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Diagnostic performance of machine learning models versus established risk stratification for intracranial aneurysm rupture: a systematic review and bivariate meta-analysis.

BACKGROUND: Machine learning (ML) models have been proposed to improve the discrimination of intracranial aneurysm rupture status beyond established clinical risk stratification tools. However, reported performance is heterogeneous and the relative contribution of model architecture and feature dominance remains unclear. METHODS: We performed a Preferred Reporting Items for Systematic Reviews and Meta-Analyses-diagnostic test accuracy systematic review and diagnostic meta-analysis of studies evaluating ML models for intracranial aneurysm rupture discrimination. PubMed, Embase and CENTRAL were searched to February 2026. Sensitivity and specificity were pooled using a bivariate random-effects model, with summary receiver operating characteristic curves generated across training, internal testing and external validation datasets. Models were compared with regression-based approaches and Population, Hypertension, Age, Size of aneurysm, Earlier subarachnoid haemorrhage, Site of aneurysm (PHASES) scores. Subgroup and meta-regression analyses explored associations between algorithm family and feature domain. RESULTS: Sixty-two retrospective cohorts (29 709 patients 209 models) met the inclusion criteria. In training datasets, pooled sensitivity and specificity for ML were 0.81 (95% CI 0.75 to 0.85) and 0.83 (0.80-0.86), with an area under the curve (AUC) of 0.878, exceeding PHASES (AUC 0.667). In testing datasets, ML retained higher discrimination (AUC 0.837) than regression models (0.806) and PHASES (0.646). In external validation, sensitivity was preserved (0.82), but specificity declined (0.66). Deep learning demonstrated the highest AUCs (training and testing). Incorporation of haemodynamic or radiomic features improved pooled discrimination relative to morphology alone. Evidence of small-study effects and mostly unclear Prediction Model Risk Of Bias Assessment Tool ratings were observed. CONCLUSIONS: ML approaches demonstrate higher pooled discrimination for aneurysm rupture status than conventional risk scores in retrospective datasets, but reduced external validation specificity and heterogeneity limit confidence for clinical translation. Prospective, externally validated, calibrated models are required before integration into routine cerebrovascular risk stratification.

Humans

Prevalence and pattern of psychological symptoms in form of dental fear and anxiety in children and adolescents with traumatic dental injuries: a systematic review.

BACKGROUND/AIMS: This systematic review aimed to evaluate the level and pattern of dental fear and anxiety (DFA) amongst children and adolescents with traumatic dental injuries (TDI) and, where available, to compare these outcomes with non-traumatised controls. METHODS: An a priori protocol was developed and registered in PROSPERO (CRD420261329946). A comprehensive literature search was conducted in PubMed, EMBASE, Web of Science, and Scopus on 3 March 2026, with additional grey literature, citation, and reference searching. No language or time restrictions were applied. Observational clinical studies assessing DFA in individuals with TDI using validated tools were included. Two reviewers independently screened studies, extracted data, and assessed risk of bias using the Joanna Briggs Institute checklist. Certainty of evidence was evaluated using the GRADE approach. RESULTS: A total of 2885 records were identified, of which 4 cross-sectional studies met the inclusion criteria after screening. Studies were conducted in Croatia and Kosovo and included paediatric populations. Sample sizes ranged from 147 to 505 participants. Different validated scales (CFSS-DS, CDAS, S-DAI) were used to assess DFA. Overall, children with TDI demonstrated predominantly low levels of dental fear and anxiety across assessment tools. However, findings were inconsistent, with some studies reporting lower or similar anxiety levels in TDI patients compared to controls. Risk of bias was moderate or high in three of the four studies, and the overall certainty of evidence was rated as low to very low due to methodological limitations, heterogeneity, and imprecision. CONCLUSION: The limited available evidence suggests that children and adolescents with TDI do not consistently present with higher levels of dental fear and anxiety than non-traumatised controls. These findings indicate that TDI does not inherently cause DFA, underscoring the critical role of empathetic behaviour support in mitigating post-traumatic dental fear. However, the evidence is based on a small number of regionally concentrated cross-sectional studies with low to very low certainty. Future prospective studies using standardised TDI classifications, validated DFA instruments, and clearly defined assessment time points are needed.

Dental anxiety

The role of the external genitalia score (EGS) in evaluation of disorders of sex development.

OBJECTIVE: To investigate the utility of the External Genitalia Score (EGS) in the diagnosis of disorders of sex development (DSD) and decision-making regarding gender assignment in affected patients. METHODS: A retrospective cohort study was conducted, enrolling 114 DSD patients aged <2 years (88 reared as males, 26 reared as females) treated at our hospital between April 2005 and June 2023, alongside 40 hypospadias patients aged <2 years who underwent surgery at our institution from January to July 2023. Demographic data (age) and EGS assessments of external genitalia were collected for all participants. Statistical analyses included independent samples t-tests, Mann-Whitney U tests and Receiver Operating Characteristic (ROC) curve analysis. Specifically, EGS scores were compared between the hypospadias group and the male-reared subgroup of the DSD cohort; additionally, EGS scores were contrasted between male-reared and female-reared DSD subgroups. RESULTS: The mean age was 20.3 months in the hypospadias group, 17.9 months in the male-reared DSD group, and 18.8 months in the female-reared DSD group. EGS ranged from 5.5 to 11.5 (median 10.5) in the hypospadias group and from 1 to 12 (median 4.75) in the DSD group. ROC curve analysis was performed to compare EGS scores between the hypospadias group and the male-reared DSD subgroup. The optimal diagnostic threshold was determined by maximizing the Youden index (sensitivity + specificity - 1), which balances sensitivity and specificity. A cut-off value of &#x2264;8.50 was identified as indicative of DSD; clinically, patients with an EGS score <9 should be prioritized for DSD screening. Further comparison between male-reared and female-reared DSD subgroups yielded a threshold of 4.00. Clinically, an EGS score &#x2264;4 may suggest a preference for female gender assignment. DISCUSSION: The EGS scale is a reliable, valid, and clinically feasible tool for characterizing external genitalia in DSD patients. An EGS score of 9 can serve as an indicator for initiating detailed sex development evaluation in hypospadias patients. While gender assignment in DSD is a complex, multifactorial process, EGS scores showed a significant association with the sex of rearing in our cohort. In settings where major determinants are balanced, EGS may serve as an adjunctive descriptive parameter rather than a standalone decision-making tool.

Humans

Low-burden metrics for monitoring healthy diets among nonpregnant females aged 15 to 49 years: a multicountry validation analysis using quantitative 24-hour dietary intake data.

BACKGROUND: Limited nationally representative quantitative dietary intake data and a lack of consensus on lower-burden tools and metrics hinder high-frequency monitoring of healthy diets globally. OBJECTIVES: This study aimed to evaluate the comparative construct validity and potential complementarity of low-burden metrics of a healthy diet among nonpregnant females aged 15 to 49 y. METHODS: Quantitative 24-h dietary intake data collected from 77,118 adolescent and adult females across 27 countries were used to construct low-burden metrics and reference metrics of dietary intake. Associations between mean-standardized low-burden measures or indicators and reference metrics were assessed using linear and logistic mixed-effect models, with Spearman's &#x3c1; used for survey-level rank correlations. Test characteristics identified low-burden indicators best differentiated adherence to reference indicators. RESULTS: An indicator reflecting nonconsumption of sweet foods and/or sweet beverages was most robustly associated with greater adherence to <10% energy from free sugars in upper-middle-income countries {odds ratio [OR] [95% confidence interval (CI)]: 5.35 [5.05, 5.66]}. Food group diversity score (FGDS) was most strongly associated with and differentiated higher mean adequacy ratio of micronutrients [&#x3b2; of 1-standard deviation (SD) change: &#x223c;11 percentage points (9, 12); &#x3c1;: 0.79], whereas noncommunicable disease-Protect score best reflected consumption of &#x2265;400 g/d of fruits and vegetables [range OR of 1-SD changes (95% CI): 2.56-3.01 (2.40, 3.13) in lower-middle and high-income countries, respectively; &#x3c1;: 0.56]. FGDS and Global Diet Quality Score Positive were most consistently associated with achieving &#x2265;25 g/d of fiber and &#x2265;3510 mg/d of potassium across contexts. CONCLUSIONS: Low-burden data collection tools yield valid metrics, enabling high-frequency monitoring of healthy diets across contexts. Specifically, avoiding sweet foods and/or sweet beverages is an indicator for adherence to WHO free sugar guidelines among nonpregnant females in upper-middle-income countries, whereas metrics reflecting nutritious food group diversity strongly reflect better micronutrient adequacy and adherence to WHO guidelines for fruits and vegetables, fiber, and potassium intakes within and across contexts.

Humans

Unanticipated Effects of Parental Social Media Use: Guidance for Clinicians.

"Sharenting," the practice of parents posting photographs, videos, and information about their children on social media, has an ever-growing presence in modern society. However, researchers and the public are now recognizing the potential consequences of sharing, including creation of permanent digital footprints, strained familial relationships, and threats to children's safety. Despite this emerging evidence, no U.S. clinical or legal guidelines exist for parents on safe sharing. Visits with behavioral health providers and family physicians can serve as key points for intervention. This column aims to provide clinicians with a better understanding of sharenting and its potential effects on patients and families, guidance on discussing safe online sharing, and a tool for parents and other caregivers to use when deciding whether to post.

Humans

Effectiveness of an educational video for caregivers of children with neurogenic bladder: A randomized controlled trial.

BACKGROUND: The complexity of neurogenic bladder (NGB) management underscores the importance of caregiver education, yet high-quality education materials remain scarce. This study aims to assess the effectiveness and acceptability of an educational video designed to improve knowledge about NGB among caregivers of children with this condition. METHODS: We identified English-speaking caregivers of patients aged zero to 18 years, diagnosed with NGB, without prior major bladder reconstructive surgery, who received care at our institution from 2018 to 2022. Caregivers were randomly assigned into control or video groups using a block randomization model based on age. The control arm completed a six-item knowledge assessment before viewing the video, while the video group watched the video first. All participants rated the video's acceptability. Qualitative analysis of the open-ended responses to the acceptability questionnaire followed principles of thematic analysis. RESULTS: Of 409 eligible participants, 106 (25.9%) completed the study. Video (n = 48) and control (n = 58) groups were demographically similar. In the video group, 64.6% answered correctly all questions in the knowledge questionnaire, compared to 31% in the control group. After adjusting for patient age, caregivers in the video group were more likely to answer any question in the knowledge assessment correctly (relative probability: 1.13, 95% CI [1.06, 1.21], p < 0.01). Evidence for a difference in correct response rate among individual questions was strongest for question #1, which asked about common urological conditions for which NGB patients are at higher risk (95.8% vs. 79.3%, p = 0.01), and question #6, which asked about indications for bladder surgery (87.5% vs. 67.2%, p = 0.01), with the video group more likely to answer correctly for both questions. Qualitative analysis identified three major themes regarding parents' acceptance of the educational video: 1) attitudes towards video content and presentation, 2) usefulness of video as an educational tool, and 3) future directions. CONCLUSIONS: Our study found that an educational video about NGB effectively enhanced parental understanding of the condition and was deemed acceptable by parents as an introductory educational tool. The literature shows the benefit of using technology and visual aids to enhance health literacy for patients and caregivers, a key first step towards optimizing health outcomes for pediatric urologic patients.

Humans

Quo vadis, BGA? A collaborative EDNAP exercise on the challenges and progress in forensic biogeographical ancestry inference.

There is a broad consensus that forensic tests for the prediction of externally visible characteristics (EVC) and analysis of biogeographic ancestry (BGA) of an individual are technically reliable. However, interpretation of the results and population-specific genotype distribution patterns remains challenging. EVC and BGA analyses provide valuable information for population genetics studies and as investigative leads for criminal cases, as well as for historical and contemporary identification tests. However, inaccurate or incorrect predictions, for example, from subjective bias in the interpretations made, have the potential to misdirect police investigations. The legal situation regarding EVC and BGA testing varies by country: ranging from countries where it is explicitly prohibited, to those without specific regulations on biogeographic ancestry prediction, and others that have already enacted laws governing its use. The reluctance to utilize these analyses is not only due to legal restrictions and data protection concerns, but also to initial limited sets of sufficiently comprehensive forensic DNA assays. Forensic BGA marker panels typically contain up to &#x223c;300 SNPs. This relatively small number of genetic markers, along with limited reference population data, complicates the interpretation of results from donors of unknown origin. This paper presents the results of a collaborative EDNAP study, which, for the first time, evaluated the approach to reporting EVC and BGA data between international laboratories. For the study, DNA from nine individuals with self-reported ancestry was collected and analysed using various forensic panels differing in the number and composition of ancestry-informative markers genotyped, comprising: the Precision ID mtDNA Whole Genome Panel, the VISAGE Basic Tool and the VISAGE Enhanced Tool for Appearance and Ancestry Prediction, and the Ion AmpliSeq&#x2122; PhenoTrivium Panel. To ensure full data protection, all SNP genotypes and uniparental marker haplotypes obtained were not shared with third parties. Instead, the genetic data were analysed using a range of commonly used population analysis software packages. These analysis outcomes were then distributed to twelve European forensic laboratories (both academic and law enforcement institutions), who were asked to prepare reports based on their interpretation of the phenotypes and ancestry they inferred from the analysis data. A questionnaire sent alongside the genetic information, aimed to evaluate which difficulties were encountered by the participants in processing the BGA analysis data they were given.

Humans

Clinical outcomes of zirconia dental restorations: A systematic review and meta-analysis.

OBJECTIVES: To evaluate the survival and success rates of zirconia dental restorations (ZDRs) and their complications. DATA & SOURCES: Electronic searches of PubMed, Cochrane, Embase and Web of Science were conducted up to January 1, 2026. Clinical studies with at least 1-year follow-up evaluating zirconia dental restorations in natural teeth were included. Survival rates, success rates, and biological and mechanical complications were analyzed. Risk of bias was assessed using RoB 2, Newcastle-Ottawa Scale (NOS), and Joanna Briggs Institute tools (JBI). Certainty of evidence was evaluated using the GRADE approach. STUDY SELECTION & RESULTS: Sixty-six studies published between 2008 and 2025 were included. Pooled survival rates ranged from 92.9% to 98.7% up to 10 years for single crowns (SCs), 77.6% over 10 to 13 years for fixed dental prostheses (FPDs), 97.4% for resin-bonded FPDs (RBFPDs) over 10 to 15 years, from 50.0% to 52.6% over 9 to 13 years for conventional cantilever FPDs (CFPDs) and 89.0% for inlay-retained FPDs (IRFPDs) over 10 years. Pooled success rates were 46.1% for SCs over 10 years, 40.1% for FDPs over 10 to 13 years, 84.3% for RBDPDs over 10 to 15 years, 12.5% to 22.6% for CFPDs over 9 to 13 years and 70.3% for IRFPDs over 10 years. Biological and mechanical complication rates were 12.1% and 53.9% for SCs at 10 years, 19.4% and 46.7% for FPDs over 10 to 13 years, 50.0% and 37.5% for CFPDs at 9 years, 21.4% and 14.3% for IRFPDs at 3 years, and 3.3% and 8.0% for RBFPDs over 10 to 15 years. Restorations treated with airborne-particle abrasion (APA) combined with 10-methacryloyloxydecyl dihydrogen phosphate (MDP) achieved favorable short-term clinical outcomes, with pooled survival and success rates of 98.6% and 97.7% for SCs, and 98.1% and 70.1% for IRFPDs, respectively. The included studies were assessed as having low to moderate risk of bias using RoB 2, NOS, and JBI tools, but GRADE assessment yielded evidence of very low certainty. CONCLUSIONS: ZDRs generally demonstrated acceptable to excellent short- to long-term survival and success outcomes. Mid- to long-term clinical performance was varied according to restoration types. The RBFPDs had relatively low complication rates, followed by the SCs, the FPDs and the IRFPDs. CFPDs exhibited relatively low success rates and high complication rates. The predominant biological complications were secondary caries and pulpitis or apical periodontitis, while chipping and debonding were the most common mechanical complications. APA treatment followed by application of MDP is capable of producing favorable short-term clinical outcomes. CLINICAL SIGNIFICANCE: ZDRs except for CFPDs could achieve favorable mid- to long-term clinical performance. CFPDs should be conducted with caution.

Zirconium

Diagnostic performance of panfungal PCR on tissue specimens for the diagnosis of invasive fungal diseases: a systematic review and meta-analysis of the Fungal PCR Initiative (FPCRI).

UNLABELLED: Invasive fungal diseases are difficult to diagnose because of the limited sensitivity of culture. Panfungal PCR amplicon sequencing assays (targeting ribosomal RNA, such as 18S, 28S, ITS) are recommended for fungal identification in histopathology samples showing fungal elements. However, data describing its overall performance and consistency are lacking. This systematic literature review and meta-analysis assessed the performance of panfungal PCR on formalin-fixed paraffin-embedded (FFPE) and non-fixed (fresh or frozen) tissue samples. A systematic literature search was performed to include studies reporting the use of panfungal PCR for fungal identification in FFPE or non-fixed tissue samples. PCR sensitivity and specificity were assessed using the reference standard of histopathology showing fungal elements. Quality assessment was performed using the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool. Pooled estimates were obtained using random-effects meta-analysis. Twenty-eight studies were included. In FFPE samples (18 studies, 852 samples), sensitivity and specificity were 75.4% (95% confidence interval [CI], 59.2-86.6) and 93.5% (70.2-98.9), respectively. Sensitivity in non-fixed samples (13 studies, 207 samples) was 86.5% (74.7-93.3), while specificity could not be assessed (insufficient data). Comparative analyses showed a significantly higher sensitivity of panfungal PCR over culture (88.2%; 76-94.7 vs 52.2%; 39-65, P = 0.001). Sub-analyses could not demonstrate the superiority of one PCR target over another due to limited data. Panfungal PCR exhibited adequate sensitivity and good specificity in FFPE samples. Sensitivity was even higher in non-fixed samples and largely superior to culture. Nevertheless, large interstudy variability was observed, warranting interlaboratory studies to define the optimal PCR target and standardized protocols. IMPORTANCE: Invasive fungal diseases are difficult to diagnose because of the low sensitivity of culture. Panfungal PCRs are widely used for fungal identification in tissue specimens but suffer from heterogeneous procedures and performance. This meta-analysis shows an acceptable sensitivity (75.4% and 86.5% in fixed and non-fixed samples, respectively) and good specificity (93.5%) of panfungal PCR, supporting its use, not only on histopathology-positive fixed samples but also in non-fixed samples concomitantly with other diagnostic tools (cultures and fungal-specific PCRs if available). These results provide a strong basis for further standardization of panfungal PCR techniques via interlaboratory assays to assess reproducibility and optimize analytical protocols. CLINICAL TRIALS: This study is registered with PROSPERO as CRD42023461148.

Humans

Viral surveillance beyond detection: JMTV and the need for ensemble approaches in emerging virus discovery.

The recent report by T. Murillo, L. E. Enrique Chaves-Gonz&#xe1;lez, S. Temmam, S. Berm&#xfa;dez, et al. (Microbiol Spectr 14:e04078-25, 2026, https://doi.org/10.1128/spectrum.04078-25) expands the known geographic and ecological range of Jingmen tick virus (JMTV) by detecting the virus in Amblyomma mixtum ticks collected from horses in Costa Rica. This is an important finding because A. mixtum can feed on wildlife, domestic animals, and humans, creating a possible interface for virus movement across various hosts. The study also places the Costa Rican virus in a wider phylogenetic context, linking it to JMTV diversity reported from other regions. However, the detection of viral RNA in ticks should not be interpreted as proof of local disease, human infection, or active transmission, especially in the absence of supporting results. Instead, it reflects an important signal for careful viral surveillance. Here, I discuss how JMTV illustrates the need for ensemble approaches that combine field sampling, phylogeny, segment-level genome analysis, serology, experimental validation, and data-driven virus discovery tools.

emerging viruses

Computational metabolomics at scale: from open data to insight.

Metabolomics data are currently generated at scale thanks to the evolution of technologies that have led to marked improvements in the number of metabolites detected, spanning all chemical classes. These data are increasingly submitted to public repositories for data reuse, integration, and interpretation. Despite the availability of public resources and associated computational tools, the field still lacks a widely adopted, consistent data and analytics infrastructure capable of transforming this wealth of information into scientific insight. Indeed, the metabolomics field is just now scratching the surface of being able to harness the power of new computational technologies. In this review, we summarize discussions from the "Dagstuhl-Seminar 24181 Computational Metabolomics: Towards Molecules, Models, and their Meaning" with a focus on public data availability, open data standards, data and knowledge integration, and education. Our goal is to raise awareness and adoption of the latest open science resources while highlighting key areas needing further development.

Metabolomics

Colorimetric gold nanosensors for monitoring protein aggregation: implications for Alzheimer's disease.

Alzheimer's disease (AD) is the leading cause of dementia worldwide. It remains a major public health challenge due to the lack of early diagnostic tools and effective disease-modifying therapies. Molecularly, AD is characterized by extracellular amyloid-&#x3b2; (A&#x3b2;) plaques and intracellular Tau tangles, as well as soluble oligomers that are likely the neurotoxic species. However, the transient and heterogeneous nature of these oligomers makes them difficult to detect using conventional biosensing approaches. Nanomaterial-based colorimetric biosensors have emerged as promising platforms for detecting protein aggregates and discovering aggregation inhibitors. Specifically, the localized surface plasmon resonance properties of metallic nanomaterials can enable rapid, label-free, and visually detectable colorimetric sensing of molecular interactions. These features can be leveraged to monitor protein aggregation processes in real time and achieve high-throughput screening of aggregation inhibitors, which may collectively enable early detection and timely intervention of AD progression. This Review Article presents the design and engineering of gold-nanomaterial-based colorimetric biosensors for monitoring protein aggregation and highlights the current challenges and emerging opportunities for applying these nanosensors to combat AD.

Journal Article

Alternative genetic codes in bacteria and archaea identified with a fast k-mer-based algorithm.

The genetic code is conserved across all domains of life and is often described as universal. Nevertheless, many exceptions to the "universal" code have now been documented, most of these through manual or semiautomated inspection of highly conserved genes. Modern bioinformatics tools improved our ability to find alternative genetic codes but remain computationally expensive, preventing widespread use on thousands of new species identified by sequencing environmental samples. Here, I report a >100-fold accelerated method for inferring the genetic code directly from assembled genomes and apply it to thousands of previously uncharacterized assemblies from archaea and bacteria. I describe three candidate genetic code variations, one of which, an alternative genetic code used by a family of Asgard archaea, is a unique example of sense codon reassignments for this domain. Identifying genetic code variations is important for understanding evolution of the standard code and improving accuracy of protein databases and open reading frame identification.

Genetic Code

MicroRNAs in Oral Bio-Fluids as Predictive Biomarkers of Orthodontic Tooth Movement: A Systematic Review.

This systematic review was designed to assess scientific evidence of the association of microRNA expression during orthodontic tooth movement through various time points. A systematic review was performed in accordance with the PRISMA checklist. A search strategy was developed in electronic databases including Med Line, Scopus, EBSCO Host and ProQuest Dissertations & Theses Global until June 2025. Eligibility criteria included studies that investigated microRNA expression in saliva/GCF during orthodontic treatment. The risk of bias of the included studies was analysed using the QUADAS-2 and RoB-2 tools. The search retrieved 2800 records, of which nine studies were selected. Minor variations in GCF collection were noted, while stimulated saliva was collected in one study. RT-PCR and the Fluro meter accounted for the majority of miRNA estimation. Thirteen miRNAs were identified as target biomarkers for OTM regulation. Despite the high risk of bias, the evidence from the current systematic review indicates that microRNAs can be considered as potential biomarkers of orthodontic tooth movement in oral biofluids. Trial Registration: Prospero ID-CRD420251153064.

Humans

Pilot Distractions and Interruptions in Airlines: Ranking of Sources by Analytic Hierarchy Process.

ObjectiveThis work establishes a methodological framework for sources of pilot distraction and interruptions in a structured model that can be used as a tool for cockpit design/procedure assessment.BackgroundPilots must complete complex tasks, and distractions can impair performance and lead to errors that can cause aircraft accidents. Although various cockpit distractors are examined individually, there is no integrated approach.MethodDistraction and interruption sources were identified through a literature review and confirmed/extended by interviews with airline pilots. Associated weights were determined through pairwise comparisons, yielding a hierarchical model using the Analytic Hierarchy Process.Results26 sources of pilot distraction and interruptions were quantified and categorized into four categories: communication, head-down time, responding to abnormal conditions & unexpected situations, and searching for traffic.ConclusionA taxonomic structure for assessment is achieved with the top 5 sources identified as communications, technical interruptions, experience in type, environmental factors, operational irregularities, and airspace high terrain, accounting for 63.07%.ApplicationThe structured system is a flexible assessment scale that provides a taxonomic framework for airline risk management, supports future research, and cockpit design efforts.

Humans

Artificial intelligence (AI) uses in stereotactic radiosurgery (SRS): diagnosis with brain metastasis (BM) - A systematic review.

BACKGROUND: Brain metastases (BM) are the most common intracranial tumors in adults, and stereotactic radiosurgery (SRS) has become a mainstay of management. However, several diagnostic challenges persist in the SRS pathway, particularly the differentiation of radiation necrosis (RN) from true tumor progression, which conventional MRI and even advanced imaging techniques often cannot reliably resolve. Recent advances in artificial intelligence (AI) offer the potential to address these diagnostic limitations. This systematic review synthesizes current literature on AI applications for MRI-based diagnostic decision support in BM patients undergoing SRS, with a focus on radiomics and deep learning tools for distinguishing RN from progression, classifying molecular and histologic subtypes, and predicting treatment response. METHODS: A systematic review was performed in accordance with PRISMA guidelines. PubMed, Web of Science, and Scopus were searched using a targeted query combining terms related to AI, brain metastasis, diagnosis or imaging, and SRS. After screening 483 records and applying strict inclusion and exclusion criteria, 18 studies published between 2015 and 2025 were included. Data were extracted on study design, cohort characteristics, imaging modality, AI methodology, validation strategy, and reported diagnostic performance. RESULTS: Among the 18 included studies, AI models demonstrated strong performance across diagnostic tasks in the BM-SRS pathway. The differentiation of RN from true tumor progression was the most extensively studied application, addressed by 14 of 18 studies, with reported AUCs ranging from 0.71 to 0.94. Support vector machines, random-forest ensembles, convolutional neural networks, and transformer-based multimodal architectures were widely used. The literature evolved from single-sequence radiomic classifiers in 2018 to multimodal deep learning frameworks fusing imaging with clinical and genomic data in 2025. Contrast-enhanced T1-weighted MRI was the dominant imaging input, and texture-based radiomic features (GLCM, GLSZM, GLDM, and wavelet-derived features) were the most consistently predictive. The highest-performing models reached AUCs of 0.85-0.91 through multimodal integration of imaging with clinical and genomic features, and consistently outperformed expert neuroradiologist read on matched cases. Remaining studies addressed longitudinal segmentation-based detection of local failure and adverse radiation effects, BRAF mutation status in melanoma BM, early Gamma Knife treatment response, and primary tumor histology classification, with more variable performance. CONCLUSION: AI models, particularly those integrating MRI-derived radiomic features with clinical and genomic data, show high accuracy in supporting diagnostic decisions for BM patients treated with SRS. The post-SRS differentiation of radiation necrosis from true tumor progression has reached the greatest level of maturity and is closest to clinical translation, with potential to reduce unnecessary biopsies, personalize surveillance intervals, and rationalize treatment-pathway decisions. Other diagnostic applications, including molecular subtyping and primary tumor histology classification, remain exploratory and require further multicenter validation. Integration of AI tools into multidisciplinary tumor-board workflows, combined with prospective validation and standardized reporting, will be essential to realize the full clinical benefits of AI in SRS for brain metastases.

Humans

Strategies for mosaic variant calling in brain disorders.

The human brain is a genomic mosaic, where postzygotic mutations arising from embryogenesis to senescence drive diverse neurodevelopmental and neurodegenerative diseases. Because of numerous sequencing artifacts at ultralow variant allele frequencies (VAFs), detecting these variants remains a significant analytical challenge. This review focuses on single-nucleotide variants and small indels, summarizing current strategies for aligning sampling methods, including bulk, laser capture microdissection, and single-cell genomics, with the expected clonal architecture of the brain. It emphasizes that mosaic detection sensitivity is fundamentally constrained by sequencing depth, since even the most advanced algorithms cannot identify variants not physically represented in the sequencing library. The review further recommends the selection of variant calling algorithms based on validated VAF detection performance, matching tools like MuTect2 and MosaicForecast to their optimal performance ranges. Furthermore, we discuss how multitissue sampling, as emphasized by the SMaHT project, addresses the matched-control dilemma and supports accurate variant classification via cross-tissue VAF gradients. Integrating these established pipelines with multiomics modalities, including transcriptomic and epigenetic data, could advance the field toward a functional understanding of how the somatic genome impacts human brain health and disease.

Humans

Breaking the Debilitating Cycle: Pathophysiology, Assessment, and Multimodal Intervention of Secondary Debilitation After Hip Fracture in Older Adults-A Narrative Review.

Hip fractures pose a serious threat to the quality of life among older adults and impose a heavy burden on both society and families. Although current surgical techniques for hip fractures have become increasingly refined, postoperative quality of life and overall function in older adult populations often steeply decline. This decline is marked by "secondary debilitation," characterized by exacerbated sarcopenia, functional impairment, and physiological reserve depletion-a process that becomes a risk factor for recurrent fractures, creating a "vicious cycle" with hip fractures. This article provides a comprehensive overview of the pathophysiological mechanisms underlying "secondary debilitation," discusses the clinical application of risk assessment tools, and presents a phased, stepwise intervention strategy aimed at interrupting the "vicious cycle." The strategy includes early rapid rehabilitation, nutritional support, and prevention of complications; a mid-phase multimodal approach involving multidisciplinary management, comanaged wards, fracture liaison services, and systematic rehabilitation; and, finally, late-phase exploration of emerging pharmacotherapies and treatment methods. This review seeks to offer an evidence-based foundation for optimizing clinical risk assessment and developing precise interventional strategies.

Humans