bluuebunny/crossref_metadata_2025 huggingface dataset:
Depressive Symptoms Among Older Gay Men: What Are the Most Important Determinants?
Authors: Asmer Khoury Hala , Band-Winterstein Tova , Bachner Yaacov G.
Published: January 2025

Background: Studies have shown that gay men experience higher levels of depression and are more likely to report suicidal ideation, plans, and attempts over their lifetime compared to heterosexual men. However, most studies have been conducted with adolescents and young adults, while there is a lack of research focusing on older adults. The aims of this study are to assess the level of depressive symptoms among older gay men and examine the associations between five key factors—loneliness, internalized homophobia, self-esteem, ageism, health behavior—and depressive symptoms. Methods: The convenience sample included seventy-nine gay men living in the community. Prospective participants were recruited by facilitators of social and support groups, who either distributed the questionnaire directly to members on-site or forwarded a link to their emails. All study measures used were valid and reliable. Results: Participants’ mean level of depression exceeded the scale’s cutoff point for detecting depression, indicating mild depression. Four variables made a significant contribution to the explanation of depression, with loneliness having the largest contribution, followed by ageism, internalized homophobia, and health behavior. The regression model explained a very high percentage of the depression variance (83%). Conclusions: These four factors are central to understanding depression among older gays. Medical and social professionals should recognize their significance and incorporate them into the treatment provided to those in need. Further studies are needed to gain a deeper understanding of the factors associated with depression in this vulnerable population.
Anti-Hail Shading Net and Kaolin Application: Protecting Grape Production to Ensure Grape Quality in Mediterranean Vineyards
Authors: Pallotti Luca , Dottori Edoardo , Lattanzi Tania , Lanari Vania , Brillante Luca , Silvestroni Oriana
Published: January 2025

Rising temperatures due to climate change pose a significant threat to viticulture, intensifying summer heat stress and accelerating berry ripening. Additionally, the increasing frequency of extreme weather events, such as hailstorms, further jeopardizes the sustainability of the viticultural sector. In recent years, mitigating these impacts has become crucial for grape production, particularly in Mediterranean regions. This study compares two mitigation strategies—using an anti-hail shading net (S) and kaolin spraying (K)—with untreated control vines (C) over three growing seasons. Vine physiology, berry ripening, grape production and pruning weight were evaluated. The S treatment significantly reduced light interception in the fruiting zone and, while limiting gas exchange, improved vine performance during extreme heat. The K treatment alleviated heat stress and enhanced the photosynthetic activity. Both S and K treatments improved grape quality by maintaining higher acidity levels and lower sugar concentrations and pH. Additionally, both treatments reduced the incidence of fungal diseases, with the net providing added protection against hailstorms. No significant changes in pruning weight were observed, and the treated vines showed a better balance between vegetative growth and production. In conclusion, both kaolin and shading nets are effective techniques for addressing the challenges of climate change, enhancing vine resilience and ensuring high-quality grape production.
Health Deficits Among People Experiencing Homelessness in an Australian Capital City: An Observational Study
Authors: Gordon Susan J. , Baker Nicky , Marin Tania S. , Steffens Margie
Published: January 2025

People experiencing, or at risk of, homelessness face challenges that result in poorer health outcomes compared to those in stable housing. This study provides the results of over 40 health measures that capture the health status of a group of people in temporary accommodation due to experiencing homelessness, aged 22 to 84 years, in an inner-city location, invited to participate in a comprehensive assessment of physical and psychological health. Evidence of accelerated ageing was found, with 44.2% of people being clinically frail, 63% having poor functional movement, and 36% having pain associated with oral health. Additionally, 90.6% of participants showed health risks due to nutritional deficiencies, over half reported poor sleep quality, 55.3% reported having psychological distress, and almost half reported fair or poor overall dental health. This study suggests a pathway to providing a relatively easily implemented series of health assessments to help respond to a group of underlying causes for accelerated ageing among a group of inner-city people experiencing homelessness. This work can be used to inform the prioritisation and development of community-based health services to address functional deficits that may contribute to accelerated ageing.
Assessing the Efficacy of Mitochondria-Accumulating Self-Assembly Peptides in Pancreatic Cancer: An Animal Study
Authors: Choi Ho Joong , Jin Seongeon , Park Junghyun , Lee Dosang , Jeong Hee Jeong , Kim Ok-Hee , Ryu Ja-Hyoung , Kim Say-June
Published: January 2025

Although pancreatic cancer presents with one of the most unfavorable prognoses, its treatment options are very limited. Mitochondria-targeting moieties, considered a new and prominent treatment modality, are expected to demonstrate synergistic anticancer effects due to their distinct mechanism compared to conventional chemotherapeutic approaches. This study evaluated the therapeutic potential of mitochondria-accumulating self-assembly peptides, referred to as Mito-FFs, utilizing both in vitro and in vivo pancreatic cancer models. Cellular viability assays revealed a concentration-dependent decrease in the survival of MIA-PACA2 pancreatic cancer cells upon exposure to Mito-FF treatment (p < 0.05). Subsequent in vitro Mito-FF treatments prompted the use of several molecular analyses, including Real-time PCR, Western blot analysis, and MitoSOX staining, which collectively indicated an upsurge in apoptosis, a concurrent reduction in the antioxidant enzyme expression, and an elevation in mitochondrial ROS levels (p < 0.05). In a murine xenograft model of pancreatic cancer, the intravenous administration of Mito-FF yielded a notable reduction in the tumor volume. Moreover, it upregulated the expression of pro-apoptotic markers, such as cleaved PARP and c-caspase 3, while concurrently downregulating the expression of an anti-apoptotic marker, MCL-1, as evidenced by both Western blot analysis and immunohistochemical staining (p < 0.05). It also resulted in the reduced expression of antioxidant enzymes like HO-1, catalase, and SOD2 within excised tumor tissues, as confirmed using Western blot analysis (p < 0.05). Cumulatively, the findings underscore the significant anticancer efficacy of Mito-FF against pancreatic cancer cells, predominantly mediated through the induction of apoptosis, suppression of antioxidant enzyme expression, and enhancement of mitochondrial ROS levels within the tumor microenvironment.
Nicking Activity of M13 Bacteriophage Protein 2
Authors: Aybakan Esma , Kocagoz Tanil , Can Ozge
Published: January 2025

Gene II Protein (Gp2/P2) is a nicking enzyme of the M13 bacteriophage that plays a role in the DNA replication of the viral genome. P2 recognizes a specific sequence at the f1 replication origin and nicks one of the strands and starts replication. This study was conducted to address the limitations of previous experiments, improve methodologies, and precisely determine the biochemical activity conditions of the P2 enzyme in vitro. For these purposes, the gene encoding P2 was cloned in Escherichia coli and expressed as a hybrid protein together with a green fluorescent protein (P2-GFP). P2-GFP was purified via metal affinity chromatography, and its nicking activity was determined by conversion of supercoiled DNA to open circular or linear forms. We discovered that, among the two loops of the f1 origin defined previously, P2 can recognize just the A1 loop. When a supercoiled plasmid containing the f1 origin was treated with P2-GFP, the plasmid was present in an open circular form, indicating that a nick was created on only one of the strands. However, when the A1 loop sequence was inserted into the 3′ ends of both strands by cloning a PCR product obtained by primers with the A1 loop sequence, the plasmid was linearized by treatment with P2-GFP, indicating that nicks were created on both strands. Certain infectious diseases are caused by single-stranded DNA viruses, and some of them have specific nicking enzymes that enable strand displacement and free 3′ end of a single strand that works as a primer for their replication mechanisms like M13 bacteriophages, such as parvovirus B19. Despite there being different host viruses such as bacteria and humans, their DNA replication mechanisms are very similar in this concept. Investigating the features of the P2-nicking enzyme may deepen the understanding of human pathogenic single-stranded viruses and facilitate the development of drugs that inhibit viral replication.
HERC1 E3 Ubiquitin Ligase Is Necessary for Autophagy Processes and for the Maintenance and Homeostasis of Vesicles in Motor Nerve Terminals, but Not for Proteasomal Activity
Authors: Pérez-Castro Miguel Ángel , Hernández-Rasco Francisco , Alonso-Bellido Isabel María , Letrán-Sánchez María S. , Pérez-Villegas Eva María , Vitallé Joana , Real Luis Miguel , Ruiz-Mateos Ezequiel , Venero José Luis , Tabares Lucía , Carrión Ángel Manuel , Armengol José Ángel , Bachiller Sara , Ruiz Rocío
Published: January 2025

The ubiquitin proteasome system (UPS) is implicated in protein homeostasis. One of the proteins involved in this system is HERC1 E3 ubiquitin ligase, which was associated with several processes including the normal development and neurotransmission at the neuromuscular junction (NMJ), autophagy in projection neurons, myelination of the peripheral nervous system, among others. The tambaleante (tbl) mouse model carries the spontaneous mutation Gly483Glu substitution in the HERC1 E3 protein. Using this model, we analyzed the implication of HERC1 E3 ubiquitin ligase in the activity of UPS, autophagy, and synaptic homeostasis in brain and muscle tissues. Regarding UPS, no differences were found in its activity nor in the specific gene expression in both brain and muscle tissues from tbl compared with the control littermates. Furthermore, the use of the specific UPS inhibitor (MG-132), did not alter the evoked neurotransmitter release in the levator auris longus (LAL) muscle. Interestingly, the expression of the autophagy-related gene p62 was significantly increased in the muscle of tbl compared to the control littermates. Indeed, impaired evoked neurotransmitter release was observed with the autophagy inhibitor Wortmannin. Finally, altered levels of Clathrin and Synaptophysin were detected in muscle tissues. Altogether, our findings show that HERC1 E3 ubiquitin ligase mutation found in tbl mice alters autophagy and vesicular recycling without affecting proteasomal function.
Gene Expression Correlates with Disability and Pain Intensity in Patients with Chronic Low Back Pain and Modic Changes in a Sex-Specific Manner
Authors: Vigeland Maria Dehli , Flåm Siri Tennebø , Vigeland Magnus Dehli , Zucknick Manuela , Wigemyr Monica , Bråten Lars Christian Haugli , Gjefsen Elisabeth , Zwart John-Anker , Storheim Kjersti , Pedersen Linda Margareth , Lie Benedicte Alexandra ,   the AIM Study Group
Published: January 2025

Chronic low back pain (cLBP) lacks clear physiological explanations, and the treatment options are of limited effect. We aimed to elucidate the underlying biology of cLBP in a subgroup of patients with Modic changes type I (suggestive of inflammatory vertebral bone marrow lesions) by correlating gene expression in blood with patient-reported outcomes on disability and pain intensity and explore sex differences. Patients were included from the placebo group of a clinical study on patients with cLBP and Modic changes. Blood was collected at the time of inclusion, after three months, and after one year, and gene expression was measured at all time points by high-throughput RNA sequencing. The patients reported disability using the Roland–Morris Disability Questionnaire, and pain intensity was assessed as a mean of three scores on a 0–10 numeric rating scale: current LBP, worst LBP within the last two weeks, and mean LBP within the last two weeks. The gene expression profiles were then correlated to the reported outcomes. Changes in gene expression over time correlated significantly with changes in both disability and pain. The findings showed distinct patterns in men and women, with negligible overlap in correlated genes between the sexes. The genes involved were enriched in immunological pathways, particularly T cell receptor complex and immune responses related to neutrophils. Several of the genes harbour polymorphisms that previously have been found to be associated with chronic pain. Taken together, our results indicate gender differences in the underlying biology of disability and pain intensity in patients with low back pain.
Methylglyoxal-Stimulated Mesothelial Cells Prompted Fibroblast-to-Proto-Myofibroblast Transition
Authors: Wei Yu-Syuan , Tsai Su-Yi , Lin Shuei-Liong , Chen Yi-Ting , Tsai Pei-Shiue
Published: January 2025

During long-term peritoneal dialysis, peritoneal fibrosis (PF) often happens and results in ultrafiltration failure, which directly leads to the termination of dialysis. The accumulation of extracellular matrix produced from an increasing number of myofibroblasts was a hallmark characteristic of PF. To date, glucose degradation products (GDPs, i.e., methylglyoxal (MGO)) that appeared during the heating and storage of the dialysate are considered to be key components to initiating PF, but how GDPs lead to the activation of myofibroblast in fibrotic peritoneum has not yet been fully elucidated. In this study, mesothelial cell line (MeT-5A) and fibroblast cell line (MRC-5) were used to investigate the transcriptomic and proteomic changes to unveil the underlying mechanism of MGO-induced PF. Our transcriptomic data from the MGO-stimulated mesothelial cells showed upregulation of genes involved in pro-inflammatory, apoptotic, and fibrotic pathways. While no phenotypic changes were noted on fibroblasts after direct MGO, supernatant from MGO-stimulated mesothelial cells promoted fibroblasts to change into proto-myofibroblasts, activated fibroblasts in the first stage toward myofibroblasts. In conclusion, this study showed that MGO-stimulated mesothelial cells promoted fibroblast-to-proto-myofibroblast transition; however, additional involvement of other factors or cells (e.g., macrophages) may be needed to complete the transformation into myofibroblasts.
Somatic DNA Variants in Epilepsy Surgery Brain Samples from Patients with Lesional Epilepsy
Authors: Schwarz Jana Marie , Becker Lena-Luise , Wahle Monika , Faßbender Jessica , Thomale Ulrich-Wilhelm , Tietze Anna , Morales-Gonzalez Susanne , Knierim Ellen , Schuelke Markus , Kaindl Angela M.
Published: January 2025

Epilepsy affects 50 million people worldwide and is drug-resistant in approximately one-third of cases. Even when a structural lesion is identified as the epileptogenic focus, understanding the underlying genetic causes is crucial to guide both counseling and treatment decisions. Both somatic and germline DNA variants may contribute to the lesion itself and/or influence the severity of symptoms. We therefore used whole exome sequencing (WES) to search for potentially pathogenic somatic DNA variants in brain samples from children with lesional epilepsy who underwent epilepsy surgery. WES was performed on 20 paired DNA samples extracted from both lesional brain tissue and reference tissue from the same patient, such as leukocytes or fibroblasts. The paired WES data were jointly analyzed using GATK Mutect2 to identify somatic single nucleotide variants (SNVs) or insertions/deletions (InDels), which were subsequently evaluated in silico for their disease-causing potential using MutationTaster2021. We identified known pathogenic somatic variants in five patients (25%) with variant allele frequencies (VAF) ranging from 3–35% in the genes MTOR, TSC2, PIK3CA, FGFR1, and PIK3R1 as potential causes of cortical malformations or central nervous system (CNS) tumors. Depending on the VAF, we used different methods such as Sanger sequencing, allele-specific qPCR, or targeted ultra-deep sequencing (amplicon sequencing) to confirm the variant. In contrast to the usually straightforward confirmation of germline variants, the validation of somatic variants is more challenging because current methods have limitations in sensitivity, specificity, and cost-effectiveness. In our study, WES identified additional somatic variant candidates in additional genes with VAFs ranging from 0.7–7.0% that could not be validated by an orthogonal method. This highlights the importance of variant validation, especially for those with very low allele frequencies.
A Haplotype GWAS in Syndromic Familial Colorectal Cancer
Authors: Vermani Litika , Samola Winnberg Johanna , Liu Wen , Soller Veronika , Sjödin Tilde , Lindblad Mats , Lindblom Annika
Published: January 2025

A previous genome-wide association study (GWAS) in colorectal cancer (CRC) patients with gastric and/or prostate cancer in their families suggested genetic loci with a shared risk for these three cancers. A second haplotype GWAS was undertaken in the same colorectal cancer patients and different controls with the aim of confirming the result and finding novel loci. The haplotype GWAS analysis involved 685 patients with colorectal cancer cases and 1642 healthy controls from Sweden. A logistic regression model was used with a sliding window haplotype approach. Whole-genome and exome sequencing datawere used to find candidate SNPs to be tested in a nested case-control study. In the analysis of 685 colorectal cancer cases and 1642 controls, all ten candidate loci from the previous study were confirmed. Fifty candidate loci were suggested with a p-value < 5 × 10−6 and odds ratios between 1.35–6.52. Two of the 50 loci, on 13q33.3 and 16q23.3, were the same as in the previous study. Whole-genome or exome data from 122 colorectal cancer patients was used to search for candidate variants in these 50 loci. A nested case-control study was performed to test genetic variants at 11 loci in a cohort of 827 familial colorectal cancer and a sub-cohort of 293 familial CRC cases with colorectal, gastric, and/or prostate cancer within their families and 1530 healthy controls. One SNP, rs115943733 on 10q11.21, reached statistical significance (OR = 3.26, p = 0.009). Seven SNPs in 4 loci had a higher OR in the smaller cohort compared to the larger study CRC cases. The results in this GWAS gave support for suggested loci with an increased shared risk of CRC, gastric, and/or prostate cancer. Further studies are needed to confirm the shared risk to be able to use this information in cancer prevention.
Enhancing HDAC Inhibitor Screening: Addressing Zinc Parameterization and Ligand Protonation in Docking Studies
Authors: Buccheri Rocco , Coco Alessandro , Pasquinucci Lorella , Amata Emanuele , Marrazzo Agostino , Rescifina Antonio
Published: January 2025

Precise binding free-energy predictions for ligands targeting metalloproteins, especially zinc-containing histone deacetylase (HDAC) enzymes, require specialized computational approaches due to the unique interactions at metal-binding sites. This study evaluates a docking algorithm optimized for zinc coordination to determine whether it could accurately differentiate between protonated and deprotonated states of hydroxamic acid ligands, a key functional group in HDAC inhibitors (HDACi). By systematically analyzing both protonation states, we sought to identify which state produces docking poses and binding energy estimates most closely aligned with experimental values. The docking algorithm was applied across HDAC 2, 4, and 8, comparing protonated and deprotonated ligand correlations to experimental data. The results demonstrate that the deprotonated state consistently yielded stronger correlations with experimental data, with R2 values for deprotonated ligands outperforming protonated counterparts in all HDAC targets (average R2 = 0.80 compared to the protonated form where R2 = 0.67). These findings emphasize the significance of proper ligand protonation in molecular docking studies of zinc-binding enzymes, particularly HDACs, and suggest that deprotonation enhances predictive accuracy. The study’s methodology provides a robust foundation for improved virtual screening protocols to evaluate large ligand libraries efficiently. This approach supports the streamlined discovery of high-affinity, zinc-binding HDACi, advancing therapeutic exploration of metalloprotein targets. A comprehensive, step-by-step tutorial is provided to facilitate a thorough understanding of the methodology and enable reproducibility of the results.
Lovastatin and Resveratrol Synergistically Improve Wound Healing and Inhibit Bacterial Growth
Authors: AlJunaydil Norah A. , Lambarte Rhodanne Nicole A. , Sumague Terrence S. , Alghamdi Osama G. , Niazy Abdurahman A.
Published: January 2025

Wound healing is a complex physiological process, with scarring and infection caused by Staphylococcus aureus and Pseudomonas aeruginosa being the most common complications. The reutilization of known medications has received increased attention for their role in cell function as small molecules. Examples of these include lovastatin, a cholesterol-lowering agent, and resveratrol, which have multiple biological properties. Both molecules have been reported to improve wound healing and possess antibacterial properties, with conflicting results. The wound-healing capabilities of human mesenchymal stem cells were evaluated after exposure to lovastatin, resveratrol, and their combination through scratch test, migrations assay, and qPCR. Protein docking was performed to assess the lovastatin/resveratrol combination as potential wound-healing targets. AlamarBlue assay was used to determine cell viability. Additionally, the impact of lovastatin and resveratrol combination to inhibit the growth of S. aureus and P. aeruginosa was tested using broth microdilution test and checkerboard assay to determine synergism. The combination of lovastatin 0.1 μM and resveratrol 0.1 μM synergistically improved wound healing and demonstrated an additive effect against S. aureus and P. aeruginosa, presenting potential antibacterial applications.
Adenovirus-Neutralizing and Infection-Promoting Activities Measured in Serum of Human Brain Cancer Patients Treated with Oncolytic Adenovirus Ad5-∆24.RGD
Authors: van der Meulen-Muileman Ida H. , Amado-Azevedo Joana , Lamfers Martine L. M. , Kleijn Anne , Idema Sander , Noske David P. , Dirven Clemens M. F. , van Beusechem Victor W.
Published: January 2025

Oncolytic adenoviruses derived from human serotype 5 (Ad5) are being developed to treat cancer. Treatment efficacy could be affected by pre-existing or induced neutralizing antibodies (NAbs), in particular in repeat administration strategies. Several oncolytic adenoviruses that are currently in clinical development have modified fiber proteins to increase their infectivity. One example is Ad5-∆24.RGD, which carries a cyclic RGD peptide insert in the fiber protein to allow cell entry via integrins. The effect of anti-Ad5 NAbs on anticancer efficacy could be different for oncolytic adenoviruses with RGD-modified fibers than for unmodified Ad5-based viruses. Here, we determine pre-existing and elicited NAb titers in the serum of patients with glioblastoma who were treated by delivering Ad5-∆24.RGD to the tumor and to the surrounding tumor-infiltrated brain. We show that intracranial infusion of Ad5-∆24.RGD induced mainly neutralization of adenovirus native tropism. Infection of cells with RGD-modified virus was significantly less affected. In cerebrospinal fluid, neutralizing activity against RGD-mediated infection remained very low. Thus, the RGD-mediated alternative cell entry route allowed to bypass pre-existing and induced anti-Ad5 neutralization. Interestingly, in the course of these experiments, we discovered that the serum of most humans promotes the uptake of RGD-modified adenovirus in human cells. The until now unidentified infection-stimulating factor seems distinct from serum proteins known to promote Ad5 infection. Together, our work supports the utility of RGD-modified oncolytic adenoviruses for the treatment of cancer in humans. Since these viruses hardly induced neutralization, they seem particularly suitable for repeat administration treatments.
Design, Synthesis, Anticancer Screening, and Mechanistic Study of Spiro-N-(4-sulfamoyl-phenyl)-1,3,4-thiadiazole-2-carboxamide Derivatives
Authors: El-Saghier Ahmed M. , Hashem Hamada , Maher Sherif A. , Enaili Souhaila S. , Alkhammash Abdullah , Bräse Stefan , Aziz Hossameldin A.
Published: January 2025

The present study aims to create spiro-N-(4-sulfamoyl-phenyl)-1,3,4-thiadiazole-2-carboxamide derivatives with anticancer activities. The in vitro anticancer evaluation showed that only the novel spiro-acenaphthylene tethered-[1,3,4]-thiadiazole (compound 1) exhibited significant anticancer efficacy as a selective inhibitor of tumor-associated isoforms of carbonic anhydrase. Compound 1 demonstrated considerable efficacy against the renal RXF393, colon HT29, and melanoma LOX IMVI cancer cell lines, with IC50 values of 7.01 ± 0.39, 24.3 ± 1.29, and 9.55 ± 0.51 µM, respectively. In comparison, doxorubicin exhibited IC50 values of 13.54 ± 0.82, 13.50 ± 0.71, and 6.08 ± 0.32 µM for the corresponding cell lines. Importantly, compound 1 exhibited lower toxicity to the normal WI 38 cell line than doxorubicin, with IC50 values of 46.20 ± 2.59 and 18.13 ± 0.93 µM, respectively, indicating greater selectivity of the target compound compared to the standard anticancer agent doxorubicin. Also, mechanistic experiments demonstrated that compound 1 exhibits inhibitory activity against human carbonic anhydrase hCA IX and XII, with IC50 values of 0.477 ± 0.03 and 1.933 ± 0.11 μM, respectively, indicating enhanced selectivity for cancer-associated isoforms over cytosolic isoforms hCA I and II, with IC50 values of 7.353 ± 0.36 and 12.560 ± 0.74 μM, respectively. Cell cycle studies revealed that compound 1 caused G1 phase arrest in RXF393 cells, and apoptosis experiments verified a substantial induction of apoptosis with significant levels of early and late apoptosis, as well as necrosis (11.69%, 19.78%, and 3.66%, respectively), comparable to those induced by the conventional cytotoxic agent doxorubicin, at 9.91%, 23.37%, and 6.16%, respectively. Molecular docking experiments confirmed the strong binding affinity of compound 1 to the active sites of hCA IX and XII, highlighting significant interactions with zinc-binding groups and hydrophobic residues. These findings underscore the target compound’s potential as a viable anticancer agent via targeting CA.
The Protective Effect of Nimodipine in Schwann Cells Is Related to the Upregulation of LMO4 and SERCA3 Accompanied by the Fine-Tuning of Intracellular Calcium Levels
Authors: Leisz Sandra , Fritzsche Saskia , Strauss Christian , Scheller Christian
Published: January 2025

Nimodipine is the current gold standard in the treatment of subarachnoid hemorrhage, as it is the only known calcium channel blocker that has been proven to improve neurological outcomes. In addition, nimodipine exhibits neuroprotective properties in vitro under various stress conditions. Furthermore, clinical studies have demonstrated a neuroprotective effect of nimodipine after vestibular schwannoma surgery. However, the molecular mode of action of nimodipine pre-treatment has not been well investigated. In the present study, using real-time cell death assays, we demonstrated that nimodipine not only reduces cell death induced by osmotic and oxidative stress but also protects cells directly at the time of stress induction in Schwann cells. Nimodipine counteracts stress-induced calcium overload and the overexpression of the Cav1.2 calcium channel. In addition, we found nimodipine-dependent upregulation of sarcoplasmic/endoplasmic reticulum calcium ATPase 3 (SERCA3) and LIM domain only 4 (LMO4) protein. Analysis of anti-apoptotic cell signaling showed an inhibition of the pro-apoptotic protein glycogen synthase kinase 3 beta (GSK3β). Nimodipine-treated Schwann cells exhibited higher levels of phosphorylated GSK3β at serine residue 9 during osmotic and oxidative stress. In conclusion, nimodipine prevents cell death by protecting cells from calcium overload by fine-tuning intracellular calcium signaling and gene expression.
Correction: Zhao et al. The SlDOG1 Affect Biosynthesis of Steroidal Glycoalkaloids by Regulating GAME Expression in Tomato. Int. J. Mol. Sci. 2023, 24, 3360
Authors: Zhao Xuecheng , Zhang Yueran , Lai Jun , Deng Yuan , Hao Yingchen , Wang Shouchuang , Yang Jun
Published: January 2025

In the original publication [...]
Morphogens and Cell-Derived Structures (Exosomes and Cytonemes) as Components of the Communication Between Cells
Authors: Chideriotis Stavros , Anastasiadi Alkmini T. , Tzounakas Vassilis L. , Fortis Sotirios P. , Kriebardis Anastasios G. , Valsami Serena
Published: January 2025

Morphogens, which are non-classical transcription factors, according to several studies, display a crucial role in tissue patterning, organ architecture establishment, and human disease pathogenesis. Recent advances have expanded the morphogen participation to a wide range of human diseases. There are many genetic syndromes caused by mutations of components of morphogen signaling pathways. The aberrant morphogen pathways also promote cancer cell maintenance, renewal, proliferation, and migration. On the other hand, exosomes and their application in the biomedical field are of evolving significance. The evidence that membrane structures participate in the creation of morphogenic gradience and biodistribution of morphogen components renders them attractive as new therapeutic tools. This intercellular morphogen transport is performed by cell-derived structures, mainly exosomes and cytonemes, and extracellular substances like heparan sulphate proteoglycans and lipoproteins. The interaction between morphogens and Extracellular Vesicles has been observed at first in the most studied insect, Drosophila, and afterwards analogous findings have been proved in vertebrates. This review presents the protagonists and mechanisms of lipid-modified morphogens (Hedgehog and Wnt/β-catenin) biodistribution.
External Morphology, Defensive Adaptations, Aposematic Coloration, and Sexual Dimorphism of the Fifth Instar Larva of Cricula Silkmoth, Cricula trifenestrata Helfer (Lepidoptera: Saturniidae) from Thailand
Authors: Magnussen Kanitsara , Sumida Motoyuki , Kangrang Anongrit , Vollrath Fritz , Katisart Teeraporn , Butiman Chirapha
Published: January 2025

This study explores the external morphology of larva of Cricula trifenestrata Helfer at the fifth instar stage, focusing on sexual dimorphism, scoli, and fluorescence hair warts. The larva displays a black body adorned with varying shades of orange to crimson–red transverse stripes and small yellow dorsal spots. Longitudinal stripes with fluorescent warts are observed in the subspiracular region, accompanied by an overall coverage of long white hairs. These distinctive features, including scoli and fluorescence hair warts, serve as effective defense mechanisms against predators and parasitoids. The results enhance our understanding of C. trifenestrata Helfer larval biology, providing valuable insights for entomology and evolutionary biology. The identification of species-specific adaptations, particularly the presence of scoli and fluorescence hair warts, underscores their significance in shaping survival strategies and ecological interactions.
Prognostic Factors of the Progression of Chronic Kidney Disease and the Development of End-Stage Renal Disease in Patients with Lupus Nephritis: A Retrospective Cohort Study
Authors: Perge Bianka , Papp Gábor , Bói Bernadett , Markóth Csilla , Bidiga László , Farmasi Nikolett , Balla József , Tarr Tünde
Published: January 2025

Background/Objectives: Lupus nephritis (LN) is one of the most severe organ manifestations of systemic lupus erythematosus (SLE). Chronic kidney disease (CKD) and its progression into end-stage renal disease (ESRD) are serious complications in LN and the main cause of death in SLE. We aimed to investigate the prognostic factors of the progression of CKD and the development of ESRD in SLE patients. Methods: In our retrospective cohort study, we assessed the clinical and laboratory data of 127 patients who were diagnosed with LN between 1990 and 2022 and received regular follow-up care at our autoimmune centre. We compared class IV (diffuse) LN patients with non-class IV LN patients and assessed the differences in clinical and laboratory data of the patients, subdivided into complete, partial, and non-responders to therapy. Results: The prevalence of class IV LN is significantly higher in patients with CKD stage 3–5. Age above 42, class IV LN, Coombs positivity, and high chronicity index are prognostic factors for the development of CKD stage 3–5. On the other hand, anti-RNP and anti-SS-B antibody positivity and a high chronicity index are prognostic factors for the development of ESRD. The chronicity index, as well as the SLICC/ACR Damage Index (SDI) score, was significantly higher in non-responders compared to patients with complete remission. Conclusions: Based on our results, the progression of CKD into stage 3–5 or the development of ESRD should be expected at a chronicity index above 3.5 points. An early diagnosis, as well as aggressive, timely, and adequate treatment, is fundamental to prevent unfavourable outcomes of LN.
Clinical Statistical Study on the Prevalence of Carious Lesions in First Permanent Molars
Authors: Țuculină Mihaela Jana , Bănățeanu Andreea Mariana , Staicu Adela Nicoleta , Popescu Alexandru Dan , Abdul-Razzak Jaqueline , Dascălu Ionela Teodora , Giuroiu Cristian Levente , Mercuț Veronica , Scrieciu Monica , Amza Oana , Ionescu Mihaela
Published: January 2025

Background: Dental caries remains one of the most widespread chronic diseases that also affects first permanent molars (FPMs). In this study, we analyzed the prevalence of carious lesions using a standardized evaluation system, while following the analysis of the influence of favoring factors represented by the type and frequency of snacks and the frequency of tooth brushing. Method: A clinical–statistical study was carried out on a group of 311 children from both urban and rural environments, aged between 6 and 19 years old. As a diagnostic system and assessment of the depth of carious processes, we used the ICDAS system. The following parameters were recorded: odontal status of the 4 FPMs, age, gender, residence, frequency of dental brushing, and frequency of between-meal snacks and their type. The ICDAS system was used as a diagnostic system and assessment of the depth of carious processes. The data were statistically analyzed with SPSS, using the Kruskal–Wallis H and Chi-Square tests. Results: The occlusal surface was the most interesting in the presence of odontal lesions. Sweet snacks were the most frequent snacks consumed by the subjects. The age group of 13–19 years presented fewer healthy FPMs, compared to the age group of 6–12 years. The higher involvement of older subjects was found for all four molars, both in the case of identified carious lesions and the presence of root debris and edentations. Brushing twice a day was more frequent in the 6–12 age group. In analyzing the status of the first molars in relation to the gender of the subjects, in the present study, no statistically significant differences were recorded between the status of the molars relative to gender, except for molar 1.6 (p > 0.05). Regarding the other types of snacks, children from rural areas consume more fruits than those from urban areas. Conclusions: The frequency of tooth brushing and the type and frequency of snacks between meals influence the prevalence of carious lesions at the level of the first permanent molars.
Additive Value of Pyridostigmine to Silodosin in the Management of Acute Urinary Retention Secondary to Benign Prostatic Hyperplasia: A Randomized Controlled Trial
Authors: Mohamed Ahmed G. , Badawy Hany F. , Said Amira S. A. , Al-Ahmad Mohammad M. , Rabie Al Shaimaa Ibrahim , Salah Hager , Massoud Ramy , Hussein Raghad R. S. , Khalil Doaa Mahmoud , Yousef Ahmed , Ibrahim Rabie M.
Published: January 2025

Background: In men with progressive benign prostatic hyperplasia (BPH), acute urine retention (AUR) stands out as one of the most severe outcomes associated with aging. AUR is characterized by a sudden, painful inability to urinate. This research investigates the potential benefits of adding pyridostigmine to silodosin in the management of acute urinary retention secondary to benign prostatic hyperplasia. Methods: Patients aged 50 and above experiencing their first episode of AUR due to BPH, with a retention volume below 1000 milliliters, were enrolled in this study. A total of 140 patients were randomized into two groups: Group A received a daily dose of pyridostigmine bromide (60 mg tablet) alongside an 8 mg silodosin capsule, while Group B received a daily dose of silodosin (8 mg capsule) only. Trial registration number: NCT06319469 13 March 2024. Results: Among the 140 patients, 58 (82.9%) in Group A successfully underwent a trial without catheter (TWOC), compared to 47 (67.1%) in Group B. Group A exhibited significant improvements in international prostatic symptom score (IPSS) and uroflowmetry (UFR) at both 2 weeks and 3 months, with p-values of 0.001 and 0.003, respectively. Regarding postvoid residual volume (PVR), both groups were initially matched at baseline, showing significant continuous improvement at the second week and third month. Conclusions: The combination of pyridostigmine bromide (60 mg tablet) with silodosin proved to be more effective than silodosin alone in managing acute urinary retention caused by BPH. This was particularly true for patients who were suspected to have detrusor underactivity in addition to BPH.
Safety and Outcomes of Catheter Ablation for Consecutive Atrial Tachycardia in Elderly Patients After Previous Cardiac Interventions
Authors: Kahle Ann-Kathrin , Alken Fares-Alexander , Scherschel Katharina , Zhu Ernan , Gunawardene Melanie A. , Metzner Andreas , Willems Stephan , Meyer Christian
Published: January 2025

Background: Age is a relevant risk factor for the development of atrial arrhythmias and an independent predictor of adverse cardiovascular outcomes. The incidence of atrial tachycardia (AT) is known to increase with aging, but so far, there are no data on elderly patients with AT. Therefore, we sought to assess the safety and outcomes of AT ablation in patients ≥75 years compared to those <75 years. Methods: A total of 420 consecutive patients undergoing AT ablation after previous cardiac interventions (mean 2.1 ± 0.1 prior ablation procedures) were analyzed. Safety, as well as acute and mid-term outcomes of AT ablation were compared between 140 patients ≥75 years (mean age 78.1 ± 0.2 years, 22.9% aged ≥80 years (range 80–86 years)) and 280 patients <75 years (mean age 62.2 ± 0.6 years). Results: Patients ≥75 years were more often female (54.3% vs. 38.2%; p = 0.0024) and presented with more cardiac comorbidities, including arterial hypertension (85.0% vs. 64.3%; p < 0.0001) and coronary artery disease (33.6% vs. 18.2%; p = 0.0006). Acute success of AT ablation was reached in 96.4% vs. 97.9% of patients (p = 0.5173). Major complications (1.4% vs. 0.7%; p = 0.6035) and duration of hospital stay (2 (IQR 2–4) days vs. 2 (IQR 2–3) days; p = 0.9125) did not differ significantly between groups. During a follow-up of 364 (IQR 183–729.5) days, arrhythmia recurrences occurred in 45.0% vs. 49.3% (p = 0.4684), whereas repeat ablation was less frequently performed in patients ≥75 years (25.7% vs. 36.1%; p = 0.0361). Conclusions: AT ablation in patients ≥75 years after previous cardiac interventions in tertiary arrhythmia centers is safe and effective. Therefore, AT ablation should not be ruled out in elderly patients due to age alone, but should be considered based on arrhythmia burden, symptom severity and concomitant clinical and procedural risk factors.
The Assessment of Sentinel Lymph Node Mapping Methods in Endometrial Cancer
Authors: Szatkowski Wiktor , Pniewska Karolina , Janeczek Maja , Ryś Janusz , Banaś Tomasz , Muzykiewicz Konrad , Iwańska Ewa , Jakubowicz Jerzy , Karolewski Kazimierz , Szadurska Agnieszka , Blecharz Paweł
Published: January 2025

Background/Objectives: Sentinel lymph node biopsy (SLNB) is a minimally invasive technique used to assess lymphatic involvement in endometrial cancer (EC), offering reduced surgical morbidity compared to routine lymphadenectomy. Despite its widespread use, the optimal combination of tracers for SLN detection remains a subject of debate. Methods: This retrospective cohort study included 119 patients with early-stage EC treated at the Maria Skłodowska-Curie National Research Institute of Oncology between 2016 and 2021. SLNB was performed using technetium-99m (Tc99m), indocyanine green (ICG), Patent Blue, or combinations of these tracers. Detection rates for unilateral and bilateral SLNs and the accuracy of metastasis identification were analyzed. Results: The overall SLN detection rate was 97.5%. Individual tracer detection rates were 100% for ICG, 100% for Patent Blue, and 96% for Tc99m. Combined tracers achieved detection rates of 96.9% (Tc99m and ICG) and 97.3% (Tc99m and Patent Blue). Bilateral detection was highest with Tc99m and ICG (90.6%) and Patent Blue alone (91%). Metastases were identified in 12% of cases, with combined methods improving metastatic detection. Tc99m yielded no “empty nodes”, compared to 1.7% with Patent Blue and 0.8% with ICG. Conclusions: While combining Tc99m with dyes did not significantly improve overall SLN detection rates, it enhanced metastatic identification and reduced false-negative results. These findings suggest that combined tracer methods optimize SLNB accuracy in endometrial cancer. Prospective studies are needed to confirm these results.
Adipocentric Strategy for the Treatment of Type 2 Diabetes Mellitus
Authors: Gorgojo-Martínez Juan J.
Published: January 2025

The global prevalence of obesity and type 2 diabetes mellitus (T2D) has risen in parallel over recent decades. Most individuals diagnosed with T2D exhibit adiposopathy-related diabetes (ARD), a condition characterized by hyperglycemia accompanied by three core features: increased ectopic and visceral fat deposition, dysregulated adipokine secretion favoring a pro-inflammatory state, and insulin resistance. Despite advancements in precision medicine, international guidelines for T2D continue to prioritize individualized therapeutic approaches focused on glycemic control and complications, and many healthcare providers predominantly maintain a glucocentric strategy. This review advocates for an adipocentric treatment paradigm for most individuals with T2D, emphasizing the importance of prioritizing weight loss and visceral fat reduction as key drivers of therapeutic intensification. By combining lifestyle modifications with pharmacological agents that promote weight loss—including SGLT-2 inhibitors, GLP-1 receptor agonists, or dual GLP-1/GIP receptor agonists—and, when appropriate, metabolic surgery, this approach offers the potential for disease remission in patients with shorter disease duration. For others, it enables superior metabolic control compared to traditional glucose-centered strategies while simultaneously delivering cardiovascular and renal benefits. In conclusion, an adipocentric treatment framework for ARD, which represents the majority of T2D cases, effectively integrates glucocentric and cardio-nephrocentric goals. This approach constitutes the optimal strategy for ARD due to its efficacy in achieving disease remission, improving metabolic control, addressing obesity-related comorbidities, and reducing cardiovascular and renal morbidity and mortality.
A Method for Estimating Fluorescence Emission Spectra from the Image Data of Plant Grain and Leaves Without a Spectrometer
Authors: Tominaga Shoji , Nishi Shogo , Ohtera Ryo , Sakai Hideaki
Published: January 2025

This study proposes a method for estimating the spectral images of fluorescence spectral distributions emitted from plant grains and leaves without using a spectrometer. We construct two types of multiband imaging systems with six channels, using ordinary off-the-shelf cameras and a UV light. A mobile phone camera is used to detect the fluorescence emission in the blue wavelength region of rice grains. For plant leaves, a small monochrome camera is used with additional optical filters to detect chlorophyll fluorescence in the red-to-far-red wavelength region. A ridge regression approach is used to obtain a reliable estimate of the spectral distribution of the fluorescence emission at each pixel point from the acquired image data. The spectral distributions can be estimated by optimally selecting the ridge parameter without statistically analyzing the fluorescence spectra. An algorithm for optimal parameter selection is developed using a cross-validation technique. In experiments using real rice grains and green leaves, the estimated fluorescence emission spectral distributions by the proposed method are compared to the direct measurements obtained with a spectroradiometer and the estimates obtained using the minimum norm estimation method. The estimated images of fluorescence emissions are presented for rice grains and green leaves. The reliability of the proposed estimation method is demonstrated.
Frequency-Based Analysis of Matching Accuracy Between Satellite Radio Frequency and AIS Data for Ship Identification
Authors: Yang Chan-Su , Chowdhury Sree Juwel Kumar
Published: January 2025

Vessels can deactivate their Automatic Identification System (AIS) to operate undetected and potentially engage in illegal activities. To address this, satellite-based radio frequency (RF) data are increasingly being used for identifying such vessels. This study evaluates the matching accuracy among RF and AIS data based on the frequency and distance. RF data were acquired on 22 September, 25 September, and 7 December 2023. According to the frequency range, the dataset was separated into frequency-1 (3.024–3.077 GHz) and frequency-2 (9.3734–9.4249 GHz). Six distance thresholds (2 km, 3 km, 6 km, 8 km, 13 km, and 18 km) were employed for the matching process. The results depicted that the average matching rates were 95%, 92%, and 92% for the RF dataset on 22 September, 25 September, and 7 December, respectively. Additionally, the results revealed that the matching rates decreased with distance, e.g., for the RF dataset on 22 September, the average highest matching rate (47%) was found at a 2 km distance and the minimum matching rate (0.9%) was observed at an 18 km distance. Furthermore, the analysis delineated that frequency-2 consistently exceeded frequency-1, particularly at longer distances, showing a more stable trend in matching accuracy.