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Computed tomography-guided precision biopsy combined with metagenomic next-generation sequencing for etiological diagnosis in patients with blood culture-negative systemic infections.

ObjectiveTo evaluate the diagnostic efficacy of computed tomography-guided percutaneous biopsy combined with metagenomic next-generation sequencing in patients with blood culture-negative systemic infections and to assess the clinical impact of using this combined strategy for etiological confirmation and guidance of targeted antimicrobial therapy.MethodsThis single-center retrospective observational cohort study enrolled 78 patients who met the Sepsis-3 consensus criteria for suspected systemic infection and had negative conventional microbiological work-ups (at least two sets of blood cultures) between April 2022 and March 2025. All patients underwent computed tomography-guided biopsy of radiologically identified infectious foci, with specimens processed concurrently for conventional culture and metagenomic next-generation sequencing. Diagnostic performance was benchmarked against the final comprehensive clinical diagnosis, and the influence of metagenomic next-generation sequencing findings on antimicrobial therapy modification was analyzed. Sample size calculation, based on a prior study estimating an metagenomic next-generation sequencing detection rate of 85% (&#x3b1;&#x2009;=&#x2009;0.05, &#x3b2;&#x2009;=&#x2009;0.2), indicated a minimum of 68 cases; accordingly, 78 patients were enrolled.ResultsComputed tomography-guided biopsy was technically successful in all 78 patients (100%). The pathogen detection rate of metagenomic next-generation sequencing (91.0%, 71/78) was significantly higher than that of conventional culture (55.1%, 43/78; p&#x2009;<&#x2009;0.001). Using the final clinical diagnosis as the reference standard, metagenomic next-generation sequencing achieved a sensitivity of 94.7% (95% confidence interval: 86.9-98.5), specificity of 100.0% (95% confidence interval: 29.2-100.0), positive predictive value of 100.0% (95% confidence interval: 94.9-100.0), and negative predictive value of 42.9% (95% confidence interval: 9.9-81.6). Among the 35 culture-negative specimens, metagenomic next-generation sequencing established a definitive microbiological diagnosis in 28 cases (80.0%) and detected polymicrobial infections in 11 cases (14.1% of the cohort). Antimicrobial therapy was rationally adjusted based on metagenomic next-generation sequencing results in 69.2% (54/78) of the patients.ConclusionsThe integration of computed tomography-guided precision biopsy with metagenomic next-generation sequencing offers a highly effective diagnostic approach for blood culture-negative systemic infections. This synergistic strategy improves etiological diagnosis by providing high-yield target specimens that enable comprehensive, unbiased pathogen screening, facilitates differentiation between infectious and non-infectious etiologies, and supplies critical evidence for guiding precision antimicrobial therapy. These findings highlight the growing role of interventional radiology in the contemporary framework of precision infectious disease management.

Humans

Higher Rates of PASS and SCB After Arthroscopic Subspine Decompression Are Associated With a Positive Diagnostic AIIS Injection: A Propensity Score-Matched Cohort Study.

BACKGROUND: Hip arthroscopy effectively treats femoroacetabular impingement syndrome (FAIS), but persistent pain may be related to concomitant extra-articular pathology such as subspine impingement syndrome (SSI). Standard diagnosis of SSI often relies on 3-dimensional computed tomography (3D-CT) morphology (Hetsroni type II/III), although this morphology is common in individuals who are asymptomatic and correlates poorly with symptoms. PURPOSE: To compare minimum 2-year clinical outcomes after arthroscopic subspine decompression in patients with concurrent FAIS and type II/III anterior inferior iliac spine (AIIS) morphology, stratified by diagnostic method: 3D-CT morphology alone versus 3D-CT morphology plus a positive ultrasound-guided diagnostic injection. STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: This study included patients aged 18 to 55 years with type II/III AIIS morphology who underwent primary hip arthroscopy for FAIS and SSI between January 2021 and November 2023 and had minimum 2-year follow-up. Patients diagnosed by CT morphology alone (CT classification group) were propensity score matched 1:1 to patients with a positive ultrasound-guided AIIS injection (injection group), with 57 patients per group. Matching variables were age, sex, body mass index, lateral center-edge angle, alpha angle, T&#xf6;nnis grade, and Beighton score. All patients underwent arthroscopic subspine decompression. Patient-reported outcomes and rates of achieving the minimal clinically important difference, Patient Acceptable Symptom State (PASS), and substantial clinical benefit (SCB) were compared. RESULTS: Preoperative patient-reported outcome scores were similar between groups (all P > .05). At minimum 2-year follow-up, the injection group had significantly better scores on the modified Harris Hip Score (90.8 vs 84.2), Hip Outcome Score-Activities of Daily Living (88.4 vs 82.4), Hip Outcome Score-Sports Subscale (71.9 vs 64.1), 12-item International Hip Outcome Tool (83.9 vs 76.1), and visual analog scale for pain (1.2 vs 2.0) (all P < .001). Minimal clinically important difference rates were high in both groups, with higher rates in the injection group for modified Harris Hip Score (93% vs 77%; P = .033) and Hip Outcome Score-Activities of Daily Living (91% vs 75%; P = .042). PASS and SCB rates were significantly higher in the injection group across all patient-reported outcome measures (all P < .05). Revision and complication rates were low and did not differ significantly between groups. CONCLUSION: Both groups improved significantly after arthroscopic subspine decompression. However, patients with a positive ultrasound-guided diagnostic AIIS injection achieved higher PASS and SCB rates than those selected by CT morphology alone, suggesting that injection-confirmed SSI may improve patient selection for subspine decompression.

Humans

The use of 3-dimensional (3D) printing in teaching musculoskeletal oncology for medical undergraduates.

INTRODUCTION: The approach to integrating relevant anatomy in the medical curriculum has been debated for many years. Current literature has explored the broad impact of 3D printing in medical education. However, there is little evidence on 3D printing for the teaching of musculoskeletal oncology (MSO). This is a self-controlled case series (SCCS) study that aims to analyse the effectiveness of 3D printed models in MSO in enhancing the learning experience, engagement and understanding of clinical and surgical anatomy for medical students. METHOD: A cross-sectional cohort study involving 75 clinical year medical students across 3 years from 2 medical schools that rotated through a single teaching hospital's orthopaedic department. Participants first viewed a set of computed-tomography (CT) images of a large pelvic osteosarcoma from a free open-source database, the Cancer Genome Atlas Sarcoma Collection (TCGA-SARC). A standardised 10-minute pre-intervention questionnaire which comprised 15 questions categorised by: 4 questions in 'anatomical knowledge', 7 questions in 'spatial awareness', 4 questions in 'surgical planning and complications', was administered to assess the baseline knowledge in their interpretation of the pathology via CT images only. Next, a 3D-printed model of the pelvic osteosarcoma, which included colour-coded adjacent structures, was provided as an adjunct to answer the same questionnaire. This concluded with a 5-point Likert scale feedback survey to gauge their perspectives and experience. RESULTS: The mean scores comparing their pre- and post-intervention assessment questionnaire increased by +1.34 from 8.15 (SD = 1.85) to 9.49 (SD = 1.7) (p < 0.001). The final year students had the greatest improvement of +1.54 from 8.00 (SD = 1.89) to 9.54 (SD = 1.59) (p = 0.004). There was no significant difference between the scores amongst the 2 medical schools. 91% of students agreed that the 3D model had helped them further their understanding of the anatomy of the sarcoma and 87% would want 3D printing models to augment their learning in anatomy. Baseline weaker students demonstrated significantly greater improvement in scores compared with baseline stronger students (mean difference +2.04 vs +0.30, p < 0.001). CONCLUSION: 3D printing is an effective teaching adjunct for musculoskeletal oncology surgical anatomy for medical undergraduates and could be used to enhance their understanding and learning experience. 3D models could be integrated in the teaching curriculum of surgical anatomy for undergraduate students.

Humans

Proteomic discovery analysis of quantitatively assessed emphysema in the general population. The MESA Lung Study.

BACKGROUND: Pulmonary emphysema occurs frequently in older adults, often without airflow limitation. Its presence predicts symptoms, respiratory hospitalizations and deaths, and all-cause mortality. Proteomics may provide further insights into emphysema pathogenesis and inform therapeutic targets. OBJECTIVE: We performed a proteomic discovery analysis of percent emphysema on computed tomography (CT) in a population-based, multiethnic sample from the Multi-Ethnic Study of Atherosclerosis (MESA) Lung Study. Replication was performed in two chronic obstructive pulmonary disease (COPD)-based studies, the SubPopulations and InteRmediate Outcome Measures in COPD Study (SPIROMICS) and the Genetic Epidemiology of COPD (COPDGene) Study. METHODS: MESA recruited participants from the general population in 2000-02. The MESA Lung Study performed full-lung CT scans in 2010-12. Percent emphysema was defined as the percentage of lung voxels&#x2009;<&#x2009;-950 Hounsfield units. Over 7,200 plasma aptamers were measured via SomaScan. Cross-sectional linear and least absolute shrinkage and selection operator (LASSO) regression models were adjusted for demographics, anthropometrics, smoking, renal function, and scanner parameters. Statistical significance was defined as a false discovery rate p-value&#x2009;<&#x2009;0.05. Gene Ontology (GO)/Reactome enrichment analyses were performed. LASSO-selected proteins' predictive performance was evaluated. RESULTS: Among 2,504 participants in the MESA Lung Study, mean age was 69.4&#xa0;years, 1,291 had ever smoked, and median percent emphysema-like lung was 1.4%. In total, 1,234 aptamers were significantly associated with percent emphysema in the MESA Lung Study, and 35 replicated in the SPIROMICS and COPDGene Studies. Novel associations included protein family with sequence similarity (FAM) 177A1, syntenin-2, ubiquitin carboxyl-terminal hydrolase 25, and uncharacterized protein C20orf173. Previously identified emphysema-associated proteins included soluble advanced glycosylation end product-specific receptor (sRAGE), protein S100-A12, high mobility group protein B1, and roundabout homolog 2. Enrichment analyses identified 40 GO biological processes, including chemokine production and regulation and cell-cell adhesion and regulation, and two Reactome pathways, including RAGE signaling. In tenfold cross-validation, novel proteins were largely retained by LASSO (R2&#x2009;=&#x2009;5.4%), improved overall model performance (R2&#x2009;=&#x2009;24.8%), and uniquely explained greater variance in percent emphysema. CONCLUSIONS: This analysis in a general population sample identified novel and previously characterized proteins whose functional roles were validated by GO/Reactome enriched pathways, offering new insights into emphysema pathophysiology and therapeutics.

Humans

Development of the zebrafish foveal analogue: a quantitative atlas of high-acuity zone growth and retinal regionalisation.

The vertebrate retina contains specialised regions for high-acuity vision, exemplified by the human fovea and its zebrafish analogue, the high-acuity zone (HAZ). Despite the widespread use of zebrafish to model retinal disease, a stage-resolved quantitative reference describing normal eye, photoreceptor layer (PRL) and lens growth has been lacking. Here, we apply contrast-enhanced micro-computed tomography (micro-CT) to construct the first three-dimensional micro-CT normative atlas of wild-type zebrafish eye development across five larval stages [3, 5, 7, 10 and 18&#x2005;days post-fertilisation (dpf)], mapping circumferential PRL thickness, eye and lens morphology, and compartment growth rates. Regional PRL thickening within the temporo-ventral region of the expected HAZ emerged by 5&#x2005;dpf and was sustained by a localised redistribution of growth, persisting and extending towards the optic nerve through 18&#x2005;dpf. The PRL, lens and eye grew through four phases, alternating between disproportionate PRL expansion and coordinated growth, while the eye remodelled from a nasal-dominant to a temporo-ventral-dominant form. This regional specialisation was protracted relative to gross ocular growth and could proceed independently of it, paralleling the extended postnatal maturation of the human fovea. This atlas provides a quantitative baseline for distinguishing disease-induced changes from normal variation, supporting zebrafish models of foveal hypoplasia and related disorders.

Animals

Advancing responsible genomic analyses of ancient mollusc shells.

The analysis of the DNA entrapped in ancient shells of molluscs has the potential to shed light on the evolution and ecology of this very diverse phylum. Ancient genomics could help reconstruct the responses of molluscs to past climate change, pollution, and human subsistence practices at unprecedented temporal resolutions. Applications are however still in their infancy, partly due to our limited knowledge of DNA preservation in calcium carbonate shells and the need for optimized methods for responsible genomic data generation. To improve ancient shell genomic analyses, we applied high-throughput DNA sequencing to 27 Mytilus mussel shells dated to ~111-6500 years Before Present, and investigated the impact, on DNA recovery, of shell imaging, DNA extraction protocols and shell sub-sampling strategies. First, we detected no quantitative or qualitative deleterious effect of micro-computed tomography for recording shell 3D morphological information prior to sub-sampling. Then, we showed that double-digestion and bleach treatment of shell powder prior to silica-based DNA extraction improves shell DNA recovery, also suggesting that DNA is protected in preservation niches within ancient shells. Finally, all layers that compose Mytilus shells, i.e., the nacreous (aragonite) and prismatic (calcite) carbonate layers, with or without the outer organic layer (periostracum) proved to be valuable DNA reservoirs, with aragonite appearing as the best substrate for genomic analyses. Our work contributes to the understanding of long-term molecular preservation in biominerals and we anticipate that resulting recommendations will be helpful for future efficient and responsible genomic analyses of ancient mollusc shells.

Animals

A Comprehensive Review of Radiomics in Pulmonary Nodule Management: Clinical Applications and Standardization Dilemmas.

Lung cancer is the most common and fatal malignant tumour. Early detection and treatment are likely to reduce mortality, but most pulmonary nodules identified during routine health checks are harmless. Consequently, a clear distinction between benign and malignant nodules is vital to improve early detection and reduce unnecessary interventions. Radiomics, a new omics technology, can be used to extract high-dimensional quantitative features from medical images, providing a profound understanding of tumour pathophysiology. Radiomics has attracted the attention of medical researchers since its formal definition by the Dutch researcher Lambin et al. in 2012. The number of research papers on radiomics has grown tremendously over the past few years. At present, it is used to predict pulmonary nodule malignancy, for noninvasive risk stratification, for integration with genomics to identify genetic mutations associated with lung cancer, and for evaluation of therapeutic responses. With this review, we summarise the literature on radiomics of pulmonary nodules, discuss how it could be used in nodule management, and address the current challenges and future directions for improving precision oncology.

Humans

Imaging-based surgical stratification of parasagittal meningiomas involving the superior sagittal sinus: a case analysis of 62 patients.

OBJECTIVE: The objective was to evaluate the Superior Sagittal Sinus Involvement Grading (SSIG) system as an imaging-based surgical stratification framework for parasagittal meningiomas adjacent to the superior sagittal sinus (SSS) and to assess its relationship with established sinus invasion grading, venous sinus patency, and operative strategy. METHODS: In this single-center retrospective cohort study, the authors included 62 consecutive parasagittal meningioma resections performed by a single surgeon. SSIG grade was assigned primarily on contrast-enhanced coronal MRI, with CT/MR venography used when available to evaluate sinus patency and collateral venous drainage. Operative variables, resection strategy, and clinicopathological factors were compared across SSIG and Sindou grades, and postoperative complications were compared between low- and high-involvement SSIG groups. RESULTS: SSIG correlated significantly with Sindou grade (rs = 0.790, &#x3c4;b = 0.702, both p < 0.001), and among patients with available venous imaging, it also correlated with the venous sinus involvement grade (rs = 0.742, &#x3c4;b = 0.665, both p < 0.001). With increasing SSIG grade, operative time, intraoperative blood loss, and intraoperative fluid administration increased (p = 0.012, p = 0.008, and p = 0.007, respectively). Compared with the low-involvement group (SSIG grades 1, 2, and 4a), the high-involvement group (SSIG grades 3, 4b, and 5) was less likely to achieve Simpson grade I resection and more likely to adopt Simpson grades II-III strategies (66.7% vs 13.6%, p < 0.001; OR 12.667). Surgery-related complication rates did not differ significantly between groups. The mean follow-up was 13.3 &#xb1; 7.9 months, with no radiographic recurrence or progression at last follow-up. CONCLUSIONS: SSIG characterizes parasagittal meningiomas by integrating sinus invasion, venous patency, falcine extension, and parasagittal convexity involvement on preoperative imaging. This surgically oriented framework may help anticipate operative exposure, sinus handling, and resection strategy. Its predictive value for complications and long-term oncological outcomes requires validation in larger cohorts with longer follow-up.

Humans

Mechanism of action of curculigoside ameliorating osteoporosis: an analysis based on network pharmacology and experimental validation.

OBJECTIVE: This study aimed to predict and verify the mechanism of curculigoside in treating osteoporosis using network pharmacology, molecular docking technology, and micro-CT technology. METHODS: Herb databases were searched to identify and screen potential targets of curculigoside. The GeneCards platform was utilized to mine osteoporosis-related targets. Cytoscape 3.6.0 software was employed to construct a compound-target-disease network. A protein-protein interaction (PPI) network for curculigoside in osteoporosis treatment was established, and core targets were screened. The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment and GO biological process analyses were performed using the Metascape database. Finally, molecular docking and micro-CT were used to validate core targets relevant to osteoporosis. RESULTS: A total of 166 potential curculigoside targets and 4,313 osteoporosis-related targets were identified, with 91 common targets. Ten key targets, including matrix metalloproteinase (MMP)3, MMP9, interleukin (IL)-6, and caspase-3, were screened. KEGG pathway enrichment analysis indicated involvement in 10 pathways, such as the Rap1 signaling pathway and tumor necrosis factor (TNF) signaling pathway. Molecular docking results demonstrated strong binding affinity between curculigoside and the core targets. Micro-CT analysis revealed that curculigoside not only improved BMD, BV/TV, BS/BV, and Tb.Th but also reduced Tb.Sp in osteoporotic bone. CONCLUSIONS: Curculigoside is likely to treat osteoporosis through targets such as MMP3, MMP9, IL-6, and caspase-3, acting on signaling pathways including Rap1 and TNF. These results indicate that curculigoside exhibits multitarget and multipathway characteristics in osteoporosis treatment, providing a theoretical basis for further clinical investigation.

Osteoporosis

Longitudinal In Vivo Imaging at Single-Lesion Resolution Identifies Allele-Associated Response and Resistance Dynamics in EGFR-Mutant Lung Cancer.

Acquired resistance to targeted therapies is inevitable in EGFR-mutant non-small cell lung cancer (NSCLC), yet the principles governing its emergence in vivo remain incompletely understood. In particular, how lesion-level response patterns vary across distinct EGFR allele contexts during therapy has not been systematically examined at single-lesion resolution. Here, we establish a longitudinal in vivo imaging platform enabling single-lesion resolution tracking of tumor behavior during therapy in genetically engineered mouse models representing clinically relevant EGFR alleles. Using high-resolution micro-computed tomography (micro-CT) and three-dimensional reconstruction, we monitor tumor growth, therapeutic response, and resistance during osimertinib treatment. EGFR genotype is associated with distinct patterns of tumor growth, response kinetics, and resistance timing. Therapeutic response is spatially heterogeneous, with coexisting lesions undergoing complete regression, persistence, or progression within the same lung. During treatment, spatially distinct lesion-level behaviors included persistent growth during therapy and initial regression followed by regrowth. These findings demonstrate the utility of longitudinal micro-CT imaging to investigate allele-associated differences in treatment response and resistance timing at single-lesion resolution in vivo.

Animals

IgM-mediated, T cell-independent suppression of humoral immunity.

The immunological unreactive state occurring in (T,G)-A-L nonresponder mice after secondary antigen challenge was investigated. Syngeneic IgM anti-(T,G)-A-L antibody-containing plasma, transferred at the time of the time of primary challenge, induced persistent suppression of autologous specific antibody production. Removal of plasma IgM with goat anti-mu antisera removed the ability of the plasma to supress. The induction and maintenance of the suppressed state were not different in thymectomized or sham-thymectomized animals. Primed animals subjected to graft-vs-host reaction (GVHR) at the time of secondary challenge switched over to IgG production. Animals suppressed by passive antibody transfer reacted to GVHR, at the time of secondary challenge, with specific IgM but not IgG antibody production. Transfused normal spleen cells partially abrogated suppression only when (suppressed) hosts had been lethally irradiated. Spleen cells from antigen-plus-antibody suppressed donors, upon transfer to previously normal, syngeneic hosts, were less immunocompetent than spleen cells from untreated donors. These data are consistent with a model of IgM mediated, T cell-independent persistent suppression of humoral immunity.

Animals