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Biopsies are only performed in less than 1% of all consultations dedicated to paediatric genital dermatology. The objectives of this paper are to review and clarify the histopathological features of the conditions most often biopsied: first, lichen sclerosus, which has a peak incidence in childhood and progresses over years; secondly, pigmented lesions, including atypical genital naevi and common naevi in the context of lichen sclerosus, both histologically differential diagnoses of melanoma, which probably does not present in childhood. And finally, Crohn’s disease, which is a cause of vulval oedema or genital ulceration. Full article

Objectives: To clarify the characteristics of Basosquamous cell carcinoma (BSC), this study compares demographic, clinical, therapeutic, histological, and outcome findings of BSCs with those of basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). Methods: The authors classified various definitions of BSC into three groups: the broadest, modest, and narrowest definitions. This study adopted the narrowest definition (both BCC and SCC features with transition zones in between) due to its wide use, its adoption by the World Health Organization, and the least heterogeneous definition. From 2009 to 2018, 20 consecutive cases of BSC presented in a single institution, along with 130 cases of BCC and 81 cases of SCC. Results: The statistically different parameters of BSC compared to BCC or SCC were age (SCC > BSC, BCC), duration (BSC, BCC > SCC), unclear border (BSC > BCC, SCC), higher NCCN classification (BSC, SCC > BCC), safety margin (SCC > BSC > BCC), operation time (BSC, SCC > BCC), reconstruction (less primary closure in BSC than BCC), microscopic size (BSC, SCC > BCC), perineural invasion (BSC > BCC), free lateral margin (BSC, SCC > BCC), and follow-up period (BSC > BCC, SCC). Regarding outcome, one distant metastasis (6.3%) in BSCs, no aggressive consequences in BCCs, and four local recurrences (11.1%), two lymph node metastases (5.6%), and one distant metastasis (2.7%) in SCCs were observed. Conclusions: In this Asian cohort, BSC has a trend toward higher rates of overall adverse outcomes compared to BCC, although this difference did not reach definitive statistical significance, unlike the findings reported in Caucasian populations. Early detection and appropriate treatment at the individual patient level are warranted to minimize rare but clinically relevant adverse events and reproduce favorable outcomes at the population level. Wide local excision followed by local flaps could be a successful surgical option with an adequate safety margin and double histopathologic intraoperative and postoperative check-up. Full article

Objective: This prospective study investigated the use of H-scan ultrasound (US) imaging as a novel component of a multiparametric radiomic analysis framework for characterizing human breast cancer response to neoadjuvant chemotherapy (NAC) before and early after treatment initiation. Methods: Thirty breast cancer patients scheduled for NAC were scanned using a clinical US system (Logiq E9, GE HealthCare) equipped with a 9L-D linear array transducer. Radiofrequency (RF) data was obtained at baseline (pre-NAC) and after 10% and 30% of the complete dose of chemotherapy. The RF data was analyzed by a bank of 256 frequency-shifted bandpass filters to form H-scan US frequency images. Grayscale texture features were extracted from both B-scan and H-scan US images. In addition, US attenuation coefficient and speckle statistics based on the Nakagami and Burr distributions were estimated from the RF data. Data classification of tumor and peri-tumoral regions was performed using a novel three-dimensional (3D) score map based on support vector machine (SVM) modeling. Unlike conventional classifiers that report only a single prediction score, a 3D score map provides a visual representation of the classifier decision space, enabling interpretation of class separation and treatment-induced shifts in multiparametric US measurements. Results: The dataset was split into 10 disjoint partitions (90% training, 10% testing) to compute area under the receiver operating characteristic curve (AUC), sensitivity, specificity, and accuracy measures. Actual patient response to NAC was assessed at surgery and categorized as either pathologic complete response (pCR) or non-pCR. Multiparametric US and data classification results at pre-NAC found AUC values of 0.78 after using only tumor information (p < 0.01), which increased to 0.81 with inclusion of peri-tumoral information (p < 0.01). Significant differences in multiparametric US measures from both cancer response types was found after integration of patient data collected at 10% completion of the NAC regimen (i.e., first NAC cycle), yielding an improved AUC of 0.86 (p < 0.001). Conclusions: Multiparametric US imaging with radiomic features from both the tumor and peri-tumoral regions is a promising noninvasive approach for monitoring early breast cancer response to NAC. Full article

Heart failure (HF) prognosis, particularly readmission and mortality, remains poor irrespective of advances in its management. Growth differentiation factor-15 (GDF-15) is a member of the transforming growth factor-beta (TGF-β) superfamily that arises as a promising biomarker to improve HF management, still despite two decades of extensive investigation some issues remain controversial. We performed a search in PubMed using the following Medical Subject Headings (MeSH) to identify relevant studies published in the last five years (after the latest updates of the guidelines by major Scientific Societies): “Growth differentiation factor-15 (GDF-15)”, “heart failure”, “prognosis” and “diagnosis”. The search was supplemented by data previous to this period, considered of utmost importance. A total of 115 articles written in English were retrieved. Extensive evidence supports GDF-15 as an independent predictor of adverse outcomes across the heterogeneous HF spectrum and its addition to risk scores based on traditional biomarkers improves prognostic power. However, limited tissue specificity restricts its diagnostic value. Tailored treatment strategies and its role as a therapeutic target remain speculative, as the effect of HF therapies on GDF-15 levels is unclear and clinical trials have been unsuccessful. Large prospective studies are needed to validate its reliability for routine clinical use. Full article

Background/Objectives: Thyroid cancer (TC) is among the most common endocrine malignancies, with incidence rates increasing worldwide. However, careful inferential analysis based on refined data is needed to provide a sharper clinical and epidemiological description of this serious condition in a biologically and technologically evolving society. This study presents an exploratory statistical analysis of data from 1470 patients who underwent thyroid surgery for differentiated TC. Methods: The analysis combines bivariate exploration of associations between variables with univariate and multivariate analyses stratified by histological subtype. We examined pathological characteristics (tumor location, nodal metastases, distant metastases, margin involvement, lymphovascular invasion, vascular invasion, and perineural invasion), clinical characteristics (clinical stage), biochemical markers (thyroglobulin, anti-thyroglobulin antibodies, and thyroid-stimulating hormone), and demographic variables (sex assigned at birth and age). In addition, exploratory multivariable models were used to investigate factors associated with lymph node metastasis and margin involvement in papillary microcarcinoma, the diffuse sclerosing variant, and the classical variant of papillary thyroid carcinoma. Results: Notably, moderate to high effect size correlations highlight the interdependence of invasive histopathological features in thyroid cancer and their collective link to adverse surgical outcomes and prognosis. Conclusions: This study provides an analysis of associations between the variables and subtype-specific descriptive estimates, serving as a foundation for future work in tailoring personalized medicine. Full article

Objectives: Prostate cancer is the most frequently diagnosed cancer among men, with Latino patients experiencing higher cancer-specific mortality compared to non-Hispanic populations. We evaluated prostate cancer outcomes across distinct Latino subpopulations. Methods: We retrospectively reviewed a single tertiary comprehensive cancer center database of patients with localized prostate cancer treated with radical prostatectomy from 2003 through 2020. Latino patients were subcategorized as Mexican, South/Central American (SCA), or Caribbean (Puerto Rico and Cuba). Non-Hispanic White (NHW) patients served as the reference group. Results: Overall, 7084 patients were included, of which 78% (n = 5518) were NHW and 10% (n = 679) were Latinos. Compared to NHW, Latino patients were younger at the time of surgery (median 62 vs. 64 years) and had higher median BMI (median 28.8 vs. 27.5 kg/m²), median baseline PSA (6.2 vs. 5.5 ng/mL), and D’Amico intermediate- (44% vs. 42%) and high-risk disease rates (16% vs. 13%) (all p < 0.001). Among Latino patients, Mexican patients had higher median baseline PSA (6.7 vs. 6.1 vs. 6.1 ng/mL, p = 0.005) compared to SCA and Caribbean patients. Survival analysis revealed shorter 5-year (97% vs. 99%) and 10-year (89% vs. 96%) overall survival (OS) rates in Mexican Latinos compared to non-Mexican Latinos (both p < 0.05). The 5-year (77% vs. 80% vs. 95%) and 10-year (63% vs. 65% vs. 86%) biochemical recurrence-free survival rates were shorter for Mexican patients compared to SCA and Caribbean patients. On multivariable analysis, SCA subpopulation status was associated with significantly better OS, and pathologic T stage > T2 was associated with worse OS. Conclusions: We identified significant differences in prostate cancer outcomes for different Latino subpopulations, underscoring the importance of population disaggregation in this ethnic group. Full article

Background: Acute myeloid leukemia (AML) with CBFB::MYH11 fusion and myeloid/lymphoid neoplasms with eosinophilia and tyrosine kinase gene fusions (MLN-TK) are genetically defined and typically mutually exclusive entities. Case Presentation: We report a unique case of de novo AML harboring two clonal, transcriptionally active class-defining fusions: CBFB::MYH11 and GOLGA4::PDGFRB. A 61-year-old woman presented with leukocytosis with neutrophilia, eosinophilia, and monocytosis; circulating blasts; and a markedly hypercellular marrow. Cytogenetic analysis revealed inv(16)(p13.1q22) and t(3;5)(p21;q32) in all 20 metaphases, and RNA sequencing confirmed expression of both CBFB::MYH11 and GOLGA4::PDGFRB fusions. In addition, an oncogenic WT1 frameshift variant was identified. Hematopathologic findings were largely consistent with AML with CBFB::MYH11 fusion but exhibited features reminiscent of PDGFRB-rearranged MLN-TK. The patient achieved complete remission following the standard 7 + 3 induction chemotherapy regimen for AML with gemtuzumab ozogamicin. Conclusions: This case illustrates the diagnostic challenges posed by concomitant class-defining alterations in hematologic neoplasms and underscores the importance of integrated genomic assessment. Full article

Feline immunodeficiency virus (FIV) is a lentivirus that exhibits significant structural and pathological similarities to human immunodeficiency virus (HIV), establishing it as a valuable model for HIV vaccine development. In this study, artificial intelligence (AI) and immunoinformatics were employed to design a novel multi-epitope DNA vaccine targeting conserved regions of the FIV gag, pol, and env genes. Predicted B-cell and T-cell epitopes were evaluated for their capacity to induce strong immune responses while minimizing allergenic or toxic effects and were linked to the immune adjuvant PADRE. Structural analysis indicated that the vaccine construct is stable, soluble, and biocompatible, with a well-folded tertiary structure that binds Toll-like receptor 9 (TLR9) and elicits robust humoral and cellular immune responses. These findings identify a promising FIV vaccine candidate and provide insights for the development of next-generation HIV vaccines. Full article

To address the limited accuracy of speech-based Alzheimer’s Disease (AD) screening and the shortage of paired multimodal data, this paper proposes a detection framework based on feature alignment and Rectified Flow-driven latent representation generation. The EEG dataset consists of 36 AD patients and 29 Healthy Controls (HC). The speech dataset contains 399 samples, which include 114 AD cases, 132 Mild Cognitive Impairment (MCI) cases, and 153 HC cases. We extracted multidimensional features of EEG signals, such as time-domain and frequency-domain characteristics, alongside behavioral representations of speech. A heterogeneous alignment network was used to map these features into a common semantic subspace, where an adaptive interpolation strategy reconstructed the missing pathological trajectories of MCI within the latent space. On this basis, a conditional Rectified Flow model was introduced to learn the optimal transport mapping from speech to EEG. This model generated physiological-information-rich latent representations to compensate for semantic gaps. Experimental results showed that the fused features from speech and latent representations achieved a three-class classification accuracy of 89.08%, a precision of 88.77%, and a recall of 88.71%. This performance represented an accuracy improvement of 9.28% compared with the speech-based baseline system. Our method combines the convenience of speech screening with the high reliability of neurophysiological signals, and it provides a new approach for low-cost early detection of AD. Full article

Advances in sequencing technologies have transformed human microbiome research, yet most analyses still rely on species-level profiles. However, strains rather than species represent the true ecological and functional units of the microbiome. Individual strains can vary substantially in gene content, metabolic capacity, virulence factors, antimicrobial resistance, and host-interaction properties. These differences critically influence immune responses, epithelial barrier integrity, disease susceptibility, and therapeutic outcomes. Here, we synthesize recent human microbiome studies that provide robust strain-resolved evidence, focusing on three major themes: (i) the emergence and long-term persistence of personalized strain repertoires, (ii) strain-specific pathobiont traits that drive host pathology, and (iii) the implications of strain-level ecology for the development of next-generation microbiome therapeutics. We also highlight key methodological innovations including high-resolution amplicon profiling, advanced metagenomic and single-cell genomics, and culture-based functional approaches that collectively enable strain-level resolution and are reshaping the field. Full article

Segmental mandibular resection may be indicated as a treatment in, for example, advanced stages of oral squamous cell carcinoma (OSCC). Osseous reconstruction of these defects is a fundamental part of static and dynamic masticatory rehabilitation, particularly when dental implants are required. The Segmental Mandibular Defect Reconstruction (SMDR) Registry aims to generate real-world evidence on SMDR through an international, prospective, multicentre case series designed as a registry. While OSCC is a common indication for segmental mandibular resection, the SMDR Registry also aims to capture outcomes for rarer mandibular conditions and the increasing number of collateral damage cases resulting from systemic medication therapies (antiresorptive drugs, immunotherapeutics) or irradiation, which may likewise lead to medication-related osteonecrosis of the mandible (MRONJ) or osteo(radio)necrosis with tumour-like segmental resection of the mandible, highlighting the value of an international database for these less frequent pathologies. Primary objectives are to describe the patient population and current treatment modalities, describe the outcomes and adverse events (AEs) for different treatment modalities, and identify potential predictors for successful autologous reconstruction of SMDs. Approximately 300 patients with a mandibular lesion resulting from bisphosphonate- and immunomodulatory drug-induced osteonecrosis of the mandible, ameloblastoma or osteosarcoma of the mandible, oral metastases related mandibular lesions indicated for segmental resection, or OSCC undergoing SMDR or intending to undergo one- or two-stage reconstruction will be prospectively recruited over a 36-month period. Baseline information, treatment details, and outcome measures will be documented. All treatments will be per the usual practice at participating sites. Outcome measures include clinical, patient-reported, and radiological outcomes; AEs related to the condition and/or treatment with a possible influence on the outcome will be recorded. Full article

Lupus nephritis (LN) is a severe complication of systemic lupus erythematosus (SLE), characterized by immune system disorders and multiple organ damage. Current clinical treatment of LN requires a complex multi-drug combination, which is often associated with severe side effects and low patient compliance. The aim of this study was to design a self-nanoemulsifying drug delivery system (SNEDDS) co-loading total glucosides of Paeonia (TGP) and dihydroartemisinin (DHA) to increase the solubility of the drug as well as achieve synergistic anti-inflammatory and immunomodulatory effects for LN therapy. Network pharmacology, molecular docking and molecular dynamics simulations were employed to predict the core therapeutic targets and related signaling pathways. The SNEDDS co-loaded with TGP and DHA was optimized via central composite design response surface methodology (CCD-RSM). Its physicochemical properties, particle size and the polydispersity index (PDI) of the optimized formulation were characterized. In vivo therapeutic efficacy was evaluated in MRL/lpr mice by measuring disease-related indicators (urinary protein, serum ANA, and anti-ds-DNA) and inflammatory cytokines (TNF-α, IL-6, and IL-1β). Renal tissue pathology was also examined. All data were analyzed by one-way analysis of variance (ANOVA) with p < 0.05 considered statistically significant. The core therapeutic targets predicted with high relevance were AKT1, MAPK1, MAPK3, and RELA. The optimized SNEDDS achieved a high loading capacity of 16.11 ± 0.43 mg/g for TGP and 12.79 ± 1.33 mg/g for DHA, with a particle size of (25.84 ± 0.30) nm and PDI of (0.07 ± 0.02). In MRL/lpr mice, SNEDDS treatment significantly reduced urinary protein levels (p < 0.01), serum ANA (p < 0.01) and anti-ds-DNA titers (p < 0.01) compared with the model group. Additionally, the levels of pro-inflammatory cytokines (TNF-α, IL-6, and IL-1β) were markedly decreased (p < 0.05), and renal tissue damage was alleviated. Conclusions: The SNEDDS co-loaded TGP and DHA is a promising oral nanotherapeutic strategy for LN, offering synergistic anti-inflammatory and immunomodulatory effects. Full article

Background: The progression of idiopathic pulmonary fibrosis (IPF) involves distal airway remodeling and bronchiolization; however, the mechanisms driving these changes, particularly the contributions of epithelial stem cells, are not fully understood. K13⁺ hillock cells, normally quiescent in proximal airways, were examined for their potential contribution to IPF pathogenesis. Methods: Spatial immunofluorescence was used to profile K13 expression along the airway axes in IPF and control lungs. Multiplex staining complemented by ex vivo culture assays was used to test expression stability. Single-cell RNA-sequencing (scRNA-seq) data were re-analyzed to identify cell subclusters and pathway enrichments. Meanwhile, cell–cell communication was inferred by using CellChat. Results: K13 was ectopically upregulated in IPF honeycomb cysts, triggering a proximal-like pseudostratified phenotype. This shift was marked by surges in K13⁺ regionally overlapping expression patterns (K5⁺, ~9%; CC10⁺, ~53%; ACE-TUB⁺, ~44%; MUC5AC⁺, ~23%) and a decline in SOX2 expression (~95% to ~64%), with ~70% of residual SOX2^low cells exhibiting elevated K13. Accompanying the expansion of K13⁺ subclusters (basal: 1.8% to 41.5%; club: 10.7% to 31.5%), it was observed that the profibrotic markers (K17, S100A2, LGALS7, IGFBP6) and ontologies related to RNA processing, stress response, and senescence were also enriched. These subclusters also amplified pro-fibrotic signaling (e.g., TGF-β, SEMA3, and GALECTIN-9) associated with epithelial subtypes and HAS1^high fibroblasts. Conclusions: Here, we demonstrate that K13⁺ cell activation is a pivotal event, driving the dysregulated proximalization of distal airways in IPF through fate reprogramming and epithelial-mesenchymal crosstalk. Thus, elucidating these K13-mediated fate dynamics provides a critical framework for understanding IPF pathogenesis. Full article

Background: Wax synthase/diacylglycerol acyltransferases (WS/DGATs), often referred to as WSD proteins, represent a class of key enzymes that catalyze the biosynthesis of wax esters in plants and other organisms. However, the WSD gene family in wheat (Triticum aestivum) has not been systematically characterized. Methods: A comprehensive genome-wide identification and bioinformatic characterization of the WSD gene family were conducted in wheat, followed by an analysis of chromosomal locations, gene structures, conserved motifs, phylogenetic relationships, expression profiles, and cis-element predictions. Results: In this study, a total of 43 TaWSDs were identified through genome-wide analysis in wheat. All identified TaWSD members exhibit highly conserved structural features and contain the core catalytic motif HHXXXDG. Phylogenetic analysis of WSD proteins from 63 species revealed that WSDs in Triticeae, including wheat, were mainly clustered into four distinct clades. Furthermore, sequence divergence among TaWSDs from different clades was primarily localized to the N-terminal region. Notably, expression profile analysis demonstrated that TaWSD genes display organ-specific expression patterns in wheat. Among them, 12 TaWSDs showed the highest expression levels in the leaf lamina joint, implying their potential involvement in the regulation of leaf angle formation. Additionally, 27 transcription factors were computationally predicted as putative regulators of TaWSDs, although their exact roles require further experimental confirmation. Conclusions: Our findings provide novel insights into the biological functions of the wheat WSD gene family and offer new perspectives for elucidating their molecular mechanisms underlying plant architecture regulation. Full article

Parasitic diseases involving invertebrate hosts, notably leishmaniasis (transmitted by sandflies) and schistosomiasis (transmitted via aquatic snails), remain public health concerns in China. Based on the Global Burden of Disease 2021 data, the age-standardized prevalence, mortality, and disability-adjusted life years (DALY) rates for both diseases declined significantly from 1990 to 2021. Men consistently experienced a higher burden than women. The age distribution of disease burden differed between the two conditions. Projections to 2036 suggest a continued decrease in schistosomiasis burden and in leishmaniasis mortality and DALYs, but a potential slight rise in leishmaniasis prevalence. Sustained control efforts have been effective, yet challenges persist due to demographic disparities, climate-related invertebrate host/intermediate host expansion, and imported cases. Future strategies require enhanced surveillance, targeted interventions, and multi-sectoral collaboration to advance toward elimination. Full article