Supratentorial pediatric ependymomas (ST-EPNs) represent a rare and biologically heterogeneous subgroup of central nervous system tumors. The 2021 WHO molecular classification has redefined their diagnostic framework, emphasizing prognostic and therapeutic implications. This study analyzes clinical, surgical, and molecular features of pediatric ST-EPNs treated at a single-institution, with particular focus on outcomes and prognostic variables. We retrospectively reviewed pediatric patients with histologically confirmed supratentorial ependymomas treated between 2007 and 2023. Tumors were reclassified according to the 2021 WHO molecular criteria. Clinical presentation, imaging characteristics, tumor location, molecular subtype, extent of resection, adjuvant therapies, recurrence patterns, and long-term outcomes were evaluated. Twelve patients were included (mean age 7.4 years). Two tumors were intraventricular and ten extraventricular. Molecular profiling identified ZFTA fusion-positivity in 11 cases and YAP1 fusion-positivity in one case. Gross total resection was achieved in 11 of 12 patients, whereas one patient underwent near-total resection because of vascular encasement of the middle cerebral artery, making complete resection unsafe. Intraventricular tumors presented earlier, required complex surgical management, and were associated with higher treatment burden. Extraventricular tumors commonly presented with seizures and cystic imaging features, with favorable postoperative recovery. Recurrence occurred in 3 patients, successfully managed with repeat surgery and adjuvant therapy. At a mean follow-up of 8 years, all patients were alive with good neurological outcomes. Secondary neoplasms were observed in isolated cases following multimodal treatment. This single-institution molecularly reclassified series highlights clinically relevant differences between intraventricular and extraventricular pediatric supratentorial ependymomas in presentation, surgical complexity, and treatment burden. Our findings support maximal safe resection as the central therapeutic strategy while emphasizing the value of integrated molecular diagnostics and prolonged surveillance, particularly in light of late recurrence and secondary neoplastic events.
Atypical spindle cell/pleomorphic lipomatous tumor and dysplastic lipoma are closely related fatty masses associated with RB1 abnormalities. While it is not yet widely agreed that they are separate entities, the distinct morphological features of dysplastic lipomata and divergent anatomic distribution suggest that this is probable. RB1 abnormalities are present in spindle cell/pleomorphic lipoma, pleomorphic liposarcoma, and pleomorphic liposarcoma with or without myxoid component. Survivors of hereditary retinoblastoma, caused by germline mutations in the RB1 gene, have a substantially increased risk of developing benign and malignant lipomatous tumors including atypical spindle cell/pleomorphic lipomatous tumor and dysplastic lipoma. This report describes the MRI findings of several such lesions in a survivor of bilateral retinoblastoma including features such as enhancement that might otherwise be concerning for higher-grade malignancy.
A defining feature of electroencephalography (EEG) data is its 1/f-like spectral structure, whereby power decreases as frequency increases. The nonoscillatory, aperiodic activity underlying this structure has regained attention as an index of cortical excitation-inhibition balance or neural noise, though its precise link to cognition remains unclear. Accordingly, this PRISMA-compliant systematic review examined 45 studies on aperiodic EEG features and cognition in healthy adults (∼18-65 years), organized across cognitive domains, which included processing speed, attention, perception, memory, working memory, executive functions, learning, language, and complex/naturalistic tasks. The aperiodic exponent showed consistent associations: steeper spectra correlated with inhibitory control, conflict resolution, and encoding; flatter spectra with sensory engagement, cognitive flexibility, and recall. Evidence from resting-state and task-based EEG indicates that aperiodic activity reflects both stable, trait-like neural efficiency and flexible, state-dependent adaptability. These findings support the functional relevance of aperiodic parameters and call for methodological standardization to guide future research.
This study aimed to develop and validate a hybrid deep learning-radiomics model that leveraged Cycle-consistent generative adversarial networks (CycleGAN)-synthesized contrast-enhanced computed tomography (CE-CT) images to differentiate advanced from non-advanced hepatic fibrosis. This retrospective study included 410 patients with biopsy-confirmed hepatic fibrosis (2017-2024). A trained CycleGAN model was used to generate synthetic three-phase CE-CT images from the corresponding non-contrast computed tomography (NC-CT) data. Each group of images was randomly split 6:4 ratio into training and test sets. After region of interest (ROI) segmentation, handcrafted radiomic (HCR) features were extracted. Concurrently, eight end-to-end deep learning (DL) models were trained; DL features were extracted from the best-performing model. Feature selection was performed using Spearman's rank correlation and the least absolute shrinkage and selection operator (LASSO). Six machine learning classifiers were developed for each feature type (HCR, DL, and late-fused DL features) using the final selected feature set. The performance of models was assessed by the area under the receiver operating characteristic curve (AUC), accuracy, calibration curves, decision curve analysis (DCA) and the DeLong test. Models utilizing synthetic CE-CT images outperformed those based on NC-CT. DL feature-based models surpassed HCR-based models. A late-fusion hybrid model integrating DL features further improved performance, achieving an AUC of 0.880 (95% CI: 0.819-0.942). The model based on synthetic CE-CT images demonstrated excellent diagnostic performance. Moreover, the hybrid model combining both real NC-CT and synthetic CE-CT images further improved diagnostic performance. The hybrid model can serve as a non-invasive diagnostic method for differentiating advanced from non-advanced hepatic fibrosis.
This study investigates possible differences of female and male patients' data in regard to the prediction of mortality and troponin level of acute pulmonary embolism (APE) patients. Radiomics features are utilized to gain insights of sex-specific image properties, which should support APE diagnosis and treatment. A database of 200 manually segmented APE patients' computed tomographic data (100 female and 100 male) was used for the prediction of 30-day mortality and biomarker troponin level. The radiomics features were extracted from the segmented thrombi and reduced via correlation analysis and 12 feature selection followed each by 12 classification methods. For comparison, the weighted F1-Score, Matthew's Correlation Coefficient, and balanced accuracy were used. For assessment of generalizability, the study was extended to 427 automatically selected datasets. Sex-dependent differences have been found in the resulting metrics and highest achieving feature selection and classification methods. Not stratifying the dataset by sex resulted in lower performance compared to the sex-stratified male and female only calculations. The subgroup of female patients achieved up to 31.04 % higher metric values compared to the other cohorts. Different thrombus properties contributed to the prediction based on the patients' sex as well. In this study, we analyzed possible correlations between sex of APE patients and mortality and troponin levels as well as radiomics features. Our analysis identified an influence of sex on the prediction task and image feature selection. Female patient data especially had higher predictive potential, which could help for further sex-stratified analysis of APE.
Desmin-related cardiomyopathy is a rare disorder caused by pathogenic variants in desmin and associated protein genes. We aimed to describe the clinical, histopathological, immunohistochemical, ultrastructural, and molecular features in a pediatric cohort. This retrospective descriptive study reviewed pediatric cases diagnosed over a 30-year period. Clinical data were extracted from electronic medical records. Archived histologic slides (H&E, desmin immunostains, and special stains) and electron photomicrographs were re-evaluated. Key features were documented and summarized. Four pediatric patients (3 males and 1 female) presented between ages 2 and 14 years with restrictive cardiomyopathy and conduction abnormalities. Endomyocardial biopsies and/or explanted heart specimens showed eosinophilic cytoplasmic inclusions that were desmin-immunoreactive, PAS-negative, and highlighted by toluidine blue. Electron microscopy revealed dense cytoplasmic granulofilamentous aggregates that were frequently continuous with the sarcoplasmic membrane, Z-bands, and intercalated discs. Two patients harbored the same pathogenic variant: DES c.1360T>C (p.Arg454Trp). Desmin-related cardiomyopathy should be considered in any child presenting with restrictive cardiomyopathy and/or rhythm disturbances. Distinctive light microscopic and ultrastructural features can aid in confirming the diagnosis. Certain pathogenic variants are increasingly linked to more severe phenotypes, highlighting the importance of genetic evaluation and its implications for family counseling.
Multi-emissive carbon quantum dots (CQDs) are attracting widespread attention across fields. Three kinds of nitrogen and phosphorus co-doped CQDs (NPCQDs) were synthesized through a two-step method. Firstly, phosphorus-doped CQDs (PCQDs) with blue fluorescence were rapidly prepared using maleic acid and disodium hydrogen phosphate as the carbon and phosphorus sources by microwave method. Subsequently, through the hydrothermal method, NPCQDs were successfully obtained using 3-aminophenylboronic acid, diethylenetriamine, and o-phenylenediamine as dopants and reacting with PCQDs. Their emission peaks are located at 437 nm exhibiting blue fluoresce (B-NPCQDs), 550 nm (yellow, Y-NPCQDs), and 600 nm (red, R-NPCQDs), respectively. Compared with PCQDs (11.7%), the QYs are high values of 17.32%, 41.37%, and 37.32% for B-NPCQDs, Y-NPCQDs, and R-NPCQDs, respectively. Y-NPCQDs exhibited superior fluorescence stability against most interferents, while B-NPCQDs and R-NPCQDs served as selective fluorescent probes for Fe2+ and Ag+/Cu2+ detection, respectively. For fingerprint imaging, Y-NPCQDs@Al2O3 composites achieved clear visualization of fingerprint first-, second-, and third-level features. In comparison, B-NPCQDs@Al2O3 only revealed first-level features with insufficient detail, while R-NPCQDs@Al2O3 led to blurred images due to excessive adhesion to the substrate. In fruit preservation, 0.5% Y-NPCQDs/PVA film showed the optimal effect on jujubes, maintaining good fruit color and plumpness for 13 d and significantly delaying ripening.
DFT calculations were conducted to investigate the Au(I)-catalyzed one-pot reaction of propargylsilane (R1) and aldehyde (R2), which exclusively provides the trans-2-silyl-4,5-dihydrofuran (tP) without the formation of the corresponding cis-isomer (cP). Key findings reveal that the unconventional chemoselectivity─wherein the nucleophilic attack of R2 occurs at Si(-Me3) rather than the alkyne C atom─originates from the stronger electrostatic interaction between the carbonyl O atom of R2 and the Si(-Me3) cation. Subsequently, following re/si-face addition, an "O(TMS) nucleophilic cyclization-promoted" catalytic mechanism was established to account for the formation of cP/tP, characterized by two key features: (i) the O(TMS) nucleophilic cyclization weakens its σ-interaction with the Si(-Me3) atom, thereby facilitating subsequent Si(-Me3)-migration─distinct from the challenging cleavage of the inherently inert O-Si σ-bond; (ii) the resultant outer-sphere protodeauration ensures significant σ-type orbital overlap between the migrating H and Au-attached C atom, circumventing the energetically unfavorable orbital angular misalignment characteristic of the classical inner-sphere pathway. Furthermore, the in situ-generated cP coordinates with the active [Au]+ catalyst, forming an oxonium cation intermediate. This intermediate features the activation of the rigid (aryl)C-O σ-bond on the dihydrofuran ring, which contributes significantly to the cis-trans isomerization (cP → tP). Consequently, the exclusive diastereoselectivity is achieved. These insights are anticipated to facilitate the rational design and optimization of innovative synergistic catalytic systems.
Peptides are versatile biomolecules that have emerged as promising scaffolds for chemical recognition. Probing their interactions with toxic oxyanions such as arsenite is important for understanding fundamental recognition mechanisms relevant to environmental chemistry. In this study, the affinity of a tetraglycine peptide, (Gly) 4 $_4$ , toward the dihydrogen arsenite, H 2 AsO 3 - ${\rm H}_2{\rm AsO}_3^-$ , is investigated using a multilevel computational approach. MD simulations identify the stable conformational landscape of tetraglycine, revealing the emergence of a preorganized pseudo-macrocyclic motif. Density functional theory (DFT) provides detailed insights into the electronic features of the peptide-anion interaction, highlighting cooperative hydrogen bonding at the binding interface. An ONIOM-based QM/MM framework incorporates explicit solvation on the (Gly) 4 $_4$ -anion complex, emphasizing the role of backbone flexibility in stabilizing the bound structure. Noncovalent interaction (NCI) and symmetry-adapted perturbation theory (SAPT0) analysis indicate that electrostatic interactions constitute the dominant stabilizing contribution. These findings deepen the mechanistic understanding of peptide-anion interactions while clarifying the scope and limitations of this simplified model system.
Pushing the resolution limit of axon diameter mapping in the living human brain requires higher gradient strength than is currently available on most clinical MRI systems. The noninvasive quantification of axon diameter not only enables the exploration of axonal damage in a wide range of neurological disorders but also provides fundamental insights into axonal organization and conduction patterns of white matter tracts. The goal of this study was to evaluate the sensitivity of axon diameter mapping to small diameter axons using the next-generation Connectome MRI scanner (Connectome 2.0), which features a maximum gradient strength of 500 mT/m and slew rate of 600 T/m/s, compared to the original Connectome 1.0 scanner with 300 mT/m gradient strength. We applied the AxCaliber-SMT model to diffusion MRI data from 40 healthy adults, comprising 20 participants scanned on Connectome 1.0 before it was decommissioned and a separate cohort of 20 age- and sex-matched participants scanned on Connectome 2.0. Our findings are based on group-level comparisons between these two cohorts. The theoretical minimum detectable axon diameter was 2.5 μm on Connectome 2.0 and 3.6 μm on Connectome 1.0. The MR-estimated axon diameter in the corticospinal tract on the Connectome 2.0 scanner was 2.66 ± 0.54 μm, significantly lower than 3.35 ± 1.00 μm on Connectome 1.0 (Welch's t-test: p = 0.0110). Comparison was performed across independently acquired datasets from age- and sex-matched individuals on different scanners; therefore, the observed group differences should be interpreted as strong and supportive, though not strictly causal, evidence of the proposed scanner capability. Furthermore, we examined 7 healthy adults for scan-rescan repeatability and demonstrated that the voxel-wise mean absolute difference in axon diameter estimates between scan and rescan decreased to 0.29 μm on the Connectome 2.0 (vs. 0.65 μm on the Connectome 1.0), indicating improved repeatability of the axon diameter estimates. These improvements are enabled not only by the higher gradient strength of Connectome 2.0, but also by the associated reduction in echo time and increase in SNR, which together enhance sensitivity to restricted diffusion and improve parameter reliability. Our findings highlight the importance of stronger and faster gradients for accurate and robust mapping of the axonal microstructure in the human brain.
Hair follicle organoids (HFOs) have demonstrated revolutionary regenerative potential in hair follicle regeneration, while their high-throughput production, uniform morphology, excellent hair growth potential, and simple and efficient intradermal transplantation are still challenges. In this paper, we present novel hair follicle seedling cryomicroneedles to achieve bionic hair regeneration by using a hierarchical microfluidic organoid-on-a-chip. Our integrated chip features a fluidic channel module and a hierarchical microneedle template module, enabling microflow-guided uniform cell distribution into needle-shaped microwells to form HFOs. Cryopreservation agents (CPA)-containing pregel solutions are injected to encapsulate HFOs following UV gelation, and the final HFO-loaded cryomicroneedle (cryoMN@HFO) is obtained after freezing and demolding. We have demonstrated that the cryoMNs@HFOs could preserve homogeneous HFO morphology, favorable viability, and excellent hair growth potential. Besides, the cryoMN@HFOs possess good skin penetration ability and biosafety, enabling rapid transplantation of HFOs into the dermis. Thus, after intradermal transplantation in animal experiments, the delivered organoids develop into fully functional hair follicles with mature structures in vivo. Based on these advantages, we believe that this technology holds promise for human hair follicle reconstruction.
This study aims to develop an optimal model for distinguishing seminoma from non-seminoma testicular tumors using machine learning classifiers based on multiparametric MRI radiomics. This multi-institutional study enrolled a total of 188 patients, including 83 with seminoma and 105 with non-seminoma. The cohort from Institution 1 (n = 137) served as the training and validation set, whereas the independent cohort from Institution 2 (n = 51) was designated as the test set. Manual segmentation of tumor regions of interest (ROIs) was performed by experienced researchers on DWI, ADC, T2WI, and CE-T1WI sequences. A comprehensive radiomics workflow was implemented, encompassing data standardization, dimensionality reduction, feature selection, and classification using six distinct machine learning classifiers. Predictive models were developed by integrating radiomics features extracted from individual sequences and multiple sequence combinations with machine learning algorithms. In parallel, clinical models were established through univariate and multivariate logistic regression to identify significant predictive factors. A combined model incorporating both radiomics signatures and clinical characteristics was subsequently developed. The discriminatory performance of all models was evaluated by comparing area under the curve (AUC) values using DeLong's test. Model 19 (DWI+T2WI+ADC+CE-T1W+Clinical/SVM) achieved the highest AUC values, reaching 0.934, 0.922, and 0.846 on the training, validation, and external test sets respectively. In terms of clinical-radiological characteristics, alpha-fetoprotein (AFP) and cystic necrosis are significant predictors. A combined model utilising DWI, ADC, T2WI, and contrast-enhanced T1WI imaging, alongside AFP and cystic necrosis, demonstrates high precision, adaptability, and robustness in distinguishing seminoma from non-seminoma testicular tumors.
Comprehensive genomic profiling has prognostic and predictive value for patients with pancreatic adenocarcinoma. We reviewed clinical and molecular data from 4,009 samples from patients who had undergone the BostonGene Tumor Portrait test between 28.10.2021 and 08.10.2024, and 2,181 samples from the BostonGene pancreatic adenocarcinoma meta-cohort, collected from various data hosts and processed by BostonGene automated pipelines. In this high-purity pancreatic adenocarcinoma cohort, 24% harbor homozygous MTAP deletion, and the co-occurrence of KRAS mutations and MTAP loss was common (18.9% of all pancreatic adenocarcinomas). This association identified a subgroup with worse survival outcomes. MTAP-deficient tumors harbor more fibrotic, less immune-enriched microenvironments and have shorter survival. Within the co-mutated tumors, the most frequently detected KRAS variants were G12D, G12V, and G12R, with the last one slightly more related to immune-enriched TME features than the other KRAS variants. Comprehensive genomic profiling is essential for patients with PAAD and carries both prognostic and predictive value. MTAP loss KRAS-mutant PAAD represents a subgroup of immune-excluded PAADs with a poor prognosis.
We aim to provide an overview of treatment patterns and outcomes in high-risk rectal cancer patients with a particular focus on total neoadjuvant therapy (TNT) use. Patients with locally advanced rectal cancer who commenced pre-operative treatment at the Royal Brisbane and Women's Hospital, the Princess Alexandra Hospital, and Redcliffe Hospital between 2020 and 2023 were included in this retrospective cohort study. Data collected included demographics, cancer stage, tumour details, treatment undertaken, disease progression, and survival. Data were analyzed using R Studio version 1.4.1717. 124 patients were included, with 47 having undergone TNT and long-course chemoradiotherapy (LCCRT) and 77 having undergone LCCRT alone ± adjuvant chemotherapy. Those who received TNT were significantly more likely to have high-risk features such as extramural venous invasion, T4 tumor, and N2 disease. 89.5% of TNT patients across our centres received FOLFOX chemotherapy, and 77.1% received ≥6 cycles. 14.7% of TNT patients went on to receive adjuvant chemotherapy compared to 35.5% of non-TNT patients, with the most common adjuvant chemotherapy in the TNT group being FOLFOX (85.7%). 15% of TNT patients achieved a pathological complete response compared with 13.8% in the non-TNT group. Disease-free survival favored the non-TNT group with a median value of 39.4 months versus 36.9 months, though this was not statistically significant. This retrospective cohort study undertaken across multiple metropolitan centres shows increased uptake of TNT, particularly in high-risk patient cohorts, consistent with changes in international guidelines for treatment of rectal adenocarcinoma.
Comorbid insomnia and sleep apnea (COMISA) is a highly burdensome phenotype with additive effects on symptoms, quality of life, and health outcomes. Although obstructive airway diseases (OAD)-including asthma and chronic obstructive pulmonary disease-commonly coexist with sleep complaints, the association between OAD and COMISA in large sleep-clinic cohorts remains unclear. We investigated whether OAD is independently associated with COMISA in a nationwide cohort undergoing full-night polysomnography (PSG). We analyzed 12,715 adults in the Turkish Sleep Apnea Database (TURKAPNE), a prospective, multicenter registry. Demographics, comorbidities, insomnia symptoms, and PSG parameters were compared between individuals with and without OAD, defined as self-reported, physician-diagnosed asthma or COPD. COMISA was defined as the coexistence of obstructive sleep apnea (apnea-hypopnea index ≥ 5 events/h) and insomnia symptoms occurring "often" or "very often." Multivariable logistic regression was used to determine the independent association between OAD and COMISA. OAD was present in 12.2% of participants (n = 1,546). COMISA prevalence was higher in those with OAD than in those without OAD (16.1% vs 10.8%, p < 0.001). After adjustment for age, sex, body mass index, education, smoking status, and comorbidities, OAD remained independently associated with COMISA (adjusted odds ratio 1.19; 95% CI 1.06-1.35; p = 0.004). Among participants with COMISA, individuals with OAD were older, more frequently female, more obese, and demonstrated shorter total sleep time, longer wake after sleep onset, higher periodic limb movement index, and poorer nocturnal oxygenation. In this nationwide sleep-clinic cohort, OAD was independently associated with COMISA. COMISA patients with OAD exhibited more adverse clinical and polysomnographic features. These findings highlight the multidimensional sleep burden in OAD and support integrated, personalized management strategies.
A spontaneous malignant trichoepithelioma is diagnosed in a CD1/ICR outbred, six-month-old, intact, nulliparous female mouse belonging to a breeding colony. Postmortem examination revealed a solitary, locally extensive, tumour mass, 3.5 × 3,2 centimetres in size, affecting the skin and subcutaneous tissues on the left side of the neck, shoulder, and chest. The overlying skin was focally ulcerated. At sagittal section, the mass was pseudolobulated, grayish pink in colour with soft consistency and adhered to deeper tissues. Regional lymph nodes were not enlarged, and no other lesions were found at necropsy. Microscopically, a pseudolobulated, well circumscribed but non-capsulated highly cellular epithelial tumour with trichogenic differentiation extends from superficial dermis, in contact and replacing hair follicles and raise the skeletal muscle was found. More than 60% of the tumour was composed by small buds of basaloid epithelial cells with incipient keratinisation, (resembling hair bulbar papilla's), admixed with cords and trabecula of squamous epithelium with central tricolemmal keratinitation (hair intermediate segment differentiation) as well as, multiple cysts, variable in size, lined by squamous epithelium, with or without a granular cell layer, and containing lamellar keratin and/or amorphous cell debris, resembling the infundibular segment of hair follicle. Nuclear atypia and the mitotic account were moderate. Emboli of tumours cells were found in the skin, pleura and lung. Nests and cords of basaloid cells with trichogenic differentiation were observed throughout ipsilateral skeletal muscles, soft tissues of the neck, thoracic wall, adventitia layers of the thyroid, pleura and lung parenchyma. The histological features and immunohistochemical profile were consistent with malignant trichoepithelioma. Although trichoepitheliomas are majority benign tumours in domestic animal and humans, this study represents the first description of malignant trichoepithelioma in a CD1/ICR mouse.
Rare genetic disorders affecting enamel pose considerable challenges for clinicians due to their scarcity, limited documentation, and variable clinical manifestations, making accurate diagnosis and effective management particularly complex. These conditions may also affect tooth number, shape, and eruption, further complicating dental rehabilitation. The authors focused this review on selected syndromic disorders characterized by distinctive phenotypic features affecting teeth and other systems, with enamel defects likely to be first encountered by dental care providers. The authors' objective was to synthesize the knowledge on genetic etiologies, functional consequences, oral manifestations, and dental management strategies, complemented by means of clinical and radiographic illustrations. The authors used searches of the PubMed and Online Mendelian Inheritance in Man databases as well as critical analysis of original research, topical reviews, and case reports. More than 115 genes and conditions were identified, and 8 conditions were selected for their genetic and clinical relevance. The authors integrated case descriptions and images to help readers understand these disorders and visualize their key features, including genetic etiology and clinical management. Due to the rare nature of these conditions, the authors relied on published reports featuring clinical photographs and radiographs. Rapid advances in the genetic understanding of rare disorders affecting teeth underscore the need for dental care providers to become familiar with these conditions. Investigating their genetic basis clarifies the origins of dental anomalies and highlights the involvement of other organ systems, reinforcing the importance of recognizing these disorders as relevant beyond oral health.
Biallelic variants in COQ7 have been associated with inherited neuropathy. COQ7 encodes a mitochondrial protein directly involved in coenzyme Q10 (CoQ10) biosynthesis. Two unreported and unrelated cases of COQ7-related neuropathy are presented, along with a review of all previously published cases to highlight the key clinical features. The frequency of COQ7 variants was assessed in our cohort of distal hereditary motor neuropathy (dHMN) patients with upper motor neuron (UMN) signs. The two patients were compound heterozygous for the COQ7 variants c.197T>A, p.(Ile66Asn) and c.478del, p.(Asp160Thrfs*11); the latter has not been reported. Symptoms began in childhood, and both were diagnosed with dHMN based on distal motor weakness predominantly affecting the lower limbs and a pure motor length-dependent axonal neuropathy on electrodiagnostic study. They had pes cavus and brisk reflexes. In the 28 patients identified in the literature, including the two reported herein, the median age at symptom onset was 10 years (IQR [5-11]). The predominant neuropathy subtype was dHMN (89%). Foot deformities were observed in 19/23 patients (83%). Signs of UMN involvement were present in 20/27 patients (74%). In fibroblasts, CoQ10 levels were low, and 6-demethoxy-CoQ10 (DMQ10) levels were elevated in all tested patients (8/8, 100%). No other case was identified in 71 patients with dHMN and UMN signs. COQ7-related neuropathy is rare but should be considered in young patients presenting with distal hereditary motor neuropathy, especially when UMN signs are present. Elevated DMQ10 levels and low CoQ10 levels in fibroblasts represent valuable diagnostic biomarkers.
Purpose To develop a machine learning-based model to identify patients with hypertrophic cardiomyopathy (HCM) at high risk of major adverse cardiac events (MACEs) and key predictors of model performance. Materials and Methods This retrospective cohort study included patients who underwent cardiac MRI for HCM evaluation between September 2015 and December 2022. Cardiac MRI included balanced cine steady-state free precession, native T1 and T2 mapping, and late gadolinium enhancement. MACEs were defined as a composite of cardiovascular death, resuscitated sudden cardiac death, or heart failure hospitalization. A penalized Cox proportional hazards model with elastic net regularization (CoxNet) was developed with 33 clinical, genetic, echocardiography, and cardiac MRI variables. Model training used 200 iterations of stratified subsampling cross-validation (80% training, 20% testing). Performance was evaluated with the Harrell C index and compared with the 2014 European Society of Cardiology sudden cardiac death risk model. Results A total of 604 patients were included (mean age, 52 years ± 15 [SD]; 417 male patients; median follow-up, 3.0 years [IQR, 1.9-4.2 years]). The CoxNet model demonstrated favorable performance for MACE prediction (C index, 0.75; 95% CI: 0.65, 0.83), similar to the European Society of Cardiology model (C index, 0.67; 95% CI: 0.57, 0.75; P = .07). Key predictors included apical aneurysm, left ventricular end-systolic volume indexed to body surface area, extensive late gadolinium enhancement, native T1 z score, and male sex. Conclusion A machine learning-based model comprising routinely available variables showed strong performance for MACE prediction in HCM. Key variables highlight the impact of cardiac MRI features on risk stratification. Keywords: MRI, Machine Learning, Model Training, Cardiac, Heart, Hyperplasia, Hypertrophy © RSNA, 2026 See also commentary by Shiwani in this issue.
Aluminum nitride (AlN) is an ultrawide-bandgap semiconductor whose large intrinsic band gap limits low-energy interband optical absorption. This work compares Ce substitution at the Al site, C substitution at the N site, and Ce-C co-substitution in wurtzite AlN to clarify how Ce 4f/5d states and C 2p states modify the local structure, band-edge electronic states, and optical response. Among five neutral CeAl-CN configurations considered in a 2 × 2 × 2 supercell, the nearest-neighbor Ce-C pair has the lowest total energy, with the other configurations lying 6.6-17.7 meV higher. The selected Ce-C pair also has a negative binding energy of -3.26 eV relative to the corresponding isolated single-substitution reference supercells. Structural relaxation shows lattice expansion after substitution, with the largest volume increase of 7.93% obtained for AlN:Ce-C. The calculated band gap of intrinsic AlN is 4.19 eV, whereas the effective electronic gaps of AlN:C, AlN:Ce, and AlN:Ce-C are 3.59, 2.18, and 2.04 eV, respectively. Since AlN:Ce-C is only 0.14 eV smaller in effective gap than AlN:Ce, the role of Ce-C co-substitution is interpreted mainly through defect-pair energetics, orbital redistribution, and local population changes rather than as a large additional band-gap narrowing. DOS/PDOS and population analyses show that C 2p states mainly modify the occupied valence-edge region, Ce 4f/5d states contribute near the band-edge and conduction-band regions, and Ce-C co-substitution induces finite spin population on C together with a nonzero Ce-C bond population. The scissors-corrected optical spectra show increased low-frequency dielectric and refractive responses, with ε₁(0)/n(0) changing from 3.805/1.951 for intrinsic AlN to 4.449/2.109 for AlN:Ce-C, while AlN:C gives the largest low-frequency values of 4.530/2.128. Additional low-energy interband absorption and attenuation features appear especially in AlN:C and AlN:Ce-C, associated with defect-related transitions involving C 2p and Ce-related states. These changes are interpreted as calculated interband optical-response redistribution within the present neutral-defect supercell framework, not as direct evidence of device-level optoelectronic performance. First-principles calculations were performed using the CASTEP module in Materials Studio. The exchange-correlation interaction was described using the generalized gradient approximation with the Perdew-Burke-Ernzerhof functional, and on-the-fly-generated ultrasoft pseudopotentials were employed. Intrinsic AlN, AlN:Ce, AlN:C, and AlN:Ce-C were constructed from a fully relaxed 2 × 2 × 2 wurtzite AlN supercell containing 32 atoms. Single-doped models were constructed by replacing one Al or one N atom, corresponding to 6.25% substitution on the relevant sublattice. The co-doped model contains one CeAl-CN pair, corresponding to xCe = yC = 0.0625 in Al1-xCexN1-yCy, or a combined sublattice substitution level of 12.5%. A plane-wave cutoff energy of 700 eV and a 4 × 4 × 3 k-point mesh were used. Intrinsic AlN was calculated using non-spin-polarized GGA-PBE, C-doped AlN using spin-polarized GGA-PBE, and the Ce-containing systems using spin-polarized GGA-PBE + U. A Hubbard U correction of 5 eV was applied only to the Ce 4f orbitals. Band structures, TDOS/PDOS, Mulliken and Hirshfeld population analyses, representative bond populations, and optical properties were calculated. The dielectric function, complex refractive index, absorption coefficient, and reflectivity were obtained within the linear-response framework using a 2.01 eV scissors correction only for optical-property calculations.