Cell Signal. 2025 May 15:111867. doi: 10.1016/j.cellsig.2025.111867. Online ahead of print.

ABSTRACT

Idiopathic pulmonary fibrosis (IPF) is a progressive interstitial lung disease characterized by irreversible scarring of the lungs, predominantly affecting older adults. The limited therapeutic options available are largely due to an insufficient understanding of IPF etiology and pathogenesis. This study investigated potential biomarkers to enhance IPF diagnosis and treatment strategies. Through single-cell RNA sequencing (scRNA-seq) and bulk RNA sequencing analyses of public datasets, four hub genes-FTH1, FABP5, DCXR, and IGFBP7-were identified as strongly associated with IPF. Subsequent validation in in vivo and in vitro models confirmed IGFBP7 as a novel biomarker. Double immunofluorescence staining and scRNA-seq analysis revealed that IGFBP7 expression is elevated in IPF epithelial cells. IGFBP7 shows potential for early diagnosis of IPF and can differentiate IPF from other diseases. Gene set enrichment analysis revealed the involvement of IGFBP7 in IPF pathogenesis, particularly through its strong connection to the TGF-β signaling pathway, which drives inflammation and fibrosis. In vitro studies with the TGF-β inhibitor SB431542 showed that inhibition of the TGF-β pathway significantly reduced IGFBP7 expression. Furthermore, IGFBP7 knockdown decreased the expression of markers associated with epithelial-mesenchymal transition and fibrosis while suppressing TGF-β1 expression. These results suggest that IGFBP7 forms a positive feedback loop with TGF-β1. In conclusion, this research identified IGFBP7 as a promising biomarker with significant diagnostic and therapeutic potential for IPF. These insights pave the way for improved diagnostics and the development of targeted antifibrosis therapies, while deepening our understanding of IPF mechanisms.

PMID:40381971 | DOI:10.1016/j.cellsig.2025.111867

Lancet Rheumatol. 2025 May 14:S2665-9913(25)00026-8. doi: 10.1016/S2665-9913(25)00026-8. Online ahead of print.

ABSTRACT

BACKGROUND: In patients with systemic sclerosis, it is common practice to treat interstitial lung disease (ILD) in patients in whom progression has already occurred. We sought to clarify whether observed progression of systemic sclerosis-associated ILD confers risk for subsequent progression.

METHODS: In this multicentre observational cohort study, based on an analysis of prospectively collected data, we included patients with systemic sclerosis-associated ILD aged 18 years or older at diagnosis, who fulfilled the 2013 American College of Rheumatology-European Association of Alliances in Rheumatology systemic sclerosis classification criteria. The main cohort (diagnosed between January 2001 and December 2019) was consecutively followed up annually over 4 years at the Department of Rheumatology at the Oslo University Hospital, Norway, and the Department of Rheumatology at the University Hospital Zurich, Switzerland. We applied four definitions of ILD progression: the primary definition was forced vital capacity (FVC) decline of 5% or more, and secondary definitions included FVC decline of 10% or more, progressive pulmonary fibrosis (PPF), and progressive fibrosing ILD (PF-ILD). We applied these definitions at each annual visit after the first (visit 1). We validated our findings in an enriched cohort that included patients from the main cohort with systemic sclerosis-associated ILD and short disease duration of less than 3 years along with patients diagnosed between January 2003 and September 2019 from the Division of Rheumatology, University of Michigan, Ann Arbor, MI, USA. Multivariable logistic regression analyses were applied to predict ILD progression and its effect on mortality. There was no involvement of people with lived experience in this study.

FINDINGS: Of 231 patients with systemic sclerosis-associated ILD from the main cohort (mean age 48·0 years [SD 14·6], 176 [76%] female and 55 [24%] male), 71 (31%) had ILD progression as defined by an FVC decline of 5% or more between visit 1 and visit 2, 38 (16%) as defined by an FVC decline of 10% or more, 39 (17%) as defined by PPF, and 89 (39%) defined by PF-ILD. In multivariable logistic regression analyses, adjusted for risk factors for progressive systemic sclerosis-associated ILD and immunosuppressive treatment, we found that ILD progression, defined by FVC decline of 5% or more, from visit 1 to visit 2 reduced the risk for further progression from visit 2 to visit 3 (odds ratio [OR] 0·28 [95% CI 0·12-0·63]; p=0·002) and that there was no risk for subsequent progression using the other definitions (FVC decline of ≥10%: 0·57 [0·16-1·99; p=0·38]; PPF: 0·93 [0·39-2·22; p=0·88]; and PF-ILD: 0·69 [0·35-1·36]; p=0·28]). Using the primary definition of progression, we found the same results in the enriched systemic sclerosis-associated ILD cohort, wherein 41 (34%) of 121 patients had progression defined by an FVC decline of 5% or more (OR 0·22 [95% CI 0·06-0·87]; p=0·031). FVC decline of 5% or more was significantly associated with mortality (hazard ratio 1·66 [95% CI 1·05-2·62]; p=0·030) adjusted for other risk factors.

INTERPRETATION: Systemic sclerosis-associated ILD progression does not predict further ILD progression at the next annual follow-up visit, even in an enriched population, but progression was associated with mortality. These results have implications for clinical practice because they support a paradigm shift in treatment strategy, advocating for initiating therapy in patients at risk of progression. Further research is needed to confirm these findings.

FUNDING: None.

TRANSLATIONS: For the German and Norwegian translations of the abstract see Supplementary Materials section.

PMID:40381640 | DOI:10.1016/S2665-9913(25)00026-8

Nat Commun. 2025 May 17;16(1):4607. doi: 10.1038/s41467-025-59780-5.

ABSTRACT

Cis-regulatory elements (CREs), including enhancers, silencers, promoters and insulators, play pivotal roles in orchestrating gene regulatory mechanisms that drive complex biological traits. However, current approaches for CRE identification are predominantly sequence-based and typically focus on individual CRE types, limiting insights into their cell-type-specific functions and regulatory dynamics. Here, we present CREATE, a multimodal deep learning framework based on Vector Quantized Variational AutoEncoder, tailored for comprehensive CRE identification and characterization. CREATE integrates genomic sequences, chromatin accessibility, and chromatin interaction data to generate discrete CRE embeddings, enabling accurate multi-class classification and robust characterization of CREs. CREATE excels in identifying cell-type-specific CREs, and provides quantitative and interpretable insights into CRE-specific features, uncovering the underlying regulatory codes. By facilitating large-scale prediction of CREs in specific cell types, CREATE enhances the recognition of disease- or phenotype-associated biological variabilities of CREs, thus advancing our understanding of gene regulatory landscapes and their roles in health and disease.

PMID:40382355 | DOI:10.1038/s41467-025-59780-5

Trends Genet. 2025 May 16:S0168-9525(25)00103-9. doi: 10.1016/j.tig.2025.04.011. Online ahead of print.

ABSTRACT

LINE-1 (long interspersed nuclear element 1, L1) retrotransposons constitute ~17% of human DNA (~0.5 million genomic L1 copies) and exhibit context-dependent expression in different cell lines. Recent studies reveal that L1 is under multilayered control by diverse factors that either collaborate or compete with each other to ensure precise L1 activity. Remarkably, L1s have been co-opted as various transcription-dependent regulatory elements, such as promoters, enhancers, and topologically associating domain (TAD) boundaries, that regulate gene expression in zygotic genome activation, aging, cancer, and other disorders. This review highlights the regulation of L1 and its regulatory functions that influence disease and development.

PMID:40382218 | DOI:10.1016/j.tig.2025.04.011

Int J Radiat Oncol Biol Phys. 2025 Jun 1;122(2):524. doi: 10.1016/j.ijrobp.2025.03.057.

NO ABSTRACT

PMID:40382175 | DOI:10.1016/j.ijrobp.2025.03.057

J Mol Biol. 2025 May 15:169222. doi: 10.1016/j.jmb.2025.169222. Online ahead of print.

NO ABSTRACT

PMID:40381984 | DOI:10.1016/j.jmb.2025.169222

Neurobiol Dis. 2025 May 15:106954. doi: 10.1016/j.nbd.2025.106954. Online ahead of print.

ABSTRACT

Pathogenic variants in the neuronal Na+/K+ ATPase transmembrane ion transporter (ATP1A3) cause a spectrum of neurological disorders including alternating hemiplegia of childhood (AHC). The most common de novo pathogenic variants in AHC are p.D801N (~40 % of patients) and p.E815K (~25 % of patients), which lead to early mortality by spontaneous death in mice. Nevertheless, knowledge of the development of clinically relevant neurological phenotypes without the obstacle of premature death, is critical for the identification of pathophysiological mechanisms and ultimately, for the testing of therapeutic strategies in disease models. Here, we used hybrid vigor attempting to mitigate the fragility of AHC mice and then performed behavioral, electrophysiological, biochemical, and molecular testing to comparatively analyze mice that carry either of the two most common AHC patient observed variants in the Atp1a3 gene. Collectively, our data reveal the presence but also the differential impact of the p.D801N and p.E815K variants on disease relevant alterations such as spontaneous and stress-induced paroxysmal episodes, motor function, behavioral and neurophysiological activity, and neuroinflammation. Our alternate AHC mouse models with their phenotypic deficits open novel avenues for the investigation of disease biology and therapeutic testing for ATP1A3 research.

PMID:40381892 | DOI:10.1016/j.nbd.2025.106954

Antiviral Res. 2025 May 15:106190. doi: 10.1016/j.antiviral.2025.106190. Online ahead of print.

ABSTRACT

LP-98 is a lipopeptide-based HIV fusion inhibitor with exceptional potency and long-acting antiviral activity, currently in phase II clinical trials. In this study, we elucidated the structural basis of LP-98's antiviral activity and resistance mechanisms. Using AlphaFold3, we first predicted the six-helical bundle (6-HB) structure formed by LP-98 and the gp41-derived NHR peptide N44, identifying key residues mediating interhelical interactions. Subsequent crystallographic analysis of the LP-98/N44 complex confirmed these binding features, revealing that a cluster of hydrophobic residues in LP-98, along with a network of 15 hydrogen bonds, two electrostatic interactions and a salt bridge, critically stabilizes the 6-HB structure. Superposition analyses of the LP-98/N44 crystal structure with either the predicted 6-HB model or the LP-40/N44 crystal structure provided further mechanistic insights into LP-98's binding mode. Additionally, structural and functional characterization of the N-terminal Tyr-127 residue using a truncated variant (LP-98-Y) demonstrated its essential role in inhibitor binding and antiviral activity. Notably, LP-98 exhibited significantly reduced efficacy against T20-resistant HIV strains harboring single or double mutations in NHR. Our structural models shed light on the molecular basis of this resistance, offering critical insights for drug optimization. Collectively, these findings provide a detailed structural understanding of LP-98's antiviral mechanism, supporting its continued development as a promising next-generation HIV fusion inhibitor.

PMID:40381660 | DOI:10.1016/j.antiviral.2025.106190

Neuron. 2025 May 13:S0896-6273(25)00298-3. doi: 10.1016/j.neuron.2025.04.015. Online ahead of print.

ABSTRACT

We report a role for activity in the development of the primary sensory neurons that detect touch. Genetic deletion of Piezo2, the principal mechanosensitive ion channel in somatosensory neurons, caused profound changes in the formation of mechanosensory end-organ structures. Peripheral-nervous-system-specific deletion of the voltage-gated sodium channel Nav1.6 (Scn8a), which resulted in altered electrophysiological responses to mechanical stimuli, also disrupted somatosensory neuron morphologies, supporting a role for neuronal activity in end-organ formation. Single-cell RNA sequencing of Piezo2 mutants revealed changes in gene expression in sensory neurons activated by light mechanical forces, whereas other neuronal classes were minimally affected, and genetic deletion of Piezo2-dependent genes partially reproduced the defects in mechanosensory neuron structures observed in Piezo2 mutants. These findings indicate that mechanically evoked neuronal activity acts early in life to shape the maturation of mechanosensory end-organs that underlie our sense of gentle touch.

PMID:40381613 | DOI:10.1016/j.neuron.2025.04.015

Pediatr Neurol. 2025 Apr 25;168:67-81. doi: 10.1016/j.pediatrneurol.2025.04.010. Online ahead of print.

ABSTRACT

Developmental and epileptic encephalopathies (DEEs) are severe neurological disorders characterized by childhood-onset seizures and significant developmental impairments. Seizures are often refractory to treatment with traditional antiseizure medications, which fail to address the underlying genetic and molecular mechanisms. This comprehensive review explores the evolving landscape of precision therapeutics for DEEs, focusing on mechanism-driven interventions across key pathophysiologic categories. Targeted approaches for channelopathies include antisense oligonucleotides and gene therapies, such as zorevunersen and ETX101 for SCN1A-related Dravet syndrome, alongside novel small molecules for other ion channel disorders. Advances in targeting neurotransmitter receptor dysfunctions, including γ-aminobutyric acid and glutamate receptor variants, highlight the use of modulators such as gaboxadol, radiprodil, and l-serine, alongside emerging gene therapies. For synaptic dysfunctions, innovative treatments such as chemical chaperones for STXBP1-related disorders and Ras-Raf-MEK-ERK inhibitors for SYNGAP1 pathologies are discussed. The review also examines precision interventions targeting cellular signaling pathways in tuberous sclerosis complex, epigenetic regulation in Rett syndrome, and metabolic interventions like ketogenic diets and targeted supplementation for specific genetic etiologies. Additionally, the importance of enhancing access to genetic testing, conducting robust natural history studies, and employing innovative clinical trial designs is emphasized. Future directions focus on addressing the challenges in developing and implementing gene-based therapies, integrating systems biology, leveraging artificial intelligence for data analysis, and fostering collaboration among stakeholders. The rapidly advancing field of precision therapeutics for DEEs holds promise to improve outcomes through tailored, equitable, and patient-centered care.

PMID:40381457 | DOI:10.1016/j.pediatrneurol.2025.04.010

Neoplasia. 2025 May 16;66:101173. doi: 10.1016/j.neo.2025.101173. Online ahead of print.

ABSTRACT

Obesity-related oesophageal adenocarcinoma (OAC), arising from Barrett's oesophagus (BO), incidence rates are rising coincident with high-fat diets. However, adipose tissue phenotype drives metabolic characteristics. Prior feeding studies demonstrated that obesogenic diets enriched in saturated fatty acids (SFA) induce a more adverse metabolic and pro-inflammatory adipose phenotype, compared to monounsaturated fatty acids (MUFA) enriched high-fat diets, despite equal obesity. We hypothesise that different fatty acids may alter the progression of BO to OAC, wherein SFA may be more pathogenic compared to MUFA. Proteomic analysis shows that SFA, not MUFA, increases fatty acid metabolism, oncogenic signalling, and mitochondrial respiratory chain to a greater extent in BO but not in OAC cells. Cellular metabolic analysis validated proteomic findings to show mitochondrial dysfunction in BO but showed an increase in glycolysis in OAC following SFA treatment compared to MUFA. Additionally, it showed a decrease in mitochondrial ATP production following treatment of SFA in BO and OAC cells. Reduction of SFA intake may be beneficial as a supplementary treatment approach to manage and/or prevent OAC progression.

PMID:40381373 | DOI:10.1016/j.neo.2025.101173

ISME J. 2025 May 17:wraf096. doi: 10.1093/ismejo/wraf096. Online ahead of print.

ABSTRACT

Phytoplankton account for nearly half of global photosynthetic carbon fixation, and the fate of that carbon is regulated in large part by microbial food web processing. We currently lack a mechanistic understanding of how interactions among heterotrophic bacteria impact the fate of photosynthetically fixed carbon. Here, we used a set of bacterial isolates capable of growing on exudates from the diatom Phaeodactylum tricornutum to investigate how bacteria-bacteria interactions affect the balance between exudate remineralization and incorporation into biomass. With exometabolomics and genome-scale metabolic modeling, we estimated the degree of resource competition between bacterial pairs. In a sequential spent media experiment, we found that pairwise interactions were more beneficial than predicted based on resource competition alone, and 30% exhibited facilitative interactions. To link this to carbon fate, we used single-cell isotope tracing in a custom cultivation system to compare the impact of different "primary" bacterial strains in close proximity to live P. tricornutum on a distal "secondary" strain. We found that a primary strain with a high degree of competition decreased secondary strain carbon drawdown by 51% at the single-cell level, providing a quantitative metric for the "cost" of competition on algal carbon fate. Additionally, a primary strain classified as facilitative based on sequential interactions increased total algal-derived carbon assimilation by 7.6 times, integrated over all members, compared to the competitive primary strain. Our findings suggest that the degree of interaction between bacteria along a spectrum from competitive to facilitative is directly linked to algal carbon drawdown.

PMID:40381217 | DOI:10.1093/ismejo/wraf096

Cell Rep. 2025 May 15;44(5):115710. doi: 10.1016/j.celrep.2025.115710. Online ahead of print.

ABSTRACT

The importance of serine as a metabolic regulator is well known for tumors and is also gaining attention in degenerative diseases. Recent data indicate that de novo serine biosynthesis is an integral component of the metabolic response to mitochondrial disease, but the roles of the response have remained unknown. Here, we report that glucose-driven de novo serine biosynthesis maintains metabolic homeostasis in energetic stress. Pharmacological inhibition of the rate-limiting enzyme, phosphoglycerate dehydrogenase (PHGDH), aggravated mitochondrial muscle disease, suppressed oxidative phosphorylation and mitochondrial translation, altered whole-cell lipid profiles, and enhanced the mitochondrial integrated stress response (ISRmt) in vivo in skeletal muscle and in cultured cells. Our evidence indicates that de novo serine biosynthesis is essential to maintain mitochondrial respiration, redox balance, and cellular lipid homeostasis in skeletal muscle with mitochondrial dysfunction. Our evidence implies that interventions activating de novo serine synthesis may protect against mitochondrial failure in skeletal muscle.

PMID:40381195 | DOI:10.1016/j.celrep.2025.115710

Mol Neurobiol. 2025 May 17. doi: 10.1007/s12035-025-05047-5. Online ahead of print.

ABSTRACT

Disruption of the Wnt signaling pathway (WSP), a highly conserved pathway essential for growth and organ development, has been proven to play a role in the pathogenesis of Alzheimer's disease (AD). This study focused on repurposing the FDA-approved drug, Voglibose to target the DKK1-LRP6 site with the goal of upregulating WSP in in vitro as well as rodent model of AD. Based on our previous computational approach, Voglibose was evaluated for the DKK1 binding, neuroprotective effects were examined using SHSY5Y cells, while WSP activation was analyzed through RTPCR in the HEK293/LRP6 cell line. Rodent model of AD was developed using intracerebroventricular administration of Aβ25-35. Male Wistar rats were randomly assigned to receive oral doses of Voglibose (1 and 10 mg/kg) for 28 days, after which behavioral assessments, biochemical analyses, RT-PCR, and histopathological evaluations were conducted. Voglibose showed significant reduction in the DKK1 binding, neuroprotective property in SHSY5Y as well as activation of WSP in LRP6 overexpressed HEK293 cells. There was a significant decrease in the island latency in rats treated with lower dose (p < 0.01) and higher dose (p < 0.05) of Voglibose when compared to the disease control rats. Similarly, in the behavioral tests, Voglibose significantly improved cognition. The deposition of amyloid plaques was found to be considerably more in the disease control rats which got reduced in the treatment groups as observed in the histopathological slides stained with Congo red. Significant alterations in mRNA levels and protein expression of glycogen synthase kinase-β (GSK-3β), β-catenin (β-cat) was observed in rat brain homogenates indicating upregulation of WSP. In conclusion, Voglibose demonstrated significant neuroprotective potential in a cell line study and showed potential cognitive benefits in a rat model of AD. Furthermore, its ability to activate WSP highlights its immense potential as AD therapeutic to enhance memory and modulate key neuroprotective mechanisms.

PMID:40381169 | DOI:10.1007/s12035-025-05047-5

Biotechnol Lett. 2025 May 17;47(3):56. doi: 10.1007/s10529-025-03596-2.

ABSTRACT

Orphan diseases comprise a range of disorders that individually affect a small percentage of people, but collectively impact millions of people worldwide. Patients with this disorder often face significant challenges in diagnosis, treatment, and access to care due to their rare nature and limited understanding and treatment options. In recent years, significant advancements have been made in the global healthcare in addressing the accessibility of essential treatments and medicines, but still challenges persist particularly related to orphan drugs (to treat rare diseases) in the developing world. The accessibility of orphan drugs remains a major challenge, where patients face barriers such as high costs, limited availability, and inadequate healthcare infrastructure. The high cost associated with orphan drugs presents a barrier to affordability for both patients and healthcare systems, causing disparities in access to life-saving treatments. The molecular farming approach utilizing plant-based production systems for recombinant protein production offers a hope for overcoming barriers to orphan drug access in resource-constrained settings. Molecular farming has the potential to produce a wide range of therapeutic proteins and biologics for the treatment of various rare diseases. The FDA approval of plant-derived proteins for the treatment of Gaucher disease (Elelyso) and Fabry disease (Elfabrio) highlights the potential of plant-based expression systems for the development of suitable drugs targeting niche and orphan diseases. This review examines the potential of the plant system in producing orphan drugs and also highlights the opportunities and challenges related to orphan drug manufacturing.

PMID:40381123 | DOI:10.1007/s10529-025-03596-2

Inflammopharmacology. 2025 May 17. doi: 10.1007/s10787-025-01771-5. Online ahead of print.

ABSTRACT

Respirable silica exposure adversely affects lung tissue immunopathology, triggering oxidative bursts in macrophages and neutrophils, releasing Damage-associated molecular patterns (DAMPs), including calprotectin proteins, S100A8, and S100A9. Calprotectin constitutes up to 45% of these innate immune cells, and serum levels of these alarmins correlate with inflammation, fibrosis, remodelling, and drug response in chronic diseases, including inflammatory bowel disease, asthma, and cystic fibrosis. The consequence of releasing calprotectin protein could trigger the pro-fibrotic effect of silicosis. This study aimed to investigate the role of calprotectin (S100A8/S100A9) as a pro-inflammatory and pro-fibrotic mediator in silica-induced lung fibrosis and evaluated the therapeutic potential of the calprotectin inhibitor, paquinimod. Using a mouse model of silicosis, silica exposure significantly elevated calprotectin expression, lung inflammation, and fibrosis, as evidenced by increased levels of epithelial-to-mesenchymal transition (EMT) markers, collagen deposition, and matrix metalloproteinases (MMPs). In vitro, stimulation of human bronchial fibroblasts with S100A8/S100A9 upregulated fibrotic markers (COL1A1 and α-SMA), which were reduced by inhibitors of TLR4 and RAGE receptors, as well as by paquinimod. Treatment with paquinimod effectively reduced these pathological changes, normalized calprotectin levels, decreased fibrosis scores, and attenuated NF-κB activation. These findings highlighted calprotectin's pivotal role in silica-induced lung fibrosis and inflammation, suggesting that its inhibition could be a promising therapeutic approach for silicosis and other fibro-inflammatory lung diseases. Further research is warranted to explore the precise mechanisms linking calprotectin to lung fibrosis and its potential as a biomarker and therapeutic target.

PMID:40381145 | DOI:10.1007/s10787-025-01771-5

Stem Cell Rev Rep. 2025 May 17. doi: 10.1007/s12015-025-10893-w. Online ahead of print.

ABSTRACT

The advent of intestinal organoids, three-dimensional structures derived from stem cells, has significantly advanced the field of biology by providing robust in vitro models that closely mimic the architecture and functionality of the human intestine. These organoids, generated from induced pluripotent stem cells (iPSCs), embryonic stem cells (ESCs), or adult stem cells, possess remarkable capabilities for self-renewal, differentiation into diverse intestinal cell types, and functional recapitulation of physiological processes, including nutrient absorption, epithelial barrier integrity, and host-microbe interactions. The utility of intestinal organoids has been extensively demonstrated in disease modeling, drug screening, and personalized medicine. Notable examples include iPSC-derived organoids, which have been effectively employed to model enteric infections, and ESC-derived organoids, which have provided critical insights into fetal intestinal development. Patient-derived organoids have emerged as powerful tools for investigating personalized therapeutics and regenerative interventions for conditions such as inflammatory bowel disease (IBD), cystic fibrosis, and colorectal cancer. Preclinical studies involving transplantation of human intestinal organoids into murine models have shown promising outcomes, including functional integration, epithelial restoration, and immune system interactions. Despite these advancements, several challenges persist, particularly in achieving reproducibility, scalability, and maturation of organoids, which hinder their widespread clinical translation. Addressing these limitations requires the establishment of standardized protocols for organoid generation, culture, storage, and analysis to ensure reproducibility and comparability of findings across studies. Nevertheless, intestinal organoids hold immense promise for transforming our understanding of gastrointestinal pathophysiology, enhancing drug development pipelines, and advancing personalized medicine. By bridging the gap between preclinical research and clinical applications, these organoids represent a paradigm shift in the exploration of novel therapeutic strategies and the investigation of gut-associated diseases.

PMID:40380985 | DOI:10.1007/s12015-025-10893-w

Radiol Med. 2025 May 17. doi: 10.1007/s11547-025-02019-6. Online ahead of print.

ABSTRACT

PURPOSE: To evaluate diagnostic accuracy and image quality of deep learning (DL) cine sequences for LV and RV parameters compared to conventional balanced steady-state free precession (bSSFP) cine sequences in cardiovascular magnetic resonance (CMR).

MATERIAL AND METHODS: From January to April 2024, patients with clinically indicated CMR were prospectively included. LV and RV were segmented from short-axis bSSFP and DL cine sequences. LV and RV end-diastolic volume (EDV), end-systolic volume (EDV), stroke volume (SV), ejection fraction, and LV end-diastolic mass were calculated. The acquisition time of both sequences was registered. Results were compared with paired-samples t test or Wilcoxon signed-rank test. Agreement between DL cine and bSSFP was assessed using Bland-Altman plots. Image quality was graded by two readers based on blood-to-myocardium contrast, endocardial edge definition, and motion artifacts, using a 5-point Likert scale (1 = insufficient quality; 5 = excellent quality).

RESULTS: Sixty-two patients were included (mean age: 47 ± 17 years, 41 men). No significant differences between DL cine and bSSFP were found for all LV and RV parameters (P ≥ .176). DL cine was significantly faster (1.35 ± .55 m vs 2.83 ± .79 m; P < .001). The agreement between DL cine and bSSFP was strong, with bias ranging from 45 to 1.75% for LV and from - 0.38 to 2.43% for RV. Among LV parameters, the highest agreement was obtained for ESV and SV, which fell within the acceptable limit of agreement (LOA) in 84% of cases. EDV obtained the highest agreement among RV parameters, falling within the acceptable LOA in 90% of cases. Overall image quality was comparable (median: 5, IQR: 4-5; P = .330), while endocardial edge definition of DL cine (median: 4, IQR: 4-5) was lower than bSSFP (median: 5, IQR: 4-5; P = .002).

CONCLUSION: DL cine allows fast and accurate quantification of LV and RV parameters and comparable image quality with conventional bSSFP.

PMID:40381163 | DOI:10.1007/s11547-025-02019-6

Interdiscip Sci. 2025 May 17. doi: 10.1007/s12539-025-00701-x. Online ahead of print.

ABSTRACT

In top-down proteomics, the accurate identification and characterization of proteoform through mass spectrometry represents a critical objective. As a result, achieving accuracy in identification results is essential. Multiple primary structure alterations in proteins generate a diverse range of proteoforms, resulting in an exponential increase in potential proteoform. Moreover, the absence of a definitive reference set complicates the standardization of results. Therefore, enhancing the accuracy of proteoform characterization continues to be a significant challenge. We introduced a ResNeXt-based deep learning model, PrSMBooster, for rescoring proteoform spectrum matches (PrSM) during proteoform characterization. As an ensemble method, PrSMBooster integrates four machine learning models, logistic regression, XGBoost, decision tree, and support vector machine, as weak learners to obtain PrSM features. The basic and latent features of PrSM are subsequently input into the ResNeXt model for final rescoring. To verify the effect and accuracy of the PrSMBooster model in rescoring proteoform characterization, it was compared with the characterization algorithm TopPIC across 47 independent mass spectrometry datasets from various species. The experimental results indicate that in most mass spectrometry datasets, the number of PrSMs obtained after rescoring with PrSMBooster increases at a false discovery rate (FDR) of 1%. Further analysis of the experimental results confirmed that PrSMBooster improves the accuracy of PrSM scoring, generates more mass spectrometry characterization results, and demonstrates strong generalization ability.

PMID:40381130 | DOI:10.1007/s12539-025-00701-x

Eur Spine J. 2025 May 17. doi: 10.1007/s00586-025-08908-8. Online ahead of print.

ABSTRACT

PURPOSE: This study aimed to develop deep learning algorithms (DLAs) utilising convolutional neural networks (CNNs) to classify cervical spondylotic myelopathy (CSM) and cervical spondylotic radiculopathy (CSR) from plain cervical spine radiographs.

METHODS: Data from 300 patients (150 with CSM and 150 with CSR) were used for internal validation (IV) using five-fold cross-validation strategy. Additionally, 100 patients (50 with CSM and 50 with CSR) were included in the external validation (EV). Two DLAs were trained using CNNs on plain radiographs from C3-C6 for the binary classification of CSM and CSR, and for the prediction of the spinal canal area rate using magnetic resonance imaging. Model performance was evaluated on external data using metrics such as area under the curve (AUC), accuracy, and likelihood ratios.

RESULTS: For the binary classification, the AUC ranged from 0.84 to 0.96, with accuracy between 78% and 95% during IV. In the EV, the AUC and accuracy were 0.96 and 90%, respectively. For the spinal canal area rate, correlation coefficients during five-fold cross-validation ranged from 0.57 to 0.64, with a mean correlation of 0.61 observed in the EV.

CONCLUSION: DLAs developed with CNNs demonstrated promising accuracy for classifying CSM and CSR from plain radiographs. These algorithms have the potential to assist non-specialists in identifying patients who require further evaluation or referral to spine specialists, thereby reducing delays in the diagnosis and treatment of CSM.

PMID:40381026 | DOI:10.1007/s00586-025-08908-8