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Marine, and more recently, freshwater sponges are known to harbor unique microbial symbiotic communities relative to the surrounding water; however, our understanding of the microbial ecology and diversity of freshwater sponges is vastly limited compared to those of marine sponges. Here we analyzed the microbiomes of three freshwater sponge species: Radiospongilla crateriformis, Eunapius fragilis, and Trochospongilla horrida, across four sites in western North Carolina, U.S.A. Our results support recent work indicating that freshwater sponges indeed harbor a distinct microbiome composition compared to the surrounding water and that these varied across sampling site indicating both environmental and host factors in shaping this distinct community. We also sampled sponges at one site over 3 months and observed that divergence in the microbial community between sponge and water occurs at least several weeks after sponges emerge for the growing season and that sponges maintain a distinct community from the water as the sponge tissue degrades. Bacterial taxa within the Gammproteobacteria, Alphproteobacteria, Bacteroidota (Flavobacteriia in particular), and Verrucomicrobia, were notable as enriched in the sponge relative to the surrounding water across sponge individuals with diverging microbial communities from the water. These results add novel information on the assembly and maintenance of microbial communities in an ancient metazoan host and is one of few published studies on freshwater sponge microbial symbiont communities. [ABSTRACT FROM AUTHOR]

Objective: To report clinical findings and outcomes of dogs surgically treated for frontal sinus mucocele., Study Design: Short case series., Animals: Eight dogs., Methods: Seven of eight dogs had evidence of previous skull trauma and developed clinical signs by 10 months of age. On computed tomography, all dogs had a fluid-attenuating, expansile lesion within the frontal sinus and multicentric bone erosion. Surgical treatments comprised frontal sinusotomy and debridement, with either stenting of nasofrontal openings or removal of all sinus lining, with or without fat graft ablation., Results: Four dogs were clinically normal 10-70 months after surgery; two of these dogs had developed swelling 1.5-3 months after surgery, which resolved within 4 months, and one temporarily developed nasal discharge 1 month after stent removal. The mucocele recurred in four dogs 1 to 9 months after surgery; three of those dogs underwent a second surgery with nasofrontal stenting. Two of those dogs were clinically normal at 6 or 20 months after the second surgery. Owners of the third dog reported intermittent swelling for 16 months after the second surgery, which was managed with guaifenesin and carprofen or prednisone. Overall, resolution occurred in one dog with debridement and fat graft ablation and in five dogs with nasofrontal stenting., Conclusion: Young dogs with skull trauma may develop aseptic sinus mucoceles that cause facial distortion and compression of surrounding structures. Re-establishment of sinus drainage or ablation of the lining may resolve clinical signs; however, multiple surgeries may be required., (© 2025 American College of Veterinary Surgeons.)

Myelodysplastic neoplasms (MDS) are stem cell disorders characterized by ineffective hematopoiesis and risk of transformation to acute myeloid leukemia (AML). Chromosomal alterations are frequent in MDS, with interstitial deletion of chromosome 5q (del(5q)) being the most common. Lenalidomide is the current first-line treatment for del(5q) MDS and its efficacy relies on degradation of CK1α which is encoded by the CSNK1A1 gene located in the commonly deleted region (CDR) of chromosome 5q. However, lenalidomide-resistance is common, often secondary to loss-of-function mutations in TP53 or RUNX1. The CDR in del(5q) harbors several genes, including noncoding miRNAs, the loss of which contribute to disease phenotypes. miR-143 and miR-145 are located within the del(5q) CDR, but precise understanding of their role in human hematopoiesis and in the pathogenesis of del(5q) MDS is lacking. Here we provide evidence that deficiency of miR-143 and miR-145 plays a role in clonal expansion of del(5q) MDS. We show that insulin-like growth factor 1 receptor (IGF-1R) is a direct target of both miR-143 and miR-145. Our data demonstrate that IGF-1R inhibition reduces proliferation and viability of del(5q) cells in vitro and in vivo, and that lenalidomide-resistant del(5q) MDS cells depleted of either TP53 or RUNX1 are sensitive to IGF-1R inhibition. Resistant del(5q) MDS-L cells, as well as primary MDS marrow cells, are also sensitive to targeting of IGF-1R-related dependencies in del(5q) MDS, which include the Abl and MAPK signaling pathways. This work thus provides potential new therapeutic avenues for lenalidomide-resistant del(5q) MDS., Competing Interests: Competing interests: The authors declare no competing interests. Ethics approval: All methods were conducted in accordance with relevant guidelines and regulations. Human umbilical cord blood cells were obtained with informed consent under a protocol approved by the University of British Columbia (UBC) Research Ethics Board (REB). Primary umbilical cord blood cells and MDS samples were collected with patient or guardian consent from the Hematology Cell Bank of British Columbia under protocols approved by the UBC REB and institutional review boards at the Royal Adelaide Hospital and Moffitt Cancer Center. Mice were bred and maintained at the BC Cancer Research Center Animal Resources Facility (Vancouver, BC, Canada), with experimental protocols approved by the UBC Animal Care Committee. Ethics approval for xenotransplantation assays (A22-0169) and human cell use (H19-01373, H19-01430) was obtained from the UBC REB for the experiments in this study., (© 2025. The Author(s).)

Background: Cost of illness (COI) studies provide crucial data to policymakers for prioritizing resource allocation, particularly in Iraq that lacks such studies. The objective of this COI study was to measure the direct medical costs for acute coronary syndrome (ACS) during hospitalization from the payer perspective., Methods: This multi-source hospital-based study collected data from patient medical records, healthcare providers, and hospital administration from December 2023 through January 2024. This study was conducted in a leading public cardiac hospital in Iraq, which serves a diverse patient population from across the country. The direct medical costs of ACS treatment were calculated from the payer's point of view (the Ministry of Health (MOH)) for patients admitted to the public department and from the patient's point of view for those admitted to the private department., Results: The study included 70 patients; 50 in the public department and 20 in the private department. The average cost of ACS treatment during hospitalization for a single patient in the public department was Iraqi Dinar (IQD) 1,101,390 ($725). The coronary angiography/angioplasty (CAA) procedure was the largest contributor to spending, accounting for 72.12 % of total expenditures. The patients who were admitted to the private department paid IQD 864,375 ($569) per patient, on average., Conclusion: This study developed a pragmatic approach to calculate cost-of-illness for health systems following the Beveridge Health Model and do not have specific fees for each service. The Iraqi MOH covers all the expenses in the public department within the public hospitals. Although the patients pay fees for ACS treatment in the private department, the MOH may provide subsidized prices to reduce the actual costs.This study opens the door to study the cost of illness for other diseases in the future and informs the payers about the required budget allocation. The study methods are potentially transferable to any country utilizing the Beveridge Model for healthcare delivery., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025 Elsevier Inc. All rights reserved.)

Background: Adenoid cystic carcinoma (ACC) is a rare glandular malignancy, commonly originating in salivary glands of the head and neck. Given its protracted growth, ACC is usually diagnosed in advanced stage. Treatment of ACC is limited to surgery and/or adjuvant radiotherapy, which often fails to prevent disease recurrence, and no FDA-approved targeted therapies are currently available. As such, identification of new therapeutic targets specific to ACC is crucial for improved patients' outcomes., Methods: After thoroughly evaluating the gene expression and signaling patterns characterizing ACC, we applied PandaOmics (an AI-driven software platform for novel therapeutic target discovery) on the unique transcriptomic dataset of 87 primary ACCs. Identifying protein arginine methyl transferase 5 (PRMT5) as a putative candidate with the top-scored druggability, we next determined the applicability of PRMT5 inhibitors (PRT543 and PRT811) using ACC cell lines, organoids, and patient derived xenograft (PDX) models. Molecular changes associated with response to PRMT5 inhibition and anti-proliferative effect of the combination therapy with lenvatinib was then analyzed., Results: Using a comprehensive AI-powered engine for target identification, PRMT5 was predicted among potential therapeutic target candidates for ACC. Here we show that monotherapy with selective PRMT5 inhibitors induced a potent anti-tumor activity across several cellular and animal models of ACC, which was paralleled by downregulation of genes associated with ACC tumorigenesis, including MYB and MYC (the recognized drivers of ACC progression). Furthermore, as a subset of genes targeted by lenvatinib is upregulated in ACC, we demonstrate that addition of lenvatinib enhanced the growth inhibitory effect of PRMT5 blockade in vitro, suggesting a potential clinical benefit for patients expressing lenvatinib favorable molecular profile., Conclusion: Taken together, our study underscores the role of PRMT5 in ACC oncogenesis and provides a strong rationale for the clinical development of PRMT5 inhibitors as a targeted monotherapy or combination therapy for treatment of patients with this rare disease, based on the analysis of their underlying molecular profile., Competing Interests: Declarations. Ethics approval and consent to participate: All human samples used in this study were obtained by the Human Tissue Resource Center at the University of Chicago following informed written consent, under the Institutional Review Boards (IRB)-approved protocols. Consent for publication: Not applicable. Competing interests: VT, KI, PS, and BR are affiliated with Prelude Therapeutics, a clinical-stage biopharmaceutical company designing and developing novel small molecule therapies that target the key drivers of cancer cell growth and resistance. MK, VS, AO, OG, IO, FP, and AZ are affiliated with InSilico Medicine, a company developing an AI-based end-to-end integrated pipeline for drug discovery and development. The remaining authors declare no conflict of interest., (© 2025. The Author(s).)