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Objective To investigate the utility of tumoral and peritumoral [ 18 F]-fluorodeoxyglucose PET-based radiomics models for predicting tumor spread through air spaces (STAS) in non-small-cell lung cancer (NSCLC). Methods A total of 104 patients with NSCLC were retrospectively included and classified as STAS-positive or STAS-negative according to postoperative histopathology. Three radiomics models were developed based on tumoral and peritumoral volumes of interest (VOIs). Peritumoral models were constructed by defining VOIs with 5 and 10 mm expansions from the tumor margin (PR-5 and PR-10). Conventional PET-derived parameters were calculated. Each group was randomly divided into training (70%) and testing (30%) sets. For prediction, five machine learning algorithms were applied. Model performance was assessed by area under the receiver operating characteristic curve (AUC), accuracy, precision, recall, and F1 score. Results Of the 104 patients, 60 (57.7%) were in the STAS-positive group, and 44 (42.3%) were in the STAS-negative group. Statistically significant differences were found in 27 tumoral, 62 PR-5, and 89 PR-10 radiomic features between the groups. Support Vector Machine achieved the best performance for the tumoral model (AUC: 0.70), whereas Logistic Regression was optimal for the PR-5 and PR-10 models, with AUCs of 0.79 and 0.74, respectively. The mean F1 score values for the tumoral, PR-5, and PR-10 models were 0.67, 0.72, and 0.68, respectively. Maximum standardized uptake value (SUV max ), SUV mean , and SUV peak did not differ significantly between groups. Tumor size, total lesion glycolysis, and metabolic tumor volume were significantly higher in the STAS-positive group. Conclusion Our findings suggest that peritumoral PET-based radiomics may help predict STAS status in NSCLC. The PR-5 model demonstrated the highest predictive performance, while conventional SUV-based parameters showed limited predictive value.

Abstract Hereditary adult-onset ataxias are a heterogeneous group of phenotypically overlapping conditions, often caused by pathogenic expansions of short tandem repeats. Currently, 18 repeat disorders with a core phenotype of adult-onset ataxia are known. Diagnosis typically relies on sequential PCR-based methods, which are labour-intensive and lack precision. Long-read sequencing (LRS) has the potential to overcome these limitations and is currently implemented and validated in clinical genetics. Using clinical nanopore Cas9-targeted sequencing (Clin-CATS) for parallel in-depth repeat analysis, we evaluated a diagnostic cohort of 513 adult-onset ataxia patients, determining frequencies of all known repeat-associated ataxias except Spinocerebellar ataxia 4 (SCA4), as well as the carrier frequencies for autosomal-recessive disorders, RFC1 spectrum disorder and Friedreich’s ataxia (FRDA). Additionally, phenotypes of patients with established genetic diagnoses were characterized, especially those of patients living with RFC1 spectrum disorder and SCA27B. Repeat-associated ataxias were confirmed in 33.3% of cases, including rare ataxias, such as SCA10, SCA36 and SCA37, alongside as the most prevalent conditions SCA27B and RFC1 spectrum disorder. Potentially pathogenic expansions in FGF14 were identified in an additional 4.7% of patients. Testing of another 347 patients for ZFHX3 expansions linked to SCA4 did not identify any cases. Dual diagnoses were frequent, occurring in 6.4% of patients with repeat-associated ataxia. We confirmed a high RFC1 spectrum disorder carrier frequency (7.2%) and reclassified certain FXN expansions as likely non-pathogenic, resulting in a lower than estimated carrier frequency for FRDA of 0.8%. We also identified novel repeat configurations in several loci and illustrated the high heterogeneity of repeat expansions in RFC1, highlighting it as a potential source of false results when using PCR-based methods. This study underscores the diagnostic advantages of LRS for comprehensive repeat analysis and recommends its adoption as a standard in clinical genetics, replacing Southern blot and PCR-based approaches. Furthermore, based on our findings in a large patient cohort a re-evaluation of existing phenotype-genotype correlations is recommended as well as evaluating additional parameters alongside the repeat length to improve diagnostic precision of repeat analysis.

Background: Primary ciliary dyskinesia (PCD) is a rare genetic disorder characterized by recurrent sinopulmonary infections due to motile cilia defects. The disease is genetically heterogeneous, with abnormalities in structural ciliary proteins. Zinc finger MYND-type containing 10 (ZMYND10) is essential for the assembly of outer dynein arms (ODA), with chaperones like Glucose-regulated protein 78 (GRP78) facilitating protein folding. This study investigates ZMYND10 and Dynein axonemal heavy chain 5 (DNAH5) mutations in individuals with PCD. Methods: Eight individuals aged 14–22 with clinical PCD symptoms and confirmed DNAH5 mutations were included. We analyzed the correlation between DNAH5 abnormalities and preassembly/chaperone proteins using immunofluorescence labeling. Nasal swabs were double-labeled (DNAH5–β-tubulin, β-tubulin–ZMYND10, β-tubulin–GRP78) and examined via fluorescence microscopy. Serum metabolomics and proteomics were also assessed. Results: The corrected total cell fluorescence (CTCF) levels of DNAH5, ZMYND10, and GRP78 were significantly different between PCD individuals and controls. Metabolomic analysis showed reduced valine, leucine, and isoleucine biosynthesis, with increased malate and triacylglycerol biosynthesis, malate-aspartate and glycerol phosphate shuttles, and arginine/proline metabolism, suggesting mitochondrial and ER stress. Conclusions: The altered expression of DNAH5, ZMYND10, and GRP78, along with metabolic shifts, points to a complex link between ciliary dysfunction and cellular stress in PCD. Further studies are needed to clarify the underlying mechanisms.

Objective To develop and validate classification criteria for pediatric chronic nonbacterial osteomyelitis (CNO) jointly supported by EULAR and the American College of Rheumatology (ACR). Methods This international initiative had 4 phases: (1) candidate items were proposed in a survey of pediatric rheumatologists, (2) criteria definition and reduction by Delphi and nominal group technique exercises, (3) criteria weighting using multicriteria decision analysis, and (4) refinement of weights and threshold score in a development cohort of 441 patients and validation in another cohort of 514 patients. Results The new EULAR/ACR classification criteria for CNO require typical radiographic or magnetic resonance imaging findings and bone pain as an obligatory entry criterion and exclusion criteria of malignancy, infection, vitamin C deficiency, and hypophosphatasia, followed by additive weighted criteria in 5 clinical (site of bone lesions, pattern of bone lesions, age at onset, coexisting conditions, fever) and 4 pathology/laboratory domains (bone biopsy findings if done, anemia, C‐reactive protein level, and erythrocyte sedimentation rate). A total score ≥55 is required for classification as CNO. The new criteria had a sensitivity of 82% and specificity of 98% in the validation cohort. Conclusion These new classification criteria for pediatric CNO developed with international input reflect current views about CNO, have high specificity and good sensitivity, and provide a key foundation for future CNO research.

Background/Objectives: Primary ciliary dyskinesia (PCD) (OMIM: 244400) is a hereditary, rare disorder with a high prevalence in Turkey due to a high rate of consanguinity. The disorder is caused by malfunctioning motile cilia and is characterized by a variety of clinical symptoms including sinusitis, otitis media and chronic obstructive pulmonary disease. This study presents the first assessment of the efficacy of immunofluorescence (IF) labeling for diagnosing PCD in Turkey by correlating IF with clinical observations when genetic data are scarce. Methods: We have a cohort of 54 PCD-suspected individuals with an age range of 5–27 years classified into two groups: group A with available genomic data (8 individuals) and group B with no available genomic data (46 individuals). We performed immunofluorescence analysis to confirm the pathogenicity of the variants in individuals with a prior genetic diagnosis and to confirm a PCD diagnosis in individuals with typical PCD symptoms and no genetic diagnosis. Results: All individuals had airway infections and displayed clinical symptoms of PCD. Our data revealed an absence of outer dynein arm dynein heavy chain DNAH5 in individuals with pathogenic variants in DNAH5 and DNAAF1 and in 17 other PCD-suspected individuals, an absence of nexin–dynein regulatory complex component GAS8 in 8 PCD-suspected individuals, an absence of outer dynein arm dynein heavy chain DNAH11 in 6 PCD-suspected individuals and an absence of radial spoke head component RSPH9 in 2 PCD-suspected individuals. Furthermore, the pathogenicity of ARMC4 variants was confirmed by the absence of the outer dynein arm docking complex component ARMC4 and the proximal localization of DNAH5. Conclusions: Immunofluorescence analysis, owing to its lower cost and quicker turnaround time, proves to be a powerful tool for diagnosing PCD even in the absence of genetic data or electron microscopy results.

OBJECTIVE Many patients recruited in the Treatment of Brain Arteriovenous Malformations Study (TOBAS) are managed conservatively. The aim of this study was to monitor what happened to those patients. METHODS TOBAS comprises two randomized controlled trials and multiple prospective registries. All patients with brain arteriovenous malformations (AVMs) can participate. This report concerns patients selected for conservative management. The primary trial outcome measure is related death or dependency (modified Rankin Scale [mRS] score > 2) at 10 years. Secondary outcomes include intracranial hemorrhages, nonhemorrhagic neurological events, and serious adverse events (SAEs). For this report, outcome results are presented using patient-years, Kaplan-Meier survival curves, and Cox log-rank tests. There was no blinding. RESULTS From June 2014 to May 2021, 1010 patients were recruited, of whom 498 (49%) were proposed the prospective observation registry. After exclusions, 434 (87%) patients remained for analysis. The majority of patients had unruptured AVMs (378/434 [87%]), of which 195 (52%) were low grade (Spetzler-Martin grade I or II). During a mean follow-up period of 3.2 years (total 1368 patient-years), the primary outcome occurred in 23 of 434 (5%) patients, corresponding to an incidence of 1.7 (95% CI 1.1–2.5) per 100 patient-years. For unruptured AVMs the incidence was 1.1 (95% CI 0.7–1.9) per 100 patient-years, and for low-grade unruptured AVMs it was 0.6 (95% CI 0.2–1.7) per 100 patient-years. Poor outcomes were more frequent in patients with a history of rupture (HR 5.6 [95% CI 2.4–13.0], p < 0.001), infratentorial AVMs (HR 2.9 [95% CI 1.1–7.3], p = 0.027), and age ≥ 55 years (HR 3.2 [95% CI 1.4–7.6], p = 0.007). Major intracranial hemorrhage occurred in 35 of 434 (8%) patients (incidence of 2.6 [95% CI 1.9–3.6] per 100 patient-years; 2.0 [95% CI 1.3–2.9] per 100 patient-years for unruptured AVMs and 1.3 [95% CI 0.6–2.6] per 100 patient-years for low-grade unruptured AVMs). Major AVM hemorrhages were more frequent in ruptured (HR 4.4 [95% CI 2.1–8.9], p < 0.001), large (HR 2.6 [95% CI 1.1–6.6], p = 0.039), and high-grade (HR 2.5 [95% CI 1.2–5.3], p = 0.013) AVMs and those with deep venous drainage (HR 2.1 [95% CI 1.1–4.2], p = 0.032). SAEs occurred in 48 of 434 (11%) patients (incidence of 3.6 [95% CI 2.7–4.8] per 100 patient-years). For unruptured AVMs the incidence was 2.8 (95% CI 2.0–4.0) per 100 patient-years, and for low-grade unruptured AVMs it was 1.8 (95% CI 1.0–3.2) per 100 patient-years. CONCLUSIONS Nearly half of TOBAS participants were observed. Rates of untoward neurological events were within expected boundaries.

ImportanceKidney light chain (AL) amyloidosis is associated with a risk of progression to kidney replacement therapy (KRT) and death. Several studies have shown that a greater reduction in proteinuria following successful anticlonal therapy is associated with improved outcomes.ObjectiveTo validate graded kidney response criteria and their association with kidney and overall survival (OS).Design, Setting, and ParticipantsThis retrospective, multicenter cohort was conducted at 10 referral centers for amyloidosis from 2010 to 2015 and included patients with kidney AL amyloidosis that was evaluable for kidney response and who achieved at least hematologic partial response within 12 months of diagnosis. The median follow-up was 69 (54-88) months. Data analysis was conducted in 2023.ExposureFour kidney response categories based on the reduction in pretreatment 24-hour urine protein (24-hour UP) levels: complete response (kidCR, 24-hour UP ≤200 mg), very good partial response (kidVGPR, &amp;gt;60% reduction in 24-hour UP), partial response (kidPR, 31%-60% reduction), and no response (kidNR, ≤30% reduction). Kidney response was assessed at landmark points (6, 12, and 24 months) and best kidney response.Main Outcomes and MeasuresCumulative incidence of progression to KRT and OS.ResultsSeven-hundred and thirty-two patients (335 women [45.8%]) were included, with a median (IQR) age of 63 (55-69) years. The median (IQR) baseline 24-hour proteinuria and estimated glomerular filtration rate was 5.3 (2.8-8.5) g per 24 hours and 72 (48-92) mL/min/1.73m2, respectively. In a competing-risk analysis, the 5-year cumulative incidence rates of progression to KRT decreased with deeper kidney responses as early as 6 months from therapy initiation (11%, 12%, 2.1%, and 0% for kidNR, kidPR, kidVGPR, and kidCR, respectively; P = .002) and were maintained at 12 months and 24 months and best kidney response. Patients able to achieve kidCR/kidVGPR by 24 months and at best response had significantly better OS compared with kidPR/kidNR. Kidney progression, defined as a 25% or greater decrease in estimated glomerular filtration rate, was associated with cumulative incidence of progression to KRT and OS.Conclusions and RelevanceThe results of this cohort study suggest that graded kidney response criteria offers clinically and prognostically meaningful information for treating patients with kidney AL amyloidosis. The response criteria potentially inform kidney survival based on the depth of reduction in 24-hour proteinuria levels and demonstrate an OS advantage for those able to achieve kidCR/kidVGPR compared with kidPR/kidNR. Taken together, achievement of at least kidVGPR by 12 months is needed to ultimately improve kidney and patient survival.

Abstract Globally, breast cancer (BC) remains a significant cause to female mortality. Early detection of BC plays an important role in reducing premature deaths. Various imaging techniques including ultrasound, mammogram, magnetic resonance imaging, histopathology, thermography, positron emission tomography, and microwave imaging have been employed for obtaining breast images (BIs). This review provides comprehensive information of different breast imaging modalities and publicly accessible BI sources. The advanced machine learning (ML) techniques offer a promising avenue to replace human involvement in detecting cancerous cells from BIs. The article outlines various ML algorithms (MLAs) which have been extensively used for identifying cancerous cells in BIs at the early stages, categorizing them based on the presence or absence of malignancy. Additionally, the review addresses current challenges associated with the application of MLAs in BC identification and proposes potential solutions.

Background and Aim: Distal radius fractures are the most frequent upper extremity fractures in the whole population. The incidence of distal radius fractures is 195.2/100,000, and the rate is increasing. It can occur with low-energy trauma in the elderly associated with osteoporosis. The purpose of this study is to compare the two different treatment groups (1. Sedation analgesia, 2. Supracondylar radial nerve block) in terms of reduction in Visual Analogue Scale (VAS) score, the length of hospital stay, complications, side effects, patient-physician satisfaction, and the ease of application. Materials and Methods: Patients diagnosed with distal radius fracture were enrolled prospectively, to whom the study’s exclusion criteria do not apply. The patients included in the study were randomly separated into two groups. Ketofol was administered to the sedation and analgesia group’s patients at a dose of 0.5 mg/kg (ketamine 0.5 mg/kg, propofol 0.5 mg/kg) intravenously, and supracondylar radial nerve block was performed on the other group’s patients under ultrasound guidance. Results: There were 20 patients (6 male, 14 female) in the sedation and analgesia group and 21 patients (11 male, 10 female) in the supracondylar radial nerve block group. There was no significant difference between the groups regarding patient-physician satisfaction and complications. The length of hospital stay was significantly shorter in the supracondylar radial nerve block group (49.25 ± 4.05) compared with the sedation and analgesia group (125 ± 5.85) (p < 0.01). The mean reduction VAS score in the block group was observed to be lower than the admission VAS score (p < 0.01). Conclusion: Consequently, ultrasound-guided supracondylar radial nerve block would be a valuable alternative to procedural sedation analgesia and could become routine clinical practice in treating distal radius fractures.

Abstract In the quest to unravel the mysteries of neurological diseases, comprehending the underlying mechanisms is supreme. The SH-SY5Y human neuroblastoma cell line serves as a crucial tool in this endeavor; however, the cells are known for its sensitivity and slow proliferation rates. Typically, this cell line is cultured with 10% Fetal Bovine Serum (FBS) supplement. Nu-Serum (NuS), a low-protein alternative to FBS, is promising to advance cell culture practices. Herein, we evaluated the substitution of NuS for FBS to test the hypothesis that an alternative serum supplement can aid and promote SH-SY5Y cell proliferation and differentiation. Our findings revealed that the NuS-supplemented group exhibited a notable increase in adhered cells compared to both the FBS and serum-free (SF) groups. Importantly, cell viability remained high in both sera treated groups, with the NuS-supplemented cells displaying significantly larger cell sizes compared to the SF-treated group. Furthermore, cell proliferation rates were higher in the NuS-treated group, and neuroblast-like morphology was observed earlier than FBS group. Notably, both FBS and NuS supported the differentiation of these cells into mature neurons. Our data supports NuS as an alternative for SH-SY5Y cell culture, with the potential to elevate the quality of research in the neuroscience field.