bluuebunny/crossref_metadata_2025 huggingface dataset:
The Role of Metal Nanoparticles in the Pathogenesis of Stone Formation
Authors: Labis Varvara , Gaiduk Igor , Bazikyan Ernest , Khmelenin Dmitry , Zhigalina Olga , Dyachkova Irina , Zolotov Denis , Asadchikov Victor , Kravtsov Ivan , Polyakov Nikita , Solovyev Andrey , Prusakov Kirill , Basmanov Dmitry , Kozlov Ivan G.
Published: September 2024

The process of stone formation in the human body remains incompletely understood, which requires clinical and laboratory studies and the formulation of a new endogenous, nanotechnological concept of the mechanism of origin and formation of crystallization centers. Previously, the mechanism of sialolithiasis was considered a congenital disease associated with the pathology of the ducts in the structure of the glands themselves. To date, such morphological changes of congenital nature can be considered from the position of the intrauterine formation of endogenous bacterial infections complicated by the migration of antigenic structures initiating the formation of crystallization centers. The present work is devoted to the study of the morphology and composition of stones obtained as a result of surgical interventions for sialolithiasis. Presumably, nanoparticles of metals and other chemical compounds can be structural components of crystallization centers or incorporated into the conditions of chronic endogenous inflammation and the composition of antigenic structures, in complexes with protein and bacterial components. X-ray microtomography, X-ray fluorescence analysis, scanning transmission electron microscopy and microanalysis, mass spectrometry, and Raman spectroscopy were used to study the pathogenesis of stone formation. Immunoglobulins (Igs) of classes A and G, as well as nanoparticles of metals Pb, Fe, Cr, and Mo, were found in the internal structure of the stones. The complex of antigenic structures was an ovoid calcified layered matrix of polyvid microbial biofilms, with the inclusion of metal nanoparticles and chemical elements, as well as immunoglobulins. The obtained results of clinical and laboratory studies allow us to broaden the view on the pathogenesis of stone formation and suggest that the occurrence of the calcification of antigenic structures may be associated with the formation of IgG4-associated disease.
Topical Delivery of Dual Loaded Nano-Transfersomes Mediated Chemo-Photodynamic Therapy against Melanoma via Inducing Cell Cycle Arrest and Apoptosis
Authors: Guo Yiping , Zhong Wenxiao , Peng Cheng , Guo Li
Published: September 2024

Melanoma is a malignant skin cancer associated with high mortality rates and drug resistance, posing a significant threat to human health. The combination of chemotherapy and photodynamic therapy (PDT) represents a promising strategy to enhance antitumor efficacy through synergistic anti-cancer effects. Topical delivery of chemotherapeutic drugs and photosensitizers (PS) offers a non-invasive and safe way to treat melanoma. However, the effectiveness of these treatments is often hindered by challenges such as limited skin permeability and instability of the PS. In this study, transfersomes (TFS) were designed to facilitate transdermal delivery of the chemotherapeutic drug 5-Fluorouracil (5-FU) and the PS Imperatorin (IMP) for combined chemo-photodynamic therapy for melanoma. The cytotoxic and phototoxic effects of TFS-mediated PDT (TFS-UVA) were investigated in A375 cells and nude mice. The study also demonstrated that TFS-UVA generated intracellular ROS, induced G2/ M phase cell cycle arrest, and promoted cell apoptosis. In conclusion, this study indicated that 5-FU/ IMP-TFS serves as an effective transdermal therapeutic strategy for chemo-PDT in treating melanoma.
Slc4a7 Regulates Retina Development in Zebrafish
Authors: Zhuang Youyuan , Li Dandan , Tang Cheng , Zhao Xinyi , Wang Ruting , Tao Di , Huang Xiufeng , Liu Xinting
Published: September 2024

Inherited retinal degenerations (IRDs) are a group of genetic disorders characterized by the progressive degeneration of retinal cells, leading to irreversible vision loss. SLC4A7 has emerged as a candidate gene associated with IRDs, yet its mechanisms remain largely unknown. This study aims to investigate the role of slc4a7 in retinal development and its associated molecular pathogenesis in zebrafish. Morpholino oligonucleotide knockdown, CRISPR/Cas9 genome editing, quantitative RT-PCR, eye morphometric measurements, immunofluorescent staining, TUNEL assays, visual motor responses, optokinetic responses, rescue experiments, and bulk RNA sequencing were used to assess the impact of slc4a7 deficiency on retinal development. Our results demonstrated that the knockdown of slc4a7 resulted in a dose-dependent reduction in eye axial length, ocular area, and eye-to-body-length ratio. The fluorescence observations showed a significant decrease in immunofluorescence signals from photoreceptors and in mCherry fluorescence from RPE in slc4a7-silenced morphants. TUNEL staining uncovered the extensive apoptosis of retinal cells induced by slc4a7 knockdown. Visual behaviors were significantly impaired in the slc4a7-deficient larvae. GO and KEGG pathway analyses reveal that differentially expressed genes are predominantly linked to aspects of vision, ion channels, and phototransduction. This study demonstrates that the loss of slc4a7 in larvae led to profound visual impairments, providing additional insights into the genetic mechanisms predisposing individuals to IRDs caused by SLC4A7 deficiency.
A Novel Microbial Dysbiosis Index and Intestinal Microbiota-Associated Markers as Tools of Precision Medicine in Inflammatory Bowel Disease Paediatric Patients
Authors: Toto Francesca , Marangelo Chiara , Scanu Matteo , De Angelis Paola , Isoldi Sara , Abreu Maria Teresa , Cucchiara Salvatore , Stronati Laura , Del Chierico Federica , Putignani Lorenza
Published: September 2024

Recent evidence indicates that the gut microbiota (GM) has a significant impact on the inflammatory bowel disease (IBD) progression. Our aim was to investigate the GM profiles, the Microbial Dysbiosis Index (MDI) and the intestinal microbiota-associated markers in relation to IBD clinical characteristics and disease state. We performed 16S rRNA metataxonomy on both stools and ileal biopsies, metabolic dysbiosis tests on urine and intestinal permeability and mucosal immunity activation tests on the stools of 35 IBD paediatric patients. On the GM profile, we assigned the MDI to each patient. In the statistical analyses, the MDI was correlated with clinical parameters and intestinal microbial-associated markers. In IBD patients with high MDI, Gemellaceae and Enterobacteriaceae were increased in stools, and Fusobacterium, Haemophilus and Veillonella were increased in ileal biopsies. Ruminococcaceae and WAL_1855D were enriched in active disease condition; the last one was also positively correlated to MDI. Furthermore, the MDI results correlated with PUCAI and Matts scores in ulcerative colitis patients (UC). Finally, in our patients, we detected metabolic dysbiosis, intestinal permeability and mucosal immunity activation. In conclusion, the MDI showed a strong association with both severity and activity of IBD and a positive correlation with clinical scores, especially in UC. Thus, this evidence could be a useful tool for the diagnosis and prognosis of IBD.
Inflammation and Elevated Osteopontin in Plasma and CSF in Cerebral Malaria Compared to Plasmodium-Negative Neurological Infections
Authors: Stins Monique F. , Mtaja Agnes , Mulendele Evans , Mwimbe Daniel , Pinilla-Monsalve Gabriel D. , Mutengo Mable , Pardo Carlos A. , Chipeta James
Published: September 2024

Cerebral malaria in young African children is associated with high mortality, and persisting neurological deficits often remain in survivors. Sequestered Plasmodium-infected red blood cells lead to cerebrovascular inflammation and subsequent neuroinflammation. Brain inflammation can play a role in the pathogenesis of neurologic sequelae. Therefore, we assessed a select set of proinflammatory analytes (IP10, IL23, MIP3α, GRO, MCP-1, and osteopontin in both the plasma and cerebrospinal fluid(CSF) of Zambian children with cerebral malaria and compared this with children with neurological symptoms that were negative for Plasmodium falciparum (non-cerebral malaria). Several similarities in plasma and CSF levels were found, as were some striking differences. We confirmed that IP10 levels were higher in the plasma of cerebral malaria patients, but this was not found in CSF. Levels of osteopontin were elevated in both the plasma and CSF of CM patients compared to the non-CM patients. These results show again a highly inflammatory environment in both groups but a different profile for CM when compared to non-cerebral malaria. Osteopontin may play an important role in neurological inflammation in CM and the resulting sequelae. Therefore, osteopontin could be a valid target for further biomarker research and potentially for therapeutic interventions in neuroinflammatory infections.
GPR40/GPR120 Agonist GW9508 Improves Metabolic Syndrome-Exacerbated Periodontitis in Mice
Authors: Li Yanchun , Yu Hong , Lopes-Virella Maria F. , Huang Yan
Published: September 2024

G protein-coupled receptor (GPR)40 and GPR120 are receptors for medium- and long-chain free fatty acids. It has been well documented that GPR40 and GPR120 activation improves metabolic syndrome (MetS) and exerts anti-inflammatory effects. Since chronic periodontitis is a common oral inflammatory disease initiated by periodontal pathogens and exacerbated by MetS, we determined if GPR40 and GPR120 activation with agonists improves MetS-associated periodontitis in animal models in this study. We induced MetS and periodontitis by high-fat diet feeding and periodontal injection of lipopolysaccharide, respectively, and treated mice with GW9508, a synthetic GPR40 and GPR120 dual agonist. We determined alveolar bone loss, osteoclast formation, and periodontal inflammation using micro-computed tomography, osteoclast staining, and histology. To understand the underlying mechanisms, we further performed studies to determine the effects of GW9508 on osteoclastogenesis and proinflammatory gene expression in vitro. Results showed that GW9508 improved metabolic parameters, including glucose, lipids, and insulin resistance. Results also showed that GW9508 improves periodontitis by reducing alveolar bone loss, osteoclastogenesis, and periodontal inflammation. Finally, in vitro studies showed that GW9508 inhibited osteoclast formation and proinflammatory gene secretion from macrophages. In conclusion, this study demonstrated for the first time that GPR40/GPR120 agonist GW9508 reduced alveolar bone loss and alleviated periodontal inflammation in mice with MetS-exacerbated periodontitis, suggesting that activating GPR40/GPR120 with agonist GW9508 is a potential anti-inflammatory approach for the treatment of MetS-associated periodontitis.
A 13-Year-Old Girl Affected by Melanocytic Tumors of the Central Nervous System—The Case
Authors: Nowosławska Emilia , Zakrzewska Magdalena , Sikorska Beata , Zakrzewski Jakub , Polis Bartosz
Published: September 2024

Primary intracranial melanoma is a very rare brain tumor, especially when accompanied by benign intramedullary melanocytoma. Distinguishing between a primary central nervous system (CNS) lesion and metastatic melanoma is extremely difficult, especially when the primary cutaneous lesion is not visible. Here we report a 13-year-old girl admitted to the Neurosurgery Department of the Institute of Polish Mother’s Health Centre in Lodz due to upper limb paresis. An intramedullary tumor of the cervical C3–C4 and an accompanying syringomyelic cavity C1–C7 were revealed. The child underwent partial removal of the tumor due to the risk of damage to spinal cord motor centers. The removed part of the tumor was diagnosed as melanocytoma. Eight months later, a neurological examination revealed paresis of the right sixth cranial nerve, accompanied by bilateral optic disc edema. Diagnostic imaging revealed a brain tumor. The girl underwent resection of both detected the tumors and an additional satellite lesion revealed during the surgery. The removed tumors were diagnosed as malignant melanomas in pathomorphological examination. Molecular analysis revealed NRASQ61K mutation in both the intracranial and the intramedullary tumor. It should be noted that in cases where available evidence is inconclusive, an integrative diagnostic process is essential to reach a definitive diagnosis.
Long Dynamic β1–β2 Loops in M. tb MazF Toxins Affect the Interaction Modes and Strengths of the Toxin–Antitoxin Pairs
Authors: Tang Ziyun , Jiang Pengcheng , Xie Wei
Published: September 2024

Tuberculosis is a worldwide plague caused by the pathogen Mycobacterium tuberculosis (M. tb). Toxin–antitoxin (TA) systems are genetic elements abundantly present in prokaryotic organisms and regulate important cellular processes. MazEF is a TA system implicated in the formation of “persisters cells” of M. tb, which contain more than 10 such members. However, the exact function and inhibition mode of each MazF are not fully understood. Here we report crystal structures of MazF-mt3 in its apo form and in complex with the C-terminal half of MazE-mt3. Structural analysis suggested that two long but disordered β1–β2 loops would interfere with the binding of the cognate MazE-mt3 antitoxin. Similar loops are also present in the MazF-mt1 and -mt9 but are sustainably shortened in other M. tb MazF members, and these TA pairs behave distinctly in terms of their binding modes and their RNase activities. Systematic crystallographic and biochemical studies further revealed that the biochemical activities of M. tb toxins were combined results between the interferences from the characteristic loops and the electrostatic interactions between the cognate TA pairs. This study provides structural insight into the binding mode and the inhibition mechanism of the MazE/F TA pairs, which facilitate the structure-based peptide designs.
Discovery of Indole–Thiourea Derivatives as Tyrosinase Inhibitors: Synthesis, Biological Evaluation, Kinetic Studies, and In Silico Analysis
Authors: Xu Yang , Liang Xuhui , Hyun Chang-Gu
Published: September 2024

Tyrosinase, a key enzyme in melanin synthesis, represents a crucial therapeutic target for hyperpigmentation disorders due to excessive melanin production. This study aimed to design and evaluate a series of indole–thiourea derivatives by conjugating thiosemicarbazones with strong tyrosinase inhibitory activity to indole. Among these derivatives, compound 4b demonstrated tyrosinase inhibitory activity with an IC50 of 5.9 ± 2.47 μM, outperforming kojic acid (IC50 = 16.4 ± 3.53 μM). Kinetic studies using Lineweaver–Burk plots confirmed competitive inhibition by compound 4b. Its favorable ADMET and drug-likeness properties make compound 4b a promising therapeutic candidate with a reduced risk of toxicity. Molecular docking revealed that the compounds bind strongly to mushroom tyrosinase (mTYR) and human tyrosinase-related protein 1 (TYRP1), with compound 4b showing superior binding energies of −7.0 kcal/mol (mTYR) and −6.5 kcal/mol (TYRP1), surpassing both kojic acid and tropolone. Molecular dynamics simulations demonstrated the stability of the mTYR−4b complex with low RMSD and RMSF and consistent Rg and SASA values. Persistent strong hydrogen bonds with mTYR, along with favorable Gibbs free energy and MM/PBSA calculations (−19.37 kcal/mol), further support stable protein–ligand interactions. Overall, compound 4b demonstrated strong tyrosinase inhibition and favorable pharmacokinetics, highlighting its potential for treating pigmentary disorders.
Deep Intronic ETFDH Variants Represent a Recurrent Pathogenic Event in Multiple Acyl-CoA Dehydrogenase Deficiency
Authors: Martino Stefania , D’Addabbo Pietro , Turchiano Antonella , Radio Francesca Clementina , Bruselles Alessandro , Cordeddu Viviana , Mancini Cecilia , Stella Alessandro , Laforgia Nicola , Capodiferro Donatella , Simonetti Simonetta , Bagnulo Rosanna , Palumbo Orazio , Marzano Flaviana , Tabaku Ornella , Garganese Antonella , Stasi Michele , Tartaglia Marco , Pesole Graziano , Resta Nicoletta
Published: September 2024

Multiple acyl-CoA dehydrogenase deficiency (MADD) is a rare inborn error of metabolism affecting fatty acid and amino acid oxidation with an incidence of 1 in 200,000 live births. MADD has three clinical phenotypes: severe neonatal-onset with or without congenital anomalies, and a milder late-onset form. Clinical diagnosis is supported by urinary organic acid and blood acylcarnitine analysis using tandem mass spectrometry in newborn screening programs. MADD is an autosomal recessive trait caused by biallelic mutations in the ETFA, ETFB, and ETFDH genes encoding the alpha and beta subunits of the electron transfer flavoprotein (ETF) and ETF-coenzyme Q oxidoreductase enzymes. Despite significant advancements in sequencing techniques, many patients remain undiagnosed, impacting their access to clinical care and genetic counseling. In this report, we achieved a definitive molecular diagnosis in a newborn by combining whole-genome sequencing (WGS) with RNA sequencing (RNA-seq). Whole-exome sequencing and next-generation gene panels fail to detect variants, possibly affecting splicing, in deep intronic regions. Here, we report a unique deep intronic mutation in intron 1 of the ETFDH gene, c.35-959A>G, in a patient with early-onset lethal MADD, resulting in pseudo-exon inclusion. The identified variant is the third mutation reported in this region, highlighting ETFDH intron 1 vulnerability. It cannot be excluded that these intronic sequence features may be more common in other genes than is currently believed. This study highlights the importance of incorporating RNA analysis into genome-wide testing to reveal the functional consequences of intronic mutations.
QTL Mapping of Fiber- and Seed-Related Traits in Chromosome Segment Substitution Lines Derived from Gossypium hirsutum × Gossypium darwinii
Authors: Wang Wenwen , Li Yan , Le Mingmei , Tian Lixia , Sun Xujing , Liu Rui , Guo Xin , Wu Yan , Li Yibing , Zhao Jiaoyun , Liu Dajun , Zhang Zhengsheng
Published: September 2024

A narrow genetic basis limits further the improvement of modern Gossypium hirsutum cultivar. The abundant genetic diversity of wild species provides available resources to solve this dilemma. In the present study, a chromosome segment substitution line (CSSL) population including 553 individuals was established using G. darwinii accession 5-7 as the donor parent and G. hirsutum cultivar CCRI35 as the recipient parent. After constructing a high-density genetic map with the BC1 population, the genotype and phenotype of the CSSL population were investigated. A total of 235 QTLs, including 104 QTLs for fiber-related traits and 132 QTLs for seed-related traits, were identified from four environments. Among these QTLs, twenty-seven QTLs were identified in two or more environments, and twenty-five QTL clusters consisted of 114 QTLs. Moreover, we identified three candidate genes for three stable QTLs, including GH_A01G1096 (ARF5) and GH_A10G0141 (PDF2) for lint percentage, and GH_D01G0047 (KCS4) for seed index or oil content. These results pave way for understanding the molecular regulatory mechanism of fiber and seed development and would provide valuable information for marker-assisted genetic improvement in cotton.
Choosing and Evaluating P2P Lending with Value Engineering as a Decision Support System: An Indonesian Case Study
Authors: Yung Sen , Langi Armein Z. R. , Arman Arry Akhmad , Simatupang Togar M.
Published: September 2024

Peer-to-peer (P2P) lending has gained significant traction in the financial landscape, particularly in developing economies such as Indonesia, where access to traditional banking services remains a challenge for many. The aim of this study is to investigate the application of value engineering as a decision support system for choosing and evaluating P2P lending platforms, using Indonesia as a case study. P2P lending is a relatively new service in the digital economy for lending money to individuals through online financial intermediaries, where borrowers and lenders often have no prior relationship. Value engineering, a systematic approach to improving the value of a product or service, can be a valuable tool in the context of P2P lending. Through applying value engineering principles, P2P lending platforms can identify and prioritize the key factors that influence lending decisions, such as risk, return, and data privacy, to enhance the overall value proposition for both borrowers and lenders. Both value engineering and P2P lending are technoeconomic systems that aim to enhance the overall value and efficiency of a system or process, albeit through different approaches. This study presents a comprehensive framework for applying value engineering as a decision support system for P2P lending in Indonesia. The findings reveal that the value engineering index developed in this study effectively differentiates between P2P lending platforms based on their performance. Specifically, platforms with a high-value index were found to offer competitive interest rates, lower fees, and superior risk management, as evidenced by their non-performing loan (NPL) rates. In contrast, platforms with a low-value index were associated with higher NPLs and less favorable terms for stakeholders. These insights provide practical guidance for P2P lending platforms, regulators, and consumers; highlight the importance of a value engineering approach in optimizing platform selection; and enhance the P2P lending ecosystem’s sustainability in Indonesia.
An Interspecific Assessment of Bergmann’s Rule in Tenebrionid Beetles (Coleoptera, Tenebrionidae) along an Elevation Gradient
Authors: Fattorini Simone
Published: September 2024

In endotherms, body size tends to increase with elevation and latitude (i.e., with decreasing temperatures) (Bergmann’s rule). These patterns are explained in terms of heat balance since larger animals need to produce less heat relative to their size to maintain stable body temperatures. In ectotherms like most insects, where this mechanism cannot operate, a reverse pattern is frequently observed, as a higher surface area-to-volume ratio in colder climates may allow for more rapid heating and cooling. However, patterns of increasing body size with decreasing temperatures can also be observed in ectotherms if selection for more stable internal temperatures leads to smaller surface area-to-volume ratios. Data on tenebrionids from Latium (Central Italy) were used to model elevational variations in average values of body size (total length, mass and volume) and surface area-to-volume ratio. Analyses were performed by considering the whole fauna and two ecological groups separately: ground-dwelling species (geophilous) and arboreal (xylophilous) species. The surface area-to-volume ratios declined with increasing elevation in all cases, indicating that the need for heat conservation is more important than rapid heating and cooling. However, in xylophilous species (which typically live under bark), body size increased with increasing elevation, and in geophilous species, an opposite pattern was observed up to about 1000 m, followed by an increasing pattern. This suggests that a reduction in resource availability with elevation limits body size in geophilous species up to a certain elevation but not in xylophilopus species, which benefit from more climatically stable conditions and constant resources and need energy for overwintering.
Pathogenic Immunoglobulin A-Producing Cells in Immunoglobulin A Nephropathy
Authors: Makita Yuko , Reich Heather N.
Published: September 2024

Immunoglobulin A nephropathy (IgAN) is the most prevalent primary glomerular disease worldwide and it remains a leading cause of kidney failure. Clinical manifestations of IgA are exacerbated by infections, and emerging data suggest that aberrant mucosal immune responses are important contributors to the immunopathogenesis of this disease. However, the exact stimuli, location and mechanism of nephritis-inducing IgA production remains unclear. In this focused review we explore recent developments in our understanding of the contribution of the mucosal immune system and mucosal-derived IgA-producing cells to the development of IgAN.
Examination of the Suitability of Vericiguat in Non-Heart Failure with Preserved Ejection Fraction Patients with Improved Ejection Fraction
Authors: Kinoshita Haruyuki , Sugino Hiroshi , Fujita Kento , Sumimoto Yoji , Masada Kenji , Shimonaga Takashi , Suga Akiyo , Toko Mayumi , Taniyasu Kaori , Ushirozako Saki , Katayama Yumiko , Hirahara Chiemi , Takada Masahiro
Published: September 2024

Background/Objectives: Vericiguat has been shown to reduce cardiovascular mortality and hospitalisation for heart failure in patients with reduced ejection fraction. While Vericiguat is considered one of the standard treatments for heart failure, it is unclear under which conditions Vericiguat would be most effective. With a focus on the prognosis and improved EF of heart failure, we aimed to investigate in which cases Vericiguat is suitable for use in addition to standard cardioprotective drugs. Methods: We prospectively compared echocardiograms taken before and after the administration of Vericiguat in 46 patients with non-dialysis and without heart failure with preserved ejection fraction (non-HFpEF) (left ventricle ejection fraction [LVEF] < 50%) who were able to continue Vericiguat in addition to other standard heart failure drugs (the “Fantastic Four”) for more than 6 months at our hospital. Patients who showed an improvement of 10 points or more in LVEF were defined as improved EF+. Results: LVEF improved significantly from 38 [33–45]% at the time of administration to 46 [35–54.5]% at 6 months (p < 0.001). When comparing patients with and without improved EF, a significant difference was observed in the Hb (OR = 1.66, 95%CI = 1.12–2.83, p = 0.028), early introduction (OR = 12.5, 95%CI = 1.58–149, p = 0.025), and initiation of Vericiguat after the administration of the Fantastic Four (OR = 9.79, 95%CI = 1.71–100.2, p = 0.022). Conclusions: In this study, the early administration of Vericiguat, haemoglobin value, and initiation of Vericiguat after the introduction of the Fantastic Four were identified as independent factors for eligibility in non-dialysis, non-HFpEF patients who were able to continue GDMT treatment for more than 6 months after adding Vericiguat.
Epidemiology of Neuro-Behçet’s Disease in Northern Spain 1999–2019: A Population-Based Study
Authors: Herrero-Morant Alba , Martín-Varillas José Luis , Álvarez-Reguera Carmen , Sánchez-Bilbao Lara , Martínez-López David , Suárez-Amorín Guillermo , Fernández-Ramón Raúl , Ferraz-Amaro Iván , Castañeda Santos , Hernández José L. , Blanco Ricardo
Published: September 2024

Background/Objectives: Neuro-Behçet’s disease (NBD) is one of the most severe complications of Behçet’s disease (BD). The incidence of NBD varies widely worldwide. This study aimed to estimate its current incidence in Northern Spain. Methods: This was a retrospective population-based cohort study of 120 patients in Northern Spain diagnosed with BD according to the 2013 International Criteria for BD (ICBD) between 1 January 1999 and 31 December 2019. NBD diagnoses were made according to International Consensus Recommendation (ICR) criteria. Overall, 96 patients were included, and their demographic and clinical data were collected. The incidence of NBD was estimated by age, gender, and year of diagnosis between 1999–2019. Results: NBD was diagnosed in 23 of 96 (24%) patients (15 women/8 men) (mean age: 44 ± 13.9 years). HLA-B51 was positive in 5 of 13 (38.4%) cases tested. A total of 10 (43.5%) patients had parenchymatous NBD, 10 (43.5%) had non-parenchymatous NBD, and 3 (13%) had mixed NBD. Incidence during the study period was 0.13 (95% CI, 0.11–0.26) per 100,000 people-years. There were no significant differences in gender in the incidence rate stratified by age (p > 0.05). Furthermore, there was a linear relationship with a mild decrease in age at diagnosis over time. Conclusions: Epidemiological characteristics of NBD in Northern Spain are similar to those of neighboring countries, except female gender predominance.
Grad-CAM-Based Investigation into Acute-Stage Fluorescein Angiography Images to Predict Long-Term Visual Prognosis of Branch Retinal Vein Occlusion
Authors: Saito Michiyuki , Mitamura Mizuho , Kimura Mayuko , Ito Yuki , Endo Hiroaki , Katsuta Satoshi , Kase Manabu , Ishida Susumu
Published: September 2024

Background/Objectives: The purpose of this study was to analyze relevant areas in acute-stage fluorescein angiography (FA) images, predicting the long-term visual prognosis of branch retinal vein occlusion (BRVO) based on gradient-weighted class activation mapping (Grad-CAM). Methods: This retrospective observational study included 136 eyes with BRVO that were followed up for more than a year post-FA. Cropped grayscale images centered on the fovea (200 × 200 pixels) were manually pre-processed from early-phase FA at the acute phase. Pairs of the cropped FA images and the best-corrected visual acuity (BCVA) in remission at least one year post-FA were used to train a 38-layer ResNet with five-fold cross-validation. Correlations between the ResNet-predicted and true (actually measured) logMAR BCVAs in remission, and between the foveal avascular zone (FAZ) area measured by ImageJ (version 1.52r) from FA images and true logMAR BCVA in remission were evaluated. The heat maps generated by Grad-CAM were evaluated to determine which areas were consumed as computational resources for BCVA prediction. Results: The correlation coefficient between the predicted and true logMAR BCVAs in remission was 0.47, and that between the acute-stage FAZ area and true logMAR BCVA in remission was 0.42 (p < 0.0001 for both). The Grad-CAM-generated heat maps showed that retinal vessels adjacent to the FAZ and the FAZ per se had high selectivity (95.7% and 62.2%, respectively). Conclusions: The Grad-CAM-based analysis demonstrated FAZ-neighboring vessels as the most relevant predictor for the long-term visual prognosis of BRVO.
Salivary Oxidative-Antioxidant Profile Following Adjunctive Gaseous Ozone Administration in Non-Surgical Periodontal Treatment: A Randomized Controlled Trial
Authors: Rapone Biagio , Scarano Antonio , Qorri Erda , Pardo Alessia , Murmura Giovanna , D’Albenzio Alessandro , Ferrara Elisabetta
Published: September 2024

Background: Periodontitis is associated with increased oxidative stress, which may impair treatment outcomes. Ozone therapy has shown promise in reducing oxidative stress and improving periodontal health. This study examined the impact of adjunctive gaseous ozone administration on salivary oxidative stress markers in patients with periodontitis stages II–IV and grades A–C undergoing non-surgical periodontal treatment (NSPT). Methods: Ninety patients with periodontitis were randomly allocated to either the test group (NSPT with gaseous ozone administration) or the control group (NSPT alone) using computer-generated randomization. The OzoneDTA system was used to deliver ozone at 2100 ppm for 60 s per site once weekly for 4 weeks. Clinical periodontal parameters (probing depth [PD], clinical attachment level [CAL], plaque index [PI], gingival index [GI]) and salivary oxidative stress markers (malondialdehyde [MDA], total antioxidant capacity [TAC], superoxide dismutase [SOD]) were assessed by blinded examiners at baseline, 3, and 6 months post-treatment. Results: Mixed ANOVA revealed significant three-way interactions between time, treatment, and stage or grade for clinical and biochemical measures (p < 0.001). The test group exhibited significant improvements in TAC (mean difference: 0.45 ± 0.12 mmol/L, p = 0.002), MDA (−0.38 ± 0.09 nmol/mL, p = 0.001), and SOD (65 ± 18 U/mL, p < 0.001) compared with the control group, with more pronounced effects in stages III and IV. Large effect sizes (Cohen’s d > 0.8) were observed for the test group between baseline and 6 months for all markers. Conclusions: Gaseous ozone administration as an adjunct to NSPT can effectively improve clinical periodontal parameters and salivary oxidative stress markers, particularly in stages III and IV periodontitis. The enhanced outcomes may be attributed to ozone’s antimicrobial and immunomodulatory properties, which synergistically reduce oxidative stress and promote periodontal healing.
A Pilot Study on the Relationship between Obstructive Sleep Apnoea–Hypopnea Syndrome, Neurodevelopment, and Ricketts’ Cephalometry
Authors: Robayna Teresa I. González , Martínez Carlos Pérez-Albacete , Gandía Jesús M. , Martínez Mª Dolores Austro , Pérez Ángela Sempere , Cascales Raúl Ferrando
Published: September 2024

Background: The aim of this research is to achieve the early detection of facial characteristics in patients diagnosed with neurodevelopmental deficits and obstructive sleep apnoea–hypopnea syndrome (OSAHS) through the analysis of the VERT index and Ricketts’ cephalometry to minimise the neurocognitive morbidity associated with these disorders. Methods: This clinical study was conducted on 44 patients aged 4 to 15 years. Participants completed an initial questionnaire about sleep disturbances, followed by a polysomnography, a radiographic study, and an oral examination. Results: The maximum variability in the data was obtained in the mandibular plane angle, where we observed that the measurement was higher in patients diagnosed with OSAHS. The relative and normalised indices of facial depth and the mandibular plane showed variations between patients with a clinical picture compatible with OSAHS and the control group without pathology. Conclusions: Our findings indicate that Ricketts’ VERT index by itself is unable to provide evidence of a diagnosis compatible with OSAHS in patients with early neurodevelopmental deficits, but, after analysing the results obtained, we observed that for the cephalometric measurements of the mandibular plane angle and facial depth relative to the patient’s age, there are sufficiently strong variations for creating a solid method of differential diagnosis, thus preventing complications at the neurocognitive level.
What Important Information Does Transesophageal Echocardiography Provide When Performed before Transvenous Lead Extraction?
Authors: Nowosielecka Dorota , Jacheć Wojciech , Stefańczyk Dzida Małgorzata , Polewczyk Anna , Mościcka Dominika , Nowosielecka Agnieszka , Kutarski Andrzej
Published: September 2024

Background: Transesophageal echocardiography (TEE) is mandatory before transvenous lead extraction (TLE), but its usefulness remains underestimated. This study aims to describe the broad range of TEE findings in TLE candidates, as well as their influence on procedure complexity, major complications (MCs) and long-term survival. Methods: Preoperative TEE was performed in 1191 patients undergoing TLE. Results: Lead thickening (OR = 1.536; p = 0.007), lead adhesion to heart structures (OR = 2.531; p < 0.001) and abnormally long lead loops (OR = 1.632; p = 0.006) increased the complexity of TLE. Vegetation-like masses on the lead (OR = 4.080; p = 0.44), lead thickening (OR = 2.389; p = 0.049) and lead adhesion to heart structures (OR = 6.341; p < 0.001) increased the rate of MCs. The presence of vegetations (HR = 7.254; p < 0.001) was the strongest predictor of death during a 1-year follow-up period. Conclusions: TEE before TLE provides a lot of important information for the operator. Apart from the visualization of possible vegetations, it can also detect various forms of lead-related scar tissue. Build-up of scar tissue and the presence of long lead loops are associated with increased complexity of the procedure and risk of MCs. Preoperative TEE performed outside the operating room may have an impact on the clinical decision-making process, such as transferring potentially more difficult patients to a more experienced center or having the procedure performed by the most experienced operator. Moreover, the presence of masses or vegetations on the leads significantly increases 1-year and all-cause mortality.
Don’t Like Them but Take What They Said: The Effectiveness of Virtual Influencers in Public Service Announcements
Authors: Mo Zichuan , Zhou Meihan
Published: September 2024

Despite the growing use of virtual influencers in communicating public service announcements (PSAs), their PSA communication effectiveness remains underexplored. Virtual influencers are digital entities who generate content on social media to establish a digital identity and personal brand. This research examines the effectiveness of virtual (vs. human) influencers in conveying PSAs, focusing on consumers’ attitudes toward the influencers and their acceptance of PSA messages. Three experimental studies (N = 1429) spanning different cultural contexts reveal that consumers hold a less favorable attitude toward virtual (vs. human) influencers who post PSAs. Nevertheless, virtual influencers are equally effective as human influencers in influencing consumers’ acceptance of PSA messages. Dual-mediation processes involving mind perception and novelty perception are identified. Furthermore, we find that incorporating emotional appeal can enhance the effectiveness of virtual (vs. human) influencers’ PSA communications. These findings contribute to the literature on virtual influencer marketing and PSA marketing, offering practical insights for leveraging virtual influencers in PSA campaigns.
Using Unmanned Aerial Vehicle Data to Improve Satellite Inversion: A Study on Soil Salinity
Authors: Liu Ruiliang , Jia Keli , Li Haoyu , Zhang Junhua
Published: September 2024

The accurate and extensive monitoring of soil salinization is essential for sustainable agricultural development. It is difficult for single remote sensing data (satellite, unmanned aerial vehicle) to simultaneously meet the requirements of wide-scale and high-precision soil salinity monitoring. Therefore, this paper adopts the upscaling method to upscale the unmanned aerial vehicle (UAV) data to the same pixel size as the satellite data. Based on the optimally upscaled UAV data, the satellite model was corrected using the numerical regression fitting method to improve the inversion accuracy of the satellite model. The results showed that the accuracy of the original UAV soil salinity inversion model (R2 = 0.893, RMSE = 1.448) was higher than that of the original satellite model (R2 = 0.630, RMSE = 2.255). The satellite inversion model corrected with UAV data had an accuracy of R2 = 0.787, RMSE = 2.043, and R2 improved by 0.157. The effect of satellite inversion correction was verified using a UAV inversion salt distribution map, and it was found that the same rate of salt distribution was improved from 75.771% before correction to 90.774% after correction. Therefore, the use of UAV fusion correction of satellite data can realize the requirements from a small range of UAV to a large range of satellite data and from low precision before correction to high precision after correction. It provides an effective technical reference for the precise monitoring of soil salinity and the sustainable development of large-scale agriculture.
RETRACTED: Di Paola et al. Assessment of 2-Pentadecyl-2-oxazoline Role on Lipopolysaccharide-Induced Inflammation on Early Stage Development of Zebrafish (Danio rerio). Life 2022, 12, 128
Authors: Di Paola Davide , Natale Sabrina , Gugliandolo Enrico , Cordaro Marika , Crupi Rosalia , Siracusa Rosalba , D’Amico Ramona , Fusco Roberta , Impellizzeri Daniela , Cuzzocrea Salvatore , Spanò Nunziacarla , Marino Fabio , Peritore Alessio Filippo
Published: September 2024

The journal retracts the article, “Assessment of 2-Pentadecyl-2-oxazoline Role on Lipopolysaccharide-Induced Inflammation on Early Stage Development of Zebrafish (Danio rerio)” [...]
Effectiveness of Home-Based Cardiac Rehabilitation with Optimized Exercise Prescriptions Using a Mobile Healthcare App in Patients with Acute Myocardial Infarction: A Randomized Controlled Trial
Authors: Jo Hyun-Seok , Kim Hyeong-Min , Go Chae-Hyun , Yu Hae-Young , Park Hyeng-Kyu , Han Jae-Young
Published: September 2024

Background: Despite the effectiveness of cardiac rehabilitation (CR), the actual participation rate in CR is low. While home-based CR offers a viable alternative, it faces challenges in participation due to factors such as a lack of self-motivation and fear of exercising without supervision. Utilizing a mobile healthcare application (app) during counseling may be an effective strategy for patients. Therefore, the aim of this study was to assess whether 6 weeks of home-based CR with exercise readjustment using a mobile app is an effective therapy for patients with acute myocardial infarction (AMI). Methods: Post-AMI patients eligible for home-based CR were randomized into the intervention group (CR-Mobile) and the control group, which followed the usual home-based CR protocol (CR-Usual). Both groups participated in a 6-week home-based CR program, with exercise readjustment and encouragement carried out every 2 weeks. The CR-Mobile group was supervised using data recorded in the mobile app, while the CR-Usual group was supervised via phone consultations. The primary outcome measured was maximal oxygen consumption (VO2max). Results: Within-group comparisons showed significant improvements in VO2max (PCR-Mobile = 0.011 vs. PCR-Usual = 0.020) and METs (PCR-Mobile = 0.011 vs. PCR-Usual = 0.011) for both groups. Conclusions: These findings suggest that a 6-week home-based CR program with exercise readjustment using a mobile app can potentially enhance exercise capacity as effectively as verbal supervision.
Aspects of Nickel, Cobalt and Lithium, the Three Key Elements for Li-Ion Batteries: An Overview on Resources, Demands, and Production
Authors: Kalungi Paul , Yao Zhuo , Huang Hong
Published: September 2024

With the booming of renewable clean energies towards reducing carbon emission, demands for lithium-ion batteries (LIBs) in applications to transportation vehicles and power stations are increasing exponentially. As a consequence, great pressures have been posed on the technological development and production of valuable elements key to LIBs, in addition to concerns about depletion of natural resources, environmental impacts, and management of waste batteries. In this paper, we compile recent information on lithium, nickel, and cobalt, the three most crucial elements utilized in LIBs, in terms of demands, current identified terrestrial resources, extraction technologies from primary natural resources and waste. Most nickel and cobalt are currently produced from high-grade sulfide ores via a pyrometallurgical approach. Increased demands have stimulated production of Ni and Co from low-grade laterites, which is commonly performed through the hydrometallurgical process. Most lithium exists in brines and is extracted via evaporation–precipitation in common industrial practice. It is noteworthy that at present, the pyrometallurgical process is energy-intensive and polluting in terms of gas emissions. Hydrometallurgical processes utilize large amounts of alkaline or acidic media in combination with reducing agents, generating hazardous waste streams. Traditional evaporation–precipitation consumes time, water, and land. Extraction of these elements from deep seas and recycling from waste are emerging as technologies. Advanced energy-saving and environmentally friendly processes are under extensive research and development and are crucial in the process of renewable clean energy implementation.
Electron Magnetic Resonance Study of Ni50.2Mn28.3Ga21.5 Powders
Authors: Dubiel Łukasz , Cieniek Bogumił , Maziarz Wojciech , Stefaniuk Ireneusz
Published: September 2024

In the present paper, we present an electron magnetic resonance (EMR) study of Ni50.2Mn28.3Ga21.5 powders obtained from melt-spun ribbons in the milling process. We registered EMR spectra in various temperatures at the X-band. In the EMR spectra recorded for the samples taken at the beginning of the milling process, the “training effect” was observed. After 2 h of milling, this phenomenon was no longer observed. To determine the basic EMR parameters, such as linewidth, resonance field, and asymmetry parameters, the experimental data were fitted using a single metallic Lorentz line. In high-temperature regions, we observed the influence of dispersion on the shape of the spectra, but as the temperature decreased, the asymmetry of line was reduced. The shift in the resonance field value at high temperatures and the temperature dependence of the linewidth below Curie temperature indicate that the investigated samples exhibited a characteristics of a spin-glass alloy.
Forensic Genomic Analysis Determines That RaTG13 Was Likely Generated from a Bat Mating Plug
Authors: Massey Steven E.
Published: September 2024

RaTG13 is phylogenomically the closest related coronavirus to SARS-CoV-2; consequently, understanding the provenance of this high-value genome sequence is important in understanding the origin of SARS-CoV-2. While RaTG13 was described as being generated from a Rhinolophus affinis fecal swab obtained from a mine in Mojiang, Yunnan, numerous investigators have pointed out that this is inconsistent with the low proportion of bacterial reads in the sequencing dataset. Metagenomic analysis confirms that only 10.3% of small-subunit (SSU) rRNA sequences in the dataset are bacterial, which is inconsistent with a fecal sample. In addition, the bacterial taxa present in the sample are shown to be inconsistent with fecal material. The assembly of mitochondrial SSU rRNA sequences in the dataset produces a sequence 98.7% identical to R. affinis mitochondrial SSU rRNA, indicating that the sample was generated from R. affinis or a closely related species. In addition, 87.5% of the reads in the dataset map to the Rhinolophus ferrumequinum genome, and 62.2% of these map to protein-coding genes, indicating that the dataset represents a Rhinolophus sp. transcriptome rather than a fecal swab sample. Differential gene expression analysis reveals that the pattern of expressed genes in the RaTG13 dataset is similar to that of RaTG15, which was also collected from the Mojiang mine. GO enrichment analysis reveals the overexpression of spermatogenesis- and olfaction-related genes in both datasets. This observation is consistent with a mating plug found in female Rhinolophid bats and suggests that RaTG13 was mis-sampled from such a plug. A validated natural provenance of the RaTG13 dataset throws into relief the unusual features of the SARS-CoV-2 genome.
Investigating the Orogenic Evolution of the Wushan–Shangdan Ocean in the Qinling–Qilian Conjunction Zone: Insights from the Early Devonian Tailu Pluton
Authors: Lin Hao , Li Zuochen , Pei Xianzhi , Li Ruibao , Zhou Hai , Wang Meng , Zhao Shaowei , Qin Li , Wang Mao
Published: September 2024

The main ocean–continent transformation stage of the Qinling and Qilian conjunction zone happened in the Early Paleozoic with the occurrence of a lot of subduction–collision–related magmatic rocks. However, there is still considerable controversy over the duration of the subduction–collision orogeny process of the Proto-Tethys Ocean, here termed as the Wushan–Shangdan Ocean. We provide geochronological, geochemical, and Lu-Hf isotopic data for typical Early Devonian igneous rocks there, named Tailu pluton. The Tailu pluton at 410 Ma comprised K-rich, calc-alkaline, metaluminous A-type granite with low Y/Nb ratios (0.85 to 1.35) and A/CNK values (0.90 to 1.01); with high SiO2 contents (65.44 to 74.46 wt%), Mg# values (39.2 to 50.7), and zircon saturation temperatures (745 to 846 °C); and with negative εHf (t) values (−8.0 to −1.9); therefore, they resulted from the partial melting of the ancient felsic lower crust accompanied by the incorporation of mantle-derived material during the intraplate magmatism process. Research on Tailu pluton has provided more sufficient evidence for the evolution process of the Qinling–Qilian conjunction zone in the Early Paleozoic, associated with evolution of the Wushan–Shangdan Ocean, the northern part of the Proto-Tethys Ocean.