bluuebunny/crossref_metadata_2025 huggingface dataset:
Prediction of Intrauterine Growth Restriction and Preeclampsia Using Machine Learning-Based Algorithms: A Prospective Study
Authors: Vasilache Ingrid-Andrada , Scripcariu Ioana-Sadyie , Doroftei Bogdan , Bernad Robert Leonard , Cărăuleanu Alexandru , Socolov Demetra , Melinte-Popescu Alina-Sînziana , Vicoveanu Petronela , Harabor Valeriu , Mihalceanu Elena , Melinte-Popescu Marian , Harabor Anamaria , Bernad Elena , Nemescu Dragos
Published: February 2024

(1) Background: Prenatal care providers face a continuous challenge in screening for intrauterine growth restriction (IUGR) and preeclampsia (PE). In this study, we aimed to assess and compare the predictive accuracy of four machine learning algorithms in predicting the occurrence of PE, IUGR, and their associations in a group of singleton pregnancies; (2) Methods: This observational prospective study included 210 singleton pregnancies that underwent first trimester screenings at our institution. We computed the predictive performance of four machine learning-based methods, namely decision tree (DT), naïve Bayes (NB), support vector machine (SVM), and random forest (RF), by incorporating clinical and paraclinical data; (3) Results: The RF algorithm showed superior performance for the prediction of PE (accuracy: 96.3%), IUGR (accuracy: 95.9%), and its subtypes (early onset IUGR, accuracy: 96.2%, and late-onset IUGR, accuracy: 95.2%), as well as their association (accuracy: 95.1%). Both SVM and NB similarly predicted IUGR (accuracy: 95.3%), while SVM outperformed NB (accuracy: 95.8 vs. 94.7%) in predicting PE; (4) Conclusions: The integration of machine learning-based algorithms in the first-trimester screening of PE and IUGR could improve the overall detection rate of these disorders, but this hypothesis should be confirmed in larger cohorts of pregnant patients from various geographical areas.
A European Multicentric Investigation of Atypical Melanocytic Skin Lesions of Palms and Soles: The iDScore-PalmoPlantar Database
Authors: Tognetti Linda , Cartocci Alessandra , Lallas Aimilios , Moscarella Elvira , Stanganelli Ignazio , Nazzaro Gianluca , Paoli John , Fargnoli Maria Concetta , Broganelli Paolo , Kittler Harald , Perrot Jean-Luc , Cataldo Gennaro , Cevenini Gabriele , Lo Conte Sofia , Simone Leonardelli , Cinotti Elisa , Rubegni Pietro
Published: February 2024

Background: The differential diagnosis of atypical melanocytic palmoplantar skin lesions (aMPLs) represents a diagnostic challenge, including atypical nevi (AN) and early melanomas (MMs) that display overlapping clinical and dermoscopic features. We aimed to set up a multicentric dataset of aMPL dermoscopic cases paired with multiple anamnestic risk factors and demographic and morphologic data. Methods: Each aMPL case was paired with a dermoscopic and clinical picture and a series of lesion-related data (maximum diameter value; location on the palm/sole in 17 areas; histologic diagnosis; and patient-related data (age, sex, family history of melanoma/sunburns, phototype, pheomelanin, eye/hair color, multiple/dysplastic body nevi, and traumatism on palms/soles). Results: A total of 542 aMPL cases—113 MM and 429 AN—were collected from 195 males and 347 females. No sex prevalence was found for melanomas, while women were found to have relatively more nevi. Melanomas were prevalent on the heel, plantar arch, and fingers in patients aged 65.3 on average, with an average diameter of 17 mm. Atypical nevi were prevalent on the plantar arch and palmar area of patients aged 41.33 on average, with an average diameter of 7 mm. Conclusions: Keeping in mind the risk profile of an aMPL patient can help obtain a timely differentiation between malignant/benign cases, thus avoiding delayed and inappropriate excision, respectively, with the latter often causing discomfort/dysfunctional scarring, especially at acral sites.
Surrogate Biomarker Prediction from Whole-Slide Images for Evaluating Overall Survival in Lung Adenocarcinoma
Authors: Murchan Pierre , Baird Anne-Marie , Ó Broin Pilib , Sheils Orla , Finn Stephen P.
Published: February 2024

Background: Recent advances in computational pathology have shown potential in predicting biomarkers from haematoxylin and eosin (H&E) whole-slide images (WSI). However, predicting the outcome directly from WSIs remains a substantial challenge. In this study, we aimed to investigate how gene expression, predicted from WSIs, could be used to evaluate overall survival (OS) in patients with lung adenocarcinoma (LUAD). Methods: Differentially expressed genes (DEGs) were identified from The Cancer Genome Atlas (TCGA)-LUAD cohort. Cox regression analysis was performed on DEGs to identify the gene prognostics of OS. Attention-based multiple instance learning (AMIL) models were trained to predict the expression of identified prognostic genes from WSIs using the TCGA-LUAD dataset. Models were externally validated in the Clinical Proteomic Tumour Analysis Consortium (CPTAC)-LUAD dataset. The prognostic value of predicted gene expression values was then compared to the true gene expression measurements. Results: The expression of 239 prognostic genes could be predicted in TCGA-LUAD with cross-validated Pearson’s R > 0.4. Predicted gene expression demonstrated prognostic performance, attaining a cross-validated concordance index of up to 0.615 in TCGA-LUAD through Cox regression. In total, 36 genes had predicted expression in the external validation cohort that was prognostic of OS. Conclusions: Gene expression predicted from WSIs is an effective method of evaluating OS in patients with LUAD. These results may open up new avenues of cost- and time-efficient prognosis assessment in LUAD treatment.
The Surgical Treatment of Infective Endocarditis: A Comprehensive Review
Authors: Arjomandi Rad Arian , Zubarevich Alina , Osswald Anja , Vardanyan Robert , Magouliotis Dimitrios E. , Ansaripour Ali , Kourliouros Antonios , Sá Michel Pompeu , Rassaf Tienush , Ruhparwar Arjang , Sardari Nia Peyman , Athanasiou Thanos , Weymann Alexander
Published: February 2024

Infective endocarditis (IE) is a severe cardiac complication with high mortality rates, especially when surgical intervention is delayed or absent. This review addresses the expanding role of surgery in managing IE, focusing on the variation in surgical treatment rates, the impact of patient demographics, and the effectiveness of different surgical approaches. Despite varying global data, a notable increase in surgical interventions for IE is evident, with over 50% of patients undergoing surgery in tertiary centres. This review synthesizes information from focused literature searches up to July 2023, covering preoperative to postoperative considerations and surgical strategies for IE. Key preoperative concerns include accurate diagnosis, appropriate antimicrobial treatment, and the timing of surgery, which is particularly crucial for patients with heart failure or at risk of embolism. Surgical approaches vary based on valve involvement, with mitral valve repair showing promising outcomes compared to replacement. Aortic valve surgery, traditionally favouring replacement, now includes repair as a viable option. Emerging techniques such as sutureless valves and aortic homografts are explored, highlighting their potential advantages in specific IE cases. The review also delves into high-risk groups like intravenous drug users and the elderly, emphasizing the need for tailored surgical strategies. With an increasing number of patients presenting with prosthetic valve endocarditis and device-related IE, the review underscores the importance of comprehensive management strategies encompassing surgical and medical interventions. Overall, this review provides a comprehensive overview of current evidence in the surgical management of IE, highlighting the necessity of a multidisciplinary approach and ongoing research to optimize patient outcomes.
The Influence of Bioclimates and Soil Physicochemical Properties on Bacterial and Archaeal Communities from Forest Ecosystems in Côte d’Ivoire (West Africa)
Authors: Ebou Anicet E. T. , Koua Dominique K. , Fossou Romain Kouakou , Amon Chiguié Estelle Raïssa , Zézé Adolphe
Published: February 2024

Archaea and bacteria communities play pivotal roles in tropical forest ecosystems’ functioning, especially nutrient cycling, plant phenology, and health. The objective of this study was to explore the diversity of archaeal and bacterial communities in forest soil ecosystem of Côte d’Ivoire and to identify abiotic factors that influence their composition. Using high-throughput amplicon sequencing targeting the V4V5 hypervariable region of the 16S ribosomal RNA gene, we analyzed 22 soil samples taken from the 2 main forest areas of Côte d’Ivoire, namely the semi-deciduous moist forest and the evergreen moist forest, both of which are located in the humid and sub-humid areas of the country. The analysis revealed that the biodiversity at the phyla level was congruent with previous studies. Richness and Shannon diversity indices revealed the dominance of bacteria over archaea in all studied soils. Moreover, the predominant bacterial community consisted of Proteobacteria (29.8%), Acidobacteria (15.5%), and Actinobacteria (14.2%), while the archaeal community was dominated by Thaumarchaeota (1.93%). However, at the genus level, patterns emerged. The most abundant and ubiquitous members at the genus level included Bradyrhizobium, Rhodoplanes, Bacillus (bacteria), and Nitrosophaera (archaea). While bacterial core microbiome members were found in almost all soils, Nitrososphaera genus were selective to sub-humid bioclimate and cropland land use. These patterns were correlated to the soils’ physicochemical characteristics, bioclimate, and land use. This study sheds light on the intricate relationships between abiotic factors and microbial communities in Côte d’Ivoire’s forest soils and helps to identify keys species for future soil management.
Temporal Analysis of Mangrove Forest Extent in Restoration Initiatives: A Remote Sensing Approach Using Sentinel-2 Imagery
Authors: Farzanmanesh Raheleh , Khoshelham Kourosh , Volkova Liubov , Thomas Sebastian , Ravelonjatovo Jaona , Weston Christopher J.
Published: February 2024

The significance of mangroves and the associated risks they face have prompted government and the private sector to invest in projects aimed at conserving and restoring mangroves. Despite this interest, there is currently little information available on the effectiveness of these investments in mangrove conservation and restoration efforts. Therefore, this study aimed to use Sentinel-2 imagery with 10-m resolution through the Google Earth Engine to evaluate the effectiveness of these projects in mangrove areas in two regions: the Tahiry Honko project in Madagascar and the Abu Dhabi Blue Carbon Demonstration Project in the United Arab Emirates. The study compared the U-Net and SVM for mangrove classification. The U-Net model demonstrated superior performance, achieving an accuracy of 90%, with a Kappa coefficient value of 0.84. In contrast, the SVM had an overall accuracy of 86% and Kappa coefficient of 0.78. The analysis of changes in the mangrove area using U-Net model revealed a decline of 355 ha over four years in the Tahiry Honko project, while in the Abu Dhabi Project, the mangrove area increased by 5857 ha over 5 years. These findings can provide valuable information for policy-makers and management strategies.
Effects of Compound Fertilizer Decrement and Water-Soluble Humic Acid Fertilizer Application on Soil Properties, Bacterial Community Structure, and Shoot Yield in Lei Bamboo (Phyllostachys praecox) Plantations in Subtropical China
Authors: Ni Huijing , Zhao Jiancheng , Yang Zhenya
Published: February 2024

Lei bamboo (Phyllostachys praecox) is an economically viable bamboo species with rich nutrition, a good taste, and a high yield. However, heavy fertilization and covering cultivation are used to produce off-season bamboo shoots, resulting in soil degradation and a decline in site productivity. This study investigated how compound fertilizer decrement and water-soluble humic acid fertilizer application affects soil properties and shoot yield in Lei bamboo plantations of subtropical China. The soil nutrients, enzyme activities, and shoot yield were examined, the bacterial community structure was determined using the high-throughput sequencing method, and their relationships were evaluated under different fertilization treatments: single compound fertilizer and compound fertilizer decrement with water-soluble humic acid fertilizer applications. Compared with those after single compound fertilizer treatments (CF1, CF2), water-soluble humic acid fertilizer addition (CF2HA1, CF2HA2) increased soil organic carbon (SOC), available phosphorus (AP), microbial biomass nitrogen (MBN) contents, the ratio of SOC to total nitrogen (C/N), and sucrase and acid phosphatase (Acp) activities, and decreased alkali hydrolyzed nitrogen (AN) and microbial biomass carbon (MBC) contents. The bacterial community phyla comprised 83.62%–86.16% Proteobacteria, Acidobacteria, Bacteroidetes, Actinobacteria, and Chloroflexi. Water-soluble humic acid fertilizer application also significantly increased yields by over 30%. AP and MBN were important drivers affecting soil bacterial communities, whereas SOC, MBN, and Chloroflexi affected Lei bamboo shoots. Overall, compound fertilizer decrement and water-soluble humic acid fertilizer application shifted the available soil nutrients, sucrase and Acp activity, bacterial community diversity, and shoot yield. An improved understanding of humic acid and the application of humic acid water-soluble fertilizer are of great significance for soil improvement, ecological restoration, and the sustainable management of bamboo forests in the future.
Dimensional Stability and Mechanical Properties of Gmelina arborea Roxb. Wood Thermally Modified through Open Reactor and Low-Pressure Closed Reactor Systems
Authors: Olaniran Samuel Oluyinka , Militz Holger
Published: February 2024

This study focused on the thermal modification of Gmelina arborea Roxb. wood following processes using the open reactor and low-pressure closed reactor systems. The aim is to determine the optimum treatment conditions suitable for gmelina wood due to its poor drying characteristics using the low-pressure closed reactor thermal modification. Subsequent to thermal modification under both processes, the dimensional stability and mechanical properties of gmelina wood were investigated. Effects of the thermal modifications under the open and low-pressure closed reactor systems on mechanical properties were additionally reported. The outcome of this investigation revealed that mass loss increased with increasing treatment temperatures, but minimal mass losses were observed for samples modified in the low-pressure closed reactor system. Due to the low-pressure regime used in the closed reactor system, a lesser improvement was found in volumetric shrinkage, fibre saturation point and tangential-to-radial swelling compared to the improvement in these properties in the open reactor system. Results further revealed that the mechanical properties of gmelina wood deteriorated more rapidly after modification in the open reactor system. Since the properties of modified gmelina wood are comparable at 180 °C under both systems, the closed reactor system will be investigated further to arrive at a suitable treatment condition under higher pressure variations. The thermal modification of gmelina wood with the closed reactor system is more promising in delivering a better quality of modified gmelina wood.
Speech Inpainting Based on Multi-Layer Long Short-Term Memory Networks
Authors: Shi Haohan , Shi Xiyu , Dogan Safak
Published: February 2024

Audio inpainting plays an important role in addressing incomplete, damaged, or missing audio signals, contributing to improved quality of service and overall user experience in multimedia communications over the Internet and mobile networks. This paper presents an innovative solution for speech inpainting using Long Short-Term Memory (LSTM) networks, i.e., a restoring task where the missing parts of speech signals are recovered from the previous information in the time domain. The lost or corrupted speech signals are also referred to as gaps. We regard the speech inpainting task as a time-series prediction problem in this research work. To address this problem, we designed multi-layer LSTM networks and trained them on different speech datasets. Our study aims to investigate the inpainting performance of the proposed models on different datasets and with varying LSTM layers and explore the effect of multi-layer LSTM networks on the prediction of speech samples in terms of perceived audio quality. The inpainted speech quality is evaluated through the Mean Opinion Score (MOS) and a frequency analysis of the spectrogram. Our proposed multi-layer LSTM models are able to restore up to 1 s of gaps with high perceptual audio quality using the features captured from the time domain only. Specifically, for gap lengths under 500 ms, the MOS can reach up to 3~4, and for gap lengths ranging between 500 ms and 1 s, the MOS can reach up to 2~3. In the time domain, the proposed models can proficiently restore the envelope and trend of lost speech signals. In the frequency domain, the proposed models can restore spectrogram blocks with higher similarity to the original signals at frequencies less than 2.0 kHz and comparatively lower similarity at frequencies in the range of 2.0 kHz~8.0 kHz.
Online Optimization of Pickup and Delivery Problem Considering Feasibility
Authors: Matsuoka Ryo , Kobayashi Koichi , Yamashita Yuh
Published: February 2024

A pickup and delivery problem by multiple agents has many applications, such as food delivery service and disaster rescue. In this problem, there are cases where fuels must be considered (e.g., the case of using drones as agents). In addition, there are cases where demand forecasting should be considered (e.g., the case where a large number of orders are carried by a small number of agents). In this paper, we consider an online pickup and delivery problem considering fuel and demand forecasting. First, the pickup and delivery problem with fuel constraints is formulated. The information on demand forecasting is included in the cost function. Based on the orders, the agents’ paths (e.g., the paths from stores to customers) are calculated. We suppose that the target area is given by an undirected graph. Using a given graph, several constraints such as the moves and fuels of the agents are introduced. This problem is reduced to a mixed integer linear programming (MILP) problem. Next, in online optimization, the MILP problem is solved depending on the acceptance of orders. Owing to new orders, the calculated future paths may be changed. Finally, by using a numerical example, we present the effectiveness of the proposed method.
IoTwins: Implementing Distributed and Hybrid Digital Twins in Industrial Manufacturing and Facility Management Settings
Authors: Bellavista Paolo , Di Modica Giuseppe
Published: February 2024

A Digital Twin (DT) refers to a virtual representation or digital replica of a physical object, system, process, or entity. This concept involves creating a detailed, real-time digital counterpart that mimics the behavior, characteristics, and attributes of its physical counterpart. DTs have the potential to improve efficiency, reduce costs, and enhance decision-making by providing a detailed, real-time understanding of the physical systems they represent. While this technology is finding application in numerous fields, such as energy, healthcare, and transportation, it appears to be a key component of the digital transformation of industries fostered by the fourth Industrial revolution (Industry 4.0). In this paper, we present the research results achieved by IoTwins, a European research project aimed at investigating opportunities and issues of adopting DTs in the fields of industrial manufacturing and facility management. Particularly, we discuss a DT model and a reference architecture for use by the research community to implement a platform for the development and deployment of industrial DTs in the cloud continuum. Guided by the devised architectures’ principles, we implemented an open platform and a development methodology to help companies build DT-based industrial applications and deploy them in the so-called Edge/Cloud continuum. To prove the research value and the usability of the implemented platform, we discuss a simple yet practical development use case.
Comparative Analysis of Chloroplast Genomes of “Tiantai Wu-Yao” (Lindera aggregata) and Taxa of the Same Genus and Different Genera
Authors: Shi Yujie , Chen Zhen , Jiang Jingyong , Li Xiaobai , Zeng Wei
Published: February 2024

Lindera aggregata is a species of the Lauraceae family, which has important medicinal, economic and ornamental values. In this study, we sequenced, assembled and annotated the chloroplast genome of L. aggregata and reannotated and corrected eight unverified annotations in the same genus. The chloroplast genomes taxa from Lindera and from different genera of Lauraceae were compared and analyzed, and their phylogenetic relationship and divergence time were speculated. All the 36 chloroplast genomes had typical quadripartite structures that ranged from 150,749 to 154,736 bp in total length. These genomes encoded 111–112 unique genes, including 78–79 protein-coding genes, 29–30 tRNA and 4 rRNA. Furthermore, there were 78–97 SSRs loci in these genomes, in which mononucleotide repeats were the most abundant; there were 24–49 interspersed repeats, and forward repeat types were the most frequent. The codon bias patterns of all species tended to use codons ending with A or U. Five and six highly variable regions were identified within genus and between genera, respectively, and three common regions (ycf1, ndhF-rpl32 and rpl32-trnL) were identified, which can be used as important DNA markers for phylogeny and species identification. According to the evaluation of the Ka/Ks ratio, most of the genes were under purifying selection, and only 10 genes were under positive selection. Finally, through the construction of the evolutionary tree of 39 chloroplast genomes, the phylogenetic relationship of Lauraceae was clarified and the evolutionary relationship of Lindera was revealed. The species of genus Lindera experienced rapid adaptive radiation from Miocene to Pleistocene. The results provided valuable insights for the study of chloroplast genomes in the Lauraceae family, especially in the genus Lindera.
Alcohol Impairs Bioenergetics and Differentiation Capacity of Myoblasts from Simian Immunodeficiency Virus-Infected Female Macaques
Authors: Levitt Danielle E. , Bourgeois Brianna L. , Rodríguez-Graciani Keishla M. , Molina Patricia E. , Simon Liz
Published: February 2024

Alcohol misuse and HIV independently induce myopathy. We previously showed that chronic binge alcohol (CBA) administration, with or without simian immunodeficiency virus (SIV), decreases differentiation capacity of male rhesus macaque myoblasts. We hypothesized that short-term alcohol and CBA/SIV would synergistically decrease differentiation capacity and impair bioenergetic parameters in female macaque myoblasts. Myoblasts from naïve (CBA−/SIV−), vehicle [VEH]/SIV, and CBA/SIV (N = 4–6/group) groups were proliferated (3 days) and differentiated (5 days) with 0 or 50 mM ethanol (short-term). CBA/SIV decreased differentiation and increased non-mitochondrial oxygen consumption rate (OCR) versus naïve and/or VEH/SIV. Short-term alcohol decreased differentiation; increased maximal and non-mitochondrial OCR, mitochondrial reactive oxygen species (ROS) production, and aldolase activity; and decreased glycolytic measures, ATP production, mitochondrial membrane potential (ΔΨm), and pyruvate kinase activity. Mitochondrial ROS production was closely associated with mitochondrial network volume, and differentiation indices were closely associated with key bioenergetic health and function parameters. Results indicate that short-term alcohol and CBA non-synergistically decrease myoblast differentiation capacity. Short-term alcohol impaired myoblast glycolytic function, driving the bioenergetic deficit. Results suggest potentially differing mechanisms underlying decreased differentiation capacity with short-term alcohol and CBA, highlighting the need to elucidate the impact of different alcohol use patterns on myopathy.
The Evolving Role of Dendritic Cells in Atherosclerosis
Authors: Britsch Simone , Langer Harald , Duerschmied Daniel , Becher Tobias
Published: February 2024

Atherosclerosis, a major contributor to cardiovascular morbidity and mortality, is characterized by chronic inflammation of the arterial wall. This inflammatory process is initiated and maintained by both innate and adaptive immunity. Dendritic cells (DCs), which are antigen-presenting cells, play a crucial role in the development of atherosclerosis and consist of various subtypes with distinct functional abilities. Following the recognition and binding of antigens, DCs become potent activators of cellular responses, bridging the innate and adaptive immune systems. The modulation of specific DC subpopulations can have either pro-atherogenic or atheroprotective effects, highlighting the dual pro-inflammatory or tolerogenic roles of DCs. In this work, we provide a comprehensive overview of the evolving roles of DCs and their subtypes in the promotion or limitation of atherosclerosis development. Additionally, we explore antigen pulsing and pharmacological approaches to modulate the function of DCs in the context of atherosclerosis.
Prostate Cancer: Insights into Disease Progression and Therapeutic Challenges
Authors: Chakroborty Debanjan , Singh Ajay Pratap
Published: February 2024

Prostate cancer (PCa) is the second most common cancer and the fifth highest cause of cancer-related death among men in the world [...]
Current Strategies for Increasing Knock-In Efficiency in CRISPR/Cas9-Based Approaches
Authors: Leal Andrés , Herreno-Pachón Angelica , Benincore-Flórez Eliana , Karunathilaka Amali , Tomatsu Shunji
Published: February 2024

Since its discovery in 2012, the clustered regularly interspaced short palindromic repeats (CRISPR) and CRISPR-associated protein 9 (Cas9) system has supposed a promising panorama for developing novel and highly precise genome editing-based gene therapy (GT) alternatives, leading to overcoming the challenges associated with classical GT. Classical GT aims to deliver transgenes to the cells via their random integration in the genome or episomal persistence into the nucleus through lentivirus (LV) or adeno-associated virus (AAV), respectively. Although high transgene expression efficiency is achieved by using either LV or AAV, their nature can result in severe side effects in humans. For instance, an LV (NCT03852498)- and AAV9 (NCT05514249)-based GT clinical trials for treating X-linked adrenoleukodystrophy and Duchenne Muscular Dystrophy showed the development of myelodysplastic syndrome and patient’s death, respectively. In contrast with classical GT, the CRISPR/Cas9-based genome editing requires the homologous direct repair (HDR) machinery of the cells for inserting the transgene in specific regions of the genome. This sophisticated and well-regulated process is limited in the cell cycle of mammalian cells, and in turn, the nonhomologous end-joining (NHEJ) predominates. Consequently, seeking approaches to increase HDR efficiency over NHEJ is crucial. This manuscript comprehensively reviews the current alternatives for improving the HDR for CRISPR/Cas9-based GTs.
Potential Mechanisms of the Protective Effects of the Cardiometabolic Drugs Type-2 Sodium–Glucose Transporter Inhibitors and Glucagon-like Peptide-1 Receptor Agonists in Heart Failure
Authors: Gallo Giovanna , Volpe Massimo
Published: February 2024

Different multifactorial pathophysiological processes are involved in the development of heart failure (HF), including neurohormonal dysfunction, the hypertrophy of cardiomyocytes, interstitial fibrosis, microvascular endothelial inflammation, pro-thrombotic states, oxidative stress, decreased nitric oxide (NO) bioavailability, energetic dysfunction, epicardial coronary artery lesions, coronary microvascular rarefaction and, finally, cardiac remodeling. While different pharmacological strategies have shown significant cardiovascular benefits in HF with reduced ejection fraction (HFrEF), there is a residual unmet need to fill the gap in terms of knowledge of mechanisms and efficacy in the outcomes of neurohormonal agents in HF with preserved ejection fraction (HFpEF). Recently, type-2 sodium–glucose transporter inhibitors (SGLT2i) have been shown to contribute to a significant reduction in the composite outcome of HF hospitalizations and cardiovascular mortality across the entire spectrum of ejection fraction. Moreover, glucagon-like peptide-1 receptor agonists (GLP1-RA) have demonstrated significant benefits in patients with high cardiovascular risk, excess body weight or obesity and HF, in particular HFpEF. In this review, we will discuss the biological pathways potentially involved in the action of SGLT2i and GLP1-RA, which may explain their effective roles in the treatment of HF, as well as the potential implications of the use of these agents, also in combination therapies with neurohormonal agents, in the clinical practice.
Sphingosine Prevents Rhinoviral Infections
Authors: Lang Judith , Soddemann Matthias , Edwards Michael J. , Wilson Gregory C. , Lang Karl S. , Gulbins Erich
Published: February 2024

Rhinoviral infections cause approximately 50% of upper respiratory tract infections and novel treatment options are urgently required. We tested the effects of 10 μM to 20 μM sphingosine on the infection of cultured and freshly isolated human cells with minor and major group rhinovirus in vitro. We also performed in vivo studies on mice that were treated with an intranasal application of 10 μL of either a 10 μM or a 100 μM sphingosine prior and after infection with rhinovirus strains 1 and 2 and determined the infection of nasal epithelial cells in the presence or absence of sphingosine. Finally, we determined and characterized a direct binding of sphingosine to rhinovirus. Our data show that treating freshly isolated human nasal epithelial cells with sphingosine prevents infections with rhinovirus strains 2 (minor group) and 14 (major group). Nasal infection of mice with rhinovirus 1b and 2 is prevented by the intranasal application of sphingosine before or as long as 8 h after infection with rhinovirus. Nasal application of the same doses of sphingosine exerts no adverse effects on epithelial cells as determined by hemalaun and TUNEL stainings. The solvent, octylglucopyranoside, was without any effect in vitro and in vivo. Mechanistically, we demonstrate that the positively charged lipid sphingosine binds to negatively charged molecules in the virus, which seems to prevent the infection of epithelial cells. These findings indicate that exogenous sphingosine prevents infections with rhinoviruses, a finding that could be therapeutically exploited. In addition, we demonstrated that sphingosine has no obvious adverse effects on the nasal mucosa. Sphingosine prevents rhinoviral infections by a biophysical mode of action, suggesting that sphingosine could serve to prevent many viral infections of airways and epithelial cells in general. Future studies need to determine the molecular mechanisms of how sphingosine prevents rhinoviral infections and whether sphingosine also prevents infections with other viruses inducing respiratory tract infections. Furthermore, our studies do not provide detailed pharmacokinetics that are definitely required before the further development of sphingosine.
Multiple Myeloma from the Perspective of Pro- and Anti-Oxidative Parameters: Potential for Diagnostic and/or Follow-Up Purposes?
Authors: Kul Ayse , Ozturk Kurt Bahar
Published: February 2024

Background: Multiple myeloma is a hematological malignancy characterized by anemia, antibodies causing kidney damage, and damage to multiple organs, which come together to cause morbidity. Although oxidative stress is not a core pathological aspect of multiple myeloma, reactive oxygen species (ROS) and antioxidant balance have been shown to play a role in the disease process and are considered in its management. In the presented study, we aim to assess the reliability of specific oxidant and antioxidant variables as potential biomarkers for multiple myeloma and to determine which of these variables might exhibit higher sensitivity in predicting multiple myeloma. Methods: This case-control study was conducted between March 2023 and August 2023. A total of 30 multiple myeloma patients, newly diagnosed according to the multiple myeloma diagnostic criteria revised by the International Myeloma Study Group in 2014, and a total of 30 volunteers without multiple myeloma were included in this study. Serum glutathione peroxidase (GSH-Px), superoxide dismutase (SOD) and catalase (CAT), and malondialdehyde (MDA) and nitric oxide (NO) levels were measured with the first blood samples taken after inclusion. Results: The groups had similar age (p = 0.623) and sex distribution (p = 1.000). MDA (cut-off: >4.35, p < 0.001), GSH-Px (<59.8, p < 0.001), CAT (<67.2, p < 0.001), SOD (<21.2, p = 0.001), and NO (>38.5, p < 0.001) could significantly detect multiple myeloma. Multivariate logistic regression revealed that increased MDA (p = 0.003) and NO (p = 0.001) levels and decreased GSH-Px (p = 0.001), CAT (p = 0.001), and SOD levels were independently associated with multiple myeloma disease. Conclusions: The presence of increased antioxidant levels and decreased antioxidant levels in patients with multiple myeloma is the clearest indicator of increased oxidative stress. These parameters may help to identify potential therapeutic targets and develop strategies to control disease progression.
Risk Factors for Recurrence of Primary Sclerosing Cholangitis after Liver Transplantation: Single-Center Data
Authors: Catanzaro Elisa , Gringeri Enrico , Cazzagon Nora , Floreani Annarosa , Cillo Umberto , Burra Patrizia , Gambato Martina
Published: February 2024

Background: Primary sclerosing cholangitis (PSC), comprising 5–15% of European liver transplantation (LT) cases, poses a significant challenge due to the risk of post-transplant disease recurrence (rPSC). This single-center study aimed to determine the rPSC rate and long-term post-LT outcomes in PSC patients and to identify potentially modifiable risk factors of rPSC. Methods: All PSC patients receiving LT at Padua Hospital from 1993 to 2021 were included. Recipient data were collected pre-LT, at LT, and during the follow-up. Donor and LT features were recorded. The rPSC rate was assessed according to Mayo Clinic criteria. Patient and graft survival were reported. Results: Thirty-three patients were included. The main indication of LT was decompensated cirrhosis (70%). Nine patients (27%) developed rPSC during a median follow-up of 59 months (45–72). A longer cold ischemia time (p = 0.026), donor female gender (p = 0.049), inflammatory bowel disease reactivation (IBD) post LT (p = 0.005) and hepaticojejunostomy (p = 0.019) were associated with a higher risk of rPSC. Graft and patient survival at 1, 5 and 10 years post LT, 94%, 86%, 74% and 97%, 89%, 77% respectively, were not affected by rPSC development. Conclusion: Specific donor and surgical features might increase the risk of rPSC. Identifying predictive factors for rPSC to prevent graft loss is challenging but could lead to a more personalized organ allocation and follow-up in PSC transplanted patients. IBD reactivation might have a pathogenic role in rPSC. In our single-center experience, rPSC did not affect patient and graft survival.
Open Retrograde Stenting of Proximal Innominate and Common Carotid Artery Stenosis
Authors: Kapalla Marvin , Busch Albert , Wolk Steffen , Reeps Christian
Published: February 2024

Purpose: The evidence regarding the treatment of open retrograde stenting of innominate artery (IA) or common carotid artery stenosis (CCA) is limited, and is suspected to carry a high risk of stroke and death. Therefore, the objective of this study was to evaluate the outcomes of such hybrid procedures. Methods: A retrospective, monocentric study of all patients who underwent retrograde stenting of proximal IA and CCA stenosis via surgical cutdown of the CCA, with or without concomitant CEA, between 2016 and 2023 was performed. Results: Overall, 33 patients were treated. A total of 15 patients (45.5%) were male, with the mean age being 67 ± 9.1 years, and 58% (n = 19) of the patients presented with neurological symptoms. Open retrograde stenting was performed in 67% (n = 22) in ACC, and in 33% (n = 11) in IA stenosis. A total of 20 patients (61%) underwent retrograde stenting with synchronous ipsilateral CEA for concomitant stenosis of the carotid bifurcation. There was no 30-day mortality. The perioperative stroke rate was 3% (n = 1) with complete symptom recovery. During the follow up at 32 months (95% CI: 24–39), three late deaths (9.1%) and one symptomatic stent occlusion were observed and, in five patients (15.2%), re-intervention for restenosis was necessary. Conclusions: Open retrograde stenting for of proximal IA or CCA stenosis with or without CEA, in case of tandem carotid lesions, can be performed safely with a low rate of early adverse events. Continuous follow up examinations are necessary due to relevant instent re-stenosis rates.
On the Realized Risk of Foreign Exchange Rates: A Fractal Perspective
Authors: Fathi Masoumeh , Grobys Klaus , Kolari James W.
Published: February 2024

While well-established literature argues that realized variances are close to a lognormal distribution, this study follows Benoit Mandelbrot by taking a fractal perspective. Using power laws to model realized foreign exchange rate variances, our findings indicate that power laws offer an alternative to the lognormal in terms of goodness-of-fit tests. Further, our analysis shows that estimated power law exponents for seven out of nine realized FX variances are α^<3, which indicates that the variance of realized variance is statistically undefined. We conclude that the foreign exchange rate market is far riskier than earlier believed. By implication, documented research in an enormous body of literature that draws conclusions from variance analyses stands on shaky grounds.
Utilization of Galvanizing Flue Dust Residue: A Sustainable Approach towards Complete Material Recycling
Authors: Pirošková Jana , Klimko Jakub , Ružičková Silvia , Laubertová Martina , Marcinov Vladimír , Múdra Erika , Vojtko Marek , Oráč Dušan
Published: February 2024

During hot-dip galvanization, wastes such as bottom dross, zinc ash, spent pre-treatment solutions, and galvanizing flue dust (GFD) are generated. In scientific publications, research devoted to GFD waste recycling is absent, and companies generating this waste require a solution to this complex problem. GFD is often landfilled in hazardous waste landfills. However, it is possible to process this waste hydrometallurgically, where GFD is first leached, the solution is refined, and finally, zinc metal is obtained by electrowinning. During specific environmentally friendly leaching, not all solid GFD is dissolved, and the aim of this study is to process the remaining solid GFD residue. The analysis shows that the GFD residue material mainly contains zinc (42.46%) in the form of oxides, but there is also a small amount of polluting elements such as Al, Fe, and Pb. This study examines the leaching of the samples in HCl and H2SO4 under different conditions with the aim of obtaining a solution with a high concentration and high leaching efficiency of zinc. The L/S ratio of 3, 4 M H2SO4, and ambient temperature proved to be optimal for the leaching of the GFD residue, where 96.24% of zinc was leached out, which represents a zinc concentration of 136.532 g/L.
An Evaluation of Three Halogens (Cl, Br, and I) Data from a Geological Survey of Japan Geochemical Reference Materials by Radiochemical Neutron Activation Analysis
Authors: Shirai Naoki , Sekimoto Shun , Ebihara Mitsuru
Published: February 2024

Fifteen Geological Survey of Japan (GSJ) geochemical reference materials were analyzed to determine the contents of three halogens (Cl, Br, and I) by using instrumental neutron activation analysis (INAA) and/or radiochemical NAA (RNAA). Two reference materials (JCp-1 and JSO-1) were analyzed using both INAA and RNAA. Although there were discrepancies in Cl and Br for JCp-1 between the INAA and RNAA data, probably due to sample heterogeneity, the INAA and RNAA data for JSO-1 were consistent with each other, within less than 7%, indicating that our RNAA data are reliable. With the repeated analyses of JR-3, the external repeatability of the data obtained using RNAA was evaluated to be 18% for Cl, 11% for Br, and 19% for I. Our RNAA data are in agreement with literature values using NAA for the three halogens, as well as those using isotope dilution mass spectrometry and ion chromatography for Cl. Systematically lower values when using neutron irradiation noble gas mass spectrometry (NI-NGMS) and inductively coupled plasma mass spectrometry (ICP-MS) with pyrohydrolysis can be observed, implying that there are losses for noble gas nuclides produced through the beta-decay of the neutron capture halogen nuclides in NI-NGMS and the non-quantitative recovery of Br and I during procedures in ICP-MS, respectively.
A Curcumin-Decorated Nanozyme with ROS Scavenging and Anti-Inflammatory Properties for Neuroprotection
Authors: Gao Feng , Liang Wenyu , Chen Qixin , Chen Bairu , Liu Yuchen , Liu Zhibo , Xu Xu , Zhu Rongrong , Cheng Liming
Published: February 2024

Disordered reactive oxygen/nitrogen species are a common occurrence in various diseases, which usually cause cellular oxidative damage and inflammation. Despite the wide range of applications for biomimetic nanoparticles with antioxidant or anti-inflammatory properties, designs that seamlessly integrate these two abilities with a synergistic effect in a simple manner are seldom reported. In this study, we developed a novel PEI-Mn composite nanoparticle (PM NP) using a chelation method, and the curcumin was loaded onto PM NPs via metal–phenol coordination to form PEI-Mn@curcumin nanoparticles (PMC NPs). PMC NPs possessed excellent dispersibility and cytocompatibility, was engineered to serve as an effective nanozyme, and exhibited specific SOD-like and CAT-like activities. In addition, the incorporation of curcumin granted PMC NPs the ability to effectively suppress the expression of inflammatory cytokines in microglia induced by LPS. As curcumin also has antioxidant properties, it further amplified the synergistic efficiency of ROS scavenging. Significantly, PMC NPs effectively scavenged ROS triggered by H2O2 in SIM-A9 microglia cells and Neuro-2a cells. PMC NPs also considerably mitigated DNA and lipid oxidation in Neuro-2a cells and demonstrated an increase in cell viability under various H2O2 concentrations. These properties suggest that PMC NPs have significant potential in addressing excessive ROS and inflammation related to neural diseases.
Advances in the Immunology of the Host–Parasite Interactions in African Trypanosomosis, including Single-Cell Transcriptomics
Authors: Choi Boyoon , Vu Hien Thi , Vu Hai Thi , Radwanska Magdalena , Magez Stefan
Published: February 2024

Trypanosomes are single-celled extracellular parasites that infect mammals, including humans and livestock, causing global public health concerns and economic losses. These parasites cycle between insect vectors, such as tsetse flies and vertebrate hosts, undergoing morphological, cellular, and biochemical changes. They have remarkable immune evasion mechanisms to escape the host’s innate and adaptive immune responses, such as surface coat antigenic variation and the induction of the loss of specificity and memory of antibody responses, enabling the prolongation of infection. Since trypanosomes circulate through the host body in blood and lymph fluid and invade various organs, understanding the interaction between trypanosomes and tissue niches is essential. Here, we present an up-to-date overview of host–parasite interactions and survival strategies for trypanosomes by introducing and discussing the latest studies investigating the transcriptomics of parasites according to life cycle stages, as well as host cells in various tissues and organs, using single-cell and spatial sequencing applications. In recent years, this information has improved our understanding of trypanosomosis by deciphering the diverse populations of parasites in the developmental process, as well as the highly heterogeneous immune and tissue-resident cells involved in anti-trypanosome responses. Ultimately, the goal of these approaches is to gain an in-depth understanding of parasite biology and host immunity, potentially leading to new vaccination and therapeutic strategies against trypanosomosis.
Influence of Sucrose and Activated Charcoal on Phytochemistry and Vegetative Growth in Zephyranthes irwiniana (Ravenna) Nic. García (Amaryllidaceae)
Authors: Dewes Neto Bertholdo , Gomes-Copeland Kicia Karinne Pereira , Silveira Dâmaris , Gomes Sueli Maria , Craesmeyer Julia Marina Muller , de Castro Nizio Daniela Aparecida , Fagg Christopher William
Published: February 2024

Zephyranthes irwiniana (Ravenna) Nic. García is an endemic, red list threatened species from the Brazilian savanna (Cerrado) with pharmacological potential to treat the symptoms of Alzheimer’s Disease (AD). This work analyzed the vegetative growth and phytochemistry of its potential compounds, in response to variations in sucrose concentration and activated carbon (AC). Seeds were germinated in vitro and in the greenhouse. The in vitro bulbs were separated in six treatments with different sucrose concentrations (30, 45 and 60 gL−1) and/or AC (1 gL−1). Biomass increases in individuals grown in the greenhouse were higher than those cultivated in vitro. Sucrose concentration significantly increased biomass and root number. AC had a positive influence on leaf and root size, and a negative influence on root number. GC–MS analyses indicated great variation in the abundance of α-terpenyl-acetate, ethyl linoleate, clionasterol and lycorine between treatments, with maximum concentrations of 53.06%, 38.68, 14.34% and 2.57%, respectively. Histolocalization tests indicated the presence of alkaloids in the leaf chlorenchyma and bulb cataphylls. Finally, the present study provided new evidence that the constitution of the culture medium directly influences the vegetative growth and phytochemistry of this species, providing a good medium condition for propagating the species under threat.