bluuebunny/crossref_metadata_2025 huggingface dataset:
The Singular Epidemiology of Plasmacytoma and Multiple Myeloma in French Guiana
Authors: Imounga Laure Manuella , Drak Alsibai Kinan , Plenet Juliette , Wang Qiannan , Virjophe-Cenciu Beatrice , Couppie Pierre , Sabbah Nadia , Adenis Antoine , Nacher Mathieu
Published: December 2023

Background: The objective was to review a decade of plasmacytoma (PC) and multiple myeloma (MM) data from French Guiana, and to study its spatial and temporal trends. Methods: This was a retrospective study of MM and PC between January 2005 and December 2014 using cancer registry data, including age-standardized incidence and mortality rates. Results: There were 110 cases of PC and MM (62 women and 48 men), representing the eighth most frequent malignancy in French Guiana. PC and MM were much more common in females. In men, 79% of cases occurred at ≥55 years, and in women, 90% of cases occurred at ≥50 years. The median age at diagnosis was 60 years for men and 66 years for women, while it was 72 years for men and 75 years for women in mainland France. The incidence rate standardized to the world population was 5.9 patients of PC and MM per 100,000 men/year and 7.8 per 100,000 women/year. Conclusions: In our territory, the incidence of PC and MM was higher and patients were diagnosed at a substantially younger age than in mainland France. Women had a greater incidence than men, and there was an increasing temporal trend of incidence among women. African ancestry and the frequency of obesity, notably among women, could have contributed to this observation.
“All for One and One for All”: The Secreted Heat Shock Protein gp96-Ig Based Vaccines
Authors: Padula Laura , Fisher Eva , Strbo Natasa
Published: December 2023

It has been 50 years since Peter Charles Doherty and Rolf M Zinkernagel proposed the principle of “simultaneous dual recognition”, according to which adaptive immune cells recognized “self” and “non-self” simultaneously to establish immunological efficacy. These two scientists shared the 1996 Nobel Prize in Physiology or Medicine for this discovery. Their basic immunological principle became the foundation for the development of numerous vaccine approaches against infectious diseases and tumors, including promising strategies grounded on the use of recombinant gp96-Ig developed by our lab over the last two decades. In this review, we will highlight three major principles of the gp96-Ig vaccine strategy: (1) presentation of pathogenic antigens to T cells (specificity); (2) activation of innate immune responses (adjuvanticity); (3) priming of T cells to home to the epithelial compartments (mucosal immunity). In summary, we provide a paradigm for a vaccine approach that can be rapidly engineered and customized for any future pathogens that require induction of effective tissue-resident memory responses in epithelial tissues.
Modulation of Suppressive Activity and Proliferation of Human Regulatory T Cells by Splice-Switching Oligonucleotides Targeting FoxP3 Pre-mRNA
Authors: Blinova Varvara G. , Gladilina Yulia A. , Abramova Anna A. , Eliseeva Daria D. , Vtorushina Valentina V. , Shishparenok Anastasia N. , Zhdanov Dmitry D.
Published: December 2023

The maturation, development, and function of regulatory T cells (Tregs) are under the control of the crucial transcription factor Forkhead Box Protein 3 (FoxP3). Through alternative splicing, the human FoxP3 gene produces four different splice variants: a full-length variant (FL) and truncated variants with deletions of each of exons 2 (∆2 variant) or 7 (∆7 variant) or a deletion of both exons (∆2∆7 variant). Their involvement in the biology of Tregs as well as their association with autoimmune diseases remains to be clarified. The aim of this work was to induce a single FoxP3 splice variant in human Tregs by splice switching oligonucleotides and to monitor their phenotype and proliferative and suppressive activity. We demonstrated that Tregs from peripheral blood from patients with multiple sclerosis preferentially expressed truncated splice variants, while the FL variant was the major variant in healthy donors. Tregs with induced expression of truncated FoxP3 splice variants demonstrated lower suppressive activity than those expressing FL variants. Reduced suppression was associated with the decreased expression of Treg-associated suppressive surface molecules and the production of cytokines. The deletion of exons 2 and/or 7 also reduced the cell proliferation rate. The results of this study show an association between FoxP3 splice variants and Treg function and proliferation. The modulation of Treg suppressive activity by the induction of the FoxP3 FL variant can become a promising strategy for regenerative immunotherapy.
Questions and Controversies in Neonatal Seizures
Authors: Cappellari Alberto M. , Palumbo Sarah , Margiotta Stefania
Published: December 2023

Neonatal seizures are relatively common, but their diagnosis and management remain challenging. We reviewed the scientific literature on neonatal seizures from July 1973 to November 2023. Several parameters were considered, including pathophysiology, diagnostic criteria, electroencephalographic findings and treatment. Recent classification system of seizures and epilepsies in the newborn, as well as treatment recommendations of neonatal seizures, have been proposed. Nonetheless, the approach to neonatal seizures varies among clinicians and centres, including detection, investigation, treatment and follow-up of patients. There are still many issues on the diagnosis and treatment of neonatal seizures, including the meaning or relevance of some electroencephalographic findings, the precise estimation of the seizure burden, the limited efficacy and side effects risk of antiseizure medications, and the best measures to establish the outcome.
RETRACTED: Díez López, I. The Assessment of Nutritional Status in Pediatrics: New Tools and Challenges. Children 2023, 10, 1151
Authors: Díez López Ignacio
Published: December 2023

The Children Editorial Office retracts the article entitled “The Assessment of Nutritional Status in Pediatrics: New Tools and Challenges” by Díez Lopez [...]
Numerical Study on Glaze Ice Accretion Characteristics over Time for a NACA 0012 Airfoil
Authors: Lu Hao , Xu Yongzhong , Li Hongchang , Zhao Wenjun
Published: December 2023

Ice accretion on wind turbine blades can significantly impact their aerodynamic performance, increasing additional load and reducing power generation. This paper utilizes numerical simulation to predict the cross-section at the blade tip of a small wind turbine and study the ice accretion process and aerodynamic characteristics of the airfoil. The research investigates the dynamic characteristics of ice accretion on NACA 0012 airfoil, as well as the influence of dynamic icing at different angles of attack and airflow velocities on the lift coefficient of the airfoil. The findings show that ice accretion leads to a more significant decrease in the lift coefficient of the airfoil at angles of attack of 8° and 12°. From 0 min to 30 min, the decrease rate of the lift coefficient is up to 48% and 46.2%, respectively. The aerodynamic performance of airfoil at 70 m/s deteriorates the most severely and the reduction degree of the lift coefficient can exceed 23.2%. These results may supply guidance for wind turbine anti-icing solutions.
Development of Topical Formulations Containing 20% of Coated and Uncoated Zinc Oxide Nanoparticles: Stability Assessment and Penetration Evaluation by Reflectance Confocal Laser Microscopy
Authors: Assis Dias Alves Geórgia de , Cuelho Camila Helena Ferreira , Fonseca Maria José Vieira , Maia Campos Patrícia Maria Berardo Gonçalves
Published: December 2023

The introduction of zinc oxide nanoparticles (ZnOn) in sunscreens solved the issue of poor spreadability of these formulations, which often left a white film on the skin. However, safety concerns have arisen regarding the topical application of ZnOn. Some studies employed commercial sunscreens to address the safety issues of the topical application of ZnOn; however, commercial formulations are often complex and contain a wide range of ingredients that could attenuate the potential damage caused by the ZnOn. Therefore, in this study we aimed to develop a simple stable formulation containing 20% of coated and uncoated ZnOn, characterize the formulations and the nanoparticles, and assess the skin penetration in a Franz diffusion cell. The Feret’s diameter for the uncoated and coated ZnOn was 137 nm and 134 nm, respectively. For the uncoated ZnOn the hydrodynamic size in water was 368 nm and for the coated ZnOn, the average hydrodynamic size in ethyl acetate was 135 nm. The incorporation of ZnOn led to formulations more consistent and easier to spread, as suggested by the lower work of shear and higher values of firmness, cohesiveness, consistency and index of viscosity compared with the vehicle. The stability assessment at 45 °C suggested that the formulations containing the ZnOn were stable for 30 days and the vehicle was stable for 90 days. The assessment of the skin penetration by reflectance confocal laser microscopy indicated that the ZnOn did not permeate into the deepest layers of the skin, but accumulated on the skin furrows, hair and hair follicles.
The Best Supportive Care in Stage III Non-Small-Cell Lung Cancer
Authors: Oliveira Thiago Bueno de , Fontes Debora Maloni Nasti , Montella Tatiane Caldas , Lewgoy Jairo , Dutra Carolina , Miola Thais Manfrinato
Published: December 2023

Lung cancer is a major cause of cancer deaths worldwide. Non-small-cell lung cancer (NSCLC) represents most lung cancer cases, and approximately one-third of patients present with stage III disease at diagnosis. As multiple treatment plans can be adopted for these patients depending on tumor size and nodal staging, stage III NSCLC management is challenging. Over the past decades, multidisciplinary teams (MDTs) have been implemented in healthcare services to coordinate actions among the different health care professionals involved in cancer care. The aim of this review was to discuss real-world evidence of the impact of MDTs on stage III NSCLC management, survival, and quality of life. Here, we performed a literature review to investigate the role of nutrition and navigational nursing in NSCLC care and the influence of MDTs in the choice of treatment plans, including immunotherapy consolidation, and in the management of chemotherapy and radiotherapy-related adverse events. We also performed a mapping review to identify gaps in the implementation of cancer care MDTs in healthcare services around the world.
Point-of-Care Orthopedic Oncology Device Development
Authors: Mavrodontis Ioannis I. , Trikoupis Ioannis G. , Kontogeorgakos Vasileios A. , Savvidou Olga D. , Papagelopoulos Panayiotis J.
Published: December 2023

Background: The triad of 3D design, 3D printing, and xReality technologies is explored and exploited to collaboratively realize patient-specific products in a timely manner with an emphasis on designs with meta-(bio)materials. Methods: A case study on pelvic reconstruction after oncological resection (osteosarcoma) was selected and conducted to evaluate the applicability and performance of an inter-epistemic workflow and the feasibility and potential of 3D technologies for modeling, optimizing, and materializing individualized orthopedic devices at the point of care (PoC). Results: Image-based diagnosis and treatment at the PoC can be readily deployed to develop orthopedic devices for pre-operative planning, training, intra-operative navigation, and bone substitution. Conclusions: Inter-epistemic symbiosis between orthopedic surgeons and (bio)mechanical engineers at the PoC, fostered by appropriate quality management systems and end-to-end workflows under suitable scientifically amalgamated synergies, could maximize the potential benefits. However, increased awareness is recommended to explore and exploit the full potential of 3D technologies at the PoC to deliver medical devices with greater customization, innovation in design, cost-effectiveness, and high quality.
Clinical Assessment of Plaque Removal Using a Novel Dentifrice Containing Cellulose Microfibrils
Authors: Labib Mohamed E. , Perazzo Antonio , Manganaro James , Tabani Yacoob , Milleman Kimberly R. , Milleman Jeffery L. , Walsh Laurence J.
Published: December 2023

Dentifrice performance in the removal of dental plaque is influenced by the interactions of dentifrice components with tooth surfaces. This randomized controlled clinical study assessed the effectiveness and safety of a novel fluoride dentifrice formulation that included a micro-fibrillated cellulose network with entangled microcrystalline cellulose and silica particles (ProtegeraTM), and compared this to a positive control fluoride dentifrice (Crest Cavity Protection™). Whole mouth dental plaque levels in 82 healthy adults were measured after the first supervised use, and following a week of twice daily use at home. Overall, the test dentifrice was at least three times and up to four times more effective in whole-mouth plaque reductions, with a 38.6% reduction on first use, a 30.9% reduction at day 7, and a 41.6% reduction from day 1 to day 7, compared to reductions of 12.0%, 9.6% and 11.6%, respectively for the positive control, and up to seven times more effective in lingual plaque reductions, than the reference dentifrice (p < 0.001), with a 27.7% reduction on first use, a 22.3% reduction at day 7, and a 31.0% reduction from day 1 to day 7, compared to reductions of 4.4%, 2.2%, and 4.5%, respectively, for the positive control. No safety issues arose from the use of the test dentifrice. These results indicate that including micro-fibrillated cellulose enhances plaque removal effectiveness, without causing adverse changes to oral soft tissues.
Effect of the Teeth Whitening Procedure on the Mineral Composition of Oral Fluid
Authors: Ryskina Elena A. , Magsumova Oksana A. , Postnikov Mikhail A. , Lobaeva Tatiana A. , Ahmedzhanov Bahovaddin B. , Shishparenok Anastasia N. , Zhdanov Dmitry D.
Published: December 2023

The basis of modern tooth whitening systems is the use of a whitening gel, which usually contains hydrogen peroxide or carbamide peroxide. The study included 81 patients aged 22 to 35 years with a tooth color A2 and a darker color on the Vita Classic scale. The purpose of our research was to identify a new approach to whitening teeth to improve safety and gentleness. To perform this, we assessed the effect of the tooth whitening procedure on the mineral composition of the oral fluid. A new approach to the teeth whitening procedure was to use a mouth retractor and a tool for aspirating the whitening gel, which we developed. Before the procedure, a protective film-forming aerosol, which included sodium ascorbate, was applied. After the tooth whitening procedure, the enamel was remineralized with a sealing liquid for 14 days. The concentrations of calcium and phosphorus in the oral fluid were determined using a spectrophotometer with a set of reagents (Human). The results obtained indicate that the new approach to the teeth whitening procedure contributed to less pronounced changes in the concentrations of calcium (+29.07, p < 0.001) and phosphorus (−14%, p < 0.001) in the oral fluid immediately after the procedure and in combination with the standard procedure for teeth whitening; immediately after this procedure, the calcium concentration increased by 74.4% (p < 0.001), and the phosphorus concentration decreased by 23.07% (p < 0.001). The use of remineralizing agents led to a faster recovery of the initial levels of calcium and phosphorus in the oral fluid.
Carbon Emission Forecasting Study Based on Influence Factor Mining and Mini-Batch Stochastic Gradient Optimization
Authors: Yang Wei , Yuan Qiheng , Wang Yongli , Zheng Fei , Shi Xin , Li Yi
Published: December 2023

With the increasing prominence of the global carbon emission problem, the accurate prediction of carbon emissions has become an increasingly urgent need. Existing carbon emission prediction methods have the problems of slow calculation speed, inaccurate prediction, and insufficient deep mining of influencing factors when dealing with large-scale data. In this study, a comprehensive carbon emission prediction method is proposed. Firstly, multiple influencing factors including economic factors and demographic factors are considered, and a pathway analysis method is introduced to mine the long-term relationship between these factors and carbon emissions. Then, indirect influence terms are added to the multiple regression equation, and the variable is used to represent the indirect influence relationship. Finally, this study proposes the PCA-PA-MBGD method, which applies the results of principal component analysis to the pathway analysis. By reducing the data dimensions and extracting the main influencing factors, and optimizing the carbon emission prediction model by using a mini-batch stochastic gradient descent algorithm, the results show that this method can process a large amount of data quickly and efficiently, and realize an accurate prediction of carbon emissions. This provides strong support for solving the carbon emission problem and offers new ideas and methods for future related research.
Experimental Investigation on SiC MOSFET Turn-Off Power Loss Reduction Using the Current Sink Capacitor Technique
Authors: Harasimczuk Michał , Kopacz Rafał , Trochimiuk Przemysław , Miśkiewicz Rafał , Rąbkowski Jacek
Published: December 2023

This paper investigates the current sink capacitor technique as a method to minimize the turn-off power losses of SiC MOSFETs operated with zero-voltage switching (ZVS). The method is simple and is based on adding auxiliary capacitors in parallel to the transistors, allowing the sink capacitor to take over part of the channel current, thus limiting the power loss while also advantageously lowering the dvds/dt ratio. The technique is validated and experimentally studied based on a single-pulse test setup with 1200 V-rated SiC MOSFETs, with several capacitances and gate resistance values, at various switched currents up to roughly 60 A. It is shown that by employing even very small capacitances, in the range of nanofarads, the turn-off power loss can be reduced by over tenfold, with a negligible impact on the volume and complexity of the system. Thus, the presented method can be effectively employed to improve soft-switched power converters.
Experimental Investigations on Pressure Drop for Subcooled Water in a Circular Channel with a Twisted Tape Insert under One-Side Heating Conditions
Authors: Zhu Ge , Mei Ge , Bi Qincheng , Tian Shujian
Published: December 2023

The pressure drop characteristics of subcooled water were experimentally investigated in a circular cooling channel with and without a twisted tape (TT) under high heat fluxes, which was designed for the water-cooling structure of the divertor target in a tokamak device. The working medium was deionized water, and the main parameters were mass flux G = 3000–8000 kg·m−2·s−1, inlet pressure of the test section p = 3, 4.2, 5 MPa, equivalent one-side heating flux qe = 5~10 MW·m−2. The off-center circular channel is electrically heated to simulate the unilateral radiation heating on the divertor target by high-temperature plasma. The pressure drop experiment of vertical upward circular cooling channels under high and unilateral heat flux is carried out. The influences of the TT and system parameters such as qe, G, and p on the pressure drop of the test section (Δp) were discussed in detail. In the single-phase (SP) flow region, Δp is mainly affected by the TT, G, and qe. The pressure drop with a TT is significantly higher than that without a TT, a higher G and a lower qe lead to a greater Δp. In the subcooled boiling (SB) flow region, Δp is correlated with the TT, qe, G, and p: the influence of the TT and G decreases, while the influence of p increases. The higher the qe, the higher the G, and the lower the p, the larger the Δp. The results show that almost all of the SP pressure drop correlations for heated circular channels overestimate the experimental pressure drop coefficient ratio for a given viscosity ratio. According to the test results, a new correlation of SP pressure drop under high and unilateral heat fluxes has been proposed, the average error (AE) and root mean square error (RMSE) of which are 0.26% and 3.17%, respectively.
An Efficient Electrothermal Model of a Thermoelectric Converter for a Thermal Energy Harvesting Process Simulation and Electronic Circuits Powering
Authors: Dziurdzia Piotr , Bratek Piotr , Markiewicz Michał
Published: December 2023

This paper deals with an electrothermal model of a thermoelectric converter dedicated to performing simulations of coupled thermal and electrical phenomena taking place in harvesting processes. The proposed model is used to estimate the electrical energy gain from waste heat that would be sufficient to supply electronic circuits, in particular autonomous battery-less nodes of wireless sensor networks (WSN) and Internet of Things (IoT) devices. The developed model is not limited to low-power electronic solutions such as WSN or IoT; it can also be scaled up and applied to simulations of considerably higher thermal power conversion. In this paper, a few practical case studies are presented that show the feasibility and suitability of the proposed model for complex simultaneous simulation processes in both the electrical and thermal domains. The first example deals with a combined simulation of the electrothermal model of a thermoelectric generator (TEG) and an electronic harvester circuit based on Analog Devices’ power management integrated circuit LTC3108. The second example relates to the thermalization effect in heat sink-less harvesting applications that could be mitigated by a pulse mode operation. The unique contribution and advancement of the model is the hierarchical structure for scaling up and down, incorporating the complexity of the Seebeck effect, the Joule effect, heat conduction, as well as the temperature dependence of the used materials and the thermoelectric pellet geometries. The simulations can be performed in steady as well as transient states under changing electrical loads and temperatures.
Biodiversity and Safety: Cohabitation Experimentation in Undefined Starter Cultures for Traditional Dairy Products
Authors: Chessa Luigi , Daga Elisabetta , Dupré Ilaria , Paba Antonio , Fozzi Maria C. , Dedola Davide G. , Comunian Roberta
Published: December 2023

Natural starter cultures, characterised by undefined microbiota, can contribute to the technological process, giving peculiar characteristics to artisanal fermented foods. Several species have a long history of safe use and have obtained Qualified Presumption of Safety (QPS) status from the European Food Safety Authority (EFSA), whereas others (non-QPS) could represent a potential risk for consumers’ health and must undergo a safety assessment. In this work, the biodiversity, at species and strain level, by pulsed-field gel electrophoresis (PFGE) and (GTG)5 rep-PCR, of an undefined natural starter culture, in frozen and lyophilized form, obtained from ewe’s raw milk avoiding thermal treatment or microbial selection, was investigated. The culture was constituted by different biotypes of Enterococcus durans, Enterococcus faecium, Enterococcus faecalis, and Lacticaseibacillus paracasei. Streptococcus oralis and Streptococcus salivarius were also found, over species belonging to the Streptococcus bovis–Streptococcus equinus complex (SBSEC), like Streptococcus gallolyticus subsp. macedonicus, Streptococcus lutetiensis, and Streptococcus equinus. Molecular investigation on virulence and antibiotic resistance genes, as well as minimum inhibitory concentration (MIC) determination, revealed that all the non-QPS strains can be considered safe in the perspective of using this culture for cheesemaking. The obtainment of a natural culture directly from ewe’s raw milk bypassing thermal treatment and selection of pro-technological bacteria can be advantageous in terms of biodiversity preservation, but non-QPS microorganisms can be included in the natural starter and also in cheeses, especially in traditional ones obtained from fermenting raw milk. Following EFSA guidelines, artisanal factories should not be allowed to produce starter cultures by themselves from raw milk, running the risk of including some non-QPS species in their culture, and only selected starters could be used for cheesemaking. A revision of the criteria of QPS guidelines should be necessary.
Vnode: Low-Overhead Transparent Tracing of Node.js-Based Microservice Architectures
Authors: Kabamba Herve M. , Khouzam Matthew , Dagenais Michel R.
Published: December 2023

Tracing serves as a key method for evaluating the performance of microservices-based architectures, which are renowned for their scalability, resource efficiency, and high availability. Despite their advantages, these architectures often pose unique debugging challenges that necessitate trade-offs, including the burden of instrumentation overhead. With Node.js emerging as a leading development environment recognized for its rapidly growing ecosystem, there is a pressing need for innovative performance debugging approaches that reduce the telemetry data collection efforts and the overhead incurred by the environment’s instrumentation. In response, we introduce a new approach designed for transparent tracing and performance debugging of microservices in cloud settings. This approach is centered around our newly developed Internal Transparent Tracing and Context Reconstruction (ITTCR) technique. ITTCR is adept at correlating internal metrics from various distributed trace files to reconstruct the intricate execution contexts of microservices operating in a Node.js environment. Our method achieves transparency by directly instrumenting the Node.js virtual machine, enabling the collection and analysis of trace events in a transparent manner. This process facilitates the creation of visualization tools, enhancing the understanding and analysis of microservice performance in cloud environments. Compared to other methods, our approach incurs an overhead of approximately 5% on the system for the trace collection infrastructure while exhibiting minimal utilization of system resources during analysis execution. Experiments demonstrate that our technique scales well with very large trace files containing huge numbers of events and performs analyses in very acceptable timeframes.
Identification and Analysis of Candidate Genes Associated with Yield Structure Traits and Maize Yield Using Next-Generation Sequencing Technology
Authors: Nowak Bartosz , Tomkowiak Agnieszka , Sobiech Aleksandra , Bocianowski Jan , Kowalczewski Przemysław Łukasz , Spychała Julia , Jamruszka Tomasz
Published: December 2023

The main challenge of agriculture in the 21st century is the continuous increase in food production. In addition to ensuring food security, the goal of modern agriculture is the continued development and production of plant-derived biomaterials. Conventional plant breeding methods do not allow breeders to achieve satisfactory results in obtaining new varieties in a short time. Currently, advanced molecular biology tools play a significant role worldwide, markedly contributing to biological progress. The aim of this study was to identify new markers linked to candidate genes determining grain yield. Next-generation sequencing, gene association, and physical mapping were used to identify markers. An additional goal was to also optimize diagnostic procedures to identify molecular markers on reference materials. As a result of the conducted research, 19 SNP markers significantly associated with yield structure traits in maize were identified. Five of these markers (28629, 28625, 28640, 28649, and 29294) are located within genes that can be considered candidate genes associated with yield traits. For two markers (28639 and 29294), different amplification products were obtained on the electrophorograms. For marker 28629, a specific product of 189 bp was observed for genotypes 1, 4, and 10. For marker 29294, a specific product of 189 bp was observed for genotypes 1 and 10. Both markers can be used for the preliminary selection of well-yielding genotypes.
Knowledge on Stroke Recognition and Management among Emergency Department Healthcare Professionals in the Republic of Cyprus
Authors: Rossis Christos , Michail Koralia A. , Middleton Nicos , Karanikola Maria , Papathanassoglou Elizabeth , Mpouzika Meropi
Published: December 2023

Stroke is a global leading cause of death and disability. Knowledge of related guidelines is crucial for emergency department (ED) staff, influencing early diagnosis and timely treatment. We investigated Greek Cypriot ED healthcare professionals’ (nurses and physicians) knowledge in recognizing and managing stroke. A descriptive cross-sectional study spanned November 2019 to April 2020, encompassing four private and seven public EDs in the Republic of Cyprus. The data were collected through a self-reported questionnaire developed by the research team, consisting of 37 questions. Eight questions focused on sociodemographic and employment characteristics, twenty-eight assessed knowledge in stroke recognition and management (each item was equally weighted without deliberate prioritization), and one question addressed self-assessment of knowledge in stroke care. A total of 255 nurses (response rate (RR): 74.1%) and 26 physicians (RR: 47.3%) completed the questionnaire. The average correct response rate was 12.9 out of 28 statements (SD: 4.2), with nurses and physicians scoring 12.6 (SD: 4.1) and 15.7 (SD: 4), respectively. Work experience significantly influenced stroke knowledge, with all groups demonstrating superiority over those with less than one year of experience. Participants with previous training scored an average of 1.45 additional correct answers while educational attainment did not significantly influence stroke knowledge. Investigating stroke knowledge among emergency department nurses and physicians in the Republic of Cyprus revealed significant deficits. This study stresses targeted interventions, including education, yearly examinations, workshops with hands-on training, and repeated training, to address these gaps and enhance the overall stroke care capabilities of the healthcare professionals.
Psychophysiological Responses in Soldiers during Close Combat: Implications for Occupational Health and Fitness in Tactical Populations
Authors: Stergiou Maria , Robles-Pérez José Juan , Rey-Mota Jorge , Tornero-Aguilera José Francisco , Clemente-Suárez Vicente Javier
Published: December 2023

This study explores the psychophysiological responses and subjective exertion experiences of soldiers in simulated hand-to-hand combat, aligning these findings with established physiological benchmarks. Active military personnel were monitored for heart rate, blood lactate levels, subjective exertion, cortical arousal, and muscle strength during combat scenarios. The results showed significant increases in heart rate and blood lactate, indicating intense cardiovascular demands and a reliance on anaerobic energy systems. Contrary to these physiological changes, soldiers reported lower levels of exertion, suggesting a possible underestimation of physical effort or individual differences in perception and mental resilience to stress. Notably, a decrease in cortical arousal post-combat was observed, potentially signaling cognitive function deficits in decision-making and information processing in high-stress environments. This decline was more pronounced than typically seen in other high-stress situations, highlighting the unique cognitive demands of hand-to-hand combat. Additionally, an increase in muscle strength was noted, underscoring the physiological adaptations arising from intensive combat training. These findings provide valuable insights into the psychophysiological effects of hand-to-hand combat, emphasizing the complex interplay between physical exertion, cognitive function, and stress response in military contexts. The study underscores the need for comprehensive training strategies that address both physical and psychological aspects to enhance combat readiness and decision-making under stress.
Genome-Wide Association Study Meta-Analysis Elucidates Genetic Structure and Identifies Candidate Genes of Teat Number Traits in Pigs
Authors: Li Tingting , Wan Pengchong , Lin Qing , Wei Chen , Guo Kaixuan , Li Xiaojing , Lu Yujin , Zhang Zhe , Li Jiaqi
Published: December 2023

The teat number is a pivotal reproductive trait that significantly influences the survival rate of piglets. A meta-analysis is a robust instrument, enhancing the universality of research findings and improving statistical power by increasing the sample size. This study aimed to identify universal candidate genes associated with teat number traits using a genome-wide association study (GWAS) meta-analysis with three breeds. We identified 21 chromosome threshold significant single-nucleotide polymorphisms (SNPs) associated with five teat number traits in single-breed and cross-breed meta-GWAS analyses. Using a co-localization analysis of expression quantitative trait loci and GWAS loci, we detected four unique genes that were co-localized with cross-breed GWAS loci associated with teat number traits. Through a meta-analysis and integrative analysis, we identified more reliable candidate genes associated with multiple-breed teat number traits. Our research provides new information for exploring the genetic mechanism affecting pig teat number for breeding selection and improvement.
Metabolomics in Animal Models of Bronchial Asthma and Its Translational Importance for Clinics
Authors: Barosova Romana , Baranovicova Eva , Hanusrichterova Juliana , Mokra Daniela
Published: December 2023

Bronchial asthma is an extremely heterogenous chronic respiratory disorder with several distinct endotypes and phenotypes. These subtypes differ not only in the pathophysiological changes and/or clinical features but also in their response to the treatment. Therefore, precise diagnostics represent a fundamental condition for effective therapy. In the diagnostic process, metabolomic approaches have been increasingly used, providing detailed information on the metabolic alterations associated with human asthma. Further information is brought by metabolomic analysis of samples obtained from animal models. This article summarizes the current knowledge on metabolomic changes in human and animal studies of asthma and reveals that alterations in lipid metabolism, amino acid metabolism, purine metabolism, glycolysis and the tricarboxylic acid cycle found in the animal studies resemble, to a large extent, the changes found in human patients with asthma. The findings indicate that, despite the limitations of animal modeling in asthma, pre-clinical testing and metabolomic analysis of animal samples may, together with metabolomic analysis of human samples, contribute to a novel way of personalized treatment of asthma patients.
Molecular Profile of Intrahepatic Cholangiocarcinoma
Authors: Andraus Wellington , Tustumi Francisco , de Meira Junior José Donizeti , Pinheiro Rafael Soares Nunes , Waisberg Daniel Reis , Lopes Liliana Ducatti , Arantes Rubens Macedo , Rocha Santos Vinicius , de Martino Rodrigo Bronze , Carneiro D’Albuquerque Luiz Augusto
Published: December 2023

Intrahepatic cholangiocarcinoma (ICC) is a relatively uncommon but highly aggressive primary liver cancer that originates within the liver. The aim of this study is to review the molecular profile of intrahepatic cholangiocarcinoma and its implications for prognostication and decision-making. This comprehensive characterization of ICC tumors sheds light on the disease’s underlying biology and offers a foundation for more personalized treatment strategies. This is a narrative review of the prognostic and therapeutic role of the molecular profile of ICC. Knowing the molecular profile of tumors helps determine prognosis and support certain target therapies. The molecular panel in ICC helps to select patients for specific therapies, predict treatment responses, and monitor treatment responses. Precision medicine in ICC can promote improvement in prognosis and reduce unnecessary toxicity and might have a significant role in the management of ICC in the following years. The main mutations in ICC are in tumor protein p53 (TP53), Kirsten rat sarcoma virus (KRAS), isocitrate dehydrogenase 1 (IDH1), and AT-rich interactive domain-containing protein 1A (ARID1A). The rate of mutations varies significantly for each population. Targeting TP53 and KRAS is challenging due to the natural characteristics of these genes. Different stages of clinical studies have shown encouraging results with inhibitors of mutated IDH1 and target therapy for ARID1A downstream effectors. Fibroblast growth factor receptor 2 (FGFR2) fusions are an important target in patients with ICC. Immune checkpoint blockade can be applied to a small percentage of ICC patients. Molecular profiling in ICC represents a groundbreaking approach to understanding and managing this complex liver cancer. As our comprehension of ICC’s molecular intricacies continues to expand, so does the potential for offering patients more precise and effective treatments. The integration of molecular profiling into clinical practice signifies the dawn of a new era in ICC care, emphasizing personalized medicine in the ongoing battle against this malignancy.
Increased Mortality Risk at Septic Condition in Inflammatory Skin Disorders and the Effect of High-Fat Diet Consumption
Authors: Nishimura Mai , Nakanishi Takehisa , Ichishi Masako , Matsushima Yoshiaki , Watanabe Masatoshi , Yamanaka Keiichi
Published: December 2023

In recent years, attention has increasingly focused on various infectious diseases. Although some fatalities are directly attributed to the causative virus, many result from complications and reactive inflammation. Patients with comorbidities are at a higher risk of mortality. Refractory skin conditions such as atopic dermatitis, psoriasis, and epidermolysis bullosa, known for an elevated risk of sepsis, partly owe this to compromised surface barrier function. However, the detailed mechanisms underlying this phenomenon remain elusive. Conversely, although the detrimental effects of a high-fat diet on health, including the onset of metabolic syndrome, are widely recognized, the association between diet and susceptibility to sepsis has not been extensively explored. In this study, we examined the potential causes and pathogenesis of increased sepsis susceptibility in inflammatory skin diseases using a mouse dermatitis model: keratin 14-driven caspase-1 is overexpressed (KCASP1Tg) in mice on a high-fat diet. Our findings reveal that heightened mortality in the dermatitis mouse model is caused by the inflamed immune system due to the chronic inflammatory state of the local skin, and administration of LPS causes a rapid increase in inflammatory cytokine levels in the spleen. Intake of a high-fat diet exacerbates these cytokine levels. Interestingly, we also observed a reduced expression of Toll-like receptor 4 (TLR4) in monocytes from KCASP1Tg mice, potentially predisposing these animals to heightened infection risks and associated complications. Histological analysis showed a clear decrease in T and B cells in the spleen of KCASP1Tg mice fed a high-fat diet. Thickening of the alveolar wall, inflammatory cell infiltration, and alveolar hemorrhage were more prominent in the lungs of KCASP1Tg and KCASP1Tg with fat mice. We postulate that the chronic, non-infectious inflammation induces a negative feedback loop within the inflammatory cascade, and the suppressed expression of TLR4 renders the mice more susceptible to infections. Therefore, it is imperative for individuals with chronic skin inflammation to closely monitor disease progression upon infection and seek timely and appropriate treatment. Additionally, chronic inflammation of adipose tissue, induced by high-fat food intake, combined with dermatitis inflammation, may exacerbate infections, necessitating a review of dietary habits.
Venetoclax and Hypomethylating Agent Combination in Myeloid Malignancies: Mechanisms of Synergy and Challenges of Resistance
Authors: Mishra Rahul , Zokaei Nikoo Maedeh , Veeraballi Sindhusha , Singh Abhay
Published: December 2023

There has been a widespread adoption of hypomethylating agents (HMA: 5-Azacytidine (5-Aza)/decitabine) and venetoclax (Ven) for the treatment of acute myeloid leukemia (AML); however, the mechanisms behind the combination’s synergy are poorly understood. Monotherapy often encounters resistance, leading to suboptimal outcomes; however, the combination of HMA and Ven has demonstrated substantial improvements in treatment responses. This study elucidates multiple synergistic pathways contributing to this enhanced therapeutic effect. Key mechanisms include HMA-mediated downregulation of anti-apoptotic proteins, notably MCL-1, and the priming of cells for Ven through the induction of genes encoding pro-apoptotic proteins such as Noxa. Moreover, Ven induces sensitization to HMA, induces overcoming resistance by inhibiting the DHODH enzyme, and disrupts antioxidant pathways (Nrf2) induced by HMA. The combination further disrupts oxidative phosphorylation in leukemia stem cells, amplifying the therapeutic impact. Remarkably, clinical studies have revealed a favorable response, particularly in patients harboring specific mutations, such as IDH1/2, NPM1, CEBPA, or ASXL1. This prompts future studies to explore the nuanced underpinnings of these synergistic mechanisms in AML patients with these molecular signatures.
Metabolomics Integration in Assisted Reproductive Technologies for Enhanced Embryo Selection beyond Morphokinetic Analysis
Authors: Pinto Soraia , Guerra-Carvalho Bárbara , Crisóstomo Luís , Rocha António , Barros Alberto , Alves Marco G. , Oliveira Pedro F.
Published: December 2023

Embryo quality evaluation during in vitro development is a crucial factor for the success of assisted reproductive technologies (ARTs). However, the subjectivity inherent in the morphological evaluation by embryologists can introduce inconsistencies that impact the optimal embryo choice for transfer. To provide a more comprehensive evaluation of embryo quality, we undertook the integration of embryo metabolomics alongside standardized morphokinetic classification. The culture medium of 55 embryos (derived from 21 couples undergoing ICSI) was collected at two timepoints (days 3 and 5). Samples were split into Good (n = 29), Lagging (n = 19), and Bad (n = 10) according to embryo morphokinetic evaluation. Embryo metabolic performance was assessed by monitoring the variation in specific metabolites (pyruvate, lactate, alanine, glutamine, acetate, formate) using 1H-NMR. Adjusted metabolite differentials were observed during the first 3 days of culture and found to be discriminative of embryo quality at the end of day 5. Pyruvate, alanine, glutamine, and acetate were major contributors to this discrimination. Good and Lagging embryos were found to export and accumulate pyruvate and glutamine in the first 3 days of culture, while Bad embryos consumed them. This suggests that Bad embryos have less active metabolic activity than Good and Lagging embryos, and these two metabolites are putative biomarkers for embryo quality. This study provides a more comprehensive evaluation of embryo quality and can lead to improvements in ARTs by enabling the selection of the best embryos. By combining morphological assessment and metabolomics, the selection of high-quality embryos with the potential to result in successful pregnancies may become more accurate and consistent.
Development and Characterization of 99mTc-scFvD2B as a Potential Radiopharmaceutical for SPECT Imaging of Prostate Cancer
Authors: Bolzati Cristina , Gobbi Carolina , Ferro-Flores Guillermina , Turato Sofia , Ocampo-Garcia Blanca , Carpanese Debora , Marzano Cristina , Spolaore Barbara , Fracasso Giulio , Rosato Antonio , Meléndez-Alafort Laura
Published: December 2023

Previously, we demonstrated that the 177Lu-labeled single-chain variable fragment of an anti-prostate-specific membrane antigen (PSMA) IgG D2B antibody (scFvD2B) showed higher prostate cancer (PCa) cell uptake and tumor radiation doses compared to 177Lu-labeled Glu-ureide-based PSMA inhibitory peptides. To obtain a 99mTc-/177Lu-scFvD2B theranostic pair, this research aimed to synthesize and biochemically characterize a novel 99mTc-scFvD2B radiotracer. The scFvD2B-Tag and scFvD2B antibody fragments were produced and purified. Then, two HYNIC derivatives, HYNIC-Gly-Gly-Cys-NH2 (HYNIC-GGC) and succinimidyl-HYNIC (S-HYNIC), were used to conjugate the scFvD2B-Tag and scFvD2B isoforms, respectively. Subsequently, chemical characterization, immunoreactivity tests (affinity and specificity), radiochemical purity tests, stability tests in human serum, cellular uptake and internalization in LNCaP(+), PC3-PIP(++) or PC3(−) PCa cells of the resulting unlabeled HYNIC-scFvD2B conjugates (HscFv) and 99mTc-HscFv agents were performed. The results showed that incorporating HYNIC as a chelator did not affect the affinity, specificity or stability of scFvD2B. After purification, the radiochemical purity of 99mTc-HscFv radiotracers was greater than 95%. A two-sample t-test of 99mTc-HscFv1 and 99mTc-HscFv1 uptake in PC3-PIP vs. PC3 showed a p-value < 0.001, indicating that the PSMA receptor interaction of 99mTc-HscFv agents was statistically significantly higher in PSMA-positive cells than in the negative controls. In conclusion, the results of this research warrant further preclinical studies to determine whether the in vivo pharmacokinetics and tumor uptake of 99mTc-HscFv still offer sufficient advantages over HYNIC-conjugated peptides to be considered for SPECT/PSMA imaging.
CRISPR/Cas9-Mediated Mutagenesis of Antennapedia in Spodoptera frugiperda
Authors: Wang Congke , Zhao Te , Liu Xiaolong , Li Tianliang , He Leiming , Wang Qinqin , Wang Li , Zhou Lin
Published: December 2023

The homeotic gene Antennapedia (Antp) has been identified as playing a pivotal role in the morphogenesis of the thorax and wings across various insect species. Leveraging insights from previous studies, the functional characterization of Antp in S. frugiperda was undertaken using RT-qPCR and the CRISPR/Cas9 genome-editing system. Phylogenetic analyses indicate that Antp shares a high degree of sequence homology among Lepidoptera species. The expression profile of SfAntp was detected by RT-qPCR. The results showed that SfAntp was expressed in the whole growth cycle of S. frugiperda, the expression level was the highest in the egg stage, and the expression level was higher from 12 h to 48 h. Tissue-specific expression profiling demonstrated that SfAntp was most abundantly expressed in the thoracic segments and legs. To functionally disrupt SfAntp, two sgRNA sites were designed at the first exon of SfAntp and the gene was knocked out by CRISPR/Cas9 via microinjection. The results showed that the deletion of SfAntp produced a mutant phenotype of thoracic fusion, thoracic leg defect, leg-like protrusions between the head and thoracic segments and pupation deformity. In addition, deletion of SfAntp resulted in high embryo mortality. Through DNA sequencing, it was found that the target site of the SfAntp mutant had different degrees of frameshift mutations, indicating that the mutant phenotype was indeed caused by the knockout of SfAntp.