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16 pages, 989 KiB  
Article
Exploring Monthly Variation of Gait Asymmetry During In-Hand Trot in Thoroughbred Racehorses in Race Training
by Thilo Pfau, Bronte Forbes, Fernanda Sepulveda-Caviedes, Zoe Chan and Renate Weller
Animals 2025, 15(16), 2449; https://doi.org/10.3390/ani15162449 (registering DOI) - 20 Aug 2025
Abstract
Based on fundamental mechanics, movement and force associate head and pelvic movement asymmetry with asymmetry of force production. We investigate, how often racehorses undergoing strenuous training regimens show evidence of switching between “preferred” limbs, i.e. one limb producing increased force, when assessed at [...] Read more.
Based on fundamental mechanics, movement and force associate head and pelvic movement asymmetry with asymmetry of force production. We investigate, how often racehorses undergoing strenuous training regimens show evidence of switching between “preferred” limbs, i.e. one limb producing increased force, when assessed at monthly intervals? We hypothesize that clinical asymmetry thresholds designed for “detecting lameness” are frequently exceeded and that when applying previously established Thoroughbred-specific repeatability values, horses rarely switch between showing left- and right-sided asymmetry. Monthly gait assessments (inertial sensors) were conducted in 256 Thoroughbred racehorses at least twice per horse (up to 16 times per horse). Descriptive statistics for absolute differences for head and pelvic movement were compared to published Thoroughbred-specific repeatability values. The percentage of left–right switches between repeat assessments was calculated in comparison to three different levels of pre-defined thresholds (perfect symmetry, clinical lameness thresholds, previously established Thoroughbred-specific repeatability values) and switch frequencies compared between the three thresholds. Ranges containing 95% of monthly differences were higher than published daily and weekly values except for pelvic vertical range of motion. Approximately 30% of monthly differences in individual symmetry parameters showed left–right switches around “perfect symmetry”. Utilizing clinical lameness thresholds for categorizing left–right switches, a significantly (p < 0.001) reduced percentage of 4–11% of measurements for head movement and 7–17% for pelvic movement showed switches. Using daily repeatability values for categorization, a further significantly (p < 0.001) reduced percentage of switches was observed: 0.3–3.6% for head movement and 0.6–7.0% for pelvic movement. While racehorses in training regularly switch between small left- or right-sided movement symmetries, they less frequently switch between more pronounced left- and right-sided movement symmetries defined based on daily variations. Further studies should investigate the reasons for these rare switches. Full article
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10 pages, 464 KiB  
Article
Cardiovascular Manifestations and Outcomes in Patients with Scrub Typhus Admitted to a Tertiary Care Center in the Coastal Karnataka Region in India
by Mugula Sudhakar Rao, Jyothi Samanth, Swathi Poojary, Krishnananda Nayak, Shubha Srinivas and Thrupthi Naik
Diseases 2025, 13(8), 270; https://doi.org/10.3390/diseases13080270 - 20 Aug 2025
Abstract
Introduction: Scrub typhus is a mite-borne infectious disease caused by “Orientia tsutsugamushi”, a bacterium that was formerly classified under the genus Rickettsia. It is transmitted to humans through the bites of infected chigger mites (larval trombiculid mites). However, clinical data [...] Read more.
Introduction: Scrub typhus is a mite-borne infectious disease caused by “Orientia tsutsugamushi”, a bacterium that was formerly classified under the genus Rickettsia. It is transmitted to humans through the bites of infected chigger mites (larval trombiculid mites). However, clinical data on the cardiac manifestations of scrub typhus and their outcomes remain limited. Methods: This research was retrospectively conducted at a tertiary care hospital in South India. The study included all patients admitted from January 2016 to September 2021 who fulfilled the clinical criteria for a diagnosis of scrub typhus. Data were collected for 426 patients. Patients with previously diagnosed heart disease and mixed infections (leptospirosis, dengue fever, blood culture positivity, and COVID-19 positivity) were excluded. Comprehensive assessments of clinical presentation, electrocardiography (ECG), 2D echocardiography, and outcomes, including all-cause mortality and probable myocarditis, were performed. Multivariate regression analysis was performed to identify independent predictors of all-cause mortality and probable myocarditis. Results: Out of 426 patients, 200 (46.9%) were male and 226 (53.1%) were female. The mean age at presentation was 49.29 ± 14.43 years. A total of 108 (25.4%) patients had diabetes and 82 (19.25%) had hypertension. Sinus tachycardia (29.3%) was the most frequent ECG finding. Echocardiographic evidence of probable myocarditis was observed in 20 (4.7%) patients, while 6 (1.4%) patients had isolated RV dysfunction, 4 (0.9%) had biventricular dysfunction, 7 (1.6%) had significant pulmonary hypertension, and 40 (9.4%) had trivial pericardial effusion. A total of 78 (18.3%) patients had acute respiratory distress syndrome. All-cause mortality was observed in 12 (2.8%) patients. A total of 56 (13.1%) patients developed multiorgan dysfunction syndrome (MODS) during their hospitalization. A total of 78 (18.3%) patients were documented to have acute kidney injury (AKI), and 22 (5.2%) patients underwent hemodialysis. Multivariable binary logistic regression analysis revealed that probable myocarditis and MODS were independent predictors of mortality among patients with scrub typhus, and age, female gender, and LV systolic dysfunction were identified as predictors of overall complications, including mortality, probable myocarditis, congestive heart failure, MODS, AKI, and the need for hemodialysis. Conclusions: Probable myocarditis was the most frequent cardiac manifestation noted in patients with scrub typhus, and in addition to MODS, probable myocarditis was an independent predictor of mortality in this cohort. Thus, it is crucial to maintain clinical vigilance regarding the cardiac status of such patients. Full article
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15 pages, 637 KiB  
Review
Intraglomerular Inflammation as a Guide for Mycophenolate Mofetil-Based Treatment in IgA Nephropathy
by Christodoulos Keskinis, Panagiotis Pateinakis and Maria Stangou
Diagnostics 2025, 15(16), 2101; https://doi.org/10.3390/diagnostics15162101 - 20 Aug 2025
Abstract
IgA nephropathy (IgAN) is the most prevalent primary glomerulonephritis worldwide, with a heterogeneous clinical course that may progress to end-stage kidney disease (ESKD) in approximately 20% of patients. Despite recent advances, including the U.S. Food and Drug Administration (FDA) approval of three novel [...] Read more.
IgA nephropathy (IgAN) is the most prevalent primary glomerulonephritis worldwide, with a heterogeneous clinical course that may progress to end-stage kidney disease (ESKD) in approximately 20% of patients. Despite recent advances, including the U.S. Food and Drug Administration (FDA) approval of three novel agents, optimal therapeutic strategies remain uncertain, and access to new drugs is often limited. This underscores the need to evaluate established and widely available options such as mycophenolate mofetil (MMF). The aim of this review is to critically assess the role of MMF, either as monotherapy or in combination with systemic corticosteroids, in the treatment of IgAN based on evidence cited in the KDIGO 2024 Draft Guidelines. We analyzed seven major clinical studies—five randomized controlled trials and two long-term observational studies—with particular focus on the influence of histological activity on treatment outcomes. The Oxford classification was applied to explore whether specific histological variables correlate with prognosis and predict treatment response. Trials conducted in Chinese cohorts demonstrated significant benefits of MMF, including proteinuria reduction, delayed progression to ESKD, and improved long-term renal outcomes, particularly in patients with recent disease onset and active proliferative lesions such as endocapillary hypercellularity and crescent formation. In contrast, studies from Western populations generally failed to demonstrate comparable benefit possibly due to differences in disease chronicity, histopathological patterns, and genetic background. Overall, MMF appears most effective when initiated early and in patients with histologic evidence of intraglomerular inflammation. It may represent a viable steroid-sparing option in appropriately selected patients, particularly where access to newly approved agents is restricted. These population- and pathology-based differences highlight the need for individualized treatment decisions and further research to refine the therapeutic role of MMF in IgAN. Full article
(This article belongs to the Special Issue Advances in Nephrology)
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14 pages, 478 KiB  
Article
A Pathogenic L2HGDH Variant Impairs Mitochondrial Targeting and Enzyme Function in L-2-Hydroxyglutaric Aciduria: Clinical and Functional Evidence from Two Affected Siblings
by Qiang Guo, Thilo Löhr, Patrick Giavalisco, Vera Riehmer and Hans Zempel
Genes 2025, 16(8), 982; https://doi.org/10.3390/genes16080982 (registering DOI) - 20 Aug 2025
Abstract
Background: L-2-hydroxyglutaric aciduria (L2HGA) is a rare autosomal recessive neurometabolic disorder caused by biallelic loss-of-function variants in the L-2-hydroxyglutarate dehydrogenase (L2HGDH) gene, leading to accumulation of L-2-hydroxyglutarate in the brain and other tissues. While various variants have been reported, the pathogenic [...] Read more.
Background: L-2-hydroxyglutaric aciduria (L2HGA) is a rare autosomal recessive neurometabolic disorder caused by biallelic loss-of-function variants in the L-2-hydroxyglutarate dehydrogenase (L2HGDH) gene, leading to accumulation of L-2-hydroxyglutarate in the brain and other tissues. While various variants have been reported, the pathogenic mechanism of specific variants remains unclear. In this study, we aimed to investigate the molecular consequences of the c.905C>T p.(Pro302Leu) variant, identified in two siblings with typical symptoms of L2HGA, by analyzing its effects on protein localization and enzymatic activity in a cell model. Methods: HA-tagged wild-type and p.(Pro302Leu) mutant L2HGDH constructs were overexpressed in HEK293T cells. We assessed protein expression, subcellular localization, and enzymatic activity using Western blot analysis, immunofluorescence microscopy, and a specific enzyme assay measuring 2,6-dichloroindophenol (DCIP) reduction to assess L2HGDH enzymatic activity. Results: Western blotting showed that wild-type L2HGDH exists primarily in the processed, mature mitochondrial form, whereas the p.(Pro302Leu) mutant remained largely in the unprocessed precursor form. Immunofluorescence and differential centrifugation revealed that wild-type protein localized to mitochondria, while the mutant protein accumulated in the cytoplasm in a diffuse or punctate pattern. Enzyme activity assays demonstrated that the mutant retained <30% of wild-type activity. Conclusions: These findings indicate that the p.(Pro302Leu) variant leads to aggregation of mislocalized protein, thereby impairing L2HGDH function rather than decreasing enzymatic function. This study provides clinical and molecular evidence supporting the pathogenicity of this previously reported mutation and highlights the importance of mitochondrial import for enzyme functionality in L2HGA. Full article
(This article belongs to the Special Issue Genetics and Treatment in Neurodegenerative Diseases)
15 pages, 1492 KiB  
Article
Opportunistic Detection of Chronic Kidney Disease Using CT-Based Measurements of Kidney Volume and Perirenal Fat
by Piotr Białek, Michał Żuberek, Adam Dobek, Krzysztof Falenta, Ilona Kurnatowska and Ludomir Stefańczyk
J. Clin. Med. 2025, 14(16), 5888; https://doi.org/10.3390/jcm14165888 - 20 Aug 2025
Abstract
Background/Objectives: Chronic kidney disease (CKD) is a prevalent condition with many cases remaining undiagnosed, although early detection is essential. Adipose tissue distribution—particularly perirenal fat thickness (PrFT)—has recently been linked to renal pathophysiology. This study assessed the association between CT-derived parameters of fat distribution [...] Read more.
Background/Objectives: Chronic kidney disease (CKD) is a prevalent condition with many cases remaining undiagnosed, although early detection is essential. Adipose tissue distribution—particularly perirenal fat thickness (PrFT)—has recently been linked to renal pathophysiology. This study assessed the association between CT-derived parameters of fat distribution and kidney morphology with CKD. Materials and Methods: This retrospective study included 237 patients (117 subjects, 120 controls) who underwent abdominal CT and had serum creatinine data. The dataset was randomly split (70% training, 30% test) to develop and evaluate a logistic regression model. CKD was defined as estimated Glomerular Filtration Rate (eGFR) < 60 mL/min/1.73 m2. PrFT was measured as the distance from the posterior renal capsule to the posterior abdominal wall; renal hilum fat was segmented using a −195 to −45 HU range. Additional parameters (measured using automated segmentation tools) included kidney volume (KV), visceral/subcutaneous fat areas, skeletal muscle area and attenuation, and liver attenuation. Bilateral measurements were averaged. Results: KV (OR = 0.249, 95% CI: 0.146–0.422, p < 0.001) and PrFT (2nd tercile: OR = 7.720, 95% CI: 2.860–20.839; 3rd tercile: OR = 16.892, 95% CI: 5.727–49.822; both p < 0.001) were identified as independent predictors of CKD. These variables were used to construct a simplified model, which demonstrated moderate clinical applicability (AUC = 0.894) when evaluated on the test subset. Conclusions: KV and PrFT emerged as independent predictors of CKD, forming the basis of a simplified model with potential for opportunistic clinical application. This approach may facilitate earlier detection of CKD in patients undergoing CT imaging for unrelated clinical reasons. These imaging parameters are not intended to replace serum creatinine or eGFR but may serve as complementary predictors in specific clinical contexts. Full article
(This article belongs to the Section Nephrology & Urology)
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14 pages, 3644 KiB  
Systematic Review
Artificial Intelligence Models for Predicting Outcomes in Spinal Metastasis: A Systematic Review and Meta-Analysis
by Vivek Sanker, Prachi Dawer, Alexander Thaller, Zhikai Li, Philip Heesen, Srinath Hariharan, Emil O. R. Nordin, Maria Jose Cavagnaro, John Ratliff and Atman Desai
J. Clin. Med. 2025, 14(16), 5885; https://doi.org/10.3390/jcm14165885 - 20 Aug 2025
Abstract
Background: Spinal metastases can cause significant impairment of neurological function and quality of life. Hence, personalized clinical decision-making based on prognosis and likely outcome is desirable. The effectiveness of AI in predicting complications and treatment outcomes for patients with spinal metastases is assessed. [...] Read more.
Background: Spinal metastases can cause significant impairment of neurological function and quality of life. Hence, personalized clinical decision-making based on prognosis and likely outcome is desirable. The effectiveness of AI in predicting complications and treatment outcomes for patients with spinal metastases is assessed. Methods: A thorough search was carried out through the PubMed, Scopus, Web of Science, Embase, and Cochrane databases up until 27 January 2025. Included were studies that used AI-based models to predict outcomes for adult patients with spinal metastases. Three reviewers independently extracted the data, and screening was conducted in accordance with PRISMA principles. AUC results were pooled using a random-effects model, and the PROBAST program was used to evaluate the study’s quality. Results: Included were 47 articles totaling 25,790 patients. For training, internal validation, and external validation, the weighted average AUCs were 0.762, 0.876, and 0.810, respectively. The Skeletal Oncology Research Group machine learning algorithms (SORG-MLAs) were the ones externally validated the most, continuously producing AUCs > 0.84 for 90-day and 1-year mortality. Models based on radiomics showed promise in preoperative planning, especially for outcomes of radiation and concealed blood loss. Most research concentrated on breast, lung, and prostate malignancies, which limited its applicability to less common tumors. Conclusions: AI models have shown reasonable accuracy in predicting mortality, ambulatory status, blood loss, and surgical complications in patients with spinal metastases. Wider implementation necessitates additional validation, data standardization, and ethical and regulatory framework evaluation. Future work should concentrate on creating multimodal, hybrid models and assessing their practical applications. Full article
(This article belongs to the Special Issue Recent Advances in Spine Tumor Diagnosis and Treatment)
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16 pages, 2267 KiB  
Article
Placenta-Derived Mesenchymal Stem Cells (pMSCs) Reverse Diabetes-Associated Endothelial Complications in a Preclinical Animal Model
by Yasser Basmaeil, Ahmed Bakillah, Abdullah Mohammed Al Subayyil, Haya Nasser Bin Kulayb, Maha Abdullah AlRodayyan, Abeer Al Otaibi, Sindiyan Al Shaikh Mubarak, Hassan S. Alamri, Altaf A. Kondkar, Jahangir Iqbal and Tanvir Khatlani
Int. J. Mol. Sci. 2025, 26(16), 8057; https://doi.org/10.3390/ijms26168057 (registering DOI) - 20 Aug 2025
Abstract
Diabetes is increasingly recognized as a chronic inflammatory disease marked by systemic metabolic disturbances, with endothelial dysfunction playing a central role in its complications. Hyperglycemia, a hallmark of diabetes, drives endothelial damage by inducing excessive reactive oxygen species (ROS) production, particularly hydrogen peroxide [...] Read more.
Diabetes is increasingly recognized as a chronic inflammatory disease marked by systemic metabolic disturbances, with endothelial dysfunction playing a central role in its complications. Hyperglycemia, a hallmark of diabetes, drives endothelial damage by inducing excessive reactive oxygen species (ROS) production, particularly hydrogen peroxide (H2O2). This oxidative stress impairs endothelial cells, which are vital for vascular health, leading to severe complications such as diabetic nephropathy, retinopathy, and coronary artery disease—major causes of morbidity and mortality in diabetic patients. Recent studies have highlighted the therapeutic potential of placenta-derived mesenchymal stem cells (pMSCs), in mitigating these complications. pMSCs exhibit anti-inflammatory, antioxidant, and tissue-repair properties, showing promise in reversing endothelial damage in laboratory settings. To explore their efficacy in a more physiologically relevant context, we used a streptozotocin (STZ)-induced diabetic mouse model, which mimics type 1 diabetes by destroying pancreatic beta cells and causing hyperglycemia. pMSCs were administered via intra-peritoneal injections, and their effects on endothelial injury and tissue damage were assessed. Metabolic tests, including glucose tolerance tests (GTTs) and insulin tolerance tests (ITTs) revealed that pMSCs did not restore metabolic homeostasis or improve glucose regulation. However, histopathological kidney, heart, and eye tissue analyses demonstrated significant protective effects. pMSCs preserved glomerular structure in the kidneys, protected cardiac blood vessels, and maintained retinal integrity, suggesting their potential to address diabetes-related tissue injuries. Although these findings underscore the therapeutic potential of pMSCs for diabetic complications, further research is needed to optimize dosing, elucidate molecular mechanisms, and evaluate long-term safety and efficacy. Combining pMSCs with other therapies may enhance their benefits, paving the way for future clinical applications. Full article
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18 pages, 5410 KiB  
Article
Cannabigerol Attenuates Memory Impairments, Neurodegeneration, and Neuroinflammation Caused by Transient Global Cerebral Ischemia in Mice
by Nathalia Akemi Neves Kohara, José Guilherme Pinhatti Carrasco, Luís Fernando Fernandes Miranda, Pablo Pompeu Quini, Elaine Del Bel Guimarães, Humberto Milani, Rúbia Maria Weffort de Oliveira and Cristiano Correia Bacarin
Int. J. Mol. Sci. 2025, 26(16), 8056; https://doi.org/10.3390/ijms26168056 (registering DOI) - 20 Aug 2025
Abstract
Evidence supporting the clinical use of neuroprotective drugs for cerebral ischemia remains limited. Spatial and temporal disorientation, along with cognitive dysfunction, are among the most prominent long-term consequences of hippocampal neurodegeneration following cerebral ischemia. Cannabigerol (CBG), a non-psychotomimetic constituent of Cannabis sativa, [...] Read more.
Evidence supporting the clinical use of neuroprotective drugs for cerebral ischemia remains limited. Spatial and temporal disorientation, along with cognitive dysfunction, are among the most prominent long-term consequences of hippocampal neurodegeneration following cerebral ischemia. Cannabigerol (CBG), a non-psychotomimetic constituent of Cannabis sativa, has demonstrated neuroprotective effects in experimental models of cerebral injury. This study investigated the neuroprotective mechanisms of CBG in mitigating memory impairments caused by transient global cerebral ischemia in C57BL/6 mice using the bilateral common carotid artery occlusion (BCCAO) model. Mice underwent sham or BCCAO surgeries and received intraperitoneal (i.p.) injections of either a vehicle or CBG (1, 5, or 10 mg/Kg), starting 1 h post-surgery and continuing daily for 7 days. Spatial memory performance and depression-like behaviors were assessed using the object location test (OLT) and tail suspension test (TST), respectively. Additional analyses examined neuronal degeneration, neuroinflammation, and neuronal plasticity markers in the hippocampus. CBG attenuated ischemia-induced memory deficits, reduced neuronal loss in the hippocampus, and enhanced neuronal plasticity. These findings suggest that CBG’s neuroprotective effects against BCCAO-induced memory impairments may be mediated by reductions in neuroinflammation and modifications in neuroplasticity within the hippocampus. Full article
(This article belongs to the Special Issue Molecular Advances on Cannabinoid and Endocannabinoid Research 2.0)
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11 pages, 678 KiB  
Article
Reliability of Body Fat Percentage Measurements and Their Impact on Airway Resistance: Does Leptin Play a Significant Role?
by Rodrigo Muñoz-Cofré, Edgardo Rojas-Mancilla, Pablo A. Lizana, Máximo Escobar-Cabello, Claudio García-Herrera, Daniel Conei, Fernando Valenzuela-Aedo, Francisco Javier Soto-Rodríguez and Mariano del Sol
Medicina 2025, 61(8), 1492; https://doi.org/10.3390/medicina61081492 - 20 Aug 2025
Abstract
Background/Objectives: The measurement of body fat percentage (%BF) could alert us to potential respiratory problems; however, differences in %BF values have been reported depending on the method used. Therefore, the objectives of this study were to determine whether there are differences in %BF [...] Read more.
Background/Objectives: The measurement of body fat percentage (%BF) could alert us to potential respiratory problems; however, differences in %BF values have been reported depending on the method used. Therefore, the objectives of this study were to determine whether there are differences in %BF obtained through skinfold measurements (SF) and bioelectrical impedance analysis (BIA), and their correlation with airflow limitation (AFL), and secondly, to observe the relationship between leptin and AFL. Materials and Methods: A cross-sectional study was conducted with 80 participants (40 men and 40 women, aged 18–30 years). Assessments of %BF were made using SF and BIA. Spirometric parameters and pulmonary volumes were measured. Plasma leptin levels were determined using ELISA. Bivariate correlations and gender differences were analyzed. Results: When comparing %BF measured by SF and BIA, no significant differences were found between the two methods in either females or males. Furthermore, in both men and women, there was a direct and significant correlation between %BF obtained through BIA and SF (r = 0.936; r = 0.789, p < 0.001, respectively). Leptin showed a significant correlation with airway resistance (Raw) and specific airway resistance (sRaw) in men (r = 0.506; r = 0.553, p < 0.001, respectively) and women (r = 0.537, p = 0.001; r = 0.489, p = 0.003, respectively). Leptin also showed a significant correlation with %BF measured by both SF and BIA in men (r = 0.675; r = 0.687, p < 0.001, respectively) and women (r = 0.583; r = 0.682, p < 0.001, respectively). Conclusions: BIA and SF offer comparable results in estimating %BF. The significant correlation between leptin, %BF, and FEV1/FVC suggests a possible pathophysiological mechanism mediated by adiposity that could affect pulmonary function even in young and clinically healthy individuals. Full article
(This article belongs to the Section Pulmonology)
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21 pages, 1621 KiB  
Systematic Review
A Systematic Review of Clinical and Experimental Periodontitis Studies Demonstrating the Expression of PPAR-Gamma: A Meta-Analysis and Bioinformatics Approach
by Marco Antonio Rimachi Hidalgo, François Isnaldo Dias Caldeira, Silvana Regina Perez Orrico, Fabio Renato Manzolli Leite and Raquel Mantuaneli Scarel-Caminaga
Biomedicines 2025, 13(8), 2028; https://doi.org/10.3390/biomedicines13082028 - 20 Aug 2025
Abstract
Aim: Peroxisome Proliferator-Activated Receptor Gamma (PPAR-γ) plays important anti-inflammatory roles, including in periodontitis. This systematic review with a meta-analysis compiles evidence on the transcriptional and translational levels of PPAR-γ in clinical and experimental periodontitis studies, alongside functional enrichment and PPAR-γ interaction network analyses. [...] Read more.
Aim: Peroxisome Proliferator-Activated Receptor Gamma (PPAR-γ) plays important anti-inflammatory roles, including in periodontitis. This systematic review with a meta-analysis compiles evidence on the transcriptional and translational levels of PPAR-γ in clinical and experimental periodontitis studies, alongside functional enrichment and PPAR-γ interaction network analyses. Method: Electronic searches were conducted in six databases for publications up to February 2024. For the meta-analysis of experimental studies of periodontitis, PPAR-γ levels in the periodontal tissues were assessed through gene expression (RT-qPCR) or protein expression (Western blotting). In the clinical periodontitis studies, PPAR-γ levels in the gingival tissues were evaluated through protein expression (immunohistochemistry). A risk of bias (RoB) assessment was performed using the Systematic Review Centre for Laboratory Animal Experimentation (SYRCLE) and Newcastle Ottawa Scale (NOS) tools for experimental and clinical studies, respectively. The enrichment analysis was performed using the g:Profiler tool, and gene interaction networks were analyzed using GeneMANIA. Results: The meta-analysis demonstrated significantly lower PPAR-γ protein levels in the periodontal tissues from animals with periodontitis. PPARG mRNA and PPAR-γ quantification through immunohistochemistry remained inconclusive. The bioinformatics analyses indicated direct or indirect PPAR-γ-associated molecules involved in the immune response to periodontitis. The PPAR-γ protein expression was higher in periodontal tissues from healthy animals compared to that from those with periodontitis. Conclusion: Given the inconclusive findings of RT-qPCR and immunohistochemistry, further PPARG mRNA and PPAR-γ protein evaluations are needed to clarify their levels in the periodontal tissues. Full article
(This article belongs to the Special Issue Molecular Mechanisms and Therapeutic Approaches for Oral Disorders)
21 pages, 626 KiB  
Article
Cannabis Use Moderates Methamphetamine- and HIV-Related Inflammation: Evidence from Human Plasma Markers
by Jeffrey M. Rogers, Victoria O. Chentsova, Crystal X. Wang, Maria Cecilia Garibaldi Marcondes, Mariana Cherner, Ronald J. Ellis, Scott L. Letendre, Robert K. Heaton, Igor Grant and Jennifer E. Iudicello
Viruses 2025, 17(8), 1143; https://doi.org/10.3390/v17081143 - 20 Aug 2025
Abstract
Background: Methamphetamine use, which is disproportionately prevalent among people with HIV, increases risk for cardio- and neurovascular pathology through persistent immune activation and inflammation. Preclinical studies indicate that cannabinoids may reduce markers of pro-inflammatory processes, but data from people with chronic inflammatory conditions [...] Read more.
Background: Methamphetamine use, which is disproportionately prevalent among people with HIV, increases risk for cardio- and neurovascular pathology through persistent immune activation and inflammation. Preclinical studies indicate that cannabinoids may reduce markers of pro-inflammatory processes, but data from people with chronic inflammatory conditions are limited. We examined potentially interacting associations of lifetime methamphetamine use disorder (MUD), recent cannabis use, and HIV with four plasma markers of immune and inflammatory functions. Method: Participants with HIV (PWH, n = 86) and without HIV (PWoH, n = 148) provided urine and blood samples and completed neuromedical, psychiatric, and substance use assessments. Generalized linear models examined main and conditional associations of lifetime MUD, past-month cannabis use, and HIV with plasma concentrations of CXCL10/IP-10, CCL2/MCP-1, ICAM-1, and VCAM-1. Results: PWH displayed higher CXCL10/IP-10 than PWoH. Past-month cannabis use was independently associated with lower CXCL10/IP-10 levels and conditionally lower CCL2/MCP-1, ICAM-1, and VCAM-1 levels among people with lifetime MUD, but only PWoH displayed cannabis-associated lower VCAM-1 levels. Conclusions: Human plasma sample evidence suggests that cannabis use is associated with lower levels of immune and inflammatory molecules in the context of MUD or HIV. Cannabinoid pathways may be worthwhile clinical targets for treating sequelae of chronic inflammatory conditions. Full article
(This article belongs to the Special Issue HIV and Drugs of Abuse, 4th Edition)
36 pages, 19275 KiB  
Article
Effect of Phosphate Phase Incorporation on 3D-Printed Hydrogel Scaffolds: Towards Customizable Bone Graft Materials
by Andreea Trifan, Eduard Liciu, Andrei-Silviu Nedelcu, Mihai Dragomir, Doru-Daniel Cristea, Ciprian-Ștefan Mateescu, David-Andrei Nițulescu, Cătălina-Ana-Maria Cîrstea, Adela Banciu, Gabriela Toader, Aurel Diacon and Cristina Busuioc
Gels 2025, 11(8), 665; https://doi.org/10.3390/gels11080665 - 20 Aug 2025
Abstract
Bone defects remain a significant clinical challenge, creating a severe need for advanced biomaterials for tissue regeneration. This study addresses this issue by developing 3D-printed composite hydrogels containing alginate, gelatine, and resorbable calcium phosphates (monetite and brushite) for bone tissue engineering. The scaffolds [...] Read more.
Bone defects remain a significant clinical challenge, creating a severe need for advanced biomaterials for tissue regeneration. This study addresses this issue by developing 3D-printed composite hydrogels containing alginate, gelatine, and resorbable calcium phosphates (monetite and brushite) for bone tissue engineering. The scaffolds were fabricated using extrusion-based 3D printing and evaluated for their morphology, porosity, mechanical strength, swelling, degradation, and in vitro mineralization, while their cytocompatibility was assessed using LIVE/DEAD cell viability assays. The key findings demonstrate that calcium phosphate incorporation enhanced the mechanical stability by 15–25% compared to the controls, and mineral deposition increased significantly in the composite scaffolds. The developed hydrogels are bioactive and represent promising, customizable scaffolds for bone regeneration. These results support their further investigation as viable alternatives to traditional bone grafts for clinical bone tissue engineering applications. Full article
(This article belongs to the Special Issue Novel Gels for 3D Bioprinting in Tissue Engineering)
12 pages, 2682 KiB  
Article
The Alveolar Gas Monitor: An Alternative to Pulse Oximetry for the Noninvasive Assessment of Impaired Gas Exchange in Patients at Risk of Respiratory Deterioration
by W. Cameron McGuire, Eli Gruenberg, Tanner C. Long, Richa Sheth, Traci Marin, Brandon Nokes, Alex K. Pearce, Ann R. Elliott, Janelle M. Fine, John B. West, Daniel R. Crouch, G. Kim Prisk and Atul Malhotra
J. Clin. Med. 2025, 14(16), 5880; https://doi.org/10.3390/jcm14165880 - 20 Aug 2025
Abstract
Background/Objectives: The COVID-19 pandemic highlighted the limitations of pulse oximetry in detecting occult hypoxemia. The superiority of the alveolar gas monitor (AGM) compared to pulse oximetry (SpO2) in predicting respiratory deterioration among COVID-19-positive individuals has previously been demonstrated. Here, we combine [...] Read more.
Background/Objectives: The COVID-19 pandemic highlighted the limitations of pulse oximetry in detecting occult hypoxemia. The superiority of the alveolar gas monitor (AGM) compared to pulse oximetry (SpO2) in predicting respiratory deterioration among COVID-19-positive individuals has previously been demonstrated. Here, we combine COVID-19 and non-COVID-19 individuals as a combined cohort of participants to determine if the AGM has similar utility across a larger, more generalizable cohort. Methods: Adult patients (n = 75) at risk of respiratory deterioration in the emergency department (ED) underwent prospective assessments of their oxygen deficit (OD) and SpO2, simultaneously measured during quiet breathing on the AGM. The OD and SpO2 were then compared for their ability to predict the dichotomous outcome of the need for supplemental oxygen. The administration of supplemental oxygen was ordered by the clinical care team with no knowledge of the patients’ enrollment in this study. Results: In the logistic regression analysis, both SpO2 and OD significantly predicted the need for supplemental oxygen among COVID-19-negative individuals. However, in the multivariable regression, only OD (p < 0.001) significantly predicted the need for supplemental oxygen, while SpO2 (p = 0.05) did not in the combined cohort of COVID-19-negative and -positive individuals. Receiver operating characteristic (ROC) curve analysis demonstrated the superior discriminative ability of OD (area under ROC curve = 0.937) relative to SpO2 (area under ROC curve = 0.888) to predict the need for supplemental oxygen. Conclusions: The noninvasive AGM, which combines the measurement of exhaled partial pressures of gas with SpO2, outperforms SpO2 alone in predicting the need for supplemental oxygen among individuals in the ED at risk of respiratory deterioration regardless of the etiology for their symptoms (COVID-19-positive or -negative). Full article
(This article belongs to the Section Respiratory Medicine)
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9 pages, 469 KiB  
Review
Deep Learning Models: Their Relationship with Embryonic Euploidies and Reproductive Outcomes
by Aikaterini Selntigia, Lucia Maresca, Diletta Montanino Oliva, Camilla Coianiz and Daniela Galliano
Genes 2025, 16(8), 981; https://doi.org/10.3390/genes16080981 (registering DOI) - 20 Aug 2025
Abstract
Background: Embryo selection in in vitro fertilization (IVF) aims to prioritize embryos with the highest reproductive potential. While preimplantation genetic testing for aneuploidy (PGT-A) remains the gold standard for identifying euploid embryos, it is invasive and not universally applicable. Deep learning (DL)-based models, [...] Read more.
Background: Embryo selection in in vitro fertilization (IVF) aims to prioritize embryos with the highest reproductive potential. While preimplantation genetic testing for aneuploidy (PGT-A) remains the gold standard for identifying euploid embryos, it is invasive and not universally applicable. Deep learning (DL)-based models, such as the intelligent data analysis (iDA) score, have emerged as non-invasive alternatives for embryo assessment. This review critically evaluates the relationship between iDAScore (versions 1.0 and 2.0), embryo euploidy, and clinical outcomes, including live birth and miscarriage rates. Methods: A narrative review was performed using PubMed and Google Scholar, covering studies published from January 2020 to May 2025. The search included terms such as “iDAScore,” “deep learning,” “euploidy,” and “live birth.” Only English-language full-text studies assessing the predictive performance of iDAScore relative to chromosomal status or reproductive outcomes were included. Results: Six retrospective studies met the inclusion criteria. All reported a statistically significant association between higher iDAScore values and embryo euploidy. AUC values for euploidy prediction ranged from 0.60 to 0.68. In several studies, iDAScore was also positively associated with live birth rates and negatively with miscarriage rates. However, the predictive accuracy was moderate when restricted to euploid embryo cohorts, indicating that iDAScore may be more effective in broader populations where chromosomal status is unknown. Conclusions: iDAScore represents a promising adjunct to traditional embryo assessment. Although it cannot replace PGT-A, it may aid in embryo prioritization when genetic testing is not feasible. Larger prospective studies are warranted to further validate its clinical utility. Full article
(This article belongs to the Section Bioinformatics)
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10 pages, 1480 KiB  
Article
Comparison Between the Human-Sourced Ellipsoid Method and Kidney Volumetry Using Artificial Intelligence in Polycystic Kidney Disease
by Jihyun Yang, Young Rae Lee, Young Youl Hyun, Hyun Jung Kim, Tae Young Shin and Kyu-Beck Lee
J. Pers. Med. 2025, 15(8), 392; https://doi.org/10.3390/jpm15080392 - 20 Aug 2025
Abstract
Background: The Mayo imaging classification (MIC) for polycystic kidney disease (PKD) is a crucial basis for clinical treatment decisions; however, the volumetric assessment for its evaluation remains tedious and inaccurate. While the ellipsoid method for measuring the total kidney volume (TKV) in patients [...] Read more.
Background: The Mayo imaging classification (MIC) for polycystic kidney disease (PKD) is a crucial basis for clinical treatment decisions; however, the volumetric assessment for its evaluation remains tedious and inaccurate. While the ellipsoid method for measuring the total kidney volume (TKV) in patients with PKD provides a practical TKV estimation using computed tomography (CT), its inconsistency and inaccuracy are limitations, highlighting the need for improved, accessible techniques in real-world clinics. Methods: We compared manual ellipsoid and artificial intelligence (AI)-based kidney volumetry methods using a convolutional neural network-based segmentation model (3D Dynamic U-Net) for measuring the TKV by assessing 32 patients with PKD in a single tertiary hospital. Results: The median age and average TKV were 56 years and 1200.24 mL, respectively. Most of the patients were allocated to Mayo Clinic classifications 1B and 1C using the ellipsoid method, similar to the AI volumetry classification. AI volumetry outperformed the ellipsoid method with highly correlated scores (AI vs. nephrology professor ICC: r = 0.991, 95% confidence interval (CI) = 0.9780–0.9948, p < 0.01; AI vs. trained clinician ICC: r = 0.983, 95% CI = 0.9608–0.9907, p < 0.01). The Bland–Altman plot also showed that the mean differences between professor and AI volumetry were statistically insignificant (mean difference 159.5 mL, 95% CI = 11.8368–330.7817, p = 0.07). Conclusions: AI-based kidney volumetry demonstrates strong agreement with expert manual measurements and offers a reliable, labor-efficient alternative for TKV assessment in clinical practice. It is helpful and essential for managing PKD and optimizing therapeutic outcomes. Full article
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