• Limbus-Sparing Congenital Central Corneal Dermoid: A Rare Developmental Anomaly.
    2 weeks ago
    The authors report a rare case of a limbus-sparing central corneal dermoid in a 1-year-old boy, contributing to the limited existing literature of only three such documented cases worldwide. This case report describes the clinical presentation, surgical management, and histopathologic characteristics of this unique developmental anomaly. A comprehensive clinical evaluation was conducted, including ophthalmic examination, B-scan ultrasonography, and surgical intervention. The dermoid was excised along with penetrating keratoplasty, with the excised specimen undergoing detailed histopathologic and immunohistochemical analysis. Immunohistochemical markers including smooth muscle actin, CD34, vimentin, and p63 were examined to characterize the tissue composition. The patient presented with a 7.5 × 7.5 mm yellowish-brown hemispherical mass occupying the central cornea while sparing the limbus. Surgical exploration revealed full-thickness corneal involvement with corneoirido-lenticular adhesions. Histopathologic analysis demonstrated stratified squamous epithelium with surface keratinization and fibrocollagenous thickening. Immunohistochemistry revealed unexpected positive staining for both epithelial (p63) and mesenchymal (SMA, CD34, vimentin) stem cell markers, challenging previous understanding of central corneal dermoid cellular origins. This case represents an exceptionally rare presentation of a limbus-sparing central corneal dermoid, highlighting the complex embryological mechanisms underlying such developmental anomalies. Although surgical intervention was performed for cosmetic rehabilitation, the guarded prognosis and potential for complications necessitate careful patient counseling and long-term follow-up.
    Cancer
    Care/Management
  • Establishment and characterization of three canine ameloblastoma cell lines with genomic and transcriptomic profiles.
    2 weeks ago
    Establishment of canine acanthomatous ameloblastoma (CAA) cell lines has profound importance in pre-clinical in vitro testing. The goal of this study was to develop, authenticate, and characterize three CAA cell lines. Cell lines were developed with standard cell culture techniques from dogs with naturally occurring CAA. Each cell line was authenticated as canine with a validated PCR panel. Epithelial cell origin was confirmed with pan-CK flow cytometry. Next generation DNA and RNA sequencing characterized features of the cell lines and compared them to the parent tumor. We confirmed that all cell lines maintained mutations seen in the parent tumors including a missense HRAS mutation and RTK-RAS pathway upregulation across all samples. Other common mutations (2/3 cell lines and their parent tumors) included ADGRA3, DNAH7, F10, KIAA1671, OGFR, SLC6A17, SNX7, SPTBN5, TENM4, and YEATS2. We compared the transcriptional profiles from our parent tumors and established cell lines to historical transcriptomic analysis of CAA and healthy gingiva. We confirmed the same canonical CAA molecular features of primary tumors across studies with distinct clustering from healthy gingiva. Further, we documented that the cell lines maintained upregulated genes that are seen within in vivo CAA across both studies including upregulated GPC4 and ETV5 as well as gene sets associated with the presence of epithelial-mesenchymal transformation, KRAS, Pi3K-AKT signaling, and hedgehog signaling pathways. Thorough characterization of the mutational and transcriptional profiles of the established cell lines, especially in context to how they differ from the parent tumors, sets the platform for translational in vitro testing.
    Cancer
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  • CDCA8 regulates ATP5F1A protein stability and malignant phenotypes in wilms tumor cells: Prognostic implications and mechanistic insights.
    2 weeks ago
    Wilms tumor (WT) is a prevalent pediatric renal malignancy, yet its molecular mechanisms remain poorly defined. Identifying key prognostic genes and understanding their functional roles is critical for improving clinical management. This study aimed to identify prognostic genes in WT and to investigate whether ATP5F1A functions as a candidate downstream effector in a CDCA8-associated regulatory axis.

    Differentially expressed genes (DEGs) were identified by analyzing RNA-seq datasets (GSE11151, GSE73209), comparing WT tissues with normal kidney samples. Functional enrichment was performed using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. A protein-protein interaction (PPI) network was constructed, and hub genes were identified using Cytoscape. Prognostic significance was assessed through univariate and multivariate Cox regression analyses, and a risk prediction model was developed. External expression validation of candidate hub genes was performed using GSE11024 and GSE110696. CDCA8's functional role in WT was validated by gene knockdown and overexpression experiments. Co-immunoprecipitation (Co-IP) and ubiquitination assays were conducted to explore the interaction between CDCA8 and ATP5F1A.

    A total of 987 DEGs were identified, with six hub genes-BUB1B, CDC45, CDCA8, KIF15, NDC80, and TOP2A-were identified. The exploratory risk score model stratified overall survival in the TARGET-WT cohort (HR = 2.973, Log-rank p = 0.000252), although time-dependent AUC values indicated modest discriminatory performance. CDCA8 was upregulated in WT tissues and associated with worse survival outcomes (HR = 2.03, p = 0.011). Functional assays suggested that CDCA8 knockdown suppressed malignant phenotypes in WiT49 cells. Mechanistically, CDCA8 knockdown reduced ATP5F1A protein levels without altering ATP5F1A mRNA expression, and this reduction was partially rescued by MG132. CDCA8 depletion was also associated with increased ATP5F1A ubiquitination, supporting a role for CDCA8 in maintaining ATP5F1A protein stability.

    These findings suggest that CDCA8 may contribute to Wilms tumor cell phenotypes partly by maintaining ATP5F1A protein stability, providing preliminary evidence for a CDCA8-ATP5F1A regulatory axis in WT.
    Cancer
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  • Unconventional functions of natural killer cells in homeostasis and disease.
    2 weeks ago
    NK cells are classically defined by their rapid cytotoxicity against tumor cells and infected cells and by early inflammatory cytokine production. However, unconventional roles for NK cells as regulators of immunity and tissue homeostasis have recently been uncovered. Beyond their classical roles, NK cells can orchestrate leukocyte trafficking, curtail responses of other immune cells, remove protein aggregates, support pregnancy, and contribute to healthy tissue regeneration. We discuss the importance of these myriad functional activities of NK cells in infection, cancer, autoimmunity, atopic and allergic disease, pregnancy, tissue injury, and neurodegenerative diseases. The functional pleiotropy of NK cells provides new avenues of translational utility for these innate lymphocytes and represents an unexplored complexity in conventional clinical applications of NK cells against infection and cancer.
    Cancer
    Care/Management
  • Malignant Odontogenic Tumors: A Clinicopathological Study of 53 Cases in Brazil.
    2 weeks ago
    This study aimed to investigate the clinicopathological features of malignant odontogenic tumors (MOTs) and to provide a comprehensive characterization that enhances the current understanding of this disease group.

    MOTs were retrieved from six Brazilian oral pathology services between 2007 and 2025. Demographic, clinical and radiographic data were collected from the charts, and the histological H&E-stained sections were revised by two blinded pathologists; previously available immunohistochemical and molecular findings were retrieved and reviewed in selected cases and the diagnosis was established according to the 2022 World Health Organization classification.

    A total of 53 malignant odontogenic tumors were identified, predominantly affecting the mandible (83%), with a slight male predominance (male-to-female ratio, 1.12:1) and a mean age of 41.4 years. Ameloblastic carcinoma was the most frequent subtype (58.5%), followed by clear cell odontogenic carcinoma (18.9%), ameloblastic fibrosarcoma (13.2%), primary intraosseous carcinoma (7.5%), and ghost cell odontogenic carcinoma (1.9%).

    This multicenter review summarizes the main features of malignant odontogenic tumors. Although rare, these tumors often exhibit locally aggressive behavior, highlighting the need for early diagnosis, accurate histopathological evaluation, and standardized reporting with long-term follow-up.
    Cancer
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  • Incidence of respiratory syncytial virus in adults ≥50 years during and following the COVID-19 pandemic in upper midwest USA: a community-based prospective cohort study.
    2 weeks ago
    Respiratory syncytial virus (RSV) is an important viral pathogen in children, older adults and adults with certain high-risk conditions. In our prospective community-based cohort study of adults 50 years and older before the COVID-19 pandemic, the incidence of RSV acute respiratory infection (ARI) was 48.6 cases/1000 person-years (PY), which decreased to near zero during the COVID-19 pandemic. Our objective was to determine the incidence of RSV-ARI during the 2 years following the initial phase of the pandemic (2021-2022 and 2022-2023).

    This is a community-based prospective cohort study.

    Adults living in southeast Minnesota from October 2021 to September 2022 (year 3) and October 2022 to September 2023 (year 4).

    Adults≥50 years (n=2500).

    We calculated incidence and attack rates for RSV-ARI as primary outcome and reported hospitalisations, pneumonia and death following ARI as secondary outcome.

    There were 2500 participants in the study with a mean age of 68.2 years (SD 9.3) at the start of year 3. Participants were predominantly female (60%), non-Hispanic white (96%) and residing in urban areas (76%). The incidence rate of RSV-ARI was 6.12/1000 PY (95% CI 3.42 to 10.09) in 2021-2022 and 16.40/1000 PY (95% CI 11.66 to 22.42) in 2022-2023. We noted higher attack rates of RSV-ARI during the winter months. There were no hospitalisations, pneumonia or deaths within 30 days of RSV-ARI.

    Compared with the period before the COVID-19 pandemic, RSV-ARI incidence was lower in both 2021-2022 and 2022-2023 periods. In 2022-2023, the incidence increased 2.7-fold compared with the 2021-2022 period. The observed incidence rates, particularly the significant increase in the most recent season, underscore the continued public health relevance of RSV-ARI and support the rationale for ongoing RSV vaccination efforts to mitigate its overall burden in the population.
    Chronic respiratory disease
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  • Nationwide trend analysis of burnout among resident physicians in Japan before and after the national workstyle reform: a repeated cross-sectional survey of 25 368 participants.
    2 weeks ago
    This study examined temporal changes in burnout and working environments among Japanese resident physicians across the COVID-19 period and the preparation and implementation phases of the national workstyle reform. Furthermore, it assesses associated changes in their working environments.

    This study was conducted as a multicentre repeated cross-sectional study.

    Data were used from the General Medicine In-Training Examination surveys conducted in 2020, 2022, 2023 and 2024.

    Participants included postgraduate year 1 (PGY-1) and PGY-2 residents across Japan.

    Data on working hours, emergency duties, inpatient load, self-study time and burnout were collected through standardised questionnaires. Multivariable logistic regression was performed to assess associations between workstyle reform phases and burnout, adjusting for demographic and institutional characteristics.

    Altogether, 25 368 residents participated (6816 in 2020; 6063 in 2022; 6584 in 2023; 5905 in 2024). Burnout prevalence was the highest during the COVID-19 pandemic in 2020 (21.7%), which decreased to 13.3% in 2024. Weekly working hours of ≥80 hours declined from 19.9% to 2.3%, and those working <45 hours increased from 2.5% to 24.7%. Compared with the pre-reform period (2020-2022), odds of burnout were significantly lower during the preparation (2023; adjusted OR (aOR) 0.60, 95% CI 0.55 to 0.66) and implementation (2024; aOR: 0.67, 95% CI 0.61 to 0.74) phases.

    Residents' burnout was the highest in 2020 and subsequently declined in parallel with improvements in job satisfaction, working hours and clinical workload. These findings suggest that system-level efforts to improve workload balance may be associated with better resident well-being, while causal attribution to the reform should be interpreted cautiously.
    Chronic respiratory disease
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  • Refractory lymphatic plastic bronchitis with chyloptysis successfully treated by thoracic duct ligation.
    2 weeks ago
    Plastic bronchitis is a rare respiratory disorder characterised by the formation and expectoration of firm, branching bronchial casts. These casts resemble plastic in their appearance and consistency, hence the name. The condition is often associated with underlying conditions, such as congenital heart disease, lymphatic abnormalities or pulmonary diseases. In some cases, patients may also present with 'chyloptysis', the expectoration of chyle-containing sputum. This article describes the case of one of our patients with refractory plastic bronchitis who was eventually cured with thoracic duct ligation.
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  • Langerhans cell histiocytosis in the adult lower gastrointestinal tract.
    2 weeks ago
    A female in her early 80s presented with chronic anal fissures which were unresponsive to conservative therapies. Examination was concerning for possible perianal Crohn's disease, but subsequent colonoscopy and biopsies revealed Langerhans cell histiocytosis (LCH) involving the colon and anus, diagnosed per 2022 WHO Classification of Haematolymphoid Tumours criteria and confirmed by BRAF V600E mutation. Systemic staging identified two unrelated malignancies of the breast and kidney. The patient was treated with cladribine as systemic chemotherapy, resulting in complete remission of LCH symptoms and lesions.This case illustrates key diagnostic and therapeutic considerations for clinicians: LCH can mimic inflammatory bowel disease and should be included in the differential for atypical or refractory perianal disease, especially in older adults. Histological confirmation and molecular profiling are essential for accurate diagnosis and treatment planning. Additionally, cladribine is a well-tolerated and effective option for adult LCH with gastrointestinal tract involvement. Early recognition and systemic staging are critical to guide therapy and identify potential coexisting malignancies.
    Chronic respiratory disease
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  • Paradigm Shifts in Cystic Fibrosis Newborn Screening and Care in Infancy.
    2 weeks ago
    There have been advances in the care of children with cystic fibrosis (CF) that allow for early disease identification and intervention in early childhood. Universal and the rise of modulator therapy have revolutionized CF care, so the life expectancy in children with CF has improved. With the changing landscape in advances in CF care, there is uncertainty in interpretation of tests and clinical phenotypes that are indeterminate for CF diagnosis.
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