bluuebunny/crossref_metadata_2025 huggingface dataset:
A Novel Apportionment Method Utilizing Particle Mass Size Distribution across Multiple Particle Size Ranges
Authors: Wang Peizhi , Wang Qingsong , Jia Yuhuan , Ma Jingjin , Wang Chunying , Qiao Liping , Fu Qingyan , Mellouki Abdelwahid , Chen Hui , Li Li
Published: August 2024

Many cities in China are facing the dual challenge of PM2.5 and PM10 pollution. There is an urgent need to develop a cost-effective method that can apportion both with high-time resolution. A novel and practical apportionment method is presented in this study. It combines the measurement of particle mass size distribution (PMSD) with an optical particle counter (OPC) and the algorithm of normalized non-negative matrix factorization (N-NMF). Applied in the city center of Baoding, Hebei, this method separates four distinct pollution factors. Their sizes (ordered from the smallest to largest) range from 0.16 μm to 0.6 μm, 0.16 μm to 1.0 μm, 0.5 μm to 17.0 μm, and 2.0 μm to 20.0 μm, respectively. They correspondingly contribute to PM2.5 (PM10) with portions of 26% (17%), 37% (26%), 33% (41%), and 4% (16%), respectively, on average. The smaller three factors are identified as combustion, secondary, and industrial aerosols because of their high correlation with carbonaceous aerosols, nitrate aerosols, and trace elements of Fe/Mn/Ca in PM2.5, respectively. The largest-sized factor is linked to dust aerosols. The primary origin regions, oxidation degrees, and formation mechanisms of each source are further discussed. This provides a scientific basis for the comprehensive management of PM2.5 and PM10 pollution.
Estimation of Particulate Matter Levels in City Center Pedestrian Routes with the Aid of Low-Cost Sensors
Authors: Plakotaris Dimos Dimitrios , Kassandros Theodosios , Bagkis Evangelos , Karatzas Kostas
Published: August 2024

Particulate matter is one of the most dangerous air pollutants, especially in urban areas, due to its significant adverse health effects. Traditionally, air quality monitoring relies on fixed reference stations, which often have a low temporal and spatial resolution. To address this limitation, a low-cost, portable air quality monitoring device with a rapid measurement response was used to assess particulate matter concentration levels in the afternoon hours in central Thessaloniki, Greece. This approach enabled the identification of local hotspots directly related to human activities. Statistical analysis and spatial mapping were employed, and data collected were categorized using k-means clustering. The findings of the study suggest that data acquired via portable low-cost sensors can describe the local variability of PM2.5 concentrations. The results indicate that local activities, such as increased human accumulation, traffic congestion at traffic lights, market working hours, together with meteorological parameters, can significantly impact air quality in specific urban locations. They also highlight the differences between data recorded in colder and warmer periods, with the concentrations of PM2.5 in the first period being 3.7 μg/m3 greater on average than in the second. These differences are also identified via the k-means clustering method, which suggest that higher concentrations appear mostly during the colder period of the study.
Accumulation of Heavy Metals in Blueberry (Vaccinium myrtillus L.) and Dominant Mosses (Pleurozium schreberi (Willd. ex Brid.) Mitt.) as Bioindicators of the Expressway Influence on Forest Ecosystems
Authors: Warczyk Arkadiusz , Gruba Piotr , Józefowska Agnieszka , Wanic Tomasz , Warczyk Agata , Świątek Bartłomiej , Bujak Julita , Pietrzykowski Marcin
Published: August 2024

The intensive use, development, and expansion of the road network is expanding the zones of direct impact of road transport on forest ecosystems. Issues related to the mobility of trace elements in forest ecosystems along motorways are very important due to the numerous environmental risks associated with the excessive accumulation of metals, the ability to migrate and accumulate in plants and animals, and the risk of transferring these elements to higher trophic levels. The aim of this article was therefore to determine the impact of road traffic on the basis of contents of trace metals Cd, Cr, Cu, Ni, Pb, and Zn and to describe the relationship of these contents in moss gametophytes and blueberry leaves taken in the vicinity of an existing and variously expanded expressway (S7, Poland, Europe). Analyses of transport impacts included the effects of distance and time of pollutant deposition and road transport on habitat and stand conditions. The highest contents of Cd, Cr, Cu, Ni, Pb, and Zn in moss tissues were found in fir stands and the contents were, respectively, 0.36 mg·kg−1, 5.91 mg·kg−1, 12.5 mg·kg−1, 3.26 mg·kg−1, 8.82 mg·kg−1, and 55.28 mg·kg−1. Mosses showed the best bioindication capacity of all of the studied ecosystem elements. The Pb, Zn, Cr, Cu, and Ni contents were particularly markedly elevated in moss tissues relative to non-anthropopressured areas and dependent on distance from the emitter (road). Blueberry proved to be a less useful bioindicator, as the contents of Cd, Cr, Cu, Ni, Pb, and Zn found were similar to the data from non-anthropopressured areas and were, respectively, 0.09 mg·kg−1, 0.98 mg·kg−1, 7.12 mg·kg−1, 2.49 mg·kg−1, 1.18 mg·kg−1, and 15.91 mg·kg−1 in fir stands and 0.04 mg·kg−1, 0.47 mg·kg−1, 6.63 mg·kg−1, 1.65 mg·kg−1, 0.72 mg·kg−1, and 17.44 mg·kg−1 in pine stands.
Advancements in Pediatric Audiological Assessments Using Wideband Acoustic Immittance: A Review
Authors: Jiang Wen , Mu Yi , Zhao Fei , Wang Peng
Published: August 2024

Objectives: This study’s objectives were to explore the potential of wideband acoustic immittance (WAI) as a diagnostic tool, examining its accuracy and efficiency in pediatric audiology. Methods: A narrative review of the contemporary literature was conducted, focusing on studies that assessed the use of WAI in diagnosing pediatric auditory conditions. Key variables such as diagnostic accuracy, efficiency, and clinical outcomes were considered. Results: This review highlighted that WAI offers a broader range of test frequencies and more comprehensive diagnostic information compared with traditional tympanometry. The studies indicated that WAI has the potential to improve diagnostic accuracy and efficiency in pediatric audiology. Distinct patterns of wideband absorbance were identified, enabling more detailed and accurate diagnostic evaluations. Conclusions: WAI shows substantial potential as a diagnostic tool in pediatric audiology, offering improvements in diagnostic accuracy and efficiency over traditional methods. While the initial findings are promising, further research is needed to fully understand its applicability and benefits across different pediatric populations. Future studies should aim to validate the clinical utility of WAI to ensure its widespread adoption in pediatric audiological assessments.
New Improvements of the Jensen–Mercer Inequality for Strongly Convex Functions with Applications
Authors: Adil Khan Muhammad , Ivelić Bradanović Slavica , Mahmoud Haitham Abbas
Published: August 2024

In this paper, we use the generalized version of convex functions, known as strongly convex functions, to derive improvements to the Jensen–Mercer inequality. We achieve these improvements through the newly discovered characterizations of strongly convex functions, along with some previously known results about strongly convex functions. We are also focused on important applications of the derived results in information theory, deducing estimates for χ-divergence, Kullback–Leibler divergence, Hellinger distance, Bhattacharya distance, Jeffreys distance, and Jensen–Shannon divergence. Additionally, we prove some applications to Mercer-type power means at the end.
The Effects of Recreational and Pharmaceutical Substance Use on Oral Microbiomes and Health
Authors: Esposito Michelle Marie , Kalinowski Julia , Mikhaeil Mirit
Published: August 2024

Oral health remains one of the most taken for granted parts of human body health, even though poor oral health has now been linked to various diseases, such as cancers, diabetes, autoimmune complications, neurological disorders, and cardiovascular disease, just to name a few. As we review in this paper, substance use or abuse, including alcohol, smoking, recreational drugs, and pharmaceutical drugs can have significant implications on oral health, which in turn can lead to more systemic diseases. In this paper, we show that oral microbiome dysbiosis and inflammatory cytokine pathways are two of the most significant mechanisms contributing to oral health complications from substance use. When substance use decreases beneficial oral species and increases periodontopathogenic strains, a subsequent cascade of oncogenic and inflammatory cytokines is triggered. In this review, we explore these mechanisms and others to determine the consequences of substance use on oral health. The findings are of significance clinically and in research fields as the substance-use-induced deterioration of oral health significantly reduces quality of life and daily functions. Overall, the studies in this review may provide valuable information for future personalized medicine and safer alternatives to legal and pharmaceutical substances. Furthermore, they can lead towards better rehabilitation or preventative initiatives and policies, as it is critical for healthcare and addiction aid specialists to have proper tools at their disposal.
Automated Lumen Segmentation in Carotid Artery Ultrasound Images Based on Adaptive Generated Shape Prior
Authors: Li Yu , Zou Liwen , Song Jiajia , Gong Kailin
Published: August 2024

Ultrasound imaging is vital for diagnosing carotid artery vascular lesions, highlighting the importance of accurately segmenting lumens in ultrasound images to prevent, diagnose and treat vascular diseases. However, noise artifacts, blood residue and discontinuous lumens significantly affect segmentation accuracy. To achieve accurate lumen segmentation in low-quality images, we propose a novel segmentation algorithm which is guided by an adaptively generated shape prior. To tackle the above challenges, we introduce a shape-prior-based segmentation method for carotid artery lumen walls. The shape prior in this study is adaptively generated based on the evolutionary trend of vessel growth. Shape priors guide and constrain the active contour, resulting in precise segmentation. The efficacy of the proposed model was confirmed using 247 carotid artery ultrasound images, with experimental results showing an average Dice coefficient of 92.38%, demonstrating superior segmentation performance compared to existing mathematical models. Our method can quickly and effectively perform accurate lumen segmentation on low-quality carotid artery ultrasound images, which is of great significance for the diagnosis of cardiovascular and cerebrovascular diseases.
Toward Fully Automated Personalized Orthopedic Treatments: Innovations and Interdisciplinary Gaps
Authors: Luo Yunhua
Published: August 2024

Personalized orthopedic devices are increasingly favored for their potential to enhance long-term treatment success. Despite significant advancements across various disciplines, the seamless integration and full automation of personalized orthopedic treatments remain elusive. This paper identifies key interdisciplinary gaps in integrating and automating advanced technologies for personalized orthopedic treatment. It begins by outlining the standard clinical practices in orthopedic treatments and the extent of personalization achievable. The paper then explores recent innovations in artificial intelligence, biomaterials, genomic and proteomic analyses, lab-on-a-chip, medical imaging, image-based biomechanical finite element modeling, biomimicry, 3D printing and bioprinting, and implantable sensors, emphasizing their contributions to personalized treatments. Tentative strategies or solutions are proposed to address the interdisciplinary gaps by utilizing innovative technologies. The key findings highlight the need for the non-invasive quantitative assessment of bone quality, patient-specific biocompatibility, and device designs that address individual biological and mechanical conditions. This comprehensive review underscores the transformative potential of these technologies and the importance of multidisciplinary collaboration to integrate and automate them into a cohesive, intelligent system for personalized orthopedic treatments.
CardioRiskNet: A Hybrid AI-Based Model for Explainable Risk Prediction and Prognosis in Cardiovascular Disease
Authors: Talaat Fatma M. , Elnaggar Ahmed R. , Shaban Warda M. , Shehata Mohamed , Elhosseini Mostafa
Published: August 2024

The global prevalence of cardiovascular diseases (CVDs) as a leading cause of death highlights the imperative need for refined risk assessment and prognostication methods. The traditional approaches, including the Framingham Risk Score, blood tests, imaging techniques, and clinical assessments, although widely utilized, are hindered by limitations such as a lack of precision, the reliance on static risk variables, and the inability to adapt to new patient data, thereby necessitating the exploration of alternative strategies. In response, this study introduces CardioRiskNet, a hybrid AI-based model designed to transcend these limitations. The proposed CardioRiskNet consists of seven parts: data preprocessing, feature selection and encoding, eXplainable AI (XAI) integration, active learning, attention mechanisms, risk prediction and prognosis, evaluation and validation, and deployment and integration. At first, the patient data are preprocessed by cleaning the data, handling the missing values, applying a normalization process, and extracting the features. Next, the most informative features are selected and the categorical variables are converted into a numerical form. Distinctively, CardioRiskNet employs active learning to iteratively select informative samples, enhancing its learning efficacy, while its attention mechanism dynamically focuses on the relevant features for precise risk prediction. Additionally, the integration of XAI facilitates interpretability and transparency in the decision-making processes. According to the experimental results, CardioRiskNet demonstrates superior performance in terms of accuracy, sensitivity, specificity, and F1-Score, with values of 98.7%, 98.7%, 99%, and 98.7%, respectively. These findings show that CardioRiskNet can accurately assess and prognosticate the CVD risk, demonstrating the power of active learning and AI to surpass the conventional methods. Thus, CardioRiskNet’s novel approach and high performance advance the management of CVDs and provide healthcare professionals a powerful tool for patient care.
Automated Multi-Class Facial Syndrome Classification Using Transfer Learning Techniques
Authors: Sherif Fayroz F. , Tawfik Nahed , Mousa Doaa , Abdallah Mohamed S. , Cho Young-Im
Published: August 2024

Genetic disorders affect over 6% of the global population and pose substantial obstacles to healthcare systems. Early identification of these rare facial genetic disorders is essential for managing related medical complexities and health issues. Many people consider the existing screening techniques inadequate, often leading to a diagnosis several years after birth. This study evaluated the efficacy of deep learning-based classifier models for accurately recognizing dysmorphic characteristics using facial photos. This study proposes a multi-class facial syndrome classification framework that encompasses a unique combination of diseases not previously examined together. The study focused on distinguishing between individuals with four specific genetic disorders (Down syndrome, Noonan syndrome, Turner syndrome, and Williams syndrome) and healthy controls. We investigated how well fine-tuning a few well-known convolutional neural network (CNN)-based pre-trained models—including VGG16, ResNet-50, ResNet152, and VGG-Face—worked for the multi-class facial syndrome classification task. We obtained the most encouraging results by adjusting the VGG-Face model. The proposed fine-tuned VGG-Face model not only demonstrated the best performance in this study, but it also performed better than other state-of-the-art pre-trained CNN models for the multi-class facial syndrome classification task. The fine-tuned model achieved both accuracy and an F1-Score of 90%, indicating significant progress in accurately detecting the specified genetic disorders.
Advances in siRNA Drug Delivery Strategies for Targeted TNBC Therapy
Authors: Subhan Md Abdus , Torchilin Vladimir P.
Published: August 2024

Among breast cancers, triple-negative breast cancer (TNBC) has been recognized as the most aggressive type with a poor prognosis and low survival rate. Targeted therapy for TNBC is challenging because it lacks estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2). Chemotherapy, radiation therapy, and surgery are the common therapies for TNBC. Although TNBC is prone to chemotherapy, drug resistance and recurrence are commonly associated with treatment failure. Combination therapy approaches using chemotherapy, mAbs, ADC, and antibody–siRNA conjugates may be effective in TNBC. Recent advances with siRNA-based therapy approaches are promising for TNBC therapy with better prognosis and reduced mortality. This review discusses advances in nanomaterial- and nanobiomaterial-based siRNA delivery platforms for TNBC therapy exploring targeted therapy approaches for major genes, proteins, and TFs upregulated in TNBC tumors, which engage in molecular pathways associated with low TNBC prognosis. Bioengineered siRNA drugs targeting one or several genes simultaneously can downregulate desired genes, significantly reducing disease progression.
The Potential of Immunotherapy for SMARCA4-Deficient Undifferentiated Uterine Sarcoma (SDUS)
Authors: Yao Xiaohong , He Ying , Xiao Chaoxin , Zhou Ruihan , Zhao Chengjian , Wang Wei
Published: August 2024

(1) Background: SMARCA4-deficient undifferentiated uterine sarcoma (SDUS) is a rare and aggressive cancer that urgently requires novel therapeutic strategies. Despite the proven efficacy of immunotherapy in various cancer types, its application in SDUS remains largely unexplored. This study aims to investigate the immune microenvironment of SDUS to evaluate the feasibility of utilizing immunotherapy. (2) Methods: Multiplex immunofluorescence (mIF) was employed to examine the immune microenvironment in two cases of SDUS in comparison to other subtypes of endometrial stromal sarcomas (ESSs). This research involved a comprehensive evaluation of immune cell infiltration, cellular interactions, and spatial organization within the tumor immune microenvironment (TiME). Statistical analysis was performed to assess differences in immune cell densities and interactions between SDUS and other ESSs. (3) Results: SDUS exhibited a significantly higher density of cytotoxic T lymphocytes (CTLs), T helper (Th) cells, B cells, and macrophages compared to other ESSs. Notable cellular interactions included Th–CTL and Th–B cell interactions, which were more prominent in SDUS. The spatial analysis revealed distinct immune niches characterized by lymphocyte aggregation and a vascular-rich environment, suggesting an active and engaged immune microenvironment in SDUS. (4) Conclusions: The results suggest that SDUS exhibits a highly immunogenic TiME, characterized by substantial lymphocyte infiltration and dynamic cellular interactions. These findings highlight the potential of immunotherapy as an effective treatment approach for SDUS. However, given the small number of samples evaluated, these conclusions should be drawn with caution. This study underscores the importance of additional investigation into immune-targeted therapies for this challenging cancer subtype, with a larger sample size to validate and expand upon these preliminary findings.
The Role of MALAT1 in Regulating the Proangiogenic Functions, Invasion, and Migration of Trophoblasts in Selective Fetal Growth Restriction
Authors: Xia Shuting , Ye Yingnan , Liu Jialiu , Qiu Hanfei , Lin Minhuan , He Zhiming , Huang Linhuan , Wang Malie , Luo Yanmin
Published: August 2024

Epigenetic regulation is an important entry point to study the pathogenesis of selective fetal growth restriction (sFGR), and an understanding of the role of long noncoding RNAs (lncRNAs) in sFGR is lacking. Our study aimed to investigate the potential role of a lncRNA, metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), in sFGR using molecular biology experiments and gain- or loss-of-function assays. We found that the levels of MALAT1, ERRγ, and HSD17B1 were downregulated and that of miR-424 was upregulated in the placental shares of the smaller twins. Moreover, angiogenesis was impaired in the placental share of the smaller fetus and MALAT1 could regulate the paracrine effects of trophoblasts on endothelium angiogenesis and proliferation by regulating miR-424. In trophoblasts, MALAT1 could competitively bind to miR-424 to regulate the expression of ERRγ and HSD17B1, thus regulating trophoblast invasion and migration. MALAT1 overexpression could decrease apoptosis and promote proliferation, alleviating cell damage induced by hypoxia. Taken together, the downregulation of MALAT1 can reduce the expression of ERRγ and HSD17B1 by competitively binding to miR-424, impairing the proangiogenic effect of trophoblasts, trophoblast invasion and migration, and the ability of trophoblasts to compensate for hypoxia, which may be involved in the pathogenesis of sFGR through various aspects.
Alternative Oxidase Alleviates Mitochondrial Oxidative Stress during Limited Nitrate Reduction in Arabidopsis thaliana
Authors: Otomaru Daisuke , Ooi Natsumi , Monden Kota , Suzuki Takamasa , Noguchi Ko , Nakagawa Tsuyoshi , Hachiya Takushi
Published: August 2024

The conversion of nitrate to ammonium, i.e., nitrate reduction, is a major consumer of reductants in plants. Previous studies have reported that the mitochondrial alternative oxidase (AOX) is upregulated under limited nitrate reduction conditions, including no/low nitrate or when ammonium is the sole nitrogen (N) source. Electron transfer from ubiquinone to AOX bypasses the proton-pumping complexes III and IV, thereby consuming reductants efficiently. Thus, upregulated AOX under limited nitrate reduction may dissipate excessive reductants and thereby attenuate oxidative stress. Nevertheless, so far there is no firm evidence for this hypothesis due to the lack of experimental systems to analyze the direct relationship between nitrate reduction and AOX. We therefore developed a novel culturing system for A. thaliana that manipulates shoot activities of nitrate reduction and AOX separately without causing N starvation, ammonium toxicity, or lack of nitrate signal. Using shoots processed with this system, we examined genome-wide gene expression and growth to better understand the relationship between AOX and nitrate reduction. The results showed that, only when nitrate reduction was limited, AOX deficiency significantly upregulated genes involved in mitochondrial oxidative stress, reductant shuttles, and non-phosphorylating bypasses of the respiratory chain, and inhibited growth. Thus, we conclude that AOX alleviates mitochondrial oxidative stress and sustains plant growth under limited nitrate reduction.
Placenta Extracellular Vesicles: Messengers Connecting Maternal and Fetal Systems
Authors: Rosenfeld Cheryl S.
Published: August 2024

The placenta operates during gestation as the primary communication organ between the mother and fetus. It is essential for gas, nutrient exchange, and fetal waste transfer. The placenta also produces a wide range of hormones and other factors that influence maternal physiology, including survival and activity of the corpus luteum of the ovary, but the means whereby the placenta shapes fetal development remain less clear, although the fetal brain is thought to be dependent upon the placenta for factors that play roles in its early differentiation and growth, giving rise to the term “placenta–brain axis”. Placental hormones transit via the maternal and fetal vasculature, but smaller placental molecules require protection from fetal and maternal metabolism. Such biomolecules include small RNA, mRNA, peptides, lipids, and catecholamines that include serotonin and dopamine. These compounds presumably shuttle to maternal and fetal systems via protective extracellular vesicles (EVs). Placental EVs (pEVs) and their components, in particular miRNA (miRs), are known to play important roles in regulating maternal systems, such as immune, cardiovascular, and reproductive functions. A scant amount is known about how pEVs affect fetal cells and tissues. The composition of pEVs can be influenced by gestational diseases. This review will provide critical insight into the roles of pEVs as the intermediary link between maternal and fetal systems, the impact of maternal pathologies on pEV cargo contents, and how an understanding of biomolecular changes within pEVs in health and disease might be utilized to design early diagnostic and mitigation strategies to prevent gestational diseases and later offspring disorders.
Discovery and Validation of Methylation Signatures in Circulating Cell-Free DNA for the Detection of Colorectal Cancer
Authors: Long Zhiping , Gao Yu , Han Zhen , Yuan Heli , Yu Yue , Pei Bing , Jia Yanjie , Ye Jingyu , Shi Ying , Zhang Min , Zhao Yashuang , Wu Di , Wang Fan
Published: August 2024

This study was conducted with the primary objective of assessing the performance of cfDNA methylation in the detection of colorectal cancer (CRC). Five tumor tissue, 20 peripheral blood leucocyte, and 169 cfDNA samples were collected for whole-genome bisulfite sequencing (WGBS) analysis. Bioinformatic analysis was conducted to identify differentially methylated regions (DMRs) and their functional characteristics. Quantitative methylation-specific PCR (qMSP) was used to validate the methylation levels of DMRs in the tissues and leucocytes. cfDNA samples from CRC patients and healthy controls were used to evaluate the performance of the DMR analysis. WGBS analysis revealed a decrease in DNA methylation levels in the CpG context in CRC tumor tissues compared with adjacent normal tissues. A total of 132 DMRs in cfDNA were identified as potential markers for diagnosing CRC. In a cohort of 95 CRC patients and 74 healthy controls, a combination of the three DMRs (DAB1, PPP2R5C, and FAM19A5) yielded an AUC of 0.763, achieving 64.21% sensitivity and 78.38% specificity in discriminating CRC patients from healthy controls. This study provides insights into DNA methylation patterns in CRC and identifies a set of DMRs in cfDNA with potential diagnostic value for CRC. These DMRs hold promise as biomarkers for CRC detection, offering promise for non-invasive CRC diagnosis. Further research is warranted to validate these findings in larger cohorts.
Charge Variants Characterization of Co-Formulated Antibodies by Three-Dimensional Liquid Chromatography–Mass Spectrometry
Authors: Jin Xiaoqing , Chen Luna , Chu Jianlin , He Bingfang
Published: August 2024

Co-formulated antibodies can bring clinical benefits to patients by combining two or more antibodies in a single dosage form. However, the quality analysis of co-formulated antibodies raises additional challenges, compared to individual antibodies, due to the need for accurate analysis of multiple antibodies in one solution. It is extremely difficult to effectively separate the charge variants of the two co-formulated antibodies using one ion exchange chromatography (IEC) method because of their similar characteristics. In this study, a novel method was developed for the charge variants characterization of co-formulated antibodies using three-dimensional liquid chromatography–mass spectrometry (3D-LC-MS). Hydrophobic interaction chromatography (HIC) was used as the first dimension to separate and collect the two co-formulated antibodies. The two collections were then injected into the second-dimension IEC separately for charge variants separation and analysis. Subsequently, the separated charge variants underwent on-line desalting in the third-dimension reverse-phase chromatography (RPC) and subsequent mass spectroscopy analysis. The novel method could simultaneously provide a charge variants ratio and post-translational modification (PTM) data for the two co-formulated antibodies. Therefore, it could be used for release testing and stability studies of co-formulated antibodies, making up for the shortcomings of the existing approaches. It was the first time that charge variants of co-formulated antibodies were characterized by the 3D-LC-MS method, to the best of our knowledge.
Correction: Yukhnovets et al. Impact of Molecule Concentration, Diffusion Rates and Surface Passivation on Single-Molecule Fluorescence Studies in Solution. Biomolecules 2022, 12, 468
Authors: Yukhnovets Olessya , Höfig Henning , Bustorff Nuno , Katranidis Alexandros , Fitter Jörg
Published: August 2024

In the original publication [...]
Development of VLA4 and CXCR4 Antagonists for the Mobilization of Hematopoietic Stem and Progenitor Cells
Authors: Ruminski Peter G. , Rettig Michael P. , DiPersio John F.
Published: August 2024

The treatment of patients diagnosed with hematologic malignancies typically includes hematopoietic stem cell transplantation (HSCT) as part of a therapeutic standard of care. The primary graft source of hematopoietic stem and progenitor cells (HSPCs) for HSCT is mobilized from the bone marrow into the peripheral blood of allogeneic donors or patients. More recently, these mobilized HSPCs have also been the source for gene editing strategies to treat diseases such as sickle-cell anemia. For a HSCT to be successful, it requires the infusion of a sufficient number of HSPCs that are capable of adequate homing to the bone marrow niche and the subsequent regeneration of stable trilineage hematopoiesis in a timely manner. Granulocyte-colony-stimulating factor (G-CSF) is currently the most frequently used agent for HSPC mobilization. However, it requires five or more daily infusions to produce an adequate number of HSPCs and the use of G-CSF alone often results in suboptimal stem cell yields in a significant number of patients. Furthermore, there are several undesirable side effects associated with G-CSF, and it is contraindicated for use in sickle-cell anemia patients, where it has been linked to serious vaso-occlusive and thrombotic events. The chemokine receptor CXCR4 and the cell surface integrin α4β1 (very late antigen 4 (VLA4)) are both involved in the homing and retention of HSPCs within the bone marrow microenvironment. Preclinical and/or clinical studies have shown that targeted disruption of the interaction of the CXCR4 or VLA4 receptors with their endogenous ligands within the bone marrow niche results in the rapid and reversible mobilization of HSPCs into the peripheral circulation and is synergistic when combined with G-CSF. In this review, we discuss the roles CXCR4 and VLA4 play in bone marrow homing and retention and will summarize more recent development of small-molecule CXCR4 and VLA4 inhibitors that, when combined, can synergistically improve the magnitude, quality and convenience of HSPC mobilization for stem cell transplantation and ex vivo gene therapy after the administration of just a single dose. This optimized regimen has the potential to afford a superior alternative to G-CSF for HSPC mobilization.
Beyond Blood Clotting: The Many Roles of Platelet-Derived Extracellular Vesicles
Authors: Muttiah Barathan , Ng Sook Luan , Lokanathan Yogeswaran , Ng Min Hwei , Law Jia Xian
Published: August 2024

Platelet-derived extracellular vesicles (pEVs) are emerging as pivotal players in numerous physiological and pathological processes, extending beyond their traditional roles in hemostasis and thrombosis. As one of the most abundant vesicle types in human blood, pEVs transport a diverse array of bioactive molecules, including growth factors, cytokines, and clotting factors, facilitating crucial intercellular communication, immune regulation, and tissue healing. The unique ability of pEVs to traverse tissue barriers and their biocompatibility position them as promising candidates for targeted drug delivery and regenerative medicine applications. Recent studies have underscored their involvement in cancer progression, viral infections, wound healing, osteoarthritis, sepsis, cardiovascular diseases, rheumatoid arthritis, and atherothrombosis. For instance, pEVs promote tumor progression and metastasis, enhance tissue repair, and contribute to thrombo-inflammation in diseases such as COVID-19. Despite their potential, challenges remain, including the need for standardized isolation techniques and a comprehensive understanding of their mechanisms of action. Current research efforts are focused on leveraging pEVs for innovative anti-cancer treatments, advanced drug delivery systems, regenerative therapies, and as biomarkers for disease diagnosis and monitoring. This review highlights the necessity of overcoming technical hurdles, refining isolation methods, and establishing standardized protocols to fully unlock the therapeutic potential of pEVs. By understanding the diverse functions and applications of pEVs, we can advance their use in clinical settings, ultimately revolutionizing treatment strategies across various medical fields and improving patient outcomes.
Small Endemic Birds and Hot Climate: Avian and Environmental Predictors of Avifauna Road Mortality in Santa Cruz Galapagos
Authors: Jiménez-Uzcátegui Gustavo , Roa-López Heydi , Penafiel Daniela , Quezada Galo , Loyola Andrea , Delgado Byron , Moity Nicolas , Devineau Olivier , Betancourt Franklyn
Published: August 2024

In the Galapagos Islands, the main road in Santa Cruz is one of the elements involved in bird road mortality along with vehicles and the impacted species. This study reports the number of roadkilled birds found on the road from the Itabaca Channel to Puerto Ayora, and the main factors, whether avian or environmental, involved in bird roadkill mortality. We collected individual carcasses in 2004, 2005, 2006, and 2018 with a prevalence of 278, 252, 265, and 294, respectively, across 21 species. The endemic Yellow Warbler Setophaga petechia aureola was the most affected bird. We used a PRIDIT model to rank the top avian and environmental predictors of road mortality. We found that for the sampled years, bird body size (i.e., 8–35 g) and the endemism status (i.e., endemic/native) were the main predictors of roadkill mortality, along with seasonality (i.e., hot season). Weaker predictors related to the bird (i.e., age and sex) and the environment (ecosystem, road slope, vegetation, or precipitation) are also reported as determinants of roadkill mortality. This study on avian mortality aims to inform conservation strategies to reduce the rate of wildlife avian roadkill on Santa Cruz Island and other islands with similar problems.
Exploring the Impact of Mindful Leadership on Employee Green Creativity in Manufacturing Firms: A Social Information Processing Perspective
Authors: Sun Baiqing , Xi Yuze
Published: August 2024

Increasingly, manufacturing enterprises are compelled to pursue innovative solutions to environmental issues. Addressing such issues requires mindful leadership to support employees and organizations in maintaining awareness during complex situations, which then promotes environmental sustainability. Drawing on social information processing theory, this study theorizes and tests the relationships between mindful leadership, employee moral reflectiveness, environmental passion, and employee green creativity. To test the model, we utilize a two-wave multisource dataset comprising 215 workers from manufacturing firms in China. The findings demonstrate that mindful leadership has a positive relationship with employee green creativity. Additionally, our research reveals that both moral reflectiveness and environmental passion serve as mediators in linking mindful leadership to employee green creativity. Crucially, our empirical analysis suggests a serial mediation model, examining the sequential role of moral reflectiveness and environmental passion in the relationship between mindful leadership and employee green creativity. The findings provide a new viewpoint on employees’ eco-friendly behaviors and have practical implications for improving environmental sustainability within organizations.
Field Study and Analysis of Passenger Density in the Beijing Subway Transfer Hall
Authors: Yu Nan , Wang Yanhu , Zhou Yihui , Hu Yukun , Wu Jinshun , Zhang Lining
Published: August 2024

Passenger density is a major factor influencing indoor climate conditions and the corresponding energy consumption in the transfer halls of metro transportation hubs. In this study, passenger flow in a subway transfer hall in Beijing was measured across three typical seasons. A differential equation model was established to account for the characteristics of passenger density. Based on this, a passenger density prediction model was developed and utilized for analysis. The results show that passenger density is primarily affected by operation time and the surrounding population composition, with a relatively weak correlation to outdoor weather conditions. Additionally, passenger density differs significantly between weekdays and weekends, with the weekday peak being 2.5 times higher than that on weekends. During the four peak hours on weekdays, both in the morning and evening, passenger density exceeds the design capacity, resulting in insufficient fresh air supply. However, for most of the weekday hours and for all hours on weekends, passenger density remains below the design capacity. This indicates a substantial potential for energy savings by adjusting the fresh air supply according to actual passenger density.
Thermal Performance Optimization of Building Envelopes in a Low-Cost and Energy-Saving Rural Dwelling in Severe Cold Region—Taking Central Area of Liaoning as an Example
Authors: Zhang Xueyan , Zhang Xingkuo , Chen Bin , Zhao Joe R. , Sun Jiaojiao , Zhao Jiayi , Wei Bingyang , Zhu Jiayin
Published: August 2024

The thermal performance of rural building envelopes is mostly non-standardized in Northern China, resulting in significant heat loss. In this study, we take, as an example, the central area of Liaoning province, with the objective of proposing some low-cost and energy-efficient solutions. Through our investigations, we found that heating energy consumption was reduced by 20% and construction costs increased by less than CNY 8000 (USD 1108), which can be accepted by rural residents. In order to achieve this target, the NSGA-II algorithm integrated with Rhino + Grasshopper and EnergyPlus simulation kernel was used to establish a thermal performance optimization model for the heat transfer of rural building envelopes in this severe cold region. Among the above-calculated Pareto optimal solutions, the recommended thickness of insulation layers for room floors, roofs, and external walls was about 70 mm, 50 mm, and 40 mm, respectively. Furthermore, we tried to reduce the window-to-wall ratio as much as possible. Finally, based on both the lower building renovation cost and energy-saving rate, three technical solutions from which rural residents could select, according to their specific needs, are put forward.
Research on the Mechanism of Loose Deformation in Weak Fracture Zone Tunnel Surrounding Rock and Support Control
Authors: Zheng Xin , Huang Feng , Wang Sheng , Xu Wenxuan
Published: August 2024

In the fractured weak fault zone, rock mass exhibits low strength and poor self-stability. The geological conditions are complex, and when tunnels cross through fractured zones, significant deformations and collapses are prone to occur, leading to geological hazards. This paper investigates the in situ stress and deformation patterns of the Dongmachang Tunnel No. 1, proposing support solutions for addressing tunnel deformations through field experiments and numerical simulations. The on-site monitoring results indicate that despite implementing measures such as grouting reinforcement and temporary steel supports to control surrounding rock deformation, significant structural damage still occurred in the tunnel support system. The manifestations included severe sinking and cracking of the arch crown, strong inward deformation of the sidewalls, widespread cracking, crushing, and spalling of shotcrete, slight arching uplift, and severe distortion and twisting of steel arches forming a “Z” or “S” shape. To ensure tunnel safety and control the stability of excavations in weak fault zones, a comparison of tunnel deformation support schemes is conducted through field experiments and numerical simulations, indicating that replacing the upper tunnel structure and invert can effectively prevent tunnel deformations. These measures are vital for the sustainable development of tunnel.
Global Trial Representation and Availability of Tyrosine Kinase Inhibitors for Treatment of Chronic Myeloid Leukemia
Authors: Casey Mycal , Odhiambo Lorriane , Aggarwal Nidhi , Shoukier Mahran , Islam K. M. , Cortes Jorge
Published: August 2024

Background: Evaluating clinical trial representation for countries with different socio-demographic index (SDI) and tyrosine kinase inhibitor (TKI) availability for chronic myeloid leukemia (CML). Methods: CML incidence rates (IRs) and disability-adjusted life years (DALYs) (1999–2019) from the Institute of Health Metrics and Evaluation were analyzed. Trials investigating TKI use in CML were obtained from ClinicalTrials.gov. Site data for eligible trials (N = 30) and DALYs were analyzed. TKI approvals, DALYs, and IRs were summarized by SDI. Results: North America (NA) had significant decreases in annual percent change (APC) in DALYs and incidence rates from 1999 to 2004. IRs were highest in Europe and Central Asia (ECA) and NA, while DALYs were highest in South Asia (SAsia) and Sub-Saharan Africa (SSA). Countries in the high-SDI quintile were likely to have lower DALYs than lower-SDI quintiles. Differences in regional DALYs vs. sites in TKI trials were significant for SAsia, SSA, and ECA. High-SDI countries were included in all 30 trials, and TKI approvals were prominent in high-SDI (142) vs. low-SDI (14) countries. Conclusions: The inclusion of disproportionately affected countries during the design of and recruitment into clinical trials should occur, as should TKI availability. The lack of representation demonstrates healthcare disparities.
Potentiating Salvage Radiotherapy in Radiorecurrent Prostate Cancer Through Anti-CTLA4 Therapy: Implications from a Syngeneic Model
Authors: Wang Hanzhi , Gong Linsey , Huang Xiaoyong , White Stephanie D. , Chung Hans T. , Vesprini Danny , Petchiny Tera N. , Fokas Emmanouil , He Hansen , Kerbel Robert S. , Liu Stanley K.
Published: August 2024

High-risk prostate cancer (PCa) is a leading cause in cancer death and can elicit significant morbidity and mortality. Currently, the salvage of local disease recurrence after radiation therapy (RT) is a major clinical problem. Immune checkpoint inhibitors (ICIs), which enhance immune activation, have demonstrated clinical therapeutic promise in combination with ionizing radiation (IR) in certain advanced cancers. We generated the TRAMP-C2 HF radiorecurrent syngeneic mouse model to evaluate the therapeutic efficacy of ICIs in combination with RT. The administration of anti-PDL1 and/or anti-CTLA4 did not achieve a significant tumor growth delay compared to the control. The combination of IR and anti-PDL1 did not yield additional a growth delay compared to IR and the isotype control. Strikingly, a significant tumor growth delay and complete cure in one-third of the mice were seen with the combination of IR and anti-CTLA4. Immune cells in tumor-draining lymph nodes and tumor-infiltrating lymphocytes from mice treated with IR and anti-CTLA4 demonstrated an upregulation of genes in T-cell functions and enrichment in both CD4+ and CD8+ T-cell populations compared to mice given IR and the isotype control. Taken together, these results indicate enhancement of T-cell response in radiorecurrent PCa by IR and anti-CTLA4.
Association of Anxiety/Depressive Symptoms with Psychotic-like Experiences: The Moderation Effect of Sex and Resilience
Authors: Long Manling , Zhang Peiyu , Shi Jingyu
Published: August 2024

Background: Psychotic-like experiences (PLEs) are a part of the continuum of psychosis and are common in the general population. While most of these experiences are transient, they are strongly correlated with an increased risk of various adverse psychological outcomes. Anxiety and depressive symptoms also occur frequently in the adolescent population. Much research has previously demonstrated a correlation between these two symptoms and PLEs. However, few investigations have examined what influences this association, and sex and resilience may be important moderators. Methods: This study selected a sample of first-year students from a university in Shanghai. A total of 2970 adolescents completed questionnaires measuring sociodemographic characteristics, anxiety/depressive symptoms by SCL-90, resilience by CD-RISC, and self-reported PLEs by PQ-16. Results: The findings indicated that PLEs were prevalent in the sample, with at least one PQ-16 item present in 42.5% of individuals. Anxiety/depressive symptoms were significantly associated with PLEs, and there was a sex difference in this association (p < 0.001). What is more, this relationship was stronger in males than in females. Additionally, we found a significant interaction (p < 0.001) between resilience and anxiety/depressive symptoms when looking at the correlates of PLEs. Those with stronger resilience showed a considerably weaker connection between PLEs and symptoms of anxiety and depression. Conclusions: These findings can potentially inform the development of targeted new clinical interventions.