bluuebunny/crossref_metadata_2025 huggingface dataset:
El Niño Onset Time Affects the Intensity of Landfalling Tropical Cyclones in China
Authors: Yang Jinyi , Xu Feng , Tu Shifei , Han Liguo , Zhang Shaojing , Zheng Meiying , Li Yongchi , Zhang Shihan , Wan Yishun
Published: March 2023

In this work, we studied the influence of spring (SP) and summer (SU) El Niño events on the landfalling tropical cyclones (TCs) in China. The results showed that compared to SU El Niño years, the average latitude of the landfalling TCs in SP El Niño years shifted significantly southward and that the average TC intensity was significantly stronger, especially in the post-landfall period. Additionally, more severe tropical storm-level TCs generated over the South China Sea made landfall in China. Meanwhile, in SP El Niño years, landfalling TCs in southern China had a greater landfall intensity, but landfalling TCs in eastern China were the opposite. These changes in TC intensity during the SP El Niño years could be attributed to more favorable dynamical and thermodynamical conditions, which are beneficial for maintaining TC intensity and duration after landfall. These results could have important implications for an in-depth understanding of TC activities, as well as TC disaster prevention and mitigation.
Thermal Modelling and Simulation Studies of Containerised Vanadium Flow Battery Systems
Authors: Shu Bing , Weber Logan S. , Skyllas-Kazacos Maria , Bao Jie , Meng Ke
Published: March 2023

With increasing commercial applications of vanadium flow batteries (VFB), containerised VFB systems are gaining attention as they can be mass produced and easily transported and configured for different energy storage applications. However, there are limited studies on the thermodynamic modelling of containerised vanadium redox flow battery systems, and thermal control designs. In this paper, a dynamic thermal model is developed for containerised VFB systems, based on which thermal design options are evaluated using simulation studies.
A Comparison of Inertial Measurement Units and Overnight Videography to Assess Sleep Biomechanics
Authors: Buckley Nicholas , Davey Paul , Jensen Lynn , Baptist Kevin , Jacques Angela , Jansen Bas , Campbell Amity , Downs Jenny
Published: March 2023

Purpose: The assessment of sleep biomechanics (comprising movement and position during sleep) is of interest in a wide variety of clinical and research settings. However, there is no standard method by which sleep biomechanics are measured. This study aimed to (1) compare the intra- and inter-rater reliability of the current clinical standard, manually coded overnight videography, and (2) compare sleep position recorded using overnight videography to sleep position recorded using the XSENS DOT wearable sensor platform. Methods: Ten healthy adult volunteers slept for one night with XSENS DOT units in situ (on their chest, pelvis, and left and right thighs), with three infrared video cameras recording concurrently. Ten clips per participant were edited from the video. Sleeping position in each clip was coded by six experienced allied health professionals using the novel Body Orientation During Sleep (BODS) Framework, comprising 12 sections in a 360-degree circle. Intra-rater reliability was assessed by calculating the differences between the BODS ratings from repeated clips and the percentage who were rated with a maximum of one section of the XSENS DOT value; the same methodology was used to establish the level of agreement between the XSENS DOT and allied health professional ratings of overnight videography. Bennett’s S-Score was used to assess inter-rater reliability. Results: High intra-rater reliability (90% of ratings with maximum difference of one section) and moderate inter-rater reliability (Bennett’s S-Score 0.466 to 0.632) were demonstrated in the BODS ratings. The raters demonstrated high levels of agreement overall with the XSENS DOT platform, with 90% of ratings from allied health raters being within the range of at least 1 section of the BODS (as compared to the corresponding XSENS DOT produced rating). Conclusions: The current clinical standard for assessing sleep biomechanics, manually rated overnight videography (as rated using the BODS Framework) demonstrated acceptable intra- and inter-rater reliability. Further, the XSENS DOT platform demonstrated satisfactory levels of agreement as compared to the current clinical standard, providing confidence for its use in future studies of sleep biomechanics.
U-Net Architecture for Prostate Segmentation: The Impact of Loss Function on System Performance
Authors: Montazerolghaem Maryam , Sun Yu , Sasso Giuseppe , Haworth Annette
Published: March 2023

Segmentation of the prostate gland from magnetic resonance images is rapidly becoming a standard of care in prostate cancer radiotherapy treatment planning. Automating this process has the potential to improve accuracy and efficiency. However, the performance and accuracy of deep learning models varies depending on the design and optimal tuning of the hyper-parameters. In this study, we examine the effect of loss functions on the performance of deep-learning-based prostate segmentation models. A U-Net model for prostate segmentation using T2-weighted images from a local dataset was trained and performance compared when using nine different loss functions, including: Binary Cross-Entropy (BCE), Intersection over Union (IoU), Dice, BCE and Dice (BCE + Dice), weighted BCE and Dice (W (BCE + Dice)), Focal, Tversky, Focal Tversky, and Surface loss functions. Model outputs were compared using several metrics on a five-fold cross-validation set. Ranking of model performance was found to be dependent on the metric used to measure performance, but in general, W (BCE + Dice) and Focal Tversky performed well for all metrics (whole gland Dice similarity coefficient (DSC): 0.71 and 0.74; 95HD: 6.66 and 7.42; Ravid 0.05 and 0.18, respectively) and Surface loss generally ranked lowest (DSC: 0.40; 95HD: 13.64; Ravid −0.09). When comparing the performance of the models for the mid-gland, apex, and base parts of the prostate gland, the models’ performance was lower for the apex and base compared to the mid-gland. In conclusion, we have demonstrated that the performance of a deep learning model for prostate segmentation can be affected by choice of loss function. For prostate segmentation, it would appear that compound loss functions generally outperform singles loss functions such as Surface loss.
Effects of Running Speeds and Exhaustion on Iliotibial Band Strain during Running
Authors: Chen Shanefei , Wang Yan , Bing Fangbo , Zhang Ming
Published: March 2023

Background: Iliotibial band syndrome (ITBS) is one of the most prevalent overuse injuries in runners. The strain rate in the iliotibial band (ITB) has been theorized to be the primary causative factor in the development of ITBS. Running speed and exhaustion might lead to an alteration in the biomechanics that influence the strain rate in the iliotibial band. Objectives: To identify how exhaustion states and running speeds affect the ITB strain and strain rate. Methods: A total of 26 healthy runners (including 16 males and 10 females) ran at a normal preferred speed and a fast speed. Then, participants performed a 30 min exhaustive treadmill run at a self-selected speed. Afterward, participants were required to run at similar speeds to those of the pre-exhaustion state. Results: Both the exhaustion and running speeds were revealed to have significant influences on the ITB strain rate. After exhaustion, an increase of approximately 3% in the ITB strain rate was observed for both the normal speed (p = 0.001) and the fast speed (p = 0.008). Additionally, a rapid increase in the running speed could lead to an increase in the ITB strain rate for both the pre- (9.71%, p = 0.000) and post-exhaustion (9.87%, p = 0.000) states. Conclusions: It should be noted that an exhaustion state could lead to an increase in the ITB strain rate. In addition, a rapid increase in running speed might cause a higher ITB strain rate, which is proposed to be the primary cause of ITBS. The risk of injury should also be considered due to the rapid increase in the training load involved. Running at a normal speed in a non-exhaustive state might be beneficial for the prevention and treatment of ITBS.
A Review of Barbed Sutures—Evolution, Applications and Clinical Significance
Authors: Nambi Gowri Karuna , King Martin W.
Published: March 2023

Surgical ligatures are a critical component of any surgical procedure since they are the device that provides immediate post-surgical tissue apposition. There have been several studies to improve the design and use of these wound closure devices for different surgical procedures. Yet, there is no standardized technique or device that can be used for any specific application. Over the last two decades, there has been an increased focus on the innovative surgical sutures known as knotless or barbed sutures, along with studies focusing on their advantages and disadvantages in clinical environments. Barbed sutures were invented to reduce the localized stress on the approximated tissues as well as facilitating the surgical technique and improving the clinical outcome for the patient. This review article discusses how barbed sutures evolved from the first patent published in 1964 and how these barbed sutures influence the surgical outcomes in different procedures ranging from cosmetic surgery to orthopedic surgery performed on both human patients and animals.
Stem Cell Therapies for Epidermolysis Bullosa Treatment
Authors: Niti Argyrw , Koliakos Georgios , Michopoulou Anna
Published: March 2023

Epidermolysis bullosa (EB) includes a group of rare skin diseases characterized by skin fragility with bullous formation in the skin, in response to minor mechanical injury, as well as varying degrees of involvement of the mucous membranes of the internal organs. EB is classified into simplex, junctional, dystrophic and mixed. The impact of the disease on patients is both physical and psychological, with the result that their quality of life is constantly affected. Unfortunately, there are still no approved treatments available to confront the disease, and treatment focuses on improving the symptoms with topical treatments to avoid complications and other infections. Stem cells are undifferentiated cells capable of producing, maintaining and replacing terminally differentiated cells and tissues. Stem cells can be isolated from embryonic or adult tissues, including skin, but are also produced by genetic reprogramming of differentiated cells. Preclinical and clinical research has recently greatly improved stem cell therapy, making it a promising treatment option for various diseases in which current medical treatments fail to cure, prevent progression, or alleviate symptoms. So far, stem cells from different sources, mainly hematopoietic and mesenchymal, autologous or heterologous have been used for the treatment of the most severe forms of the disease each one of them with some beneficial effects. However, the mechanisms through which stem cells exert their beneficial role are still unknown or incompletely understood and most importantly further research is required to evaluate the effectiveness and safety of these treatments. The transplantation of skin grafts to patients produced by gene-corrected autologous epidermal stem cells has been proved to be rather successful for the treatment of skin lesions in the long term in a limited number of patients. Nevertheless, these treatments do not address the internal epithelia-related complications manifested in patients with more severe forms.
The Role of Epicardial Adipose Tissue-Derived MicroRNAs in the Regulation of Cardiovascular Disease: A Narrative Review
Authors: Kim Il-Kwon , Song Byeong-Wook , Lim Soyeon , Kim Sang-Woo , Lee Seahyoung
Published: March 2023

Cardiovascular diseases have been leading cause of death worldwide for many decades, and obesity has been acknowledged as a risk factor for cardiovascular diseases. In the present review, human epicardial adipose tissue-derived miRNAs reported to be differentially expressed under pathologic conditions are discussed and summarized. The results of the literature review indicate that some of the epicardial adipose tissue-derived miRNAs are believed to be cardioprotective, while some others show quite the opposite effects depending on the underlying pathologic conditions. Furthermore, they suggest that that the epicardial adipose tissue-derived miRNAs have great potential as both a diagnostic and therapeutic modality. Nevertheless, mainly due to highly limited availability of human samples, it is very difficult to make any generalized claims on a given miRNA in terms of its overall impact on the cardiovascular system. Therefore, further functional investigation of a given miRNA including, but not limited to, the study of its dose effect, off-target effects, and potential toxicity is required. We hope that this review can provide novel insights to transform our current knowledge on epicardial adipose tissue-derived miRNAs into clinically viable therapeutic strategies for preventing and treating cardiovascular diseases.
Integration of Selection Signatures and Protein Interactions Reveals NR6A1, PAPPA2, and PIK3C2B as the Promising Candidate Genes Underlying the Characteristics of Licha Black Pig
Authors: Xie Qinqin , Zhang Zhenyang , Chen Zitao , Sun Jiabao , Li Meng , Wang Qishan , Pan Yuchun
Published: March 2023

Licha black (LI) pig has the specific characteristics of larger body length and appropriate fat deposition among Chinese indigenous pigs. Body length is one of the external traits that affect production performance, and fat deposition influences meat quality. However, the genetic characteristics of LI pigs have not yet been systematically uncovered. Here, the genomic information from 891 individuals of LI pigs, commercial pigs, and other Chinese indigenous pigs was used to analyze the breed characteristics of the LI pig with runs of homozygosity, haplotype, and FST selection signatures. The results showed the growth traits-related genes (i.e., NR6A1 and PAPPA2) and the fatness traits-related gene (i.e., PIK3C2B) were the promising candidate genes that closely related to the characteristics of LI pigs. In addition, the protein–protein interaction network revealed the potential interactions between the promising candidate genes and the FASN gene. The RNA expression data from FarmGTEx indicated that the RNA expression levels of NR6A1, PAPPA2, PIK3C2B, and FASN were highly correlated in the ileum. This study provides valuable molecular insights into the mechanisms that affect pig body length and fat deposition, which can be used in the further breeding process to improve meat quality and commercial profitability.
Effect of Rice Straw and Stubble Burning on Soil Physicochemical Properties and Bacterial Communities in Central Thailand
Authors: Arunrat Noppol , Sereenonchai Sukanya , Sansupa Chakriya , Kongsurakan Praeploy , Hatano Ryusuke
Published: March 2023

Rice straw and stubble burning is widely practiced to clear fields for new crops. However, questions remain about the effects of fire on soil bacterial communities and soil properties in paddy fields. Here, five adjacent farmed fields were investigated in central Thailand to assess changes in soil bacterial communities and soil properties after burning. Samples of soil prior to burning, immediately after burning, and 1 year after burning were obtained from depths of 0 to 5 cm. The results showed that the pH, electrical conductivity, NH4-N, total nitrogen, and soil nutrients (available P, K, Ca, and Mg) significantly increased immediately after burning due to an increased ash content in the soil, whereas NO3-N decreased significantly. However, these values returned to the initial values. Chloroflexi were the dominant bacteria, followed by Actinobacteria and Proteobacteria. At 1 year after burning, Chloroflexi abundance decreased remarkably, whereas Actinobacteria, Proteobacteria, Verrucomicrobia, and Gemmatimonadetes abundances significantly increased. Bacillus, HSB OF53-F07, Conexibacter, and Acidothermus abundances increased immediately after burning, but were lower 1 year after burning. These bacteria may be highly resistant to heat, but grow slowly. Anaeromyxobacter and Candidatus Udaeobacter dominated 1 year after burning, most likely because of their rapid growth and the fact that they occupy areas with increased soil nutrient levels after fires. Amidase, cellulase, and chitinase levels increased with increased organic matter levels, whereas β-glucosidase, chitinase, and urease levels positively correlated with the soil total nitrogen level. Although clay and soil moisture strongly correlated with the soil bacterial community’s composition, negative correlations were found for β-glucosidase, chitinase, and urease. In this study, rice straw and standing stubble were burnt under high soil moisture and within a very short time, suggesting that the fire was not severe enough to raise the soil temperature and change the soil microbial community immediately after burning. However, changes in soil properties due to ash significantly increased the diversity indices, which was noticeable 1 year after burning.
Strategies for Improving Vascularization in Kidney Organoids: A Review of Current Trends
Authors: Konoe Ran , Morizane Ryuji
Published: March 2023

Kidney organoids possess the potential to revolutionize the treatment of renal diseases. However, their growth and maturation are impeded by insufficient growth of blood vessels. Through a PubMed search, we have identified 34 studies that attempted to address this challenge. Researchers are exploring various approaches including animal transplantation, organ-on-chips, and extracellular matrices (ECMs). The most prevalent method to promote the maturation and vascularization of organoids involves transplanting them into animals for in vivo culture, creating an optimal environment for organoid growth and the development of a chimeric vessel network between the host and organoids. Organ-on-chip technology permits the in vitro culture of organoids, enabling researchers to manipulate the microenvironment and investigate the key factors that influence organoid development. Lastly, ECMs have been discovered to aid the formation of blood vessels during organoid differentiation. ECMs from animal tissue have been particularly successful, although the underlying mechanisms require further research. Future research building upon these recent studies may enable the generation of functional kidney tissues for replacement therapies.
Functional Genome Analysis for Immune Cells Provides Clues for Stratification of Systemic Lupus Erythematosus
Authors: Fujio Keishi
Published: March 2023

Systemic lupus erythematosus (SLE) is caused by a combination of genetic and environmental factors. Recently, analysis of a functional genome database of genetic polymorphisms and transcriptomic data from various immune cell subsets revealed the importance of the oxidative phosphorylation (OXPHOS) pathway in the pathogenesis of SLE. In particular, activation of the OXPHOS pathway is persistent in inactive SLE, and this activation is associated with organ damage. The finding that hydroxychloroquine (HCQ), which improves the prognosis of SLE, targets toll-like receptor (TLR) signaling upstream of OXPHOS suggests the clinical importance of this pathway. IRF5 and SLC15A4, which are regulated by polymorphisms associated with SLE susceptibility, are functionally associated with OXPHOS as well as blood interferon activity and metabolome. Future analyses of OXPHOS-associated disease-susceptibility polymorphisms, gene expression, and protein function may be useful for risk stratification of SLE.
Regulation of the SUV39H Family Methyltransferases: Insights from Fission Yeast
Authors: Nakamura Rinko , Nakayama Jun-ichi
Published: March 2023

Histones, which make up nucleosomes, undergo various post-translational modifications, such as acetylation, methylation, phosphorylation, and ubiquitylation. In particular, histone methylation serves different cellular functions depending on the location of the amino acid residue undergoing modification, and is tightly regulated by the antagonistic action of histone methyltransferases and demethylases. The SUV39H family of histone methyltransferases (HMTases) are evolutionarily conserved from fission yeast to humans and play an important role in the formation of higher-order chromatin structures called heterochromatin. The SUV39H family HMTases catalyzes the methylation of histone H3 lysine 9 (H3K9), and this modification serves as a binding site for heterochromatin protein 1 (HP1) to form a higher-order chromatin structure. While the regulatory mechanism of this family of enzymes has been extensively studied in various model organisms, Clr4, a fission yeast homologue, has made an important contribution. In this review, we focus on the regulatory mechanisms of the SUV39H family of proteins, in particular, the molecular mechanisms revealed by the studies of the fission yeast Clr4, and discuss their generality in comparison to other HMTases.
Endogenous Glycoprotein GPM6a Is Involved in Neurite Outgrowth in Rat Dorsal Root Ganglion Neurons
Authors: Aparicio Gabriela I. , León Antonella , Gutiérrez Fuster Rocío , Ravenscraft Baylen , Monje Paula V. , Scorticati Camila
Published: March 2023

The peripheral nervous system (PNS) has a unique ability for self-repair. Dorsal root ganglion (DRG) neurons regulate the expression of different molecules, such as neurotrophins and their receptors, to promote axon regeneration after injury. However, the molecular players driving axonal regrowth need to be better defined. The membrane glycoprotein GPM6a has been described to contribute to neuronal development and structural plasticity in central-nervous-system neurons. Recent evidence indicates that GPM6a interacts with molecules from the PNS, although its role in DRG neurons remains unknown. Here, we characterized the expression of GPM6a in embryonic and adult DRGs by combining analysis of public RNA-seq datasets with immunochemical approaches utilizing cultures of rat DRG explants and dissociated neuronal cells. M6a was detected on the cell surfaces of DRG neurons throughout development. Moreover, GPM6a was required for DRG neurite elongation in vitro. In summary, we provide evidence on GPM6a being present in DRG neurons for the first time. Data from our functional experiments support the idea that GPM6a could contribute to axon regeneration in the PNS.
Triphenyltin(IV) Carboxylates with Exceptionally High Cytotoxicity against Different Breast Cancer Cell Lines
Authors: Predarska Ivana , Saoud Mohamad , Morgan Ibrahim , Lönnecke Peter , Kaluđerović Goran N. , Hey-Hawkins Evamarie
Published: March 2023

Organotin(IV) carboxylates are a class of compounds explored as alternatives to platinum-containing chemotherapeutics due to propitious in vitro and in vivo results, and distinct mechanisms of action. In this study, triphenyltin(IV) derivatives of non-steroidal anti-inflammatory drugs (indomethacin (HIND) and flurbiprofen (HFBP)) are synthesized and characterized, namely [Ph3Sn(IND)] and [Ph3Sn(FBP)]. The crystal structure of [Ph3Sn(IND)] reveals penta-coordination of the central tin atom with almost perfect trigonal bipyramidal geometry with phenyl groups in the equatorial positions and two axially located oxygen atoms belonging to two distinct carboxylato (IND) ligands leading to formation of a coordination polymer with bridging carboxylato ligands. Employing MTT and CV probes, the antiproliferative effects of both organotin(IV) complexes, indomethacin, and flurbiprofen were evaluated on different breast carcinoma cells (BT-474, MDA-MB-468, MCF-7 and HCC1937). [Ph3Sn(IND)] and [Ph3Sn(FBP)], unlike the inactive ligand precursors, were found extremely active towards all examined cell lines, demonstrating IC50 concentrations in the range of 0.076–0.200 µM. Flow cytometry was employed to examine the mode of action showing that neither apoptotic nor autophagic mechanisms were triggered within the first 48 h of treatment. However, both tin(IV) complexes inhibited cell proliferation potentially related to the dramatic reduction in NO production, resulting from downregulation of nitric oxide synthase (iNOS) enzyme expression.
A Systematic Review on Dementia and Translocator Protein (TSPO): When Nuclear Medicine Highlights an Underlying Expression
Authors: Conte Miriam , De Feo Maria Silvia , Corica Ferdinando , Gorica Joana , Sidrak Marko Magdi Abdou , De Cristofaro Flaminia , Filippi Luca , Ricci Maria , De Vincentis Giuseppe , Frantellizzi Viviana
Published: March 2023

Background: Translocator protein (TSPO) is a neuroinflammation hallmark. Different TSPO affinity compounds have been produced and over time, the techniques of radiolabeling have been refined. The aim of this systematic review is to summarize the development of new radiotracers for dementia and neuroinflammation imaging. Methods: An online search of the literature was conducted in the PubMed, Scopus, Medline, Cochrane Library, and Web of Science databases, selecting published studies from January 2004 to December 2022. The accepted studies considered the synthesis of TSPO tracers for nuclear medicine imaging in dementia and neuroinflammation. Results: A total of 50 articles was identified. Twelve papers were selected from the included studies’ bibliographies and 34 were excluded. Thus, 28 articles were ultimately selected for quality assessment. Conclusion: Huge efforts in developing specific and stable tracers for PET/SPECT imaging have been made. The long half-life of 18F makes this isotope a preferable choice to 11C. An emerging limitation to this however is that neuroinflammation involves all of the brain which inhibits the possibility of detecting a slight inflammation status change in patients. A partial solution to this is using the cerebellum as a reference region and developing higher TSPO affinity tracers. Moreover, it is necessary to consider the presence of distomers and racemic compounds interfering with pharmacological tracers’ effects and increasing the noise ratio in images.
NMR-Based Metabolomics to Analyze the Effects of a Series of Monoamine Oxidases-B Inhibitors on U251 Cells
Authors: Guo Zili , Gu Jinping , Zhang Miao , Su Feng , Su Weike , Xie Yuanyuan
Published: March 2023

Alzheimer’s disease (AD) is a typical progressive neurodegenerative disorder, and with multiple possible pathogenesis. Among them, coumarin derivatives could be used as potential drugs as monoamine oxidase-B (MAO-B) inhibitors. Our lab has designed and synthesized coumarin derivatives based on MAO-B. In this study, we used nuclear magnetic resonance (NMR)-based metabolomics to accelerate the pharmacodynamic evaluation of candidate drugs for coumarin derivative research and development. We detailed alterations in the metabolic profiles of nerve cells with various coumarin derivatives. In total, we identified 58 metabolites and calculated their relative concentrations in U251 cells. In the meantime, the outcomes of multivariate statistical analysis showed that when twelve coumarin compounds were treated with U251cells, the metabolic phenotypes were distinct. In the treatment of different coumarin derivatives, there several metabolic pathways changed, including aminoacyl-tRNA biosynthesis, D-glutamine and D-glutamate metabolism, glycine, serine and threonine metabolism, taurine and hypotaurine metabolism, arginine biosynthesis, alanine, aspartate and glutamate metabolism, phenylalanine, tyrosine and tryptophan biosynthesis, glutathione metabolism and valine, leucine and isoleucine biosynthesis. Our work documented how our coumarin derivatives affected the metabolic phenotype of nerve cells in vitro. We believe that these NMR-based metabolomics might accelerate the process of drug research in vitro and in vivo.
Recent Progress in Development and Application of DNA, Protein, Peptide, Glycan, Antibody, and Aptamer Microarrays
Authors: Aparna G. M. , Tetala Kishore K. R.
Published: March 2023

Microarrays are one of the trailblazing technologies of the last two decades and have displayed their importance in all the associated fields of biology. They are widely explored to screen, identify, and gain insights on the characteristics traits of biomolecules (individually or in complex solutions). A wide variety of biomolecule-based microarrays (DNA microarrays, protein microarrays, glycan microarrays, antibody microarrays, peptide microarrays, and aptamer microarrays) are either commercially available or fabricated in-house by researchers to explore diverse substrates, surface coating, immobilization techniques, and detection strategies. The aim of this review is to explore the development of biomolecule-based microarray applications since 2018 onwards. Here, we have covered a different array of printing strategies, substrate surface modification, biomolecule immobilization strategies, detection techniques, and biomolecule-based microarray applications. The period of 2018–2022 focused on using biomolecule-based microarrays for the identification of biomarkers, detection of viruses, differentiation of multiple pathogens, etc. A few potential future applications of microarrays could be for personalized medicine, vaccine candidate screening, toxin screening, pathogen identification, and posttranslational modifications.
Colostrum and Lactoferrin Protect against Side Effects of Therapy with Antibiotics, Anti-inflammatory Drugs and Steroids, and Psychophysical Stress: A Comprehensive Review
Authors: Artym Jolanta , Zimecki Michał
Published: March 2023

In this article, we review the benefits of applying bovine colostrum (BC) and lactoferrin (LF) in animal models and clinical trials that include corticosteroid application and psychic stress, treatment with non-steroid anti-inflammatory drugs (NSAIDs) and antibiotics. A majority of the reported investigations were performed with native bovine or recombinant human LF, applied alone or in combination with probiotics, as nutraceutics and diet supplements. Apart from reducing adverse side effects of the applied therapeutics, BC and LF augmented their efficacy and improved the wellness of patients. In conclusion, LF and complete native colostrum, preferably administered with probiotic bacteria, are highly recommended for inclusion in therapeutic protocols in NSAIDs and corticosteroid anti-inflammatory, as well as antibiotic, therapies. These colostrum-based products can also be of value for individuals subjected to prolonged psychophysical stress (mediated by endogenous corticosteroids), especially at high ambient temperatures (soldiers and emergency services), as well as physically active people and training athletes. They are also recommended for patients during recovery from trauma and surgery, which are always associated with severe psychophysical stress.
Immune Checkpoint Inhibitors in Hepatocellular Carcinoma: Current Strategies and Biomarkers Predicting Response and/or Resistance
Authors: Pelizzaro Filippo , Farinati Fabio , Trevisani Franco
Published: March 2023

In recent years, immune checkpoint inhibitors (ICIs) have revolutionized the treatment of patients with hepatocellular carcinoma (HCC). Following the positive results of the IMbrave150 trial, the combination of atezolizumab (an anti-PD-L1 antibody) and bevacizumab (an anti-VEGF antibody) became the standard of care frontline treatment for patients with advanced stage HCC. Several other trials evaluated immunotherapy in HCC, demonstrating that ICIs-based regimens are currently the most effective treatment strategies and expanding the therapeutic possibilities. Despite the unprecedent rates of objective tumor response, not all patients benefit from treatment with ICIs. Therefore, in order to select the appropriate therapy as well as to correctly allocate medical resources and avoid unnecessary treatment-related toxicities, there is great interest in identifying the predictive biomarkers of response or resistance to immunotherapy-based regimens. Immune classes of HCC, genomic signatures, anti-drug antibodies, and patient-related factors (e.g., etiology of liver disease, gut microbiota diversity) have been associated to the response to ICIs, but none of the proposed biomarkers have been translated into clinical practice so far. Considering the crucial importance of this topic, in this review we aim to summarize the available data on tumor and clinical features associated with the response or resistance of HCC to immunotherapies.
Efficacy, Safety and Feasibility of Superior Vena Cava Isolation in Patients Undergoing Atrial Fibrillation Catheter Ablation: An Up-to-Date Review
Authors: Vrachatis Dimitrios A. , Papathanasiou Konstantinos A. , Kossyvakis Charalampos , Giotaki Sotiria G. , Deftereos Gerasimos , Kousta Maria S. , Iliodromitis Konstantinos E. , Bogossian Harilaos , Avramides Dimitrios , Giannopoulos George , Lambadiari Vaia , Siasos Gerasimos , Papaioannou Theodore G. , Deftereos Spyridon
Published: March 2023

Pulmonary vein isolation (PVI) is the cornerstone in atrial fibrillation (AF) ablation; yet, the role of arrhythmogenic superior vena cava (SVC) is increasingly recognized and different ablation strategies have been employed in this context. SVC can act as a trigger or perpetuator of AF, and its significance might be more pronounced in patients undergoing repeated ablation. Several cohorts have examined efficacy, safety and feasibility of SVC isolation (SVCI) among AF patients. The majority of these studies explored as-needed SVCI during index PVI, and only a minority of them included repeated ablation subjects and non-radiofrequency energy sources. Studies of heterogeneous design and intent have explored both empiric and as-needed SVCI on top of PVI and reported inconclusive results. These studies have largely failed to demonstrate any clinical benefit in terms of arrhythmia recurrence, although safety and feasibility are undisputable. Mixed population demographics, small number of enrollees and short follow-up are the main limitations. Procedural and safety data are comparable between empiric SVCI and as-needed SVCI, and some studies suggested that empiric SVCI might be associated with reduced AF recurrences in paroxysmal AF patients. Currently, no study has compared different ablation energy sources in the setting of SVCI, and no randomized study has addressed as-needed SVCI on top of PVI. Furthermore, data regarding cryoablation are still in their infancy, and regarding SVCI in patients with cardiac devices more safety and feasibility data are needed. PVI non-responders, patients undergoing repeated ablation and patients with long SVC sleeves could be potential candidates for SVCI, especially via an empiric approach. Although many technical aspects remain unsettled, the major question to answer is which clinical phenotype of AF patients might benefit from SVCI?
The Effect of the Sodium—Glucose Cotransporter Inhibitor on Cognition and Metabolic Parameters in a Rat Model of Sporadic Alzheimer’s Disease
Authors: Osmanović Barilar Jelena , Babić Perhoč Ana , Knezović Ana , Homolak Jan , Virag Davor , Šalković-Petrišić Melita
Published: March 2023

Type 2 diabetes mellitus increases the risk of sporadic Alzheimer’s disease (sAD), and antidiabetic drugs, including the sodium–glucose cotransporter inhibitors (SGLTI), are being studied as possible sAD therapy. We have explored whether the SGLTI phloridzin may influence metabolic and cognitive parameters in a rat model of sAD. Adult male Wistar rats were randomized to a control (CTR), an sAD-model group induced by intracerebroventricular streptozotocin (STZ-icv; 3 mg/kg), a CTR+SGLTI, or an STZ-icv+SGLTI group. Two-month-long oral (gavage) SGLTI treatment (10 mg/kg) was initiated 1 month after STZ-icv and cognitive performance tested prior to sacrifice. SGLTI treatment significantly decreased plasma glucose levels only in the CTR group and failed to correct STZ-icv-induced cognitive deficit. In both the CTR and STZ-icv groups, SGLTI treatment diminished weight gain, decreased amyloid beta (Aβ) 1-42 in duodenum, and decreased the plasma levels of total glucagon-like peptide 1 (GLP-1), while the levels of active GLP-1, as well as both total and active glucose-dependent insulinotropic polypeptide, remained unchanged, compared to their respective controls. The increment in GLP-1 levels in the cerebrospinal fluid and its effect on Aβ 1-42 in duodenum could be one of the molecular mechanisms by which SGLTIs indirectly induce pleiotropic beneficial effects.
The Association of Leptin with Left Ventricular Hypertrophy in End-Stage Kidney Disease Patients on Dialysis
Authors: Coimbra Susana , Catarino Cristina , Sameiro Faria Maria , Nunes José Pedro L. , Rocha Susana , Valente Maria João , Rocha-Pereira Petronila , Bronze-da-Rocha Elsa , Bettencourt Nuno , Beco Ana , Marques Sofia Homem de Melo , Oliveira José Gerardo , Madureira José , Fernandes João Carlos , Miranda Vasco , Belo Luís , Santos-Silva Alice
Published: March 2023

Left ventricular hypertrophy (LVH) is a common cardiovascular complication in end-stage kidney disease (ESKD) patients. We aimed at studying the association of LVH with adiponectin and leptin levels, cardiovascular stress/injury biomarkers and nutritional status in these patients. We evaluated the LV mass (LVM) and calculated the LVM index (LVMI) in 196 ESKD patients on dialysis; the levels of hemoglobin, calcium, phosphorus, parathyroid hormone, albumin, adiponectin, leptin, N-terminal pro B-type natriuretic peptide (NT-proBNP) and growth differentiation factor (GDF)-15 were analyzed. ESKD patients with LVH (n = 131) presented higher NT-proBNP and GDF-15, lower hemoglobin and, after adjustment for gender, lower leptin levels compared with non-LVH patients. LVH females also showed lower leptin than the non-LVH female group. In the LVH group, LVMI presented a negative correlation with leptin and a positive correlation with NT-proBNP. Leptin emerged as an independent determinant of LVMI in both groups, and NT-proBNP in the LVH group. Low hemoglobin and leptin and increased calcium, NT-proBNP and dialysis vintage are associated with an increased risk of developing LVH. In ESKD patients on dialysis, LVH is associated with lower leptin values (especially in women), which are negatively correlated with LVMI, and with higher levels of biomarkers of myocardial stress/injury. Leptin and NT-proBNP appear as independent determinants of LVMI; dialysis vintage, hemoglobin, calcium, NT-proBNP and leptin emerged as predicting markers for LVH development. Further studies are needed to better understand the role of leptin in LVH in ESKD patients.
Differences in the Profile of Circulating Immune Cell Subsets in Males with Type 2 Cardiorenal Syndrome versus CKD Patients without Established Cardiovascular Disease
Authors: Duni Anila , Kitsos Athanasios , Bechlioulis Aris , Markopoulos Georgios S. , Lakkas Lampros , Baxevanos Gerasimos , Mitsis Michail , Vartholomatos George , Naka Katerina K. , Dounousi Evangelia
Published: March 2023

Maladaptive activation of the immune system plays a key role in the pathogenesis of chronic kidney disease (CKD). Our aim was to investigate differences in circulating immune cells between type 2 cardiorenal syndrome (CRS-2) patients and CKD patients without cardiovascular disease (CVD). CRS-2 patients were prospectively followed up, with the primary endpoint being all-cause and cardiovascular mortality. Method: A total of 39 stable males with CRS-2 and 24 male CKD patients matched for eGFR (CKD-EPI) were enrolled. A selected panel of immune cell subsets was measured by flow cytometry. Results: Compared to CKD patients, CRS-2 patients displayed higher levels of proinflammatory CD14++CD16+ monocytes (p = 0.04) and T regulatory cells (Tregs) (p = 0.03), lower lymphocytes (p = 0.04), and lower natural killer cells (p = 0.001). Decreased lymphocytes, T-lymphocytes, CD4+ T-cells, CD8+ T-cells, Tregs, and increased CD14++CD16+ monocytes were associated with mortality at a median follow-up of 30 months (p < 0.05 for all). In a multivariate model including all six immune cell subsets, only CD4+ T-lymphocytes remained independent predictors of mortality (OR 0.66; 95% CI 0.50–0.87; p = 0.004). Conclusion: Patients with CRS-2 exhibit alterations in immune cell profile compared to CKD patients of similar kidney function but without CVD. In the CRS-2 cohort, CD4+ T-lymphocytes independently predicted fatal cardiovascular events.
Development of a Microfluidic Chip Powered by EWOD for In Vitro Manipulation of Bovine Embryos
Authors: Karcz Adriana , Van Soom Ann , Smits Katrien , Van Vlierberghe Sandra , Verplancke Rik , Pascottini Osvaldo Bogado , Van den Abbeel Etienne , Vanfleteren Jan
Published: March 2023

Digital microfluidics (DMF) holds great potential for the alleviation of laboratory procedures in assisted reproductive technologies (ARTs). The electrowetting on dielectric (EWOD) technology provides dynamic culture conditions in vitro that may better mimic the natural embryo microenvironment. Thus far, EWOD microdevices have been proposed for in vitro gamete and embryo handling in mice and for analyzing the human embryo secretome. This article presents the development of the first microfluidic chip utilizing EWOD technology designed for the manipulation of bovine embryos in vitro. The prototype sustains the cell cycles of embryos manipulated individually on the chips during in vitro culture (IVC). Challenges related to the chip fabrication as well as to its application during bovine embryo IVC in accordance with the adapted on-chip protocol are thoroughly discussed, and future directions for DMF in ARTs are indicated.
Aggregation-Induced Emission Luminogen-Encapsulated Fluorescent Hydrogels Enable Rapid and Sensitive Quantitative Detection of Mercury Ions
Authors: Zhan Wenchao , Su Yu , Chen Xirui , Xiong Hanpeng , Wei Xiaxia , Huang Xiaolin , Xiong Yonghua
Published: March 2023

Hg2+ contamination in sewage can accumulate in the human body through the food chains and cause health problems. Herein, a novel aggregation-induced emission luminogen (AIEgen)-encapsulated hydrogel probe for ultrasensitive detection of Hg2+ was developed by integrating hydrophobic AIEgens into hydrophilic hydrogels. The working mechanism of the multi-fluorophore AIEgens (TPE-RB) is based on the dark through-bond energy transfer strategy, by which the energy of the dark tetraphenylethene (TPE) derivative is completely transferred to the rhodamine-B derivative (RB), thus resulting in intense photoluminescent intensity. The spatial networks of the supporting hydrogels further provide fixing sites for the hydrophobic AIEgens to enlarge accessible reaction surface for hydrosoluble Hg2+, as well create a confined reaction space to facilitate the interaction between the AIEgens and the Hg2+. In addition, the abundant hydrogen bonds of hydrogels further promote the Hg2+ adsorption, which significantly improves the sensitivity. The integrated TPE-RB-encapsulated hydrogels (TR hydrogels) present excellent specificity, accuracy and precision in Hg2+ detection in real-world water samples, with a 4-fold higher sensitivity compared to that of pure AIEgen probes. The as-developed TR hydrogel-based chemosensor holds promising potential as a robust, fast and effective bifunctional platform for the sensitive detection of Hg2+.
miRNAs as Predictors of Barrier Integrity
Authors: Bovari-Biri Judit , Garai Kitti , Banfai Krisztina , Csongei Veronika , Pongracz Judit E.
Published: March 2023

The human body has several barriers that protect its integrity and shield it from mechanical, chemical, and microbial harm. The various barriers include the skin, intestinal and respiratory epithelia, blood–brain barrier (BBB), and immune system. In the present review, the focus is on the physical barriers that are formed by cell layers. The barrier function is influenced by the molecular microenvironment of the cells forming the barriers. The integrity of the barrier cell layers is maintained by the intricate balance of protein expression that is partly regulated by microRNAs (miRNAs) both in the intracellular space and the extracellular microenvironment. The detection of changes in miRNA patterns has become a major focus of diagnostic, prognostic, and disease progression, as well as therapy-response, markers using a great variety of detection systems in recent years. In the present review, we highlight the importance of liquid biopsies in assessing barrier integrity and challenges in differential miRNA detection.
Parkinson’s Disease Diagnosis Using Laplacian Score, Gaussian Process Regression and Self-Organizing Maps
Authors: Nilashi Mehrbakhsh , Abumalloh Rabab Ali , Alyami Sultan , Alghamdi Abdullah , Alrizq Mesfer
Published: March 2023

Parkinson’s disease (PD) is a complex degenerative brain disease that affects nerve cells in the brain responsible for body movement. Machine learning is widely used to track the progression of PD in its early stages by predicting unified Parkinson’s disease rating scale (UPDRS) scores. In this paper, we aim to develop a new method for PD diagnosis with the aid of supervised and unsupervised learning techniques. Our method is developed using the Laplacian score, Gaussian process regression (GPR) and self-organizing maps (SOM). SOM is used to segment the data to handle large PD datasets. The models are then constructed using GPR for the prediction of the UPDRS scores. To select the important features in the PD dataset, we use the Laplacian score in the method. We evaluate the developed approach on a PD dataset including a set of speech signals. The method was evaluated through root-mean-square error (RMSE) and adjusted R-squared (adjusted R²). Our findings reveal that the proposed method is efficient in the prediction of UPDRS scores through a set of speech signals (dysphonia measures). The method evaluation showed that SOM combined with the Laplacian score and Gaussian process regression with the exponential kernel provides the best results for R-squared (Motor-UPDRS = 0.9489; Total-UPDRS = 0.9516) and RMSE (Motor-UPDRS = 0.5144; Total-UPDRS = 0.5105) in predicting UPDRS compared with the other kernels in Gaussian process regression.
Cyclin-Dependent Kinase Inhibitor 2A/B Homozygous Deletion Prediction and Survival Analysis
Authors: Yang Jing , Li Lei , Luo Tao , Nie Chengsong , Fan Rui , Li Deqiang , Yang Rui , Zhou Changru , Li Qian , Hu Xiaofei , Chen Wei
Published: March 2023

Cyclin-Dependent Kinase Inhibitor 2A/B (CDKN2A/B) homozygous deletion was a significant prognostic factor for gliomas and affected the treatment strategy. However, the radiomic features of CDKN2A/B homozygous deletion in gliomas have not been developed, and whether the radiomic features and molecular subgroups can provide prognostic value in low-grade gliomas (LGGs) has yet to be studied. Thus, this study aimed to develop a predictive model of CDKN2A/B in gliomas and investigate the prognostic value of this biomarker and radiomic features in isocitrate dehydrogenase (IDH)-mutant LGGs. First, we developed the predictive model of CDKN2A/B homozygous deletion in 292 patients. The results revealed that radiomic features predict CDKN2A/B homozygous deletion with high accuracy and reliability. Subsequently, the prognostic survival models of 104 patients (IDH-mutant LGGs) were established, which provided an essential value for prognostic evaluation and indicated that CDKN2A/B homozygous deletion can be used as an independent predictor of prognosis in LGGs.