Literature Watch
The effectiveness and risks of Treating people with Idiopathic Pulmonary fibrosis with the Addition of Lansoprazole (TIPAL): study protocol for a randomised placebo-controlled multicentre clinical trial
BMJ Open. 2025 Feb 5;15(2):e088604. doi: 10.1136/bmjopen-2024-088604.
ABSTRACT
INTRODUCTION: Idiopathic pulmonary fibrosis (IPF) is a chronic progressive fibrotic lung disease frequently complicated by gastro-oesophageal reflux disease. Although several observational studies and a pilot study have investigated the role of proton pump inhibitors (PPIs) in IPF, their efficacy is unknown and there is much debate in international IPF guidelines on their use. We aim to undertake an adequately powered double-blind placebo-controlled randomised multicentre clinical trial to assess the change in forced vital capacity (FVC), cough and other important patient-reported outcomes, following 12-month therapy with PPIs in people with IPF.
METHODS AND ANALYSIS: A total of 298 patients with IPF diagnosed by a multidisciplinary team according to international guidelines who are not receiving PPIs will be enrolled. Patients are randomised equally to receive two capsules of lansoprazole or two placebo capsules, two times per day for 12 months. The primary outcome for the trial is change in FVC, measured at home, between the first week and last week of the study period. Secondary assessments include cough frequency (in a subgroup) measured using the VitaloJAK cough monitor, the King's Brief Interstitial Lung Disease questionnaire, the Raghu Scale for Pulmonary Fibrosis, Medical Research Council dyspnoea score, EQ-5D-5L, Leicester Cough Questionnaire, modified DeMeester reflux symptoms questionnaire and opportunistically captured routine lung function measurements. High-resolution CT scoring will be undertaken in a subgroup. The trial is designed to determine whether treating people with IPF with lansoprazole will reduce the reduction in FVC over a year. The COVID-19 pandemic required the study to be undertaken as a remote trial.
ETHICS AND DISSEMINATION: This study received ethical approval from the East of England Cambridgeshire and Hertfordshire Research Ethics Committee (reference 20/EE/0043; integrated research application system number 269050). Trial results will be published in a peer-reviewed journal upon completion.
TRIAL REGISTRATION NUMBER: ISRCTN13526307; ClinicalTrials.gov NCT04965298.
PMID:39909521 | DOI:10.1136/bmjopen-2024-088604
The role of vascularity and the fibrovascular interface in interstitial lung diseases
Eur Respir Rev. 2025 Feb 5;34(175):240080. doi: 10.1183/16000617.0080-2024. Print 2025 Jan.
ABSTRACT
Interstitial lung disease (ILD) is a clinical term that refers to a diverse group of non-neoplastic lung diseases. This group includes idiopathic and secondary pulmonary entities that are often associated with progressive pulmonary fibrosis. Currently, therapeutic approaches based on specific structural targeting of pulmonary fibrosis are limited to nintedanib and pirfenidone, which can only slow down disease progression leading to a lower mortality rate. Lung transplantation is currently the only available curative treatment, but it is associated with high perioperative mortality. The pulmonary vasculature plays a central role in physiological lung function, and vascular remodelling is considered a hallmark of the initiation and progression of pulmonary fibrosis. Different patterns of pulmonary fibrosis commonly exhibit detectable pathological features such as morphomolecular changes, including intussusceptive and sprouting angiogenesis, vascular morphometry, broncho-systemic anastomoses, and aberrant angiogenesis-related gene expression patterns. Dynamic cellular interactions within the fibrovascular interface, such as endothelial activation and endothelial-mesenchymal transition, are also observed. This review aims to summarise the current clinical, radiological and pathological diagnostic algorithm for different ILDs, including usual interstitial pneumonia/idiopathic pulmonary fibrosis, non-specific interstitial pneumonia, alveolar fibroelastosis/pleuroparenchymal fibroelastosis, hypersensitivity pneumonitis, systemic sclerosis-related ILD and coronavirus disease 2019 injury. It emphasises an interdisciplinary clinicopathological perspective. Additionally, the review covers current therapeutic strategies and knowledge about associated vascular abnormalities.
PMID:39909504 | DOI:10.1183/16000617.0080-2024
Analysis of ILD-RADS reproducibility and validity: Can different degrees of experience affect the interpretation?
Eur J Radiol. 2025 Jan 30;184:111961. doi: 10.1016/j.ejrad.2025.111961. Online ahead of print.
ABSTRACT
PURPOSE: To evaluate the reliability, validity and applicability of ILD-RADS among readers with different levels of experience.
METHODS: This prospective tri-center study included 159 patients with clinically diagnosed ILD who underwent high-resolution CT (HRCT). Two experienced thoracic radiologists, two general radiologists, and one pulmonologist independently evaluated the HRCT images blinded to the patient's clinical data and assigned ILD-RADS category for each patient. The Fleiss kappa test was employed to estimate the inter-reader agreement among all readers. Cohen's kappa test was applied to measure the pairwise inter-reader agreement. The multi-disciplinary team discussion (MDD) was used as a reference test to estimate the validity of ILD-RADS for diagnosing idiopathic pulmonary fibrosis (IPF). A 5-point Likert short survey was accomplished by the pulmonologists about the applicability of ILD-RADS in clinical practice.
RESULTS: The current study included 124 non-IPF and 35 IPF cases. Based on the radiologists, the ILD-RADS showed moderate inter-reader agreement (K = 0.515, P < 0.001) while being fair after the inclusion of the pulmonologist's input (K = 0.333, P < 0.001). The agreement was substantial among thoracic radiologists (K = 0.716, p < 0.001) and moderate among general radiologists (K = 0.461, p < 0.001). ILD-RADS ≤ 2 was the optimal cut-off for predicting IPF, with an accuracy ranging from 62.84 % to 80.54 %. Seventy-five percent of pulmonologists rated ILD-RADS as highly applicable in practice.
CONCLUSIONS: ILD-RADS is reliable and valid among radiologists but requires further refinement to enhance consistency and applicability in diverse clinical settings. Moreover, pulmonologists support its use in clinical practice.
PMID:39908937 | DOI:10.1016/j.ejrad.2025.111961
sORFdb - a database for sORFs, small proteins, and small protein families in bacteria
BMC Genomics. 2025 Feb 5;26(1):110. doi: 10.1186/s12864-025-11301-w.
ABSTRACT
Small proteins with fewer than 100, particularly fewer than 50, amino acids are still largely unexplored. Nonetheless, they represent an essential part of bacteria's often neglected genetic repertoire. In recent years, the development of ribosome profiling protocols has led to the detection of an increasing number of previously unknown small proteins. Despite this, they are overlooked in many cases by automated genome annotation pipelines, and often, no functional descriptions can be assigned due to a lack of known homologs. To understand and overcome these limitations, the current abundance of small proteins in existing databases was evaluated, and a new dedicated database for small proteins and their potential functions, called 'sORFdb', was created. To this end, small proteins were extracted from annotated bacterial genomes in the GenBank database. Subsequently, they were quality-filtered, compared, and complemented with proteins from Swiss-Prot, UniProt, and SmProt to ensure reliable identification and characterization of small proteins. Families of similar small proteins were created using bidirectional best BLAST hits followed by Markov clustering. Analysis of small proteins in public databases revealed that their number is still limited due to historical and technical constraints. Additionally, functional descriptions were often missing despite the presence of potential homologs. As expected, a taxonomic bias was evident in over-represented clinically relevant bacteria. This new and comprehensive database is accessible via a feature-rich website providing specialized search features for sORFs and small proteins of high quality. Additionally, small protein families with Hidden Markov Models and information on taxonomic distribution and other physicochemical properties are available. In conclusion, the novel small protein database sORFdb is a specialized, taxonomy-independent database that improves the findability and classification of sORFs, small proteins, and their functions in bacteria, thereby supporting their future detection and consistent annotation. All sORFdb data is freely accessible via https://sorfdb.computational.bio .
PMID:39910485 | DOI:10.1186/s12864-025-11301-w
Association between Healthy Eating Index 2015 and metabolic syndrome among US cancer survivors: evidence from NHANES 2005-2016
Int J Food Sci Nutr. 2025 Feb 5:1-11. doi: 10.1080/09637486.2025.2461144. Online ahead of print.
ABSTRACT
Our study examined the relationship between diet quality and the prevalence of metabolic syndrome (MetS) among 1779 U.S. cancer survivors using data from the National Health and Nutrition Examination Survey (NHANES, 2005-2016). Diet quality was assessed using the Healthy Eating Index 2015 (HEI-2015). Higher HEI-2015 scores were linked to significantly lower MetS prevalence (OR: 0.51, 95% CI: 0.32-0.80). Specifically, a higher intake of seafood and plant proteins, and fatty acids, coupled with a reduced intake of added sugars, was associated with decreased odds of MetS prevalence (OR: 0.93; 95% CI, 0.86-0.99) in cancer survivors. Additionally, a better diet quality was linked to lower prevalence of high waist circumference, elevated triglycerides, reduced high-density lipoprotein (HDL) cholesterol and high fasting glucose levels (OR, 0.44; 95% CI, 0.27-0.72). These results suggest that adopting healthy dietary habits may prevent MetS in cancer survivors.
PMID:39910439 | DOI:10.1080/09637486.2025.2461144
Author Correction: A microfluidic assay for the quantification of the metastatic propensity of breast cancer specimens
Nat Biomed Eng. 2025 Feb 5. doi: 10.1038/s41551-025-01359-y. Online ahead of print.
NO ABSTRACT
PMID:39910377 | DOI:10.1038/s41551-025-01359-y
Engineering a genomically recoded organism with one stop codon
Nature. 2025 Feb 5. doi: 10.1038/s41586-024-08501-x. Online ahead of print.
ABSTRACT
The genetic code is conserved across all domains of life, yet exceptions have revealed variations in codon assignments and associated translation factors1-3. Inspired by this natural malleability, synthetic approaches have demonstrated whole-genome replacement of synonymous codons to construct genomically recoded organisms (GROs)4,5 with alternative genetic codes. However, no efforts have fully leveraged translation factor plasticity and codon degeneracy to compress translation function to a single codon and assess the possibility of a non-degenerate code. Here we describe construction and characterization of Ochre, a GRO that fully compresses a translational function into a single codon. We replaced 1,195 TGA stop codons with the synonymous TAA in ∆TAG Escherichia coli C321.∆A4. We then engineered release factor 2 (RF2) and tRNATrp to mitigate native UGA recognition, translationally isolating four codons for non-degenerate functions. Ochre thus utilizes UAA as the sole stop codon, with UGG encoding tryptophan and UAG and UGA reassigned for multi-site incorporation of two distinct non-standard amino acids into single proteins with more than 99% accuracy. Ochre fully compresses degenerate stop codons into a single codon and represents an important step toward a 64-codon non-degenerate code that will enable precise production of multi-functional synthetic proteins with unnatural encoded chemistries and broad utility in biotechnology and biotherapeutics.
PMID:39910296 | DOI:10.1038/s41586-024-08501-x
Whole genome sequencing in early onset advanced heart failure
Sci Rep. 2025 Feb 5;15(1):4306. doi: 10.1038/s41598-025-88465-8.
ABSTRACT
The genetic contributions to early onset heart failure (HF) are incompletely understood. Genetic testing in advanced HF patients undergoing heart transplantation (HTx) may yield clinical benefits, but data is limited. We performed deep-coverage whole genome sequencing (WGS) in 102 Swedish HTx recipients. Gene lists were compiled through a systematic literature review. Variants were prioritized for pathogenicity and classified manually. We also compared polygenic HF risk scores to a population-based cohort. We found a pathogenic (LP/P) variant in 34 individuals (34%). Testing yield was highest in hypertrophic (63% LP/P carriers), dilated (40%) and arrhythmogenic right ventricular (33%) cardiomyopathy and lower in ischemic cardiomyopathy (10%). A family history was more common in LP/P variant carriers than in non-carriers but was present in less than half of carriers (44% vs 13%, P < 0.001), whereas age was similar. Polygenic risk scores were similar in HTx recipients and the population cohort. In conclusion, we observed a high prevalence of pathogenic cardiomyopathy gene variants in individuals with early-onset advanced HF, which could not accurately be ruled out by family history and age. In contrast, we did not observe higher polygenic risk scores in early onset advanced HF cases than in the general population.
PMID:39910139 | DOI:10.1038/s41598-025-88465-8
Leveraging public AI tools to explore systems biology resources in mathematical modeling
NPJ Syst Biol Appl. 2025 Feb 4;11(1):15. doi: 10.1038/s41540-025-00496-z.
ABSTRACT
Predictive mathematical modeling is an essential part of systems biology and is interconnected with information management. Systems biology information is often stored in specialized formats to facilitate data storage and analysis. These formats are not designed for easy human readability and thus require specialized software to visualize and interpret results. Therefore, comprehending modeling and underlying networks and pathways is contingent on mastering systems biology tools, which is particularly challenging for users with no or little background in data science or system biology. To address this challenge, we investigated the usage of public Artificial Intelligence (AI) tools in exploring systems biology resources in mathematical modeling. We tested public AI's understanding of mathematics in models, related systems biology data, and the complexity of model structures. Our approach can enhance the accessibility of systems biology for non-system biologists and help them understand systems biology without a deep learning curve.
PMID:39910106 | DOI:10.1038/s41540-025-00496-z
Archaea methanogens are associated with cognitive performance through the shaping of gut microbiota, butyrate and histidine metabolism
Gut Microbes. 2025 Dec;17(1):2455506. doi: 10.1080/19490976.2025.2455506. Epub 2025 Feb 5.
ABSTRACT
The relationship between bacteria, cognitive function and obesity is well established, yet the role of archaeal species remains underexplored. We used shotgun metagenomics and neuropsychological tests to identify microbial species associated with cognition in a discovery cohort (IRONMET, n = 125). Interestingly, methanogen archaeas exhibited the strongest positive associations with cognition, particularly Methanobrevibacter smithii (M. smithii). Stratifying individuals by median-centered log ratios (CLR) of M. smithii (low and high M. smithii groups: LMs and HMs) revealed that HMs exhibited better cognition and distinct gut bacterial profiles (PERMANOVA p = 0.001), characterized by increased levels of Verrucomicrobia, Synergistetes and Lentisphaerae species and reduced levels of Bacteroidetes and Proteobacteria. Several of these species were linked to the cognitive test scores. These findings were replicated in a large-scale validation cohort (Aging Imageomics, n = 942). Functional analyses revealed an enrichment of energy, butyrate, and bile acid metabolism in HMs in both cohorts. Global plasma metabolomics by CIL LC-MS in IRONMET identified an enrichment of methylhistidine, phenylacetate, alpha-linolenic and linoleic acid, and secondary bile acid metabolism associated with increased levels of 3-methylhistidine, phenylacetylgluamine, adrenic acid, and isolithocholic acid in the HMs group. Phenylacetate and linoleic acid metabolism also emerged in the Aging Imageomics cohort performing untargeted HPLC-ESI-MS/MS metabolic profiling, while a targeted bile acid profiling identified again isolithocholic acid as one of the most significant bile acid increased in the HMs. 3-Methylhistidine levels were also associated with intense physical activity in a second validation cohort (IRONMET-CGM, n = 116). Finally, FMT from HMs donors improved cognitive flexibility, reduced weight, and altered SCFAs, histidine-, linoleic acid- and phenylalanine-related metabolites in the dorsal striatum of recipient mice. M. smithii seems to interact with the bacterial ecosystem affecting butyrate, histidine, phenylalanine, and linoleic acid metabolism with a positive impact on cognition, constituting a promising therapeutic target to enhance cognitive performance, especially in subjects with obesity.
PMID:39910065 | DOI:10.1080/19490976.2025.2455506
Impaired primitive erythropoiesis and defective vascular development in Trim71-KO embryos
Life Sci Alliance. 2025 Feb 5;8(4):e202402956. doi: 10.26508/lsa.202402956. Print 2025 Apr.
ABSTRACT
The transition of an embryo from gastrulation to organogenesis requires precisely coordinated changes in gene expression, but the underlying mechanisms remain unclear. The RNA-binding protein Trim71 is essential for development and serves as a potent regulator of post-transcriptional gene expression. Here, we show that global deficiency of Trim71 induces severe defects in mesoderm-derived cells at the onset of organogenesis. Murine Trim71-KO embryos displayed impaired primitive erythropoiesis, yolk sac vasculature, heart function, and circulation, explaining the embryonic lethality of these mice. Tie2 Cre Trim71 conditional knockout did not induce strong defects, showing that Trim71 expression in endothelial cells and their immediate progenitors is dispensable for embryonic survival. scRNA-seq of E7.5 global Trim71-KO embryos revealed that transcriptomic changes arise already at gastrulation, showing a strong up-regulation of the mesodermal pioneer transcription factor Eomes. We identify Eomes as a direct target of Trim71-mediated mRNA repression via the NHL domain, demonstrating a functional link between these important regulatory genes. Taken together, our data suggest that Trim71-dependent control of gene expression at gastrulation establishes a framework for proper development during organogenesis.
PMID:39909558 | DOI:10.26508/lsa.202402956
The unusual suspect: A novel role for intermediate filament proteins in mitochondrial morphology
Mitochondrion. 2025 Feb 3:102008. doi: 10.1016/j.mito.2025.102008. Online ahead of print.
ABSTRACT
Mitochondrial dynamics is crucial for cellular homeostasis. However, not all proteins involved are known. Using a protein-protein interaction (PPI) approach, we identified ITPRIPL2 for involvement in mitochondrial dynamics. ITPRIPL2 co-localizes with intermediate filament protein vimentin, supported by protein simulations. ITPRIPL2 knockdown reveals mitochondrial elongation, disrupts vimentin processing, intermediate filament formation, and alters vimentin-related pathways. Interestingly, vimentin knockdown also leads to mitochondrial elongation. These findings highlight ITPRIPL2 as vimentin-associated protein essential for intermediate filament structure and suggest a role for intermediate filaments in mitochondrial morphology. Our study demonstrates that PPI analysis is a powerful approach for identifying novel mitochondrial dynamics proteins.
PMID:39909388 | DOI:10.1016/j.mito.2025.102008
Rhodoquinone carries electrons in the mammalian electron transport chain
Cell. 2025 Jan 10:S0092-8674(24)01420-X. doi: 10.1016/j.cell.2024.12.007. Online ahead of print.
ABSTRACT
Ubiquinone (UQ), the only known electron carrier in the mammalian electron transport chain (ETC), preferentially delivers electrons to the terminal electron acceptor oxygen (O2). In hypoxia, ubiquinol (UQH2) diverts these electrons onto fumarate instead. Here, we identify rhodoquinone (RQ), an electron carrier detected in mitochondria purified from certain mouse and human tissues that preferentially delivers electrons to fumarate through the reversal of succinate dehydrogenase, independent of environmental O2 levels. The RQ/fumarate ETC is strictly present in vivo and is undetectable in cultured mammalian cells. Using genetic and pharmacologic tools that reprogram the ETC from the UQ/O2 to the RQ/fumarate pathway, we establish that these distinct ETCs support unique programs of mitochondrial function and that RQ confers protection upon hypoxia exposure in vitro and in vivo. Thus, in discovering the presence of RQ in mammals, we unveil a tractable therapeutic strategy that exploits flexibility in the ETC to ameliorate hypoxia-related conditions.
PMID:39909039 | DOI:10.1016/j.cell.2024.12.007
Vacuum ultraviolet radiation from gaseous plasma for destruction of water contaminants
J Environ Manage. 2025 Feb 4;375:124396. doi: 10.1016/j.jenvman.2025.124396. Online ahead of print.
ABSTRACT
Innovative technological solutions are needed for water decontamination to combat the diverse pollutants present in water systems, as no single optimal decontamination technique is appropriate for all circumstances. Vacuum-ultraviolet (V-UV) radiation is a source of energetic photons that break molecular bonds, producing a plethora of chemically reactive agents, most notably OH● radicals, which can cause the degradation of harmful pollutants. Low-pressure gaseous plasma is a good source of V-UV radiation; however, its application to liquid water poses challenges. We constructed an inductively coupled radiofrequency plasma to produce high-intensity V-UV radiation, which was applied to contaminated water via a V-UV-transparent window. Plasma was sustained in hydrogen, as it produces the highest V-UV intensity among all gases at selected discharge parameters. Bacteriophage MS2 was used as an indicator of microbial decontamination efficiency. Reactive oxygen and nitrogen species were measured at various treatment setups to quantify their effect on MS2 inactivation and elucidate the primary inactivation factors. At optimal conditions, the concentration of active virus dropped by 9 log10 PFU/mL in 60 s. The optimal experimental setup was then used to treat bacteria E. coli, S. aureus, antibiotic tetracycline, and synthetic dye methylene blue as representatives of other types of pollutants, all of which were effectively removed/degraded within 10 min of treatment. A comparison of energy efficiency (EEO) to other disinfection setups was made for bacteriophage inactivation. With a low EEO value, we showcase the potential of this technique for further work in this field.
PMID:39908620 | DOI:10.1016/j.jenvman.2025.124396
Digital Health Technology Interventions for Improving Medication Safety: Systematic Review of Economic Evaluations
J Med Internet Res. 2025 Feb 5;27:e65546. doi: 10.2196/65546.
ABSTRACT
BACKGROUND: Medication-related harm, including adverse drug events (ADEs) and medication errors, represents a significant iatrogenic burden in clinical care. Digital health technology (DHT) interventions can significantly enhance medication safety outcomes. Although the clinical effectiveness of DHT for medication safety has been relatively well studied, much less is known about the cost-effectiveness of these interventions.
OBJECTIVE: This study aimed to systematically review the economic impact of DHT interventions on medication safety and examine methodological challenges to inform future research directions.
METHODS: A systematic search was conducted across 3 major electronic databases (ie, PubMed, Scopus, and EBSCOhost). The PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines were followed for this systematic review. Two independent investigators conducted a full-text review after screening preliminary titles and abstracts. We adopted recommendations from the Panel on Cost-Effectiveness in Health and Medicine for data extraction. A narrative analysis was conducted to synthesize clinical and economic outcomes. The quality of reporting for the included studies was assessed using the CHEERS (Consolidated Health Economic Evaluation Reporting Standards) guidelines.
RESULTS: We included 13 studies that assessed the cost-effectiveness (n=9, 69.2%), cost-benefit (n=3, 23.1%), and cost-utility (n=1, 7.7%) of DHT for medication safety. Of the included studies, more than half (n=7, 53.9%) evaluated a clinical decision support system (CDSS)/computerized provider order entry (CPOE), 4 (30.8%) examined automated medication-dispensing systems, and 2 (15.4%) focused on pharmacist-led outreach programs targeting health care professionals. In 12 (92.3% ) studies, DHT was either cost-effective or cost beneficial compared to standard care. On average, DHT interventions reduced ADEs by 37.12% (range 8.2%-66.5%) and medication errors by 54.38% (range 24%-83%). The key drivers of cost-effectiveness included reductions in outcomes, the proportion of errors resulting in ADEs, and implementation costs. Despite a significant upfront cost, DHT showed a return on investment within 3-4.25 years due to lower cost related with ADE treatment and improved workflow efficiency. In terms of reporting quality, the studies were classified as good (n=10, 76.9%) and moderate (n=3, 23.1%). Key methodological challenges included short follow-up periods, the absence of alert compliance tracking, the lack of ADE and error severity categorization, and omission of indirect costs.
CONCLUSIONS: DHT interventions are economically viable to improve medication safety, with a substantial reduction in ADEs and medication errors. Future studies should prioritize incorporating alert compliance tracking, ADE and error severity classification, and evaluation of indirect costs, thereby increasing clinical benefits and economic viability.
PMID:39909404 | DOI:10.2196/65546
The University of Wisconsin Undiagnosed Disease Program: Unveiling Rare Neurodevelopmental Disorders in Exome-Negative Patients
WMJ. 2024;123(6):619-624.
ABSTRACT
INTRODUCTION: The University of Wisconsin Undiagnosed Disease Program employs a "beyond the exome" approach to diagnose rare disease patients.
CASE PRESENTATIONS: We present 2 cases of rare neurodevelopmental disorders identified by whole genome sequencing. The first is a 12-year-old boy with global developmental delay/intellectual disability (GDD/ID) and congenital hypotonia who was diagnosed with CAPZA2-related disorder. The second is a 13-year-old boy with microcephaly, GDD/ID, and seizures who was diagnosed with neurodevelopmental disorder with language delay and behavioral abnormalities, with or without seizures (NEDLAS).
DISCUSSION: Our use of whole genome sequencing identified the fifth reported case of CAPZA2-related neurodevelopmental disorder. Fewer than 40 patients have been reported with NEDLAS, and we identified the fourth patient with the AGO1 in-frame deletion p.Glu376del.
CONCLUSIONS: Whole genome sequencing can be effective in diagnosing patients with suspected genetic disorders despite negative standard of care clinical genetic testing and enables the practice of precision medicine.
PMID:39908527
Detection of Alzheimer Disease in Neuroimages Using Vision Transformers: Systematic Review and Meta-Analysis
J Med Internet Res. 2025 Feb 5;27:e62647. doi: 10.2196/62647.
ABSTRACT
BACKGROUND: Alzheimer disease (AD) is a progressive condition characterized by cognitive decline and memory loss. Vision transformers (ViTs) are emerging as promising deep learning models in medical imaging, with potential applications in the detection and diagnosis of AD.
OBJECTIVE: This review systematically examines recent studies on the application of ViTs in detecting AD, evaluating the diagnostic accuracy and impact of network architecture on model performance.
METHODS: We conducted a systematic search across major medical databases, including China National Knowledge Infrastructure, CENTRAL (Cochrane Central Register of Controlled Trials), ScienceDirect, PubMed, Web of Science, and Scopus, covering publications from January 1, 2020, to March 1, 2024. A manual search was also performed to include relevant gray literature. The included papers used ViT models for AD detection versus healthy controls based on neuroimaging data, and the included studies used magnetic resonance imaging and positron emission tomography. Pooled diagnostic accuracy estimates, including sensitivity, specificity, likelihood ratios, and diagnostic odds ratios, were derived using random-effects models. Subgroup analyses comparing the diagnostic performance of different ViT network architectures were performed.
RESULTS: The meta-analysis, encompassing 11 studies with 95% CIs and P values, demonstrated pooled diagnostic accuracy: sensitivity 0.925 (95% CI 0.892-0.959; P<.01), specificity 0.957 (95% CI 0.932-0.981; P<.01), positive likelihood ratio 21.84 (95% CI 12.26-38.91; P<.01), and negative likelihood ratio 0.08 (95% CI 0.05-0.14; P<.01). The area under the curve was notably high at 0.924. The findings highlight the potential of ViTs as effective tools for early and accurate AD diagnosis, offering insights for future neuroimaging-based diagnostic approaches.
CONCLUSIONS: This systematic review provides valuable evidence for the utility of ViT models in distinguishing patients with AD from healthy controls, thereby contributing to advancements in neuroimaging-based diagnostic methodologies.
TRIAL REGISTRATION: PROSPERO CRD42024584347; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=584347.
PMID:39908541 | DOI:10.2196/62647
Fuzz Testing Molecular Representation Using Deep Variational Anomaly Generation
J Chem Inf Model. 2025 Feb 5. doi: 10.1021/acs.jcim.4c01876. Online ahead of print.
ABSTRACT
Researchers are developing increasingly robust molecular representations, motivating the need for thorough methods to stress-test and validate them. Here, we use a variational auto-encoder (VAE), an unsupervised deep learning model, to generate anomalous examples of SELF-referencIng Embedded Strings (SELFIES), a popular molecular string format. These anomalies defy the assertion that all SELFIES convert into valid SMILES strings. Interestingly, we find specific regions within the VAE's internal landscape (latent space), whose decoding frequently generates inconvertible SELFIES anomalies. The model's internal landscape self-organization helps with exploring factors affecting molecular representation reliability. We show how VAEs and similar anomaly generation methods can empirically stress-test molecular representation robustness. Additionally, we investigate reasons for the invalidity of some discovered SELFIES strings (version 2.1.1) and suggest changes to improve them, aiming to spark ongoing molecular representation improvement.
PMID:39908426 | DOI:10.1021/acs.jcim.4c01876
Surface defect detection on industrial drum rollers: Using enhanced YOLOv8n and structured light for accurate inspection
PLoS One. 2025 Feb 5;20(2):e0316569. doi: 10.1371/journal.pone.0316569. eCollection 2025.
ABSTRACT
Drum roller surface defect detection is of great research significance for control production quality. Aiming at solving the problems that the traditional light source visual imaging system, which does not clearly reflect defect features, the defect detection efficiency is low, and the accuracy is not enough, this paper designs an image acquisition system based on line fringe structured light and proposes an improved deep learning network model based on YOLOv8n to achieve efficient detection of defects on the rolling surface of a drum roller. In the aspect of image acquisition, this paper selected the line fringe structured light as the system light source, which made up for the problem that the traditional light source does not reflect the defect characteristics. In terms of algorithms, firstly, using deformable convolution instead of standard convolution to enhance the feature extraction ability of the backbone network. Then, a new feature fusion module was proposed to enable the fusion network to learn additional original information. Finally, Wise-IoU was applied to replace CIoU in the loss function, so that the network pays more attention to the high-quality samples. The experimental results show that the improved YOLOv8n algorithm has a certain improvement in detection accuracy. The main average accuracy (mAP) is 97.2%, and the detection time is 4.3ms. The system and algorithm designed in this paper can better ensure the production quality of drum rollers. While effective, the model's standard rectangular bounding boxes may limit precision for elongated defects. Future work could explore rotated bounding boxes and broader dataset diversity to enhance generalization in real-world applications.
PMID:39908278 | DOI:10.1371/journal.pone.0316569
CD4+ T-Cell Lymphoma Harboring a Chimeric Antigen Receptor Integration in <em>TP53</em>
N Engl J Med. 2025 Feb 6;392(6):577-583. doi: 10.1056/NEJMoa2411507.
ABSTRACT
Malignant T-cell transformation after chimeric antigen receptor (CAR) T-cell therapy has been described, but the contribution of CAR integration to oncogenesis is not clear. Here we report a case of a T-cell lymphoma harboring a lentiviral integration in a known tumor suppressor, TP53, which developed in a patient with multiple myeloma after B-cell maturation antigen (BCMA) CAR T-cell therapy.
PMID:39908432 | DOI:10.1056/NEJMoa2411507
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