bluuebunny/crossref_metadata_2025 huggingface dataset:
Eosinophilic Chronic Rhinosinusitis and Pathogenic Role of Protease
Authors: Kim Jaehyeong , Kwak Sooun , Lee Juhyun , Park Il-Ho , Lee Seung Hoon , Shin Jae Min , Kim Tae Hoon
Published: December 2023

Chronic rhinosinusitis (CRS) is an inflammation of the nasal and paranasal sinus mucosa, and eosinophilic CRS (eCRS) is a subtype characterized by significant eosinophil infiltration and immune response by T-helper-2 cells. The pathogenesis of eCRS is heterogeneous and involves various environmental and host factors. Proteases from external sources, such as mites, fungi, and bacteria, have been implicated in inducing type 2 inflammatory reactions. The balance between these proteases and endogenous protease inhibitors (EPIs) is considered important, and their imbalance can potentially lead to type 2 inflammatory reactions, such as eCRS. In this review, we discuss various mechanisms by which exogenous proteases influence eCRS and highlight the emerging role of endogenous protease inhibitors in eCRS pathogenesis.
Minding the Gap: Exploring Neuroinflammatory and Microglial Sex Differences in Alzheimer’s Disease
Authors: Reed Erin G. , Keller-Norrell Phaedra R.
Published: December 2023

Research into Alzheimer’s Disease (AD) describes a link between AD and the resident immune cells of the brain, the microglia. Further, this suspected link is thought to have underlying sex effects, although the mechanisms of these effects are only just beginning to be understood. Many of these insights are the result of policies put in place by funding agencies such as the National Institutes of Health (NIH) to consider sex as a biological variable (SABV) and the move towards precision medicine due to continued lackluster therapeutic options. The purpose of this review is to provide an updated assessment of the current research that summarizes sex differences and the research pertaining to microglia and their varied responses in AD.
Oncolytic Viruses in the Era of Omics, Computational Technologies, and Modeling: Thesis, Antithesis, and Synthesis
Authors: Menotti Laura , Vannini Andrea
Published: December 2023

Oncolytic viruses (OVs) are the frontier therapy for refractory cancers, especially in integration with immunomodulation strategies. In cancer immunovirotherapy, the many available “omics” and systems biology technologies generate at a fast pace a challenging huge amount of data, where apparently clashing information mirrors the complexity of individual clinical situations and OV used. In this review, we present and discuss how currently big data analysis, on one hand and, on the other, simulation, modeling, and computational technologies, provide invaluable support to interpret and integrate “omic” information and drive novel synthetic biology and personalized OV engineering approaches for effective immunovirotherapy. Altogether, these tools, possibly aided in the future by artificial intelligence as well, will allow for the blending of the information into OV recombinants able to achieve tumor clearance in a patient-tailored way. Various endeavors to the envisioned “synthesis” of turning OVs into personalized theranostic agents are presented.
Targeting Fatty Acid Amide Hydrolase Counteracts the Epithelial-to-Mesenchymal Transition in Keratinocyte-Derived Tumors
Authors: Kovacs Daniela , Flori Enrica , Bastonini Emanuela , Mosca Sarah , Migliano Emilia , Cota Carlo , Zaccarini Marco , Briganti Stefania , Cardinali Giorgia
Published: December 2023

The endocannabinoid system regulates physiological processes, and the modulation of endogenous endocannabinoid (eCB) levels is an attractive tool to contrast the development of pathological skin conditions including cancers. Inhibiting FAAH (fatty acid amide hydrolase), the degradation enzyme of the endocannabinoid anandamide (AEA) leads to the increase in AEA levels, thus enhancing its biological effects. Here, we evaluated the anticancer property of the FAAH inhibitor URB597, investigating its potential to counteract epithelial-to-mesenchymal transition (EMT), a process crucially involved in tumor progression. The effects of the compound were determined in primary human keratinocytes, ex vivo skin explants, and the squamous carcinoma cell line A431. Our results demonstrate that URB597 is able to hinder the EMT process by downregulating mesenchymal markers and reducing migratory potential. These effects are associated with the dampening of the AKT/STAT3 signal pathways and reduced release of pro-inflammatory cytokines and tumorigenic lipid species. The ability of URB597 to contrast the EMT process provides insight into effective approaches that may also include the use of FAAH inhibitors for the treatment of skin cancers.
Improved Glycaemic Control and Nephroprotective Effects of Empagliflozin and Paricalcitol Co-Therapy in Mice with Type 2 Diabetes Mellitus
Authors: Mujalli Abdulrahman , Farrash Wesam F. , Obaid Ahmad A. , Khan Anmar A. , Almaimani Riyad A. , Idris Shakir , Elzubier Mohamed E. , Khidir Elshiekh Babiker A. , Aslam Akhmed , Minshawi Faisal , Alobaidy Mohammad A. , Alharbi Adel B. , Almasmoum Hussain A. , Ghaith Mazen , Alqethami Khalid , Refaat Bassem
Published: December 2023

Herein, we measured the antidiabetic and nephroprotective effects of the sodium–glucose cotransporter-2 inhibitor (empagliflozin; SGLT2i) and synthetic active vitamin D (paricalcitol; Pcal) mono- and co-therapy against diabetic nephropathy (DN). Fifty mice were assigned into negative (NC) and positive (PC) control, SGLT2i, Pcal, and SGLT2i+Pcal groups. Following establishment of DN, SGLT2i (5.1 mg/kg/day) and/or Pcal (0.5 µg/kg/day) were used in the designated groups (5 times/week/day). DN was affirmed in the PC group by hyperglycaemia, dyslipidaemia, polyuria, proteinuria, elevated urine protein/creatinine ratio, and abnormal renal biochemical parameters. Renal SREBP-1 lipogenic molecule, adipokines (leptin/resistin), pro-oxidant (MDA/H2O2), pro-inflammatory (IL1β/IL6/TNF-α), tissue damage (iNOS/TGF-β1/NGAL/KIM-1), and apoptosis (TUNEL/Caspase-3) markers also increased in the PC group. In contrast, renal lipolytic (PPARα/PPARγ), adiponectin, antioxidant (GSH/GPx1/SOD1/CAT), and anti-inflammatory (IL10) molecules decreased in the PC group. Both monotherapies increased insulin levels and mitigated hyperglycaemia, dyslipidaemia, renal and urine biochemical profiles alongside renal lipid regulatory molecules, inflammation, and oxidative stress. While SGLT2i monotherapy showed superior effects to Pcal, their combination demonstrated enhanced remedial actions related to metabolic control alongside renal oxidative stress, inflammation, and apoptosis. In conclusion, SGLT2i was better than Pcal monotherapy against DN, and their combination revealed better nephroprotection, plausibly by enhanced glycaemic control with boosted renal antioxidative and anti-inflammatory mechanisms.
Comprehensive Analysis of NAC Transcription Factors Reveals Their Evolution in Malvales and Functional Characterization of AsNAC019 and AsNAC098 in Aquilaria sinensis
Authors: Yang Zhuo , Mei Wenli , Wang Hao , Zeng Jun , Dai Haofu , Ding Xupo
Published: December 2023

NAC is a class of plant-specific transcription factors that are widely involved in the growth, development and (a)biotic stress response of plants. However, their molecular evolution has not been extensively studied in Malvales, especially in Aquilaria sinensis, a commercial and horticultural crop that produces an aromatic resin named agarwood. In this study, 1502 members of the NAC gene family were identified from the genomes of nine species from Malvales and three model plants. The macroevolutionary analysis revealed that whole genome duplication (WGD) and dispersed duplication (DSD) have shaped the current architectural structure of NAC gene families in Malvales plants. Then, 111 NAC genes were systemically characterized in A. sinensis. The phylogenetic analysis suggests that NAC genes in A. sinensis can be classified into 16 known clusters and four new subfamilies, with each subfamily presenting similar gene structures and conserved motifs. RNA-seq analysis showed that AsNACs presents a broad transcriptional response to the agarwood inducer. The expression patterns of 15 AsNACs in A. sinensis after injury treatment indicated that AsNAC019 and AsNAC098 were positively correlated with the expression patterns of four polyketide synthase (PKS) genes. Additionally, AsNAC019 and AsNAC098 were also found to bind with the AsPKS07 promoter and activate its transcription. This comprehensive analysis provides valuable insights into the molecular evolution of the NAC gene family in Malvales plants and highlights the potential mechanisms of AsNACs for regulating secondary metabolite biosynthesis in A. sinensis, especially for the biosynthesis of 2-(2-phenyl) chromones in agarwood.
Indenopyrene and Blue-Light Co-Exposure Impairs the Tightly Controlled Activation of Xenobiotic Metabolism in Retinal Pigment Epithelial Cells: A Mechanism for Synergistic Toxicity
Authors: Zinflou Corinne , Rochette Patrick J.
Published: December 2023

High energy visible (HEV) blue light is an increasing source of concern for visual health. Polycyclic aromatic hydrocarbons (PAH), a group of compounds found in high concentrations in smokers and polluted environments, accumulate in the retinal pigment epithelium (RPE). HEV absorption by indeno [1,2,3-cd]pyrene (IcdP), a common PAH, synergizes their toxicities and promotes degenerative changes in RPE cells comparable to the ones observed in age-related macular degeneration. In this study, we decipher the processes underlying IcdP and HEV synergic toxicity in human RPE cells. We found that IcdP-HEV toxicity is caused by the loss of the tight coupling between the two metabolic phases ensuring IcdP efficient detoxification. Indeed, IcdP/HEV co-exposure induces an overactivation of key actors in phase I metabolism. IcdP/HEV interaction is also associated with a downregulation of proteins involved in phase II. Our data thus indicate that phase II is hindered in response to co-exposure and that it is insufficient to sustain the enhanced phase I induction. This is reflected by an accelerated production of endogenous reactive oxygen species (ROS) and an increased accumulation of IcdP-related bulky DNA damage. Our work raises the prospect that lifestyle and environmental pollution may be significant modulators of HEV toxicity in the retina.
Classic Galactosemia: Clinical and Computational Characterization of a Novel GALT Missense Variant (p.A303D) and a Literature Review
Authors: Forte Giovanna , Buonadonna Antonia Lucia , Pantaleo Antonino , Fasano Candida , Capodiferro Donatella , Grossi Valentina , Sanese Paola , Cariola Filomena , De Marco Katia , Lepore Signorile Martina , Manghisi Andrea , Guglielmi Anna Filomena , Simonetti Simonetta , Laforgia Nicola , Disciglio Vittoria , Simone Cristiano
Published: December 2023

Classic galactosemia is an autosomal recessive inherited liver disorder of carbohydrate metabolism caused by deficient activity of galactose-1-phosphate uridylyltransferase (GALT). While a galactose-restricted diet is lifesaving, most patients still develop long-term complications. In this study, we report on a two-week-old female patient who is a compound heterozygote for a known pathogenic variant (p.K285N) and a novel missense variant (p.A303D) in the GALT gene. Segregation analysis showed that the patient inherited the p.K285N pathogenic variant from her father and the p.A303D variant from her mother. A bioinformatics analysis to predict the impact of the p.A303D missense variant on the structure and stability of the GALT protein revealed that it may be pathogenic. Based on this finding, we performed a literature review of all GALT missense variants identified in homozygous and compound heterozygous galactosemia patients carrying the p.K285N pathogenic variant to explore their molecular effects on the clinical phenotype of the disease. Our analysis revealed that these missense variants are responsible for a wide range of molecular defects. This study expands the clinical and mutational spectrum in classic galactosemia and reinforces the importance of understanding the molecular consequences of genetic variants to incorporate genetic analysis into clinical care.
Molecular Mechanism of the Asarum–Angelica Drug Pair in the Treatment of Periodontitis Based on Network Pharmacology and Experimental Verification
Authors: Chen Qianyang , Wang Yuhan , Shi Chun , Tong Meichen , Sun Haibo , Dong Ming , Liu Shuo , Wang Lina
Published: December 2023

(1) To examine the potential mechanism of the Asarum–Angelica drug pair against periodontitis and provide an experimental basis for the treatment of periodontitis with herbal medicine. (2) The core components and core targets of the Asarum–Angelica drug pair in the treatment of periodontitis were detected according to network pharmacology methods. Finally, the effect of the Asarum–Angelica drug pair on osteogenic differentiation was observed in mouse embryonic osteoblast precursor cells. (3) According to the results of network pharmacology, there are 10 potential active ingredients in the Asarum–Angelica drug pair, and 44 potential targets were obtained by mapping the targets with periodontitis treatment. Ten potential active ingredients, such as kaempferol and β-sitosterol, may play a role in treating periodontitis. Cell experiments showed that the Asarum–Angelica drug pair can effectively promote the expression of osteoblast markers alkaline phosphatase (ALP), Runt-related Transcription Factor 2 (RUNX2), and BCL2 mRNA and protein in an inflammatory environment (p < 0.05). (4) Network pharmacology effectively analyzed the molecular mechanism of Asarum–Angelica in the treatment of periodontitis, and the Asarum–Angelica drug pair can promote the differentiation of osteoblasts.
Regioselective and Stereoselective Synthesis of Parthenolide Analogs by Acyl Nitroso-Ene Reaction and Their Biological Evaluation against Mycobacterium tuberculosis
Authors: Gioia Bruna , Ruggieri Francesca , Biela Alexandre , Landry Valérie , Roussel Pascal , Piveteau Catherine , Leroux Florence , Hartkoorn Ruben C. , Willand Nicolas
Published: December 2023

Historically, natural products have played a major role in the development of antibiotics. Their complex chemical structures and high polarity give them advantages in the drug discovery process. In the broad range of natural products, sesquiterpene lactones are interesting compounds because of their diverse biological activities, their high-polarity, and sp3-carbon-rich chemical structures. Parthenolide (PTL) is a natural compound isolated from Tanacetum parthenium, of the family of germacranolide-type sesquiterpene lactones. In recent years, parthenolide has been studied for its anti-inflammatory, antimigraine, and anticancer properties. Recently, PTL has shown antibacterial activities, especially against Gram-positive bacteria. However, few studies are available on the potential antitubercular activities of parthenolide and its analogs. It has been demonstrated that parthenolide’s biological effects are linked to the reactivity of α-exo-methylene-γ-butyrolactone, which reacts with cysteine in targeted proteins via a Michael addition. In this work, we describe the ene reaction of acylnitroso intermediates with parthenolide leading to the regioselective and stereoselective synthesis of new derivatives and their biological evaluation. The addition of hydroxycarbamates and hydroxyureas led to original analogs with higher polarity and solubility than parthenolide. Through this synthetic route, the Michael acceptor motif was preserved and is thus believed to be involved in the selective activity against Mycobacterium tuberculosis.
Plasma microRNA Profiling in Type 2 Diabetes Mellitus: A Pilot Study
Authors: Tonyan Ziravard N. , Barbitoff Yury A. , Nasykhova Yulia A. , Danilova Maria M. , Kozyulina Polina Y. , Mikhailova Anastasiia A. , Bulgakova Olga L. , Vlasova Margarita E. , Golovkin Nikita V. , Glotov Andrey S.
Published: December 2023

Type 2 diabetes mellitus (T2D) is a chronic metabolic disease characterized by insulin resistance and β-cell dysfunction and leading to many micro- and macrovascular complications. In this study we analyzed the circulating miRNA expression profiles in plasma samples from 44 patients with T2D and 22 healthy individuals using next generation sequencing and detected 229 differentially expressed miRNAs. An increased level of miR-5588-5p, miR-125b-2-3p, miR-1284, and a reduced level of miR-496 in T2D patients was verified. We also compared the expression landscapes in the same group of patients depending on body mass index and identified differential expression of miR-144-3p and miR-99a-5p in obese individuals. Identification and functional analysis of putative target genes was performed for miR-5588-5p, miR-125b-2-3p, miR-1284, and miR-496, showing chromatin modifying enzymes and apoptotic genes being among the significantly enriched pathways.
Influence of the Core Branching Density on Drug Release from Arborescent Poly(γ-benzyl L-glutamate) End-Grafted with Poly(ethylene oxide)
Authors: Alsehli Mosa , Gauthier Mario
Published: December 2023

Amphiphilic dendritic copolymers of arborescent poly(γ-benzyl L-glutamate) (PBG) of generations G1 and G2, grafted at their chain ends with poly(ethylene oxide) (PEO) segments (PBG-eg-PEO) were synthesized, characterized, and evaluated as nanocarriers for doxorubicin (DOX). The copolymers were designed with hydrophobic PBG cores having three different branching densities and were characterized by proton nuclear magnetic resonance (1H NMR) spectroscopy, size exclusion chromatography (SEC), transmission electron microscopy (TEM), and atomic force microscopy (AFM). Dynamic light scattering (DLS) measurements revealed that these amphiphilic molecules behaved like unimolecular micelles without significant aggregation in aqueous media such as phosphate-buffered saline (PBS), with diameters in the 13–29 nm range depending on the generation number and the core structure. Efficient encapsulation of DOX by these unimolecular micelles was demonstrated with drug loading capacities of up to 11.2 wt%, drug loading efficiencies of up to 67%, and pH-responsive sustained drug release, as determined by UV spectroscopy. The generation number of the copolymers and the branching density of the dendritic PBG core were found to have influenced the encapsulation and release properties of the micelles. Given the tailorable characteristics, good water dispersibility, and biocompatibility of the components used to synthesize the amphiphilic arborescent copolymers, these systems should be useful as robust nanocarriers for a broad range of therapeutic and diagnostic agents.
Exploring the Potential of Ensembles of Deep Learning Networks for Image Segmentation
Authors: Nanni Loris , Lumini Alessandra , Fantozzi Carlo
Published: December 2023

To identify objects in images, a complex set of skills is needed that includes understanding the context and being able to determine the borders of objects. In computer vision, this task is known as semantic segmentation and it involves categorizing each pixel in an image. It is crucial in many real-world situations: for autonomous vehicles, it enables the identification of objects in the surrounding area; in medical diagnosis, it enhances the ability to detect dangerous pathologies early, thereby reducing the risk of serious consequences. In this study, we compare the performance of various ensembles of convolutional and transformer neural networks. Ensembles can be created, e.g., by varying the loss function, the data augmentation method, or the learning rate strategy. Our proposed ensemble, which uses a simple averaging rule, demonstrates exceptional performance across multiple datasets. Notably, compared to prior state-of-the-art methods, our ensemble consistently shows improvements in the well-studied polyp segmentation problem. This problem involves the precise delineation and identification of polyps within medical images, and our approach showcases noteworthy advancements in this domain, obtaining an average Dice of 0.887, which outperforms the current SOTA with an average Dice of 0.885.
DAG-Based Formal Modeling of Spark Applications with MSVL
Authors: Fan Kaixuan , Wang Meng
Published: December 2023

Apache Spark is a high-speed computing engine for processing massive data. With its widespread adoption, there is a growing need to analyze its correctness and temporal properties. However, there is scarce research focused on the verification of temporal properties in Spark programs. To address this gap, we employ the code-level runtime verification tool UMC4M based on the Modeling, Simulation, and Verification Language (MSVL). To this end, a Spark program S has to be translated into an MSVL program M, and the negation of the property P specified by a Propositional Projection Temporal Logic (PPTL) formula that needs to be verified is also translated to an MSVL program M1; then, a new MSVL program “M and M1” can be compiled and executed. Whether program S violates the property P is determined by the existence of an acceptable execution of “M and M1”. Thus, the key issue lies in how to formalize model Spark programs using MSVL programs. We previously proposed a solution to this problem—using the MSVL functions to perform Resilient Distributed Datasets (RDD) operations and converting the Spark program into an MSVL program based on the Directed Acyclic Graph (DAG) of the Spark program. However, we only proposed this idea. Building upon this foundation, we implement the conversion from RDD operations to MSVL functions and propose, as well as implement, the rules for translating Spark programs to MSVL programs based on DAG. We confirm the feasibility of this approach and provide a viable method for verifying the temporal properties of Spark programs. Additionally, an automatic translation tool, S2M, is developed. Finally, a case study is presented to demonstrate this conversion process.
Improving a Deep Learning Model to Accurately Diagnose LVNC
Authors: Barón Jaime Rafael , Bernabé Gregorio , González-Férez Pilar , García José Manuel , Casas Guillem , González-Carrillo Josefa
Published: December 2023

Accurate diagnosis of Left Ventricular Noncompaction Cardiomyopathy (LVNC) is critical for proper patient treatment but remains challenging. This work improves LVNC detection by improving left ventricle segmentation in cardiac MR images. Trabeculated left ventricle indicates LVNC, but automatic segmentation is difficult. We present techniques to improve segmentation and evaluate their impact on LVNC diagnosis. Three main methods are introduced: (1) using full 800 × 800 MR images rather than 512 × 512; (2) a clustering algorithm to eliminate neural network hallucinations; (3) advanced network architectures including Attention U-Net, MSA-UNet, and U-Net++.Experiments utilize cardiac MR datasets from three different hospitals. U-Net++ achieves the best segmentation performance using 800 × 800 images, and it improves the mean segmentation Dice score by 0.02 over the baseline U-Net, the clustering algorithm improves the mean Dice score by 0.06 on the images it affected, and the U-Net++ provides an additional 0.02 mean Dice score over the baseline U-Net. For LVNC diagnosis, U-Net++ achieves 0.896 accuracy, 0.907 precision, and 0.912 F1-score outperforming the baseline U-Net. Proposed techniques enhance LVNC detection, but differences between hospitals reveal problems in improving generalization. This work provides validated methods for precise LVNC diagnosis.
The Influence of Interval Training Combined with Occlusion and Cooling on Selected Indicators of Blood, Muscle Metabolism and Oxidative Stress
Authors: Ptaszek Bartłomiej , Podsiadło Szymon , Czerwińska-Ledwig Olga , Zając Bartosz , Niżankowski Rafał , Mika Piotr , Teległów Aneta
Published: December 2023

There is increasing evidence to support the use of interval training and/or low-impact blood flow restriction exercises in musculoskeletal rehabilitation. The aim of the study was to assess the effect of interval training combined with occlusion and cooling in terms of changes in selected blood parameters affecting the development and progression of atherosclerosis of the lower limbs, as well as selected parameters of muscle metabolism and oxidative stress affecting the growth of muscle mass and regeneration after training. Material and methods: The study included 30 young, healthy and untrained people. The VASPER (Vascular Performance) training system was used—High-Intensity Interval Training with the simultaneous use of occlusion and local cryotherapy. Blood from the project participants was collected six times (2 weeks before the start of training, on the day of training, after the first training, after the 10th training, after the 20th training and two weeks after the end of training). The subjects were randomly divided into three groups: exercises only (controlled), with occlusion and with occlusion and local cryotherapy. Results: Statistical analysis of changes in the average values of indicators in all study groups showed a significant change increase due to the time of testing IGF-1 (F = 2.37, p = 0.04), XOD (F = 14.26, p = 0.00), D-Dimer (F = 2.90, p = 0.02), and decrease in MDA (F = 7.14, p = 0.00), T-AOC (F = 11.17, p = 0.00), PT Quick (F = 26.37, p = 0.00), INR (F = 8.79, p = 0.00), TT (F = 3.81, p = 0.00). The most pronounced changes were observed in the occlusion and cooling group. Conclusions: Both interval training without and with the modifications used in the study influences coagulation and oxidative stress parameters and, to a small extent, muscle metabolism. It seems reasonable to use occlusion and local cryotherapy in combination with occlusion.
The Immediate Effects of Immersive Virtual Reality on Autonomic Nervous System Function in Patients with Disorders of Consciousness after Severe Acquired Brain Injury: A Pilot Study
Authors: Reale Giuseppe , Fusco Augusto , Calciano Rossella , Vallario Noemi , Vagnarelli Gabriele , Caliandro Pietro , Castelli Letizia , Moci Marco , Tieri Gaetano , Iasevoli Luigi , Padua Luca
Published: December 2023

Disorders of Consciousness (DoCs) after severe acquired brain injury involve substantial impairment of cognition and physical functioning, requiring comprehensive rehabilitation and support. Technological interventions, such as immersive Virtual Reality (VR), have shown promising results in promoting neural activity and enhancing cognitive and motor recovery. VR can induce physical sensations that may activate the Autonomic Nervous System (ANS) and induce ANS-regulated responses. This study aimed to investigate the effects of immersive VR on the ANS in patients with DoCs through the analysis of the electrodermal activity (EDA). EDA was measured with a wearable device during a single immersive VR session consisting of static and dynamic videos depicting naturalistic environments. A pilot case–control study was conducted with 12 healthy participants and 12 individuals with DoCs. Results showed higher EDA values in patients than in healthy participants (p = 0.035), suggesting stronger autonomic activation during immersive VR exposure, while healthy subjects, in turn, showed a decrease in EDA values. Our results revealed a significant interaction between conditions and groups (p = 0.003), with patients showing significantly increased EDA values from the baseline compared to dynamic video observation (p = 0.014) and final rest (p = 0.007). These results suggest that immersive VR can elicit sympathetic arousal in patients with DoCs. This study highlights the potential of immersive VR as a tool to strengthen autonomic responses in patients with impaired consciousness.
Impairment of Social-Related Quality of Life in COVID-19 Pneumonia Survivors: A Prospective Longitudinal Study
Authors: Ando Takahiro , Shimada Sho , Sugihara Jun , Takayama Koji , Kobayashi Masayoshi , Miyashita Yoshihiro , Ito Tatsuya , Okayasu Kaori , Tsuyuki Shun , Ohba Takehiko , Doi Masafumi , Saito Hiroaki , Fujie Toshihide , Chiaki Tomoshige , Nakagawa Atsushi , Anzai Tatsuhiko , Takahashi Kunihiko , Shibata Sho , Tateishi Tomoya , Miyazaki Yasunari
Published: December 2023

The post-acute sequelae of SARS-CoV-2 (PASC) pose a threat to patients’ health-related quality of life (HRQOL). Here, the impact of COVID-19 on HRQOL and the clinical factors associated with impaired HRQOL were examined. Discharged COVID-19 patients were assessed at 3 and 6 months after disease onset. The patients completed a medical examination and the SF-36 questionnaire at these two time points and underwent pulmonary function testing at 6 months after disease onset. All had undergone computed tomography (CT) imaging upon hospital admission. Of the 74 included patients, 38% reported respiratory symptoms at 3 months, and 26% reported respiratory symptoms at 6 months after disease onset. The aggregated SF-36 scores declined in the role/social component summary (RCS), a category related to social activity. Patients with lower RCS tended to have respiratory sequelae or a relatively lower forced vital capacity. The CT score that reflected the extent of COVID-19 pneumonia was inversely correlated with the RCS score (3 months, p = 0.0024; 6 months, p = 0.0464). A high CT score (≥10 points) predicted a low RCS score at 6 months (p = 0.013). This study highlights the impairment of RCS and its associations with respiratory sequelae. The study also emphasizes the importance of radiological findings in predicting long-term HRQOL outcomes after COVID-19.
Multimodality Imaging in Advanced Heart Failure for Diagnosis, Management and Follow-Up: A Comprehensive Review
Authors: Pergola Valeria , Cameli Matteo , Mattesi Giulia , Mushtaq Saima , D’Andrea Antonello , Guaricci Andrea Igoren , Pastore Maria Concetta , Amato Filippo , Dellino Carlo Maria , Motta Raffaella , Perazzolo Marra Martina , Dellegrottaglie Santo , Pedrinelli Roberto , Iliceto Sabino , Nodari Savina , Perrone Filardi Pasquale , Pontone Gianluca ,   on behalf of the Cluster Imaging of Italian Society of Cardiology (SIC)
Published: December 2023

Advanced heart failure (AHF) presents a complex landscape with challenges spanning diagnosis, management, and patient outcomes. In response, the integration of multimodality imaging techniques has emerged as a pivotal approach. This comprehensive review delves into the profound significance of these imaging strategies within AHF scenarios. Multimodality imaging, encompassing echocardiography, cardiac magnetic resonance imaging (CMR), nuclear imaging and cardiac computed tomography (CCT), stands as a cornerstone in the care of patients with both short- and long-term mechanical support devices. These techniques facilitate precise device selection, placement, and vigilant monitoring, ensuring patient safety and optimal device functionality. In the context of orthotopic cardiac transplant (OTC), the role of multimodality imaging remains indispensable. Echocardiography offers invaluable insights into allograft function and potential complications. Advanced methods, like speckle tracking echocardiography (STE), empower the detection of acute cell rejection. Nuclear imaging, CMR and CCT further enhance diagnostic precision, especially concerning allograft rejection and cardiac allograft vasculopathy. This comprehensive imaging approach goes beyond diagnosis, shaping treatment strategies and risk assessment. By harmonizing diverse imaging modalities, clinicians gain a panoramic understanding of each patient’s unique condition, facilitating well-informed decisions. The aim is to highlight the novelty and unique aspects of recently published papers in the field. Thus, this review underscores the irreplaceable role of multimodality imaging in elevating patient outcomes, refining treatment precision, and propelling advancements in the evolving landscape of advanced heart failure management.
Progressive Fatigue Modelling of Open-Hole Glass-Fibre Epoxy Laminates
Authors: Maneval Victor , Vedvik Nils-Petter , Echtermeyer Andreas T.
Published: December 2023

The failure of composite laminates under cyclic fatigue loads is complex, as multiple failure mechanisms are in play at different scales and interact with each other. Predicting the remaining fatigue life as well as the residual capacities of a composite laminate or component is crucial, particularly for safety-critical applications. A progressive fatigue model is proposed to describe the catastrophic failure of open-hole laminates under tensile cyclic fatigue. To represent both intra-laminar and inter-laminar damage, a combination of a continuum damage mechanics model (CDM) and a discrete cohesive zone model (CZM) is implemented in the finite element (FE) software Abaqus. The CDM combines fibre- and matrix-dominated S-N curves with the Palmgren–Miner accumulation rule and Hashin’s residual strength to form a fatigue failure criterion differentiating between fibre failure (FF) and matrix failure (MF). The CZM implemented in this work is the CF20 model proposed by NASA. Fatigue cycling is simulated using an external cycle-jump scheme, where the stiffness degradation is conducted between the FE simulations outside of the implicit solver [90/0] s. Glass fibre reinforced polymer (GFRP) open-hole specimens were tested in tensile cyclic fatigue at a load ratio of 0.1. The experiments were reproduced numerically and the results compared. After calibration of a set of parameters based on one load level, the model was able to reproduce the experimental S-N curve very well, predicting a slope of −0.10, while the experimental value was −0.11. The failure sequence of the laminate was also successfully reproduced. The growth of the split from the hole, and its interaction with inter-laminar delamination, was successfully captured. The proposed approach was able to describe the fatigue failure of an open-hole laminate with a minimal set of material inputs using a simplified fatigue damage model while avoiding convergence issues.
Special Nuclear Structures in the Germinal Vesicle of the Common Frog with Emphasis on the So-Called Karyosphere Capsule
Authors: Bogolyubov Dmitry S. , Shabelnikov Sergey V. , Travina Alexandra O. , Sulatsky Maksim I. , Bogolyubova Irina O.
Published: December 2023

The karyosphere (karyosome) is a structure that forms in the oocyte nucleus—germinal vesicle (GV)—at the diplotene stage of meiotic prophase due to the assembly of all chromosomes in a limited portion of the GV. In some organisms, the karyosphere has an extrachromosomal external capsule, the marker protein of which is nuclear F-actin. Despite many years of theories about the formation of the karyosphere capsule (KC) in the GV of the common frog Rana temporaria, we present data that cast doubt on its existence, at least in this species. Specific extrachromosomal strands, which had been considered the main elements of the frog’s KC, do not form a continuous layer around the karyosphere and, according to immunogold labeling, do not contain structural proteins, such as actin and lamin B. At the same time, F-actin is indeed noticeably concentrated around the karyosphere, creating the illusion of a capsule at the light microscopy/fluorescence level. The barrier-to-autointegration factor (BAF) and one of its functional partners—LEMD2, an inner nuclear membrane protein—are not localized in the strands, suggesting that the strands are not functional counterparts of the nuclear envelope. The presence of characteristic strands in the GV of R. temporaria late oocytes may reflect an excess of SMC1 involved in the structural maintenance of diplotene oocyte chromosomes at the karyosphere stage, since SMC1 has been shown to be the most abundant protein in the strands. Other characteristic microstructures—the so-called annuli, very similar in ultrastructure to the nuclear pore complexes—do not contain nucleoporins Nup35 and Nup93, and, therefore, they cannot be considered autonomous pore complexes, as previously thought. Taken together, our data indicate that traditional ideas about the existence of the R. temporaria KC as a special structural compartment of the GV are to be revisited.
Phase Separation as a Driver of Stem Cell Organization and Function during Development
Authors: Parra Amalia S. , Johnston Christopher A.
Published: December 2023

A properly organized subcellular composition is essential to cell function. The canonical organizing principle within eukaryotic cells involves membrane-bound organelles; yet, such structures do not fully explain cellular complexity. Furthermore, discrete non-membrane-bound structures have been known for over a century. Liquid–liquid phase separation (LLPS) has emerged as a ubiquitous mode of cellular organization without the need for formal lipid membranes, with an ever-expanding and diverse list of cellular functions that appear to be regulated by this process. In comparison to traditional organelles, LLPS can occur across wider spatial and temporal scales and involves more distinct protein and RNA complexes. In this review, we discuss the impacts of LLPS on the organization of stem cells and their function during development. Specifically, the roles of LLPS in developmental signaling pathways, chromatin organization, and gene expression will be detailed, as well as its impacts on essential processes of asymmetric cell division. We will also discuss how the dynamic and regulated nature of LLPS may afford stem cells an adaptable mode of organization throughout the developmental time to control cell fate. Finally, we will discuss how aberrant LLPS in these processes may contribute to developmental defects and disease.
Evaluating the Detection of Oceanic Mesoscale Eddies in an Operational Eddy-Resolving Global Forecasting System
Authors: Mo Huier , Qin Yinghao , Wan Liying , Zhang Yu , Huang Xing , Wang Yi , Xing Jianyong , Yu Qinglong , Wu Xiangyu
Published: December 2023

In this study, a global analysis and forecasting system at 1/12° is built for operational oceanography at the National Marine Environmental Forecasting Center (NMEFC) by using the NEMO ocean model (NMEFC-NEMO). First, statistical analysis methods are designed to evaluate the performance of sea level anomaly (SLA) forecasting. The results indicate that the NMEFC-NEMO performs well in SLA forecasting when compared with the Mercator-PSY4, Mercator-PSY3, UK-FOAM, CONCEPTS-GIOPS and Bluelink-OceanMAPS forecasting systems. The respective root-mean-squared errors (RMSEs) of NMEFC-NEMO (Mercator PSY4) are 0.0654 m (0.0663 m) and 0.0797 m (0.0767 m) for the lead times of 1 and 7 days. The anomaly correlation coefficients between forecasting and observations exceed 0.8 for the NMEFC-NEMO and Mercator-PSY4 systems, suggesting that the accuracy of SLA predicted using NMEFC-NEMO is comparable to Mercator PSY4 and superior to other forecasting systems. Moreover, the global spatial distribution of oceanic eddies are effectively represented in NMEFC-NEMO when compared to that in the HYCOM reanalysis, and the detection rate reaches more than 90% relative to HYCOM reanalysis. Regarding the strong eddies in the Kuroshio region, the NMEFC-NEMO reproduces the characteristic for anticyclonic and cyclonic eddies merging and splitting alternatively. As for the detective eddies in the Gulf Stream, NMEFC-NEMO effectively represents the spatial distribution of mesoscale eddies from different seasons. The amplitude of oceanic eddies, including both cyclones and anticyclones, were much stronger on 1 July 2019 than 1 January 2019. Overall, NMEFC-NEMO has a superior performance in SLA forecasting and effectively represents the oceanic mesoscale eddies for operational oceanography.
Hydrodynamic Performance and Flow Field Characteristics of Tidal Current Energy Turbine with and without Winglets
Authors: Wang Yi , Guo Bin , Jing Fengmei , Mei Yunlei
Published: December 2023

In order to gain a more comprehensive understanding of the influence of winglets on the hydrodynamic performance and flow field characteristics of tidal current energy turbines, two different shapes of winglets are designed, and numerical simulation results for turbines with and without winglets are compared and analyzed. The results show that both shapes of winglets can improve the energy conversion efficiency, and the winglets with a cant angle (60°) are more effective than the flat (0°) winglets; the winglets transfer the tip vortices to the winglet tips and weaken the tip vortices, increase the pressure coefficients of the cross-section in the tip region, and inhibit the three-dimensional flow phenomenon in the tip region; the winglets will make the wake axial velocity deficit larger in the near-wake region, and with the axial distance increases, the axial velocity of the wake flow with winglets recovers faster than that without winglets; winglets can make the vortex pairing and breaking of the turbine tip vortex faster, which can also be observed by the change in the turbulent kinetic energy (TKE).
In Vitro Susceptibility Tests in the Context of Antifungal Resistance: Beyond Minimum Inhibitory Concentration in Candida spp.
Authors: Franconi Iacopo , Lupetti Antonella
Published: December 2023

Antimicrobial resistance is a matter of rising concern, especially in fungal diseases. Multiple reports all over the world are highlighting a worrisome increase in azole- and echinocandin-resistance among fungal pathogens, especially in Candida species, as reported in the recently published fungal pathogens priority list made by WHO. Despite continuous efforts and advances in infection control, development of new antifungal molecules, and research on molecular mechanisms of antifungal resistance made by the scientific community, trends in invasive fungal diseases and associated antifungal resistance are on the rise, hindering therapeutic options and clinical cures. In this context, in vitro susceptibility testing aimed at evaluating minimum inhibitory concentrations, is still a milestone in the management of fungal diseases. However, such testing is not the only type at a microbiologist’s disposal. There are other adjunctive in vitro tests aimed at evaluating fungicidal activity of antifungal molecules and also exploring tolerance to antifungals. This plethora of in vitro tests are still left behind and performed only for research purposes, but their role in the context of invasive fungal diseases associated with antifungal resistance might add resourceful information to the clinical management of patients. The aim of this review was therefore to revise and explore all other in vitro tests that could be potentially implemented in current clinical practice in resistant and difficult-to-treat cases.
Survey of Transfer Learning Approaches in the Machine Learning of Digital Health Sensing Data
Authors: Chato Lina , Regentova Emma
Published: December 2023

Machine learning and digital health sensing data have led to numerous research achievements aimed at improving digital health technology. However, using machine learning in digital health poses challenges related to data availability, such as incomplete, unstructured, and fragmented data, as well as issues related to data privacy, security, and data format standardization. Furthermore, there is a risk of bias and discrimination in machine learning models. Thus, developing an accurate prediction model from scratch can be an expensive and complicated task that often requires extensive experiments and complex computations. Transfer learning methods have emerged as a feasible solution to address these issues by transferring knowledge from a previously trained task to develop high-performance prediction models for a new task. This survey paper provides a comprehensive study of the effectiveness of transfer learning for digital health applications to enhance the accuracy and efficiency of diagnoses and prognoses, as well as to improve healthcare services. The first part of this survey paper presents and discusses the most common digital health sensing technologies as valuable data resources for machine learning applications, including transfer learning. The second part discusses the meaning of transfer learning, clarifying the categories and types of knowledge transfer. It also explains transfer learning methods and strategies, and their role in addressing the challenges in developing accurate machine learning models, specifically on digital health sensing data. These methods include feature extraction, fine-tuning, domain adaptation, multitask learning, federated learning, and few-/single-/zero-shot learning. This survey paper highlights the key features of each transfer learning method and strategy, and discusses the limitations and challenges of using transfer learning for digital health applications. Overall, this paper is a comprehensive survey of transfer learning methods on digital health sensing data which aims to inspire researchers to gain knowledge of transfer learning approaches and their applications in digital health, enhance the current transfer learning approaches in digital health, develop new transfer learning strategies to overcome the current limitations, and apply them to a variety of digital health technologies.
Flight-to-Liquidity and Excess Stock Return: Empirical Evidence from a Dynamic Panel Model
Authors: Ali Asif , Rahman Habib Ur , Arian Adam , Sands John
Published: December 2023

This study examines the impact of the flight-to-liquidity (FTL) phenomenon on the excess stock return by applying the previously developed generalised method of moments (GMM) framework. For this purpose, we use the data covering the period from 2004 to 2018 for 122 public companies listed on the Pakistan Stock Exchange (PSX). This study uses six proxies to measure the expected and unexpected illiquidity. The empirical investigation reveals that expected and unexpected illiquidities greatly influence smaller firms more notably than larger ones, which induces FTL phenomena into the market. Moreover, a FTL phenomenon triggered the Pakistani equity market during the financial crisis, when a significant decline appeared and the less liquid stocks were strongly affected. The results reveal that FTL risk is priced in the Pakistan equity market, making large stocks relatively more attractive in times of dire liquidity. These findings further suggest that the market participants in the Pakistan equity market, including policymakers, regulators and investors, should not ignore FTL phenomena while designing their portfolios.
The View of Pediatric Nephrotic Syndrome as a Podocytopathy
Authors: Vaz de Castro Pedro Alves Soares , Fujihara Ide Thomas , Crespo Torres Fernando , Simões e Silva Ana Cristina
Published: December 2023

Nephrotic syndrome (NS) is a complex clinical entity characterized by proteinuria, hypoalbuminemia, and edema. In this review, we propose the view of NS as a podocytopathy, highlighting the importance of understanding the role of podocytes in the development of this condition. We discuss the various etiologies of NS, ranging from congenital to primary renal diseases, as well as secondary forms due to systemic diseases. We also delve into the mechanisms underlying podocyte injury, which plays a crucial role in the development of NS. By viewing NS as a podocytopathy, we suggest potential implications for the diagnosis and treatment of this condition, including the use of podocyte-specific biomarkers and targeted therapies. Our review provides a comprehensive overview of NS and its underlying mechanisms, emphasizing the importance of a multidisciplinary approach to the diagnosis and management of this condition. Further research is essential to better understand the complex interplay between podocyte injury and the development of NS, with the ultimate goal of improving patient outcomes.