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The prevalence of isthmic and degenerative lumbar spondylolisthesis: an analysis of 1376 patients.

INTRODUCTION: Typically, spondylolisthesis is an asymptomatic spinal condition that is often captured accidently in radiographic studies. The limited studies reviewing incidence primarily used lateral radiographs, which lack the granularity of advanced imaging. In response, computed tomography (CT) has been recommended to enhance the accuracy of spondylolisthesis diagnosis (degenerative versus isthmic). In the present study, we sought to determine the prevalence of isthmic and degenerative spondylolisthesis using CT imaging. METHODS: We conducted a retrospective study of 1,680 patients who underwent abdominal/pelvic CT scans at a single level-1 trauma center from January 1, 2017, to January 31, 2017. RESULTS: A total of 1,680 CT scans were screened, of which 1,376 patient scans met the inclusion criteria of having undergone complete imaging (axial and sagittal images). The average age of the study population was 57.1 (standard deviation, 18.7) years; 51.1% were female, and 83.2% were Caucasian. The prevalence of isthmic spondylolisthesis was 5.4% (n&#xa0;=&#xa0;71): 3.6% of cases were at the L5-S1 level, 2.1% were at the L4-L5 level, and 0.6% were at the L3-L4 level. The female-to-male ratio was 0.73:1. The prevalence of degenerative spondylolisthesis was higher at 21.5% (n&#xa0;=&#xa0;285), and the level most commonly affected was L4-L5 (11.8%), followed by L5-S1 (9.7%) and L3-L4 (4.6%). The female-to-male ratio was 1.3:1. There was a higher prevalence of degenerative spondylolisthesis in women at L4-L5 (51.2% vs. 35.6%; P&#xa0;<&#xa0;0.001). CONCLUSION: We found that degenerative spondylolisthesis was more prevalent, occurring primarily in older women, between the L4-L5 vertebrae. On the other hand, isthmic spondylolisthesis more commonly occurred within male patients between the L5-S1 vertebrae. Our study is one of the first to recognize a high rate of degenerative spondylolisthesis within the L5-S1 region, highlighting the utility of CT scan to visualize spinal translation. LEVEL OF EVIDENCE: IV.

Humans

Applications of artificial intelligence in robot-assisted surgery: a systematic review.

To characterize applications of artificial intelligence (AI) in robot-assisted surgery, summarize technical and clinical performance, and assess the quality of the available evidence. PubMed, Web of Science Core Collection, and Scopus were searched for English-language journal articles published from 1 January 2020 through 31 October 2025. Randomized, observational, model-development, validation, and feasibility studies evaluating AI in robot-assisted surgery or closely related image-guided minimally invasive workflows were eligible. Two reviewers independently performed study selection, data extraction, and risk-of-bias assessment. Owing to heterogeneity in surgical procedures, AI tasks, analytical units, validation strategies, and outcomes, findings were synthesized descriptively without statistical pooling. The review was registered in the International Prospective Register of Systematic Reviews (CRD420251175699). Seventeen studies were included: seven clinical prediction or decision-support studies, eight intraoperative recognition, segmentation, or image-guided studies, and two training or workflow studies. Five prediction studies reported area-under-the-curve values of 0.74-0.95. Technical studies reported F1 or Dice scores of 0.525-0.995 and task-specific accuracies of 0.840-0.998. Two randomized studies suggested benefits for personalized suturing feedback and automated camera control, but neither established improved patient outcomes. Only one study had low overall risk of bias; the remaining studies were at high or unclear risk or raised some concerns. AI applications in robot-assisted surgery show promise for prediction, intraoperative perception, training, and workflow support. Evidence primarily demonstrates technical feasibility rather than established clinical effectiveness. Independent multicenter validation and prospective evaluation of patient, educational, and workflow outcomes are required before widespread implementation.

Robotic Surgical Procedures

A conserved distal-tail helical extension defines a tailspike attachment architecture in Gram-negative siphophages.

Rapid growth of bacteriophage genome collections has outpaced functional annotation of tail-tip proteins, limiting comparative analysis of host-recognition structures. Starting from a shared distal-tail gene organization in the Salmonella phages 9NA and Jersey, I developed a morphogenetic bioinformatic framework integrating gene synteny, sequence comparison, profile hidden Markov model (HMM) screening, structural evidence, structure-aware searching, and AlphaFold modeling. Comparison with the experimentally characterized lambda and Sf11 tail assemblies identified a predominantly alpha-helical C-terminal extension of the distal-tail (DT) protein associated with tailspike attachment, termed the distal-tail helical extension (DT-helix). Screening 541,986 proteins from 5167 complete NCBI RefSeq tailed-phage genomes, followed by evidence-based evaluation of sequence, genomic context, and structural architecture, identified 165 curated DT-helical-extension-associated phages. Their DT proteins segregated into six sequence groups. In the four principal multi-member groups, cognate tailspikes showed group-specific conservation in proximal N-terminal regions but substantially greater downstream diversity, consistent with sequence constraint at the DT-tailspike attachment boundary. A complementary ProstT5/Foldseek search supported the established groups but revealed no convincing additional highly divergent family. Together with the experimentally characterized Sf11 attachment interface, these findings define a recurrent morphogenetic architecture linking conserved distal-tail scaffolds to more variable receptor-binding proteins across siphophages infecting Gram-negative bacteria. Although universal exchangeability is not established, the identified scaffold-receptor-binding boundaries provide a framework for molecular characterization and rational phage engineering. Accession-level information for the 165 curated phages is available through PhageTailDB.

Viral Tail Proteins

Improving insurance deduction identification: a hybrid artificial intelligence model using machine learning and expert systems.

PURPOSE: Financial challenges in healthcare systems worldwide, especially in low- and middle-income countries like Iran, have increased hospitals' reliance on insurance reimbursements. Unrecognized insurance deductions often cause severe financial shortages, making efficient deduction management crucial. This study aimed to design a hybrid intelligent system for identifying and predicting insurance deductions by combining machine learning and expert system frameworks. DESIGN/METHODOLOGY/APPROACH: A mixed-methods design was applied in four stages. First, a scoping review identified the causes and patterns of insurance deductions. Second, interviews with 15 insurance experts produced a validated checklist and a dataset from inpatient billing records. Third, using the CRISP-DM methodology, machine learning algorithms were developed and tested in SPSS Modeler alongside a fuzzy expert system developed in MATLAB. Finally, the model was validated using the holdout method. FINDINGS: Four categories of deduction drivers were identified: service provision, registration errors, document submission issues, and revenue conversion processes. The CHAID decision tree outperformed other algorithms with a 99% precision rate and the lowest Mean Absolute Error (9.43). A brief assessment of potential overfitting was conducted to ensure that the CHAID model's high accuracy was interpreted cautiously and supported by the validation results. The fuzzy expert system with validated rules was adaptable for deduction classification, especially for cases unsuitable for quantitative modeling. ORIGINALITY/VALUE: The hybrid model improves detection and prevention of deductions, offering actionable insights for hospital administrators, insurers, and policymakers. Its implementation can enhance hospital information systems, streamline claims processing, and optimize revenue management amid financial constraints.

Machine Learning

Upscaling Genotyping by Amplicon Sequencing With GBAS-GUI.

Genotyping by amplicon sequencing (GBAS) is a relatively low-cost approach for generating genotypic data compared with established genomic methods, making it highly scalable and particularly suitable for large-scale genetic monitoring projects. However, most existing analytical pipelines are either marker-specific, insufficiently scalable, or lacking efficient data management systems for the long-term integration of genotypic information, limiting the full potential of GBAS. Here, we address this gap by introducing GBAS-GUI (https://github.com/sonnenbe-dot/GBAS-GUI), a pipeline capable of generating GBAS-based genotypic data for a wide variety of loci at scale. GBAS-GUI integrates a graphical user interface with multiple checkpoints to improve accessibility and robustness. It implements multiprocessing architecture and a relational database that links genotypic data with associated sample metadata to enhance scalability and data management. The pipeline further enables marker screening through automated calculation of polymorphism information content (PIC) and implements a strategy to recover homologous genotypic information from paralogous loci with non-overlapping amplicon length ranges. Using multiple empirical datasets, we demonstrate substantial improvements in processing speed, database management and handling artefacts related to co-amplification of unspecific regions and duplicates of the same genomic region. We further show that incorporating the full sequence information captured by an amplicon increases marker information content beyond what is achievable with length-based genotyping alone and expands the analytical versatility of GBAS. Overall, GBAS-GUI provides a robust, scalable and versatile framework that unlocks the potential of GBAS for large-scale population genetic and phylogeographic studies.

Genotyping Techniques

ReMeDy: A Flexible Statistical Framework for Region-Based Detection of DNA Methylation Dysregulation.

Region-based epigenome-wide association studies have demonstrated improved statistical power and biological interpretability compared with probe-wise analyses of DNA methylation data. However, most existing region-based methods characterize methylation dysregulation primarily through changes in mean methylation levels associated with a phenotype of interest. Substantial evidence indicates that phenotype-associated methylation alterations may also manifest through changes in methylation variability or through joint shifts in mean and variability. Despite this, no existing statistical framework jointly models mean-variance methylation changes in a region-based manner. We propose ReMeDy, a flexible statistical framework that uses a hierarchical likelihood approach within a generalized linear model setting to identify differentially methylated regions, variably methylated regions, and regions exhibiting joint differential and variable methylation at a genome-wide scale. Unlike existing models, ReMeDy operates directly on biologically defined co-methylated regions, allowing it to naturally capture spatial correlation inherent in DNA methylation array data, while avoiding reliance on heuristic, user-defined tuning parameters such as smoothing spans and kernel bandwidths that can substantially influence results and introduce subjectivity. Through extensive simulation studies and comprehensive benchmarking against popular models, we demonstrate that ReMeDy maintains false discovery and Type-I error rates at nominal levels while achieving consistently higher statistical power across a wide range of realistic scenarios. Application to population-level DNA methylation data further shows that ReMeDy identifies biologically meaningful regions and pathways implicated in complex human diseases that are not captured by conventional mean-based analyses alone. ReMeDy is implemented as an open-source R package and is freely available at https://github.com/SChatLab/ReMeDy.

DNA Methylation

Robust optimisation for photon radiotherapy: A scoping review of models, paradigms, and reporting.

BACKGROUND AND PURPOSE: Robust optimisation offers an alternative to conventional margin-based photon radiotherapy planning by explicitly modelling uncertainty, but practice is variable and not standardised. MATERIALS AND METHODS: A scoping review was conducted to map robust optimisation for photon external beam radiotherapy. Electronic searches of Scopus, PubMed and Google Scholar (2000-2025, English language) identified planning studies that incorporated modelled uncertainties into the optimisation process and reported at least one robustness-related outcome. Data were charted on clinical context, uncertainty models, optimisation paradigms, robustness metrics and evidence for clinical implementation. RESULTS: Seventy-one studies were included. Most investigated prostate, breast or lung cancer and used intensity-modulated radiotherapy or volumetric-modulated arc therapy in commercial or research treatment planning systems. Scenario-based worst-case (minimax) optimisation was the dominant paradigm in clinically oriented work, while chance-constrained, conditional value at-risk, distributionally robust and adaptive formulations were confined to small methodological series. Uncertainty modelling focused mainly on rigid set-up error; fewer studies incorporated respiratory motion, inter-fraction anatomical change, dose-calculation uncertainty or biological variation. Robustness was evaluated with diverse scenario-based dose-volume metrics, probabilistic coverage measures, composite robustness indices and, less often, biological endpoints. Direct clinical implementation reports were scarce. CONCLUSION: Robust photon planning is technically feasible and generally maintains or improves target coverage and organ sparing compared with margin-based planning. However, heterogeneity in uncertainty models, optimisation configuration and robustness reporting limits comparison and synthesis. Pragmatic minimum standards are proposed to support future consensus and wider clinical adoption.

Humans

Nociception-guided opioid administration within multimodal analgesia for laparoscopic endometriosis surgery: a randomized controlled trial.

Women with endometriosis are at increased risk of severe postoperative pain due to nociceptive sensitization. While multimodal analgesia reduces opioid use, the added value of objective nociception monitoring remains unclear. This study evaluated whether NOL&#xae;-guided opioid titration improves perioperative outcomes within a standardized multimodal regimen. In this prospective, randomized, single-blinded trial, premenopausal women undergoing laparoscopic surgery for suspected endometriosis or adenomyosis were assigned to NOL&#xae;-guided analgesia or standard care based on clinical assessment. All patients received a standardized multimodal protocol. The primary outcome was total perioperative opioid consumption. Secondary outcomes included postoperative pain scores (NRS) and PACU length of stay. Exploratory analyses assessed the association between preoperative pain (Mankoski Pain Scale, MPS) and postoperative outcomes. A total of 111 patients were analyzed (NOL&#xae;: n&#x2009;=&#x2009;54; control: n&#x2009;=&#x2009;57). Total perioperative opioid consumption did not differ significantly between groups (adjusted mean difference&#x2009;=&#x2009;14&#xa0;&#x3bc;g for Fentanyl and 52&#xa0;&#x3bc;g for Remifentanil; p&#x2009;=&#x2009;0.8). Surgery duration was an independent predictor of opioid use (p&#x2009;<&#x2009;0.001) and PACU length of stay (p&#x2009;=&#x2009;0.01), whereas treatment group had no significant effect. Postoperative pain scores were comparable between groups at all time points. NOL&#xae;-derived metrics were not associated with opioid consumption or pain. Higher preoperative MPS scores independently predicted higher pain scores in the late PACU phase. NOL&#xae;-guided opioid titration did not reduce perioperative opioid consumption or improve early postoperative outcomes compared with standard multimodal analgesia in women undergoing laparoscopic surgery for endometriosis.

Humans

Comparative in silico analysis of Apis mellifera immune responses to Varroa destructor and Tropilaelaps mercedesae: Common and mite-specific molecular signatures.

Parasitic mites Varroa destructor and Tropilaelaps mercedesae represent major threats to global honey bee (Apis mellifera) health and productivity, yet comparative molecular insights into host responses remain limited. To address this, we systematically compiled published studies (2015-2025) reporting genes associated with honey bee interactions with V. destructor (11 studies, 87 genes), T. mercedesae (4 studies, 35 genes), and hygienic behavior (6 studies, 44 genes). Gene identifiers were harmonized to the Amel_HAv3.1 genome assembly, yielding three non-redundant sets: 64 Varroa-associated, 34 Tropilaelaps-associated, and 44 hygienic behavior-associated genes. Venn analysis identified 10 overlapping genes (including A0A088A8D5, A0A088ADL8, ABAE_APIME, Def1, Def2, Gapdh, HYTA_APIME, Imd, LOC726783, and Vg), suggesting conserved defense mechanisms, while 41 and 24 genes were uniquely associated with Varroa and Tropilaelaps, respectively. Enrichment analyses revealed Varroa-responsive genes were enriched in immune processes, chitin catabolism, and signaling pathways (Toll/Imd, MAPK, Wnt). Tropilaelaps-associated genes were enriched for antibacterial defense and stress response, with Toll/Imd signaling as the sole significantly enriched pathway. Overlapping genes reinforced core innate immunity activation. Protein-protein interaction network centrality analysis identified key hub genes: Def1, HYTA_APIME, ABAE_APIME, PPO, Imd, PGRP-LC, Vg for Varroa; and ACPH1_APIME, MRJP1, Vg, LOC726783 for Tropilaelaps. Results demonstrate that, despite differences in mite biology, honey bees show a conserved immune response against both parasites, centered on antibacterial defense, humoral immunity, and activation of the Toll/Imd pathway. Although limited by the in-silico nature and research asymmetries reflecting Tropilaelaps' emergence, this curated resource establishes a comprehensive framework for elucidating shared and distinct molecular defense mechanisms. Ultimately, this approach prioritizes diagnostic markers and candidate genes for functional validation and breeding strategies to enhance colony resilience against mite&#x2011;driven disease globally.

Animals

Privacy, security, and reliability risks of artificial intelligence in healthcare: a systematic review of empirical evidence.

BACKGROUND: Artificial intelligence (AI) is increasingly integrated into healthcare information systems, supporting clinical decision-making, imaging analysis, and predictive modeling. While these applications offer operational and clinical benefits, they also introduce emerging risks to patient privacy, data security, and system reliability. OBJECTIVE: To systematically review empirical evidence on privacy breaches, security vulnerabilities, and misuse associated with AI applications in healthcare settings. METHODS: PubMed, Embase, Web of Science, Scopus, IEEE Xplore, and ACM Digital Library were searched for empirical studies published between January 2015 and November 2025 that evaluated AI use or misuse in clinical diagnosis, treatment, or decision-making. Two reviewers independently screened studies and extracted data using a standardized form. Findings were synthesized narratively due to heterogeneity in study designs, AI methods, and reported outcomes. RESULTS: Of 7,285 records identified through database searches and 205 through citation screening, 22 empirical studies met the inclusion criteria, spanning multiple clinical domains and data modalities, predominantly medical imaging applications. Five recurring threat categories were identified: patient re-identification, membership inference, unauthorized access and adversarial exploitation, input manipulation, and misuse or overinterpretation of AI outputs. Across studies, AI models were shown to encode latent biometric signals across diverse data types, limiting the effectiveness of traditional anonymization and synthetic data approaches. Adversarial attacks and input manipulation were also shown to compromise diagnostic performance and system integrity. CONCLUSION: This systematic review provides empirical evidence suggesting that contemporary AI systems in healthcare introduce privacy and security risks that may challenge traditional assumptions about data protection. These findings underscore the need for privacy- and security-by-design approaches and governance frameworks that address risks across the AI lifecycle.

Humans

RR-interval-based atrial fibrillation detection and burden estimation: cross-dataset validation and calibration-aware probability analysis.

Objective.Atrial fibrillation (AF) burden has become an increasingly important endpoint in long-duration rhythm monitoring, but reliable burden estimation requires more than accurate AF detection alone. In particular, when burden is derived by aggregating predicted AF probabilities over time, probability calibration may directly affect burden validity under external dataset shift.Approach.This study developed an interpretable-interval feature model for AF detection and evaluated it using record-wise cross-validation on a development cohort and independent cross-dataset external validation on public Holter electrocardiographic databases. Window-level performance was assessed using the area under the receiver operating characteristic curve (ROC-AUC), area under the precision-recall curve (PR-AUC), Brier score, expected calibration error (ECE), and calibration intercept and calibration slope. Recording-level AF burden was estimated using both probability-based and hard-label aggregation and evaluated using mean absolute error (MAE) and agreement analyses.Main results.The model showed high discrimination in both development and external evaluation, with external ROC-AUC ofand PR-AUC of. However, external calibration deteriorated despite preserved ranking performance, with Brier score of, ECE(15) of, calibration intercept of, and calibration slope of. In the external cohort, probability-based burden estimation preserved strong association with reference burden but showed weaker raw agreement than hard-label aggregation, with MAE ofversus, consistent with systematic probability underprediction. Repeated external recalibration across record-level splits substantially improved probability quality and probability-based burden estimation. Median probability-burden MAE decreased fromwithout recalibration toafter Platt recalibration andafter isotonic recalibration, while median ECE(15) decreased fromtoand, respectively.Significance.These findings indicate that-interval-based AF detection maintained strong ranking performance in the tested external cohort, but probability calibration should be evaluated explicitly when predicted probabilities are aggregated into AF-burden estimates.

Atrial Fibrillation

Artificial intelligence-assisted detection and optical differentiation of colorectal lesions in Lynch syndrome surveillance (CADLY2): a multicentre, open-label, randomised controlled superiority trial.

BACKGROUND: Artificial intelligence (AI)-based computer-aided detection (CADe) systems improve adenoma detection in average-risk colorectal cancer screening. Meanwhile, evidence in Lynch syndrome surveillance is sparse and inconsistent. We assessed the effect of CADe on adenoma detection during Lynch syndrome surveillance. Computer-aided optical diagnosis (CADx) performance for optical differentiation of colorectal lesions was evaluated as a secondary aim. METHODS: CADLY2 was an international, multicentre, open-label, randomised controlled superiority trial at nine specialised hereditary cancer surveillance centres in Belgium, Germany, the Netherlands, and Spain. Adults aged 18 years or older with genetically confirmed Lynch syndrome scheduled for surveillance colonoscopy were randomly assigned (1:1) to high-definition white-light (HD-WL) colonoscopy alone or to HD-WL colonoscopy with computer-aided assistance from CAD EYE (Fujifilm, Tokyo, Japan). CAD EYE was used for CADe during withdrawal and for CADx after lesion detection. Randomisation was done centrally through a secure web-based system using Pocock's minimisation algorithm with a stochastic component and was stratified by centre, sex, previous colorectal cancer, underlying pathogenic variant, and interval since previous colonoscopy. Allocation concealment was ensured through the centralised web-based system. Patients were masked to group allocation until the start of withdrawal in procedures with mild sedation, or until completion of the procedure in procedures with propofol-based sedation. Endoscopists were not masked. The primary outcome was adenoma detection rate, defined as the proportion of patients with at least one histopathologically confirmed adenoma, analysed in the full analysis set (defined as all randomly allocated patients with available data for the primary outcome). The diagnostic performance of the CADx system was evaluated as a secondary outcome. The safety analysis set comprised all randomly allocated patients who underwent a study colonoscopy. This study is registered with the German Clinical Trials Register, DRKS00030695, and is completed. FINDINGS: Between May 9, 2023, and Oct 30, 2025, 757 patients were randomly allocated to HD-WL colonoscopy (377 patients) or to AI-assisted colonoscopy (380 patients); 733 patients were included in the full analysis set (369 HD-WL and 364 AI-assisted). The median age was 49 years (IQR 38-59) in the HD-WL group and 50 years (38-59) in the AI-assisted group; 213 (58%) were female and 156 (42%) male in the HD-WL group, and 207 (57%) were female and 157 (43%) male in the AI-assisted group. The adenoma detection rate was 30&#xb7;9% (114 of 369 patients) with HD-WL versus 33&#xb7;8% (123 of 364 patients) with CADe assistance (odds ratio 1&#xb7;14 [95% CI 0&#xb7;83-1&#xb7;57], p=0&#xb7;41). For CADx differentiation of neoplastic versus non-neoplastic lesions in the paired lesion-level analysis, with histopathology as the reference standard and sessile serrated lesions and traditional serrated adenomas classified as non-neoplastic, CADx sensitivity was 85&#xb7;9% (95% CI 82&#xb7;0-89&#xb7;1) and specificity was 91&#xb7;4% (89&#xb7;4-93&#xb7;0). Three adverse events occurred in the AI-assisted group: two mild post-polypectomy bleedings and one serious pulmonary embolism or deep venous thrombosis unrelated to the procedure. No adverse events occurred in the HD-WL group. INTERPRETATION: CADe-assisted colonoscopy did not show the absolute improvement in adenoma detection rate that was assumed in the prespecified sample-size calculation. CADx did not clearly improve lesion differentiation beyond expert optical diagnosis in expert Lynch syndrome surveillance settings. FUNDING: Third-party research funding of the National Center for Hereditary Tumor Syndromes, University Hospital Bonn.

Humans

The impact of absolute change in tibiofemoral morphology on patient reported outcome measures post total knee arthroplasty.

BACKGROUND: Reconstructing knee morphology and alignment is important for outcomes post total knee arthroplasty (TKA). Personalised alignment strategies are proposed to improve outcomes by replicating native alignment. However, how change in morphology affects patient outcomes is unclear. This study aimed to investigate the relationship between absolute change in morphological measures post-TKA and patient reported outcome measures (PROMs). METHOD: An observational analysis of a randomised clinical trial was conducted. Participants received preoperative and postoperative CT scans and completed PROMs at six-months post-TKA. Absolute change in hip-knee-ankle angle, medial proximal tibial angle, lateral distal femoral angle, non-weightbearing joint line convergence angle, tibial and femoral rotation, and posterior tibial slope (PTS) were calculated. PROMs included visual analogue scales of pain and satisfaction (0-100), Oxford Knee Score, Forgotten Joint Score, and the Kujala Score. Regression and principal component (PCA) analyses investigated relationships between PROMs and change in morphology. RESULTS: Sixty-one participants were included for analysis (61% women, age 66.9&#xa0;&#xb1;&#xa0;9.1 [mean&#xa0;&#xb1;&#xa0;SD] years, BMI 32.8&#xa0;&#xb1;&#xa0;6.8&#xa0;kg/m2). The PCA demonstrated coronal, axial, and sagittal plane measures were interdependent, with over 65% of variability driven by change in tibial rotation (PC1) and the PTS (PC2). The regression analysis showed no relationships between morphological change and PROMs postoperatively. CONCLUSION: Tibiofemoral morphology was interrelated across coronal, axial, and sagittal planes. However, this study suggests absolute morphological change had minimal impact upon PROMs at six-months post-TKA. Future research should clearly distinguish between osteoarthritic versus prearthritic alignment and consider the influence of soft-tissue releases upon PROMs.

Humans

Comprehensive analysis of mRNA-microRNA-lncRNA expression profiles in post-traumatic elbow heterotopic ossification using RNA sequencing and experimental validation.

BACKGROUND: This study aimed to profile the molecular signatures of post-traumatic elbow heterotopic ossification (HO) to identify key regulators and potential therapeutic targets. METHODS: Total RNA from post-traumatic elbow HO tissues (n=4) and normal bone tissues (n=6) was subjected to high-throughput sequencing to identify differentially expressed mRNAs (DEGs), microRNAs (DEMs), and lncRNAs (DELs). Bioinformatics analyses included Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment, protein-protein interaction network construction, and transcription factor (TF)-microRNA-mRNA network analysis. The expression trends of four most upregulated and four most downregulated DEGs were validated by real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR). RESULTS: We identified 2,138 DEGs, 40 DEMs, and 905 DELs. DEGs were significantly enriched in biological process "bone mineralization," cellular component "plasma membrane," molecular function "integrin binding," and pathways including PI3K-Akt, NF-&#x3ba;B, JAK-STAT, and TNF signaling pathways. Hub genes with high connectivity included MMP9, IL6, MMP3, CTSK, and BGLAP. Integrated network analysis highlighted the transcription factor JUN and key microRNAs (hsa-miR-124-3p, hsa-miR-548c-3p, and hsa-miR-135b). The qRT-PCR results confirmed the expression trends of selected DEGs. CONCLUSIONS: This study, for the first time, profiled the differentially expressed mRNAs, microRNAs, and lncRNAs in post-traumatic elbow HO using high-throughput RNA sequencing. These findings provide valuable insights into the molecular mechanisms of HO following elbow trauma. The identified hub genes (MMP9, IL6, MMP3, CTSK, and BGLAP), key TF (JUN), and key microRNAs (hsa-miR-124-3p, hsa-miR-548c-3p, and hsa-miR-135b) may serve as potential therapeutic targets for preventing and treating post-traumatic elbow HO.

Humans

Discrepancies in CPAK classification between CT and long-leg radiography: a systematic review and meta-analysis.

OBJECTIVE: To determine whether substantial differences in coronal plane alignment of the knee phenotype distribution, as well as systematic angular measurement discrepancies, exist between CT and long-leg radiography. MATERIALS AND METHODS: From February 2021 to April 2025, we searched PubMed, Embase, and the Cochrane Central Register of Controlled Trials for studies comparing CT- and long-leg radiography-derived coronal plane alignment classifications of the knee in patients with osteoarthritis. The primary outcome was distribution of coronal plane alignment phenotypes. Secondary outcomes included differences in medial proximal tibial angle, lateral distal femoral angle, arithmetic hip-knee-ankle angle, and joint line obliquity. RESULTS: Four studies (1,134 knees) were included. Compared with long-leg radiography-derived classification, CT-derived classification increased type I phenotypes (risk difference: 0.10; 95% confidence interval: 0.01-0.20; P&#x2009;=&#x2009;0.040) and decreased type III (risk difference: -0.04; 95% confidence interval: -0.07 to -0.01; P&#x2009;=&#x2009;0.020) and type V phenotypes (risk difference: -0.04; 95% confidence interval: -0.07 to -0.01; P&#x2009;=&#x2009;0.004). CT yielded significantly lower medial proximal tibial angle (weighted mean difference:&#x2009;-&#x2009;1.18&#xb0;; P&#x2009;<&#x2009;0.001), arithmetic hip-knee-ankle angle (weighted mean difference:&#x2009;-&#x2009;0.95&#xb0;; P&#x2009;<&#x2009;0.001), and joint line obliquity (weighted mean difference:&#x2009;-&#x2009;1.40&#xb0;; P&#x2009;<&#x2009;0.001) than long-leg radiography. Heterogeneity was high for type I phenotype (I2&#x2009;=&#x2009;81%), lateral distal femoral angle (I2&#x2009;=&#x2009;70%), and joint line obliquity (I2&#x2009;=&#x2009;69%). CONCLUSION: Discrepancies between CT-based software-generated and long-leg radiography-derived measurements substantially affect coronal plane alignment classification and angular parameters. Surgeons should consider these modality-specific variations and employ compensatory verification strategies to ensure optimal alignment.

Humans

Post-intervention effectiveness of a computerized personalized cognitive stimulation program adapted according to cognitive reserve in older adults without cognitive impairment in Primary Care: A randomized clinical trial.

BACKGROUND: Cognitive reserve may influence responsiveness to cognitive interventions, yet it is rarely used to tailor computerized stimulation. OBJECTIVE: To evaluate the effectiveness of a computerized cognitive stimulation program personalized according to cognitive reserve on cognition, reserve-related activities, and digital competence in community-dwelling older adults without cognitive impairment in Primary Care. METHODS: In this randomized clinical trial, 102 adults aged &#x2265;65 years with normal cognitive performance were recruited from three primary care centers in Zaragoza, Spain, and stratified by cognitive reserve level before random allocation to intervention or control. The intervention comprised digital literacy sessions followed by 8 weeks of home-based computerized cognitive stimulation tailored to participants' cognitive reserve profiles and life history. Controls received a single group-based health education session focused on maintaining everyday cognitive activity. Outcomes were assessed at baseline and post-intervention using global cognition (MEC-35), the Cognitive Reserve Questionnaire, the Mobile Device Proficiency Questionnaire-16, and domain-specific neuropsychological tests. A total of 100 participants completed the final evaluation and were included in complete-case analyses. RESULTS: Compared with controls, the intervention group showed greater adjusted post-intervention improvements in global cognition (MEC-35 between-group difference: 1.8 points) and several cognitive measures, including temporal orientation, calculation, attention, praxis, verbal fluency, processing speed, executive functions, and verbal learning. CRQ scores and digital competence also improved, with small-to-large effect sizes. CONCLUSIONS: A computerized cognitive stimulation program adapted according to cognitive reserve appears feasible in Primary Care and may improve cognition, engagement in reserve-related activities, and digital competence in older adults without cognitive impairment.

Humans

Stage shift, histological differentiation, and survival patterns of lung squamous cell carcinoma versus adenocarcinoma in low-dose CT screening.

BACKGROUND: Whether LDCT-associated stage shift translates into similar survival patterns across lung cancer histologies remains uncertain. We compared stage shift, histological differentiation, tumor characteristics, and survival between lung squamous cell carcinoma (LUSC) and adenocarcinoma (LUAD) in the National Lung Screening Trial. METHODS: Among participants diagnosed with LUSC or LUAD, stage distribution and histological differentiation were compared between LDCT and chest X-ray (CXR) arms. Survival among diagnosed cases was measured from randomization. Multivariable models tested screening arm-by-histology interactions. Screen-detected LDCT tumors were compared by histology. RESULTS: During 6.5 years of median follow-up, 498 LUAD and 249 LUSC cases were diagnosed in the LDCT arm, and 374 and 212, respectively, were diagnosed in the CXR arm. LDCT was associated with higher odds of stage I disease for LUAD (adjusted odds ratio [aOR], 2.48; 95% CI 1.88-3.28) and LUSC (aOR, 1.71; 95% CI 1.17-2.48), without significant interaction (P&#x202f;=&#x202f;0.116). LDCT was associated with lower hazard of lung cancer-specific death among diagnosed LUAD cases (adjusted hazard ratio [aHR], 0.54; 95% CI 0.43-0.66), but not among diagnosed LUSC cases (aHR, 1.04; 95% CI 0.78-1.39; P for interaction<0.001). LUSC had lower screening sensitivity, more frequent detection in annual screening rounds, greater prediagnostic tumor size increase, and fewer well-differentiated stage I tumors than LUAD. CONCLUSION: LDCT was associated with stage shift for both subtypes, but favorable survival patterns among diagnosed cases were mainly observed for LUAD. Lower screening sensitivity, greater prediagnostic tumor size increase, and poorer histological differentiation may help explain why stage shift did not translate into similar survival patterns for LUSC. TRIAL REGISTRATION: ClinicalTrials.gov, NCT00047385.

Humans

Safety and efficacy of distal versus conventional radial artery cannulation for invasive blood pressure monitoring: a systematic review and meta-analysis.

To compare the safety and effectiveness of distal radial artery (DRA) versus conventional radial artery (CRA) catheterization for invasive arterial blood pressure monitoring. This meta-analysis followed PRISMA guidelines. Randomized controlled trials published up to December 30, 2025 were systematically searched in PubMed, Embase, Web of Science, the Cochrane Library, CINAHL, CNKI, Wanfang, VIP, and SinoMed. Two reviewers independently screened studies, extracted data, and assessed risk of bias. Meta-analyses were conducted using Review Manager 5.4 and Stata 18.0, and evidence quality was evaluated with the GRADE system. 12 randomized controlled trials (RCTs) involving 1,790 participants were included. For the primary outcomes, compared with CRA, DRA was associated with lower incidences of haematoma (RR&#x2009;=&#x2009;0.42, 95% CI: 0.24-0.73), catheter blockage (RR&#x2009;=&#x2009;0.33, 95% CI: 0.14-0.81), and bleeding (RR&#x2009;=&#x2009;0.25, 95% CI: 0.11-0.59), but a longer catheter insertion time (MD&#x2009;=&#x2009;26.89, 95% CI: 5.28-48.50). For the secondary outcomes, DRA was associated with a shorter haemostasis time and reduced waveform instability, with no significant differences in first-attempt success rate or pain scores. Subgroup analysis showed a higher first-attempt success rate in patients aged&#x2009;&#x2264;&#x2009;65 years (RR&#x2009;=&#x2009;1.14, 95% CI: 1.02-1.28). DRA catheterization for invasive arterial blood pressure monitoring appears to be associated with fewer complications and more stable arterial waveform acquisition than CRA catheterization, despite a longer insertion time. DRA may represent a feasible alternative in surgical and intensive care settings; however, further high-quality studies are needed to confirm its long-term safety and generalizability.

Humans