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28 pages, 3251 KiB  
Article
Predictors of ISUP Grade Group Discrepancies Between Biopsy and Radical Prostatectomy: A Single-Center Analysis of Clinical, Imaging, and Histopathological Parameters
by Victor Pasecinic, Dorin Novacescu, Flavia Zara, Cristina-Stefania Dumitru, Vlad Dema, Silviu Latcu, Razvan Bardan, Alin Adrian Cumpanas, Raluca Dumache, Talida Georgiana Cut, Hossam Ismail and Ademir Horia Stana
Cancers 2025, 17(15), 2595; https://doi.org/10.3390/cancers17152595 - 7 Aug 2025
Abstract
Background/Objectives: ISUP grade group discordance between prostate biopsy and radical prostatectomy (RP) impacts treatment decisions in over a third (~25–40%) of prostate cancer (PCa) patients. We aimed to identify ISUP grade migration predictors and assess the impact of preoperative imaging (MRI) in [...] Read more.
Background/Objectives: ISUP grade group discordance between prostate biopsy and radical prostatectomy (RP) impacts treatment decisions in over a third (~25–40%) of prostate cancer (PCa) patients. We aimed to identify ISUP grade migration predictors and assess the impact of preoperative imaging (MRI) in a contemporary Romanian PCa cohort. Methods: We retrospectively analyzed 142 PCa patients undergoing RP following biopsy between January 2021 and December 2024 at Pius Brinzeu County Hospital, Timișoara: 90 without and 52 with preoperative MRI. Clinical parameters, MRI findings (PI-RADS), and biopsy characteristics were evaluated. Machine learning models (gradient boosting, random forest) were developed with SHAP analysis for interpretability. Results: Grade migration occurred in 69/142 patients (48.6%): upstaging in 55 (38.7%) and downstaging in 14 (9.9%). In the non-MRI cohort, 37/90 (41.1%) were upstaged and 9/90 (10.0%) were downstaged, versus 18/52 (34.6%) upstaged and 5/52 (9.6%) downstaged in the MRI cohort. The MRI group showed a 6.5% absolute reduction in upstaging (34.6% vs. 41.1%), a promising non-significant trend (p = 0.469) that requires further investigation. Grade 1 patients showed the highest upstaging (69.4%), while Grades 3–4 showed the highest downstaging (11/43, 25.6%). PI-RADS 4 lesions had the highest upstaging (43.5%). PSA density > 0.20 ng/mL2 emerged as the strongest predictor. Gradient boosting achieved superior performance (AUC = 0.812) versus logistic regression (AUC = 0.721), representing a 13% improvement in discrimination. SHAP analysis revealed PSA density as the most influential (importance: 0.287). Grade migration associated with adverse pathology: extracapsular extension (52.7% vs. 28.7%, p = 0.008) and positive margins (38.2% vs. 21.8%, p = 0.045). Conclusions: ISUP grade migration affects 48.6% of Romanian patients, with 38.7% upstaged and 9.9% downstaged. The 69.4% upstaging in Grade 1 patients emphasizes the need for enhanced risk stratification tools, while 10% downstaging suggests potential overtreatment. Machine learning with SHAP analysis provides superior predictive performance (13% AUC improvement) while offering clinically interpretable risk assessments. PSA density dominates risk assessment, while PI-RADS 4 lesions warrant closer scrutiny than previously recognized. Full article
(This article belongs to the Special Issue Prostate Cancer: Contemporary Standards and Challenges)
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14 pages, 1372 KiB  
Article
Risk Factors of Histopathological Crescent Formation in Pediatric IgA Vasculitis Nephritis
by Yanyan Jin, Yi Xie, Qian Lin, Yu Zhu, Limin Huang, Yang He and Haidong Fu
Medicina 2025, 61(8), 1421; https://doi.org/10.3390/medicina61081421 - 6 Aug 2025
Abstract
Background and Objectives: This study aimed to explore the risk factors of histopathological crescent formation in pediatric IgA vasculitis nephritis (IgAVN). Materials and Methods: Enrolled patients with biopsy-proven IgAVN from Zhejiang University’s hospital were split into two groups: 377 with no [...] Read more.
Background and Objectives: This study aimed to explore the risk factors of histopathological crescent formation in pediatric IgA vasculitis nephritis (IgAVN). Materials and Methods: Enrolled patients with biopsy-proven IgAVN from Zhejiang University’s hospital were split into two groups: 377 with no crescents on histopathology (Group 1) and 364 with crescentic nephritis (Group 2). Collected data included clinical features, lab indicators, histopathological grading, and factors causing glomerular sclerosis. Logistic regression was used to assess factors affecting crescent formation in IgAVN. Double-immunofluorescence assay was used to detect TGF-β1, MCP-1, α-SMA, Collagen I, and FN1 in kidney biopsy specimens. The relationship between kidney fibrosis factors and histopathological grade were analyzed using Chi-square and Pearson tests. Results: A total of 741 patients with IgAVN were included in the study. Univariate logistic regression identified potential factors related to crescent formation, including age, gender, clinical classification, hematuria grade, 24 h urine protein level, peripheral white blood cells (WBCs), serum albumin, Cystatin-C, APTT, and PT. Multivariate analysis revealed statistical significance for age, 24 h urine protein, and WBCs across pathological grades (p < 0.05). Mantel–Haenszel Chi-square tests indicated a linear relationship between IgAVN pathological grade and α-SMA, TGF-β1, MCP-1, and FN1. Pearson correlation analysis confirmed a positive correlation between pathological grade and these markers. Conclusions: Age, 24 h urinary protein, and blood WBCs are identified as risk factors for histopathological crescent formation in children with IgAVN. Additionally, a higher pathological grade is associated with more pronounced fibrosis indicators. Full article
(This article belongs to the Section Pediatrics)
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21 pages, 838 KiB  
Systematic Review
Systematic Review of Hip Fractures and Regional Anesthesia: Efficacy of the Main Blocks and Comparison for a Multidisciplinary and Effective Approach for Patients in the Hospital Setting of Anesthesiology and Resuscitation
by Enrique González Marcos, Inés Almagro Vidal, Rodrigo Arranz Pérez, Julio Morillas Martinez, Amalia Díaz Viudes, Ana Rodríguez Martín, Alberto José Gago Sánchez, Carmen García De Leániz and Daniela Rodriguez Marín
Surg. Tech. Dev. 2025, 14(3), 27; https://doi.org/10.3390/std14030027 - 6 Aug 2025
Abstract
Background: Hip fractures represent a major clinical challenge, particularly in elderly and frail patients, where postoperative pain control must balance effective analgesia with motor preservation to facilitate early mobilization. Various regional anesthesia techniques are used in this setting, including the pericapsular nerve group [...] Read more.
Background: Hip fractures represent a major clinical challenge, particularly in elderly and frail patients, where postoperative pain control must balance effective analgesia with motor preservation to facilitate early mobilization. Various regional anesthesia techniques are used in this setting, including the pericapsular nerve group (PENG) block, fascia iliaca compartment block (FICB), femoral nerve block (FNB), and quadratus lumborum block (QLB), yet optimal strategies remain debated. Objectives: To systematically review the efficacy, safety, and clinical applicability of major regional anesthesia techniques for pain management in hip fractures, including considerations of fracture type, surgical approach, and functional outcomes. Methods: A systematic literature search was conducted following PRISMA 2020 guidelines in PubMed, Scopus, Web of Science, and the virtual library of the Hospital Central de la Defensa “Gómez Ulla” up to March 2025. Inclusion criteria were RCTs, systematic reviews, and meta-analyses evaluating regional anesthesia for hip surgery in adults. Risk of bias in RCTs was assessed using RoB 2.0, and certainty of evidence was evaluated using the GRADE approach. Results: Twenty-nine studies were included, comprising RCTs, systematic reviews, and meta-analyses. PENG block demonstrated superior motor preservation and reduced opioid consumption compared to FICB and FNB, particularly in intracapsular fractures and anterior surgical approaches. FICB and combination strategies (PENG+LFCN or sciatic block) may provide broader analgesic coverage in extracapsular fractures or posterior approaches. The overall risk of bias across RCTs was predominantly low, and certainty of evidence ranged from moderate to high for key outcomes. No significant safety concerns were identified across techniques, although reporting of adverse events was inconsistent. Conclusions: PENG block appears to offer a favorable balance of analgesia and motor preservation in hip fracture surgery, particularly for intracapsular fractures. For extracapsular fractures or posterior approaches, combination strategies may enhance analgesic coverage. Selection of block technique should be tailored to fracture type, surgical approach, and patient-specific functional goals. Full article
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29 pages, 5769 KiB  
Article
Genetic Complexity in Spondyloarthritis: Contributions of HLA-B Alleles Beyond HLA-B*27 in Romanian Patients
by Ruxandra-Elena Nagit, Mariana Pavel-Tanasa, Corina Cianga, Elena Rezus and Petru Cianga
Int. J. Mol. Sci. 2025, 26(15), 7617; https://doi.org/10.3390/ijms26157617 - 6 Aug 2025
Abstract
This study examined the distribution and disease associations of non-HLA-B*27 HLA-B alleles in Romanian spondyloarthritis (SpA) patients, aiming to address the underrepresentation of Eastern European populations in immunogenetic research. Methods: We analyzed 263 HLA-B*27-negative patients from Northeastern Romania fulfilling ASAS criteria. HLA-B genotyping [...] Read more.
This study examined the distribution and disease associations of non-HLA-B*27 HLA-B alleles in Romanian spondyloarthritis (SpA) patients, aiming to address the underrepresentation of Eastern European populations in immunogenetic research. Methods: We analyzed 263 HLA-B*27-negative patients from Northeastern Romania fulfilling ASAS criteria. HLA-B genotyping was performed at two-digit resolution, and allele distributions were compared with two Romanian HLA-B*27-negative control groups (n = 335 and n = 1705 cases), using chi-square testing and logistic regression. Compared to controls, HLA-B*47 (p = 0.0007) and HLA-B*54 (p = 0.0013) were significantly enriched, while HLA-B*40 was underrepresented (p = 0.0287). Notably, HLA-B*54 was observed exclusively in axial SpA. Within the cohort, both HLA-B*13 and HLA-B*57 alleles were associated with psoriasis, while HLA-B*37 and HLA-B*41 alleles were clustered within the reactive arthritis group. The HLA-B*35 and HLA-B*18 alleles were the most frequently observed alleles across most clinical phenotypes. When comparing the frequency of HLA-B associations, the most common genotypes among SpA patients were B*08-B*18, B*13-B*35, and B*35-B*51. Notably, B*08-B*18 was more frequent in patients with radiographic sacroiliitis grade ≥ 2, while B*35-B*51 was more frequent in those with confirmed systemic inflammation, as indicated by elevated CRP or ESR levels. Analysis of peptide-binding patterns revealed a cluster of risk alleles, HLA-B*08, B*18, B*35, B*40, and B*54, sharing similar features, distinct from the canonical profile of B*27. These findings highlight the contribution of non-B*27 HLA-B alleles to SpA susceptibility in an Eastern European population and support the notion that HLA-B*27-negative SpA may represent a distinct clinical and immunological entity, driven by alternative pathogenic mechanisms. They also emphasize the importance of population-specific immunogenetic profiling and support expanding genetic characterization in HLA-B*27-negative patients. Full article
(This article belongs to the Special Issue Role of HLA (Human Leucocyte Antigen) in Human Diseases)
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23 pages, 406 KiB  
Systematic Review
Advances in Bidirectional Therapy for Peritoneal Metastases: A Systematic Review of Pressurized Intraperitoneal Aerosol Chemotherapy (PIPAC) Combined with Systemic Chemotherapy
by Manuela Robella, Marco Vitturini, Andrea Di Giorgio, Matteo Aulicino, Martin Hubner, Emanuele Koumantakis, Felice Borghi, Paolo Catania, Armando Cinquegrana and Paola Berchialla
Cancers 2025, 17(15), 2580; https://doi.org/10.3390/cancers17152580 - 6 Aug 2025
Abstract
Background: Peritoneal metastases (PM) represent a common and challenging manifestation of several gastrointestinal and gynecologic malignancies. Bidirectional treatment—combining Pressurized Intraperitoneal Aerosol Chemotherapy (PIPAC) with systemic chemotherapy—has emerged as a strategy to enhance locoregional control while maintaining systemic coverage. Objective: This systematic [...] Read more.
Background: Peritoneal metastases (PM) represent a common and challenging manifestation of several gastrointestinal and gynecologic malignancies. Bidirectional treatment—combining Pressurized Intraperitoneal Aerosol Chemotherapy (PIPAC) with systemic chemotherapy—has emerged as a strategy to enhance locoregional control while maintaining systemic coverage. Objective: This systematic review aimed to analyze the study design, characteristics, and timing of the treatments administered—including the type of systemic chemotherapy, intraperitoneal agents used in PIPAC, and interval between administrations—as well as the clinical outcomes, safety profile, and overall methodological quality of the available literature on bidirectional treatment for peritoneal metastases. Methods: A systematic literature search was conducted across the PubMed, Embase, and Cochrane Library databases up to April 2025. Studies were included if they reported clinical outcomes of patients undergoing bidirectional treatment. Data extraction focused on survival, response assessment (PRGS, PCI), adverse events, systemic and intraperitoneal regimens, treatment interval, and study methodology. Results: A total of 22 studies involving 1015 patients (742 treated with bidirectional therapy) were included. Median overall survival ranged from 2.8 to 19.6 months, with the most favorable outcomes observed in gastric and colorectal cancer cohorts. PRGS improvement after multiple PIPAC cycles was reported in >80% of evaluable cases. High-grade adverse events (CTCAE ≥ 3) occurred in up to 17% of patients in most studies, with only one study reporting treatment-related mortality. However, methodological quality was generally moderate, with considerable heterogeneity in treatment protocols, response criteria, systemic regimens, and toxicity attribution. Conclusions: Bidirectional therapy with PIPAC and systemic chemotherapy appears to be a feasible and potentially effective strategy for selected patients with peritoneal metastases. Despite encouraging outcomes, definitive conclusions are limited by the retrospective nature and heterogeneity of available studies. Prospective standardized trials are needed to confirm efficacy, clarify patient selection, and optimize treatment protocols. Full article
(This article belongs to the Section Cancer Therapy)
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28 pages, 1985 KiB  
Review
Feline Mammary Tumors: A Comprehensive Review of Histological Classification Schemes, Grading Systems, and Prognostic Factors
by Joana Rodrigues-Jesus, Hugo Vilhena, Ana Canadas-Sousa and Patrícia Dias-Pereira
Vet. Sci. 2025, 12(8), 736; https://doi.org/10.3390/vetsci12080736 - 5 Aug 2025
Abstract
As the body of knowledge on feline mammary tumors (FMTs) continues to grow, their histological classification and grading systems have undergone revisions and updates to better reflect the biological behavior of these tumors. In this review, the historical evolution of these frameworks is [...] Read more.
As the body of knowledge on feline mammary tumors (FMTs) continues to grow, their histological classification and grading systems have undergone revisions and updates to better reflect the biological behavior of these tumors. In this review, the historical evolution of these frameworks is traced and later revisited in the context of their prognostic relevance. Numerous studies have investigated clinicopathological prognostic factors in feline mammary carcinomas (FMCs); however, the heterogeneity in assessment methods, inclusion criteria for survival analysis, and the clinical endpoints considered can often complicate direct comparisons across different studies and may contribute to seemingly conflicting results. Furthermore, the small cohort size of many studies limits the robustness and transferability of their findings. This paper provides an updated overview of the epidemiological, clinical, and pathological prognostic factors of these tumors, while also highlighting current challenges, methodological limitations, and areas for future improvement. Full article
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22 pages, 688 KiB  
Review
The Evolving Treatment Landscape for the Elderly Multiple Myeloma Patient: From Quad Regimens to T-Cell Engagers and CAR-T
by Matthew James Rees and Hang Quach
Cancers 2025, 17(15), 2579; https://doi.org/10.3390/cancers17152579 - 5 Aug 2025
Abstract
Multiple myeloma (MM) is predominantly a disease of the elderly. In recent years, a surge of highly effective plasma cell therapies has revolutionized the care of elderly multiple myeloma (MM) patients, for whom frailty and age-related competing causes of mortality determine management. Traditionally, [...] Read more.
Multiple myeloma (MM) is predominantly a disease of the elderly. In recent years, a surge of highly effective plasma cell therapies has revolutionized the care of elderly multiple myeloma (MM) patients, for whom frailty and age-related competing causes of mortality determine management. Traditionally, the treatment of newly diagnosed elderly patients has centered on doublet or triplet combinations composed of immunomodulators (IMIDs), proteasome inhibitors (PIs), anti-CD38 monoclonal antibodies (mAbs), and corticosteroids producing median progression-free survival (PFS) rates between 34 and 62 months. However, recently, a series of large phase III clinical trials examining quadruplet regimens of PIs, IMIDs, corticosteroids, and anti-CD38 mAbs have shown exceptional outcomes, with median PFS exceeding 60 months, albeit with higher rates of peripheral neuropathy (≥Grade 2: 27% vs. 10%) when PIs and IMIDs are combined, and infections (≥Grade 3: 40% vs. 29–41%) with the addition of anti-CD38mAbs. The development of T-cell redirecting therapies including T-cell engagers (TCEs) and CAR-T cells has further expanded the therapeutic arsenal. TCEs have shown exceptional activity in relapsed disease and are being explored in the newly diagnosed setting with promising early results. However, concerns remain regarding the logistical challenges of step-up dosing, which often necessitates inpatient admission, the infectious risks, and the financial burden associated with TCEs in elderly patients. CAR-T, the most potent commercially available therapy for MM, offers the potential of a ‘one and done’ approach. However, its application to elderly patients has been tempered by significant concerns of cytokine release syndrome, early and delayed neurological toxicity, and its overall tolerability in frail patients. Robust data in frail patients are still needed. How CAR-T and TCEs will be sequenced among the growing therapeutic armamentarium for elderly MM patients remains to be determined. This review explores the safety, efficacy, cost, and logistical barriers associated with the above treatments in elderly MM patients. Full article
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11 pages, 219 KiB  
Article
TKI Use and Treatment-Free Remission in Chronic Myeloid Leukemia: Evidence from a Regional Cohort Study in the Canary Islands
by Santiago Sánchez-Sosa, Ruth Stuckey, Adrián Segura Díaz, José David González San Miguel, Ylenia Morales Ruiz, Sunil Lakhawani Lakhawani, Jose María Raya Sánchez, Melania Moreno Vega, María Tapia Torres, Pilar López-Coronado, María de las Nieves Saez Perdomo, Marta Fernández, Cornelia Stoica, Cristina Bilbao Sieyro and María Teresa Gómez Casares
Hematol. Rep. 2025, 17(4), 39; https://doi.org/10.3390/hematolrep17040039 - 4 Aug 2025
Viewed by 136
Abstract
Background/Objectives: The advent of tyrosine kinase inhibitors (TKIs) revolutionized the management of chronic myeloid leukemia (CML), achieving survival rates near those of the general population. Despite this success, prolonged therapy presents challenges, including physical, emotional, and financial burdens. Treatment-free remission (TFR), defined [...] Read more.
Background/Objectives: The advent of tyrosine kinase inhibitors (TKIs) revolutionized the management of chronic myeloid leukemia (CML), achieving survival rates near those of the general population. Despite this success, prolonged therapy presents challenges, including physical, emotional, and financial burdens. Treatment-free remission (TFR), defined as sustained deep molecular response (DMR) after discontinuing TKIs, has emerged as a viable clinical goal. This study evaluates real-world data from the Canary Islands Registry of CML (RCLMC) to explore outcomes, predictors, and the feasibility of TFR. Methods: This retrospective observational study included 393 patients diagnosed with CML-CP between 2007 and 2023. Molecular response was monitored according to international guidelines. Survival probabilities were estimated using the Kaplan–Meier method. Logistic regression analysis was performed to identify predictors of molecular relapses after TKI discontinuation. Results: Of the 383 patients who received TKI treatment, 58.3% achieved molecular response grade 2 (MR2) (BCR-ABL1 ≤ 1%), 95.05% achieved MR2, and 50.5% reached MR4 within the first year. Of the 107 patients attempting TFR, 73.2% maintained remission at 36 months. Relapses occurred in 24 patients, all regaining molecular response upon reintroduction of TKIs. No cases of disease progression were observed. Conclusions: Our findings support the feasibility and safety of TFR in a real-world clinical setting for well-selected patients, with outcomes consistent with international studies. The study underscores the importance of molecular monitoring and patient-specific strategies to optimize outcomes. Full article
27 pages, 2005 KiB  
Article
Glyoxalase 1 Inducer, trans-Resveratrol and Hesperetin–Dietary Supplement with Multi-Modal Health Benefits
by Mingzhan Xue, Naila Rabbani and Paul J. Thornalley
Antioxidants 2025, 14(8), 956; https://doi.org/10.3390/antiox14080956 - 4 Aug 2025
Viewed by 208
Abstract
A dietary supplement, trans-resveratrol and hesperetin (tRES+HESP)—also known as GlucoRegulate—induces increased expression of glyoxalase 1 (Glo1) by activation of transcription factor Nrf2, countering accumulation of the reactive dicarbonyl glycating agent, methylglyoxal. tRES+HESP corrected insulin resistance and decreased fasting and postprandial plasma glucose [...] Read more.
A dietary supplement, trans-resveratrol and hesperetin (tRES+HESP)—also known as GlucoRegulate—induces increased expression of glyoxalase 1 (Glo1) by activation of transcription factor Nrf2, countering accumulation of the reactive dicarbonyl glycating agent, methylglyoxal. tRES+HESP corrected insulin resistance and decreased fasting and postprandial plasma glucose and low-grade inflammation in overweight and obese subjects in a clinical trial. The aim of this study was to explore, for the first time, health-beneficial gene expression other than Glo1 induced by tRES+HESP in human endothelial cells and fibroblasts in primary culture and HepG2 hepatoma cell line and activity of cis-resveratrol (cRES) as a Glo1 inducer. We measured antioxidant response element-linked gene expression in these cells in response to 5 µM tRES+HESP by the NanoString method. tRES+HESP increases gene expression linked to the prevention of dicarbonyl stress, lipid peroxidation, oxidative stress, proteotoxicity and hyperglycemia-linked glycolytic overload. Downstream benefits were improved regulation of glucose and lipid metabolism and decreased inflammation, extracellular matrix remodeling and senescence markers. The median effective concentration of tRES was ninefold lower than cRES in the Glo1 inducer luciferase reporter assay. The GlucoRegulate supplement provides a new treatment option for the prevention of type 2 diabetes and metabolic dysfunction–associated steatotic liver disease and supports healthy aging. Full article
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21 pages, 3562 KiB  
Article
scRNA-seq Can Identify Different Cell Populations in Ovarian Cancer Bulk RNA-seq Experiments
by Sofia Gabrilovich, Eric Devor, Nicholas Cardillo, David Bender, Michael Goodheart and Jesus Gonzalez-Bosquet
Int. J. Mol. Sci. 2025, 26(15), 7512; https://doi.org/10.3390/ijms26157512 - 4 Aug 2025
Viewed by 172
Abstract
High-grade serous ovarian cancer (HGSC) is a heterogeneous disease. RNA sequencing (RNAseq) of bulk solid tissue is of limited use in these populations due to heterogeneity. Single-cell RNA-seq (scRNA-seq) allows for the identification of diverse genetic compositions of heterogeneous cell populations. New computational [...] Read more.
High-grade serous ovarian cancer (HGSC) is a heterogeneous disease. RNA sequencing (RNAseq) of bulk solid tissue is of limited use in these populations due to heterogeneity. Single-cell RNA-seq (scRNA-seq) allows for the identification of diverse genetic compositions of heterogeneous cell populations. New computational methodologies are now available that use scRNAseq results to estimate cell type proportions in bulk RNAseq data. We performed bulk RNA-seq gene expression analysis on 112 HGSC specimens and 12 benign fallopian tube (FT) controls. We identified several publicly available scRNAseq datasets for use as annotation and reference datasets. Deconvolution was performed with MUlti-Subject SIngle Cell Deconvolution (MuSiC) to estimate cell type proportions in the bulk RNA-seq data. Datasets from the Cancer Genome Atlas (TCGA). HGSC repositories were also evaluated. Clinical variables and percentages of cell types were compared for differences in clinical outcomes and treatment results. Pathway enrichment analysis was also performed. Different annotations for referenced scRNA-seq datasets used for deconvolution of bulk RNA-seq data revealed different cellular proportions that were significantly associated with clinical outcomes; for example, higher proportions of macrophages were associated with a better response to primary chemotherapy. Our deconvolution study of bulk RNAseq HGSC samples identified cell populations within the tumor that may be associated with some of the observed clinical outcomes. Full article
(This article belongs to the Section Molecular Informatics)
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15 pages, 1476 KiB  
Article
Laboratory, Clinical, and Pathohistological Significance of the Outcomes of Patients with Membranous Nephropathy After 10 Year of Follow-Up
by Marko Baralić, Selena Gajić, Mihajlo Kostić, Milorad Stojadinović, Kristina Filić, Danka Bjelić, Vidna Karadžić-Ristanović, Ivana Mrđa, Jovana Gavrilović, Danica Ćujić, Aleksandar Sič, Stefan Janković, Ivan Putica, Sanja Stankovic, Dušan Vićentijević, Maja Životić, Sanja Radojević-Škodrić, Jelena Pavlović, Ana Bontić and Aleksandra Kezić
Life 2025, 15(8), 1221; https://doi.org/10.3390/life15081221 - 1 Aug 2025
Viewed by 365
Abstract
Membranous nephropathy (MN) is the most prevalent cause of nephrotic syndrome (NS) in adults, and it can be primary (idiopathic) with an unknown cause or secondary due to a variety of conditions (lupus, infections, malignancies, medications, etc.). It progresses to chronic kidney disease [...] Read more.
Membranous nephropathy (MN) is the most prevalent cause of nephrotic syndrome (NS) in adults, and it can be primary (idiopathic) with an unknown cause or secondary due to a variety of conditions (lupus, infections, malignancies, medications, etc.). It progresses to chronic kidney disease (CKD) in up to 60% of patients, and 10 to 30% develop end-stage kidney disease (ESKD). This retrospective study examines the importance of specific factors, including baseline demographic and clinical data, kidney biopsy PH findings, and selected biochemical parameters, influencing MN outcomes after 10 years of follow-up. The cohort included 94 individuals in whom a diagnosis of MN was established by percutaneous biopsy of the left kidney’s lower pole at the University Clinical Center of Serbia (UCCS) between 2008 and 2013. According to the outcomes, patients were divided into three groups: the recovery (Rec) group, with complete remission, including normal serum creatinine (Scr) and proteinuria (Prt), the group with development of chronic kidney disease (CKD), and the group with development of end-stage kidney disease (ESKD). Nephropathologists graded pathohistological (PH) results from I to III based on the observed PH findings. During the follow-up period, 33 patients were in the Rec group, CKD developed in 53 patients, and ESKD developed in 8 patients. Baseline creatinine clearance levels (Ccr), Scr, and uric acid (urate) were found to be significantly associated with the outcomes (p < 0.001). The lowest values of baseline Scr and urate were observed in the Rec group. The presence of acute kidney injury (AKI) or CKD at the time of kidney biopsy was associated with the more frequent development of ESKD (p = 0.02). Lower Ccr was associated with a higher likelihood of progressing to CKD (B = −0.021, p = 0.014), whereas older age independently predicted progression to ESKD (B = 0.02, p = 0.032). Based on this study, it was concluded that the most important biochemical and clinical factors that are associated with the outcomes of this disease are the values of Scr, Ccr, and urate and the existence of CKD at the time of kidney biopsy. Unlike most previous studies, the presence of HTN had no statistical significance in the outcome of the disease. Full article
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10 pages, 1883 KiB  
Article
In Vitro Biofilm Formation Kinetics of Pseudomonas aeruginosa and Escherichia coli on Medical-Grade Polyether Ether Ketone (PEEK) and Polyamide 12 (PA12) Polymers
by Susana Carbajal-Ocaña, Kristeel Ximena Franco-Gómez, Valeria Atehortúa-Benítez, Daniela Mendoza-Lozano, Luis Vicente Prado-Cervantes, Luis J. Melgoza-Ramírez, Miguel Delgado-Rodríguez, Mariana E. Elizondo-García and Jorge Membrillo-Hernández
Hygiene 2025, 5(3), 32; https://doi.org/10.3390/hygiene5030032 - 1 Aug 2025
Viewed by 192
Abstract
Biofilms, structured communities of microorganisms encased in an extracellular matrix, are a major cause of persistent infections, particularly when formed on medical devices. This study investigated the kinetics of biofilm formation by Escherichia coli and Pseudomonas aeruginosa, two clinically significant pathogens, on [...] Read more.
Biofilms, structured communities of microorganisms encased in an extracellular matrix, are a major cause of persistent infections, particularly when formed on medical devices. This study investigated the kinetics of biofilm formation by Escherichia coli and Pseudomonas aeruginosa, two clinically significant pathogens, on two medical-grade polymers: polyether ether ketone (PEEK) and polyamide 12 (PA12). Using a modified crystal violet staining method and spectrophotometric quantification, we evaluated biofilm development over time on polymer granules and catheter segments composed of these materials. Results revealed that PEEK surfaces supported significantly more biofilm formation than PA12, with peak accumulation observed at 24 h for both pathogens. Conversely, PA12 demonstrated reduced bacterial adhesion and lower biofilm biomass, suggesting surface characteristics less conducive to microbial colonization. Additionally, the study validated a reproducible protocol for assessing biofilm formation, providing a foundation for evaluating anti-biofilm strategies. While the assays were performed under static in vitro conditions, the findings highlight the importance of material selection and early prevention strategies in the design of infection-resistant medical devices. This work contributes to the understanding of how surface properties affect microbial adhesion and underscores the critical need for innovative surface modifications or coatings to mitigate biofilm-related healthcare risks. Full article
(This article belongs to the Section Hygiene in Healthcare Facilities)
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24 pages, 3243 KiB  
Article
Design of Experiments Leads to Scalable Analgesic Near-Infrared Fluorescent Coconut Nanoemulsions
by Amit Chandra Das, Gayathri Aparnasai Reddy, Shekh Md. Newaj, Smith Patel, Riddhi Vichare, Lu Liu and Jelena M. Janjic
Pharmaceutics 2025, 17(8), 1010; https://doi.org/10.3390/pharmaceutics17081010 - 1 Aug 2025
Viewed by 235
Abstract
Background: Pain is a complex phenomenon characterized by unpleasant experiences with profound heterogeneity influenced by biological, psychological, and social factors. According to the National Health Interview Survey, 50.2 million U.S. adults (20.5%) experience pain on most days, with the annual cost of prescription [...] Read more.
Background: Pain is a complex phenomenon characterized by unpleasant experiences with profound heterogeneity influenced by biological, psychological, and social factors. According to the National Health Interview Survey, 50.2 million U.S. adults (20.5%) experience pain on most days, with the annual cost of prescription medication for pain reaching approximately USD 17.8 billion. Theranostic pain nanomedicine therefore emerges as an attractive analgesic strategy with the potential for increased efficacy, reduced side-effects, and treatment personalization. Theranostic nanomedicine combines drug delivery and diagnostic features, allowing for real-time monitoring of analgesic efficacy in vivo using molecular imaging. However, clinical translation of these nanomedicines are challenging due to complex manufacturing methodologies, lack of standardized quality control, and potentially high costs. Quality by Design (QbD) can navigate these challenges and lead to the development of an optimal pain nanomedicine. Our lab previously reported a macrophage-targeted perfluorocarbon nanoemulsion (PFC NE) that demonstrated analgesic efficacy across multiple rodent pain models in both sexes. Here, we report PFC-free, biphasic nanoemulsions formulated with a biocompatible and non-immunogenic plant-based coconut oil loaded with a COX-2 inhibitor and a clinical-grade, indocyanine green (ICG) near-infrared fluorescent (NIRF) dye for parenteral theranostic analgesic nanomedicine. Methods: Critical process parameters and material attributes were identified through the FMECA (Failure, Modes, Effects, and Criticality Analysis) method and optimized using a 3 × 2 full-factorial design of experiments. We investigated the impact of the oil-to-surfactant ratio (w/w) with three different surfactant systems on the colloidal properties of NE. Small-scale (100 mL) batches were manufactured using sonication and microfluidization, and the final formulation was scaled up to 500 mL with microfluidization. The colloidal stability of NE was assessed using dynamic light scattering (DLS) and drug quantification was conducted through reverse-phase HPLC. An in vitro drug release study was conducted using the dialysis bag method, accompanied by HPLC quantification. The formulation was further evaluated for cell viability, cellular uptake, and COX-2 inhibition in the RAW 264.7 macrophage cell line. Results: Nanoemulsion droplet size increased with a higher oil-to-surfactant ratio (w/w) but was no significant impact by the type of surfactant system used. Thermal cycling and serum stability studies confirmed NE colloidal stability upon exposure to high and low temperatures and biological fluids. We also demonstrated the necessity of a solubilizer for long-term fluorescence stability of ICG. The nanoemulsion showed no cellular toxicity and effectively inhibited PGE2 in activated macrophages. Conclusions: To our knowledge, this is the first instance of a celecoxib-loaded theranostic platform developed using a plant-derived hydrocarbon oil, applying the QbD approach that demonstrated COX-2 inhibition. Full article
(This article belongs to the Special Issue Quality by Design in Pharmaceutical Manufacturing)
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14 pages, 5672 KiB  
Article
Multiplex Immunofluorescence Reveals Therapeutic Targets EGFR, EpCAM, Tissue Factor, and TROP2 in Triple-Negative Breast Cancer
by T. M. Mohiuddin, Wenjie Sheng, Chaoyu Zhang, Marwah Al-Rawe, Svetlana Tchaikovski, Felix Zeppernick, Ivo Meinhold-Heerlein and Ahmad Fawzi Hussain
Int. J. Mol. Sci. 2025, 26(15), 7430; https://doi.org/10.3390/ijms26157430 - 1 Aug 2025
Viewed by 254
Abstract
Triple-negative breast cancer (TNBC) is a clinically and molecularly heterogeneous subtype defined by the absence of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) expression. In this study, tumor specimens from 104 TNBC patients were analyzed to [...] Read more.
Triple-negative breast cancer (TNBC) is a clinically and molecularly heterogeneous subtype defined by the absence of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) expression. In this study, tumor specimens from 104 TNBC patients were analyzed to characterize molecular and clinicopathological features and to assess the expression and therapeutic potential of four key surface markers: epidermal growth factor receptor (EGFR), epithelial cell adhesion molecule (EpCAM), tissue factor (TF), and trophoblast cell surface antigen (TROP2). Multiplex immunofluorescence (mIF) demonstrated elevated EGFR and TROP2 expression in the majority of samples. Significant positive correlations were observed between EGFR and TF, as well as between TROP2 and both TF and EpCAM. Expression analyses revealed increased EGFR and TF levels with advancing tumor stage, whereas EpCAM expression declined in advanced-stage tumors. TROP2 and TF expression were significantly elevated in higher-grade tumors. Additionally, EGFR and EpCAM levels were significantly higher in patients with elevated Ki-67 indices. Binding specificity assays using single-chain variable fragment (scFv-SNAP) fusion proteins confirmed robust targeting efficacy, particularly for EGFR and TROP2. These findings underscore the therapeutic relevance of EGFR and TROP2 as potential biomarkers and targets in TNBC. Full article
(This article belongs to the Section Molecular Pathology, Diagnostics, and Therapeutics)
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68 pages, 2838 KiB  
Review
Unravelling the Viral Hypothesis of Schizophrenia: A Comprehensive Review of Mechanisms and Evidence
by Mădălina Georgeta Sighencea and Simona Corina Trifu
Int. J. Mol. Sci. 2025, 26(15), 7429; https://doi.org/10.3390/ijms26157429 - 1 Aug 2025
Viewed by 374
Abstract
Schizophrenia is a challenging multifactorial neuropsychiatric disease that involves interactions between genetic susceptibility and environmental insults. Increasing evidence implicates viral infections as significant environmental contributors, particularly during sensitive neurodevelopmental periods. This review synthesises current findings on the viral hypothesis of schizophrenia, encompassing a [...] Read more.
Schizophrenia is a challenging multifactorial neuropsychiatric disease that involves interactions between genetic susceptibility and environmental insults. Increasing evidence implicates viral infections as significant environmental contributors, particularly during sensitive neurodevelopmental periods. This review synthesises current findings on the viral hypothesis of schizophrenia, encompassing a wide array of neurotropic viruses, including influenza viruses, herpesviruses (HSV-1 and 2, CMV, VZV, EBV, HHV-6 and 8), hepatitis B and C viruses, HIV, HERVs, HTLV, Zika virus, BoDV, coronaviruses (including SARS-CoV-2), and others. These pathogens can contribute to schizophrenia through mechanisms such as direct microinvasion, persistent central nervous system infection, immune-mediated neuroinflammation, molecular mimicry, and the disturbance of the blood–brain barrier. Prenatal exposure to viral infections can trigger maternal immune activation, resulting in cytokine-mediated alterations in the neurological development of the foetus that persist into adulthood. Genetic studies highlight the role of immune-related loci, including major histocompatibility complex polymorphisms, in modulating susceptibility to infection and neurodevelopmental outcomes. Clinical data also support the “mild encephalitis” hypothesis, suggesting that a subset of schizophrenia cases involve low-grade chronic neuroinflammation. Although antipsychotics have some immunomodulatory effects, adjunctive anti-inflammatory therapies show promise, particularly in treatment-resistant cases. Despite compelling associations, pathogen-specific links remain inconsistent, emphasising the need for longitudinal studies and integrative approaches such as viromics to unravel causal relationships. This review supports a “multi-hit” model in which viral infections interfere with hereditary and immunological susceptibilities, enhancing schizophrenia risk. Elucidating these virus–immune–brain interactions may facilitate the discovery of biomarkers, targeted prevention, and novel therapeutic strategies for schizophrenia. Full article
(This article belongs to the Special Issue Schizophrenia: From Molecular Mechanism to Therapy)
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