Search Results (1,040)

Ovarian cancer remains a significant global health concern, and its diagnosis heavily relies on whole-slide images (WSIs). Due to their gigapixel spatial resolution, WSIs must be split into patches and are usually modeled via multi-instance learning (MIL). Although previous studies have achieved remarkable performance comparable to that of humans, in clinical practice WSIs are distributed across multiple hospitals with strict privacy restrictions, necessitating secure, efficient, and effective federated MIL. Moreover, heterogeneous data distributions across hospitals lead to model heterogeneity, requiring a framework flexible to both data and model variations. This paper introduces HFed-MIL, a heterogeneous federated MIL framework that leverages gradient-based attention distillation to tackle these challenges. Specifically, we extend the intuition of Grad-CAM to the patch level and propose Patch-CAM,which computes gradient-based attention scores for each patch embedding, enabling structural knowledge distillation without explicit attention modules while minimizing privacy leakage. Beyond conventional logit distillation, we designed a dual-level objective that enforces both class-level and structural-level consistency, preventing the vanishing effect of naive averaging and enhancing the discriminative power and interpretability of the global model. Importantly, Patch-CAM scores provide a balanced solution between privacy, efficiency, and heterogeneity: they contain sufficient information for effective distillation (with minimal membership inference risk, MIA AUC ≈ 0.6) while significantly reducing communication cost (0.32 MB per round), making HFed-MIL practical for real-world federated pathology. Extensive experiments on multiple cancer subtypes and cross-domain datasets (Camelyon16, BreakHis) demonstrate that HFed-MIL achieves state-of-the-art performance with enhanced robustness under heterogeneity conditions. Moreover, the global attention visualizations yield sharper and clinically meaningful heatmaps, offering pathologists transparent insights into model decisions. By jointly balancing privacy, efficiency, and interpretability, HFed-MIL improves the practicality and trustworthiness of deep learning for ovarian cancer WSI analysis, thereby increasing its clinical significance. Full article

Background: Hormone receptor-positive (HR+), HER2− negative metastatic breast cancer (MBC) is the most common subtype of advanced breast cancer. Resistance to endocrine therapy often develops, particularly after CDK4/6 inhibitors. Everolimus, an mTOR inhibitor, may restore hormone sensitivity, but real-world data after CDK4/6 and chemotherapy are limited. Methods: This retrospective, single-center study included 70 patients with HR+/HER2− MBC who progressed on CDK4/6 inhibitors and at least one line of chemotherapy. All received daily oral everolimus (10 mg) plus exemestane (25 mg). Tumor response was assessed via RECIST v1.1, and survival outcomes were estimated using the Kaplan–Meier method. Results: Median progression-free survival was 6.6 months and overall survival was 22.6 months. The disease control rate was 88.6%, with 57.1% showing partial response. Fatigue (20%), skin toxicity (8.6%), and stomatitis (5.7%) were the most common adverse events. No grade 3–4 toxicities or discontinuations occurred. No clinical or pathological variables significantly influenced survival. Conclusions: Everolimus plus exemestane provided meaningful clinical benefit and manageable toxicity in heavily pretreated HR+/HER2− MBC patients. This regimen remains a valid later-line option, particularly in settings with limited access to newer targeted therapies or genomic testing. Full article

Yin Yang 1 (YY1) is a multifunctional transcription factor implicated in gene regulation, cell proliferation, and survival. While its role in breast cancer (BC) has been explored, its prognostic significance remains controversial. In this study, we evaluated nuclear YY1 expression in 276 BC tissue samples using immunohistochemistry (IHC), tissue microarrays (TMAs), and digital pathology (DP). Nuclear staining was quantified using Aperio ImageScope software, focusing on tumor regions to avoid confounding from stromal or non-tumor tissues. This selective and standardized approach enabled precise quantification of YY1 expression. Our results show elevated median YY1 expression in tumor vs. normal matched tissues (p < 0.001). The optimal cutoff for medium-intensity nuclear YY1 expression in tumor areas for overall survival (OS) was established by a receiver operating characteristic (ROC) curve (AUC = 0.718, 95% CI: 0.587–0.849, p = 0.008). In contrast, ROC curves showed no prognostic impact (AUC and p-value) for YY1 quantification in whole spots (tumor + normal). As a categorical variable, high YY1 expression was correlated with more aggressive BC features, including tumor size > 3 cm (57.7% vs. 44.2% p = 0.037), the triple-negative breast cancer (TNBC) molecular subtype (27.3% vs. 13.9% p = 0.026), and advanced prognostic stage (III) (31.8% vs. 16.7% p = 0.003), while as a continuous variable, YY1 was associated with higher histological (p = 0.003) and nuclear grades (p = 0.022). High YY1 expression was significantly associated with a reduced OS of BC patients, as shown by Kaplan–Meier curves (HR = 2.227, p = 0.002). Since YY1 was significantly enriched in TNBC, we evaluated its prognostic resolution in this subgroup. But, probably due to the small number of patients within this subset, our results were not statistically significant (HR = 1.317, 95% CI: 0.510–3.405, p = 0.566). Next, we performed multivariate Cox regression, confirming YY1 as an independent prognostic factor for overall survival (HR = 1.927, 95% CI: 1.144–3.247, p = 0.014). In order to improve prognostic value, we constructed a mathematical model derived from the multivariate Cox regression results, including YYI, AJCC prognostic stage (STA), and axillary lymph node dissection (ALN), with the following equation: h(t) = h₀(t) × exp (0.695 × YY1 + 1.103 × STA − 0.503 × ALN). ROC analysis of this model showed a better AUC of 0.915, similar sensitivity (83.3%), and much higher specificity (92%). Bioinformatic analysis of public datasets supported these findings in BC, showing YY1 overexpression in multiple cancer types and its association with poor outcomes in BC. These results suggest that YY1 may play a role in tumor progression and serve as a valuable prognostic biomarker in BC. DP combined with molecular data enhanced biomarker accuracy, supporting clinical applications of YY1 in routine diagnostics and personalized therapy. Additionally, developing a combined score based on the modeling of multiple prognostic factors significantly enhanced survival predictions, representing a practical tool for risk stratification and the guidance of therapeutic decisions. Full article

Background and Objectives: Cervical cancer (CC), primarily caused by human papillomavirus (HPV) infection, is the most common gynecological cancer and a leading cause of cancer-related death in women. The immune microenvironment, particularly CD4+ T-helper cells and FOXP3 (forkhead box P3)+ regulatory T cells (Tregs), plays a crucial role in tumor progression. However, the exact relationship between immune cell infiltration and clinical outcomes in CC is not fully understood. This study aimed to examine the association between CD4+ T-helper cells, FOXP3+ Tregs, and clinical/pathological parameters in CC patients. Methods: We conducted a retrospective analysis of 150 patients with T1-stage cervical cancers diagnosed between 2015 and 2021. Tumor samples were evaluated using immunohistochemistry (IHC) to assess CD4+ and FOXP3+ TILs in intratumoral and stromal regions. Additionally, deconvoluted transcriptomic data from the TCGA cohort were used to assess immune infiltration within the tumor immune microenvironment (TIME). Results: High infiltration of CD4+ T-helper cells was significantly associated with better overall survival (OS) in node-negative CC patients (p = 0.0006). However, no significant prognostic value was found for Tregs. CD4+ cells were more prevalent in patients with well-differentiated tumors (G1 and G2) and lower levels of CD4+ infiltration were found in squamous cell carcinoma (SCC) compared to other histological subtypes. Multivariate regression analysis showed that only tumor size (T1b3) and undifferentiated tumor morphology (G3) were significantly associated with poorer OS. In contrast, infiltration of CD4+ or FOXP3+ cells did not significantly correlate with OS after adjusting for clinical factors. Competing risk analysis for death from cancer showed no significant associations with immune cell infiltration levels. Conclusions: This study underscores the complex relationship between immune cell infiltration and clinical outcomes in CC. While CD4+ T-helper cell infiltration is associated with improved prognosis in node-negative cases, further research is necessary to clarify the role of Tregs and other immune components in the tumor microenvironment. These findings suggest potential avenues for therapeutic strategies, including immune checkpoint inhibitors, in CC. Full article

The current classification of Hodgkin lymphoma (HL) is the result of an integrated approach that combines the evaluation of morphological patterns, immunophenotypic characteristics, molecular features, and clinical presentation. Evolving from its origins based solely on histological observation to the latest updates in the WHO 5th Edition, this system has become an essential tool for accurate diagnosis and personalized therapeutic strategies. Each subtype of classic HL (cHL)—nodular sclerosis, mixed cellularity, lymphocyte-rich, and lymphocyte-depleted—exhibits distinctive pathological and clinical features, now better understood through multidisciplinary studies and international collaborations. HL also includes nodular lymphocyte-predominant HL (NLPHL), a distinct entity with unique morphologic, immunophenotypic, and clinical features. A hallmark morphological feature of cHL is the presence of Hodgkin and Reed-Sternberg (HRS) cells, large and often multinucleated cells derived from B lymphocytes that have lost their typical B-cell phenotype. Identifying these cells is critical for diagnosis and for differentiating HL from other hematologic malignancies. HL is characterized by the rarity of malignant cells, a high curability rate, and a rich immune cell microenvironment that is both shaped and exploited by the tumor. Understanding these core aspects paves the way for exploring the role of immunologic and genetic biomarkers in refining classification, enhancing diagnosis, improving prognostic assessment, and guiding therapy for patients with cHL. Full article

Congenital heart disease (CHD) is associated with neurodevelopmental and cognitive impairments, but the underlying molecular mechanisms remain unclear. This study investigated cardiac neuronal genomics in CHD using single-nucleus RNA-sequencing data (GSE203274) from 157,273 cardiac nuclei of healthy donors and patients with hypoplastic left heart syndrome (HLHS), Tetralogy of Fallot (TOF), dilated (DCM), and hypertrophic (HCM) cardiomyopathies. The Uniform Manifold Approximation and Projection (UMAP) clustering identified major cardiac cell types, revealing neuron-specific transcriptional programmes. Neuronal populations showed enriched expression of neurodevelopmental disorder-linked genes (NRXN3, CADM2, ZNF536) and synaptic signalling pathways. CHD cardiac neurons exhibited upregulated markers of cognitive dysfunction (APP, SNCA, BDNF) and neurodevelopment regulators (DNMT1, HCFC1) across subtypes. Cardiomyocyte troponin elevation correlated with neuronal exosome receptor expression (TLR2, LRP1), suggesting intercellular communication. Gene ontology analysis highlighted overlaps between cardiovascular disease pathways and neurodevelopmental disorder signatures in CHD neurons. These findings provide the first neuro-genomic map of cardiac neurons in CHD, linking cardiac pathology to neural outcomes through transcriptional dysregulation. Further, the systemic analysis of clinical findings in CHD further supports the risk of neurodevelopmental impacts. In summary, this study identifies transcriptional dysregulation within cardiac neurons in CHD and, together with a systemic analysis of clinical data, provides molecular evidence linking cardiac pathology to neurodevelopmental and cognitive impairments. Full article

Acute ischemic stroke (AIS) is one of the leading global causes of mortality and morbidity. Clearer understanding of stroke etiology is a major clinical objective to determine appropriate strategies for secondary stroke prevention. Histological and molecular analysis of clots retrieved during mechanical thrombectomy (MT) in AIS offers a unique opportunity to study clot composition and its relation to stroke etiology. The field of clot composition analysis has undergone substantial growth in recent years, driven in part by the establishment of MT as the standard of care, as well as its expanding indications. Although many features differ between large-artery atherosclerosis (LAA) and cardioembolic (CE) clots, application of these findings to predicting stroke etiology at a clinical level remains challenging. Moreover, a significant number of patients have multiple comorbidities or suffer a cryptogenic subtype. Next-generation techniques such as multiomic sequencing offer a powerful potential to elevate our understanding of clot pathology and provide the level of granularity required for clinical diagnosis and management. Herein, we provide an updated review of the current state of the field by exploring stroke etiologies and their relationship to clot pathology, including classic histologic features as well as more recent, emerging results from proteomic and transcriptomic analyses. Full article

Background and Objectives: Lung cancer (LC) remains a significant global health issue with poor prognosis. The COVID-19 pandemic has caused delays in cancer patient management worldwide. However, its impact on the incidence of LCs in Romania has not yet been discussed. We aimed to evaluate the impact of lockdown restrictions during the COVID-19 pandemic on new LC diagnoses in a Romanian cohort and the potential associations between demographic characteristics and histological features. Materials and Methods: This retrospective study analyzed 750 patients with lung tumors diagnosed in the Pathology Department, Mureș County Clinical Hospital, Romania, between 2018 and 2022. The target population was divided in two cohorts: pre-COVID-19 (1 January 2018–15 March 2020) and COVID-19 (16 March 2020–31 December 2022). Results: The temporal trend of LC diagnosis followed a descending pattern over the study period, with a significant 72% reduction (p < 0.001) in the first year of the COVID-19 pandemic (2020 vs. 2019). In terms of histology, several subtypes displayed a notable reduction in the COVID-19 cohort compared to the pre-pandemic period: squamous carcinoma (SQC) (p < 0.001), adenocarcinoma (ADK) (p < 0.001), and lung metastases (p = 0.0008). On the other hand, cases of non-small-cell lung carcinomas not otherwise specified (NSCLCs NOS) experienced a significant increase in the pandemic years (p = 0.0406). SQC was the most frequent subtype of LC and was significantly more frequent in men (p < 0.001, RR = 1.3004, 95% CI [1.1786–1.4347]). Furthermore, a notable shift in the male-to-female ratio was observed between the two cohorts, caused by a larger decrease in the incidence of LC among men compared to females in the COVID-19 period (p = 0.0002; pre-COVID-19 M/F = 4/1 versus COVID-19 M/F = 2/1). Conclusions: COVID-19-related restrictions led to a significant drop in new LC diagnoses during the first year of the pandemic, which was followed by a slight upward trend in the subsequent years. Additionally, the sharp decline in the number of cases among men narrowed the gender gap in LC patients. Full article

Background and Objectives: To investigate the clinical significance of adipokines’ [leptin, leptin receptor (leptin-R), adiponectin, and resistin] expression on the characteristics and survival outcomes of patients with renal cell carcinoma (RCC). Materials and Methods: A total of 81 patients were included. The expressions of adipokines in the nephrectomy material of the patients were assessed using immunohistochemistry. Staining patterns were divided into two groups for statistical analyses: negative (no staining) and positive. Univariable and multivariable Cox regression models were used to evaluate the impact of the expression of adipokines on the survival outcomes of the patients. Results: The percentages of patients expressing leptin, leptin-R, adiponectin, and resistin were 36.4%, 30.7%, 32%, and 60.2%, respectively. The median overall survival (OS) of all patients was 53.7 months (95% confidence interval [CI]: 39.9–67.5). In the multivariate analyses, only leptin expression status was associated with OS among adipokines (hazard ratio [HR]: 1.98, 95%CI: 1.03–3.78, p = 0.039) in addition to the presence of distant metastasis (HR: 2.48, 95%CI: 1.16–5.29, p = 0.018). No significant associations were determined between adipokine expression and pathologic determinants of RCC, including tumor stage, grade, and histological subtype. Conclusions: Our study demonstrated that leptin expression was an independent prognostic factor for inferior OS in RCC patients treated with nephrectomy, even after adjusting for disease stage in multivariate analysis. Full article

Background: Functional Neurological Disorder (FND) encompasses conditions with neurological symptoms inconsistent with structural pathology, arising instead from complex interactions between psychological, biological, and social factors. Despite growing research, the etiological and risk factor landscape remains only partially understood, complicating diagnosis and treatment. Objective: This systematic review maps risk factors for major FND subtypes such as functional seizures (psychogenic non-epileptic seizures or PNES), functional cognitive disorder (FCD), functional movement disorders (FMD), functional weakness and sensory disturbances, functional visual symptoms, and functional gait abnormalities by categorizing predisposing, precipitating, and perpetuating influences. Methods: A systematic search of PubMed, PsycINFO, Scopus, and Web of Science initially identified 245 records. After removal of 64 duplicates, 181 studies were screened by title and abstract. Of these, 96 full texts were examined in detail, and finally 23 studies met the predefined inclusion criteria. Data were extracted and analyzed thematically within a biopsychosocial framework, with results summarized in subtype-specific profiles. Results: Childhood adversity, especially emotional, physical, or sexual abuse, emerged as a robust and consistent predisposing factor across PNES cohorts. Psychiatric history (notably anxiety, depression, and PTSD), neurodevelopmental traits (more frequent in FCD), and personality patterns such as alexithymia and somatization also contributed to vulnerability. Precipitating influences included acute psychological stress, intrapersonal conflict, or concurrent medical illness. Perpetuating factors comprise maladaptive illness beliefs, avoidance behaviors, insufficient explanation or validation by healthcare providers, and secondary gains related to disability. While several risk factors were shared across subtypes, others appeared subtype-specific (trauma was especially associated with PNES, whereas neurodevelopmental traits were more characteristic of FCD). Conclusions: FND arises from a dynamic interplay of predisposing, precipitating, and perpetuating factors, with both shared and subtype-specific influences. Recognizing this heterogeneity can enhance diagnostic precision, guide tailored intervention, and inform future research into the neurobiological and psychosocial mechanisms underlying FND. Full article

Background and Objectives: Breast cancer is a leading cause of cancer-related mortality, particularly in aggressive subtypes such as HER2-positive and triple-negative breast cancer (TNBC). Achieving a pathological complete response (pCR) after neoadjuvant therapy is strongly associated with improved survival outcomes in these subgroups, making the prediction of pCR a clinical priority. Sarcopenia, a progressive loss of skeletal muscle mass and strength, is increasingly recognized in cancer patients and has been linked to chemotherapy toxicity and poorer survival. However, its specific impact on pCR in HER2-positive and TNBC patients remains unclear. This study aimed to evaluate the association between radiologically defined sarcopenia, or a low skeletal muscle index (SMI), and pathological response in these subtypes, and to explore its potential as a predictive biomarker. Materials and Methods: This retrospective study included patients with HER2-positive or TNBC who received neoadjuvant therapy between January 2015 and October 2023. SMI was assessed using pre-treatment positron emission tomography images at the L3 vertebral level, with values < 38.5 cm²/m² considered as low. Univariate and multivariate logistic regression analyses were performed to identify factors associated with pCR. Results: A total of 85 patients were included, with low SMI present in 35 (41.2%). In univariate analysis, clinical stage and low SMI were associated with pCR. However, in the multivariate model, only low SMI remained an independent predictor. Patients without low SMI had higher odds of achieving pCR (odds ratio [OR] 4.13; 95% confidence interval [CI] 1.55–10.95; p = 0.004). Low SMI was also associated with higher rates of treatment-related toxicity (42.9% vs. 20.0%, p = 0.023). Conclusions: Pre-treatment low SMI is strongly associated with lower pCR rates in patients with HER2-positive and TNBC undergoing neoadjuvant therapy. These findings underscore the importance of early identification and management of radiologically defined sarcopenia to optimize treatment response and improve clinical outcomes. Full article

Background: Anemia is a common comorbidity in heart failure (HF) and has been associated with adverse clinical consequences. This retrospective, descriptive cohort study examined phenotype-specific differences in anemia severity, clinical presentation, comorbid burden, and in-hospital management across HF subtypes classified by left ventricular ejection fraction (LVEF). Methods: We retrospectively analyzed 443 adult patients hospitalized with concurrent HF and anemia from January 2022 to December 2024. Patients were stratified by LVEF into HFrEF (<40%), HFmrEF (40–49%), and HFpEF (≥50%). All patients included met WHO criteria for anemia. Demographic, clinical, paraclinical, and therapeutic data were extracted, and descriptive statistical methods were used to evaluate intergroup differences. No formal time-to-event analyses (e.g., Kaplan–Meier curves) were performed; instead, exploratory cumulative readmission analyses using fixed follow-up windows were conducted. In-hospital mortality was recorded and stratified by HF phenotype. Results: The cohort comprised 213 (48.0%) HFrEF, 118 (26.6%) HFmrEF, and 112 (25.3%) HFpEF patients. The distribution of anemia severity, management strategies, and comorbidity profiles varied significantly across phenotypes. Severe anemia predominated in the HFmrEF cohort (54.2%), whereas mild anemia was most common in HFpEF (52.1%) and HFrEF (52.1%). Mean hemoglobin concentrations were 8.39 ± 1.79 g/dL (HFmrEF), 9.07 ± 2.47 g/dL (HFpEF), and 8.62 ± 1.94 g/dL (HFrEF). Rates of atrial fibrillation (48.2% in HFpEF), hypertensive ECG changes (63.4% in HFpEF), and ischemic-lesion patterns (>50% in HFrEF) differed by cohort. Echocardiographically, grade III mitral regurgitation and severe pulmonary hypertension each affected 25.4% of HFmrEF patients, whereas HFpEF patients most often exhibited grade II mitral regurgitation (42.9%) and moderate pulmonary hypertension (42.9%). HFrEF patients had severe pulmonary hypertension. Intravenous (IV) iron was the primary treatment modality, with highest utilization in HFmrEF. IV iron use ranged from 69.9% (HFrEF) to 84.8% (HFmrEF), with transfusion rates of 5.6% (HFrEF)–16.1% (HFpEF). Comorbid burdens differed by phenotype: HFrEF was associated with structural heart disease, HFmrEF with vascular and hepatic pathology, and HFpEF with metabolic and degenerative comorbidities. Discharge pharmacotherapy reflected phenotype-specific treatment patterns. Conclusions: This real-world descriptive analysis highlights substantial variation in anemia burden and management across the HF spectrum. While limited to descriptive findings, our analysis highlights the heterogeneity of anemia in HF and describes observed associations across phenotypes, without implying causality. These findings should be interpreted as hypothesis-generating. These findings are observational, exploratory, and cannot establish a causal relationship between intravenous iron use and survival. Full article

Background: Mucopolysaccharidoses (MPSs) are rare lysosomal storage disorders characterized by multisystem involvement; notably, skeletal abnormalities known as dysostosis multiplex and varying degrees of central nervous system impairment. Accurate radiological evaluation is crucial for accurate diagnosis and effective planning. This study aims to describe the clinical and radiological features of patients with MPS managed at our tertiary care center. Methods: We retrospectively reviewed clinical and radiological data from eight patients with confirmed MPS treated at S. Orsola University Hospital (Bologna, Italy) since 2000. Imaging included conventional radiography, supplemented by MRI and CT. The findings were analyzed by MPS subtype and correlated with clinical evolution and therapeutic interventions. A literature review complemented the analysis. Results: The cohort included one patient with MPS I, two with MPS II, one with MPS III, and four with MPS IV. Common skeletal findings were vertebral deformities, hip dysplasia, and shortening of long bones. Patients with MPS IV showed the most severe bone involvement, including pronounced platyspondyly and odontoid hypoplasia. Follow-up imaging demonstrated progression of bone and CNS pathology despite enzyme replacement therapy (ERT). Conclusions: Our findings underscore the pivotal role of imaging in MPS management. Tailored radiological protocols and multidisciplinary care are crucial for optimizing diagnosis and monitoring disease progression. Full article

Background/Objectives: This study aimed to evaluate the diagnostic performance of simplified intravoxel incoherent motion (IVIM) diffusion-weighted imaging (DWI) parameters in distinguishing malignant from benign breast lesions, and to explore their association with clinicopathological features. Methods: This retrospective study included 108 women who underwent breast MRI with multi-b-value DWI (0, 20, 200, 500, 800 s/mm²). Of those 108 women, 73 had pathologically confirmed malignant lesions. IVIM maps (ADC_map, D, D*, and perfusion fraction f) were generated using IB-Diffusion™ software version 21.12. Lesions were manually segmented by radiologists, and clinicopathological data including receptor status, Ki-67 index, cancer type, histologic grade, and molecular subtype were extracted from medical records. Nonparametric tests and ROC analysis were used to assess group differences and diagnostic performance. Additionally, a binary logistic regression model combining D, D*, and f was developed to evaluate their joint diagnostic utility, with ROC analysis applied to the model’s predicted probabilities. Results: Malignant lesions demonstrated significantly lower diffusion parameters compared to benign lesions, including ADC_map (p = 0.004), D (p = 0.009), and D* (p = 0.016), indicating restricted diffusion in cancerous tissue. In contrast, the perfusion fraction (f) did not show a significant difference (p = 0.202). ROC analysis revealed moderate diagnostic accuracy for ADC_map (AUC = 0.671), D (AUC = 0.657), and D* (AUC = 0.644), while f showed poor discrimination (AUC = 0.576, p = 0.186). A combined logistic regression model using D, D*, and f significantly improved diagnostic performance, achieving an AUC of 0.725 (p < 0.001), with 67.1% sensitivity and 74.3% specificity. ADC_map achieved the highest sensitivity (100%) but had low specificity (11.4%). Among clinicopathological features, only histologic grade was significantly associated with IVIM metrics, with higher-grade tumors showing lower ADC_map and D* values (p = 0.042 and p = 0.046, respectively). No significant associations were found between IVIM parameters and ER, PR, HER2 status, Ki-67 index, cancer type, or molecular subtype. Conclusions: Simplified IVIM DWI offers moderate accuracy in distinguishing malignant from benign breast lesions, with diffusion-related parameters (ADC_map, D, D*) showing the strongest diagnostic value. Incorporating D, D*, and f into a combined model enhanced diagnostic performance compared to individual IVIM metrics, supporting the potential of multivariate IVIM analysis in breast lesion characterization. Tumor grade was the only clinicopathological feature consistently associated with diffusion metrics, suggesting that IVIM may reflect underlying tumor differentiation but has limited utility for molecular subtype classification. Full article

Background: Alternative splicing is an important mechanism of transcriptomic and proteomic diversity and is progressively involved in cardiovascular disease (CVD) pathogenesis. Serum response factor (SRF), a critical transcription factor in cardiac development and function, may itself undergo splicing regulation, potentially altering its function in disease states. Objective: The objective of this study is to identify SRF-associated alternative splicing events in cardiac pathological conditions and examine regulatory interactions with splicing factors using RNA-seq data. Methods: Three human heart RNA-seq databases (PRJNA198165, PRJNA477855, PRJNA678360) were used, comprising various cardiac conditions like non-ischemic cardiomyopathy (NICM), ischemic cardiomyopathy (ICM), dilated cardiomyopathy (DCM), and heart failure with reduced ejection fraction (HFrEF), with and without left ventricular assist device (LVAD) support. Splicing events were identified using the rMATS tool, and correlation analyses were performed between SRF and predicted splicing factors. Functional enrichment of SRF-correlated genes was assessed via Gene Ontology (GO) and KEGG pathways. Results: The skipped exon (SE) events were the predominant splicing type across all datasets. SRF chr6, including (Exon 2, 43,173,847–43,174,113), (Exon 4, 43,176,548–43,176,667), and (Exon 5, 43,178,294-43,178,485), were most frequently involved in SE and mutually exclusive exon (MXE) events across multiple heart failure subtypes. Correlation analysis revealed strong positive associations between SRF and several splicing factors (HNRNPL, HNRNPD, SRSF5, and SRSF8). GO and KEGG analyses revealed enrichment of muscle development, sarcomere structure, lipid metabolism, and immune signaling pathways. Conclusions: Our study shows that SRF is subject to extensive alternative splicing in heart failure, particularly at Exon 2 and Exon 5, suggesting isoform-specific roles in cardiac remodeling. The strong co-expression with specific splicing factors delineates a regulatory axis that may explain the pathological transcriptome in cardiomyopathy. These findings provide a foundation for exploring splicing-based biomarkers and therapeutic targets in cardiac pathology for SRF. Full article