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Search Results (4,607)

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13 pages, 1291 KiB  
Article
Preoperative Expression Profiles of miR-146a and miR-221 as Potential Biomarkers for Differentiating Benign from Malignant Thyroid Nodules
by Mervat Matei, Sergiu-Ciprian Matei, Cristina Stefania Dumitru, Roxana Popescu, Ligia Petrica, Ioana Golu, Marioara Cornianu, Isabella Ionela Stoian and Mihaela Maria Vlad
Int. J. Mol. Sci. 2025, 26(15), 7564; https://doi.org/10.3390/ijms26157564 (registering DOI) - 5 Aug 2025
Abstract
Thyroid cancer is the most common endocrine malignancy, and preoperative distinction between benign and malignant nodules remains challenging, especially in cytologically indeterminate cases. Circulating microRNAs (miRNAs) have gained interest as non-invasive biomarkers due to their stability and involvement in tumorigenesis. This study aimed [...] Read more.
Thyroid cancer is the most common endocrine malignancy, and preoperative distinction between benign and malignant nodules remains challenging, especially in cytologically indeterminate cases. Circulating microRNAs (miRNAs) have gained interest as non-invasive biomarkers due to their stability and involvement in tumorigenesis. This study aimed to assess the preoperative diagnostic value of circulating miR-146a and miR-221 in patients undergoing thyroidectomy. A total of 56 patients were included, of whom 24 had malignant and 32 had benign thyroid lesions confirmed by histopathology. Preoperative plasma levels of miR-146a and miR-221 were quantified using qRT-PCR, and relative expression was calculated with the 2−ΔΔCt method. miR-221 expression was significantly higher in malignant cases, with an area under the ROC curve of 1.00, achieving 100% sensitivity and specificity at the optimal threshold. miR-146a showed no significant discriminatory ability. Weak correlations were observed between miRNA expression and clinical parameters such as age, TIRADS score, or thyroid volume. Logistic regression including miR-221 led to perfect separation, indicating strong predictive capacity but precluding multivariate modeling. These findings suggest that circulating miR-221 may serve as a highly accurate biomarker for thyroid malignancy and warrant further validation in larger, prospective cohorts. Full article
(This article belongs to the Special Issue Advancements in Cancer Biomarkers)
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14 pages, 1058 KiB  
Article
Sex- and Age-Specific Utilization Patterns of Nuclear Medicine Procedures at a Public Tertiary Hospital in Jamaica
by Tracia-Gay Kennedy-Dixon, Mellanie Didier, Fedrica Paul, Andre Gordon, Marvin Reid and Maxine Gossell-Williams
Hospitals 2025, 2(3), 21; https://doi.org/10.3390/hospitals2030021 - 5 Aug 2025
Abstract
Understanding the utilization patterns of nuclear medicine (NM) services is essential for optimizing resource allocation and service provision. This study aimed to address the regional evidence gap by reporting the demand for NM services by sex and age at a public hospital in [...] Read more.
Understanding the utilization patterns of nuclear medicine (NM) services is essential for optimizing resource allocation and service provision. This study aimed to address the regional evidence gap by reporting the demand for NM services by sex and age at a public hospital in Jamaica. This was a non-experimental, retrospective study of NM scans that were completed at the University Hospital of the West Indies from 1 June 2022 to 31 May 2024. While all scans were reported in the descriptive totals, for patients with multiple scans during the study period, only the data from the first visit was used in the inferential statistical analysis. This was performed with the IBM SPSS (version 29.0) software and involved the use of chi-square goodness of fit and multinomial logistic regression. A total of 1135 NM scans for 1098 patients were completed (37 patients had more than one scan); 596 (54.3%) were female and 502 (45.7%) were male, with the ages ranging from 3 days to 94 years old. Among the female patients, there was a greater demand in the ≥60 years age group for cardiac amyloid scans (χ2 = 6.40, p < 0.05), while females 18–59 years had a greater demand for thyroid scans (χ2 = 7.714, p < 0.05) and bone scans (χ2 = 3.904, p < 0.05). On the other hand, significantly more males in the ≥60 age group presented for cardiac amyloid (χ2 = 4.167; p < 0.05) and bone scans (χ2 = 145.79, p < 0.01). Males were significantly less likely to undergo a thyroid scan than females (p < 0.01, OR = 0.072, 95% CI: 0.021, 0.243) while individuals aged 18–59 years were more likely to undergo this scan than patients aged 60 or older (p = 0.02, OR = 3.565, 95% CI: 1.258, 10.104). Males were more likely to do a cardiac amyloid scan (p < 0.05, OR = 2.237, 95% CI: 1.023, 4.891) but less likely to undergo a cardiac rest/stress test than females (p = 0.02, OR = 0.307, 95% CI: 0.114, 0.828). Prolonged life expectancy and an aging population have the potential to impact NM utilization, thus requiring planning for infrastructure, equipment, work force, and supplies. Cancer-related and cardiovascular indications are a top priority at this facility; hence, age- and sex-specific analysis are useful in establishing models for policy makers with regard to the allocation of economic and human resources for the sustainability of this specialized service. Full article
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36 pages, 6047 KiB  
Review
Prevalence and Levels of Thyroid Autoantibodies in Polycystic Ovary Syndrome—Impact of TSH- and BMI-Matched Comparisons: A Systematic Review and Meta-Analysis
by Jakub Kwiatkowski, Nicole Akpang, Lucja Zaborowska and Artur Ludwin
Int. J. Mol. Sci. 2025, 26(15), 7525; https://doi.org/10.3390/ijms26157525 (registering DOI) - 4 Aug 2025
Abstract
Polycystic ovary syndrome (PCOS) is a complex condition affecting women of reproductive age, characterized by menstrual irregularities, hyperandrogenism, polycystic ovarian morphology, and low-grade inflammation accompanied by oxidative stress and increased autoimmune risk, particularly Hashimoto’s thyroiditis. Many studies have examined thyroid autoantibodies—anti-thyroid peroxidase antibodies [...] Read more.
Polycystic ovary syndrome (PCOS) is a complex condition affecting women of reproductive age, characterized by menstrual irregularities, hyperandrogenism, polycystic ovarian morphology, and low-grade inflammation accompanied by oxidative stress and increased autoimmune risk, particularly Hashimoto’s thyroiditis. Many studies have examined thyroid autoantibodies—anti-thyroid peroxidase antibodies (anti-TPO) and anti-thyroglobulin antibodies (anti-TG)—in PCOS; however, observed differences in baseline thyroid-stimulating hormone (TSH) levels and body mass indices (BMIs) impede a direct interpretation of the results. This systematic review and meta-analysis aimed to summarize the available evidence on the prevalence and levels of anti-TPO and anti-TG in women with PCOS. We conducted a systematic search of PubMed, Scopus, and Embase, which yielded 40 eligible, observational studies including 6045 women with PCOS and 4527 controls. Subgroup analyses were conducted separately for TSH- and BMI-matched populations. Anti-TPO prevalence (odds ratio [OR] = 2.03; 95% confidence interval [CI]: 1.35–3.04; p = 0.0006) and levels (standardized mean difference [SMD] = 0.63; 95% CI: 0.37–0.88; p < 0.00001) were significantly higher in PCOS patients. Anti-TG prevalence (OR = 1.92; 95% CI: 1.23–3.01; p = 0.004) and levels (SMD = 0.41; 95% CI: 0.18–0.64; p = 0.0004) were also significantly elevated. In matched subgroups, prevalence differences were no longer significant, though anti-TPO levels remained significantly elevated and anti-TG levels were borderline significant in the TSH-matched subgroup of PCOS women. Although differences in thyroid autoantibody prevalence in women with PCOS appear to be driven by elevated TSH levels and BMIs, the persistently increased antibody levels in the majority of matched subgroups suggest that PCOS itself may contribute independently to heightened autoimmune activation. Full article
(This article belongs to the Section Molecular Oncology)
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13 pages, 2643 KiB  
Review
Primary Hyperparathyroidism: 18F-Fluorocholine PET/CT vs. 4D-CT for Parathyroid Identification: Toward a Comprehensive Diagnostic Framework—An Updated Review and Recommendations
by Gregorio Scerrino, Nunzia Cinzia Paladino, Giuseppa Graceffa, Giuseppina Melfa, Giuseppina Orlando, Renato Di Vuolo, Chiara Lo Cicero, Alessandra Murabito, Stefano Radellini, Pierina Richiusa and Antonio Lo Casto
J. Clin. Med. 2025, 14(15), 5468; https://doi.org/10.3390/jcm14155468 - 4 Aug 2025
Abstract
Introduction: Primary hyperparathyroidism (pHPT) is an endocrine disorder characterized by excessive parathyroid hormone production, typically due to adenomas, hyperplasia, or carcinoma. Preoperative imaging plays a critical role in guiding surgical planning, particularly in selecting patients for minimally invasive procedures. While first-line imaging [...] Read more.
Introduction: Primary hyperparathyroidism (pHPT) is an endocrine disorder characterized by excessive parathyroid hormone production, typically due to adenomas, hyperplasia, or carcinoma. Preoperative imaging plays a critical role in guiding surgical planning, particularly in selecting patients for minimally invasive procedures. While first-line imaging techniques, such as ultrasound and 99mTc-sestamibi scintigraphy, are standard, advanced second-line imaging modalities like 18F-fluorocholine PET/CT (FCH-PET) and four-dimensional computed tomography (4D-CT) have emerged as valuable tools when initial diagnostics are inconclusive. Methods: This article provides an updated review and recommendations of the role of these advanced imaging techniques in localizing parathyroid adenomas. Results: FCH-PET has shown exceptional sensitivity (94% per patient, 96% per lesion) and is particularly useful in detecting small or ectopic adenomas. Despite its higher sensitivity, it can yield false positives, particularly in the presence of thyroid disease. On the other hand, 4D-CT offers detailed anatomical imaging, aiding in the identification of parathyroids in challenging cases, including recurrent disease and ectopic glands. Studies suggest that FCH-PET and 4D-CT exhibit similar diagnostic performance and could be complementary in preoperative planning of most difficult situations. Conclusions: This article also emphasizes a multimodal approach, where initial imaging is followed by advanced techniques only in cases of uncertainty. Although 18F-fluorocholine PET/CT is favored as a second-line option, 4D-CT remains invaluable for its high spatial resolution and ability to guide surgery in complex cases. Despite limitations in evidence, these imaging modalities significantly enhance the accuracy of parathyroid localization, contributing to more targeted and minimally invasive surgery. Full article
(This article belongs to the Section General Surgery)
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12 pages, 463 KiB  
Article
Association Between BRAF V600E Allele Frequency and Aggressive Behavior in Papillary Thyroid Microcarcinoma
by Luiza Tatar, Saruchi Bandargal, Marc P. Pusztaszeri, Véronique-Isabelle Forest, Michael P. Hier, Jasmine Kouz, Raisa Chowdhury and Richard J. Payne
Cancers 2025, 17(15), 2553; https://doi.org/10.3390/cancers17152553 - 1 Aug 2025
Viewed by 178
Abstract
Background/Objectives: Papillary thyroid microcarcinoma (MPTC), a subset of papillary thyroid carcinoma (PTC), is increasingly detected with advanced imaging. While most MPTCs are indolent, some exhibit aggressive behavior, complicating clinical management. The BRAF V600E mutation, common in PTC, is linked to aggressive features, [...] Read more.
Background/Objectives: Papillary thyroid microcarcinoma (MPTC), a subset of papillary thyroid carcinoma (PTC), is increasingly detected with advanced imaging. While most MPTCs are indolent, some exhibit aggressive behavior, complicating clinical management. The BRAF V600E mutation, common in PTC, is linked to aggressive features, and its allele frequency (AF) may serve as a biomarker for tumor aggressiveness. This study explored the association between BRAF V600E AF and aggressive histopathological features in MPTC. Methods: Data from 1 January 2016 to 23 December 2023 were retrieved from two McGill University teaching hospitals. Inclusion criteria comprised patients aged ≥ 18 years with thyroid nodules ≤ 1 cm, documented BRAF V600E mutation and AF results, and available surgical pathology reports. Tumor aggressiveness was defined as the presence of lymph node metastasis, aggressive histological subtype (tall cell, hobnail, columnar, solid/trabecular or diffuse sclerosing), extra thyroidal extension, or extensive lymphovascular extension. Associations were explored using t-tests. Results: Among 1564 records, 34 met the inclusion criteria and were included in analyses. The mean BRAF V600E AF was significantly higher in aggressive tumors (23.58) compared to non-aggressive tumors (13.73) (95% CI: −18.53 to −1.16, p = 0.03). Although not statistically significant, trends were observed for higher BRAF V600E AF in tumors with lymph node metastasis (mean AF: 25.4) compared to those without (mean AF: 16.67, p = 0.08). No significant difference was noted in BRAF V600E AF by histological subtype (mean AF for aggressive: 19.57; non-aggressive: 19.15, p = 0.94). Conclusions: Elevated BRAF V600E AF is associated with aggressive behavior in MPTC, highlighting its potential as a biomarker to inform treatment strategies. Larger studies are warranted to validate these findings and enhance clinical management of MPTC patients. Full article
(This article belongs to the Special Issue Thyroid Cancer: Diagnosis, Prognosis and Treatment (2nd Edition))
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16 pages, 575 KiB  
Article
Polycystic Ovary Syndrome Attenuates TSH-Lowering Effect of Metformin in Young Women with Subclinical Hypothyroidism
by Robert Krysiak, Karolina Kowalcze, Johannes Ott, Sofia Burgio, Simona Zaami and Bogusław Okopień
Pharmaceuticals 2025, 18(8), 1149; https://doi.org/10.3390/ph18081149 - 1 Aug 2025
Viewed by 176
Abstract
Background/Objectives: The effect of metformin on the secretory function of thyrotropic cells is sex-dependent. The current study aimed to investigate whether the impact of this drug on activity of the hypothalamic–pituitary–thyroid axis in women is impacted by the androgen status of patients. Methods: [...] Read more.
Background/Objectives: The effect of metformin on the secretory function of thyrotropic cells is sex-dependent. The current study aimed to investigate whether the impact of this drug on activity of the hypothalamic–pituitary–thyroid axis in women is impacted by the androgen status of patients. Methods: The study population included 48 levothyroxine-naïve reproductive-aged women with subclinical hypothyroidism and prediabetes receiving 3.0 g of metformin daily. Women with (n = 24) and without (n = 24) polycystic ovary syndrome were matched for age, insulin sensitivity, TSH, and reasons for thyroid hypofunction. Circulating levels of glucose, glycated hemoglobin, insulin, TSH, thyroid hormones, gonadotropins, androgens, estradiol, SHBG, prolactin, ACTH, and IGF-1 were measured before metformin treatment and six months later. Results: At entry, women with and without polycystic ovary syndrome differed in LH, LH/FSH ratio, androgens, and estradiol. The decrease in TSH, fasting glucose and glycated hemoglobin, and the improvement in insulin sensitivity were less pronounced in women with than in women without polycystic ovary syndrome. In each group, there were no differences in the impact on TSH and thyroid hormones between patients with subclinical hypothyroidism of autoimmune and non-autoimmune origin. The changes in TSH inversely correlated with total testosterone and free androgen index. Only in women with coexisting polycystic ovary syndrome, did metformin slightly reduce LH, LH/FSH ratio, testosterone, and free androgen index. Conclusions: The results suggest that concurrent polycystic ovary syndrome attenuates metformin action on TSH secretion, which can be explained by increased androgen production. Moreover, the drug seems to alleviate PCOS-associated changes in the activity of the reproductive axis. Full article
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22 pages, 3527 KiB  
Review
Applications of Organoids and Spheroids in Anaplastic and Papillary Thyroid Cancer Research: A Comprehensive Review
by Deepak Gulwani, Neha Singh, Manisha Gupta, Ridhima Goel and Thoudam Debraj Singh
Organoids 2025, 4(3), 18; https://doi.org/10.3390/organoids4030018 - 1 Aug 2025
Viewed by 87
Abstract
Organoid and spheroid technologies have rapidly become pivotal in thyroid cancer research, offering models that are more physiologically relevant than traditional two-dimensional culture. In the study of papillary and anaplastic thyroid carcinomas, two subtypes that differ both histologically and clinically, three-dimensional (3D) models [...] Read more.
Organoid and spheroid technologies have rapidly become pivotal in thyroid cancer research, offering models that are more physiologically relevant than traditional two-dimensional culture. In the study of papillary and anaplastic thyroid carcinomas, two subtypes that differ both histologically and clinically, three-dimensional (3D) models offer unparalleled insights into tumor biology, therapeutic vulnerabilities, and resistance mechanisms. These models maintain essential tumor characteristics such as cellular diversity, spatial structure, and interactions with the microenvironment, making them extremely valuable for disease modeling and drug testing. This review emphasizes recent progress in the development and use of thyroid cancer organoids and spheroids, focusing on their role in replicating disease features, evaluating targeted therapies, and investigating epithelial–mesenchymal transition (EMT), cancer stem cell behavior, and treatment resistance. Patient-derived organoids have shown potential in capturing individualized drug responses, supporting precision oncology strategies for both differentiated and aggressive subtypes. Additionally, new platforms, such as thyroid organoid-on-a-chip systems, provide dynamic, high-fidelity models for functional studies and assessments of endocrine disruption. Despite ongoing challenges, such as standardization, limited inclusion of immune and stromal components, and culture reproducibility, advancements in microfluidics, biomaterials, and machine learning have enhanced the clinical and translational potential of these systems. Organoids and spheroids are expected to become essential in the future of thyroid cancer research, particularly in bridging the gap between laboratory discoveries and patient-focused therapies. Full article
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18 pages, 1782 KiB  
Review
Nutrition and Micronutrient Interactions in Autoimmune Thyroid Disorders: Implications for Cardiovascular Health
by Michał Mazur, Magdalena Szymańska, Agnieszka Malik, Wojciech Szlasa and Joanna Popiołek-Kalisz
Pathophysiology 2025, 32(3), 37; https://doi.org/10.3390/pathophysiology32030037 - 1 Aug 2025
Viewed by 141
Abstract
Thyroid hormones play a crucial role in regulating metabolism and cardiovascular function, with even mild dysfunction—such as subclinical hypothyroidism—negatively impacting heart health. While previous studies have confirmed the effects of iodine, selenium, and vitamin D on thyroid regulation and inflammation, the combined role [...] Read more.
Thyroid hormones play a crucial role in regulating metabolism and cardiovascular function, with even mild dysfunction—such as subclinical hypothyroidism—negatively impacting heart health. While previous studies have confirmed the effects of iodine, selenium, and vitamin D on thyroid regulation and inflammation, the combined role of these nutrients in reducing cardiovascular disease (CVD) risk in autoimmune thyroid disorders remains insufficiently understood. This review explores the influence of specific micronutrients—including selenium, iodine, and zinc—and dietary patterns, particularly the Mediterranean diet, on the pathophysiology of hypothyroidism and Hashimoto’s thyroiditis. We introduce a novel framework that integrates emerging data on sex-specific micronutrient interactions and nutritional immunomodulation. Unlike the existing literature, this review introduces original hypotheses related to sex-specific nutritional immunomodulation and proposes a novel framework for micronutrient-driven dietary intervention in Hashimoto’s thyroiditis. Full article
(This article belongs to the Section Metabolic Disorders)
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13 pages, 721 KiB  
Article
The Influence of Hyperthyroid Metabolic Status on the Coagulation and Fibrinolysis System and the Risk of Thrombosis: A Prospective Cohort Study
by Manuela Andrea Hoffmann, Anne Zinndorf, Florian Rosar, Inge Scharrer, Nicolas Fischer, Tobias Gruebl, Pia-Elisabeth Baqué, Stefan Reuss and Mathias Schreckenberger
Biomedicines 2025, 13(8), 1869; https://doi.org/10.3390/biomedicines13081869 - 1 Aug 2025
Viewed by 208
Abstract
Background: Risk assessment in hyperthyroidism remains challenging. The aim of the present study is to determine the influence of hyperthyroid metabolic status on blood clotting and an increased risk of thrombosis. Methods: This prospective study included 50 patients after radical thyroidectomy [...] Read more.
Background: Risk assessment in hyperthyroidism remains challenging. The aim of the present study is to determine the influence of hyperthyroid metabolic status on blood clotting and an increased risk of thrombosis. Methods: This prospective study included 50 patients after radical thyroidectomy and ablative radioiodine therapy because of thyroid carcinoma who were compared with 50 control subjects in a euthyroid metabolic state. Latent hyperthyroid patients with basal thyroid-stimulating hormone (TSH) ≤ 0.15 mU/L on levothyroxine hormone therapy were included. The control group was selected to match the patient group based on age and sex. The evaluation data were collected using laboratory coagulation tests and patient questionnaires. A bleeding and a thrombosis score were determined. Results: The coagulation parameters between the patient and control groups showed statistically significant differences. In particular, the patients’ group showed a significantly shortened activated partial thromboplastin time (aPTT/p = 0.009) and a significantly higher plasminogen activator inhibitor 1 (PAI-1/p < 0.001) compared to the control group. Age, sex, and medication use were not found to influence the patients’ laboratory results. Only body mass index was higher in the patient group than in the control group. Conclusions: Our results support a shift in the coagulation system in latent hyperthyroid metabolism towards increased coagulability and reduced fibrinolysis. A latent hyperthyroid metabolic state appears to be associated with an increased risk of thrombosis. Further prospective cohort studies with large patient populations are needed to verify the association between (latent) hyperthyroidism and thromboembolic events as well as to determine therapeutic anticoagulation or to adjust the indication for exogenous administration of thyroid hormone. Full article
(This article belongs to the Section Endocrinology and Metabolism Research)
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29 pages, 959 KiB  
Review
Machine Learning-Driven Insights in Cancer Metabolomics: From Subtyping to Biomarker Discovery and Prognostic Modeling
by Amr Elguoshy, Hend Zedan and Suguru Saito
Metabolites 2025, 15(8), 514; https://doi.org/10.3390/metabo15080514 - 1 Aug 2025
Viewed by 199
Abstract
Cancer metabolic reprogramming plays a critical role in tumor progression and therapeutic resistance, underscoring the need for advanced analytical strategies. Metabolomics, leveraging mass spectrometry and nuclear magnetic resonance (NMR) spectroscopy, offers a comprehensive and functional readout of tumor biochemistry. By enabling both targeted [...] Read more.
Cancer metabolic reprogramming plays a critical role in tumor progression and therapeutic resistance, underscoring the need for advanced analytical strategies. Metabolomics, leveraging mass spectrometry and nuclear magnetic resonance (NMR) spectroscopy, offers a comprehensive and functional readout of tumor biochemistry. By enabling both targeted metabolite quantification and untargeted profiling, metabolomics captures the dynamic metabolic alterations associated with cancer. The integration of metabolomics with machine learning (ML) approaches further enhances the interpretation of these complex, high-dimensional datasets, providing powerful insights into cancer biology from biomarker discovery to therapeutic targeting. This review systematically examines the transformative role of ML in cancer metabolomics. We discuss how various ML methodologies—including supervised algorithms (e.g., Support Vector Machine, Random Forest), unsupervised techniques (e.g., Principal Component Analysis, t-SNE), and deep learning frameworks—are advancing cancer research. Specifically, we highlight three major applications of ML–metabolomics integration: (1) cancer subtyping, exemplified by the use of Similarity Network Fusion (SNF) and LASSO regression to classify triple-negative breast cancer into subtypes with distinct survival outcomes; (2) biomarker discovery, where Random Forest and Partial Least Squares Discriminant Analysis (PLS-DA) models have achieved >90% accuracy in detecting breast and colorectal cancers through biofluid metabolomics; and (3) prognostic modeling, demonstrated by the identification of race-specific metabolic signatures in breast cancer and the prediction of clinical outcomes in lung and ovarian cancers. Beyond these areas, we explore applications across prostate, thyroid, and pancreatic cancers, where ML-driven metabolomics is contributing to earlier detection, improved risk stratification, and personalized treatment planning. We also address critical challenges, including issues of data quality (e.g., batch effects, missing values), model interpretability, and barriers to clinical translation. Emerging solutions, such as explainable artificial intelligence (XAI) approaches and standardized multi-omics integration pipelines, are discussed as pathways to overcome these hurdles. By synthesizing recent advances, this review illustrates how ML-enhanced metabolomics bridges the gap between fundamental cancer metabolism research and clinical application, offering new avenues for precision oncology through improved diagnosis, prognosis, and tailored therapeutic strategies. Full article
(This article belongs to the Special Issue Nutritional Metabolomics in Cancer)
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17 pages, 666 KiB  
Review
Three Major Deficiency Diseases Harming Mankind (Protein, Retinoid, Iron) Operate Under Tryptophan Dependency
by Yves Ingenbleek
Nutrients 2025, 17(15), 2505; https://doi.org/10.3390/nu17152505 - 30 Jul 2025
Viewed by 173
Abstract
This story began half a century ago with the discovery of an unusually high presence of tryptophan (Trp, W) in transthyretin (TTR), one of the three carrier proteins of thyroid hormones. With the Trp-rich retinol-binding protein (RBP), TTR forms a plasma complex implicated [...] Read more.
This story began half a century ago with the discovery of an unusually high presence of tryptophan (Trp, W) in transthyretin (TTR), one of the three carrier proteins of thyroid hormones. With the Trp-rich retinol-binding protein (RBP), TTR forms a plasma complex implicated in the delivery of retinoid compounds to body tissues. W has the lowest concentration among all AAs involved in the sequencing of human body proteins. The present review proposes molecular maps focusing on the ratio of W/AA residues found in the sequence of proteins involved in immune events, allowing us to ascribe the guidance of inflammatory processes as fully under the influence of W. Under the control of cytokine stimulation, plasma biomarkers of protein nutritional status work in concert with major acute-phase reactants (APRs) and with carrier proteins to release, in a free and active form, their W and hormonal ligands, interacting to generate hot spots affecting the course of acute stress disorders. The prognostic inflammatory and nutritional index (PINI) scoring formula contributes to identifying the respective roles played by each of the components prevailing during the progression of the disease. Glucagon demonstrates ambivalent properties, remaining passive under steady-state conditions while displaying stronger effects after cytokine activation. In developing countries, inappropriate weaning periods lead to toddlers eating W-deficient cereals as a staple, causing a dramatic reduction in the levels of W-rich biomarkers in plasma, constituting a novel nutritional deficiency at the global scale. Appropriate counseling should be set up using W implementations to cover the weaning period and extended until school age. In adult and elderly subjects, the helpful immune protections provided by W may be hindered by the surge in harmful catabolites with the occurrence of chronic complications, which can have a significant public health impact but lack the uncontrolled surges in PINI observed in young infants and teenagers. Biomarkers of neurodegenerative and neoplastic disorders measured in elderly patients indicate the slow-moving elevation of APRs due to rampant degradation processes. Full article
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13 pages, 615 KiB  
Article
Euthyroid Sick Syndrome as an Index of Prognosis in Severe COVID-19 Disease
by Lambros Athanassiou, Ifigenia Kostoglou-Athanassiou, Georgia Kaiafa, Sofia Nikolakopoulou, Alexandra Konstantinou, Olga Mascha, Charilaos Samaras, Christos Savopoulos, Yehuda Shoenfeld and Panagiotis Athanassiou
Medicina 2025, 61(8), 1372; https://doi.org/10.3390/medicina61081372 - 29 Jul 2025
Viewed by 206
Abstract
Background and Objectives: Euthyroid sick syndrome, or non-thyroidal illness syndrome, has been observed in severely ill patients and has been found to be an index of prognosis. It has been detected in patients with severe infectious diseases, e.g., those with severe COVID-19 [...] Read more.
Background and Objectives: Euthyroid sick syndrome, or non-thyroidal illness syndrome, has been observed in severely ill patients and has been found to be an index of prognosis. It has been detected in patients with severe infectious diseases, e.g., those with severe COVID-19 infection. Prognostic indicators of the outcome of severe COVID-19 disease are important for the prognosis of individual as well as groups of patients. The aim of this study was to identify euthyroid sick syndrome in patients admitted for severe COVID-19 disease and its relationship to disease severity and outcome. Materials and Methods: In a cohort of patients admitted to hospital for severe COVID-19 disease, thyroid function in patients requiring hospitalization was evaluated by measuring TSH, FreeT3 (FT3), and FreeT4 (FT4) levels. Patients were classified into four groups: a group with uncompromised respiratory function (pO2 > 70 mmHg, without need of oxygen supplementation) (disease severity 1); a group with mild respiratory insufficiency (pO2 50–60 mmHg, in need of oxygen supplementation with nasal cannula) (disease severity 2); a group with severe respiratory insufficiency (pO2 < 50 mmHg, in need of oxygen supplementation with high flow oxygen) (disease severity 3); and a group with severe respiratory insufficiency requiring intubation (pO2 < 60 mmHg on high flow oxygen supplementation) (disease severity 4). Results: In this cohort, euthyroid sick syndrome was diagnosed in 57.1% of the patients. The presence of euthyroid sick syndrome was related to increased disease severity and adverse disease outcome, i.e., death. FT3 levels were inversely related to CRP levels. Conclusions: Euthyroid sick syndrome may be observed in severe COVID-19 disease and is related to increased disease severity and adverse outcomes. Measurement of thyroid hormones in patients hospitalized for severe COVID-19 infection may aid in the prognosis of the disease. Full article
(This article belongs to the Section Epidemiology & Public Health)
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27 pages, 1569 KiB  
Review
Bisphenols: Endocrine Disruptors and Their Impact on Fish: A Review
by Nikola Peskova and Jana Blahova
Fishes 2025, 10(8), 365; https://doi.org/10.3390/fishes10080365 - 29 Jul 2025
Viewed by 327
Abstract
Bisphenols (BPs), particularly bisphenol A (BPA) and its structural analogues, are synthetic compounds widely used in plastics and industrial materials. These substances are also recognised as endocrine-disrupting chemicals (EDCs) due to their ability to interfere with hormonal systems, which has significant implications for [...] Read more.
Bisphenols (BPs), particularly bisphenol A (BPA) and its structural analogues, are synthetic compounds widely used in plastics and industrial materials. These substances are also recognised as endocrine-disrupting chemicals (EDCs) due to their ability to interfere with hormonal systems, which has significant implications for aquatic organisms. This review summarises the occurrence, environmental distribution, and toxicity of BPs in fish, with a focus on estrogenic, androgenic, thyroid, and glucocorticoid disruptions. Studies consistently show that exposure to BPs leads to altered gene expression, developmental abnormalities, impaired reproduction, and disrupted hormonal signalling in various fish species. Although BPA alternatives like bisphenol S, bisphenol F, or bisphenol AF were introduced as safer options, emerging evidence suggests they may pose equal or greater risks. Regulatory measures are evolving, particularly within the European Union, but legislation remains limited for many bisphenol analogues. This review emphasises the need for comprehensive environmental monitoring, stricter regulatory frameworks, and the development of genuinely safer alternatives to minimise the ecological and health impacts of BPs in aquatic systems. Full article
(This article belongs to the Section Environment and Climate Change)
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13 pages, 873 KiB  
Article
Integrating Clinical Parameters into Thyroid Nodule Malignancy Risk: A Retrospective Evaluation Based on ACR TI-RADS
by Nikolaos Angelopoulos, Ioannis Androulakis, Dimitrios P. Askitis, Nicolas Valvis, Rodis D. Paparodis, Valentina Petkova, Anastasios Boniakos, Dimitra Zianni, Andreas Rizoulis, Dimitra Bantouna, Juan Carlos Jaume and Sarantis Livadas
J. Clin. Med. 2025, 14(15), 5352; https://doi.org/10.3390/jcm14155352 - 29 Jul 2025
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Abstract
Background/Objectives: Thyroid nodules are commonly found through sensitive imaging methods like ultrasonography. While most nodules are benign and asymptomatic, certain characteristics may indicate malignancy, prompting fine needle aspiration biopsy. Factors like age and gender affect cancer risk, complicating ultrasound-based risk systems. We [...] Read more.
Background/Objectives: Thyroid nodules are commonly found through sensitive imaging methods like ultrasonography. While most nodules are benign and asymptomatic, certain characteristics may indicate malignancy, prompting fine needle aspiration biopsy. Factors like age and gender affect cancer risk, complicating ultrasound-based risk systems. We aimed to determine whether the cytological malignancy rate of thyroid nodules could be adjusted for several clinical parameters. Methods: Data from patients aged 18 and above with thyroid nodules assessed via fine needle aspiration (FNA) were retrospectively reviewed. Malignancy classification was based on cytopathology and histopathology results. The study examined how various clinical parameters, adjusted for the ACR TI-RADS category, affected thyroid nodule malignancy rates, including age, sex, Body Mass Index (BMI), nodule size, presence of autoimmunity, and thyroxine therapy. Additionally, we analyzed the performance of ACR TI-RADS in predicting malignant cytology across different age subgroups of thyroid nodules. Results: The study included 1128 thyroid nodules from 1001 adult patients, with a median age of 48 years and predominantly female (76.68%). Malignancy rates varied across ACR TI-RADS categories, with higher rates associated with larger nodules and younger age groups. Age emerged as a significant predictor of malignancy, with a consistent decrease in the odds ratio for malignant cytology with advancing age across all ACR TI-RADS categories, indicating its potential utility in risk assessment alongside nodule size and sex. Conclusions: Raising the size threshold for recommending FNA of TR3-3 nodules and incorporating patients’ age and gender into the evaluation process could enhance the system’s accuracy in assessing thyroid nodules and guiding clinical management decisions. Full article
(This article belongs to the Special Issue Thyroid Disease: Updates from Diagnosis to Treatment)
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Article
Association Between Hypothyroidism and Depression in Individuals with Down Syndrome: A Retrospective Analysis
by Gregory Sabel, Alishah Ahmadi, Dhruba Podder, Olivia Stala, Rahim Hirani and Mill Etienne
Life 2025, 15(8), 1199; https://doi.org/10.3390/life15081199 - 28 Jul 2025
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Abstract
Background: Down syndrome (DS) is a genetic disorder characterized by an extra copy of chromosome 21, often leading to intellectual disabilities, developmental delays, and an increased risk of various comorbidities, including thyroid dysfunction and mental health disorders. The relationship between thyroid dysfunction [...] Read more.
Background: Down syndrome (DS) is a genetic disorder characterized by an extra copy of chromosome 21, often leading to intellectual disabilities, developmental delays, and an increased risk of various comorbidities, including thyroid dysfunction and mental health disorders. The relationship between thyroid dysfunction and mood disorders, particularly depression in DS populations, requires further investigation. Objective: This study aims to investigate the presence of a correlative relationship between hypothyroidism and depression in 178,840 individuals with DS, utilizing data from the National Inpatient Sample (NIS) to determine if those with comorbid hypothyroidism exhibit higher rates of depression compared to their counterparts without hypothyroidism. Methods: A retrospective analysis of the 2016–2019 NIS dataset was conducted, focusing on patients with DS, hypothyroidism, and depression diagnoses. The diagnoses were determined and labeled based on ICD-10 codes associated with NIS datapoints. Survey-weighted linear regression analyses were employed to assess the association between hypothyroidism and depression within the DS cohort, adjusting for demographic factors such as age, gender, and race. Results: This study found that individuals with DS exhibit a significantly higher prevalence of hypothyroidism (29.88%) compared to the general population (10.28%). Additionally, individuals with DS and comorbid hypothyroidism demonstrated a higher prevalence of depression (8.67%) compared to those without hypothyroidism (3.00%). These findings suggest a significant association between hypothyroidism and increased depression risk among individuals with DS. However, the overall prevalence of depression in DS (4.69%) remains substantially lower than in the general population (12.27%). Conclusions: This study highlights the importance of considering hypothyroidism as a potential contributor to depression in individuals with DS. Further research is needed to explore the underlying mechanisms of this association and potential screening and management strategies to address thyroid dysfunction and its potential psychiatric implications in DS. Full article
(This article belongs to the Section Physiology and Pathology)
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