bluuebunny/crossref_metadata_2025 huggingface dataset:
Performance control during longitudinal activation fMRI studies
Authors: Lotze Martin
Published: October 2024

The documentation of performance during functional imaging represents a standard procedure employed to control for compliance, sensorimotor, and cognitive demands. In the case of motor tasks, preciseness, force, and frequency have a significant impact on the magnitude of functional activation. Questionnaires are used in psychological investigations to control for cognitive demand, while psychophysiological documentation is employed to record bodily responses. For longitudinal intervention studies, it is of utmost importance to implement meticulous pre- and post-performance controls and balance to accurately assess changes over time. Any changes in compliance may introduce additional uncontrolled variables, which can hinder the interpretation of functional magnetic resonance imaging (fMRI)-related changes. This narrative review presents strategies for controlling and balancing performance in functional imaging approaches to document neuroplasticity in rehabilitative studies. These strategies include not only motor-related aspects, such as precision, velocity, and force, but also timing aspects, such as the start and stop of movement periods. In addition, it discusses strategies for the modulation and control of movement aspects with visual feedback, as well as for the control of physiological changes during experimental modulation. Although these measures require additional care, which is often more demanding than the neuroimaging part of the study, they are crucial for a relevant interpretation and publication of fMRI studies.
TGF-β signaling in the cranial neural crest affects late-stage mandibular bone resorption and length
Authors: Houchen Claire J. , Ghanem Saif , Kaartinen Vesa , Bumann Erin Ealba
Published: October 2024

Malocclusions are common craniofacial malformations that cause quality of life and health problems if left untreated. Unfortunately, the current treatment for severe skeletal malocclusion is invasive surgery. Developing improved therapeutic options requires a deeper understanding of the cellular mechanisms responsible for determining jaw bone length. We have recently shown that neural crest mesenchyme (NCM) can alter jaw length by controlling the recruitment and function of mesoderm-derived osteoclasts. Transforming growth factor beta (TGF-β) signaling is critical to craniofacial development by directing bone resorption and formation, and heterozygous mutations in the TGF-β type I receptor (TGFBR1) are associated with micrognathia in humans. To identify the role of TGF-β signaling in NCM in controlling osteoclasts during mandibular development, the mandibles of mouse embryos deficient in the gene encoding Tgfbr1, specifically in NCM, were analyzed. Our laboratory and others have demonstrated that Tgfbr1fl/fl;Wnt1-Cre mice display significantly shorter mandibles with no condylar, coronoid, or angular processes. We hypothesize that TGF-β signaling in NCM can also direct late bone remodeling and further regulate late embryonic jaw bone length. Interestingly, analysis of mandibular bone based on micro-computed tomography and Masson’s trichrome revealed no significant difference in bone quality between the Tgfbr1fl/fl;Wnt1-Cre mice and controls, as measured by the bone perimeter/bone area, trabecular rod-like diameter, number and separation, and gene expression of collagen type 1 alpha 1 (Col1α1) and matrix metalloproteinase 13 (Mmp13). Although there was not a difference in localization of bone resorption within the mandible indicated by tartrate-resistant acid phosphatase (TRAP) staining, Tgfbr1fl/fl;Wnt1-Cre mice had approximately three-fold less osteoclast number and perimeter than controls. Gene expression of receptor activator of nuclear factor kappa-β (Rank) and Mmp9, markers of osteoclasts and their activity, also showed a three-fold decrease in Tgfbr1fl/fl;Wnt1-Cre mandibles. Evaluation of osteoblast-to-osteoclast signaling revealed no significant difference between Tgfbr1fl/fl;Wnt1-Cre mandibles and controls, leaving the specific mechanism unresolved. Finally, pharmacological inhibition of Tgfbr1 signaling during the initiation of bone mineralization and resorption significantly shortened jaw length in embryos. We conclude that TGF-β signaling in NCM decreases mesoderm-derived osteoclast number, that TGF-β signaling in NCM impacts jaw length late in development, and that this osteoblast-to-osteoclast communication may be occurring through an undescribed mechanism.
Low-dose carbon monoxide inhalation to increase total hemoglobin mass and endurance performance: scientific evidence and implications
Authors: Gatterer Hannes , Dünnwald Tobias , Woyke Simon , Faulhaber Martin , Schumacher Yorck Olaf , Schobersberger Wolfgang
Published: October 2024

Recently, chronic intermittent inhalation of low-dose carbon monoxide (CO) has been postulated as a practice to increase total hemoglobin mass with potential beneficial effects on endurance performance. In this perspective article, we discuss the potential performance enhancing capabilities as well as the safety concerns, which include individual variability in CO response, and acute and chronic health effects. It is also important to note that according to the World-Anti-Doping-Agency (WADA), CO inhalation could fall under “M1. Manipulation of Blood and Blood Components“ and therefore could be considered a prohibited method if used as a non-diagnostic tool.
Six years of spreading BLSD skills in schools: empowering teachers as trainers
Authors: Calicchia Sara , Capanna Silvia , De Rosa Mariangela , Papaleo Bruno , Pera Alessandra
Published: October 2024

Introduction

To increase the population's ability to handle emergencies, life-saving maneuvers should be universally acquired as an automatic skill starting from school through frequent and practical retraining. Teachers could be ideal multipliers, but it is necessary to design pathways that train and motivate them, since Basic Life Support and Defibrillation (BLSD) skills are not part of their academic curricula. This study explores innovative training solutions and facilitating factors to enhance BLSD education in schools by focusing on the training and motivation of teachers.

Methods

In the 1st year, an in-service training program for teachers was provided and assessed in a lower middle school in central Italy. The study compared the skills of a group of students trained by teachers with those trained by certified instructors, immediately after the course and 6 months later. Both the procedural skills and the quality of cardiopulmonary resuscitation (CPR) were evaluated, through a hands-on simulation. Over the next 5 years, the project was expanded to three more schools, and a field study was conducted where researchers monitored the teachers in their classroom work, supporting them in resolving critical issues.

Results

Quantitative assessments showed significant differences in student abilities immediately after the course, which diminished after 6 months. Qualitative evaluations indicated that teachers, initially reluctant, gained confidence and effectively taught BLSD skills. Over 5 academic years, the project expanded to additional schools, training 5,661 students in life-saving maneuvers with a ratio of 1 teacher for every 111 trained students, over the whole period of time. Sustainability factors included regular retraining of teachers, continually updated and free didactic materials and equipment, internal coordinators, allowing teachers the freedom to structure a customized course schedule in terms of timing and delivery methods.

Conclusion

The study highlights the effectiveness of trained teachers as BLSD knowledge multipliers. Standardizing teacher training, including follow-up retraining, is crucial, but flexibility in student training is beneficial, allowing adaptation to the specific needs of schools. Future research should focus on the long-term sustainability of chain training in larger areas, identifying strategies to overcome organizational and motivational barriers.
Validation of the burnout assessment tool-core symptoms in Spanish veterinarians, sex invariance, and cutoff points
Authors: Osca Amparo , Barrado Jesús , Millán Lorena
Published: October 2024

Notably, most studies on burnout in Veterinary Medicine have used the Maslach Burnout Inventory; however, it has limitations and does not evaluate severe burnout. Therefore, in this study, we validated the Burnout Assessment Tool-Core Symptoms (BAT-C) in a sample of Spanish veterinarians. Its invariance concerning sex and cutoff points were also calculated using the receiver operating characteristic curve analysis and Youden’s index. The sample included 1,215 Spanish veterinarians (70% women). The analyses confirmed that the BAT-C evaluates four dimensions: exhaustion (eight items), mental distance (five items), emotional impairment (five items), and cognitive impairment (five items). Reliability analyses offered adequate results, and the high correlation of the BAT-C with a measure of work stress demonstrates its criterion validity. The invariance analyses showed that it evaluates psychometric guarantees, regardless of the sex of the veterinarian. Regarding the cutoff points, there were more women than men in the high (36.9% vs. 25.5%) and medium (22.4% vs. 18.6%) burnout groups and fewer women in the low burnout group (40.7% vs. 55.9%). Our results support the Spanish version of the BAT-C as a valid instrument to assess the core symptoms of severe burnout among veterinarians. Based on our findings, we provide some practical recommendations to reduce burnout in veterinarians.
A Novel Approach to Predict the Asian Exchange Stock Market Index Using Artificial Intelligence
Authors: Salgotra Rohit , Singh Harmanjeet , Kaur Gurpreet , Singh Supreet , Singh Pratap , Lukasik Szymon
Published: October 2024

This study uses real-world illustrations to explore the application of deep learning approaches to predict economic information. In this, we investigate the effect of deep learning model architecture and time-series data properties on prediction accuracy. We aim to evaluate the predictive power of several neural network models using a financial time-series dataset. These models include Convolutional RNNs, Convolutional LSTMs, Convolutional GRUs, Convolutional Bi-directional RNNs, Convolutional Bi-directional LSTMs, and Convolutional Bi-directional GRUs. Our main objective is to utilize deep learning techniques for simultaneous predictions on multivariable time-series datasets. We utilize the daily fluctuations of six Asian stock market indices from 1 April 2020 to 31 March 2024. This study’s overarching goal is to evaluate deep learning models constructed using training data gathered during the early stages of the COVID-19 pandemic when the economy was hit hard. We find that the limitations prove that no single deep learning algorithm can reliably forecast financial data for every state. In addition, predictions obtained from solitary deep learning models are more precise when dealing with consistent time-series data. Nevertheless, the hybrid model performs better when analyzing time-series data with significant chaos.
Building Resilience during Compassion Fatigue: Autoethnographic Accounts of College Students and Faculty
Authors: Nelson Riley N. , Johnson Bertucci Amanda , Swenson Sara , Seguine Angel , Rana Meenal
Published: October 2024

Compassion fatigue (CF) is a well-researched topic in the fields of mental health and nursing. However, studies on CF in the fields of primary, secondary, and higher education are very recent and scant. Compassion fatigue (CF) can be defined as the empathic strain or general exhaustion experienced by helping professionals such as psychotherapists, nurses, social workers, healthcare workers, family caregivers, and elderly caregivers. In this paper, utilizing the Double ABC-X Stress Model, we explored the antecedents, experiences, and consequences of compassion fatigue among college students and professionals who have previous personal experiences with stress and trauma, work with children and families, and work in higher education to prepare professionals to work in such fields. This study uses an autoethnographic approach, where the five authors of the study were also the participants. Utilizing the lifespan and ecological perspectives, we examined the symptoms preceding compassion fatigue and preventative strategies, as well as risk factors and protective factors. This study covers a breadth of compassion fatigue, from predisposition to onset and recovery, and considers alternative strategies for coping, including creating meaning from difficult experiences.
A Survey of Security Strategies in Federated Learning: Defending Models, Data, and Privacy
Authors: Manzoor Habib Ullah , Shabbir Attia , Chen Ao , Flynn David , Zoha Ahmed
Published: October 2024

Federated Learning (FL) has emerged as a transformative paradigm in machine learning, enabling decentralized model training across multiple devices while preserving data privacy. However, the decentralized nature of FL introduces significant security challenges, making it vulnerable to various attacks targeting models, data, and privacy. This survey provides a comprehensive overview of the defense strategies against these attacks, categorizing them into data and model defenses and privacy attacks. We explore pre-aggregation, in-aggregation, and post-aggregation defenses, highlighting their methodologies and effectiveness. Additionally, the survey delves into advanced techniques such as homomorphic encryption and differential privacy to safeguard sensitive information. The integration of blockchain technology for enhancing security in FL environments is also discussed, along with incentive mechanisms to promote active participation among clients. Through this detailed examination, the survey aims to inform and guide future research in developing robust defense frameworks for FL systems.
Validating Disease Associations of Drug-Metabolizing Enzymes through Genome-Wide Association Study Data Analysis
Authors: Leskiw Evan , Whaley Adeline , Hopwood Peter , Houston Tailyn , Murib Nehal , Al-Falih Donna , Fujiwara Ryoichi
Published: October 2024

Background and Objectives: Phase I and phase II drug-metabolizing enzymes are crucial for the metabolism and elimination of various endogenous and exogenous compounds, such as small-molecule hormones, drugs, and xenobiotic carcinogens. While in vitro and animal studies have suggested a link between genetic mutations in these enzymes and an increased risk of cancer, human in vivo studies have provided limited supportive evidence. Methods: Genome-wide association studies (GWASs) are a powerful tool for identifying genes associated with specific diseases by comparing two large groups of individuals. In the present study, we analyzed a GWAS database to identify key diseases genetically associated with drug-metabolizing enzymes, focusing on UDP-glucuronosyltransferases (UGTs). Results: Our analysis confirmed a strong association between the UGT1 gene and hyperbilirubinemia. Additionally, over ten studies reported a link between the UGT1 gene and increased low-density lipoprotein (LDL) cholesterol levels. UGT2B7 was found to be associated with testosterone levels, total cholesterol levels, and vitamin D levels. Conclusions: Despite the in vitro capability of UGT1 and UGT2 family enzymes to metabolize small-molecule carcinogens, the GWAS data did not indicate their genetic association with cancer, except for one study that linked UGT2B4 to ovarian cancer. Further investigations are necessary to fill the gap between in vitro, animal, and human in vivo data.
Unravelling Different Water Management Strategies in Three Olive Cultivars: The Role of Osmoprotectants, Proteins, and Wood Properties
Authors: Parri Sara , Faleri Claudia , Romi Marco , del Río José C. , Rencoret Jorge , Dias Maria Celeste Pereira , Anichini Sara , Cantini Claudio , Cai Giampiero
Published: October 2024

Understanding the responses of olive trees to drought stress is crucial for improving cultivation and developing drought-tolerant varieties. Water transport and storage within the plant is a key factor in drought-tolerance strategies. Water management can be based on a variety of factors such as stomatal control, osmoprotectant molecules, proteins and wood properties. The aim of the study was to evaluate the water management strategy under drought stress from an anatomical and biochemical point of view in three young Italian olive cultivars (Giarraffa, Leccino and Maurino) previously distinguished for their physiological and metabolomic responses. For each cultivar, 15 individuals in pots were exposed or not to 28 days of water withholding. Every 7 days, the content of sugars (including mannitol), proline, aquaporins, osmotins, and dehydrins, in leaves and stems, as well as the chemical and anatomical characteristics of the wood of the three cultivars, were analyzed. ‘Giarraffa’ reduced glucose levels and increased mannitol production, while ‘Leccino’ accumulated more proline. Both ‘Leccino’ and ‘Maurino’ increased sucrose and aquaporin levels, possibly due to their ability to remove embolisms. ‘Maurino’ and ‘Leccino’ accumulated more dehydrins and osmotins. While neither genotype nor stress affected wood chemistry, ‘Maurino’ had a higher vessel-to-xylem area ratio and a larger hydraulic diameter, which allows it to maintain a high transpiration rate but may make it more susceptible to cavitation. The results emphasized the need for an integrated approach, highlighting the importance of the relative timing and sequence of each parameter analyzed, allowing, overall, to define a “strategy” rather than a “response” to drought of each cultivar.
Increased Cytokine Levels in Seronegative Myositis: Potential Th17 Immune Response Implications
Authors: Aguilar-Vazquez Andrea , Chavarria-Avila Efrain , Gutiérrez-Hernández José Manuel , Toriz-González Guillermo , Salazar-Paramo Mario , Medrano-Ramirez Gabriel , Vargas-Cañas Steven , Pizano-Martinez Oscar , Gomez-Rios Cynthia-Alejandra , Juarez-Gomez Christian , Medina-Preciado José-David , Cabrera-López Maribell , Quirarte-Tovar Edgar-Federico , Magaña-García Ligia , García-Gallardo Alejandra-Rubí , Rubio-Arellano Edy-David , Vazquez-Del Mercado Monica
Published: October 2024

Th17 cells are known for producing IL-17 and their role in the pathogenesis of various autoimmune diseases, including myositis. Likewise, the participation of the IL-23/IL-17 pathway in autoimmunity has been confirmed. In this study, we aimed to evaluate the behavior of cytokines in myositis, focusing on the autoantibodies profile and the myositis core set measures. Twenty-five myositis patients were enrolled in this cross-sectional study. An expert rheumatologist evaluated the myositis core set measures. Serum levels of cytokines and chemokines were quantified using the LEGENDplex Multi-Analyte Flow Assay Kit from BioLegend. The autoantibodies detection was carried out using the line-blot assay kit Euroline: Autoimmune Inflammatory Myopathies from EUROIMMUN. We found higher serum levels of IL-33, CXCL8, IL-6, IL-23, and IL-12p70 in seronegative patients. A multiple linear regression analysis revealed that MYOACT scores could be predicted by the increment of IL-23 and the decrement of CCL2, IL-10, and CXCL8 serum levels. These findings suggest that the immune response in seronegative myositis patients exhibits an IL-23-driven Th17 immune response. The relevance of this discovery lies in its potential therapeutic implications. Insights into the IL-23-driven Th17 immune response in seronegative patients highlight the potential for targeted therapies aimed at modulating Th17 activity.
Efficacy and Potential Mechanisms of Naringin in Atopic Dermatitis
Authors: Yoo Seung-Ah , Kim Ki-Chan , Lee Ji-Hyun
Published: October 2024

Atopic dermatitis (AD) is one of the most prevalent chronic inflammatory skin diseases. Topical treatments are recommended for all patients regardless of severity, making it essential to develop an effective topical AD treatment with minimal side effects; We investigated the efficacy of topical application of naringin in AD and explored the possible mechanisms using an AD mouse model induced by 1-chloro-2,4-dinitrobenzene (DNCB). Clinical, histological, and immunological changes related to AD and Janus kinase (JAK)-signal transducer and activator of transcription (STAT) signaling proteins in the skin tissues were measured as outcomes; Naringin treatment resulted in a significant improvement in dermatitis severity score and reduced epidermal thickness and mast cell count in the skin (p < 0.05). Naringin also demonstrated the ability to inhibit DNCB-induced changes in interleukin (IL) 4, chemokine (C-C motif) ligand (CCL) 17, CCL22, IL1β, interferon-gamma (IFN-γ), and tumor necrosis factor-alpha (TNF-α) levels by quantitative real-time polymerase chain reaction (qRT-PCR) and IL13 by enzyme-linked immunosorbent assay (ELISA) (p < 0.05). Western blot results exhibited the decreased JAK1, JAK2, STAT1, STAT3, phospho-STAT3, and STAT6 expression in the naringin-treated groups (p < 0.05); The findings of this study suggest that topical naringin may effectively improve the symptoms of AD and could be used as a therapeutic agent for AD.
Plastocyanin and Cytochrome f Complex Structures Obtained by NMR, Molecular Dynamics, and AlphaFold 3 Methods Compared to Cryo-EM Data
Authors: Kovalenko Ilya , Fedorov Vladimir , Khruschev Sergei , Antal Taras , Riznichenko Galina , Rubin Andrey
Published: October 2024

Plastocyanin is a small mobile protein that facilitates electron transfer through the formation of short-lived protein–protein complexes with cytochrome bf and photosystem 1. Due to the transient nature of plastocyanin–cytochrome f complex, the lack of a long-lived tight complex makes it impossible to determine its structure by X-ray diffraction analysis. Up to today, a number of slightly different structures of such complexes have been obtained by experimental and computer methods. Now, artificial intelligence gives us the possibility to predict the structures of intermolecular complexes. In this study, we compare encounter and final complexes obtained by Brownian and molecular dynamics methods, as well as the structures predicted by AlphaFold 3, with NMR and cryo-EM data. Surprisingly, the best match for the plastocyanin electron density obtained by cryo-EM was demonstrated by an AlphaFold 3 structure. The orientation of plastocyanin in this structure almost completely coincides with its orientation obtained by molecular dynamics calculation, and, at the same time, it is different from the orientation of plastocyanin predicted on the basis of NMR data. This is even more unexpected given that only NMR structures for the plastocyanin-cytochrome f complex are available in the PDB database, which was used to train AlphaFold 3.
Performance Study of Stabilized Recycled Aggregate Base Material with Two-Gray Components
Authors: Wang Kai , Hu Xianhu , Yuan Yingjie , Lian Feng , Zhong Mingchen , Meng Kun
Published: October 2024

This article studies the practical road performance of recycled materials from construction waste, relying on the paving test section of the supporting project for the Qingdao Cross-Sea Bridge. The research focuses on the construction technology and road performance of using recycled construction waste materials in urban road sub-base construction. Through indoor tests such as sieving and unconfined compressive strength tests, relevant technical indicators were obtained and analyzed. Additionally, periodic core sampling, compaction tests, and rebound deflection tests were conducted on-site according to relevant standards to thoroughly investigate the specific effects of using construction waste in practice and to analyze and evaluate the actual feasibility of the materials for road use. The results indicate that the particle gradation of the construction mix in the test section aligns well with the target gradation, and the dosage of the mixing agent meets the design requirements. The 7-day unconfined compressive strength already satisfied the technical requirements for heavy and extremely heavy traffic on highways as specified in the “Technical Specifications for Construction of Highway Pavement Subbase” (JTG/T F20-2015), with the 14-day strength generally reaching 7 MPa. Core sampling revealed good aggregate gradation, smooth and straight profiles, and the thickness and strength of all parts meet the specifications. The compaction levels met the testing requirements, the surface deflection values showed a decreasing trend, and the deformation resistance was good, consistent with the general development patterns of semi-rigid sub-bases.
Prevalence of Overweight and Obesity among Primary School Students in Split, Croatia
Authors: Šimunović Ivan , Mrčela Dina , Karin Željka , Pogorelić Zenon , Markić Joško
Published: October 2024

The rising prevalence of obesity among children and adolescents is a global public health concern, significantly contributing to noncommunicable chronic diseases such as cardiovascular disease, diabetes and cancer. In Croatia, obesity rates are alarmingly high, affecting both children and adults. Data from the Institute of the Public Health of Split-Dalmatian County were analyzed to identify trends in body mass index (BMI) among primary school students in Split, Croatia and possible connection with sports participation and parental education levels. A longitudinal analysis of students was conducted across three medical examinations during primary school education. The findings showed an increase in the prevalence of overweight and obesity from 23.4% in the first to 30.2% in the fifth grade, returning back to 23.4% in the eighth grade. Significant differences among students were associated with parental education level. Boys who participated in sports demonstrated a higher BMI in the first grade but there was no difference in BMI in later grades. Sports participation had no significant impact on the BMI of girls. The study underscores the critical role of parental education in influencing children’s weight status and highlights the necessity of tailored public health interventions to address these trends from an early age. The implementation of comprehensive strategies, including educational programs and policy measures as part of the national health policy, is the only way to combat childhood obesity and promote long-term health benefits.
Validation of the Modified Yale Food Addiction Scale 2.0 (mYFAS 2.0) in Spanish University Students
Authors: López-Moreno Miguel , Marchena-Giráldez Carlos , Garcés-Rimón Marta , Miguel-Castro Marta , Iglesias-López María Teresa
Published: October 2024

Objective: The aim of this study was to explore the factorial structure, psychometric properties and association with anthropometric and clinical variables of the Modified Yale Addiction Scale 2.0 (mYFAS 2.0) in a Spanish university population. Methods: A cross-sectional study of n = 270 university students in Spain was conducted. Variables measured: mYFAS 2.0, Emotional Eater Questionnaire (EEQ), Alcohol Use Disorder Identification Test (AUDIT), Pittsburg Sleep Quality index (PSQI) and Perceived Stress Scale (PSS). In mYFAS 2.0 were performed an Exploratory Factor Analysis (EFA), an Unweight Least Square (ULS), a model fit using comparative fit index (CFI) and nomological validity. Results: EFA revealed that a two-factor structure is the most appropriate in a non-clinical population of Spanish university students. The factors accounted for 18.54% and 16.33% of the variance, and the correlation between them was moderate—0.487 (p < 0.001). This different structure from that reported in the original scale could be derived from the cultural characteristics and intrinsic eating habits of the study population. The correlation matrix reported an inverse association of mYFAS 2.0 with Body Mass Index (BMI). In addition, participants with a BMI below 25 showed a higher mYFAS 2.0 and EEQ score. Conclusions: These results suggest some changes in the psychometric assessment structure of the mYFAS 2.0 in a non-clinical population of university students, as well as the usefulness of this questionnaire to identify individuals with an adequate BMI but with compensatory behaviours that predispose to different eating disorders.
Pembrolizumab-Associated Cardiotoxicity: A Retrospective Analysis of the FDA Adverse Events Reporting System
Authors: Milutinovic Stefan , Jancic Predrag , Jokic Vera , Petrovic Marija , Dumic Igor , Rodriguez Ambar Morales , Tanasijevic Nikola , Begosh-Mayne Dustin , Stanojevic Dragana , Escarcega Ricardo O. , Lopez-Mattei Juan , Cao Xiangkun
Published: October 2024

Background: Immune checkpoint inhibitors (ICIs) have been successfully used in the previous decade for the treatment of a variety of malignancies. Adverse events (AEs) can cause many symptoms, most notably cardiac. We analyzed the frequency of these adverse events, comparing pembrolizumab and other ICIs. Methods: Using the Food and Drug Administration (FDA) adverse event reporting database (FAERS), we searched for all adverse events of interest reported for every ICI included in this study. After obtaining the data, we conducted a disproportionality analysis using the reporting odds ratio (ROR) and the information component (IC). Results: A total of 6719 ICI-related cardiac adverse events of interest were reported in the database. Serious outcomes were reported in 100% of the cases, with 34.3% of the cases ending fatally. Compared with all other medications in the database, pembrolizumab use was more frequently associated with myocarditis, pericardial disease, heart failure, and atrial fibrillation. No difference was found in cardiotoxicity between different ICIs. Conclusions: Although infrequent, cardiac AEs in pembrolizumab use are associated with serious outcomes and high mortality. Prospective studies are needed to further research the connection between ICI use and cardiotoxicity.
A Highly CO2-Sensitive Wood-Based Smart Tag for Strawberry Freshness Monitoring
Authors: Xu Jin , Ning Yuping , Yun Yalu , Cheng Xiling , Li Jian , Wang Lijuan
Published: October 2024

Smart tags are used for monitoring the freshness of foods. However, they often lack significant color changes, and their accuracy needs to be improved. In this study, a poplar veneer with a natural pore structure was selected as a matrix to prepare a smart tag with high pH sensitivity for tracking the freshness of strawberries. The delignified veneer was modified using 2,3-epoxypropyltrimethylammonium chloride (EPTAC) to be given positive charges to adsorb bromothymol blue (BTB) through electrostatic interactions. The adsorption capacity of the veneer reached 7.0 mg/g at 50 °C for 4 h, and the veneer showed an obvious blue color. The smart tags exhibited distinct color changes at different pHs and showed quick color changes in response to acetic acid. As the freshness of strawberries decreased, the color of the smart tags changed from blue to yellow-green, which indicated that the accuracy was high. In this study, an effective method was fabricated to prepare a highly sensitive tag, promoting popular application to ensure food quality.
Dispersion of Hydrophilic Nanoparticles in Natural Rubber with Phospholipids
Authors: Kitjanon Jiramate , Nisoh Nililla , Phongphanphanee Saree , Chattham Nattaporn , Karttunen Mikko , Wong-ekkabut Jirasak
Published: October 2024

Coarse-grained molecular dynamics (CGMD) simulations were employed to investigate the effects of phospholipids on the aggregation of hydrophilic, modified carbon-nanoparticle fillers in cis-polyisoprene (cis-PI) composites. The MARTINI force field was applied to model dipalmitoylphosphatidylcholine (DPPC) lipids and hydrophilic modified fullerenes (HMFs). The simulations of DPPC in cis-PI composites show that the DPPC lipids self-assemble to form a reverse micelle in a rubber matrix. Moreover, HMF molecules readily aggregate into a cluster, in agreement with the previous studies. Interestingly, the mixture of the DPPC and HMF in the rubber matrix shows a cluster of HMF is encapsulated inside the DPPC reverse micelle. The HMF encapsulated micelles disperse well in the rubber matrix, and their sizes are dependent on the lipid concentration. Mechanical and thermal properties of the composites were analyzed by calculating the diffusion coefficients (D), bulk modulus (κ), and glass transition temperatures (Tg). The results suggest that DPPC acts as a plasticizer and enhances the flexibility of the HMF-DPPC rubber composites. These findings provide valuable insights into the design and process of high-performance rubber composites, offering improved mechanical and thermal properties for various applications.
Structure Design on Thermoplastic Composites Considering Forming Effects
Authors: Xie Wei , Song Kai , Yang Ju , Wang Fengyu , Dong Linjie , Jin Shengjie , Zhu Guohua , Wang Zhen
Published: October 2024

Carbon fiber reinforced polypropylene (CF/PP) thermoplastics integrate the superior formability of fabrics with the recoverable characteristics of polypropylene, making them a pivotal solution for achieving lightweight designs in new energy vehicles. However, the prevailing methodologies for designing the structural performance of CF/PP vehicular components often omit the constraints imposed by the manufacturing process, thereby compromising product quality and reliability. This research presents a novel approach for developing a stamping–bending coupled finite element model (FEM) utilizing ABAQUS/Explicit. Initially, the hot stamping simulation is implemented, followed by the transmission of stamping information, including fiber yarn orientation and fiber yarn angle, to the follow-up step for updating the material properties of the cured specimen. Then, the structural performance analysis is conducted, accounting for the stamping effects. Furthermore, the parametric study reveals that the shape and length of the blank holding ring exerted minimal influence on the maximum fiber angle characteristic. However, it is noted that the energy absorption and crushing force efficiency metrics of the CF/PP specimens can be enhanced by increasing the length of the blank holding ring. Finally, a discrete optimization design is implemented to enhance the bending performance of the CF/PP specimen, accounting for the constraint of the maximum shear angle resulting from the stamping process. The optimized design resulted in a mass reduction of 14.3% and an improvement in specific energy absorption (SEA) by 17.5% compared to the baseline sample.
Confessional Cross-Pollination: Basel Humanists as Suppliers of Lutheran and Catholic Exempla
Authors: Strecker Serena
Published: October 2024

Basel humanists shaped religious discourse beyond the Reformed sphere through their collections of exempla, short narratives designed to illustrate a moral or doctrinal message. Because scholars of early modern exempla typically focus on either Lutheran or Catholic exempla collections, the role of Reformed compilers as mediators between confessions has been obscured. This article uses methods from the field of digital humanities and corpus linguistics to examine the lasting influence of Theodor Zwinger (1533–1588), Conrad Lycosthenes (1518–1561), and Johannes Herold (1514–1567) on Lutheran and Catholic exempla collections in a newly quantitative way. Using the concordance software AntConc, this study identifies numerous citations that demonstrate that Zwinger and Lycosthenes facilitated confessional cross-pollination of exemplary narratives from the mid-sixteenth through the early eighteenth century. Although citations of Zwinger, Lycosthenes, and Herold are more frequent in Lutheran exempla collections, the existence of several Catholic editions of Zwinger’s Theatrum vitae humanae indicates that Catholic readers also valued Zwinger’s work. This examination showcases the vital role of Swiss humanists in cross-confessional networks of information exchange and religious discourse in early modern Europe.
Emitter Signal Deinterleaving Based on Single PDW with Modulation-Hypothesis-Augmented Transformer
Authors: Liu Huajun , Wang Longfei , Wang Gan
Published: October 2024

Radar emitter signal deinterleaving based on pulse description words (PDWs) is a challenging task in the field of electronic warfare because of the parameter sparsity and uncertainty of PDWs. In this paper, a modulation-hypothesis-augmented Transformer model is proposed to identify emitters from a single PDW with an end-to-end manner. Firstly, the pulse features are enriched by the modulation hypothesis mechanism to generate I/Q complex signals from PDWs. Secondly, a multiple-parameter embedding method is proposed to expand the signal discriminative features and to enhance the identification capability of emitters. Moreover, a novel Transformer deep learning model, named PulseFormer and composed of spectral convolution, multi-layer perceptron, and self-attention based basic blocks, is proposed for discriminative feature extraction, emitter identification, and signal deinterleaving. Experimental results on synthesized PDW dataset show that the proposed method performs better on emitter signal deinterleaving in complex environments without relying on the pulse repetition interval (PRI). Compared with other deep learning methods, the PulseFormer performs better in noisy environments.
Revealing Cropping Intensity Dynamics Using High-Resolution Imagery: A Case Study in Shaanxi Province, China
Authors: Liu Yadong , Li Hongmei , Zhu Lin , Chen Bin , Li Meirong , He Huijuan , Zhou Hui , Wang Zhao , Yu Qiang
Published: October 2024

Reliable and continuous information on cropping intensity is crucial for assessing cropland utilization and formulating policies regarding cropland protection and management. However, there is still a lack of high-resolution cropping intensity maps for recent years, particularly in fragmented agricultural regions. In this study, we combined Landsat-8 and Sentinel-2 imagery to generate cropping intensity maps from 2019 to 2023 at a 10 m resolution for Shaanxi Province, China. First, the satellite imagery was harmonized to construct 10-day composite enhanced vegetation index (EVI) time series. Then, the cropping intensity was determined by counting the number of valid EVI peaks within a year. Assessment based on 578 sample points showed a high level of accuracy, with overall accuracy and Kappa coefficient values exceeding 0.96 and 0.93, respectively. We further analyzed the spatiotemporal patterns of cropping intensity and generated a map of abandoned cropland in Shaanxi. The results indicated that cropland in Shaanxi Province was mainly utilized for single-cropping (52.9% of area), followed by double-cropping (35.2%), with non-cropping accounting for 11.9%. Cropping intensity tended to be lower in the north and higher in the south. Temporally, the average cropping intensity of Shaanxi increased from 1.1 to over 1.3 from 2019 to 2023. Despite this upward trend, large areas of cropland were abandoned in northern Shaanxi. These results demonstrate the potential of utilizing Landsat-8 and Sentinel-2 imagery to identify cropping intensity dynamics in fragmented agricultural regions and to guide more efficient cropland management.
A Computational DFT Study of the Stereoinversion of Succinimide Residues Formed in Proteins and Peptides Catalyzed by a Hydrogen Phosphate Ion: An Unsymmetrical SE1 Mechanism
Authors: Takahashi Ohgi
Published: October 2024

Succinimide residues formed spontaneously from aspartic acid (Asp) and asparagine (Asn) residues in proteins and peptides are stereochemically unstable, undergoing partial l-to-d stereoinversion, and this is responsible for the d-Asp and d-β-Asp residues found in long-lived proteins. These stereoinverted abnormal amino acid residues are believed to be related to aging and some age-related diseases such as cataracts. Although the succinimide stereoinversion is nonenzymatic, a catalyst is required for it to occur at physiological temperature. In this study, it was found by density functional theory (DFT) calculations that a hydrogen phosphate ion (HPO42−) can effectively catalyze the stereoinversion of the succinimide intermediate. The HPO42− ion abstracts a proton from the asymmetric carbon atom of the succinimide residue to form an enolate intermediate. Then, while the resultant dihydrogen phosphate ion (H2PO4−) remains bound to the enolate ion, a water molecule donates a proton to the enolate intermediate on the opposite side from the phosphate (which is the rate-determining step) to produce the inverted carbon atom. The calculated activation barrier (ca. 90 kJ mol−1) is consistent with a slow in vivo reaction. The present found mechanism can be termed the “unsymmetrical SE1” or “pseudo-SE2” mechanism.
Expanding Insights: Harnessing Expansion Microscopy for Super-Resolution Analysis of HIV-1–Cell Interactions
Authors: Petrich Annett , Hwang Gyu Min , La Rocca Laetitia , Hassan Mariam , Anders-Össwein Maria , Sonntag-Buck Vera , Heuser Anke-Mareil , Laketa Vibor , Müller Barbara , Kräusslich Hans-Georg , Klaus Severina
Published: October 2024

Expansion microscopy has recently emerged as an alternative technique for achieving high-resolution imaging of biological structures. Improvements in resolution are achieved by physically expanding samples through embedding in a swellable hydrogel before microscopy. However, expansion microscopy has been rarely used in the field of virology. Here, we evaluate and characterize the ultrastructure expansion microscopy (U-ExM) protocol, which facilitates approximately four-fold sample expansion, enabling the visualization of different post-entry stages of the HIV-1 life cycle, focusing on nuclear events. Our findings demonstrate that U-ExM provides robust sample expansion and preservation across different cell types, including cell-culture-adapted and primary CD4+ T-cells as well as monocyte-derived macrophages, which are known HIV-1 reservoirs. Notably, cellular targets such as nuclear bodies and the chromatin landscape remain well preserved after expansion, allowing for detailed investigation of HIV-1–cell interactions at high resolution. Our data indicate that morphologically distinct HIV-1 capsid assemblies can be differentiated within the nuclei of infected cells and that U-ExM enables detection of targets that are masked in commonly used immunofluorescence protocols. In conclusion, we advocate for U-ExM as a valuable new tool for studying virus–host interactions with enhanced spatial resolution.
The Replicase Protein of Potato Virus X Is Able to Recognize and Trans-Replicate Its RNA Component
Authors: Dutta Pinky , Lõhmus Andres , Ahola Tero , Mäkinen Kristiina
Published: October 2024

The trans-replication system explores the concept of separating the viral RNA involved in the translation of the replicase protein from the replication of the viral genome and has been successfully used to study the replication mechanisms of alphaviruses. We tested the feasibility of this system with potato virus X (PVX), an alpha-like virus, in planta. A viral RNA template was designed which does not produce the replicase and prevents virion formation but remains recognizable by the replicase. The replicase construct encodes for the replicase protein, while lacking other virus-specific recognition sequences. Both the constructs were delivered into Nicotiana benthamiana leaves via Agrobacterium-mediated infiltration. Templates of various lengths were tested, with the longer templates not replicating at 4 and 6 days post inoculation, when the replicase protein was provided in trans. Co-expression of helper component proteinase with the short template led to its trans-replication. The cells where replication had been initiated were observed to be scattered across the leaf lamina. This study established that PVX is capable of trans-replicating and can likely be further optimized, and that the experimental freedom offered by the system can be utilized to delve deeper into understanding the replication mechanism of the virus.
Host Response Markers of Inflammation and Endothelial Activation Associated with COVID-19 Severity and Mortality: A GeoSentinel Prospective Observational Cohort
Authors: Weckman Andrea M. , Guagliardo Sarah Anne J. , Crowley Valerie M. , Moro Lucia , Piubelli Chiara , Ursini Tamara , van Ierssel Sabrina H. , Gobbi Federico G. , Emetulu Hannah , Rizwan Aisha , Angelo Kristina M. , Licitra Carmelo , Connor Bradley A. , Barkati Sapha , Ngai Michelle , Zhong Kathleen , Huits Ralph , Hamer Davidson H. , Libman Michael , Kain Kevin C.
Published: October 2024

Background: The effect of the COVID-19 pandemic on healthcare systems emphasized the need for rapid and effective triage tools to identify patients at risk of severe or fatal infection. Measuring host response markers of inflammation and endothelial activation at clinical presentation may help to inform appropriate triage and care practices in patients with SARS-CoV-2 infection. Methods: We enrolled patients with COVID-19 across five GeoSentinel clinical sites (in Italy, Belgium, Canada, and the United States) from September 2020 to December 2021, and analyzed the association of plasma markers, including soluble urokinase-type plasminogen activator receptor (suPAR), soluble tumor necrosis factor receptor-1 (sTREM-1), interleukin-6 (IL-6), interleukin-8 (IL-8), complement component C5a (C5a), von Willebrand factor (VWF-a2), and interleukin-1 receptor antagonist (IL-1Ra), with 28-day (D28) mortality and 7-day (D7) severity (discharged, hospitalized on ward, or died/admitted to the ICU). Results: Of 193 patients, 8.9% (16 of 180) died by D28. Higher concentrations of suPAR were associated with increased odds of mortality at D28 and severity at D7 in univariable and multivariable regression models. The biomarkers sTREM-1 and IL-1Ra showed bivariate associations with mortality at D28 and severity at D7. IL-6, VWF, C5a, and IL-8 were not as indicative of progression to severe disease or death. Conclusions: Our findings confirm previous studies’ assertions that point-of-care tests for suPAR and sTREM-1 could facilitate the triage of patients with SARS-CoV-2 infection, which may help guide hospital resource allocation.
Effect of Pipe Materials and Interspecific Interactions on Biofilm Formation and Chlorine Resistance: Turn Enemies into Friends
Authors: Shan Lili , Pei Yunyan , Xu Siyang , Cui Yuhong , Liu Zhengqian , Zhu Zebing , Yuan Yixing
Published: October 2024

Drinking water distribution systems (DWDSs) may be contaminated to various degrees when different microorganisms attach to the pipe walls. Understanding the characteristics of biofilms on pipe walls can help prevent and control microbial contamination in DWDSs. The biofilm formation, interspecific interactions, and chlorine resistance of 10 dual-species biofilms in polyethylene (PE) and cast iron (CI) pipes were investigated in this paper. The biofilm biomass (heterotrophic bacterial plate count and crystal violet) of dual species in CI pipes is significantly higher than that in PE pipes, but the biofilm activity in CI pipes is significantly lower than that in PE pipes. The interspecific interaction of Sphingomonas-containing group presented synergistic or neutral relationship in PE pipes, whereas the interspecific interaction of the Acidovorax-containing group showed a competitive relationship in CI pipes. Although interspecific relationships may help bacteria resist chlorine, the chlorine resistance was more reliant on dual-species groups and pipe materials. In CI pipes, the Microbacterium containing biofilm groups showed better chlorine resistance, whereas in PE pipes, most biofilm groups with Bacillus exhibited better chlorine resistance. The biofilm groups with more extracellular polymeric substance (EPS) secretion showed stronger chlorine resistance. The biofilm in the PE pipe is mainly protected by EPS, while both EPS and corrosion products shield the biofilms within CI pipe. These results supported that dual-species biofilms are affected by pipe materials and interspecific interactions and provided some ideas for microbial control in two typical pipe materials.