bluuebunny/crossref_metadata_2025 huggingface dataset:
Quasi-Static Finite Cylindrical Cavity Expansion Model for Long-Rod Penetration into Cylindrical Metal Thick Targets with Finite Diameters
Authors: Lu Yunke , Tao Xigui , Chen Yicun , Zhang Bei , Song Jiageng , Xu Xiangyu , Wang Jianshuai
Published: February 2024

A quasi-static finite cavity cylindrical expansion model is proposed to investigate the lateral boundary effect during long-rod penetration. Analytical solutions for the cavity pressure in the elastic–plastic stage and plastic stage are obtained, through which a decay function for the lateral boundary effect is constructed. The resistance of the target with finite diameter RT is obtained by multiplying the decay function with the resistance of infinite target RT*. Then, a theoretical model for the penetration into the metal targets with finite diameters by long rods is proposed by substituting RT into the Alekseevskii–Tate model. The proposed model is verified by comparison with existing experimental results. Furthermore, the effect of the target diameter, initial impact velocity and yield criterion on the penetration depth and resistance are investigated. The results showed that the lateral boundary effect should be taken into account if the ratio of the target radius to the rod radius (rt0/RP) is less than 25.
An Online Multicriteria—Spatial Decision Support System for Public Services Planning
Authors: Krügel Falko , Mäs Stephan , Hindorf Paul , Buthmann Erik
Published: February 2024

Dynamic processes in society and demographics require a rapid response and adaptation of the existing public service infrastructure. Responsible planners must be able to analyse the situation, identify gaps in provision and derive decisions. The paper presents a web application that supports finding answers to various questions and planning decisions in the context of public service infrastructures (e.g., schools, pharmacies, supermarkets). Due to the high complexity, the combination of multi-criteria decision analysis and geographical information systems, especially in the web context, is still rarely implemented. With this spatial decision support system, we are pursuing an approach that makes multi-criteria analyses with spatially explicit methods available to the planning domain. By using this application, the user can select and adjust input parameters independently and thus strongly influence the analysis process and results—without a deep knowledge of decision-making methods or software skills. With such a centrally provided online multi-criteria spatial decision support system, the transparency and the quality of the analysis increase, while the workload for the planners is reduced, since they no longer have to spend time on preliminary data search and integration or on building complex methods and models themselves.
Visualising the Relevance of Climate Change for Spatial Planning by the Example of Serbia
Authors: Pantić Marijana , Maričić Tamara , Milijić Saša
Published: February 2024

After decades of rising awareness and undertaken actions, climate change is still one of several focal global challenges. Additionally, the latest report by researchers at the International Panel for Climate Change indicates that the crisis has deepened. With its comprehensive nature, spatial planning is one of the management tools responsible for dealing with climate change and combating its effects. Land use definition is the foundation on which we build mitigation and adaptation systems. It is a complex process that involves (or should involve) a range of stakeholders—experts, politicians, the civil sector, and citizens—in which the clear transmission of messages to stakeholders regarding the state of the art and planned actions is significant. The use of visualisation tools is one of the important ways to achieve this. This research aims to present a set of visualisation tools, applying them in analysis and decision making in the field of spatial planning with regard to climate change. We combined content analysis, colour-graded classification, and the spider method applied to the example of Serbia. The results showed that application of the suggested visualisation methods in combination with regular planning tools (maps) facilitates an understanding of the problem and its presentation to other stakeholders. In the case of Serbia, visualisation tools have shown that adaptation measures prevail over mitigation measures and that the effects of climate change addressed in spatial-planning documents do not significantly match the most challenging effects as perceived from the citizens’ perspective. These are aspects that should be corrected in the next generation of planning documents. The suggested visualisation tools are replicable, with slight adjustments to a specific case, to any other region in the world.
Orthogonal Neural Network: An Analytical Model for Deep Learning
Authors: Pan Yonghao , Yu Hongtao , Li Shaomei , Huang Ruiyang
Published: February 2024

In the current deep learning model, the computation between each feature and parameter is defined in the real number field. This, together with the nonlinearity of the deep learning model, makes it difficult to analyze the relationship between the values of the computational process and the original features from computation in the real number field. We extend the operational rules of the deep learning model in space and propose the orthogonal neural network (ONN) model, in which the features are set orthogonally to each other in space by “modulating” each input feature of the deep learning model to different orthogonal bases. Because the modulated numerical features are orthogonal to each other, they can be separated from the computations of the ONN model. By “demodulating” the model during and after the calculation, we can obtain a numerical relationship between the results and the original features, which can further provide theoretical and computational support for our analysis of the model. Finally, we compute the weights for each input feature as an interpretable deep learning approach, and describe how the model focuses attention on each feature based on the application of the orthogonal neural network model on two typical models: convolutional neural networks and graph neural networks.
A Global Minimizer for Mass-Constrained Problem Revisited
Authors: Long Chun-Fei , Li Gui-Dong
Published: February 2024

We investigate the existence of solutions to the scalar field equation −Δu=g(u)−λuinRN, with mass constraint ∫RN|u|2dx=a>0,u∈H1(RN). Here, N≥3; g is a continuous function satisfying the conditions of the Berestycki–Lions type; λ is a Lagrange multiplier. Our results supplement and generalize some of the results in L. Jeanjean, S.-S. Lu, Calc. Var. Partial Differential Equations. 61 (2022), Paper No. 214, 18, and J. Hirata, K. Tanaka, Adv. Nonlinear Stud. 19 (2019), 263–290.
Direct Interaction of Zirconia Nanoparticles with Human Immune Cells
Authors: Barbasz Anna M. , Dyba Barbara
Published: February 2024

Nanomaterials play a crucial role in various aspects of modern life. Zirconia nanoparticles, extensively employed in medicine for fortifying and stabilizing implants in reconstructive medicine, exhibit unique electrical, thermal, catalytic, sensory, optical, and mechanical properties. While these nanoparticles have shown antibacterial activity, they also exhibit cytotoxic effects on human cells. Our research focuses on understanding how the cells of the human immune system (both the innate response, namely HL-60 and U-937, and the acquired response, namely HUT-78 and COLO-720L) respond to the presence of zirconium (IV) oxide nanoparticles (ZrO2-NPs). Viability tests indicate that ZrO2-NPs exert the highest cytotoxicity on HL-60 > U-937 > HUT-78 > COLO 720L cell lines. Notably, concentrations exceeding 100 μg mL−1 of ZrO2-NPs result in significant cytotoxicity. These nanoparticles readily penetrate the cell membrane, causing mitochondrial damage, and their cytotoxicity is associated with heightened oxidative stress in cells. The use of ZrO2-NP-based materials may pose a risk to immune system cells, the first responders to foreign entities in the body. Biofunctionalizing the surface of ZrO2-NPs could serve as an effective strategy to mitigate cytotoxicity and introduce new properties for biomedical applications.
Radon, Concrete, Buildings and Human Health—A Review Study
Authors: Bulut H. Alperen , Şahin Remzi
Published: February 2024

A comprehensive evaluation of the results obtained according to the measurement of radon gas in buildings and concrete, which is the most consumed material in the world after water, in accessible studies carried out in the last 40 years is the main objective of this study. The paper additionally aims to address the gap in the literature by comparatively determining which parameters affect radon–concrete and radon–building relationships. The scientific knowledge compiled within the scope of this article was presented under the main headings of radon and radon gas measurements in concrete and buildings. Radon gas, also known as the “invisible killer”, is considered the second most important cause of lung cancer after smoking (the gas is responsible for 3–14% of lung cancer cases in the world). The results determined that radon concentration limits have been applied in the range of 100–400 Bqm−3 in houses and 100–3700 Bqm−3 in workplaces. Studies conducted on the exhalation rate of radon showed that the radon exhalation rate of concrete may be in the range of 0.23–510 Bqm−2 h−1. The results of indoor radon concentration measurements revealed that values between 4.6 Bqm−3 and 583 Bqm−3 were obtained. Despite the existing literature, some researchers state that there is an urgent need for an improved and widely accepted protocol based on reliable measurement techniques to standardize measurements of the radon exhalation rate of construction materials and the indoor radon concentration of buildings.
An Energy Self-Sufficient Alpine Hut: The Refurbishment of an Ex-Tobacco Farm Using Building Integrated Photovoltaics
Authors: Bottino-Leone Dario , Exner Dagmar Elisabet , Adami Jennifer , Troi Alexandra , Balest Jessica
Published: February 2024

The abandonment and deterioration of historic rural buildings in Europe raise significant issues, including hydrogeological risks, the loss of productive land, and cultural heritage decline. Despite being underestimated, these structures hold significant potential for cultural and productive activities. Renovating these structures is crucial for local communities committed to preserving their heritage, and it is a more sustainable approach than constructing new buildings. This study explores activities undertaken in the Interreg IT/AT project “SHELTER” in Valbrenta (IT): through a participatory approach involving communities, stakeholders, designers, and researchers, an energy concept is developed for refurbishing an abandoned tobacco farm, chosen by the community, to be an alpine hut. Due to the inability to connect to the city electricity grid, the new energy concept focuses on minimizing consumption through envelope refurbishment, efficient heating, and domestic hot water systems. Additionally, the integration of renewable energy sources, particularly Building Integrated Photovoltaics (BIPV), is emphasized to preserve the building’s original appearance. This study demonstrates the feasibility of meeting seasonal energy needs entirely through renewables and explores the potential integration of biomass for meeting annual energy requirements.
Enhancing the Accuracy of Low-Cost Inclinometers with Artificial Intelligence
Authors: Lozano Fidel , Emadi Seyyedbehrad , Komarizadehasl Seyedmilad , Arteaga Jesús González , Xia Ye
Published: February 2024

The development of low-cost structural and environmental sensors has sparked a transformation across numerous fields, offering cost-effective solutions for monitoring infrastructures and buildings. However, the affordability of these solutions often comes at the expense of accuracy. To enhance precision, the LARA (Low-cost Adaptable Reliable Anglemeter) system averaged the measurements of a set of five different accelerometers working as inclinometers. However, it is worth noting that LARA’s sensitivity still falls considerably short of that achieved by other high-accuracy commercial solutions. There are no works presented in the literature to enhance the accuracy, precision, and resolution of low-cost inclinometers using artificial intelligence (AI) tools for measuring structural deformation. To fill these gaps, artificial intelligence (AI) techniques are used to elevate the precision of the LARA system working as an inclinometer. The proposed AI-driven tool uses Multilayer Perceptron (MLP) to glean insight from high-accuracy devices’ responses. The efficacy and practicality of the proposed tools are substantiated through the structural and environmental monitoring of a real steel frame located in Cuenca, Spain.
Identifying Problematic Soils Using Compressibility and Suction Characteristics
Authors: Dafalla Muawia , Al-Mahbashi Ahmed M.
Published: February 2024

The major problematic soils in semi-arid regions include expansive soils and collapsible soils. These two types of soils cause problems and are hazardous for buildings when moisture is introduced following a dry or semi-dry season. In order to assess the risk and damage likely to occur, a protocol of investigation needs to be considered by geotechnical engineers to quantify and assess the possible heave or collapse that may occur. The characterization and prediction of unsaturated soil behavior in semi-arid areas can now be enabled following the advancement of unsaturated soil mechanics. Heave is associated with the wetting of expansive soils, while excessive settlement or the sudden loss of support may occur when water is introduced to collapsible soils. This work calls for more than one parameter for the assessment of problematic soils to avoid misleading predictions based on a single test. This study presents an investigation of two sets of soil samples obtained from semi-arid areas in Saudi Arabia known for their collapsible or expansive nature. Tests under controlled suction and variable effective stress were conducted. The air entry values, inflection points, and residual points were established and compared for the two problematic soils. A series of oedometer tests was conducted for typical soils, and settlement and collapse were measured and assessed. The swell potential for the tested clays varied from 4% to 22%. It is possible to integrate the data from the soil–water characteristic curve (SWCC) and compressibility tests with any project specification and applied stresses to produce reliable recommendations for the construction and protection of structures in hazardous soils.
Perspective Strategies for Interventions in Parkinsonism: Remedying the Neglected Role of TPPP
Authors: Oláh Judit , Norris Vic , Lehotzky Attila , Ovádi Judit
Published: February 2024

Neurological disorders such as Parkinsonism cause serious socio-economic problems as there are, at present, only therapies that treat their symptoms. The well-established hallmark alpha-synuclein (SYN) is enriched in the inclusion bodies characteristic of Parkinsonism. We discovered a prominent partner of SYN, termed Tubulin Polymerization Promoting Protein (TPPP), which has important physiological and pathological activities such as the regulation of the microtubule network and the promotion of SYN aggregation. The role of TPPP in Parkinsonism is often neglected in research, which we here attempt to remedy. In the normal brain, SYN and TPPP are expressed endogenously in neurons and oligodendrocytes, respectively, whilst, at an early stage of Parkinsonism, soluble hetero-associations of these proteins are found in both cell types. The cell-to-cell transmission of these proteins, which is central to disease progression, provides a unique situation for specific drug targeting. Different strategies for intervention and for the discovery of biomarkers include (i) interface targeting of the SYN-TPPP hetero-complex; (ii) proteolytic degradation of SYN and/or TPPP using the PROTAC technology; and (iii) depletion of the proteins by miRNA technology. We also discuss the potential roles of SYN and TPPP in the phenotype stabilization of neurons and oligodendrocytes.
Lattice Rotation Dependence on Microstructural Characteristics in a Low Carbon Steel
Authors: Shekhawat Satish , Khatirkar Rajesh , Demiral Murat
Published: February 2024

The lattice rotation behavior of low-carbon (LC) steel subjected to tensile deformation was studied by electron backscatter diffraction (EBSD). The EBSD scans of the same region were taken before and after tensile deformation. The rotation of the grains was found to depend on a number of factors like the initial orientation, the size of the grains, the number of neighboring grains and the region of the grain. The region near the grain boundaries was found to have significant deviation from that of the interior of the grain. The lattice rotations were also simulated using DAMASK software. The simulations gave information about the state of stress for each grain and the strain gradients developed during the deformation. The orientation dependence of misorientation and geometrically necessary dislocations (GNDs) was also studied. It was found that the misorientations changed more gradually in α-fiber grains than in γ-fiber grains.
Thermodynamics of Iron Ammonia Synthesis Catalyst Sintering
Authors: Arabczyk Walerian , Pelka Rafał , Jasińska Izabella , Lendzion-Bieluń Zofia
Published: February 2024

The sintering of iron ammonia synthesis catalysts (nanocrystalline iron promoted with: Al2O3, CaO and K2O) was studied under a hydrogen atmosphere, in a temperature range of 773 to 973 K to obtain stationary states. The catalysts were characterized by measuring the nitriding reaction rate under an ammonia atmosphere at 748 K to obtain steady states and the measurement of specific surface area. Chemical processes were conducted in a tubular differential reactor enabling thermogravimetric measurements and the chemical composition analysis of a gas phase under conditions allowing experiments to be carried out in the kinetic region of chemical reactions. An extended model of the active surface of the iron ammonia synthesis catalyst was presented, taking into account the influence of the gas phase composition and process temperature. The surface of iron nanocrystallites was wetted using promoters in an exothermic process associated with the formation of the surface Fes-O- bond and the change in the surface energy of iron nanocrystallites. Promoters formed on the surface of iron nanocrystallites with different structures of chemisorbed dipoles, depending on the composition of the gas phase. The occupied sites stabilized the structure, and the free sites were active sites in the process of adsorption of chemical reagents and in sintering. Based on the bonding energy of the promoter oxides and the difference in surface energy between the covered and uncovered surfaces, the wetting abilities of promoters, which can be arranged according to the order K2O > Fe3O4 > Al2O3 > CaO, were estimated. By increasing the temperature in the endothermic sintering process, the degree of surface coverage with dipoles of promoters decreased, and thus the catalyst underwent sintering. The size distribution of nanocrystallites did not change with decreasing temperature. Only the equilibrium between the glass phase and the surface of iron nanocrystallites was then established.
Insulin Resistance: The Increased Risk of Cancers
Authors: Szablewski Leszek
Published: February 2024

Insulin resistance, also known as impaired insulin sensitivity, is the result of a decreased reaction of insulin signaling to blood glucose levels. This state is observed when muscle cells, adipose tissue, and liver cells, improperly respond to a particular concentration of insulin. Insulin resistance and related increased plasma insulin levels (hyperinsulinemia) may cause metabolic impairments, which are pathological states observed in obesity and type 2 diabetes mellitus. Observations of cancer patients confirm that hyperinsulinemia is a major factor influencing obesity, type 2 diabetes, and cancer. Obesity and diabetes have been reported as risks of the initiation, progression, and metastasis of several cancers. However, both of the aforementioned pathologies may independently and additionally increase the cancer risk. The state of metabolic disorders observed in cancer patients is associated with poor outcomes of cancer treatment. For example, patients suffering from metabolic disorders have higher cancer recurrence rates and their overall survival is reduced. In these associations between insulin resistance and cancer risk, an overview of the various pathogenic mechanisms that play a role in the development of cancer is discussed.
Vertebro-Vertebral Arteriovenous Fistulae: A Case Series of Endovascular Management at a Single Center
Authors: Withayasuk Pattarawit , Wichianrat Ritthikrai , Sangpetngam Boonrerk , Aurboonyawat Thaweesak , Chankaew Ekawut , Homsud Saowanee , Churojana Anchalee
Published: February 2024

Objective: Vertebro-vertebral arteriovenous fistulae (VVFs) are a rare disorder characterized by a direct shunt between the extracranial vertebral artery and the veins of the vertebral venous plexus. This study aims to comprehensively review the characteristics and outcomes of endovascular treatments for VVFs at our center. Methods: A retrospective review was conducted on 14 patients diagnosed with a VVF who underwent endovascular treatment at Siriraj Hospital from January 2000 to January 2023. The study assessed patient demographics, presentation, fistula location, treatment strategies, endovascular techniques employed, and treatment outcomes. Results: Among the 14 patients, 11 (78.6%) were female, with an age range from 25 to 79 years (median: 50 years). Spontaneous VVFs were observed in 64.3% of the cases, including three associated with neurofibromatosis type 1 (NF-1). Iatrogenic injury accounted for two cases, and three patients had VVFs resulting from traffic accidents. A pulsatile neck mass and tinnitus, with or without neurological deficits, were common presenting symptoms. Active bleeding was observed in three cases with vascular injury, while unilateral proptosis, congestive heart failure, and incidental findings each presented in one patient. All the VVFs were successfully obliterated without major treatment complications. Parent vessel sacrifice was performed in 85.7% of the cases, while vertebral artery preservation was achieved in the remaining two patients. Embolic materials included detachable balloons, detachable coils, and n-butyl cyanoacrylate (NBCA) glue. All the presenting symptoms showed improvement, and no morbidity or mortality was observed. Conclusions: Endovascular embolization is a feasible and effective approach for achieving complete VVF obliteration with safety. Parent artery sacrifice should not be reluctantly performed, particularly when adequate collateral circulation is demonstrated.
Host-Pathogen Interactions in K. pneumoniae Urinary Tract Infections: Investigating Genetic Risk Factors in the Taiwanese Population
Authors: Chen Chi-Sheng , Hung Kuo-Sheng , Jian Ming-Jr , Chung Hsing-Yi , Chang Chih-Kai , Perng Cherng-Lih , Chen Hsiang-Cheng , Chang Feng-Yee , Wang Chih-Hung , Hung Yi-Jen , Shang Hung-Sheng
Published: February 2024

Background: Klebsiella pneumoniae (K. pneumoniae) urinary tract infections pose a significant challenge in Taiwan. The significance of this issue arises because of the growing concerns about the antibiotic resistance of K. pneumoniae. Therefore, this study aimed to uncover potential genomic risk factors in Taiwanese patients with K. pneumoniae urinary tract infections through genome-wide association studies (GWAS). Methods: Genotyping data are obtained from participants with a history of urinary tract infections enrolled at the Tri-Service General Hospital as part of the Taiwan Precision Medicine Initiative (TPMI). A case-control study employing GWAS is designed to detect potential susceptibility single-nucleotide polymorphisms (SNPs) in patients with K. pneumoniae-related urinary tract infections. The associated genes are determined using a genome browser, and their expression profiles are validated via the GTEx database. The GO, Reactome, DisGeNET, and MalaCards databases are also consulted to determine further connections between biological functions, molecular pathways, and associated diseases between these genes. Results: The results identified 11 genetic variants with higher odds ratios compared to controls. These variants are implicated in processes such as adhesion, protein depolymerization, Ca2+-activated potassium channels, SUMOylation, and protein ubiquitination, which could potentially influence the host immune response. Conclusions: This study implies that certain risk variants may be linked to K. pneumoniae infections by affecting diverse molecular functions that can potentially impact host immunity. Additional research and follow-up studies are necessary to elucidate the influence of these risk variants on infectious diseases and develop targeted interventions for mitigating the spread of K. pneumoniae urinary tract infections.
Exploring the Gender Gap: Motivation, Procrastination, Environment, and Academic Performance in an Introductory Physics Course in a Human-Centered Private University in Northeast Mexico—A Case Study
Authors: Martínez-Huerta Humberto , Chavarría-Garza Wendy Xiomara , Aquines-Gutiérrez Osvaldo , Santos-Guevara Ayax
Published: February 2024

Progress has been made in recent decades toward achieving gender equality, but today, the gender gap is still noticeable, especially in STEM fields. In support of Goal 5 of the 2030 Sustainable Development Agenda: achieve gender equality and empower all women and girls, we analyze the context of a private university in northeastern Mexico using a sample of 249 students (157 males and 92 females) enrolled in the first-year engineering course Physics I. The sample presents better academic performance in favor of women by the end of the course as reported through the final course score (F); thus, we explore potential gender differences in student profiles, such as their motivation and level of procrastination using Kruskal–Wallis correlation tests, and measuring the effect size with Cohen’s d. Our tests reported here reveal significant differences in extrinsic motivation (EMO) and intrinsic motivation (IMO), where females obtained higher means in IMO, while males reported higher levels of procrastination (PRO). Contrary to other cases in the literature, the sample presents better academic performance in favor of women. Our findings here aim to encourage programs and strategies that strengthen women’s intrinsic motivation to support women’s empowerment and keep reducing the gender gap.
Knowledge, Attitudes, and Practices of Nurses toward Risk Factors and Prevention of Falls in Older Adult Patients in a Large-Sized Tertiary Care Setting
Authors: Alsaad Saad Mohammad , Alabdulwahed Mshari , Rabea Nabeel Mohammed , Tharkar Shabana , Alodhayani Abdulaziz A.
Published: February 2024

The objective was to assess the knowledge, attitudes, and practices of nurses toward the prevention of falls in older hospitalized patients. A cross-sectional study employing a 54-item questionnaire was conducted on 370 nurses at a tertiary care referral center. The mean age of the study population was 36.3 ± 7.7 years, with the majority being females (282; 76.8%). Most of them had attended fall prevention training (335; 90.5%). More than 98% knew fall prevention policies and safety goals, according to their response to a fall and risk assessment, but were less aware of the risk factors of falls, such as recurrent falls (61%), depression (44%), and lower-extremity numbness (40.5%). Similarly, 99% had positive attitudes toward risk assessment, fall prevention intervention, and response to a fall. Around 55% thought they were responsible for patients’ falls, and 96% felt the need to undergo more training on fall prevention. Furthermore, 92% strictly followed fall prevention policies and 85.4% followed the color-coding system for high-risk patients. Despite the preventive measures in place, 33% encountered patient falls, and 82.2% experienced unwitnessed patient fall incidents in their units. Although the nurses had higher levels of knowledge about the policies, they lacked information on the risk factors. There is a significant scope that warrants great attention concerning the adherence to guidelines and the provision of fall prevention training programs, with a focus on the intrinsic causative factors of falls.
The Interplay between Neurotransmitters and Calcium Dynamics in Retinal Synapses during Development, Health, and Disease
Authors: Boff Johane M. , Shrestha Abhishek P. , Madireddy Saivikram , Viswaprakash Nilmini , Della Santina Luca , Vaithianathan Thirumalini
Published: February 2024

The intricate functionality of the vertebrate retina relies on the interplay between neurotransmitter activity and calcium (Ca2+) dynamics, offering important insights into developmental processes, physiological functioning, and disease progression. Neurotransmitters orchestrate cellular processes to shape the behavior of the retina under diverse circumstances. Despite research to elucidate the roles of individual neurotransmitters in the visual system, there remains a gap in our understanding of the holistic integration of their interplay with Ca2+ dynamics in the broader context of neuronal development, health, and disease. To address this gap, the present review explores the mechanisms used by the neurotransmitters glutamate, gamma-aminobutyric acid (GABA), glycine, dopamine, and acetylcholine (ACh) and their interplay with Ca2+ dynamics. This conceptual outline is intended to inform and guide future research, underpinning novel therapeutic avenues for retinal-associated disorders.
Association of MDM2 Overexpression in Ameloblastomas with MDM2 Amplification and BRAFV600E Expression
Authors: Tosios Konstantinos I. , Kalogirou Eleni-Marina , Koutlas Ioannis G.
Published: February 2024

Ameloblastoma is a rare tumor but represents the most common odontogenic neoplasm. It is localized in the jaws and, although it is a benign, slow-growing tumor, it has an aggressive local behavior and high recurrence rate. Therefore, alternative treatment options or complementary to surgery have been evaluated, with the most promising one among them being a targeted therapy with the v-Raf murine sarcoma viral oncogene homologue B (BRAF), as in ameloblastoma the activating mutation V600E in BRAF is common. Studies in other tumors have shown that the synchronous inhibition of BRAF and human murine double minute 2 homologue (MDM2 or HDM2) protein is more effective than BRAF monotherapy, particularly in the presence of wild type p53 (WTp53). To investigate the MDM2 protein expression and gene amplification in ameloblastoma, in association with BRAFV600E and p53 expression. Forty-four cases of ameloblastoma fixed in 10% buffered formalin and embedded in paraffin were examined for MDM2 overexpression and BRAFV600E and p53 expression by immunohistochemistry, and for MDM2 ploidy with fluorescence in situ hybridization. Sixteen of forty-four (36.36%) cases of ameloblastoma showed MDM2 overexpression. Seven of sixteen MDM2-positive ameloblastomas (43.75%) were BRAFV600E positive and fifteen of sixteen MDM2-positive ameloblastomas (93.75%) were p53 negative. All MDM2 overexpressing tumors did not show copy number alterations for MDM2. Overexpression of MDM2 in ameloblastomas is not associated with MDM2 amplification, but most probably with MAPK activation and WTp53 expression. Further verification of those findings could form the basis for the use of MDM2 expression as a marker of MAPK activation in ameloblastomas and the trial of dual BRAF/MDM2 inhibition in the management of MDM2-overexpressing/BRAFV600E-positive/WTp53 ameloblastomas.
Factor H’s Control of Complement Activation Emerges as a Significant and Promising Therapeutic Target for Alzheimer’s Disease Treatment
Authors: Hasantari Iris , Nicolas Nabil , Alzieu Philippe , Leval Léa , Shalabi Andree , Grolleau Sylvain , Dinet Virginie
Published: February 2024

The complement is a component of the innate immune system designed to fight infections and tissue- or age-related damages. Complement activation creates an inflammatory microenvironment, which enhances cell death. Excessive complement inflammatory activity has been linked to alterations in the structure and functions of the blood–brain barrier, contributing to a poor prognosis for Alzheimer’s disease (AD). In the AD preclinical phase, individuals are often clinically asymptomatic despite evidence of AD neuropathology coupled with heightened inflammation. Considering the involvement of the complement system in the risk of developing AD, we hypothesize that inhibiting complement activation could reduce this inflammatory period observed even before clinical signs, thereby slowing down the onset/progression of AD. To validate our hypothesis, we injected complement inhibitor factor H into the brain of APP/PS1 AD mice at early or late stages of this pathology. Our results showed that the injection of factor H had effects on both the onset and progression of AD by reducing proinflammatory IL6, TNF-α, IL1β, MAC and amyloid beta levels. This reduction was associated with an increase in VGLUT1 and Psd95 synaptic transmission in the hippocampal region, leading to an improvement in cognitive functions. This study invites a reconsideration of factor H’s therapeutic potential for AD treatment.
Different Forms of TFF3 in the Human Endocervix, including a Complex with IgG Fc Binding Protein (FCGBP), and Further Aspects of the Cervico-Vaginal Innate Immune Barrier
Authors: Laskou Aikaterini , Znalesniak Eva B. , Harder Sönke , Schlüter Hartmut , Jechorek Dörthe , Langer Kathrin , Strecker Carina , Matthes Claudia , Tchaikovski Svetlana N. , Hoffmann Werner
Published: February 2024

TFF3 is a typical secretory poplypeptide of mucous epithelia belonging to the trefoil factor family (TFF) of lectins. In the intestine, respiratory tract, and saliva, TFF3 mainly exists as a high-molecular-mass complex with IgG Fc binding protein (FCGBP), which is indicative of a role in mucosal innate immunity. For the first time, we identified different forms of TFF3 in the endocervix, i.e., monomeric and homodimeric TFF3, as well as a high-molecular-mass TFF3-FCGBP complex; the latter also exists in a hardly soluble form. Immunohistochemistry co-localized TFF3 and FCGBP. Expression analyses of endocervical and post-menopausal vaginal specimens revealed a lack of mucin and TFF3 transcripts in the vaginal specimens. In contrast, genes encoding other typical components of the innate immune defense were expressed in both the endocervix and vagina. Of note, FCGBP is possibly fucosylated. Endocervical specimens from transgender individuals after hormonal therapy showed diminished expression, particularly of FCGBP. Furthermore, mucus swabs from the endocervix and vagina were analyzed concerning TFF3, FCGBP, and lysozyme. It was the aim of this study to illuminate several aspects of the cervico-vaginal innate immune barrier, which is clinically relevant as bacterial and viral infections are also linked to infertility, pre-term birth and cervical cancer.
Revolutionizing Women’s Health: A Comprehensive Review of Artificial Intelligence Advancements in Gynecology
Authors: Brandão Marta , Mendes Francisco , Martins Miguel , Cardoso Pedro , Macedo Guilherme , Mascarenhas Teresa , Mascarenhas Saraiva Miguel
Published: February 2024

Artificial intelligence has yielded remarkably promising results in several medical fields, namely those with a strong imaging component. Gynecology relies heavily on imaging since it offers useful visual data on the female reproductive system, leading to a deeper understanding of pathophysiological concepts. The applicability of artificial intelligence technologies has not been as noticeable in gynecologic imaging as in other medical fields so far. However, due to growing interest in this area, some studies have been performed with exciting results. From urogynecology to oncology, artificial intelligence algorithms, particularly machine learning and deep learning, have shown huge potential to revolutionize the overall healthcare experience for women’s reproductive health. In this review, we aim to establish the current status of AI in gynecology, the upcoming developments in this area, and discuss the challenges facing its clinical implementation, namely the technological and ethical concerns for technology development, implementation, and accountability.
Ultrasonographic Evaluation of the Second Stage of Labor according to the Mode of Delivery: A Prospective Study in Greece
Authors: Mitta Kyriaki , Tsakiridis Ioannis , Dagklis Themistoklis , Kalogiannidis Ioannis , Mamopoulos Apostolos , Michos Georgios , Virgiliou Andriana , Athanasiadis Apostolos
Published: February 2024

Background and Objectives: Accurate diagnosis of labor progress is crucial for making well-informed decisions regarding timely and appropriate interventions to optimize outcomes for both the mother and the fetus. The aim of this study was to assess the progress of the second stage of labor using intrapartum ultrasound. Material and methods: This was a prospective study (December 2022–December 2023) conducted at the Third Department of Obstetrics and Gynecology, School of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, Greece. Maternal–fetal and labor characteristics were recorded, and two ultrasound parameters were measured: the angle of progression (AoP) and the head–perineum distance (HPD). The correlation between the two ultrasonographic values and the maternal–fetal characteristics was investigated. Multinomial regression analysis was also conducted to investigate any potential predictors of the mode of delivery. Results: A total of 82 women at the second stage of labor were clinically and sonographically assessed. The mean duration of the second stage of labor differed between vaginal and cesarean deliveries (65.3 vs. 160 min; p-value < 0.001) and between cesarean and operative vaginal deliveries (160 vs. 88.6 min; p-value = 0.015). The occiput anterior position was associated with an increased likelihood of vaginal delivery (OR: 24.167; 95% CI: 3.8–152.5; p-value < 0.001). No significant differences were identified in the AoP among the three different modes of delivery (vaginal: 145.7° vs. operative vaginal: 139.9° vs. cesarean: 132.1°; p-value = 0.289). The mean HPD differed significantly between vaginal and cesarean deliveries (28.6 vs. 41.4 mm; p-value < 0.001) and between cesarean and operative vaginal deliveries (41.4 vs. 26.9 mm; p-value = 0.002); it was correlated significantly with maternal BMI (r = 0.268; p-value = 0.024) and the duration of the second stage of labor (r = 0.256; p-value = 0.031). Low parity (OR: 12.024; 95% CI: 6.320–22.876; p-value < 0.001) and high HPD (OR: 1.23; 95% CI: 1.05–1.43; p-value = 0.007) were found to be significant predictors of cesarean delivery. Conclusions: The use of intrapartum ultrasound as an adjunctive technique to the standard clinical evaluation may enhance the diagnostic approach to an abnormal labor progress and predict the need for operative vaginal or cesarean delivery.
Incidence and Course of Joint Inflammation Associated with Inflammatory Bowel Disease in Patients Undergoing Treatment with Vedolizumab/Ustekinumab: The VEDUSTAR Study
Authors: Gonzalez Diaz Irene , Gutierrez Riart Mariana , Martin-Arranz Maria Dolores , Plasencia Rodriguez Chamaida , Suarez Ferrer Cristina ,   on behalf of VEDUSTAR Research Team
Published: February 2024

Background: The role of ustekinumab (UST) and vedolizumab (VDZ) in the extraintestinal joint manifestations of inflammatory bowel disease (IBD) remain unclear, and most existing studies are retrospective. The aim of this prospective study was to analyze the incidence of new-onset joint disease or the worsening of pre-existing IBD-associated joint disease in patients treated with UST and VDZ. Methods: The study population comprised IBD patients with previous spondyloarthritis (SpA) or new-onset arthropathy undergoing treatment with VDZ or UST. Results: Eighty patients were referred to rheumatology because of previous SpA or onset of symptoms. Most patients (90%) were anti-TNF experienced. Two patients with previous SpA (2/22; 9%) experienced a flare-up (one with UST and one with VDZ), and two patients with VDZ developed SpA during follow-up (2/58; 3%). Only one of these four patients did not have gastrointestinal symptoms, and VDZ was discontinued because of joint symptoms. The other three patients had concomitant intestinal activity, and treatment was not discontinued. Conclusion: Our experience shows that treatment with UST and VDZ did not worsen joint disease in patients with SpA. Most remained stable or improved. In addition, poor control of IBD in patients with joint flare-ups could be the main cause of worsening SpA.
Do Postural and Walking Stabilities Change over a Decade by Aging? A Longitudinal Study
Authors: Segi Naoki , Nakashima Hiroaki , Ito Sadayuki , Ouchida Jun , Oishi Ryotaro , Yamauchi Ippei , Miyairi Yuichi , Morita Yoshinori , Takegami Yasuhiko , Ishizuka Shinya , Seki Taisuke , Hasegawa Yukiharu , Imagama Shiro
Published: February 2024

Background: Previous studies have demonstrated that the center of gravity (COG) is more unstable in the elderly than in young people. However, it is unclear whether aging itself destabilizes the COG. This study aimed to investigate changes in COG sway and gait kinematics over time by a longitudinal study of middle-aged and elderly adults. Methods: This study included 198 healthy middle-aged and elderly people who underwent stabilometry at ten-year intervals. The participants’ mean age at baseline was 62.9 ± 6.5 years, and 77 (39%) of them were male. The results of stabilometry (mean velocity, sway area, postural sway center in the medial–lateral direction [X center], and postural sway center in the anterior–posterior direction [Y center]), and results of exercise tests (the height-adjusted maximum stride length [HMSL] and the 10 m walk test [10MWT]) were analyzed. The destabilized group with 11 participants, whose mean velocity exceeded 3 cm/s after 10 years, was compared with the stable group with 187 participants, whose mean velocity did not exceed 3 cm/s. Results: Mean velocity increased significantly over ten years (open-eye, from 1.53 ± 0.42 cm to 1.86 ± 0.67 cm, p < 0.001); however, the sway area did not change significantly. X center showed no significant change, whereas Y center showed a significant negative shift (open-eye, from −1.03 ± 1.28 cm to −1.60 ± 1.56 cm, p < 0.001). Although the results of 10MWT and initial HMSL did not differ significantly, the HMSL in the destabilized group at ten years was 0.64, which was significantly smaller than the 0.72 of others (p = 0.019). Conclusions: The ten-year changes in COG sway in middle-aged and elderly adults were characterized by a significant increase in mean velocity but no significant difference in sway area. Because the destabilized group had significantly smaller HMSL at ten years, instability at the onset of movement is likely to be affected by COG instability.
Unmet Horizons: Assessing the Challenges in the Treatment of TP53-Mutated Acute Myeloid Leukemia
Authors: Stafylidis Christos , Vlachopoulou Dimitra , Kontandreopoulou Christina-Nefeli , Diamantopoulos Panagiotis Τ.
Published: February 2024

Acute myeloid leukemia (AML) remains a challenging hematologic malignancy. The presence of TP53 mutations in AML poses a therapeutic challenge, considering that standard treatments face significant setbacks in achieving meaningful responses. There is a pressing need for the development of innovative treatment modalities to overcome resistance to conventional treatments attributable to the unique biology of TP53-mutated (TP53mut) AML. This review underscores the role of TP53 mutations in AML, examines the current landscape of treatment options, and highlights novel therapeutic approaches, including targeted therapies, combination regimens, and emerging immunotherapies, as well as agents being explored in preclinical studies according to their potential to address the unique hurdles posed by TP53mut AML.
Inpatient vs. Outpatient: A Systematic Review of Information Needs throughout the Heart Failure Patient Journey
Authors: Cotie Lisa M. , Pakosh Maureen , Ghisi Gabriela Lima de Melo
Published: February 2024

The objective of this systematic review was to identify and describe information needs for individuals with heart failure (HF) throughout their patient journey. Six databases were searched (APA PsycINFO, CINAHL Ultimate, Embase, Emcare Nursing, Medline ALL, and Web of Science Core Collection) from inception to February 2023. Search strategies were developed utilizing the PICO framework. Potential studies of any methodological design were considered for inclusion through a snowball hand search. Data from the included articles were extracted by a reviewer, and the extraction accuracy was independently cross-checked by another author. Quality appraisal was assessed using the Mixed-Methods Appraisal Tool. A narrative synthesis was used to analyze all the outcomes according to the Synthesis Without Meta-analysis reporting guidelines. Twenty-five studies (15 quantitative and 10 qualitative) were included. Socioeconomic, cultural, and demographic factors influencing information needs were considered. The top three information needs for outpatients included general HF information, signs and symptoms and disease management strategies. For inpatients, medications, risk factors, and general HF were reported as the top needs. These divergent needs emphasize the importance of tailored education at different stages. Additionally, the review identified gaps in global representation, with limited studies from Africa and South America, underscoring the need for inclusive research. The findings caution against overgeneralization due to varied reporting methods. Practical implications call for culturally sensitive interventions to address nuanced HF patients’ needs, while future research must prioritize standardized reporting, consider diverse patient journey timepoints, and minimize biases for enhanced reliability and applicability.