Biomedicines

26 pages, 660 KiB

Open AccessReview

Relationship Between Depression and Neurodegeneration: Risk Factor, Prodrome, Consequence, or Something Else? A Scoping Review

by Dario Papa, Alessandro Ingenito, Alessandro von Gal, Maria Francesca De Pandis and Laura Piccardi

Biomedicines 2025, 13(5), 1023; https://doi.org/10.3390/biomedicines13051023 - 23 Apr 2025

Abstract

Background: The link between depression and neurodegeneration is complex and unclear. It is debated whether depression is a risk factor, a prodrome, a consequence, or unrelated. Objectives: This review examines these possibilities to clarify their connection, focusing primarily on Alzheimer’s disease, [...] Read more.

Background: The link between depression and neurodegeneration is complex and unclear. It is debated whether depression is a risk factor, a prodrome, a consequence, or unrelated. Objectives: This review examines these possibilities to clarify their connection, focusing primarily on Alzheimer’s disease, vascular dementia, Parkinson’s disease, and other highly comorbid neurodegenerative diseases. Methods: Eligibility criteria: The studies included in this review focused on neurodegenerative diseases with high comorbidity with depression, published in peer-reviewed English-language journals, providing empirical evidence on the link between the two conditions or theoretical frameworks that point to other studies. Non-human studies and those irrelevant to this connection were excluded. Source of evidence: AI-supported tools identified relevant articles. Results: Most studies suggest depression may contribute to neurodegeneration, but clinical, neuroimaging, and longitudinal evidence also support its role as a prodrome or consequence, indicating a bidirectional relationship. Conclusions: Despite extensive research, the connection remains unclear, highlighting the need for further investigation into underlying mechanisms and interdependencies, focusing on longitudinal studies by examining causality. Full article

(This article belongs to the Special Issue Neurodegeneration in Cognitive Impairment and Mood Disorders for Experimental, Clinical, and Translational Neuropsychiatry—Second Edition)

18 pages, 7762 KiB

Open AccessArticle

Identification of Therapeutic Targets for Hyperuricemia: Systematic Genome-Wide Mendelian Randomization and Colocalization Analysis

by Na Chen, Leilei Gong, Li Zhang, Yali Li, Yunya Bai, Dan Gao and Lan Zhang

Biomedicines 2025, 13(5), 1022; https://doi.org/10.3390/biomedicines13051022 - 23 Apr 2025

Abstract

Background: At present, there are still limitations and challenges in the treatment of hyperuricemia (HUA). Mendelian randomization (MR) has been widely used to identify new therapeutic targets. Therefore, we conducted a systematic druggable genome-wide MR to explore potential therapeutic targets and drugs [...] Read more.

Background: At present, there are still limitations and challenges in the treatment of hyperuricemia (HUA). Mendelian randomization (MR) has been widely used to identify new therapeutic targets. Therefore, we conducted a systematic druggable genome-wide MR to explore potential therapeutic targets and drugs for HUA. Methods: We integrated druggable genome data; blood, kidney, and intestinal expression quantitative trait loci (eQTLs); and HUA-associated genome-wide association study (GWAS) data to analyze the potential causal relationships between drug target genes and HUA using the MR method. Summary-data-based MR (SMR) analysis and Bayesian colocalization were used to assess causality. In addition, we conducted phenome-wide association studies, protein network construction, and enrichment analysis of significant targets to evaluate their biological functions and potential side effects. Finally, we performed drug prediction and molecular docking to identify potential drugs targeting these genes for HUA treatment. Results: Overall, we identified 22 druggable genes significantly associated with HUA through MR, SMR, and colocalization analyses. Among them, two prior druggable genes (ADORA2B and NDUFC2) reached statistically significant levels in at least two tissues in the blood, kidney, and intestine. Further results from phenome-wide studies revealed that there were no potential side effects of ADORA2B or NDUFC2. Moreover, we screened 15 potential drugs targeting the 22 druggable genes that could serve as candidates for HUA drug development. Conclusions: This study provides genetic evidence supporting the potential benefits of targeting 22 druggable genes for HUA treatment, offering new insights into the development of targeted drugs for HUA. Full article

(This article belongs to the Section Drug Discovery, Development and Delivery)

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20 pages, 6217 KiB

Open AccessArticle

SNX10 Is Involved in Ovarian Cancer Cell Metastasis by Repolarizing Tumor-Associated Macrophages Through mTOR1/Lysosomes Pathway

by Ranran Chai, Kewei Zheng, Ting Xu, Hui Wang, Xiaobo Cheng, Chong Lu and Yu Kang

Biomedicines 2025, 13(5), 1021; https://doi.org/10.3390/biomedicines13051021 - 23 Apr 2025

Abstract

Background: Tumor-associated macrophages (TAMs) are prevalent in advanced ovarian cancer tissues and ascites, significantly influencing disease prognosis. However, the mechanisms driving TAM polarization and their tumor-promoting effects remain poorly understood. Methods: The subcellular distribution of SNX10 in ovarian cancer tissues was analyzed [...] Read more.

Background: Tumor-associated macrophages (TAMs) are prevalent in advanced ovarian cancer tissues and ascites, significantly influencing disease prognosis. However, the mechanisms driving TAM polarization and their tumor-promoting effects remain poorly understood. Methods: The subcellular distribution of SNX10 in ovarian cancer tissues was analyzed using single-cell datasets (GSE147082, GSE58937). The Kaplan–Meier Plotter and GEPIA2 databases were used to evaluate SNX10’s prognostic relevance. Lentivirus-mediated SNX10 overexpression in THP-1 cells was employed in tumor cell–macrophage co-culture experiments. Transwell assays and flow cytometry assessed SNX10’s effects on ovarian cancer cell metastasis and cisplatin-induced apoptosis. RNA sequencing, Western blotting, lysosomal pH detection, lipid droplet staining, and RT-qPCR were performed to explore SNX10’s molecular mechanisms in TAM polarization and immune modulation. Results: SNX10 was specifically expressed in TAMs, promoting their polarization into the M2 phenotype. This enhanced the migration and invasion of ovarian cancer cell lines A2780 and A2780/CP70 while reducing cisplatin-induced apoptosis. SNX10 decreased lipid droplet content, downregulated p-mTOR1, and impaired lysosomal function in TAMs. Additionally, SNX10 differentially modulated PD-L1 mRNA expression in platinum-sensitive and platinum-resistant ovarian cancer cells. Conclusions: SNX10 regulates the mTOR1/lysosome pathway in TAMs, influencing lipid metabolism and indirectly modulating ovarian cancer cell metastasis. It also alters PD-L1 mRNA expression, suggesting a role in shaping the tumor immune microenvironment. Full article

(This article belongs to the Section Cancer Biology and Oncology)

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11 pages, 596 KiB

Open AccessSystematic Review

Novel Biomarkers in Hepatocellular Carcinoma from Embryogenic Antigens to cfDNA

by Robeer Ghantus, Răzvan Alexandru Ciocan, Diana Schlanger, Călin Popa, Claudia Diana Gherman, Călin Vaida, Bogdan Gherman, Doina Pîslă, Nadim Al Hajjar and Andra Ciocan

Biomedicines 2025, 13(5), 1020; https://doi.org/10.3390/biomedicines13051020 - 23 Apr 2025

Abstract

Background: Hepatocellular carcinoma (HCC), a primary liver cancer, continues to pose a significant challenge to the healthcare system because of its elevated incidence and fatality rates. This study aims to assess new biomarkers for early diagnosis and prognosis, comparing them to the established [...] Read more.

Background: Hepatocellular carcinoma (HCC), a primary liver cancer, continues to pose a significant challenge to the healthcare system because of its elevated incidence and fatality rates. This study aims to assess new biomarkers for early diagnosis and prognosis, comparing them to the established gold standard alpha-fetoprotein (AFP) and liver ultrasonography. Methods: A literature review was conducted in accordance with the preferred reporting items for systematic reviews and meta-analyses (PRISMA) guideline. A total of 670 papers were identified using internet databases. After applying the exclusion criteria, eight studies were included in this literature review. Results: It was identified that certain analyzed biomarkers, or the combinations thereof, exhibited superior sensitivity compared to the existing gold standard. The circulating cell-free DNA (cfDNA) and microRNAs (miRNAs), proved to have encouraging outcomes, particularly for the early identification of HCC. Additional indicators, such as circulating tumor cells (CTCs) and the alkaline phosphatase plus gamma-glutamyl transpeptidase to lymphocyte ratio (AGLR), may forecast disease progression, particularly regarding vascular invasion. Conclusions: These biomarkers may assist clinicians in making better therapeutical choices in order to provide personalized treatment and optimal follow-up for HCC patients. Full article

(This article belongs to the Special Issue Advances in Liver Oncology: Molecular Mechanisms and Therapeutic Innovations)

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20 pages, 1091 KiB

Open AccessReview

Hearts, Data, and Artificial Intelligence Wizardry: From Imitation to Innovation in Cardiovascular Care

by Panteleimon Pantelidis, Polychronis Dilaveris, Samuel Ruipérez-Campillo, Athina Goliopoulou, Alexios Giannakodimos, Panagiotis Theofilis, Raffaele De Lucia, Ourania Katsarou, Konstantinos Zisimos, Konstantinos Kalogeras, Evangelos Oikonomou and Gerasimos Siasos

Biomedicines 2025, 13(5), 1019; https://doi.org/10.3390/biomedicines13051019 - 23 Apr 2025

Abstract

Artificial intelligence (AI) is transforming cardiovascular medicine by enabling the analysis of high-dimensional biomedical data with unprecedented precision. Initially employed to automate human tasks such as electrocardiogram (ECG) interpretation and imaging segmentation, AI’s true potential lies in uncovering hidden disease data patterns, predicting [...] Read more.

Artificial intelligence (AI) is transforming cardiovascular medicine by enabling the analysis of high-dimensional biomedical data with unprecedented precision. Initially employed to automate human tasks such as electrocardiogram (ECG) interpretation and imaging segmentation, AI’s true potential lies in uncovering hidden disease data patterns, predicting long-term cardiovascular risk, and personalizing treatments. Unlike human cognition, which excels in certain tasks but is limited by memory and processing constraints, AI integrates multimodal data sources—including ECG, echocardiography, cardiac magnetic resonance (CMR) imaging, genomics, and wearable sensor data—to generate novel clinical insights. AI models have demonstrated remarkable success in early dis-ease detection, such as predicting heart failure from standard ECGs before symptom on-set, distinguishing genetic cardiomyopathies, and forecasting arrhythmic events. However, several challenges persist, including AI’s lack of contextual understanding in most of these tasks, its “black-box” nature, and biases in training datasets that may contribute to disparities in healthcare delivery. Ethical considerations and regulatory frameworks are evolving, with governing bodies establishing guidelines for AI-driven medical applications. To fully harness the potential of AI, interdisciplinary collaboration among clinicians, data scientists, and engineers is essential, alongside open science initiatives to promote data accessibility and reproducibility. Future AI models must go beyond task automation, focusing instead on augmenting human expertise to enable proactive, precision-driven cardiovascular care. By embracing AI’s computational strengths while addressing its limitations, cardiology is poised to enter an era of transformative innovation beyond traditional diagnostic and therapeutic paradigms. Full article

(This article belongs to the Special Issue Cardiovascular Diseases in the Era of Precision Medicine)

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Graphical abstract

15 pages, 1467 KiB

Open AccessArticle

Modelling Population Genetic Screening in Rare Neurodegenerative Diseases

by Thomas P. Spargo, Alfredo Iacoangeli, Mina Ryten, Francesca Forzano, Neil Pearce and Ammar Al-Chalabi

Biomedicines 2025, 13(5), 1018; https://doi.org/10.3390/biomedicines13051018 - 23 Apr 2025

Abstract

Importance: Genomic sequencing enables the rapid identification of a breadth of genetic variants. For clinical purposes, sequencing for small genetic variations is considered a solved problem, while challenges remain for structural variants, given the lower sensitivity and specificity. Interest has recently risen among [...] Read more.

Importance: Genomic sequencing enables the rapid identification of a breadth of genetic variants. For clinical purposes, sequencing for small genetic variations is considered a solved problem, while challenges remain for structural variants, given the lower sensitivity and specificity. Interest has recently risen among governing bodies in developing protocols for population-wide genetic screening. However, usefulness is constrained when the probability of being affected by a rare disease remains low, despite a positive genetic test. This is a common scenario in neurodegenerative disorders. The problem is recognised among statisticians and statistical geneticists but is less well-understood by clinicians and researchers who will act on these results, and by the general public who might access screening services directly without the appropriate support for interpretation. Observations: We explore the probability of subsequent disease following genetic screening of several variants, both single nucleotide variants (SNVs) and larger repeat expansions, for two neurological conditions, Huntington’s disease (HD) and amyotrophic lateral sclerosis (ALS), comparing these results with screening for phenylketonuria, which is well-established. The risk following a positive screening test was 0.5% for C9orf72 in ALS and 0.4% for HTT in HD when testing repeat expansions, for which the test had sub-optimal performance (sensitivity = 99% and specificity = 90%), and 12.7% for phenylketonuria and 10.9% for ALS SOD1 when testing pathogenic SNVs (sensitivity = 99.96% and specificity = 99.95%). Subsequent screening confirmation via PCR for C9orf72 led to a 2% risk of developing ALS as a result of the reduced penetrance (44%). Conclusions and Relevance: We show that risk following a positive screening test result can be strikingly low for rare neurological diseases, even for fully penetrant variants such as HTT, if the test has sub-optimal performance. Accordingly, to maximise the utility of screening, it is vital to prioritise protocols with very high sensitivity and specificity, and a careful selection of markers for screening, giving regard to clinical interpretability, actionability, high penetrance, and secondary testing to confirm positive findings. Full article

(This article belongs to the Special Issue Diagnosis and Treatment of Neurodegenerative Diseases in the Era of Precision Medicine)

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9 pages, 5125 KiB

Open AccessArticle

Cardiovascular Risk Factors Evaluated Using the Framingham Method in a University Community Setting

by Angela Mendoza, Sylvia Hidalgo and Luis Oviedo

Biomedicines 2025, 13(5), 1017; https://doi.org/10.3390/biomedicines13051017 - 23 Apr 2025

Abstract

Background/Objectives: Due to their work and lifestyle, many members of the university faculty, as well as administrative staff and students, are at risk of developing health problems. These risk factors can be assessed to find out their contribution to developing heart disease. [...] Read more.

Background/Objectives: Due to their work and lifestyle, many members of the university faculty, as well as administrative staff and students, are at risk of developing health problems. These risk factors can be assessed to find out their contribution to developing heart disease. The main objective of this study is to determine cardiovascular risk factors in a university setting based on the Framingham method. Methods: A quantitative approach, cross-sectional design, and an observational descriptive level were used in the study. The sample was made up of 85 members of the university community, and an adapted Framingham scale was used for data collection. Results: The results obtained show high percentages of obesity and overweight, especially in the administrative staff, with 55% and 35%, respectively, and in teachers, with 23% and 54%, respectively. Women are at higher risk of cardiovascular events and diabetes mellitus as measured by abdominal circumference (53%), with administrative staff (65%) being the most at risk, followed by teachers (50%). In addition, the community is at risk of developing metabolic disorders (61%) as determined by the insulin secretion coefficient. HDL in administrative staff was also moderately abnormal (45%). Conclusions: Significant cardiovascular risks are found in the university community and an intervention based on a program to develop healthy behaviors is suggested. Full article

(This article belongs to the Section Molecular and Translational Medicine)

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19 pages, 1804 KiB

Open AccessReview

Management of Acquired Hypothalamic Obesity After Childhood-Onset Craniopharyngioma—A Narrative Review

by Hermann L. Müller

Biomedicines 2025, 13(5), 1016; https://doi.org/10.3390/biomedicines13051016 - 22 Apr 2025

Abstract

Introduction: Craniopharyngiomas are rare sellar embryonic malformational tumors of low-grade histological malignancy. Despite high overall survival rates (92%), quality of life is frequently reduced due to adverse late effects caused by hypothalamic obesity. It is well known that morbid hypothalamic obesity is [...] Read more.

Introduction: Craniopharyngiomas are rare sellar embryonic malformational tumors of low-grade histological malignancy. Despite high overall survival rates (92%), quality of life is frequently reduced due to adverse late effects caused by hypothalamic obesity. It is well known that morbid hypothalamic obesity is associated with the grade of hypothalamic damage. Accordingly, craniopharyngioma should be considered a paradigmatic disease, reflecting challenges in the diagnosis and treatment of acquired hypothalamic obesity. Methods: A narrative review was performed after searching the MEDLINE/PubMed, Embase, and Web of Science databases for initial identifying articles. The search terms childhood-onset craniopharyngioma and hypothalamic obesity were used. Results: Despite the availability of promising therapeutic approaches, such as medication with central stimulating agents, antidiabetic drugs, glucagon-like peptide 1 (GLP1) receptor agonists, and Setmelanotide, it must be emphasized that there is currently no pharmaceutical treatment for hypothalamic obesity in craniopharyngioma proven to be effective in randomized controlled trials. For Setmelanotide, a prospective blinded randomized trial over a 12-month treatment period is ongoing. Bariatric interventions are effective, but non-reversible procedures such as bypass operations are controversial in the pediatric age group due to legal and ethical concerns. Recently, a treatment algorithm was introduced to improve the management of hypothalamic syndrome/obesity by offering more personalized treatment. Decisions on treatment strategies focusing on the preservation of visual, neuroendocrine, and hypothalamic integrity should be made by experienced multidisciplinary teams. Conclusions: Treatment approaches for hypothalamic obesity are limited. Further research on novel treatment approaches for hypothalamic obesity is warranted to improve the quality of life after childhood-onset craniopharyngioma. Full article

(This article belongs to the Special Issue Feature Reviews on Cardiovascular and Metabolic Diseases)

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16 pages, 1955 KiB

Open AccessArticle

Defective Intracortical Inhibition as a Marker of Impaired Neural Compensation in Amputees Undergoing Rehabilitation

by Guilherme J. M. Lacerda, Lucas Camargo, Fernanda M. Q. Silva, Marta Imamura, Linamara R. Battistella and Felipe Fregni

Biomedicines 2025, 13(5), 1015; https://doi.org/10.3390/biomedicines13051015 - 22 Apr 2025

Abstract

Background/Objectives: Lower-limb amputation (LLA) leads to disability, impaired mobility, and reduced quality of life, affecting 1.6 million people in the USA. Post-amputation, motor cortex reorganization occurs, contributing to phantom limb pain (PLP). Transcranial magnetic stimulation (TMS) assesses changes in cortical excitability, helping [...] Read more.

Background/Objectives: Lower-limb amputation (LLA) leads to disability, impaired mobility, and reduced quality of life, affecting 1.6 million people in the USA. Post-amputation, motor cortex reorganization occurs, contributing to phantom limb pain (PLP). Transcranial magnetic stimulation (TMS) assesses changes in cortical excitability, helping to identify compensatory mechanisms. This study investigated the association between TMS metrics and clinical and neurophysiological outcomes in LLA patients. Methods: A cross-sectional analysis of the DEFINE cohort, with 59 participants, was carried out. TMS metrics included resting motor threshold (rMT), motor-evoked potential (MEP) amplitude, short intracortical inhibition (SICI), and intracortical facilitation (ICF). Results: Multivariate analysis revealed increased ICF and rMT in the affected hemisphere of PLP patients, while SICI was reduced with the presence of PLP. A positive correlation between SICI and EEG theta oscillations in the frontal, central, and parietal regions suggested compensatory mechanisms in the unaffected hemisphere. Increased MEP was associated with reduced functional independence. Conclusions: SICI appears to be a key factor linked to the presence of PLP, but not its intensity. Reduced SICI may indicate impaired cortical compensation, contributing to PLP. Other neural mechanisms, including central sensitization and altered thalamocortical connectivity, may influence PLP’s severity. Our findings align with those of prior studies, reinforcing low SICI as a marker of maladaptive neuroplasticity in amputation-related pain. Additionally, longer amputation duration was associated with disrupted SICI, suggesting an impact of long-term plasticity changes. Full article

(This article belongs to the Section Neurobiology and Clinical Neuroscience)

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17 pages, 2564 KiB

Open AccessArticle

Protective Action of 3,5-Diiodo-L-Thyronine on Cigarette Smoke-Induced Mitochondrial Dysfunction in Human Alveolar Epithelial Cells

by Francesca Panico, Davida Mirra, Giuseppe Petito, Giuseppe Spaziano, Vitale Del Vecchio, Renata Esposito, Rosalba Senese, Vincenzo Desiderio, Antonia Lanni and Bruno D’Agostino

Biomedicines 2025, 13(5), 1014; https://doi.org/10.3390/biomedicines13051014 - 22 Apr 2025

Abstract

Background: Cigarette smoke (CS) is a major risk factor for chronic lung conditions. Oxidative stress and mitochondrial dysfunction play a crucial role in CS-induced pulmonary injury. 3,5-Diiodothyronine (T2) affects energy metabolism, having mitochondria as a major target. However, the underlying mechanisms of [...] Read more.

Background: Cigarette smoke (CS) is a major risk factor for chronic lung conditions. Oxidative stress and mitochondrial dysfunction play a crucial role in CS-induced pulmonary injury. 3,5-Diiodothyronine (T2) affects energy metabolism, having mitochondria as a major target. However, the underlying mechanisms of T2 related to lung diseases are poorly understood. Aims: To investigate the protective action of T2 on CS-induced mitochondrial dysfunction in an in vitro model of human epithelial alveolar cells. Methods: ATP synthesis and cytochrome c oxidase (COX) activity, as a marker of mitochondrial function, was assessed in A549 cells pretreated with T2 and exposed to CS using a bioluminescence assay and an Oroboros 2k-Oxygraph system, respectively. An evaluation of the oxidative status was conducted by assessing superoxide radical production, superoxide dismutase (SOD) activity, and H₂O₂ levels. Moreover, we investigated the mitochondrial mass via Mito-Tracker Green (MTG) staining and flow cytometry analysis. Results: CS significantly reduced ATP production. T2 pretreatment was found to prevent CS-induced impairments in ATP synthesis, enhancing COX activity. Additionally, the 2 h T2 pretreatment of CS-exposed cells mitigated CS-induced oxidative stress, thereby enhancing SOD activity and reducing the superoxide anion and H₂O₂ levels. Finally, MTG labeling was correlated with CS-induced mitochondrial mass gain, which is associated with cell senescence. Unexpectedly, T2 was not able to significantly prevent this mass increment, probably due to its rapid mode of action. Conclusions: Our results provide new insights into the protective effects of T2 against CS-induced mitochondrial damage. Full article

(This article belongs to the Section Cell Biology and Pathology)

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14 pages, 1405 KiB

Open AccessReview

An In-Depth Review of the Azygos Vein and Its Clinical Significance

by Alexander Stolarczyk, Nazar Włodarczyk, Nicol Zielinska, Kacper Ruzik, George Triantafyllou, Maria Piagkou and Łukasz Olewnik

Biomedicines 2025, 13(5), 1013; https://doi.org/10.3390/biomedicines13051013 - 22 Apr 2025

Abstract

The azygos vein is a vessel that drains deoxygenated blood from the posterior wall of the thorax and upper abdomen into the superior vena cava. It can vary morphologically in both adults and fetuses in origin, termination, diameter, course, and tributaries, especially the [...] Read more.

The azygos vein is a vessel that drains deoxygenated blood from the posterior wall of the thorax and upper abdomen into the superior vena cava. It can vary morphologically in both adults and fetuses in origin, termination, diameter, course, and tributaries, especially the hemiazygos vein and accessory hemiazygos vein, which, together with the azygos vein, form the azygos venous system. The main aim of this review is to summarize the current state of knowledge regarding the azygos vein. Another aim is to present the morphological variations of the azygos vein and their clinical significance. This information may be useful to clinicians, especially surgeons. This review also provides an overview of the embryological development of the azygos venous system and the consequences of its developmental errors, as well as their relationship to certain clinical cases and pathologies. Full article

(This article belongs to the Section Cell Biology and Pathology)

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13 pages, 869 KiB

Open AccessArticle

Detection of SARS-CoV-2 Using the Abbott™ PANBIO™ COVID-19 SELF-TEST Rapid Test in Patients Seen at INER

by Kenny Alonso Cantón Cruz, Martha Angella Durán Barrón, Israel Agustín Morales Lozada, Mario Alberto Mujica Sánchez, Grecia Gabriela Deloya Brito, María del Carmen García Colín, Hansel Hugo Chávez Morales, José Nicolás Aguirre Pineda, Cinthya Karen Cid del Prado Rojas, Stephanie Jara Valdés and Eduardo Becerril Vargas

Biomedicines 2025, 13(5), 1012; https://doi.org/10.3390/biomedicines13051012 - 22 Apr 2025

Abstract

The COVID-19 pandemic has highlighted the need for rapid and accurate tests to detect SARS-CoV-2. Objectives: This study evaluates the effectiveness of the Panbio™ COVID-19 Antigen Self-Test rapid test compared to reverse transcriptase polymerase chain reaction (RT-PCR). Methods: A prospective diagnostic testing [...] Read more.

The COVID-19 pandemic has highlighted the need for rapid and accurate tests to detect SARS-CoV-2. Objectives: This study evaluates the effectiveness of the Panbio™ COVID-19 Antigen Self-Test rapid test compared to reverse transcriptase polymerase chain reaction (RT-PCR). Methods: A prospective diagnostic testing study was performed. Patients with respiratory symptoms who provided informed consent were included. Results: We included 205 patients with COVID-19 symptoms who underwent both tests. The mean age was 35.55 ± 12.62 years, and 64% of the participants were female. Sensitivity and specificity were 71.2% (95% CI: 62.5–79.9%) and 100% (95% CI: 96.4–100%), respectively. Conclusions: If a test is positive within the first 72 h after the onset of symptoms, we can be sure that it is a case of COVID-19; however, when the antigen test is negative, confirmation with RT-PCR is necessary. Its ease of use and results with moderate precision make it a valuable tool for early detection. Full article

(This article belongs to the Special Issue High-Sensitivity Lateral Flow Assays for SARS-CoV-2 and Other Infections, 2nd Edition)

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15 pages, 1397 KiB

Open AccessArticle

The Impact of Resection Margins in Primary Resection of High-Grade Soft Tissue Sarcomas: How Far Is Far Enough?

by Julian Miles Steffens, Tymoteusz Budny, Georg Gosheger, Marieke De Vaal, Anna Maria Rachbauer, Andrea Laufer, Nina Myline Engel and Niklas Deventer

Biomedicines 2025, 13(5), 1011; https://doi.org/10.3390/biomedicines13051011 - 22 Apr 2025

Abstract

Background/Objectives: The World Health Organization’s (WHO) classification of tumors contains around 80 entities of soft tissue sarcomas (STSs). Currently, surgery is the standard treatment for patients with localized STS, but the adequacy of resection margins in soft tissue sarcomas (STSs) remains a [...] Read more.

Background/Objectives: The World Health Organization’s (WHO) classification of tumors contains around 80 entities of soft tissue sarcomas (STSs). Currently, surgery is the standard treatment for patients with localized STS, but the adequacy of resection margins in soft tissue sarcomas (STSs) remains a topic of intense discussion. Methods: This single-center study retrospectively reviewed 203 patients with primary high-grade soft tissue sarcoma, including a follow-up period of at least 24 months. Patients with prior resection, secondary STS, metastasis at presentation, or those who required amputational surgery were excluded from the study. Patients were categorized based on their margin thickness: positive (n = 13, 6.4%), 0–1 mm (n = 67, 33.0%), 1–5 mm (n = 70, 34.5%), and >5 mm (n = 27, 13.3%). Results: A total of 64 out of 203 (31.5%) patients developed a local recurrence. The estimated 5-year local-recurrence-free survival (LRFS) was 11.5% (CI 4–25%) for positive margins, 58% (CI 51–64%) for margins 0–1 mm, 76% (CI 70–81%) for margins > 1–5 mm, and 93% (CI 88–98%) for margins > 5 mm. No local recurrences occurred in patients with margins > 5 mm and adjuvant radiotherapy. Margin status significantly influenced the development of distant metastasis and overall survival. Adjuvant radiotherapy improved both local control and overall survival. Conclusions: To minimize the risk of local recurrence (LR), a resection margin greater than 5 mm should be attained. When adjuvant radiotherapy is applied, the likelihood of LR decreases even more. In scenarios where preserving critical structures is essential, a resection margin of less than 5 mm can be acceptable for ensuring local control. Full article

(This article belongs to the Special Issue Advanced Cancer Diagnosis and Treatment: Second Edition)

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22 pages, 3303 KiB

Open AccessArticle

Disparate Molecular Properties of Two Hypertrophic Cardiomyopathy-Associated cMyBP-C Mutants Reveal Distinct Pathogenic Mechanisms Beyond Haploinsufficiency

by Angelos Thanassoulas, Emna Riguene, Maria Theodoridou, Laila Barrak, Hamad Almaraghi, Mohammed Hussain, Sahar Isa Da’as, Mohamed A. Elrayess, F. Anthony Lai and Michail Nomikos

Biomedicines 2025, 13(5), 1010; https://doi.org/10.3390/biomedicines13051010 - 22 Apr 2025

Abstract

Background/Objectives: Hypertrophic cardiomyopathy (HCM) is a common genetic cardiac disorder marked by abnormal thickening of the left ventricular myocardium, often leading to arrhythmias and heart failure. Mutations in sarcomeric protein genes, particularly MYBPC3, which encodes cardiac myosin-binding protein C (cMyBP-C), are [...] Read more.

Background/Objectives: Hypertrophic cardiomyopathy (HCM) is a common genetic cardiac disorder marked by abnormal thickening of the left ventricular myocardium, often leading to arrhythmias and heart failure. Mutations in sarcomeric protein genes, particularly MYBPC3, which encodes cardiac myosin-binding protein C (cMyBP-C), are major contributors to HCM pathogenesis. This study aims to investigate the structural and functional effects of two HCM-associated missense mutations, p.S236G and p.E334K, located within the C0–C2 domains of cMyBP-C. Methods: Following in silico analysis, a bacterial expression system was applied, enabling the discrete C0–C2 domains of wild-type (cMyBP-C^WT) and mutant (cMyBP-C^S236G and cMyBP-C^E334K) cMyBP-C proteins to be expressed and purified as recombinant proteins. Structural and stability changes were assessed using circular dichroism (CD), differential scanning calorimetry (DSC), and chemical denaturation assays. Functional impact on actin binding was also evaluated in vitro. Results: CD analysis revealed altered secondary structure in both mutants compared to the wild-type protein. Thermal and chemical stability assays indicated increased stability in the cMyBP-C^E334K mutant, suggesting that it exhibits a more rigid conformation. This increased rigidity corresponded with a significant reduction in the actin-binding affinity relative to the wild-type protein. Conclusions: Our findings demonstrate specific detrimental effects of the p.E334K mutation and underscore the importance of understanding the structural and functional consequences of HCM-associated mutations to assist the development of targeted therapeutic strategies. Full article

(This article belongs to the Special Issue Pathogenesis, Diagnosis and Treatment of Cardiomyopathy and Cardiac Arrhythmias (2nd Edition))

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13 pages, 1183 KiB

Open AccessArticle

Can Progressive Supranuclear Palsy Be Accurately Identified via MRI with the Use of Visual Rating Scales and Signs?

by George Anyfantakis, Stamo Manouvelou, Vasilios Koutoulidis, Georgios Velonakis, Nikolaos Scarmeas and Sokratis G. Papageorgiou

Biomedicines 2025, 13(5), 1009; https://doi.org/10.3390/biomedicines13051009 - 22 Apr 2025

Abstract

Introduction: Neurodegenerative diseases like progressive supranuclear palsy (PSP) present challenges concerning their diagnosis. Neuroimaging using magnetic resonance (MRI) may add diagnostic value. However, modern techniques such as volumetric assessment using Voxel-Based Morphometry (VBM), although proven to be more accurate and superior compared to [...] Read more.

Introduction: Neurodegenerative diseases like progressive supranuclear palsy (PSP) present challenges concerning their diagnosis. Neuroimaging using magnetic resonance (MRI) may add diagnostic value. However, modern techniques such as volumetric assessment using Voxel-Based Morphometry (VBM), although proven to be more accurate and superior compared to MRI, have not gained popularity among scientists in the investigation of neurological disorders due to their higher cost and time-consuming applications. Conventional brain MRI methods may present a quick, practical, and easy-to-use imaging rating tool for the differential diagnosis of PSP. The purpose of this study is to evaluate a string of existing visual MRI rating scales and signs regarding their impact for the diagnosis of PSP. Materials and Methods: The population study consisted of 30 patients suffering from PSP and 72 healthy controls. Each study participant underwent a brain MRI, which was subsequently examined by two independent researchers in a double-blinded fashion. Fifteen visual rating scales and signs were evaluated, including pontine atrophy, cerebellar atrophy, midbrain atrophy, aqueduct of Sylvius enlargement, cerebellar peduncle hyperintensities, enlargement of the fourth ventricle (100% sensitivity and 71% specificity) and left temporal lobe atrophy (97% sensitivity and 78% specificity). Conclusions: Enlargement of the Sylvius aqueduct, enlargement of the fourth ventricle and atrophy of both temporal lobes together with the presence of morning glory and hummingbird signs can be easily and quickly distinguished and identified by an experienced radiologist without involving any complex analysis, making them useful tools for PSP diagnosis. MRI visual scale measurements could be added to the diagnostic criteria of PSP and may serve as an alternative to highly technical and more sophisticated quantification methods. Full article

(This article belongs to the Special Issue Advances in Neurological Diseases: Pathogenesis, Diagnosis and Therapeutic Strategies)

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13 pages, 2296 KiB

Open AccessCase Report

A Novel Bradycardia-Associated Variant in HCN4 as a Candidate Modifier in Type 3 Long QT Syndrome: Case Report and Deep In Silico Analysis

by Anna A. Bukaeva, Anastasia V. Blokhina, Maria S. Kharlap, Marija Zaicenoka, Evgenia D. Zotova, Anna V. Petukhova, Elizaveta V. Garbuzova, Anastasia A. Zharikova, Mikhail G. Divashuk, Anna V. Kiseleva, Alexandra I. Ershova, Alexey N. Meshkov and Oxana M. Drapkina

Biomedicines 2025, 13(4), 1008; https://doi.org/10.3390/biomedicines13041008 - 21 Apr 2025

Abstract

Background: Genetic testing for long QT syndrome (LQTS) is straightforward in many families; however, in severe and complex cases, a single disease-causing variant may not be enough to explain all clinical features. In such cases, the search for genetic modifiers may be beneficial [...] Read more.

Background: Genetic testing for long QT syndrome (LQTS) is straightforward in many families; however, in severe and complex cases, a single disease-causing variant may not be enough to explain all clinical features. In such cases, the search for genetic modifiers may be beneficial for precise diagnosis and management. Case presentation: We describe a three-generational family affected with clinically heterogeneous LQTS type 3 and bradycardia in which a novel missense variant p.V642M in HCN4 was identified in addition to the known pathogenic variant p.E1784K in SCN5A. We performed the detailed clinical investigation of the family and a deep in silico analysis of the discovered variants, showing the causal role of a new HCN4 variant in sinus bradycardia and its possible contribution to the phenotypic heterogeneity of LQTS type 3. Conclusions: This case is the first description of a functional variant in HCN4 as a candidate modifier in LQTS type 3 and demonstrates the importance of analyzing additional genetic variations in families with complex LQTS phenotypes. Full article

(This article belongs to the Special Issue Cardiovascular Diseases in the Era of Precision Medicine)

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14 pages, 2090 KiB

Open AccessSystematic Review

The Clinicopathological and Prognostic Value of CCR7 Expression in Breast Cancer Throughout the Literature: A Systematic Review and Meta-Analysis

by Mohamed Elhadary, Basel Elsayed, Amgad Mohamed Elshoeibi, Omar Karen, Ibrahim Elmakaty, Jehad Alhmoud, Ahmad Hamdan and Mohammed Imad Malki

Biomedicines 2025, 13(4), 1007; https://doi.org/10.3390/biomedicines13041007 - 21 Apr 2025

Abstract

Background/Objective: This study aimed to determine the clinicopathological findings and prognostic value of chemokine receptor 7 (CCR7) expression in patients with breast cancer (BC). Methods: Up to the 25th of March 2025, a search was conducted using five databases: PubMed, Embase, Scopus, Medline, [...] Read more.

Background/Objective: This study aimed to determine the clinicopathological findings and prognostic value of chemokine receptor 7 (CCR7) expression in patients with breast cancer (BC). Methods: Up to the 25th of March 2025, a search was conducted using five databases: PubMed, Embase, Scopus, Medline, and Web of Science. The methodological standards for the epidemiological research scale were used to assess the quality of the included articles, and Stata software (Stata 19) was used to synthesize the meta-analysis. Results: We considered 12 of 853 studies that included 3119 patients with BC. High CCR7 expression was not associated with age (odds ratio [OR] 0.82, 95% confidence interval [CI] 0.66–1.03); clinicopathological findings, including tumor size (OR 1.062, 95% CI 0.630–1.791); clinical stage (OR 1.753, 95% CI 0.231–13.304); nodal metastasis (OR 1.252, 95% CI 0.571–2.741); or histological differentiation (OR 1.167, 95% CI 0.939–1.450). CCR7 expression did not affect overall survival (hazard ratio 0.996, 95% CI 0.659–1.505). Conclusions: Our quantitative analysis did not reveal an association between CCR7 expression and poor clinicopathological or prognostic features in BC patients. Because of the high heterogeneity and potential publication bias, large high-quality studies are required to further confirm these findings. Full article

(This article belongs to the Special Issue The Role of Cytokines in Health and Disease: 2nd Edition)

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14 pages, 2415 KiB

Open AccessArticle

Prostate Tissue-Induced Platelet Activation and Platelet–Neutrophil Aggregation Following Transurethral Resection of the Prostate Surgery: An In Vitro Study

by Po-An Lin, Hsiang-Han Huang, Mei-Hua Hu, Go-Shine Huang, En Meng, Yi-Lin Chiu, Yung-Chi Hsu and Wei-Hung Chan

Biomedicines 2025, 13(4), 1006; https://doi.org/10.3390/biomedicines13041006 - 21 Apr 2025

Abstract

Background: This study aimed to investigate the effects of prostate tissue on platelet activation markers, primarily assessed through P-selectin expression, and to assess the formation of platelet–leukocyte aggregations in response to prostate tissue exposure. Furthermore, we compared platelet activation induced by prostate [...] Read more.

Background: This study aimed to investigate the effects of prostate tissue on platelet activation markers, primarily assessed through P-selectin expression, and to assess the formation of platelet–leukocyte aggregations in response to prostate tissue exposure. Furthermore, we compared platelet activation induced by prostate tissue homogenates with that induced by thrombin stimulation. These processes may play a role in the development of disseminated intravascular coagulation (DIC) following transurethral resection of the prostate (TURP). Methods: We collected prostate tissue samples from 12 patients undergoing TURP. The samples were homogenized and used to stimulate platelet-rich plasma in vitro. Flow cytometry was used to measure platelet P-selectin expression and platelet–leukocyte aggregation. Additionally, four experimental groups were established: (A) saline control, (B) thrombin stimulation, (C) phosphate-buffered saline (PBS) control, and (D) prostate tissue homogenate. Data were analyzed to assess the impact of prostate tissue and thrombin on platelet activation and platelet–leukocyte interactions. Results: Prostate tissue homogenates significantly increased platelet P-selectin expression and platelet–neutrophil aggregation compared with the control groups (p < 0.05). Overall, platelet–leukocyte aggregation was not significantly different between the thrombin and prostate tissue groups. However, prostate tissue exposure did not significantly affect platelet–monocyte and platelet–lymphocyte aggregations. Conclusions: Prostate tissue exposure during TURP induces platelet activation, particularly platelet P-selectin expression and platelet–neutrophil aggregation, suggesting a potential mechanism for DIC development. These findings highlight the importance of monitoring platelet activity in patients undergoing TURP and indicate that interventions targeting platelet P-selectin expression and platelet–neutrophil interactions may help mitigate DIC risk. Full article

(This article belongs to the Section Cell Biology and Pathology)

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Graphical abstract

11 pages, 427 KiB

Open AccessArticle

Temporal Patterns of Holter-Detected Arrhythmias in Hypertrophic Cardiomyopathy Patients Treated with Mavacamten

by Amro Badr, Kaitlin Roehl, Mustafa Suppah, Humam Abo Abdullah, Reza Arsanjani, Konstantinos C. Siontis, Jeffrey B. Geske, Steve R. Ommen, John R. Giudicessi and Said Alsidawi

Biomedicines 2025, 13(4), 1005; https://doi.org/10.3390/biomedicines13041005 - 21 Apr 2025

Abstract

Background: Hypertrophic cardiomyopathy (HCM) is a genetic cardiomyopathy marked by increased left ventricular wall thickness, leading in some cases to left ventricular outflow tract (LVOT) obstruction, heart failure, and arrhythmias. Mavacamten, a selective allosteric inhibitor of cardiac myosin, has demonstrated benefits in improving [...] Read more.

Background: Hypertrophic cardiomyopathy (HCM) is a genetic cardiomyopathy marked by increased left ventricular wall thickness, leading in some cases to left ventricular outflow tract (LVOT) obstruction, heart failure, and arrhythmias. Mavacamten, a selective allosteric inhibitor of cardiac myosin, has demonstrated benefits in improving hemodynamics and reducing LVOT obstruction. However, its impact on arrhythmic burden remains unclear, with reports of early atrial fibrillation (AF) risk contrasting with long-term reductions in arrhythmias. This study assesses the temporal patterns of Holter-detected arrhythmias in HCM patients treated with mavacamten. Methods: This retrospective study included HCM patients from three Mayo Clinic sites. Baseline demographic, clinical, and echocardiographic data were collected. Holter monitoring was performed at baseline, short-term (<6 months), and long-term (>6 months) follow-up. Arrhythmic events, including premature atrial contractions (PACs), premature ventricular contractions (PVCs), and supraventricular tachycardia (SVT), were analyzed using standardized rates per 24 h. Statistical comparisons utilized the Wilcoxon signed-rank test. Results: Twenty-seven patients (56% female, median age 66 years) were included. PACs, PVCs, and SVT duration transiently but not significantly increased at short-term follow-up but returned to baseline at long-term follow-up. No sustained or high-risk ventricular arrhythmias were observed. Conclusions: Mavacamten is associated with transient arrhythmic fluctuations early in treatment, followed by stabilization. These findings support its long-term electrophysiological safety and underscore the need for early rhythm monitoring. Further research should explore its role in arrhythmic risk stratification in HCM patients. Full article

(This article belongs to the Special Issue Advanced Research in Hypertrophic Cardiomyopathy)

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