bluuebunny/crossref_metadata_2025 huggingface dataset:
AI Applied to Volatile Organic Compound (VOC) Profiles from Exhaled Breath Air for Early Detection of Lung Cancer
Authors: Vinhas Manuel , Leitão Pedro M. , Raimundo Bernardo S. , Gil Nuno , Vaz Pedro D. , Luis-Ferreira Fernando
Published: June 2024

Volatile organic compounds (VOCs) are an increasingly meaningful method for the early detection of various types of cancers, including lung cancer, through non-invasive methods. Traditional cancer detection techniques such as biopsies, imaging, and blood tests, though effective, often involve invasive procedures or are costly, time consuming, and painful. Recent advancements in technology have led to the exploration of VOC detection as a promising non-invasive and comfortable alternative. VOCs are organic chemicals that have a high vapor pressure at room temperature, making them readily detectable in breath, urine, and skin. The present study leverages artificial intelligence (AI) and machine learning algorithms to enhance classification accuracy and efficiency in detecting lung cancer through VOC analysis collected from exhaled breath air. Unlike other studies that primarily focus on identifying specific compounds, this study takes an agnostic approach, maximizing detection efficiency over the identification of specific compounds focusing on the overall compositional profiles and their differences across groups of patients. The results reported hereby uphold the potential of AI-driven techniques in revolutionizing early cancer detection methodologies towards their implementation in a clinical setting.
Immune Microenvironment in Childhood Cancers: Characteristics and Therapeutic Challenges
Authors: Pathania Anup Singh
Published: June 2024

The tumor immune microenvironment is pivotal in cancer initiation, advancement, and regulation. Its molecular and cellular composition is critical throughout the disease, as it can influence the balance between suppressive and cytotoxic immune responses within the tumor’s vicinity. Studies on the tumor immune microenvironment have enriched our understanding of the intricate interplay between tumors and their immunological surroundings in various human cancers. These studies illuminate the role of significant components of the immune microenvironment, which have not been extensively explored in pediatric tumors before and may influence the responsiveness or resistance to therapeutic agents. Our deepening understanding of the pediatric tumor immune microenvironment is helping to overcome challenges related to the effectiveness of existing therapeutic strategies, including immunotherapies. Although in the early stages, targeted therapies that modulate the tumor immune microenvironment of pediatric solid tumors hold promise for improved outcomes. Focusing on various aspects of tumor immune biology in pediatric patients presents a therapeutic opportunity that could improve treatment outcomes. This review offers a comprehensive examination of recent literature concerning profiling the immune microenvironment in various pediatric tumors. It seeks to condense research findings on characterizing the immune microenvironment in pediatric tumors and its impact on tumor development, metastasis, and response to therapeutic modalities. It covers the immune microenvironment’s role in tumor development, interactions with tumor cells, and its impact on the tumor’s response to immunotherapy. The review also discusses challenges targeting the immune microenvironment for pediatric cancer therapies.
S-Scheme Heterojunction Photocatalysts for CO2 Reduction
Authors: Li Mingli , Cui He , Zhao Yi , Li Shunli , Wang Jiabo , Ge Kai , Yang Yongfang
Published: June 2024

Photocatalytic technology, which is regarded as a green route to transform solar energy into chemical fuels, plays an important role in the fields of energy and environmental protection. An emerging S-scheme heterojunction with the tightly coupled interface, whose photocatalytic efficiency exceeds those of conventional type II and Z-scheme photocatalysts, has received much attention due to its rapid charge carrier separation and strong redox capacity. This review provides a systematic description of S-scheme heterojunction in the photocatalysis, including its development, reaction mechanisms, preparation, and characterization methods. In addition, S-scheme photocatalysts for CO2 reduction are described in detail by categorizing them as 0D/1D, 0D/2D, 0D/3D, 2D/2D, and 2D/3D. Finally, some defects of S-scheme heterojunctions are pointed out, and the future development of S-scheme heterojunctions is proposed.
The Expression of a Subset of Aging and Antiaging Markers Following the Chondrogenic and Osteogenic Differentiation of Mesenchymal Stem Cells of Placental Origin
Authors: Zhra Mahmoud , Magableh Ahmad M. , Samhan Lara M. , Fatani Lein M. , Qasem Rani J. , Aljada Ahmad
Published: June 2024

Mesenchymal stem cells (MSCs) of placental origin hold great promise in tissue engineering and regenerative medicine for diseases affecting cartilage and bone. However, their utility has been limited by their tendency to undergo premature senescence and phenotypic drift into adipocytes. This study aimed to explore the potential involvement of a specific subset of aging and antiaging genes by measuring their expression prior to and following in vitro-induced differentiation of placental MSCs into chondrocytes and osteoblasts as opposed to adipocytes. The targeted genes of interest included the various LMNA/C transcript variants (lamin A, lamin C, and lamin A∆10), sirtuin 7 (SIRT7), and SM22α, along with the classic aging markers plasminogen activator inhibitor 1 (PAI-1), p53, and p16INK4a. MSCs were isolated from the decidua basalis of human term placentas, expanded, and then analyzed for phenotypic properties by flow cytometry and evaluated for colony-forming efficiency. The cells were then induced to differentiate in vitro into chondrocytes, osteocytes, and adipocytes following established protocols. The mRNA expression of the targeted genes was measured by RT-qPCR in the undifferentiated cells and those fully differentiated into the three cellular lineages. Compared to undifferentiated cells, the differentiated chondrocytes demonstrated decreased expression of SIRT7, along with decreased PAI-1, lamin A, and SM22α expression, but the expression of p16INK4a and p53 increased, suggesting their tendency to undergo premature senescence. Interestingly, the cells maintained the expression of lamin C, which indicates that it is the primary lamin variant influencing the mechanoelastic properties of the differentiated cells. Notably, the expression of all targeted genes did not differ from the undifferentiated cells following osteogenic differentiation. On the other hand, the differentiation of the cells into adipocytes was associated with decreased expression of lamin A and PAI-1. The distinct patterns of expression of aging and antiaging genes following in vitro-induced differentiation of MSCs into chondrocytes, osteocytes, and adipocytes potentially reflect specific roles for these genes during and following differentiation in the fully functional cells. Understanding these roles and the network of signaling molecules involved can open opportunities to improve the handling and utility of MSCs as cellular precursors for the treatment of cartilage and bone diseases.
Hybrid Architectures Used in the Protection of Large Healthcare Records Based on Cloud and Blockchain Integration: A Review
Authors: Lopez Leonardo Juan Ramirez , Millan Mayorga David , Martinez Poveda Luis Hernando , Amaya Andres Felipe Carbonell , Rojas Reales Wilson
Published: June 2024

The management of large medical files poses a critical challenge in the health sector, with conventional systems facing deficiencies in security, scalability, and efficiency. Blockchain ensures the immutability and traceability of medical records, while the cloud allows scalable and efficient storage. Together, they can transform the data management of electronic health record applications. The method used was the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) methodology to choose and select the relevant studies that contribute to this research, with special emphasis set on maintaining the integrity and security of the blockchain while tackling the potential and efficiency of cloud infrastructures. The study’s focus is to provide a comprehensive and insightful examination of the modern landscape concerning the integration of blockchain and cloud advances, highlighting the current challenges and building a solid foundation for future development. Furthermore, it is very important to increase the integration of blockchain security with the dynamic potential of cloud computing while guaranteeing information integrity and security remain uncompromised. In conclusion, this paper serves as an important resource for analysts, specialists, and partners looking to delve into and develop the integration of blockchain and cloud innovations.
Research on the Short-Term Prediction of Offshore Wind Power Based on Unit Classification
Authors: Zhang Jinhua , Liu Xin , Yan Jie
Published: June 2024

The traditional power prediction methods cannot fully take into account the differences and similarities between units. In the face of the complex and changeable sea climate, the strong coupling effect of atmospheric circulation, ocean current movement, and wave fluctuation, the characteristics of wind processes under different incoming currents and different weather are very different, and the spatio-temporal correlation law of offshore wind processes is highly complex, which leads to traditional power prediction not being able to accurately predict the short-term power of offshore wind farms. Therefore, aiming at the characteristics and complexity of offshore wind power, this paper proposes an innovative short-term power prediction method for offshore wind farms based on a Gaussian mixture model (GMM). This method considers the correlation between units according to the characteristics of the measured data of units, and it divides units with high correlation into a category. The Bayesian information criterion (BIC) and contour coefficient method (SC) were used to obtain the optimal number of groups. The average intra-group correlation coefficient (AICC) was used to evaluate the reliability of measurements for the same quantized feature to select the representative units for each classification. Practical examples show that the short-term power prediction accuracy of the model after unit classification is 2.12% and 1.1% higher than that without group processing, and the mean square error and average absolute error of the short-term power prediction accuracy are reduced, respectively, which provides a basis for the optimization of prediction accuracy and economic operation of offshore wind farms.
Prospective Directions in the Computer Systems Industry Foundation Classes (IFC) for Shaping Data Exchange in the Sustainability and Resilience of Cities
Authors: Okonta Ebere Donatus , Vukovic Vladimir , Hayat Ezri
Published: June 2024

Sustainability and resilience in addressing construction’s environmental, social, and economic challenges rely on interoperability. A model-centred approach using standardised information structures like industry foundation classes (IFC) is essential for data sharing in architecture, engineering, construction, and facility management. Achieving complete interoperability across domains requires further research. This review paper focuses on IFC schema, highlighting upcoming developments like IFC 5 and “IFC x”, with a core emphasis on modularisation to enhance domain interoperability, improved links between building information modelling (BIM) and geographic information systems (GIS), along with IoT integration into BIM, cloud-based collaboration, and support for other advanced technologies such as augmented reality (AR), virtual reality (VR), artificial intelligence (AI), and digital twins. Through a critical examination of the IFC and an outlook towards its future enhancements, the research has the potential to offer valuable insights into shaping the trajectory of future advancements within the AEC and facility management sectors. The study’s discoveries could aid in establishing standardised data exchange protocols in these industries, promoting uniformity across projects, facilitating smoother communication, and mitigating errors and inefficiencies. Anticipating enhancements in the IFC could catalyse innovation, fostering the adoption of emerging technologies and methodologies. Consequently, this could drive the creation of more sophisticated tools and procedures, ultimately enhancing project outcomes and operational effectiveness.
Cloning, Expression, Enzymatic Characterization and Mechanistic Studies of M13 Mutant Acetohydroxyacid Synthase That Rescues Valine Feedback Inhibition
Authors: Tan Yaqing , Gao Xingxing , An Zhiqiang , Wang Nan , Ma Yaqian , Zhang Hailing
Published: June 2024

Acetohydroxyacid synthase (AHAS) is a key enzyme in the first step of the branched-chain amino acid synthesis pathway, and the production of acetohydroxybutyrate from one molecule of 2-ketobutyric acid and one molecule of pyruvate. AHAS is inhibited by feedback from L-valine, L-leucine, and L-isoleucine, and the expression of ilvBN, the gene encoding AHAS, is regulated by all three branched-chain amino acids. A change in amino acids 20–22 on the regulatory subunit (M13 mutation) removes the feedback inhibition by valine. We cloned the gene encoding AHAS (ilvBN) into a vector and then transfected it into Escherichia coli BL21 for expression with targeted changes in amino acids 20–22 on the regulatory subunit, and then determined the activity of the mutated AHAS and its inhibitory effects on valine, isoleucine, and leucine. The enzyme containing the M13 mutation was feedback resistant to all three amino acids. Previous studies have suggested that the binding sites for the three branched-chain amino acids may be at the same variable center. We investigated the enzymatic properties of wild-type and mutant AHAS, modeled their crystal structures, and resolved the mechanism of feedback inhibition induced by mutant M13, which will be useful for continuing the modification of AHAS and the design of broad-spectrum herbicides.
Clip Closure and PuraStat for Prevention of Clinically Significant Delayed Bleeding after Colorectal Endoscopic Submucosal Dissection: A Prospective, Observational Study
Authors: Ciocîrlan Mihai , Bilous Dana , Gîla Andrei , Leucuta Daniel-Corneliu , Mihailă Daniela , Tulin Adrian , Gheorghiu Anca , Tianu Elena , Vlăduț Cătălina
Published: June 2024

Background and aims. Clinically significant delayed bleeding (CSDB) may complicate endoscopic colorectal submucosal dissection (ESD). We aimed to assess the efficacy of preventive measures for CSDB. Methods. We assessed the results of a prospective registry of colorectal ESD for laterally spreading lesions. We evaluated the effect of clip closure and PuraStat application on the prevention of CSDB. Results. A total of 40 patients with 41 colorectal ESDs were included. ESD was successful in 38 lesions (92.7%), 35 with R0 resection (92.1%) and 33 with curative resection (86.8%). CSDB occurred in 3 of 38 lesions (7.9%, 95% CI [1.7–21.4%]), exclusively after rectal ESD (3 of 22 rectal lesions vs. 0 of 16 colonic lesions, p = 0.249). Clip closure was more frequently used after colonic ESD (12 of 16 colonic lesions vs. 2 of 22 rectal lesions, p < 0.001) and was not protective for CSDB in the univariate analysis, even though no events occurred after clip closure (0 of 14 lesions with clip closure vs. 3 of 24 lesions without, p = 0.283). PuraStat was more frequently applied after ESD for rectal lesions (16 of 22 rectal lesions vs. 2 of 16 colonic lesions, p < 0.001) and was not protective for CSDB, with all three events occurring after PuraStat application (3 of 18 lesions with PuraStat application vs. 0 of 20 lesions without, p = 0.097). Conclusions. CSDB occurred exclusively after rectal ESD, and no predictive factors were identified in the univariate analysis. Clip closure and PuraStat application were not protective for CSDB.
A Subset of Microsatellite Unstable Cancer Genomes Prone to Short Insertions over Deletions Is Associated with Elevated Anticancer Immunity
Authors: Kim Sunmin , Han Dong-Jin , Lee Seo-Young , Moon Youngbeen , Kang Su Jung , Kim Tae-Min
Published: June 2024

Deficiencies in DNA mismatch repair (MMRd) leave characteristic footprints of microsatellite instability (MSI) in cancer genomes. We used data from the Cancer Genome Atlas and International Cancer Genome Consortium to conduct a comprehensive analysis of MSI-associated cancers, focusing on indel mutational signatures. We classified MSI-high genomes into two subtypes based on their indel profiles: deletion-dominant (MMRd-del) and insertion-dominant (MMRd-ins). Compared with MMRd-del genomes, MMRd-ins genomes exhibit distinct mutational and transcriptomic features, including a higher prevalence of T>C substitutions and related mutation signatures. Short insertions and deletions in MMRd-ins and MMRd-del genomes target different sets of genes, resulting in distinct indel profiles between the two subtypes. In addition, indels in the MMRd-ins genomes are enriched with subclonal alterations that provide clues about a distinct evolutionary relationship between the MMRd-ins and MMRd-del genomes. Notably, the transcriptome analysis indicated that MMRd-ins cancers upregulate immune-related genes, show a high level of immune cell infiltration, and display an elevated neoantigen burden. The genomic and transcriptomic distinctions between the two types of MMRd genomes highlight the heterogeneity of genetic mechanisms and resulting genomic footprints and transcriptomic changes in cancers, which has potential clinical implications.
Isolation and Characterization of Phenylalanine Ammonia Lyase (PAL) Genes in Ferula pseudalliacea: Insights into the Phenylpropanoid Pathway
Authors: Shahidi Pegah , Bahramnejad Bahman , Vafaee Yavar , Dastan Dara , Heidari Parviz
Published: June 2024

Phenylalanine ammonia lyase (PAL) is a key enzyme regulating the biosynthesis of the compounds of the phenylpropanoid pathway. This study aimed to isolate and characterize PAL genes from Ferula pseudalliacea Rech.f. (Apiales: Apiaceae) to better understand the regulation of metabolite production. Three PAL gene isoforms (FpPAL1-3) were identified and cloned using the 3′-RACE technique and confirmed by sequencing. Bioinformatics analysis revealed important structural features, such as phosphorylation sites, physicochemical properties, and evolutionary relationships. Expression analysis by qPCR demonstrated the differential transcription profiles of each FpPAL isoform across roots, stems, leaves, flowers, and seeds. FpPAL1 showed the highest expression in stems, FpPAL2 in roots and flowers, and FpPAL3 in flowers. The presence of three isoforms of PAL in F. pseudalliacea, along with the diversity of PAL genes and their tissue-specific expression profiles, suggests that complex modes of regulation exist for phenylpropanoid biosynthesis in this important medicinal plant. The predicted interaction network revealed associations with key metabolic pathways, emphasizing the multifaceted roles of these PAL genes. In silico biochemical analyses revealed the hydrophilicity of the FpPAL isozyme; however, further analysis of substrate specificity and enzyme kinetics can clarify the specific role of each FpPAL isozyme. These comprehensive results increase the understanding of PAL genes in F. pseudalliacea, helping to characterize their contributions to secondary metabolite biosynthesis.
Correction: Yi et al. SFS-AGGL: Semi-Supervised Feature Selection Integrating Adaptive Graph with Global and Local Information. Information 2024, 15, 57
Authors: Yi Yugen , Zhang Haoming , Zhang Ningyi , Zhou Wei , Huang Xiaomei , Xie Gengsheng , Zheng Caixia
Published: June 2024

In the original publication [...]
Implications of Temperature and Prey Density on Predatory Mite Amblyseius swirskii (Acari: Phytoseiidae) Functional Responses
Authors: Elmoghazy Mohammed M. E. , Elsherbini Dalia Mahmoud Abdelmonem , Mashlawi Abadi M. , Ibrahim Ateya Megahed , El-Mansi Ahmed A. , El-Sherbiny Mohamed
Published: June 2024

Amblyseius swirskii are predaceous mites that feed on phytophagous mites, pollens, and plant exudates and are known as one of the most potent biological pest management agents. Tetranychus urticae is a global mite that is difficult to manage because of its high population growth rates, necessitating alternative management measures like biological control. Regarding the functional response, the effects of temperature and prey density are some of the essential behaviors of natural enemies. This study investigates the effect of varying temperatures and prey densities on A. swirskii, a biological control agent for T. urticae. The present results demonstrated the change in the functional response estimates when A. swirskii was reared at various temperatures and different prey densities. The results of the estimates regarding the searching efficiency (a′) showed the highest value (a′ = 0.919) at 26 °C and the lowest value (a′ = 0.751) at 14 °C. The handling time per prey item (Th) for the predatory mites changed with the temperature and prey density, showing the shortest handling time at 26 °C (Th = 0.005) and the highest value at 14 °C (Th = 0.015). The functional response curves matched the type II functional response model, demonstrating the inverse dependence of temperatures and prey density with a positive quadratic coefficient. The predation curves for A. swirskii showed a significant difference between the mean numbers of T. urticae consumed at various prey densities and temperatures, illustrating a relationship between A. swirskii and T. urticae. Therefore, the results of this research may be utilized to forecast the behavior of A. swirskii and its usefulness in controlling T. urticae populations.
Surgical Management of Chiari Malformation Type I in the Pediatric Population: A Single-Center Experience
Authors: Venanzi Maria Sole , Pavanello Marco , Pacetti Mattia , Secci Francesca , Rossi Andrea , Consales Alessandro , Piatelli Gianluca
Published: June 2024

Background: Chiari malformation type 1 (CM-1) involves the cerebellar tonsils’ descent below the foramen magnum. In Chiari malformation type 1.5 (CM-1.5), both the cerebellar tonsils and the brainstem are herniated. Common symptoms include headaches and cervical pain, often associated with conditions like syringomyelia and hydrocephalus. Surgical treatment is not performed in asymptomatic patients, while the presence of syringomyelia represents an indication for surgery. Methods: This study retrospectively examined pediatric patients with CM-1 and CM-1.5 at Giannina Gaslini Hospital from 2006 to 2020, analyzing demographics, radiological findings, surgical interventions, and outcomes. Results: Out of 211 patients who underwent surgery, 83.9% were diagnosed with CM-1 and 16.1% with CM-1.5. Headaches were prevalent (69%) and cerebellar signs were noted in 29% of patients. Syringomyelia and hydrocephalus were present in 28.4% and 8% of cases, respectively. Intraoperative ultrasonography guided interventions, with 59.8% requiring bony and ligamentous decompression, and 27.1% undergoing duraplasty. Conclusions: The surgical treatment of CM-1/CM-1.5 involves posterior cranial fossa decompression. Choosing between bony decompression alone and its combination with duraplasty has always been controversial in the pediatric population. If we consider as surgical endpoint the restoration of cerebrospinal fluid (CSF) flux, intraoperative ultrasound may be a real-time helpful tool in orienting the surgical strategy, yet refinement with quantitative measures is needed.
Urine Nephrin and Podocalyxin Reflecting Podocyte Damage and Severity of Kidney Disease in Various Glomerular Diseases—A Cross-Sectional Study
Authors: Giannou Panagiota , Gakiopoulou Harikleia , Stambolliu Emelina , Petras Dimitrios , Chalkia Aglaia , Kapota Athanasia , Palamaris Kostas , Hadziyannis Emilia , Thomas Konstantinos , Alexakou Zoe , Bora Margarita , Mintzias Theodoros , Vassilopoulos Dimitrios , Patsouris Eustratios , Deutsch Melanie
Published: June 2024

Background/Objectives: Glomerulopathy is a term used to describe a broad spectrum of renal diseases, characterized by dysfunction of glomerular filtration barrier, especially of podocytes. Several podocyte-associated proteins have been found and proved their usefulness as urine markers of podocyte dysfunction. Two of them are nephrin (NEP) and prodocalyxin (PDC). This study aims to evaluate the association of podocyte damage, as it is demonstrated via the concentrations of urinary proteins, with clinical and histological data from patients with several types of glomerulonephritis. Methods: We measured urine levels of two podocyte-specific markers, NEP and PDC (corrected for urine creatinine levels), in patients with a wide range of glomerulopathies. Serum and urine parameters as well as histological parameters from renal biopsy were recorded. Results: In total, data from 37 patients with glomerulonephritis and 5 healthy controls were analyzed. PDC and NEP concentrations correlated between them and with serum creatinine levels (p = 0.001 and p = 0.013 respectively), and with histological lesions associated with chronicity index of renal cortex, such as severe interstitial fibrosis, severe tubular atrophy and hyalinosis (for PDC/NEP, all p < 0.05). In addition, the PDC and NEP demonstrated statistically significant correlations with interstitial inflammation (p = 0.018/p = 0.028). Regarding electron microscopy evaluation, PDC levels were correlated with distinct characteristics, such as fibrils and global podocyte foot process fusion, whereas the NEP/CR ratio was uniquely significantly associated with podocyte fusion only in non-immune-complex-mediated glomerulonephritis (p = 0.02). Among the other clinical and histological parameters included in our study, a strong correlation between proteinuria >3 g/24 h and diffuse fusion of podocyte foot processes (p = 0.016) was identified. Conclusions: Podocalyxin and nephrin concentrations in urine are markers of podocyte dysfunction, and in our study, they were associated both with serum creatinine and histological chronicity indices.
Switching from a Fixed Monthly Aflibercept Regimen to Bi-Monthly Brolucizumab in Refractory Cases of Neovascular Age-Related Macular Degeneration
Authors: Kim Minhee , Kang Ji Eon , Park Young Gun
Published: June 2024

Background/Objectives: This study aimed to assess the effectiveness of bi-monthly brolucimumab treatment in patients with neovascular age-related macular degeneration (nAMD) refractory to monthly aflibercept treatment. Methods: A retrospective chart review included 32 eyes of patients with refractory nAMD who switched from monthly intravitreal aflibercept treatment to bi-monthly intravitreal brolucizumab treatment. This study evaluated changes in visual acuity (VA), intraretinal fluid (IRF), subretinal fluid (SRF), pigment epithelial detachment (PED), and central macular thickness (CMT), at specific times as follows: baseline before switching (T0), 2 months after switching (T1), 4 months after switching (T2), and 6 months after switching (T3). Results: The mean best-corrected visual acuity (BCVA) did not significantly change across all time points (0.52 ± 0.12, 0.48 ± 0.27, 0.48 ± 0.28, and 0.50 ± 0.27 logarithms of the minimum angle of resolution in T0, T1, T2, and T3, respectively). CMT significantly decreased after additional brolucizumab injections compared to the baseline (218.2 ± 48.6 and 207.9 ± 49.8 μm, respectively; p = 0.001). The PED height also significantly decreased from 251.0 ± 165.4 to 154.4 ± 115.65 μm (p < 0.001), with complete resolution in nine patients (28%). The mean subfoveal choroidal thickness (SFCT) before brolucizumab treatment was 262.8 ± 79.7 μm, which decreased to 233.0 ± 71.2 μm (p = 0.001) after the first injection. The final SFCT also significantly decreased after additional brolucizumab injections compared to the baseline SFCT (p = 0.012). Conclusions: Bi-monthly brolucizumab treatment proves effective for patients refractory to monthly fixed aflibercept, resulting in positive anatomical changes without significant deterioration in visual acuity. This approach provides a promising prognosis while reducing the treatment burden on refractory patients.
El Hierro Genome Study: A Genomic and Health Study in an Isolated Canary Island Population
Authors: Puga Marta , Serrano Javier G. , García Elsa L. , González Carracedo Mario A. , Jiménez-Canino Rubén , Pino-Yanes María , Karlsson Robert , Sullivan Patrick F. , Fregel Rosa
Published: June 2024

El Hierro is the smallest and westernmost island of the Canary Islands, whose population derives from an admixture of different ancestral components and that has been subjected to genetic isolation. We established the “El Hierro Genome Study” to characterize the health status and the genetic composition of ~10% of the current population of the island, accounting for a total of 1054 participants. Detailed demographic and clinical data and a blood sample for DNA extraction were obtained from each participant. Genomic genotyping was performed with the Global Screening Array (Illumina). The genetic composition of El Hierro was analyzed in a subset of 416 unrelated individuals by characterizing the mitochondrial DNA (mtDNA) and Y-chromosome haplogroups and performing principal component analyses (PCAs). In order to explore signatures of isolation, runs of homozygosity (ROHs) were also estimated. Among the participants, high blood pressure, hypercholesterolemia, and diabetes were the most prevalent conditions. The most common mtDNA haplogroups observed were of North African indigenous origin, while the Y-chromosome ones were mainly European. The PCA showed that the El Hierro population clusters near 1000 Genomes’ European population but with a shift toward African populations. Moreover, the ROH analysis revealed some individuals with an important portion of their genomes with ROHs exceeding 400 Mb. Overall, these results confirmed that the “El Hierro Genome” cohort offers an opportunity to study the genetic basis of several diseases in an unexplored isolated population.
Soil Organic Carbon Content and Its Relationship with the Stand Age in Tea Plantations (Camellia sinensis L.) in Fujian Province, China
Authors: Wang Miaomiao , Zhao Jian , Chen Jinghua , Zhang Xinyi , Zhu Shilei
Published: June 2024

Optimizing soil carbon content is essential for mitigating climate change. Understanding the soil organic carbon (SOC) contents and their relationship with plantation age is important for enhancing SOC in tea plantations. However, there is still a lack of studies in quantifying the SOC–age curve of the whole life cycle in tea plantations. Thus, in this study, we collected 140 soil samples aged 3 to 60 years in the four representative regions (Anxi, Datian, Qingliu, and Fuzhou) in Fujian Province to quantify the SOC contents and their relationship with plantation age. We found that the average SOC was 14.6 ± 6.1 g/kg in the four sampling regions. Nitrogen (N) emerged as having a highly significant positive correlation with SOC (R2 = 0.9). We also found a significant negative correlation between SOC and mean annual temperature (MAT) (R2 = 0.6), and a significant positive correlation with mean annual precipitation (MAP) (R2 = 0.6). The SOC increased with plantation age at 3–20 years old and peaked at 16–20 years old. After 35 years, the SOC decreased gradually with the aging of the plantation. The results indicated that tea plantations could be renewed after the age of 35. These results showed that optimizing age structure is important in enhancing SOC in tea plantations and is meaningful in achieving carbon neutrality.
The Effect of Stress-Reducing Interventions on Heart Rate Variability in Cardiovascular Disease: A Systematic Review and Meta-Analysis
Authors: El-Malahi Ouahiba , Mohajeri Darya , Bäuerle Alexander , Mincu Raluca , Rothenaicher Korbinian , Ullrich Greta , Rammos Christos , Teufel Martin , Rassaf Tienush , Lortz Julia
Published: June 2024

Stress is recognized as a significant trigger and exacerbator of various medical conditions, particularly in the field of cardiovascular disease (CVD). Given that heart rate variability (HRV) offers insight into the functioning of the autonomic nervous system and has been identified as a predictive factor for increased cardiovascular mortality, exploring the correlation between stress and HRV is pertinent. We systematically reviewed trials where researchers investigated the effects of stress-reducing interventions on biomarkers and time-domain/frequency-domain parameters of HRV in CVD. Eligible studies underwent meta-analysis utilizing a random-effects model. The meta-analysis showed overall beneficial effects of stress-reducing interventions on HRV for the standard deviation of Normal-to-Normal intervals (SDNN) in short-term and 24 h assessments, as well as for the low-frequency power (LF) in short-term assessment. Overall effect sizes were notably high and showed significant p-values (short-term SDNN: MD = 6.43, p = 0.01; 24 h SDNN: MD = 10.92, p = 0.004; short-term LF: MD = 160.11, p < 0.001). Our findings highlight the significant impact of stress-reducing interventions in modulating HRV by influencing short-term SDNN and LF parameters, as well as the 24 h assessment of SDNN. These results emphasize the importance of stress-reducing measures in lowering the risk of further progression in CVD and improving patient outcomes.
Fracture Model of Al–Cu Alloys with Gradient Crystals Based on Crystal Plasticity
Authors: Xiao Mao , Yao Ji , Huang Chunyang
Published: June 2024

Gradient grain structure materials with superior mechanical properties of high strength and high toughness have attracted widespread attention. Gradient materials can effectively improve toughness by constructing a microstructure from fine to coarse crystals inside the material, which has gradually become a hotspot of attention in the academic and engineering communities. In this paper, based on the crystal plasticity intrinsic theory, dislocation density is introduced as a characterization quantity, and cohesive units are added at grain boundaries to simulate damage fractures. The results of this study reveal the fracture damage mechanism of gradient crystal structure materials, providing new ideas and methods for the design of gradient materials.
The Effects of Nucleating Agents and Processing on the Crystallization and Mechanical Properties of Polylactic Acid: A Review
Authors: Gao Peng , Masato Davide
Published: June 2024

Polylactic acid (PLA) is a biobased, biodegradable, non-toxic polymer widely considered for replacing traditional petroleum-based polymer materials. Being a semi-crystalline material, PLA has great potential in many fields, such as medical implants, drug delivery systems, etc. However, the slow crystallization rate of PLA limited the application and efficient fabrication of highly crystallized PLA products. This review paper investigated and summarized the influence of formulation, compounding, and processing on PLA’s crystallization behaviors and mechanical performances. The paper reviewed the literature from different studies regarding the impact of these factors on critical crystallization parameters, such as the degree of crystallinity, crystallization rate, crystalline morphology, and mechanical properties, such as tensile strength, modulus, elongation, and impact resistance. Understanding the impact of the factors on crystallization and mechanical properties is critical for PLA processing technology innovations to meet the requirements of various applications of PLA.
Radiation-Induced Synthesis and Superparamagnetic Properties of Ferrite Fe3O4 Nanoparticles
Authors: Zorai Amel , Souici Abdelhafid , Adjei Daniel , Dragoe Diana , Rivière Eric , Ouhenia Salim , Mostafavi Mehran , Belloni Jacqueline
Published: June 2024

Ultra-small magnetic Fe3O4 nanoparticles are successfully synthesized in basic solutions by using the radiolytic method of the partial reduction in FeIII in the presence of poly-acrylate (PA), or by using the coprecipitation method of FeIII and FeII salts in the presence of PA. The optical, structural, and magnetic properties of the nanoparticles were examined using UV–Vis absorption spectroscopy, high-resolution transmission electron microscopy (HRTEM), X-ray diffraction (XRD), and SQUID magnetization measurements. The HRTEM and XRD analysis confirmed the formation of ultra-small magnetite nanoparticles in a spinel structure, with a smaller size for radiation-induced particles coated by PA (5.2 nm) than for coprecipitated PA-coated nanoparticles (11 nm). From magnetization measurements, it is shown that the nanoparticles are superparamagnetic at room temperature. The magnetization saturation value Ms = 50.1 A m2 kg−1 of radiation-induced nanoparticles at 60 kGy is higher than Ms = 18.2 A m2 kg−1 for coprecipitated nanoparticles. Both values are compared with nanoparticles coated with other stabilizers in the literature.
Artificial and Natural Sweeteners Biased T1R2/T1R3 Taste Receptors Transactivate Glycosylated Receptors on Cancer Cells to Induce Epithelial–Mesenchymal Transition of Metastatic Phenotype
Authors: Skapinker Elizabeth , Aldbai Rashelle , Aucoin Emilyn , Clarke Elizabeth , Clark Mira , Ghokasian Daniella , Kombargi Haley , Abraham Merlin J. , Li Yunfan , Bunsick David A. , Baghaie Leili , Szewczuk Myron R.
Published: June 2024

Understanding the role of biased taste T1R2/T1R3 G protein-coupled receptors (GPCR) agonists on glycosylated receptor signaling may provide insights into the opposing effects mediated by artificial and natural sweeteners, particularly in cancer and metastasis. Sweetener-taste GPCRs can be activated by several active states involving either biased agonism, functional selectivity, or ligand-directed signaling. However, there are increasing arrays of sweetener ligands with different degrees of allosteric biased modulation that can vary dramatically in binding- and signaling-specific manners. Here, emerging evidence proposes the involvement of taste GPCRs in a biased GPCR signaling crosstalk involving matrix metalloproteinase-9 (MMP-9) and neuraminidase-1 (Neu-1) activating glycosylated receptors by modifying sialic acids. The findings revealed that most natural and artificial sweeteners significantly activate Neu-1 sialidase in a dose-dependent fashion in RAW-Blue and PANC-1 cells. To confirm this biased GPCR signaling crosstalk, BIM-23127 (neuromedin B receptor inhibitor, MMP-9i (specific MMP-9 inhibitor), and oseltamivir phosphate (specific Neu-1 inhibitor) significantly block sweetener agonist-induced Neu-1 sialidase activity. To assess the effect of artificial and natural sweeteners on the key survival pathways critical for pancreatic cancer progression, we analyzed the expression of epithelial-mesenchymal markers, CD24, ADLH-1, E-cadherin, and N-cadherin in PANC-1 cells, and assess the cellular migration invasiveness in a scratch wound closure assay, and the tunneling nanotubes (TNTs) in staging the migratory intercellular communication. The artificial and natural sweeteners induced metastatic phenotype of PANC-1 pancreatic cancer cells to promote migratory intercellular communication and invasion. The sweeteners also induced the downstream NFκB activation using the secretory alkaline phosphatase (SEAP) assay. These findings elucidate a novel taste T1R2/T1R3 GPCR functional selectivity of a signaling platform in which sweeteners activate downstream signaling, contributing to tumorigenesis and metastasis via a proposed NFκB-induced epigenetic reprogramming modeling.
Impact of Effort–Reward Imbalance and Burnout on the Compliance with Standard Precautions among Nurses and Midwives in Lebanese Hospitals
Authors: Sayrafi Noha A. , Salami Ali , Ghssein Ghassan
Published: June 2024

Background: Effort–reward imbalance (ERI) refers to the situation where there is a mismatch between the effort that healthcare workers (HCWs) put into their work and the rewards they receive in return. Burnout, on the other hand, is a psychological syndrome characterized by emotional exhaustion, depersonalization, and reduced personal accomplishment. This study aimed to assess the impact of ERI and burnout on the compliance with standard precautions (SPs) among nurses and midwives in Lebanese hospitals under the economic crisis and after the COVID-19 pandemic. Methods: Cross-sectional correlational study, based on self-administered questionnaire data, measuring the compliance with SPs, ERI, and burnout, in addition to the relationship between these factors, was performed among 409 nurses and midwives, working in Lebanese hospitals. Results: ERI was significantly associated with exposure to burnout among nurses and midwives, and burnout was found to be a significant predictor of nurses and midwives’ self-reported adherence with SPs. Conclusions: This study highlights the contribution of ERI and burnout to the chain of infection by decreased adherence to infection control SPs of nurses and midwives.
Brief Insights into mRNA Vaccines: Their Successful Production and Nanoformulation for Effective Response against COVID-19 and Their Potential Success for Influenza A and B
Authors: Parveen Amerah , Elkordy Amal Ali
Published: June 2024

A mRNA vaccine is a type of vaccine that induces an immune response. Antigen-encoding mRNA is delivered via vaccine carriers into the immune cells, which are produced because of antigen-encoding mRNA translation, a protein. For example, COVID-19 mRNA vaccines produce the spike protein of the COVID-19 virus, whereas for influenza virus, mRNA vaccines target the haemagglutinin protein to treat the flu, and it requires modifications depending on the pandemic or seasonal viruses as it is capable of adapting the immune response, which makes the development of vaccines arduous. The protein molecule promotes an adaptive immune response that eliminates and terminates the corresponding virus or pathogen. There are many challenges to delivering an mRNA vaccine into the body; hence, the encapsulation of the mRNA (usually within lipid nanoparticles) is necessary to protect the mRNA from the body’s surrounding environment. In this review article, we focus mainly on the production, formulation, and stabilization of mRNA vaccines in general, elaborating more on and focusing more on SARS-CoV-2, or COVID-19, and influenza viruses, which have become a major concern as these viruses have turned into life-threatening diseases.
MOF-Based Platform for Kidney Diseases: Advances, Challenges, and Prospects
Authors: Deng Li-Er , Guo Manli , Deng Yijun , Pan Ying , Wang Xiaoxiong , Maduraiveeran Govindhan , Liu Jianqiang , Lu Chengyu
Published: June 2024

Kidney diseases are important diseases that affect human health worldwide. According to the 2020 World Health Organization (WHO) report, kidney diseases have become the top 10 causes of death. Strengthening the prevention, primary diagnosis, and action of kidney-related diseases is of great significance in maintaining human health and improving the quality of life. It is increasingly challenging to address clinical needs with the present technologies for diagnosing and treating renal illness. Fortunately, metal-organic frameworks (MOFs) have shown great promise in the diagnosis and treatment of kidney diseases. This review summarizes the research progress of MOFs in the diagnosis and treatment of renal disease in recent years. Firstly, we introduce the basic structure and properties of MOFs. Secondly, we focus on the utilization of MOFs in the diagnosis and treatment of kidney diseases. In the diagnosis of kidney disease, MOFs are usually designed as biosensors to detect biomarkers related to kidney disease. In the treatment of kidney disease, MOFs can not only be used as an effective adsorbent for uremic toxins during hemodialysis but also as a precise treatment of intelligent drug delivery carriers. They can also be combined with nano-chelation technology to solve the problem of the imbalance of trace elements in kidney disease. Finally, we describe the current challenges and prospects of MOFs in the diagnosis and treatment of kidney diseases.
Phytochemical Profiles and Cytotoxic Activity of Bursera fagaroides (Kunth) Engl. Leaves and Its Callus Culture
Authors: Pérez-Mejía Nancy , Villarreal María Luisa , Sánchez-Carranza Jessica Nayelli , González-Maya Leticia , González-Cortazar Manasés , Ortíz-Caltempa Anabel , Alvarez Laura
Published: June 2024

Bursera fagaroides, popularly used in México, possesses bioactive lignans. These compounds are low in the bark, and its extraction endangers the life of the trees. The aim of the present investigation was to search for alternative sources of cytotoxic compounds in B. fagaroides prepared as leaves and in vitro callus cultures. The friable callus of B. fagaroides was established using a combination of plant growth regulators: 4 mgL−1 of 2,4-dichlorophenoxyacetic acid (2,4-D), 1 mgL−1 Naphthaleneacetic Acid (NAA) and 1 mgL−1 Zeatin. The maximum cell growth was at day 28 with a specific growth rate of μ = 0.059 days−1 and duplication time td = 11.8 days. HPLC quantification of the dichloromethane callus biomass extract showed that Scopoletin, with a concentration of 10.7 µg g−1 dry weight, was the main compound inducible as a phytoalexin by the addition of high concentrations of 2,4-D, as well as by the absence of nutrients in the culture medium. In this same extract, the compounds γ-sitosterol and stigmasterol were also identified by GC-MS analysis. Open column chromatography was used to separate and identify yatein, acetyl podophyllotoxin and 7′,8′-dehydropodophyllotoxin in the leaves of the wild plant. Cytotoxic activity on four cancer cell lines was tested, with PC-3 prostate carcinoma (IC50 of 12.6 ± 4.6 µgmL−1) being the most sensitive to the wild-type plant extract and HeLa cervical carcinoma (IC50 of 72 ± 5 µgmL−1) being the most sensitive to the callus culture extract.
Elucidation of Dithiol-yne Comb Polymer Architectures by Tandem Mass Spectrometry and Ion Mobility Techniques
Authors: Williams-Pavlantos Kayla , Mokarizadeh Abdol Hadi , Curole Brennan J. , Grayson Scott M. , Tsige Mesfin , Wesdemiotis Chrys
Published: June 2024

Polymers have a wide range of applications depending on their composition, size, and architecture. Varying any of these three characteristics can greatly impact the resulting chemical, physical, and mechanical properties. While many techniques are available to determine polymer composition and size, determining the exact polymer architecture is more challenging. Herein, tandem mass spectrometry (MS/MS) and ion mobility mass spectrometry (IM-MS) methods are utilized to derive crucial architectural information about dithiol-yne comb polymers. Based on their unique fragmentation products and IM drift times, dithiol-yne oligomers with distinct architectures were successfully differentiated and characterized. Additionally, experimental collision cross-sections (Ω) derived via IM-MS were compared to theoretically extracted Ω values from molecular dynamics simulated structures to deduce the architectural motif of these comb oligomers. Overall, this work demonstrates the benefits of combining various mass spectrometry techniques in order to gain a complete understanding of a complex polymer mixture.