Allergy. 2025 May 22. doi: 10.1111/all.16604. Online ahead of print.

NO ABSTRACT

PMID:40401397 | DOI:10.1111/all.16604

Nanomedicine (Lond). 2025 May 22:1-12. doi: 10.1080/17435889.2025.2508133. Online ahead of print.

ABSTRACT

AIMS: To develop a nano-immunotherapy system combining autophagy inhibition and innate immune activation to reverse the immunosuppressive tumor microenvironment (TME) in pancreatic ductal adenocarcinoma (PDAC).

MATERIALS & METHODS: The pH-responsive polymer PC7A was utilized to co-deliver the autophagy inhibitor chloroquine (CQ) and the STING agonist cyclic diguanylate (CDG), forming the CQCP nanosystem. In vitro and in vivo experiments evaluated autophagy inhibition, MHC-I expression, dendritic cell activation, tumor infiltration of lymphocytes, and survival in PDAC-bearing mice.

RESULTS: CQCP enhanced MHC-I expression on PDAC cells by 2.1-fold (p < 0.001) and increased activated dendritic cells (CD86+/CD40+) by 3.5-fold (p < 0.01) in the TME. Tumor-infiltrating CD8+ T cells rose by 42.6% (p < 0.001), and systemic immune activation in peripheral lymphoid tissues was observed. CQCP achieved an 86% survival rate in tumor-bearing mice, significantly outperforming monotherapies or free drug combinations.

CONCLUSIONS: The CQCP system synergistically reverses PDAC immunosuppression by restoring antigen presentation and activating innate immunity. This dual-targeted strategy demonstrates robust antitumor efficacy and offers a promising immunotherapy approach for PDAC.

PMID:40401367 | DOI:10.1080/17435889.2025.2508133

Brief Bioinform. 2025 May 1;26(3):bbaf223. doi: 10.1093/bib/bbaf223.

ABSTRACT

Network analysis has become an essential tool in biological and biomedical research, providing insights into complex biological mechanisms. Since biological systems are inherently time-dependent, incorporating time-varying methods is crucial for capturing temporal changes, adaptive interactions, and evolving dependencies within networks. Our study explores key time-varying methodologies for network structure estimation and network inference based on observed structures. We begin by discussing approaches for estimating network structures from data, focusing on the time-varying Gaussian graphical model, dynamic Bayesian network, and vector autoregression-based causal analysis. Next, we examine analytical techniques that leverage pre-specified or observed networks, including other autoregression-based methods and latent variable models. Furthermore, we explore practical applications and computational tools designed for these methods. By synthesizing these approaches, our study provides a comprehensive evaluation of their strengths and limitations in the context of biological data analysis.

PMID:40401349 | DOI:10.1093/bib/bbaf223

BMC Methods. 2025;2(1):10. doi: 10.1186/s44330-025-00029-4. Epub 2025 May 19.

ABSTRACT

BACKGROUND: Collaborative efforts, such as the Human Cell Atlas, are rapidly accumulating large amounts of single-cell data. To ensure that single-cell atlases are representative of human genetic diversity, we need to determine the ancestry of the donors from whom single-cell data are generated. Self-reporting of race and ethnicity, although important, can be biased and is not always available for the datasets already collected.

METHODS: Here, we introduce scAI-SNP, a tool to infer ancestry directly from single-cell genomics data. To train scAI-SNP, we identified 4.5 million ancestry-informative single-nucleotide polymorphisms (SNPs) in the 1000 Genomes Project dataset across 3201 individuals from 26 population groups. For a query single-cell dataset, scAI-SNP uses these ancestry-informative SNPs to compute the contribution of each of the 26 population groups to the ancestry of the donor from whom the cells were obtained.

RESULTS: Using diverse single-cell datasets with matched whole-genome sequencing data, we show that scAI-SNP is robust to the sparsity of single-cell data, can accurately and consistently infer ancestry from samples derived from diverse types of tissues and cancer cells, and can be applied to different modalities of single-cell profiling assays, such as single-cell RNA-seq and single-cell ATAC-seq.

DISCUSSION: Finally, we argue that ensuring that single-cell atlases represent diverse ancestry, ideally alongside race and ethnicity, is ultimately important for improved and equitable health outcomes by accounting for human diversity.

SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s44330-025-00029-4.

PMID:40401145 | PMC:PMC12089154 | DOI:10.1186/s44330-025-00029-4

Pathog Immun. 2025 May 19;10(2):87-96. doi: 10.20411/pai.v10i2.801. eCollection 2025.

ABSTRACT

BACKGROUND: The dissemination of highly pathogenic avian influenza (HPAI) A(H5N1) in US poultry and dairy cows poses a public health threat. Farm workers caring for infected animals are at risk to acquire infections due to exposure to contaminated milk or poultry feces and secretions. Far ultraviolet-C (UV-C) light could provide continuous decontamination of surfaces and air in agricultural settings, but efficacy against organisms in whole milk or chicken manure is unclear.

METHODS: We examined the efficacy of far UV-C light against bacteriophage MS2 and methicillin-resistant Staphylococcus aureus (MRSA) in phosphate-buffered saline (PBS), 5% fetal calf serum, whole milk, or 5%, 10%, and 25% chicken manure, both in liquid suspension and dried on surfaces. We also compared the efficacy of 300 mJ/cm2 doses of far UV-C and 254-nm UV-C light against the test organisms in liquid droplets or droplets dried on surfaces.

RESULTS: For both test organisms, far UV-C achieved significantly smaller log10 reductions in whole milk and in chicken manure suspensions than in PBS or 5% fetal calf serum, both in liquid suspension and when dried on surfaces (P<0.0001). In whole milk, average reductions of both organisms with all doses were ≤1.2 log10 in liquid suspensions and ≤2.4 log10 when dried on surfaces. We found 254-nm UV-C was significantly more effective in reducing MRSA and MS2 dried on surfaces in whole milk or in 10% chicken manure (P≤0.02) but not in liquid droplets (P>0.05) except 5% chicken manure (P<0.001).

CONCLUSIONS: Our results suggest that in the absence of prior cleaning and disinfection far UV-C and 254-nm UV-C light technologies may have limited efficacy as an adjunctive method to reduce the risk for transmission of HPAI from surfaces in high-risk settings on farms.

PMID:40400617 | PMC:PMC12094166 | DOI:10.20411/pai.v10i2.801

Environ Health (Wash). 2025 Feb 11;3(5):526-538. doi: 10.1021/envhealth.4c00206. eCollection 2025 May 16.

ABSTRACT

Perfluorooctanesulfonate (PFOS), an emerging contaminant with widespread concern, has been associated with the pathogenesis of atherosclerosis (AS). As a substitute for PFOS, sodium p-perfluorous nonenoxybenzenesulfonate (OBS) is extensively utilized in various applications and detected in human blood. However, its potential health risk in AS remain unclear. In this study, we investigated the comparative impacts of PFOS and OBS on endothelial dysfunction and atherogenesis. In the in vivo study, Apolipoprotein E knockout (ApoE-/-) mice were exposed to 0.4 or 4 mg/L PFOS/OBS for 12 weeks. We found that dyslipidemia developed more rapidly in the OBS-exposed mice than in the PFOS-exposed mice. PFOS exhibited a higher enrichment capacity in both blood and aortic tissues than OBS. Remarkably, OBS induced a more pronounced inflammatory response and caused a more significant disruption of the endothelial barrier in the aorta of ApoE-/- mice compared to PFOS. In vitro experiments showed that OBS, at the same exposure concentrations and durations as PFOS (0.1-20 μmol/L, 48 h), more effectively inhibited cell viability of human umbilical vein endothelial cells (HUVECs), caused higher levels of lactate dehydrogenase (LDH) release, and enhanced cell adhesion between HUVECs and monocytes. Both PFOS and OBS were found to activate the NF-κB signaling pathway and upregulate the expression of inflammatory factors. Notably, the use of OBS, but not PFOS, was shown to disrupt cell junctions and increase endothelial permeability by activating the MAPK/ERK signaling pathway. Our findings suggest that OBS may lead to endothelial dysfunction and have a greater impact on AS compared to PFOS, presenting significant health risks in cardiovascular diseases.

PMID:40400551 | PMC:PMC12090012 | DOI:10.1021/envhealth.4c00206

Genes Cells. 2025 May;30(3):e70027. doi: 10.1111/gtc.70027.

ABSTRACT

Fibulin 2 (FBLN2) is an extracellular matrix glycoprotein. Exclusion of exon 9 of FBLN2 is one of the most recurrent splicing events across multiple types of cancer, but its functional relevance in cancer has remained unexplored. We here reveal that the exclusion of exon 9 of FBLN2 results in the loss of a single N-glycosylation site that leads to misfolding of the FBLN2 protein as well as to a reduction in both its stability and secretion efficiency. Indeed, the extracellular matrix of human colorectal cancer tissue exhibits a reduced abundance of FBLN2. This deficiency of FBLN2 together with a concomitant increase in the abundance of fibronectin 1 in the tumor microenvironment promotes the adhesion and migration of colorectal cancer cells. Our data thus suggest that the alternative splicing of FBLN2 exon 9 generates a prometastatic extracellular environment in cancer tissue by determining FBLN2 glycosylation.

PMID:40400104 | DOI:10.1111/gtc.70027

J Nurs Manag. 2025 May 14;2025:9921349. doi: 10.1155/jonm/9921349. eCollection 2025.

ABSTRACT

Background: Adverse drug reactions (ADRs), particularly in the context of polypharmacy, remain a persistent, unresolved problem for patients and healthcare professionals. The ADRe Profile identifies medicine-related harms, and supports their resolution, thereby improving care quality and preventing future problems. Objective: The objective of this study was to assess the validity and reliability of the ADRe Profile (https://www.swansea.ac.uk/adre/) in U.K. primary care general practices, building on assessments in other settings. Methods: The ADRe Profile's validity and reliability were investigated using complementary mixed methods: content validity index, contrast group construct validity, cognitive interviewing, and inter-rater reliability. Results: Cognitive interviews (n = 5) confirmed that the ADRe Profile needed only minor adjustments. The scale-level content validity index was 0.67 (n = 14), items ranging from 0.08 to 1. Significant differences in signs and symptoms associated with ADRs between service users taking different numbers of regular prescribed medicines confirmed construct validity (n = 68, U = 870.50, p < 0.001). Inter-rater reliability testing showed substantial agreement between service users and research nurse: 10 items had 100% agreement. Overall kappa mean was 0.71 (range: 0.31-1), (n = 42). Conclusions and Relevance: The ADRe Profile is suitable for use with older service users in primary care who live at home. Users understood the questions and provided meaningful answers. ADRe Profile responses were sufficiently reliable to be used as a basis for further investigations, prescriber referral and clinical actions. However, clinician judgement of content validity may depend on knowledge and experience, highlighting the importance of training. Clinicians acknowledged that the ADRe Profile was comprehensive but identified practical difficulties. Instruments to reduce ADRs should be validated before testing in feasibility studies and randomised controlled trials. Implications for Nursing Management: Managers need to optimise patient safety by introducing patient-centred symptom monitoring, with decision support. Before instruments are adopted, managers should check the reliability and validity data. Trial Registration: ClinicalTrials.gov identifier: NCT04663360.

PMID:40401039 | PMC:PMC12094870 | DOI:10.1155/jonm/9921349

Hosp Pharm. 2025 May 19:00185787251337621. doi: 10.1177/00185787251337621. Online ahead of print.

ABSTRACT

Background: Tendinopathies and ligament disorders are significant musculoskeletal adverse events associated with various drugs, leading to restricted mobility and reduced quality of life. Although certain drug classes such as fluoroquinolones and corticosteroids have established links to these conditions, there is limited research on other potential drug associations. This study aimed to comprehensively evaluate drugs associated with tendinopathies and ligament disorders using data from the USFDA Adverse Event Reporting System (AERS). Methods: A retrospective pharmacovigilance study utilizing spontaneous reports from the USFDA AERS database between March 2004 and June 2024 was conducted. The Standardized Medical Dictionary for Regulatory Activities (MedDRA) query "Tendinopathies and ligament disorders" and relevant Preferred Terms were used to identify cases. Disproportionality analysis was performed using both frequentist and Bayesian methods. Subgroup analyses were conducted by age, gender, and clinical outcomes. Results: Out of 29 153 222 reports, 40 485 unique reports were included, with 6641 related to tendon rupture and 2121 to ligament rupture. Fluoroquinolones, corticosteroids, lipid-modifying agents, immunosuppressants, and bisphosphonates were confirmed to have strong associations with tendon and ligament disorders. Emergent signals were identified for anti-inflammatory drugs, and various other drugs, including vaccines. Hospitalization rates were significantly higher in cases of tendon rupture compared to ligament rupture (P < .0001). Conclusion: This study confirms established drug associations and identifies new signals for tendinopathies and ligament disorders. Continued pharmacovigilance is necessary to validate these findings and enhance our understanding of drug-induced musculoskeletal disorders.

PMID:40400906 | PMC:PMC12089119 | DOI:10.1177/00185787251337621

Front Med (Lausanne). 2025 May 7;12:1467001. doi: 10.3389/fmed.2025.1467001. eCollection 2025.

ABSTRACT

Drug-induced pneumonia is a rare and potentially life-threatening adverse drug reaction. Moxifloxacin is a fluoroquinolone antibiotic with broad-spectrum antimicrobial activity. Despite reports of moxifloxacin-related side effects such as interstitial nephritis, recurrent tendinitis, and pseudoallergic reactions, moxifloxacin-induced pneumonia is exceedingly rare. We report the case of a 45-year-old male who developed fever and cough, and progressed to hypersensitivity syndrome related to drug-induced pneumonia following moxifloxacin therapy. Discontinuation of moxifloxacin led to resolution of fever with significant resolution of pulmonary lesions. Comprehensive laboratory investigations ruled out other causes, confirming drug-induced pneumonia due to moxifloxacin. This case report provides typical clinical manifestations and pulmonary imaging changes, as well as an analysis of differential diagnosis of pulmonary lesions and key management strategies. The case and related literature review contribute to enhancing our understanding of moxifloxacin-related pneumonia, with important clinical significance in promptly correcting adverse reactions and improving patient outcomes.

PMID:40400635 | PMC:PMC12092464 | DOI:10.3389/fmed.2025.1467001

Genome Med. 2025 May 22;17(1):58. doi: 10.1186/s13073-025-01467-z.

ABSTRACT

BACKGROUND: Only half of individuals with suspected rare diseases receive a genetic diagnosis following genomic testing. A genetic diagnosis allows access to appropriate care, restores reproductive confidence and reduces the number of potentially unnecessary interventions. A major barrier is the lack of disease agnostic functional tests suitable for implementation in routine diagnostics that can provide evidence supporting pathogenicity of novel variants, especially those refractory to RNA sequencing.

METHODS: Focusing on mitochondrial disease, we describe an untargeted mass-spectrometry based proteomics pipeline that can quantify proteins encoded by > 50% of Mendelian disease genes and > 80% of known mitochondrial disease genes in clinically relevant sample types, including peripheral blood mononuclear cells (PBMCs). In total we profiled > 90 individuals including undiagnosed individuals suspected of mitochondrial disease and a supporting cohort of disease controls harbouring pathogenic variants in nuclear and mitochondrial genes. Proteomics data were benchmarked against pathology accredited respiratory chain enzymology to assess the performance of proteomics as a functional test. Proteomics testing was subsequently applied to individuals with suspected mitochondrial disease, including a critically ill infant with a view toward rapid interpretation of variants identified in ultra-rapid genome sequencing.

RESULTS: Proteomics testing provided evidence to support variant pathogenicity in 83% of individuals in a cohort with confirmed mitochondrial disease, outperforming clinical respiratory chain enzymology. Freely available bioinformatic tools and criteria developed for this study ( https://rdms.app/ ) allow mitochondrial dysfunction to be identified in proteomics data with high confidence. Application of proteomics to undiagnosed individuals led to 6 additional diagnoses, including a mitochondrial phenocopy disorder, highlighting the disease agnostic nature of proteomics. Use of PBMCs as a sample type allowed rapid return of proteomics data supporting pathogenicity of novel variants identified through ultra-rapid genome sequencing in as little as 54 h.

CONCLUSIONS: This study provides a framework to support the integration of a single untargeted proteomics test into routine diagnostic practice for the diagnosis of mitochondrial and potentially other rare genetic disorders in clinically actionable timelines, offering a paradigm shift for the functional validation of genetic variants.

PMID:40400026 | DOI:10.1186/s13073-025-01467-z

J Biomed Sci. 2025 May 21;32(1):50. doi: 10.1186/s12929-025-01137-7.

ABSTRACT

BACKGROUND: Type 2 diabetes is an increasingly prevalent metabolic disorder with moderate to high heritability. Glycemic indices are crucial for diagnosing and monitoring the disease. Previous genome-wide association study (GWAS) have identified several risk loci associated with type 2 diabetes, but data from the Taiwanese population remain relatively sparse and primarily focus on type 2 diabetes status rather than glycemic trait levels.

METHODS: We conducted a comprehensive genome-wide meta-analysis to explore the genetics of glycemic traits. The study incorporated a community-based cohort of 145,468 individuals and a hospital-based cohort of 35,395 individuals. The study integrated genetics, transcriptomics, biological pathway analyses, polygenic risk score calculation, and drug repurposing for type 2 diabetes.

RESULTS: This study assessed hemoglobin A1c and fasting glucose levels, validating known loci (FN3K, SPC25, MTNR1B, and FOXA2) and discovering new genes, including MAEA and PRC1. Additionally, we found that diabetes, blood lipids, and liver- and kidney-related traits share genetic foundations with glycemic traits. A higher PRS was associated with an increased risk of type 2 diabetes. Finally, eight repurposed drugs were identified with evidence to regulate blood glucose levels, offering new avenues for the management and treatment of type 2 diabetes.

CONCLUSIONS: This research illuminates the unique genetic landscape of glucose regulation in Taiwanese Han population, providing valuable insights to guide future treatment strategies for type 2 diabetes.

PMID:40399988 | DOI:10.1186/s12929-025-01137-7

Sci Rep. 2025 May 21;15(1):17704. doi: 10.1038/s41598-025-00547-9.

ABSTRACT

This study explores the efficacy of glibenclamide, a KATP channel inhibitor, for treating Cantú syndrome (CS), a genetic disorder characterized by hypertrichosis and cardiovascular abnormalities. Treatment with glibenclamide for Cantú syndrome has only been reported in a single case report. In this study, we tested this repurposed drug in both a zebrafish model and an open-label trial with CS patients. CS zebrafish embryos, created using CRISPR/Cas9, were treated with glibenclamide. Their cardiac function was assessed using high-speed imaging. In the trial part of the study, four adults with CS used 2.5 mg glibenclamide daily for 8 months. Hypertrichosis, cardiac function, and edema were evaluated and glucose levels were monitored continuously. In the zebrafish model of CS glibenclamide reversed cardiac abnormalities. However, in the clinical trial, the effects on hypertrichosis were mixed, and there were no significant changes in cardiac phenotype or leg edema. One participant reported reduced facial erythema and puffiness, which relapsed post-trial. The treatment was generally safe, with multiple instances of level 1 hypoglycemia but no severe adverse events. In conclusion, glibenclamide can reverse cardiac abnormalities in a CS zebrafish model. Its effect on hypertrichosis and cardiovascular features in humans with CS are unclear and dosage increases are challenging due to hypoglycemia, which is important knowledge for treatment considerations in this rare genetic syndrome.Trial registration: EudraCT Number 2019-004651-36. Date of first registration 21/05/2021.

PMID:40399303 | DOI:10.1038/s41598-025-00547-9