Gigascience. 2025 Jan 6;14:giaf028. doi: 10.1093/gigascience/giaf028.

ABSTRACT

We introduce RWRtoolkit, a multiplex generation, exploration, and statistical package built for R and command-line users. RWRtoolkit enables the efficient exploration of large and highly complex biological networks generated from custom experimental data and/or from publicly available datasets, and is species agnostic. A range of functions can be used to find topological distances between biological entities, determine relationships within sets of interest, search for topological context around sets of interest, and statistically evaluate the strength of relationships within and between sets. The command-line interface is designed for parallelization on high-performance cluster systems, which enables high-throughput analysis such as permutation testing. Several tools in the package have also been made available for use in reproducible workflows via the KBase web application.

PMID:40272882 | DOI:10.1093/gigascience/giaf028

Probiotics Antimicrob Proteins. 2025 Apr 24. doi: 10.1007/s12602-025-10549-8. Online ahead of print.

ABSTRACT

The rise of antimicrobial-resistant infections highlights the need for novel therapeutic strategies. Class IIb microcins, a subclass of ribosomally synthesized bacteriocins, play a significant role in modulating bacterial communities by targeting iron acquisition systems in competitive environments, such as the gastrointestinal tract. In this study, we describe and characterize Ec W, a novel class IIb microcin from Escherichia coli strain NCTC10444. This strain is the first known to harbor two homologs of the class IIb microcin biosynthesis cluster and to encode four class IIb microcins in its genome. Sequence analysis revealed that Ec W shows similarity to class IIb microcin Gq W, extending the known repertoire of this microcin class to 18. Heterologous expression and inhibition assays demonstrated potent antimicrobial activity of Ec W against numerous enteric pathogens from the Enterobacteriaceae family, including drug-resistant and hypervirulent strains of E. coli and Klebsiella pneumoniae. These findings suggest that Ec W holds substantial promise as an antimicrobial agent, providing a potential alternative to traditional antibiotics for combating multidrug-resistant pathogens. This study emphasizes the importance of exploring microcins as a novel strategy to tackle the growing threat of infections caused by multidrug-resistant bacteria.

PMID:40272760 | DOI:10.1007/s12602-025-10549-8

Inflamm Res. 2025 Apr 24;74(1):69. doi: 10.1007/s00011-025-02036-1.

ABSTRACT

BACKGROUND: Due to the possible influence of inflammation and gut microbiota in cancers.

METHODS: Fc gamma receptor IIb deficient (FcGRIIb-/-) and cyclic GMP-AMP synthase deficient (cGAS-/-) mice, the model with hyperinflammation and hypo-inflammation, respectively, were subcutaneously injected with MC38 cells (a murine colon cancer cell line).

RESULTS: As such, the tumor burdens were most prominent in cGAS-/- mice, while FcGRIIb-/- mice demonstrated the least tumor sizes compared with wild-type (WT). Intra-tumoral mononuclear cells of FcGRIIb-/- (hematoxylin and eosin staining) were more prominent than other groups with the most dominant CD86-positive cells (mostly M1 proinflammatory macrophages) and the least CD206-positive cells (mostly M2 anti-inflammatory macrophages). While fecal microbiome analysis demonstrated a subtle difference among mouse strains with tumors at 24 days post-cancer injection, serum cytokines (TNF-α, IL-6, IL-1α, IFN-β, IFN-γ, IL-23, IL-12p70, GM-CSF, IL-27, and IL-17A) (fluorescence-encoded bead multiplex assay) and the expansion of immune cells in the spleens of FcGRIIb-/- mice (flow cytometry) were more prominent than others. With bone marrow-derived macrophages, prominent M1 (LPS) and M2 polarization (IL4 and cancer supernatant) in FcGRIIb-/- and cGAS-/- macrophages, respectively, were demonstrated using polymerase chain reaction and flow cytometry. The most prominent tumoricidal activity (percentage of F4/80-negative flexible780 viable dye-positive cells using flow cytometry) of LPS-stimulated FcGRIIb-/- macrophages compared with other groups supported dominant pro-inflammatory characteristics of FcGRIIb-/- macrophages.

CONCLUSIONS: In conclusion, the protective and promoting effects of FcGRIIb-/- and cGAS-/- mice, respectively, against cancers are partly related to macrophage functions with a subtle correlation to fecal microbiota, and FcGRIIb inhibitors and cGAS enhancers might be helpful for cancer adjuvant treatment.

PMID:40272597 | DOI:10.1007/s00011-025-02036-1

Clin Chem. 2025 Apr 24:hvaf043. doi: 10.1093/clinchem/hvaf043. Online ahead of print.

ABSTRACT

BACKGROUND: In 2009, the Minimum Information for Publication of Quantitative Real-Time PCR Experiments (MIQE) guidelines established standards for the design, execution, and reporting of quantitative PCR (qPCR) in research. The expansion of qPCR into numerous new domains has driven the development of new reagents, methods, consumables, and instruments, requiring revisions to best practices that are tailored to the evolving complexities of contemporary qPCR applications.

CONTENT: Transparent, clear, and comprehensive description and reporting of all experimental details are necessary to ensure the repeatability and reproducibility of qPCR results. These revised MIQE guidelines reflect recent advances in qPCR technology, offering clear recommendations for sample handling, assay design, and validation, along with guidance on qPCR data analysis. Instrument manufacturers are encouraged to enable the export of raw data to facilitate thorough analyses and re-evaluation by manuscript reviewers and interested researchers. The guidelines emphasize that quantification cycle (Cq) values should be converted into efficiency-corrected target quantities and reported with prediction intervals, along with detection limits and dynamic ranges for each target, based on the chosen quantification method. Additionally, best practices for normalization and quality control are outlined and reporting requirements have been clarified and streamlined. The aim is to encourage researchers to provide all necessary information without undue burden, thereby promoting more rigorous and reproducible qPCR research.

SUMMARY: Building on the collaborative efforts of an international team of researchers, we present updates, simplifications, and new recommendations to the original MIQE guidelines, designed to maintain their relevance and applicability in the context of emerging technologies and evolving qPCR applications.

PMID:40272429 | DOI:10.1093/clinchem/hvaf043

Nucleic Acids Res. 2025 Apr 22;53(8):gkaf329. doi: 10.1093/nar/gkaf329.

ABSTRACT

Inverted repeats are repetitive elements that can form hairpin and cruciform structures. They are linked to genomic instability; however, they also have various biological functions. Their distribution differs markedly across taxonomic groups in the tree of life, and they exhibit high polymorphism due to their inherent genomic instability. Advances in sequencing technologies and declined costs have enabled the generation of an ever-growing number of complete genomes for organisms across taxonomic groups in the tree of life. However, a comprehensive database encompassing inverted repeats across diverse organismal genomes has been lacking. We present invertiaDB, the first comprehensive database of inverted repeats spanning multiple taxa, featuring repeats identified in the genomes of 118 101 organisms across all major taxonomic groups. For each organism, we derived inverted repeats with arm lengths of at least 10 bp, spacer lengths up to 8 bp, and no mismatches in the arms. The database currently hosts 34 330 450 inverted repeat sequences, serving as a centralized, user-friendly repository to perform searches and interactive visualizations, and download existing inverted repeat data for independent analysis. invertiaDB is implemented as a web portal for browsing, analyzing, and downloading inverted repeat data. invertiaDB is publicly available at https://invertiadb.netlify.app/homepage.html.

PMID:40272360 | DOI:10.1093/nar/gkaf329

Microscopy (Oxf). 2025 Apr 24:dfaf020. doi: 10.1093/jmicro/dfaf020. Online ahead of print.

ABSTRACT

Genome-wide profiling of gene expression levels in cells, such as transcriptomics and proteomics, is a powerful experimental approach in modern biology, allowing not only efficient exploration of the genetic elements responsible for biological phenomena of interest, but also characterization of the global constraints behind plastic phenotypic changes of cells that accompany large-scale remodeling of omics profiles. To understand how individual cells change their molecular profiles to achieve specific phenotypic changes in phenomena such as differentiation, cancer metastasis and adaptation, it is crucial to characterize the dynamics of cellular phenotypes and omics profiles simultaneously at the single-cell level. Especially in the last decade, significant technical progress has been made in the in situ identification of omics profiles of cells on the microscope. However, most approaches still remain destructive and cannot unravel the post-measurement dynamics. In recent years, Raman spectroscopy-based methods for omics inference have emerged, allowing the characterization of genome-wide molecular profile dynamics in living cells. In this review, we give a brief overview of the recent development of imaging-based omics profiling methods. We then present the approach to infer omics profiles from single-cell Raman spectra. Since Raman spectra can be obtained from living cells in a non-destructive and non-staining manner, this method may open the door to live-cell omics.

PMID:40271815 | DOI:10.1093/jmicro/dfaf020

Nucleic Acids Res. 2025 Apr 24:gkaf335. doi: 10.1093/nar/gkaf335. Online ahead of print.

ABSTRACT

The Bakta command line application is widely used and one of the most established tools for bacterial genome annotation. It balances comprehensive annotation with computational efficiency via alignment-free sequence identifications. However, the usage of command line software tools and the interpretation of result files in various formats might be challenging and pose technical barriers. Here, we present the recent updates on the Bakta web server, a user-friendly web interface for conducting and visualizing annotations using Bakta without requiring command line expertise or local computing resources. Key features include interactive visualizations through circular genome plots, linear genome browsers, and searchable data tables facilitating the interpretation of complex annotation results. The web server generates standard bioinformatics outputs (GFF3, GenBank, EMBL) and annotates diverse genomic features, including coding sequences, non-coding RNAs, small open reading frames (sORFs), and many more. The development of an auto-scaling cloud-native architecture and improved database integration led to substantially faster processing times and higher throughputs. The system supports FAIR principles via extensive cross-reference links to external databases, including RefSeq, UniRef, and Gene Ontology. Also, novel features have been implemented to foster sharing and collaborative interpretation of results. The web server is freely available at https://bakta.computational.bio.

PMID:40271661 | DOI:10.1093/nar/gkaf335

iScience. 2025 Mar 26;28(5):112167. doi: 10.1016/j.isci.2025.112167. eCollection 2025 May 16.

ABSTRACT

Dormant lung adenocarcinoma (LUAD) cells in the bone microenvironment can re-emerge as metastatic disease through osteoclast interactions. Using a 3D dormancy model and a mouse bone metastasis model, this study reveals that arachidonic acid (AA) is the initiating molecule transferred from osteoclasts to dormant LUAD cells, triggering their activation. Dormant LUAD cells uptake AA through CD36, which activates the PPARγ-ANGPTL4 pathway and activates tumor cells. There is a dose-response relationship in the activation effect of AA, and inhibiting AA metabolism prevents this reactivation. The study also finds that the serum levels of AA and ANGPTL4 are significantly elevated in patients with clinical bone metastases compared to those without. This research confirms that osteoclasts transmit AA via the CD36-PPARγ-ANGPTL4 axis to activate dormant LUAD cells, suggesting that AA and ANGPTL4 may serve as valuable biomarkers and potential clinical applications in treatment and prediction of LUAD bone metastasis.

PMID:40271019 | PMC:PMC12018030 | DOI:10.1016/j.isci.2025.112167

Front Immunol. 2025 Apr 9;16:1509805. doi: 10.3389/fimmu.2025.1509805. eCollection 2025.

ABSTRACT

INTRODUCTION: Uveitis accounts for up to 25% of global legal blindness and involves intraocular inflammation, classifed as infectious or non-infectious. Its complex pathophysiology includes dysregulated cytokines, particularly interferons (IFNs). However, the global signature of type I, II, and III interferon-regulated genes (Interferome) remains largely uncharacterized in uveitis.

METHODS: In this study, we conducted an integrative systems biology analysis of blood transcriptome data from 169 non-infectious uveitis patients (56 isolated uveitis, 113 systemic disease-associated uveitis) and 82 healthy controls.

RESULTS: Modular co-expression analysis identified distinct cytokine signaling networks, emphasizing interleukin and interferon pathways. A meta-analysis revealed 110 differentially expressed genes (metaDEGs) in isolated uveitis and 91 in systemic disease-associated uveitis, predominantly linked to immune responses. The Interferome database confirmed a predominance of type I and II IFN signatures in both groups. Pathway enrichment analysis highlighted inflammatory responses, including cytokine production (IL-8, IL1-β, IFN-γ, β, and α) and toll-like receptor signaling (TLR4, TLR7, TLR8, CD180). Principal component analysis emphasized the IFN signature's discriminative power, particularly in systemic disease-associated uveitis. Machine learning identified IFN-associated genes as robust predictors, while linear discriminant analysis pinpointed CCR2, CD180, GAPT, and PTGS2 as key risk factors in isolated uveitis and CA1, SIAH2, and PGS in systemic disease-associated uveitis.

CONCLUSION: These findings highlight IFN-driven imune dysregulation and potential molecular targets for precision therapies in uveitis.

PMID:40270958 | PMC:PMC12014655 | DOI:10.3389/fimmu.2025.1509805

Front Public Health. 2025 Apr 9;13:1459060. doi: 10.3389/fpubh.2025.1459060. eCollection 2025.

ABSTRACT

Nowadays, heavy metal (HM) contamination and their ecological risk in coastal sediments are global issues. This research provides insight into the heavy metals' contamination, source apportionment, and potential ecological risks in the surface sediments of the Xiang-Shan wetland in Taiwan, which is undergoing rapid economic development, mainly by the semiconductor industries. The levels of twelve metals and total organic matter (TOM) were measured in 44 samples of surface sediment during the spring and winter seasons of 2022. Subsequently, the single and comprehensive pollution indices were assessed. The findings showed that the average of HM contents exhibited a descending sequence of Al > Fe > Mn > Zn > Co > Ga > Cr > Cu > In > Ni > Pb = Cd during both seasons. The E f , I geo , and PI showed that the majority of sediment samples were uncontaminated to heavily contaminated by Fe, Al, Zn, Cu, Mn, Cr, Ni, Co and Ga, and extremely contaminated by In. Moreover, PLI and mC deg unveiled that the surface sediments of DJ, OB, and KY stations were strongly or extremely polluted. PERI revealed that the sediment shows minimal to moderate ecological risk. The findings of multivariate analyses suggested that Fe, Al, Cu, Zn, and Ni derived from natural sources, while Ga, In, Co, Cr, and Mn originated from both anthropogenic and natural origins. Hence, it is critical that HM contamination, particularly Co, In, and Ga, be continuously monitored in the study area. Our data provide significant insights for more effective prevention and evaluation of HM contamination in the aquatic-sedimentary ecosystems of Taiwan.

PMID:40270744 | PMC:PMC12014647 | DOI:10.3389/fpubh.2025.1459060

MicroPubl Biol. 2025 Apr 8;2025. doi: 10.17912/micropub.biology.001567. eCollection 2025.

ABSTRACT

We examined the effects of X-ray irradiation on Xenopus laevis , focusing on pre- and post-fertilization exposure. We applied X-ray doses of 10, 50, 100, 250, and 500 Gy. Fifty percent of the 360 eggs irradiated at 250 Gy failed to fertilize, while fertilized eggs developed normally until the gastrula stage. Doses ranging from 10 to 250 Gy caused developmental anomalies. High mortality rates were observed at doses of 100 to 500 Gy. Post-fertilization irradiation at 50 to 100 Gy resulted in 100% lethality, while exposure to 10 Gy led to only 13% lethality, although both exposure levels produced similar types of developmental anomalies compared to pre-fertilization irradiation. This study highlights how the timing and intensity of exposure critically affect embryo viability, especially during the sensitive stages of fertilization and gastrulation. We establish the necessary and sufficient dosage to further investigate the molecular mechanisms of X-ray damage to DNA and protein.

PMID:40270682 | PMC:PMC12015645 | DOI:10.17912/micropub.biology.001567

Front Mol Biosci. 2025 Apr 9;12:1557835. doi: 10.3389/fmolb.2025.1557835. eCollection 2025.

ABSTRACT

The human protein kinome is a group of over 500 therapeutically relevant kinases. Exemplified by over 10,000 phosphorylated sites reported in global phosphoproteomes, kinases are also highly regulated by phosphorylation. Currently, 1008 phosphorylated sites in 273 kinases are associated with their regulation of activation/inhibition, and a few in 30 kinases are associated with altered activity. Phosphorylated sites in 196 kinases are related to other molecular functions such as localization and protein interactions. Over 8,000 phosphorylated sites, including all those in 517 kinases are unassigned to any functions. This imposes a significant bias and challenge for the effective analysis of global phosphoproteomics datasets. Hence, we derived a set of stably and frequently detected phosphorylated sites (representative phosphorylated sites) across diverse experimental conditions annotated in the PhosphoSitePlus database and presumed them to be relevant to the human kinase regulatory network. Analysis of these representative phosphorylated sites led to the classification of 449 kinases into four distinct categories (kinases with phosphorylated sites apportioned (PaKD) and enigmatic (PeKD), and those with predominantly within kinase domain (PiKD) and outside kinase domain (PoKD)). Knowledge-based functional analysis and sequence conservation across the family/subfamily identified phosphorylated sites unique to specific kinases that could contribute to their unique functions. This classification of representative kinase phosphorylated sites enhance our understanding of prioritized validation and provides a novel framework for targeted phosphorylated site enrichment approaches. Phosphorylated sites in kinases associated with dysregulation in diseases were frequently located outside the kinase domain, and suggesting their regulatory roles and opportunities for phosphorylated site-directed therapeutic approaches.

PMID:40270594 | PMC:PMC12015135 | DOI:10.3389/fmolb.2025.1557835

Bioact Mater. 2025 Apr 14;50:246-272. doi: 10.1016/j.bioactmat.2025.04.008. eCollection 2025 Aug.

ABSTRACT

We produced a microstructured, electroconductive and nano-functionalized drug eluting cardiac patch (MENDEP) designed to attract endogenous precursor cells, favor their differentiation and counteract adverse ventricular remodeling in situ. MENDEP showed mechanical anisotropy and biaxial strength comparable to porcine myocardium, reduced impedance, controlled biodegradability, molecular recognition ability and controlled drug release activity. In vitro, cytocompatibility and cardioinductivity were demonstrated. Migration tests showed the chemoattractive capacity of the patches and conductivity assays showed unaltered cell-cell interactions and cell beating synchronicity. MENDEP was then epicardially implanted in a rat model of ischemia/reperfusion (I/R). Histological, immunofluorescence and biomarker analysis indicated that implantation did not cause damage to the healthy myocardium. After I/R, MENDEP recruited precursor cells into the damaged myocardium and triggered their differentiation towards the vascular lineage. Under the patch, the myocardial tissue appeared well preserved and cardiac gap junctions were correctly distributed at the level of the intercalated discs. The fibrotic area measured in the I/R group was partially reduced in the patch group. Overall, these results demonstrate that MENDEP was fully retained on the epicardial surface of the left ventricle over 4-week implantation period, underwent progressive vascularization, did not perturb the healthy myocardium and showed great potential in repairing the infarcted area.

PMID:40270551 | PMC:PMC12017858 | DOI:10.1016/j.bioactmat.2025.04.008

Future Oncol. 2025 Apr 24:1-11. doi: 10.1080/14796694.2025.2495543. Online ahead of print.

ABSTRACT

AIM: The present study assessed the incidence of drug-induced interstitial lung disease (ILD) recurrence among breast cancer patients who underwent rechallenge with cancer-directed therapy.

MATERIALS & METHODS: Japanese insurance claims data and the Diagnosis Procedure Combination database (2009-2022) involving 81,601 patients were analyzed to evaluate 1,042 breast cancer patients who developed ILD. Of these, 566 patients underwent cancer-directed therapy rechallenge, and 42.1% of them were re-challenged with the same therapeutic regimen that caused the initial ILD.

RESULTS: ILD recurrence was observed in 18.9% of the patients, with a median recurrence time of 40 days. The drugs most commonly causing ILD were cytotoxic agents, and those most frequently used for rechallenge were cytotoxic agents.

CONCLUSION: A notable ILD recurrence rate was observed in breast cancer patients after a cancer-directed therapy rechallenge, highlighting the need for cautious treatment planning and personalised strategies to balance cancer control while mitigating ILD risk.

PMID:40272014 | DOI:10.1080/14796694.2025.2495543

Toxicol Rep. 2025 Apr 5;14:102021. doi: 10.1016/j.toxrep.2025.102021. eCollection 2025 Jun.

ABSTRACT

Immunotherapy has revolutionized cancer treatment, offering significant survival superiority for advanced malignancies. However, immunotherapy is associated with various immune-related adverse events, one of the most common of them being dermatologic toxicities. Previous studies have reported dermatologic adverse events in almost half of the cancer patients undergoing immunotherapy. The spectrum of dermatologic toxicities ranges from mild, self-limiting reactions to severe, life-threatening conditions, and includes maculopapular rash, pruritus, vitiligo-like depigmentation, psoriasiform eruption, lichenoid eruption, bullae, photosensitivity, hair loss, nail changes, Stevens-Johnson syndrome, and toxic epidermal necrolysis. The management strategies are based on personalized treatment plans, multidisciplinary approaches, and timely therapeutic interventions aimed at addressing dermatologic toxicities while preserving immunotherapy efficacy. Based on the latest findings, this paper offers a novel perspective and provides an evidence-based review of the pathogenesis, manifestations, incidence, grading, clinical management, and prognostic significance of these toxicities, underlining the importance of balancing the efficacy of immunotherapy with timely and proactive management of their dermatological toxicities to enhance patient outcomes and quality of life.

PMID:40271531 | PMC:PMC12017974 | DOI:10.1016/j.toxrep.2025.102021

J Cardiol Cases. 2024 Nov 7;31(2):42-45. doi: 10.1016/j.jccase.2024.10.001. eCollection 2025 Feb.

ABSTRACT

Pemafibrate is a selective peroxisome proliferator-activated receptor alpha (PPARα) activator. Pemafibrate has been shown to reduce serum triglyceride levels to an equivalent or greater extent than traditional fibrates, with a lower incidence of drug-related adverse events. Pemafibrate may have the potential to improve clinical outcomes in carefully selected patients with cardiovascular diseases by ameliorating dyslipidemia and stabilizing systemic arteriosclerosis. Additionally, several experimental studies have demonstrated a novel potential for pemafibrate in improving heart failure through its pleiotropic effects. We encountered two patients with systolic heart failure that was refractory to guideline-directed medical therapy. Both patients experienced further cardiac reverse remodeling and an improvement in hypertriglyceridemia following a six-month course of pemafibrate add-on therapy. Pemafibrate might facilitate cardiac reverse remodeling when incorporated into conventional heart failure medications. Further prospective randomized controlled studies are warranted to evaluate the clinical implications of incorporating pemafibrate into medical therapy for heart failure patients. Future research should also explore the long-term effects of pemafibrate on cardiovascular outcomes, the underlying mechanisms of its pleiotropic benefits, and its efficacy in diverse patient populations to solidify its role in heart failure management.

LEARNING OBJECTIVE: Pemafibrate, a recently introduced selective peroxisome proliferator-activated receptor alpha activator that improves hypertriglyceridemia, may facilitate cardiac reverse remodeling when incorporated into conventional heart failure medications.

PMID:40270895 | PMC:PMC12013756 | DOI:10.1016/j.jccase.2024.10.001

Stud Health Technol Inform. 2025 Apr 24;324:234-239. doi: 10.3233/SHTI250194.

ABSTRACT

BACKGROUND: Standardizing laboratory data is essential for interoperability and secondary use in clinical research and healthcare. However, many laboratory information systems (LIS) still rely on internal codes rather than internationally recognized terminologies, hindering data exchange, queryability, and integration into health data infrastructures.

OBJECTIVES: This study aimed to automate the extraction and mapping of internal lab codes to LOINC to improve structured data integration by utilizing web scraping and terminology mapping, we sought to create a FHIR-compliant ConceptMap.

METHODS: Guided by key requirements for structured data integration, we developed a Python-based workflow to extract and process laboratory data from an internal lab index. Using Selenium, BeautifulSoup, and Pandas, the extracted data was mapped to LOINC codes and transformed into a FHIR-compliant ConceptMap.

RESULTS: The workflow extracted 2,870 analytes, mapping 768 (27%) to LOINC. The automated process demonstrated feasibility and scalability.

CONCLUSION: The approach enables structured laboratory data integration but highlights the need for direct LIS integration and expanded LOINC coverage for legacy data.

PMID:40270418 | DOI:10.3233/SHTI250194

Stroke. 2025 Apr 24. doi: 10.1161/STROKEAHA.124.050207. Online ahead of print.

ABSTRACT

BACKGROUND: Women less frequently receive secondary prevention medications at discharge poststroke than men. It is unclear whether similar sex differences exist in the long term poststroke, after accounting for age and clinical characteristics. We aimed to evaluate sex differences in medication prescription, initiation, and discontinuation poststroke or transient ischemic attack.

METHODS: A retrospective cohort study using person-level linked data from the Australian Stroke Clinical Registry (42 hospitals; Victoria and Queensland; 2012-2016). We included all adults with first-ever ischemic stroke, intracerebral hemorrhage, or transient ischemic attack who survived >60 days post-discharge. For each major class of secondary prevention medication (antihypertensive, antithrombotic, or lipid lowering), we evaluated sex differences in prescription at hospital discharge, initiation within 60 days, and discontinuation within 2 years post-discharge. Sex differences were assessed using multivariable models, adjusted for sociodemographics and comorbidities. Where effect modification by age was found (Pinteraction≤0.05), age-specific odds ratios were reported.

RESULTS: Among 8108 women (median age, 74.3 years) and 10 344 men (median age, 70.5 years) with first-ever stroke (≈8% intracerebral hemorrhage) or transient ischemic attack, women were less likely to be prescribed antihypertensive medications on discharge (odds ratio, 0.82 [95% CI, 0.74-0.91]). Women were less likely to initiate antihypertensive (odds ratio, 0.76 [95% CI, 0.69-0.84]) and antithrombotic (odds ratio, 0.89 [95% CI, 0.82-0.96]) medications within 60 days than men. While there was no overall difference in discontinuation between men and women, interactions were observed with age (Pinteraction, all <0.002). Younger women (aged <45 years) and older women (aged >90 years) were more likely to discontinue secondary prevention medications than men of equivalent age.

CONCLUSIONS: Sex differences exist for prescription, initiation, and discontinuation of secondary prevention medications poststroke. With many sex differences being age specific, there is a critical need for targeted interventions to improve prevention medication use in these patient subgroups.

PMID:40270283 | DOI:10.1161/STROKEAHA.124.050207

Cardiooncology. 2025 Apr 23;11(1):39. doi: 10.1186/s40959-025-00337-2.

ABSTRACT

BACKGROUND: Anthracyclines are essential in early breast cancer chemotherapy but pose long-term cardiotoxicity risks.

OBJECTIVES: This study aims to investigate the long-term incidence of cancer therapy-related cardiac dysfunction (CTRCD), bridging with the miRNAs profiler representing acute cardiac injury.

METHODS: We conducted a prospective cohort including stage I-III breast cancer patients who received anthracycline between 2007 and 2012. Echocardiography was performed before and 12 weeks after anthracycline administration. The miRNAs profiler was conducted by NanoString and RT-PCR. Long-term cardiac magnetic resonance imaging (CMR) was evaluated in 24.2% of asymptomatic participants.

RESULTS: At a median follow-up of 11 [IQR 6-12] years, 194 patients who completed follow-up echocardiography after anthracycline were included in the analysis. The median age at diagnosis was 50 [26-72] years. An early LVEF decline of ≥ 10% was found in 32.9% of participants. The cumulative equivalent dose of doxorubicin was 223.2 ± 21.6 mg/m2. At the time of censoring, sixty-four participants (32.9%) died, 70% from breast cancer. Nine participants (4.6%) reported cardiovascular events compatible with the CTRCD definition. Forty-seven participants (24.2%) underwent long-term cardiac evaluation. The miRNAs profiler and RT-PCR at different time points, 3 weeks and 6 weeks, respectively, revealed significantly diverse expressions of miR-1-3p and miR-16-5p in participants with and without an early LVEF decline of ≥ 10%. Despite cardiac injury demonstrated by dynamic miR-1-3p and miR-16-5p, CMR parameters revealed no significant differences.

CONCLUSIONS: Our study demonstrates a very low incidence of long-term symptomatic CTRCD. The diverse expression patterns of miR-16-5p and miR-1-3p at different time points also provide valuable biological insights. Within-normal results of an exact and comprehensive CMR, in asymptomatic and any LVEF change participants, indicate the long-term safety of limited-dose anthracycline-containing use.

PMID:40270054 | DOI:10.1186/s40959-025-00337-2

Commun Biol. 2025 Apr 23;8(1):653. doi: 10.1038/s42003-025-07877-4.

ABSTRACT

Cystic fibrosis (CF) is a genetic disease caused by dysfunction in the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) chloride channel. Patients with CF are hypersusceptible to Mycobacterium abscessus infection, a fast-growing mycobacterium and harmful opportunistic pathogen. Although CFTR dysfunction is known as a host susceptibility factor for M. abscessus infection, the functional impact of the trimeric Epithelial sodium Channel (ENaC), whose activity is negatively regulated by CFTR, towards M. abscessus infection has not been explored yet. To address this issue, we took advantage of miR-263a deficient Drosophila presenting a CF-like phenotype due to ENaC hyperactivity (ENaC+ ). We observed that the ENaC+ flies were as hypersusceptible to M. abscessus infection as the Cftr-deficient flies. The hypersensitivity of ENaC+ flies to M. abscessus infection was fully rescued by blocking ENaC hyperactivity, both chemically and genetically. Furthermore, we observed that ENaC hyperactivity per se was detrimental to ENaC+ Drosophila, as they were unable to mount an efficient humoral immune response. Upon infection, ENaC+ flies failed to upregulate 20-hydroxyecdysone production, which subsequently altered the production of protective antimicrobial peptides against M. abscessus. Overall, our results show that ENaC plays a key role in host susceptibility to M. abscessus infection and, correlatively to other CF pathogens.

PMID:40269088 | DOI:10.1038/s42003-025-07877-4