Zebrafish ETS transcription factor Fli1b functions upstream of Scl/Tal1 during embryonic hematopoiesis.

During embryonic development vascular endothelial and hematopoietic cells are thought to originate from a common precursor, the hemangioblast. An evolutionarily conserved ETS transcription factor FLI1 has been previously implicated in the hemangioblast formation and hematopoietic and vascular development. However, its role in regulating hemangioblast transition into hematovascular lineages is still incompletely understood.

Retinoid X receptor agonist 9CDHRA mitigates retinal ganglion cell apoptosis and neuroinflammation in a mouse model of glaucoma.

Glaucoma, a leading cause of irreversible blindness, is characterized by the progressive loss of retinal ganglion cells (RGCs) and optic nerve damage, often associated with elevated intraocular pressure (IOP). Retinoid X receptors (RXRs) are ligand-activated transcription factors crucial for neuroprotection, as they regulate gene expression to promote neuronal survival via several biochemical networks and reduce neuroinflammation. This study investigated the therapeutic potential of 9-cis-13,14-dihydroretinoic acid (9CDHRA), an endogenous retinoid RXR agonist, in mitigating RGC degeneration in a high-IOP-induced experimental model of glaucoma.

Exploring the impact of RPN1 on tumorigenesis and immune response in cancer.

The ribophorin family, including RPN1, has been associated with tumor progression, but its specific role in pan-cancer dynamics remains unclear. Using data from TCGA, GTEx, and Ualcan databases, we investigated the relationship of RPN1 with prognosis, genomic alterations, and epigenetic modifications across various cancers. Differential analysis revealed elevated RPN1 expression in multiple cancer types, indicating a potential prognostic value.

Impact of a Multiplex PCR Assay for Rapid Diagnosis and Antibiotic Utilization in Trauma Intensive Care Unit Patients with Ventilator-Acquired Pneumonia.

Ventilator-associated pneumonia (VAP) is a frequent complication in injured patients. Multiplex polymerase chain reaction (PCR) facilitates rapid identification of many respiratory pathogens prior to formal culture results. Our objective was to evaluate the effect of multiplex PCR implementation in a trauma intensive care unit (TICU) on antibiotic utilization and de-escalation.

Developing and Implementing a Colorectal Cancer Screening Program in Uganda: Stakeholder Perceived Barriers and Opportunities.

Introduction: Colorectal cancer (CRC) incidence is increasing in Uganda. Despite this, and the disproportionately high burden of early onset and late-stage CRC cases, no CRC screening program exists in Uganda. To guide and inform future CRC prevention efforts, interviews with key stakeholders were undertaken to better understand the perceived barriers and opportunities relevant to the development and implementation of a CRC screening program in Uganda.

March2 Alleviates Aortic Aneurysm/Dissection by Regulating PKM2 Polymerization.

Background: Aortic aneurysm/dissection (AAD) is a life-threatening disease lacking effective pharmacological treatment. Protein ubiquitination plays a pivotal role in cardiovascular diseases. However, the possible contribution of the E3 ubiquitin ligase March2 (membrane-associated RING finger protein 2) to the cause of AAD remains elusive.

Assessment of Risk of Malignancy by Application of the Proposed IAC-IARC-WHO Cytopathology System for Classification and Reporting of Soft Tissue Lesions: An Experience From Tertiary Care Center From India.

Introduction: Soft tissue lesions encompass a diverse category of diseases from benign to malignant, and their morphology might overlap; therefore, accurate categorization is needed to approach the reporting of soft tissue cytology. The cytology of these lesions is helpful in detecting the features of malignancy, which helps in guiding further management. In this study, we applied the proposed IAC-IARC-WHO cytopathology system to assess the risk of malignancy (ROM) and diagnostic accuracy (DA) for the determination of its clinical and diagnostic utility.

Regulation of immune responses to therapeutic factor VIII by transplacental delivery of Fc-fused immunodominant factor VIII domains or peptides.

Patients with severe hemophilia A (HA) often develop undesired immune responses to therapeutic factor VIII (FVIII) that hamper replacement therapy with FVIII-derived products. The transplacental delivery of two Fc-fused FVIII domains in pregnant HA mice was shown to induce partial FVIII-specific immune tolerance in the offspring. Here, we evaluated whether the transplacental delivery of Fc-fused FVIII (rFVIIIFc) induces complete immune tolerance towards FVIII.

p16INK4a Deletion Alleviated Obesity-Associated Kidney Fibrosis by Regulating Metabolic Reprogramming and the Inflammasome Pathway.

Recent research has revealed a close association between obesity and various metabolic disorders, including renal metabolic diseases, but the mechanism is still unknown. This study explored the role of p16INK4a in obesity-related kidney fibrosis and evaluated its potential as a therapeutic target. Using wild-type (WT) mice and p16 KO mice, we fed both groups a high-fat diet (HFD) for 6 months.

Enforcement of stem-cell dormancy by nucleophosmin mutation is a critical determinant of unrestricted self-renewal during myeloid leukemogenesis.

Mutations in the NPM1 gene (NPMc+) and in the FLT3 gene (FLT3-ITD) represent the most frequent co-occurring mutations in Acute Myeloid Leukemia (AML), yet the cellular and molecular mechanisms of their cooperation remain largely unexplored. Using mouse models that faithfully recapitulate human AML, we investigated the impact of these oncogenes on pre-leukemic and leukemic hematopoietic stem cells (HSCs), both separately and in combination. While both NPMc+ and Flt3-ITD promote the proliferation of pre-leukemia HSCs, only NPMc+ drives extended selfrenewal by preventing the depletion of the quiescent HSC pool.

Leukemic presentation in nodal mantle cell lymphoma is characterized by frequent SOX11 negativity, a poor risk genomic landscape including higher alterations, and worse overall survival.

Not available.

Primary Angiitis of the Central Nervous System and Its Mimics: A Pattern-Based Approach to Biopsies for Central Nervous System Vasculitis.

Context.—: Primary angiitis of the central nervous system is a rare vasculitis that affects small parenchymal and leptomeningeal vessels in the brain and spinal cord. As brain biopsy remains the gold standard in diagnosis, the diagnostic approach to brain biopsies for vasculitis is well described.

Surgical management of oligometastatic recurrence in primary esophageal melanoma: a feasible approach in resource-limited settings.

Primary esophageal melanoma (PEM) is a rare and aggressive malignancy with limited treatment options. Due to its rarity, no standardized guidelines exist for managing oligometastatic recurrence, particularly in resource-limited settings. We present a case of a 60-year-old male with PEM who underwent esophagectomy followed by surgical resection of an adrenal metastasis.

Invasive ductal carcinoma at the site of a cosmetic nipple piercing.

We report a young female patient diagnosed with an invasive ductal carcinoma at the site of a prior cosmetic nipple piercing. She had no significant familial, genetic, or other carcinogenic risk factors to account for her presentation. A review of the literature confirms that trauma can occasionally be associated with invasive breast cancer, but such a connection has not previously been related to nipple piercing procedures.

Case Report: Coexistence of Rosai-Dorfman disease and B-cell acute lymphoblastic leukemia in an adolescent.

Rosai-Dorfman disease (RDD) is an unusual, non-malignant proliferative disorder involving non-Langerhans cell histiocytes, characterized by a wide range of clinical presentations and distinctive atypical morphological patterns. The concurrent manifestation of acute lymphoblastic leukemia (ALL) alongside RDD is exceptionally rare. Here, we present the case of a 14-year-old male patient diagnosed with ALL who, during the consolidation phase of chemotherapy, developed multifocal bone, dural, and liver lesions, as confirmed through CT and MRI imaging.

Analysis of single-cell and spatial transcriptomics in TNBC cell-cell interactions.

Triple-negative breast cancer (TNBC) is a highly malignant tumor in women, characterized by high morbidity, mortality, and recurrence rates. Although surgical treatment, radiotherapy, and chemotherapy are the mainstays of current treatment methods, the high heterogeneity of TNBC results in unsatisfactory outcomes with low 5-year survival rates. Rapid advancements in omics technology have propelled the understanding of TNBC molecular biology.

The role of tumor-associated macrophages in lung cancer.

Lung cancer remains a leading cause of cancer-related deaths worldwide, necessitating innovative treatments. Tumor-associated macrophages (TAMs) are primary immunosuppressive effectors that foster tumor proliferation, angiogenesis, metastasis, and resistance to therapy. They are broadly categorized into proinflammatory M1 and tumor-promoting M2 phenotypes, with elevated M2 infiltration correlating with poor prognosis.

Multiparameter flow cytometric and transcriptional analyis of CD20 positive T-cells in bone marrow in patients of multiple myeloma and monoclonal gammopathy of undetermined significance.

Introduction: CD20+ T-cells were described firstly in peripheral blood and later in bone marrow in patients with hematological tumors, and certain immune-mediated diseases. During our hematological diagnostic work, this peculiar subgroup of lymphocytes has been consistently observed associated with untreated monoclonal gammopathy of undetermined significance (MGUS) and myeloma (MM). Despite the expanding literature data, the exact function of CD20+ T cells remains unclear.

Immune repertoire sequencing reveals differences in treatment response to camrelizumab plus platinum-based chemotherapy in advanced ESCC.

This study evaluated the efficacy and safety of camrelizumab combined with platinum-based chemotherapy (taxanes [T] or fluorouracil agents [F] plus platinum [P] drugs) as the first-line treatment in advanced esophageal squamous cell carcinoma (ESCC), using immune repertoire sequencing (IRS) to explore treatment response mechanism. In this multi-center, prospective cohort study, 88 patients received camrelizumab plus TP or FP, achieving a 1-year progression-free survival of 56.8% and overall survival of 68.

Development of a tertiary lymphoid structure-based prognostic model for breast cancer: integrating single-cell sequencing and machine learning to enhance patient outcomes.

Background: Breast cancer, a highly prevalent global cancer, poses significant challenges, especially in advanced stages. Prognostic models are crucial to enhance patient outcomes. Tertiary lymphoid structures (TLS) within the tumor microenvironment have been associated with better prognostic outcomes.

Cross-protectivity of henipavirus soluble glycoprotein in an model of Nipah virus disease.

Introduction: Nipah virus (NiV) is one of a group of highly pathogenic viruses classified within the Henipavirus genus. Since 2012 at least 11 new henipa-like viruses have been identified, including from new locations and reservoir hosts; the pathogenicity of these new viruses has yet to be determined, but two of them have been associated with morbidity, including fatalities.

Methods: The efficacy and cross-reactivity of two vaccine candidates derived from the soluble glycoproteins of both NiV and Hendra virus (HeV) was evaluated in our recently established hamster model.

Advances in primary large B-cell lymphoma of immune-privileged sites.

Primary large B-cell lymphoma of immune-privileged sites (IP-LBCL) encompasses a spectrum of relatively rare aggressive B-cell lymphomas, such as primary central nervous system lymphoma (PCNSL), primary testicular large B-cell lymphoma (PTL), and primary vitreoretinal large B-cell lymphoma (PVRL). Macroscopically, the development of IPI-LBCL may be associated with the dysfunction of meningeal lymphatic vessels (mLVs) and the perivascular channel system formed by astrocytes. Microscopically, mutation in MYD88 and CD79B genes plays a pivotal role in the pathogenesis of IP-LBCL.

Single-cell RNA-sequencing reveals cellular heterogeneity and immune microenvironment characteristics between ocular adnexal mucosa-associated lymphoid lymphoma and IgG4-related ophthalmic disease.

Introduction: The molecular pathogenesis of ocular adnexal mucosa-associated lymphoid tissue (MALT) lymphoma and IgG4-related ophthalmic disease (IgG4-ROD) remains incompletely understood. Differentiating between the two diseases is vital given that the diagnostic evaluation and treatment approaches can vary significantly; this difficulty in distinction is exacerbated by the absence of specific biomarkers. This study aimed to investigate the differences between these two diseases based on their cellular composition, transcriptional heterogeneity, and the immune microenvironment using single-cell RNA transcriptional sequencing (scRNA-seq) technology.

Biomarkers to aid in diagnosis of allergic contact dermatitis.

Allergic contact dermatitis (ACD) is an increasingly common skin condition characterized by itchy rashes in response to allergens. The most common diagnostic test involves patch testing (PT), but despite the efficacy of PT for identifying and guiding patients toward avoidance of allergens, PT alone does not elucidate the underlying biomechanistic changes which may be useful for sub-categorizing ACD further. In addition, some patients may never be able to identify their causative allergens unless they go to highly specialized ACD centers.

Profiling hippocampal neuronal populations reveals unique gene expression mosaics reflective of connectivity-based degeneration in the Ts65Dn mouse model of Down syndrome and Alzheimer's disease.

Introduction: Individuals with Down syndrome (DS) exhibit neurological deficits throughout life including the development of in Alzheimer's disease (AD) pathology and cognitive impairment. At the cellular level, dysregulation in neuronal gene expression is observed in postmortem human brain and mouse models of DS/AD. To date, RNA-sequencing (RNA-seq) analysis of hippocampal neuronal gene expression including the characterization of discrete circuit-based connectivity in DS remains a major knowledge gap.