interstitial lung disease characterized by the relentless deposition of extracellular matrix (ECM), causing lung distortions and dysfunction. Animal models of human IPF can provide great insight into the mechanistic pathways underlying disease progression and a means for evaluating novel therapeutic approaches. In this study, we describe the effect of bleomycin concentration on disease progression in the classical rat bleomycin model. In a dose–response study (1.5, 2, 2.5 U/kg i.t), we characterized lung fibrosis at day 14 after bleomycin challenge using endpoints including clinical signs, inflammatory cell infiltration, collagen content, and bronchoalveolar lavage fluid-soluble profibrotic mediators. Furthermore, we investigated fibrotic disease progression after 2 U/kg i.t. bleomycin administration at days 3, 7, and 14 by quantifying the expression of clinically relevant signaling molecules and pathways, epithelial mesenchymal transition (EMT) biomarkers, ECM components, and histopathology of the lung. A single bleomycin challenge resulted in a progressive fibrotic response in rat lung tissue over 14 days based on lung collagen content, histopathological changes, and modified Ashcroft score. The early fibrogenesis phase (days 3 to 7) is associated with an increase in profibrotic mediators including TGFβ1, IL6, TNFα, IL1β, CINC1, WISP1, VEGF, and TIMP1. In the mid and late fibrotic stages, the TGFβ/Smad and PDGF/AKT signaling pathways are involved, and clinically relevant proteins targeting galectin-3, LPA1, transglutaminase-2, and lysyl oxidase 2 are upregulated on days 7 and 14. Between days 7 and 14, the expressions of vimentin and α-SMA proteins increase, which is a sign of EMT activation. We confirmed ECM formation by increased expressions of procollagen-1Aα, procollagen-3Aα, fibronectin, and CTGF in the lung on days 7 and 14. Our data provide insights on a complex network of several soluble mediators, clinically relevant signaling pathways, and target proteins that contribute to drive the progressive fibrotic phenotype from the early to late phase (active) in the rat bleomycin model. The framework of endpoints of our study highlights the translational value for pharmacological interventions and mechanistic studies using this model.
Neonatal Brains Exhibit Higher Neural Reparative Activities than Adult Brains in a Mouse Model of Ischemic Stroke
Authors: Nishiyama Ryo , Nakagomi Takayuki , Nakano-Doi Akiko , Kuramoto Yoji , Tsuji Masahiro , Yoshimura Shinichi
Published: March 2024

The neonatal brain is substantially more resistant to various forms of injury than the mature brain. For instance, the prognosis following ischemic stroke is generally poor in the elderly but favorable in neonates. Identifying the cellular and molecular mechanisms underlying reparative activities in the neonatal brain after ischemic injury may provide feasible targets for therapeutic interventions in adults. To this end, we compared the reparative activities in postnatal day 13 and adult (8–12-week-old) mouse brain following middle cerebral artery occlusion. Immunohistochemistry revealed considerably greater generation of ischemia-induced neural stem/progenitor cells (iNSPCs) expressing nestin or Sox2 in ischemic areas of the neonatal brain. The iNSPCs isolated from the neonatal brain also demonstrated greater proliferative activity than those isolated from adult mice. In addition, genes associated with neuronal differentiation were enriched in iNSPCs isolated from the neonatal brain according to microarray and gene ontogeny analyses. Immunohistochemistry further revealed considerably greater production of newborn doublecortin+ neurons at the sites of ischemic injury in the neonatal brain compared to the adult brain. These findings suggest that greater iNSPC generation and neurogenic differentiation capacities contribute to the superior regeneration of the neonatal brain following ischemia. Together, our findings may help identify therapeutic targets for enhancing the reparative potential of the adult brain following stroke.
The Risks of Phosphate Enemas in Toddlers: A Life-Threatening Unawareness
Authors: Zago Alessandro , Occhipinti Alessandro Agostino , Bramuzzo Matteo , Ceconi Viola , Colacino Vincenzo , Barbi Egidio , Poropat Federico
Published: March 2024

Background: While oral laxatives represent the first-line treatment of fecal impaction, enemas are frequently used in clinical practice in pediatric emergency departments (PEDs) and by family pediatricians (FPs). Objectives: Phosphate-containing enemas (PcEs) are commonly employed, even causing the risk of rare but lethal toxicity. We investigated pediatricians’ awareness of PcE risks. Methods: We conducted an online survey by sending a multiple-choice questionnaire to the referents of 51 PEDs and 101 FPs. We collected and compared the answers with recommendations reported by the Italian Drug Agency (AIFA) and the available literature about PcE administration. Results: Of the institutions and pediatricians receiving the questionnaire, 23 PEDs (45%) and 63 FP (62.3%) participated in the survey. Of PEDs, 95% and 33.0% of FPs treated fecal impaction with PcE. Moreover, 54% of PEDs and 86.0% of FPs did not provide treatment according to the AIFA recommendations for the daily dose. Conclusions: This study shows limited pediatricians’ awareness of the potential risks related to PcE.
Fabrication of Particle-Stacking Microporous Metal Using Laser Powder Bed Fusion
Authors: Qiu Jinyong , Xu Xiaoqiang , Chen Xu , Liu Yaxiong , Wu Yanlong
Published: March 2024

Laser powder bed fusion can fabricate porous structures through lattices, but the preparation of micropores (<50 μm) with a specific pore distribution remains a challenge. Microporous 316L was fabricated by controlling the melting and solidification behavior of the particles using laser energy. The laser energy density was not a determining factor for the porosity and micropore formation, except for the single-factor condition. The high-speed scanning mode required a higher laser power to disorder the pore distribution, whereas low-speed scanning with a low laser impact on the stacking particles formed organized pores. The hatch distance significantly affected the pore distribution and pore size. The pore distribution in the XY plane was organized and homogenous, with channeled pores mainly interconnected along the laser scanning tracks, whereas in the Z direction, it showed a relatively disordered distribution, mainly linked along the layered direction. The microporous 316L displayed a mean pore size and median pore size of 10–50 μm with a high-percentage size distribution in 1–10 μm, a controllable porosity of 17.06%–45.33% and a good yield strength of 79.44–318.42 MPa, superior to the lattice porous 316L with 250.00 MPa at similar porosity.
Decoding Material Structures with Scanning Electron Diffraction Techniques
Authors: Yoon Sangmoon
Published: March 2024

Recent advancements in electron detectors and computing power have revolutionized the rapid recording of millions of 2D diffraction patterns across a grid of probe positions, known as four-dimensional scanning transmission electron microscopy (4D-STEM). These datasets serve as the foundation for innovative STEM imaging techniques like integrated center of mass (iCOM) and symmetry STEM (S-STEM). This paper delves into the application of 4D-STEM datasets for diffraction analysis. We therefore use the term scanning electron diffraction (SED) instead of 4D-STEM in this review. We comprehensively explore groundbreaking diffraction methods based on SED, structured into two main segments: (i) utilizing an atomic-scale electron probe and (ii) employing a nanoscale electron probe. Achieving an atomic-scale electron probe necessitates a significant convergence angle (α > 30 mrad), leading to interference between direct and diffracted beams, distinguishing it from its nanoscale counterpart. Additionally, integrating machine learning approaches with SED experiments holds promise in various directions, as discussed in this review. Our aim is to equip materials scientists with valuable insights for characterizing atomic structures using cutting-edge SED techniques.
Comparative Analysis of Room Temperature Structures Determined by Macromolecular and Serial Crystallography
Authors: Nam Ki Hyun
Published: March 2024

Temperature directly influences the function and structure of proteins. Crystal structures determined at room temperature offer more biologically relevant structural information regarding flexibility, rigidity, and thermal motion than those determined by conventional cryocrystallography. Crystal structures can be determined at room temperature using conventional macromolecular crystallography (MX) or serial crystallography (SX) techniques. Among these, MX may theoretically be affected by radiation damage or X-ray heating, potentially resulting in differences between the room temperature structures determined by MX and SX, but this has not been fully elucidated. In this study, the room temperature structure of xylanase GH11 from Thermoanaerobacterium saccharolyticum was determined by MX (RT-TsaGH11-MX). The RT-TsaGH11-MX exhibited both the open and closed conformations of the substrate-binding cleft within the β-sandwich fold. The RT-TsaGH11-MX showed distinct structural changes and molecular flexibility when compared with the RT-TsaGH11 determined via serial synchrotron crystallography. The notable molecular conformation and flexibility of the RT-TsaGH11-MX may be induced by radiation damage and X-ray heating. These findings will broaden our understanding of the potential limitations of room temperature structures determined by MX.
Structural Evolution and Mechanical Behavior of Ytterbia Doped Hafnia Biphasic Ceramics under Annealing at 1500 °C
Authors: Wu Yang , Lan Hao , Sun Xiaoming , Hu Zihao , Sun Yonghui , Zhang Huifeng , Huang Chuanbing , Zhang Weigang
Published: March 2024

HfO2 has become a promising thermal barrier coating material due to its similarity in structure and chemical properties with ZrO2 and its higher phase structure transition temperature. However, the fracture toughness of HfO2 is not ideal, greatly limiting its application. In this report, we find a special sandwich structure of ceramics, comprising a cubic (C) phase /monoclinic (M) phase/cubic (C) phase. The microstructural evolution and mechanical properties of these ceramics were investigated under annealing at 1500 °C. The results indicate that, with an increase in annealing duration, there was a gradual augmentation in the proportion of the monoclinic (M) phase and the fracture toughness increased from 2.18 MPa·m0.5 to 2.83 MPa·m0.5 after 48 h of annealing, which is higher than many potential TBC materials. The residual compressive stress present in the M phases during the progression of crack propagation served to facilitate the bridging and deflection of cracks. As such, this process led to the alleviation of stress concentration at the crack tip, ultimately enhancing the toughening effect.
A Review of Game Theory Models to Support Production Planning, Scheduling, Cloud Manufacturing and Sustainable Production Systems
Authors: Renna Paolo
Published: March 2024

Cyber-physical systems, cloud computing, the Internet of Things, and big data play significant roles in shaping digital and automated landscape manufacturing. However, to fully realize the potential of these technologies and achieve tangible benefits, such as reduced manufacturing lead times, improved product quality, and enhanced organizational performance, new decision support models need development. Game theory offers a promising approach to address multi-objective problems and streamline decision-making processes, thereby reducing computational time. This paper aims to provide a comprehensive and up-to-date systematic review of the literature on the application of game theory models in various areas of digital manufacturing, including production and capacity planning, scheduling, sustainable production systems, and cloud manufacturing. This review identifies key research themes that have been explored and examines the main research gaps that exist within these domains. Furthermore, this paper outlines potential future research directions to inspire both researchers and practitioners to further explore and develop game theory models that can effectively support the digital transformation of manufacturing systems.