bluuebunny/crossref_metadata_2025 huggingface dataset:
Beyond NMDA Receptors: A Narrative Review of Ketamine’s Rapid and Multifaceted Mechanisms in Depression Treatment
Authors: Antos Zuzanna , Żukow Xawery , Bursztynowicz Laura , Jakubów Piotr
Published: December 2024

The rising prevalence of depression, with its associated suicide risk, demands effective fast-acting treatments. Ketamine has emerged as promising, demonstrating rapid antidepressant effects. While early studies show swift mood improvements, its precise mechanisms remain unclear. This article aims to compile and synthesize the literature on ketamine’s molecular actions. Ketamine primarily works by antagonizing NMDA receptors, reducing GABAergic inhibition, and increasing glutamate release. This enhanced glutamate activates AMPA receptors, triggering crucial downstream cascades, including BDNF-TrkB and mTOR pathways, promoting synaptic proliferation and regeneration. Moreover, neuroimaging studies have demonstrated alterations in brain networks involved in emotional regulation, including the Default Mode Network (DMN), Central Executive Network (CEN), and Salience Network (SN), which are frequently disrupted in depression. Despite the promising findings, the literature reveals significant inaccuracies and gaps in understanding the full scope of ketamine’s therapeutic potential. For instance, ketamine engages with opioid receptors, insinuating a permissive role of the opioid system in amplifying ketamine’s antidepressant effects, albeit ketamine does not operate as a direct opioid agonist. Further exploration is requisite to comprehensively ascertain its safety profile, long-term efficacy, and the impact of genetic determinants, such as BDNF polymorphisms, on treatment responsiveness.
Identification of Protein Networks and Biological Pathways Driving the Progression of Atherosclerosis in Human Carotid Arteries Through Mass Spectrometry-Based Proteomics
Authors: Kalló Gergő , Zaman Khadiza , Potor László , Hendrik Zoltán , Méhes Gábor , Tóth Csaba , Gergely Péter , Tőzsér József , Balla György , Balla József , Prokai Laszlo , Csősz Éva
Published: December 2024

Vulnerable atherosclerotic plaques, especially hemorrhaged lesions, are the major cause of mortalities related to vascular pathologies. The early identification of vulnerable plaques helps to stratify patients at risk of developing acute vascular events. In this study, proteomics analyses of human carotid artery samples collected from patients with atheromatous plaques and complicated lesions, respectively, as well as from healthy controls were performed. The proteins isolated from the carotid artery samples were analyzed by a bottom-up shotgun approach that relied on nanoflow liquid chromatography–tandem mass spectrometry analyses (LC–MS/MS) using both data-dependent (DDA) and data-independent (DIA) acquisitions. The data obtained by high-resolution DIA analyses displayed a stronger distinction among groups compared to DDA analyses. Differentially expressed proteins were further examined using Ingenuity Pathway Analysis® with focus on pathological and molecular processes driving atherosclerosis. From the more than 150 significantly regulated canonical pathways, atherosclerosis signaling and neutrophil extracellular trap signaling were verified by protein-targeted data extraction. The results of our study are expected to facilitate a better understanding of the disease progression’s molecular drivers and provide inspiration for further multiomics and hypothesis-driven studies.
The Role of ctDNA in the Management of Non-Small-Cell Lung Cancer in the AI and NGS Era
Authors: Costa Jacopo , Membrino Alexandro , Zanchetta Carol , Rizzato Simona , Cortiula Francesco , Rossetto Ciro , Pelizzari Giacomo , Aprile Giuseppe , Macerelli Marianna
Published: December 2024

Liquid biopsy (LB) involves the analysis of circulating tumour-derived DNA (ctDNA), providing a minimally invasive method for gathering both quantitative and qualitative information. Genomic analysis of ctDNA through next-generation sequencing (NGS) enables comprehensive genetic profiling of tumours, including non-driver alterations that offer prognostic insights. LB can be applied in both early-stage disease settings, for the diagnosis and monitoring of minimal residual disease (MRD), and advanced disease settings, for monitoring treatment response and understanding the mechanisms behind disease progression and tumour heterogeneity. Currently, LB has limited use in clinical practice, primarily due to its significant costs, limited diagnostic yield, and uncertain prognostic role. The application of artificial intelligence (AI) in the medical field is a promising approach to processing extensive information and applying it to individual cases to enhance therapeutic decision-making and refine risk assessment.
Darolutamide in Combination with Radium-223 Exhibits Synergistic Antitumor Efficacy in LNCaP Prostate Cancer Models
Authors: Hagemann Urs B. , Schatz Christoph A. , Suominen Mari I. , Schlicker Andreas , Knuuttila Matias , Wilson Timothy , Alhoniemi Esa , Käkönen Sanna-Maria , Haendler Bernard , Scholz Arne
Published: December 2024

Despite treatment, prostate cancer commonly progresses into castration-resistant prostate cancer (CRPC), which remains largely incurable, requiring the development of new interventions. Darolutamide is an orally administered second-generation androgen receptor inhibitor indicated for patients with non-metastatic CRPC or metastatic hormone-sensitive prostate cancer. Here, we evaluated the effect of androgen receptor (AR) inhibition by darolutamide in combination with DNA double-strand-break-inducing targeted radium-223 alpha therapy in vitro and in an intratibial LNCaP xenograft model mimicking prostate cancer metastasized to bone. The results highlight the synergistic antitumor efficacy of darolutamide in combination with radium-223 both in vitro and in vivo. This effect was most likely driven by the downregulation of genes involved in DDR signaling, which was demonstrated in vitro by a gene set enrichment analysis. The combination treatment also reduced pathological tumor-induced effects in bone by decreasing the number of osteoblasts and osteoclasts and reducing abnormal bone formation in tumor-bearing bone. Additionally, it was shown that darolutamide does not affect the uptake of radium-223 into bone tissue. These results support the investigation of darolutamide in combination with radium-223 for the treatment of patients with CRPC metastasized to bone.
Molecular Mechanisms of Somatic Cell Cloning and Other Assisted Reproductive Technologies in Mammals: Which Determinants Have Been Unraveled Thus Far?—Current Status, Further Progress and Future Challenges
Authors: Samiec Marcin
Published: December 2024

Taking into consideration recent reports on the successful creation of cloned rhesus monkeys [...]
Inflammatory Stimulation Upregulates the Receptor Transporter Protein 4 (RTP4) in SIM-A9 Microglial Cells
Authors: Fujita Wakako , Kuroiwa Yusuke
Published: December 2024

The receptor transporter protein 4 (RTP4) is a receptor chaperone protein that targets class A G-protein coupled receptor (GPCR)s. Recently, it has been found to play a role in peripheral inflammatory regulation, as one of the interferon-stimulated genes (ISGs). However, the detailed role of RTP4 in response to inflammatory stress in the central nervous system has not yet been fully understood. While we have previously examined the role of RTP4 in the brain, particularly in neuronal cells, this study focuses on its role in microglial cells, immunoreactive cells in the brain that are involved in inflammation. For this, we examined the changes in the RTP4 levels in the microglial cells after exposure to inflammatory stress. We found that lipopolysaccharide (LPS) treatment (0.1~1 µg/mL, 24 h) significantly upregulated the RTP4 mRNA levels in the microglial cell line, SIM-A9. Furthermore, the interferon (IFN)-β mRNA levels and extracellular levels of IFN-β were also increased by LPS treatment. This upregulation was reversed by treatment with neutralizing antibodies targeting either the interferon receptor (IFNR) or toll-like receptor 4 (TLR4), and with a TLR4 selective inhibitor, or a Janus kinase (JAK) inhibitor. On the other hand, the mitogen-activated protein kinase kinase (MEK) inhibitor, U0126, significantly enhanced the increase in RTP4 mRNA following LPS treatment, whereas the PKC inhibitor, calphostin C, had no effect. These findings suggest that in microglial cells, LPS-induced inflammatory stress activates TLR4, leading to the production of type I IFN, the activation of IFN receptor and JAK, and finally, the induction of RTP4 gene expression. Based on these results, we speculate that RTP4 functions as an inflammation-responsive molecule in the brain. However, further research is needed to fully understand its role.
What Can Be Learned by Knowing Only the Amino Acid Composition of Proteins?
Authors: Lobanov Michail Yu. , Surin Alexey A. , Galzitskaya Oxana V.
Published: December 2024

The amino acid composition of proteins depends on many factors. It varies in organisms that are distant in taxonomic position. The amino acid composition of proteins depends on the localization of proteins in cells and tissues and the structure of proteins. The question arises: is it possible to separate different proteomes using only the amino acid composition of proteins? Is it possible to determine, considering only its amino acid composition, to what structural class the protein under study will belong? We have developed a method and a measure that maximally separate two sets of proteins. As a result, we assign each protein an R-value, positive values of which are more characteristic of the first set, and negative ones—of the second. By studying the distribution of R in two sets, we can determine how much these sets differ in composition. Also, when examining a new protein, we can determine if it is more similar to the first set or the second. In this paper, we show that using only amino acid composition, it is possible to separate sets of proteins belonging to different organisms, as well as proteins that differ in function or structure. In all cases, we assign to proteins a measure R that maximally separates the studied sets. This approach can be further used to annotate proteins with unknown functions.
Methodological Assessment of ExoGAG for Isolation of Cerebrospinal Fluid Extracellular Vesicles as a Source of Biomarkers
Authors: Salvat-Rovira Nil , Vazquez-Oliver Anna , Rivas-Asensio Elisa , Herrero-Lorenzo Marina , Gámez-Valero Ana , Pérez-Pérez Jesús , Izquierdo Cristina , Campolongo Antonia , Martí Eulàlia , Kulisevsky Jaime , Pérez-González Rocío
Published: December 2024

Extracellular vesicles (EVs) in cerebrospinal fluid (CSF) represent a valuable source of biomarkers for central nervous system (CNS) diseases, offering new pathways for diagnosis and monitoring. However, existing methods for isolating EVs from CSF often prove to be labor-intensive and reliant on specialized equipment, hindering their clinical application. In this study, we present a novel, clinically compatible method for isolating EVs from CSF. We optimized the use of ExoGAG, a commercially available reagent that has been tested in plasma, urine and semen, and compared it directly with differential ultracentrifugation using Western blotting, protein quantification, nanoparticle tracking analysis, and cryogenic electron microscopy. Additionally, we analyzed the presence of specific microRNAs (miRNAs) known to be present in CSF-derived EVs. Our data demonstrate that ExoGAG is an effective method for isolating EVs from CSF, yielding a higher amount of EVs compared to traditional ultracentrifugation methods, and with comparable levels of specific miRNAs. In conclusion, the use of ExoGAG in a clinical setting may facilitate the testing of biomarkers essential for tracking brain pathology in CNS diseases.
Untargeted Mutation Triggered by Ribonucleoside Embedded in DNA
Authors: Suzuki Tetsuya , Yasui Kiyoharu , Komatsu Yasuo , Kamiya Hiroyuki
Published: December 2024

DNA polymerases frequently misincorporate ribonucleoside 5′-triphosphates into nascent DNA strands. This study examined the effects of an incorporated ribonucleoside on untargeted mutations in human cells. Riboguanosine (rG) was introduced into the downstream region of the supF gene to preferentially detect the untargeted mutations. The plasmid containing rG was transfected into U2OS cells and the replicated DNA was recovered after 48 h. The mutation analysis using the indicator Escherichia coli RF01 strain showed the frequent induction of untargeted base substitutions at the G bases of 5′-GpA-3′ dinucleotides, similar to action-at-a-distance mutations induced by an oxidatively damaged base, 8-oxo-7,8-dihydroguanine, and an apolipoprotein B mRNA-editing enzyme, catalytic polypeptide-like 3 (APOBEC3) cytosine deaminase. APOBEC3B was then knocked down by RNA interference and the plasmid bearing rG was introduced into the knockdown cells. The untargeted mutations at 5′-GpA-3′ sites were reduced by ~80%. These results suggested that ribonucleosides embedded in DNA induce base substitution mutations at G bases in the same strand by an APOBEC3B-dependent mechanism, implying that ribonucleosides contribute to APOBEC3-dependent cancer initiation events.
Sexual Dimorphism of Ethanol-Induced Mitochondrial Dynamics in Purkinje Cells
Authors: Khatoon Rehana , Fick Jordan , Elesinnla Abosede , Waddell Jaylyn , Kristian Tibor
Published: December 2024

The cerebellum, a key target of ethanol’s toxic effects, is associated with ataxia following alcohol consumption. However, the impact of ethanol on Purkinje cell (PC) mitochondria remains unclear. To investigate how ethanol administration affects mitochondrial dynamics in cerebellar Purkinje cells, we employed a transgenic mouse model expressing mitochondria-targeted yellow fluorescent protein in Purkinje cells (PC-mito-eYFP). Both male and female PC-mito-eYFP mice received an intraperitoneal injection of ethanol or vehicle. One hour after ethanol administration, the animals were perfusion fixed or their cerebellum tissue or isolated mitochondria were collected. Cerebellum sections were analyzed using confocal microscopy to assess changes in mitochondrial length distribution. In vivo superoxide levels were measured using dihydroethidium (DHE), and mitochondrial NAD levels were determined by high-performance liquid chromatography (HPLC). Our findings revealed a sex-dependent response to ethanol administration in mitochondrial size distribution. While male Purkinje cell mitochondria exhibited no significant changes in size, female mitochondria became more fragmented after one hour of ethanol administration. This coincided with elevated phosphorylation of the fission protein Drp1 and increased superoxide production, as measured by DHE fluorescence intensity. Similarly, mitochondrial NAD levels were significantly reduced in female mice, but no changes were observed in males. Our results demonstrate that ethanol induced mitochondrial fragmentation through increased free radical levels, due to reduced NAD and increased p-Drp1, in PC cells of the female cerebellum.
Compartmentalization of the Inflammatory Response in the Pericardial Cavity in Patients Undergoing Cardiac Surgery
Authors: El-Diasty Mohammad M. , Rodríguez Javier , Pérez Luis , Souaf Souhayla , Eiras Sonia , Fernández Angel L.
Published: December 2024

The systemic inflammatory response after cardiopulmonary bypass has been widely studied. However, there is a paucity of studies that focus on the local inflammatory changes that occur in the pericardial cavity. The purpose of this study is to assess the inflammatory mediators in the pericardial fluid of patients undergoing cardiac surgery. We conducted a prospective cohort study on patients undergoing aortic valve replacement. Pericardial fluid and peripheral venous blood samples were collected after the opening of the pericardium. Additional samples were obtained from peripheral blood and the pericardial fluid shed through mediastinal drains 24 and 48 h after surgery. Levels of interleukin 1α (IL-1α), interleukin 1β (IL-1β), interleukin 2 (IL-2), interleukin 4 (IL-4), interleukin 6 (IL-6), interleukin 8 (IL-8), interleukin 10 (IL-10), tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ), vascular endothelial growth factor (VEGF), monocyte chemotactic protein-1 (MCP-1), epidermal growth factor (EGF), soluble E-selectin, L-selectin, P-selectin, intercellular adhesion molecule-1 (ICAM-1), and vascular cell adhesion molecule-1 (VCAM-1) were determined in all pericardial fluid and serum samples. A total of 45 patients with a mean age of 74 years were included, of which 66% were males. Serum levels of IL-6, IL-8, and MCP-1 were significantly increased at 24 and 48 h after surgery. No significant changes were observed in the serum levels of the remaining mediators. A significant increase of postoperative pericardial fluid levels of IL-1α, IL-1β, IL-6, IL-8, IL-10, IFN-γ, VEGF, MCP-1, VCAM-1, and P-selectin was observed at 24 and 48 h after surgery. There is a robust systemic and pericardial inflammatory response after cardiac surgery on cardiopulmonary bypass. However, postoperative pericardial inflammatory activity shows a distinct pattern and is more marked than at the systemic level. These findings suggest that there is a compartmentalization of the inflammatory response within the pericardial cavity after cardiac surgery.
A Possible Phenotype-to-Genotype Association of Novel Single-Nucleotide Variants in the Coding Exons of the ZNF469 Gene to Arterial Aneurysmal and Dissection Diseases
Authors: Wolf Adam , Moore Peyton , Hong Charles , Sathyamoorthy Mohanakrishnan
Published: December 2024

After reporting the first known clinical case associating compound heterozygous single-nucleotide variants in Exon 2 of ZNF469 to aortic aneurysmal and iliac dissection, we began prospective surveillance in our vascular genetic practice for similar cases. Herein, we present nine (9) subjects from a total cohort of 135 with arterial aneurysms or dissections who revealed single-nucleotide variants in ZNF469 with no other alterations in a panel of 35 genes associated with aneurysmal and dissection disorders. Five out of nine (5/9) single-nucleotide variants were in Exon 1, and four out of nine (4/9) mutations were in Exon 2, both of which are principal coding exons for this gene. Eight out of nine (8/9) were ACMG variants of unknown significance (VUSs), and one out of nine (1/9) was an ACMG pathogenic mutation previously associated to brittle cornea syndrome (BCS). Of our nine subjects, four (44.4%) experienced clinically significant vascular dissection, and four (44.4%) had a family history of one or more first-degree relatives with aneurysmal or dissection diseases. This novel genetic case series significantly strengthens our initial discovery of ZNF469’s potential association with arterial aneurysmal/dissection diseases through the study of this cohort of unrelated patients.
Identification and Transcriptome Analysis of Bursaphelenchus xylophilus with Excellent Low Temperature Resistance
Authors: Zhang Yue , Zhao Ruiwen , Jing Tingting , Lin Sixi , Ding Xiaolei
Published: December 2024

Bursaphelenchus xylophilus is one of the most destructive quarantine pests, causing irreversible damage to pine trees. However, the unexpected identification of pine wilt disease in Northern China indicates that Bursaphelenchus xylophilus can survive under low temperatures. In this study, we analyzed the reproductivity variations among 18 different isolates, and SC13 was identified to have excellent low temperature resistance. Subsequent molecular analysis of SC13 indicated its distinct gene expression under low temperatures. The epidermal growth factor, nematode cuticle collagen and G-protein-coupled receptor genes with environmental adaptation functions were demonstrated to be differentially expressed under low temperatures. Meanwhile, morphological observations also indicated that SC13 contained significantly more lipid drops in low-temperature treatments. Generally, the identification of representative Bursaphelenchus xylophilus isolates will facilitate relevant studies in the future, and the discovery of the gene expression and morphological changes of Bursaphelenchus xylophilus under low temperatures could expand the current understanding of the environmental adaption abilities of such invasive nematodes.
Cytotoxic Natural Products from Cryptomeria japonica (Thunb. ex L.) D.Don
Authors: Heieren Bjørn Tobiassen , Dyrdal Anja Strandvoll , Herfindal Lars , Holmelid Bjarte , Brede Cato , Andersen Heidi Lie , Fossen Torgils
Published: December 2024

Cryptomeria japonica is a commercially important tree native to Japan. The tree belongs to the ancient genus Cryptomeria and has found important uses as a medicinal plant, as well as a main source of timber in Japan. In recent years, there has been an increased interest in discovering extended uses of C. japonica as a source of novel bioactive natural products with potential applications as lead compounds for active principles of future drugs. The compounds were isolated by a combination of two-phase extraction, XAD-7 Amberlite column chromatography, Sephadex LH-20 column chromatography and preparative High Performance Liquid Chromatography (HPLC). The structures were determined by a combination of several 1D and 2D Nuclear Magnetic Resonance (NMR) experiments and high-resolution mass spectrometry. Here, we report on the isolation and characterization of the novel biflavone glucoside hinokiflavone 7″-O-β-glucopyranoside, in addition to sixteen known compounds including the flavonols quercetin, quercetin 3-O-α-rhamnopyranoside and quercetin 3-O-β-galactopyranoside, the dihydroflavonols taxifolin 3-O-β-glucopyranoside, taxifolin 7-O-β-glucopyranoside, the flavanones naringenin, naringenin 7-O-β-galactopyranoside and eriodictyol 4′-O-β-glucopyranoside, the flavanol catechin, the biflavonoid amentoflavone, the dihydrochalcone phloretin 2′-O-β-glucopyranoside, the sesquiterpenoid roseoside, the polyphenolic compounds chlorogenic acid, methyl chlorogenate and the flavanocoumarins catechin-(7,8)-7″-(3,4 dihydroxyphenyl)-dihydro-8″(3H)-pyranone, and mururin A. The compounds exhibited low-to-moderate cytotoxic activity against MOLM-13 leukemia cells.
Advancing LVAD Technology: Overcoming Challenges and Shaping the Future of Mechanical Circulatory Support
Authors: Kozakov Kostiantyn , Provaznik Zdenek , Schmid Christof , Camboni Daniele
Published: December 2024

Ventricular assist devices (VADs) invigorated the management of patients with advanced heart failure, providing a lifeline for patients awaiting transplantation or requiring long-term circulatory support. This article reviews recent advances in VAD technologies, focusing on key areas of progress to overcome existing challenges and the potential for future applications. The reduction or possible elimination of infection-prone components and the evolution to transcutaneous energy transfer systems are two main research fields to reach a new quality of life category for VADs patients. Miniaturization and enhanced biocompatibility have resulted in smaller, less invasive devices with a significantly reduced risk of complications and mortality. Advances in percutaneous ventricular assist devices have emerged, contributing to the creation of less invasive options with or without intracardiac pumps, and facilitating their use for both left and right ventricles. These devices have gained more and more features, including the use of artificial intelligence. Moreover, the possibility of long-term use of intracardiac pumps offers a potential bridge to transplantation, allowing ambulation and probably also long-term circulatory support. Despite considerable advances, challenges remain, particularly in terms of improving durability, reducing the risk of ischemic events, further refining materials, and more sophisticated control and synchronization between systems that adapt to changing physiological demands.
The First Report on Liver Resection Using the Novel Japanese hinotori™ Surgical Robot System: First Case Series Report of 10 Cases
Authors: Nakamura Kenichi , Koide Tetsuya , Higashiguchi Takahiko , Matsuo Kazuhiro , Endo Tomoyoshi , Kikuchi Kenji , Morohara Koji , Katsuno Hidetoshi , Uyama Ichiro , Suda Koichi , Morise Zenichi
Published: December 2024

Background: In Japan, the hinotori™ surgical robot system (Medicaroid Corporation, Kobe, Japan) was approved for gastrointestinal surgeries in October 2022. This report details our initial experience performing liver resection using the hinotori™ system. Methods: Ten patients, who were assessed as cases that would benefit from the robot-assisted procedure, underwent liver resections using the hinotori™ system at Fujita Health University, Okazaki Medical Center, between August 2023 and October 2024. The backgrounds (patient, tumor, and liver function conditions, along with types of liver resections and previous surgical procedures) and short-term outcomes (operation time, blood loss, postoperative complications, open conversion, length of hospital stay, and mortality) of the cases were evaluated. Results: Eight cases of partial liver resection, one extended left medial sectionectomy, and one left hemi-hepatectomy were performed. Six cases of hepatocellular carcinomas, three cases of liver metastases, and one case of hepatolithiasis were included. There were seven male and three female patients with a median age of 70 years. Three physical status class III and seven class II patients were included. The median body mass index was 24. Five patients had previous upper abdominal surgical histories and five patients had liver cirrhosis. The median operation time was 419.5 min, and the median intraoperative blood loss was 276 mL. An open conversion in one hepatocellular carcinoma case was carried out due to bleeding from collateral vessels in the round ligament. The median length of hospital stay was 7.5 days. A grade IIIa complication (delayed bile leakage) was developed in one case. All patients with tumors underwent R0 resection. There were no cases of mortality. Conclusions: Liver resection using the hinotori™ system was feasibly performed. This study reports the first global use of the hinotori™ system for liver resection.
The Importance of Bright Spotty Lesions on Magnetic Resonance Imaging in Predicting Chronic Neuropathic Pain in Myelitis
Authors: Min Je Hong , Sohn Sung-Yeon , Joo In Soo
Published: December 2024

Background/Objectives: Chronic neuropathic pain (CNP) stands as one of the most debilitating complications in patients with myelitis owing to its challenging management. Bright spotty lesions (BSLs) are frequently observed in neuromyelitis optica spectrum disorder (NMOSD), but few reports have discussed CNP in myelitis. We aim to demonstrate that BSLs could be one of the potential prognostic factors for CNP development in myelitis. Methods: We examined 63 patients diagnosed with myelitis. Patients were categorized into CNP and non-CNP groups. We assessed the severity of clinical symptoms and the oral steroid dose administered after pulse therapy. Spine magnetic resonance imaging (MRI) of each patient was reviewed to analyze the characteristics of myelitis. Serological and cerebrospinal fluid (CSF) findings were also examined to confirm the etiology. Results: CNP was observed in 27 patients (42.9%). The mean onset age of patients with CNP was 45.26 ± 14.16 years. The MRI lesions exhibited more enhanced features and bright spotty lesions (BSLs) in the CNP group (χ2 test, p < 0.05). Patients with CNP received a lower oral steroid dose during the first month after symptom onset (χ2 test, p < 0.05). Multivariate logistic regression analysis revealed that patients with CNP exhibited significant BSLs in their myelitis lesions on spine MRI (OR 4.965; 95% CI, 1.282 to 19.235, p = 0.02). Conclusions: Although the exact mechanism remains unknown, the presence of BSLs on spine MRI could serve as an independent prognostic factor for CNP development. Additionally, our study suggests that lower oral steroid doses administered immediately after symptom onset are associated with CNP development. Further investigation with a larger cohort is warranted to validate our findings.
Successful Desensitization to Irinotecan in a Patient with Metastatic Esophageal Squamous Cell Carcinoma and a History of Anaphylaxis in Response to Irinotecan—Case Report and Literature Review
Authors: Ali Selda , Nedelcu Denisa-Mihaela , Serescu Radu , Bumbăcea Roxana Silvia
Published: December 2024

Background: Irinotecan is a topoisomerase I inhibitor used for the treatment of various cancers, such as gastrointestinal, pancreatic, pulmonary, ovarian, and cervical cancers. Among chemotherapy agents, it represents a rare trigger of drug hypersensitivity reactions, with few cases being reported until today. Methods: We present the case of a patient with metastatic esophageal cancer and a history of irinotecan-induced grade IV (WAO classification) anaphylaxis. An IgE-mediated reaction was confirmed in our case, as evidenced by a positive intradermal skin test result, and we carried out a successful desensitization protocol, given irinotecan’s indispensability in the treatment regimen. Our case underscores the fact that in such situations where the culprit drug is also the only therapeutic option available for such a patient, implementing a desensitization protocol may represent the only viable approach to ensure safe and successful dosing. Results: A comprehensive review of the literature was also conducted to assess previously reported irinotecan-induced hypersensitivity reactions, the utility of skin tests in identifying sensitisation to irinotecan, and the existing desensitization protocols. We found a total of seventeen cases of hypersensitivity reactions to irinotecan in the literature, out of which four provided the skin test results obtained and six performed desensitization protocols for irinotecan. Conclusions: Our literature review highlights that skin testing and desensitization protocols can provide suitable solutions for managing hypersensitivity reactions to irinotecan.
Retinal Vascular Complications in Cocaine Abuse: A Case Report and a Literature Review
Authors: Armentano Marta , Alisi Ludovico , Visioli Giacomo , Saturno Maria Carmela , Barba Arianna , Speranzini Alessio , Albanese Giuseppe Maria , Gharbiya Magda , Iannetti Ludovico
Published: December 2024

This comprehensive review examines the ocular vascular complications of cocaine use, focusing on its effects on retinal vasculature and inflammation. A rare case of bilateral frosted branch angiitis (FBA) in a 48-year-old man with a history of intranasal cocaine abuse is presented as an illustrative example to stimulate discussion. The case highlights severe retinal ischemia and vascular sheathing, with no identifiable infectious or autoimmune cause, ultimately complicated by systemic vascular events. Integrating this case with a review of the literature, we discuss cocaine’s vasoconstrictive and immunomodulatory effects and their role in retinal pathology, including vasculitis, vascular occlusions, hemorrhages, and optic neuropathy. Although often a diagnosis of exclusion, and with rare and poorly understood consequences, this review underscores the importance of considering cocaine abuse in the differential diagnosis of complex retinal presentations.
Rates of School Absences in Pediatric Scoliosis Patients and Work Absences in Their Parents/Caregivers: A Retrospective Analysis
Authors: Paradkar Ria , Regan Christina , Nolte Charles P. , Stans Anthony , Shaughnessy William , Mulford Kellen , Milbrandt Todd A. , Larson A. Noelle
Published: December 2024

Background/Objectives: The burden of scoliosis care extends beyond treatment costs and includes missed school for patients and lost income for parents. Chronic absenteeism, defined as more than 18 days of missed school, can have a significant impact on a child’s educational progression, but missed school and work due to scoliosis treatment are not well quantified in the literature. This study investigates absenteeism among scoliosis patients and their caregivers. Methods: We conducted a retrospective comparative study of survey results based on surgery timing and surgery type. Patients and caregivers presenting for clinic visits for scoliosis treatment at a single large tertiary care center from 2014 to 2022 were queried. Results: We collected 2772 surveys from 1104 unique patients. Of these, 223 surveys from 132 patients were within one year of surgery: 140 post-fusion surveys, 71 post-nonfusion surveys, and 11 post-halo/multistage surgery surveys. A total of 2280 surveys were from 1022 nonoperatively treated patients. School absenteeism was significantly higher for surgeries during the school year compared to summer in both the fusion and nonfusion groups, though work absenteeism showed no significant differences. Halo/multistage surgery patients had the highest rates of absenteeism. Conclusions: This study highlights the impacts of scoliosis surgery timing and type on absenteeism among patients and their caregivers. Surgery during summer breaks reduces school absenteeism and academic disruption. Halo/multistage surgery patients face the greatest risk of chronic absenteeism from school, indicating a need for targeted interventions. Optimized surgical timing and planning can help families navigate the educational and financial challenges of scoliosis treatment.
Micro-CT Assessment During Embedding of Prototype Ti Alloy Multi-Spiked Connecting Scaffold in Subchondral Trabecular Bone of Osteoarthritic Femoral Heads, Depending on Host BMI
Authors: Uklejewski Ryszard , Winiecki Mariusz , Patalas Adam , Mietliński Patryk , Zawadzki Paweł , Dąbrowski Mikołaj
Published: December 2024

The prototype of a biomimetic multi-spiked connecting scaffold (MSC-Scaffold) represents an essential innovation in the fixation in subchondral trabecular bone of components for a new generation of entirely cementless hip resurfacing arthroplasty (RA) endoprostheses. In designing such a functional biomaterial scaffold, identifying the microstructural and mechanical properties of the host bone compromised by degenerative disease is crucial for proper post-operative functioning and long-term maintenance of the endoprosthesis components. This study aimed to explore, depending on the occurrence of obesity, changes in the microstructure and mechanical properties of the subchondral trabecular bone in femoral heads of osteoarthritis (OA) patients caused by the MSC-Scaffold embedding. Computed microtomography (micro-CT) scanning of femoral heads from OA patients was conducted before and after the mechanical embedding of the MSC-Scaffold. Bone morphometric parameters such as bone volume/total volume (BV/TV), trabecular thickness (Tb.Th), and trabecular number (Tb.N) for regions surrounding the MSC-Scaffold were computed, and the mechanical properties such as bone density (ρB), bone compressive strength (S), and the Young’s modulus (E) within these regions were calculated. A statistically significant increase in BV/TV (by 15.0% and 24.9%) and Tb.Th (by 13.1% and 42.5%) and a decrease in Tb.N (by 15.2% and 23.6%) were observed, which translates to an increase in ρB (by 15.0% and 24.9%), S (by 28.8% and 49.5%), and E (by 18.0% and 29.8%) in non-obese patients and obese patients, respectively. These changes in properties are favorable for the mechanical loads’ transfer from the artificial joint surface via the MSC-Scaffold to the periarticular trabecular bone of the OA femoral head in the postoperative period.
Evaluation of Internal Fit in Custom-Made Posts and Cores Fabricated with Fully Digital Versus Conventional Techniques
Authors: Jensen Eric , Sayardoust Shariel
Published: December 2024

Objective: This study aimed to assess and compare the internal fit of custom-made posts and cores fabricated using digital impressions (DI) and conventional vinyl polysiloxane (VPS) impressions in restorative dentistry. Materials and Methods: A typodont tooth model, simulating the anatomy of the root canal of a central incisor, was utilized for the study. Two groups were formed, Group A and Group B, and each group provided a total of 18 impressions of two types: DIs and VPS impressions. In Group A, posts and cores (PCs) were fabricated using Selective Laser Melting (SLM) from the DIs. Meanwhile, in Group B, conventionally cast (CC) PCs were created from the VPS impressions. Silicone replicas of the internal surfaces were produced, and measurements were made at seven different points for each group. A statistical analysis was performed to assess the differences in internal fit between the two impression techniques. Results: The results revealed a statistically significant difference in mean internal fit between Group A (DI and SLM) and Group B (VPS and CC), with Group A exhibiting a mean internal fit of 182.6 µm and Group B showing a mean of 205.9 µm. While both groups demonstrated considerable variability in internal fit measurements, the digital impression technique showed promise for achieving superior internal fit, with a significantly greater fit for measuring points on sides and the most apical part of the post for Group A. Variations were observed across different measuring points, emphasizing the impact of impression technique on specific regions within the tooth. Conclusion: This study contributes to the growing body of knowledge in digital dentistry by highlighting the potential benefits of DIs in achieving a superior internal fit for custom-made PCs. Clinicians may consider the advantages of digital techniques to enhance the precision of their restorative procedures, although further research is warranted to evaluate the clinical impact of these findings.
Design of a Freely Accessible Web Application (Instrument for the Measurement of Balance in Primary Education, IMEP) for the Assessment of Static and Dynamic Balance in Children Aged 6–9 Years Based on Force Platforms
Authors: Martín-Ruiz Julio , Tamarit-Grancha Ignacio , Cordente-Martínez Carlos , Santamaría-Fernández Raúl , Ros Ros Concepción , Ruiz-Sanchis Laura
Published: December 2024

Background: The proper development of balance is essential in the acquisition of a correct physical condition, as well as in the evolutionary follow-up at early ages, and its periodic evaluation is very relevant in the educational environment. Objectives: The objective of this research was to design an accessible web application for static and dynamic balance assessment, based on a force platform and motion analysis software. Methods: The Single leg balance test (SLB), Tandem balance test (TBT), and Y balance test (YBT) were performed on a sample of 75 children aged 6 to 9 years. Results: The results show that static balance is more complex at an older age, greater standing height, and with eyes closed (p < 0.001). Regarding the center of pressure (COP), its variability was greater in girls owing to a lower Total Force (TF) at the time of the test (p < 0.05). Parallel observation with the Kinovea software has made it possible to elaborate a scale from 1 to 10 points for integration into an open-access web application (IMEP) to assess static and dynamic balance. Conclusions: The creation of an ad hoc application for primary school teachers and students has been possible by using validated devices obtaining a rating scale, which facilitate the monitoring of students’ functional evolution and offers the possibility of scheduling physical education sessions with a preventive approach as well as a focus on improving physical condition.
The Use of Hybrid CNN-RNN Deep Learning Models to Discriminate Tumor Tissue in Dynamic Breast Thermography
Authors: Munguía-Siu Andrés , Vergara Irene , Espinoza-Rodríguez Juan Horacio
Published: December 2024

Breast cancer is one of the leading causes of death for women worldwide, and early detection can help reduce the death rate. Infrared thermography has gained popularity as a non-invasive and rapid method for detecting this pathology and can be further enhanced by applying neural networks to extract spatial and even temporal data derived from breast thermographic images if they are acquired sequentially. In this study, we evaluated hybrid convolutional-recurrent neural network (CNN-RNN) models based on five state-of-the-art pre-trained CNN architectures coupled with three RNNs to discern tumor abnormalities in dynamic breast thermographic images. The hybrid architecture that achieved the best performance for detecting breast cancer was VGG16-LSTM, which showed accuracy (ACC), sensitivity (SENS), and specificity (SPEC) of 95.72%, 92.76%, and 98.68%, respectively, with a CPU runtime of 3.9 s. However, the hybrid architecture that showed the fastest CPU runtime was AlexNet-RNN with 0.61 s, although with lower performance (ACC: 80.59%, SENS: 68.52%, SPEC: 92.76%), but still superior to AlexNet (ACC: 69.41%, SENS: 52.63%, SPEC: 86.18%) with 0.44 s. Our findings show that hybrid CNN-RNN models outperform stand-alone CNN models, indicating that temporal data recovery from dynamic breast thermographs is possible without significantly compromising classifier runtime.
Finite Element and Experimental Analysis of Microstructural and Hardness Variations in Plasma Arc Welding of AISI 304 Stainless Steel
Authors: Caruso Serafino , Borda Francesco , Sanguedolce Michela , Filice Luigino
Published: December 2024

AISI 304 is widely regarded as the most common austenitic stainless steel and is utilized in various household and industrial applications, including food handling equipment, machinery components, and heat exchangers. Its popularity stems from its excellent mechanical properties, corrosion resistance, and ease of manufacturing. Given its diverse applications, it is crucial to study the microstructural evolution and mechanical properties of the welded zone, especially considering the potential for weld decay during fusion welding. In this context, two critical thermal-dependent factors for ensuring high-quality welds are grain growth and hardness variation in the heat-affected zone (HAZ) during the welding process. This paper presents an innovative finite element (FE) model developed to analyze the grain growth and hardness reduction that occur in the HAZ during plasma arc welding (PAW) of AISI 304 steel for solid expansion tube (SET) technology. Using the commercial FE software SFTC DEFORM-3D™, a user subroutine was created that integrates a physics-based model with the Hall–Petch (H-P) equation to predict changes in grain size and hardness. This study introduces a comprehensive numerical model, encompassing the user subroutine, heat source fitting, and geometry, which accurately predicts the thermal phenomena associated with grain coarsening and hardness reduction in the HAZ during the welding of austenitic stainless steel. The results from the numerical model, including the customized user routines, show good agreement with experimental data, leading to a maximum error prediction of 10 HV in hardness, 30 µm in grain size, and 10% in HAZ extension.
Study on the Sealing Performance of Flexible Pipe End-Fittings Considering the Creep Behavior of PVDF Material at Different Temperatures
Authors: Lu Qingzhen , Xu Shengjie , Zhang Tao , Yin Yuanchao , Lu Hailong , Yan Jun
Published: December 2024

Current designs of sealing systems for non-adhesive flexible pipe end-fittings primarily address short-term loading conditions, often overlooking the creep behavior of polyvinylidene fluoride (PVDF) and the material used in the sealing layer. Over time, the creep of PVDF, particularly at elevated temperatures, can lead to excessive reduction in the sealing layer’s thickness, thereby compromising the sealing performance of the end-fittings. In this study, to address the creep-related issues in the sealing layer, the compression and compression creep tests of PVDF were conducted at different temperatures to establish the material’s elastic-plastic constitutive relationship and develop a creep constitutive model based on the time hardening model. Using the pressure penetration method within ABAQUS software, a two-dimensional axisymmetric finite element model of the end-fitting sealing system was constructed, incorporating the effects of internal fluid pressure. This model was employed to analyze the sealing performance while accounting for the materials’ creep behavior across varying temperature conditions. The results demonstrate that creep in the sealing layer occurs predominantly in the early stages post-installation. Furthermore, the API 17J standard, which stipulates that reduction in sealing layer thickness should not exceed 30%, is found to be conservative at high temperatures. In these conditions, although the thickness reduction exceeds 30% before the maximum contact pressure drops below the fluid pressure, no fluid leakage is observed. Thus, in the initial phase following installation, especially at elevated temperatures, monitoring for potential leakage is critical. This research is the first to quantify the long-term impact of PVDF creep behavior on the sealing performance of flexible pipe end-fittings through comprehensive experiments and simulation analysis. The findings provide both a theoretical foundation and practical guidance for enhancing the long-term sealing performance of flexible pipe end-fittings.
Determinants of Tax Decisions in Jordan: Income and Sales Auditor Perspective
Authors: Al-Khleifat Sajed , Abu Siam Yousef , Nassar Mahmoud , Sharairi Mohammed Haroun
Published: December 2024

This study examines the factors influencing tax decision-making from the perspectives of income and sales auditors in Jordan. It explores how internal and external factors shape auditing processes and compliance. Using a sample of 215 tax auditors from 2018 to 2022, this study adopts a quantitative methodology and collects data through structured surveys. The findings highlight key variables such as auditor independence, professional experience, and taxpayer knowledge as significant factors influencing tax decisions. The study recommends enhancing auditor training, fostering independence, and improving taxpayer education to promote transparency and fairness in tax systems.
Dry Etching Characteristics of InGaZnO Thin Films Under Inductively Coupled Plasma–Reactive-Ion Etching with Hydrochloride and Argon Gas Mixture
Authors: Oh Changyong , Ju Myeong Woo , Jeong Hojun , Song Jun Ho , Kim Bo Sung , Lee Dae Gyu , Cho ChoongHo
Published: December 2024

Inductively coupled plasma–reactive etching (ICP-RIE) of InGaZnO (IGZO) thin films was studied with variations in gas mixtures of hydrochloride (HCl) and argon (Ar). The dry etching characteristics of the IGZO films were investigated according to radiofrequency bias power, gas mixing ratio, and chamber pressure. The IGZO film showed an excellent etch rate of 83.2 nm/min from an optimized etching condition such as a plasma power of 100 W, process pressure of 3 mTorr, and HCl ratio of 75% (HCl:Ar at 30 sccm:10 sccm). In addition, this ICP-RIE etching condition with a high HCl composition ratio at a moderate RIE power of 100 W showed a low etched pattern skew and low photoresist damage on the IGZO patterns. It also provided excellent surface morphology of the SiO2 film underneath after the entire dry etching of the IGZO layer. The IGZO thin film as an active layer was successfully patterned under the ICP-RIE dry etching under the HCl-Ar gas mixture, affording an excellent electrical characteristic in the resultant top-gate IGZO thin-film transistor.