Deep learning-based fully automatic Risser stage assessment model using abdominal radiographs.

BACKGROUND: Artificial intelligence has been increasingly used in medical imaging and has demonstrated expert level performance in image classification tasks. OBJECTIVE: To develop a fully automatic approach for determining the Risser stage using deep learning on abdominal radiographs. MATERIALS AND METHODS: In this multicenter study, 1,681 supine abdominal radiographs (age range, 9-18 years, 50% female) obtained between January 2019 and April 2022 were collected retrospectively from three medical institutions and graded manually using the United States Risser staging system. A total of 1,577 images from Hospitals 1 and 2 were used for development, and 104 images from Hospital 3 for external validation. From each radiograph, right and left iliac crest patch images were extracted using the pelvic bone segmentation model DeepLabv3 + with the EfficientNet-B0 encoder trained with 90 digitally reconstructed radiographs from pelvic computed tomography scans with a pelvic bone mask. Using these patch images, ConvNeXt-B was trained to grade according to the Risser classification. The model's performance was evaluated using accuracy, area under the receiver operating characteristic curve (AUROC), and mean absolute error. RESULTS: The fully automatic Risser stage assessment model showed an accuracy of 0.87 and 0.75, mean absolute error of 0.13 and 0.26, and AUROC of 0.99 and 0.95 on internal and external test sets, respectively. CONCLUSION: We developed a deep learning-based, fully automatic segmentation and classification model for Risser stage assessment using abdominal radiographs.

Clinical and radiographic results of locking plate with medial support screw in Proximal Humerus fracture - the more, the better?

BACKGROUND: The calcar of the proximal humerus is a fundamental structure for medial humeral column support. This study aimed to assess the outcome of osteosynthesis across cases of unstable proximal humerus fractures (PHFs) with medial calcar comminution, following treatment with a PHILOS locking plate and medial support screw (MSS). METHODS: Between January 2010 and December 2018, we retrospectively analyzed the outcomes of 121 cases of osteosynthesis for PHFs with medial column disruption. For the medial support, at least one oblique screw was inserted within 5 mm of the subchondral bone in the inferomedial quadrant of the humeral head. All patients were categorized into two groups: 26 patients in the single MSS group, and 95 in the multiple MSS group. Follow-up after at least an year involved clinical and radiographic outcome evaluations, and correspondingly measuring the Constant-Murley score, University of California, Los Angeles (UCLA) shoulder scale, pain visual analogue scale (VAS), major complications, neck-shaft angle (NSA), humeral head height (HHH), and the eventual time to bone union. Risk factors for the major complications were assessed by multivariate logistic regression analyses. RESULTS: The cohort's mean age was 64.4 ± 15.4 years, and the mean follow-up duration was 19.5 ± 7.6 months. At the final follow-up, between the single MSS and multiple MSS groups, no significant differences in the Constant-Murley score (p = 0.367), UCLA score (p = 0.558), VAS (p = 0.571), time to bone union (p = 0.621), NSA loss (p = 0.424), and HHH loss (p = 0.364) were observed. The incidence of complications (p = 0.446) based on the number of MSS were not significantly different. The initial insufficient reduction after surgery (of NSA < 125°) was found to be a significant risk factor for post-surgical complications. CONCLUSIONS: To treat unstable PHFs, the use of at least one MSS along with a locking plate system is sufficient to achieve satisfactory outcomes. Successful operative treatment using a locking plate for PHF treatment is inherent in anatomical fracture reduction, coupled with medial column support.

Safety of Gadoxetate Disodium for Hepatobiliary MRI in Children and Adolescents.

Background Despite a proven role in the characterization of liver lesions, use of the gadolinium-based contrast agent (GBCA) gadoxetate disodium at MRI is limited in children due to a lack of comparative safety data. Purpose To evaluate the safety of the GBCA gadoxetate disodium (a linear ionic hepatobiliary contrast agent [HBA]) in children and adolescents, compared with extracellular contrast agents (ECA). Materials and Methods A retrospective analysis was conducted in children and adolescents aged 18 years or younger who underwent HBA-enhanced MRI at one of three tertiary hospitals from January 2010 to December 2022. The incidence of GBCA-associated acute adverse events was compared between MRI examinations with a HBA and those with ECA. Severity was categorized according to American College of Radiology guidelines (mild, moderate, or severe). (a) Propensity score matching using multivariable logistic regression models and (b) inverse probability of treatment weighting analysis based on nine covariates (age, sex, asthma, allergic rhinitis, chronic urticaria or atopy, food allergy, drug allergy, premedication, and history of GBCA-associated adverse events) were used for confounder adjustment. Results A total of 1629 MRI examinations (ECA, n = 1256; HBA, n = 373) in 1079 patients were included (mean age, 8.6 years ± 6.5; 566 girls). The per-examination incidence of GBCA-associated acute adverse events showed no evidence of a difference, with rates of 0.9% (11 of 1256 examinations) for ECA and 1.3% (five of 373 examinations) for HBA (odds ratio [OR], 1.55 [95% CI: 0.54, 4.46]; P = .42). Acute adverse events were all mild with ECA, whereas with HBA, they were mild for four patients and moderate for one patient. There was no evidence of a difference in the incidence of acute adverse events, even in propensity score matching (OR, 1.33 [95% CI: 0.30, 5.96]; P = .71) and inverse probability of treatment weighting analysis (OR, 0.84 [95% CI: 0.25, 2.86]; P = .78). Conclusion Gadoxetate disodium showed no difference in acute adverse events compared with ECA in children and adolescents, with further large-scale pediatric studies required to confirm its safety. © RSNA, 2024 Supplemental material is available for this article. See also the editorial by Otero in this issue.

Feasibility of a deep learning artificial intelligence model for the diagnosis of pediatric ileocolic intussusception with grayscale ultrasonography.

PURPOSE: This study explored the feasibility of utilizing a deep learning artificial intelligence (AI) model to detect ileocolic intussusception on grayscale ultrasound images. METHODS: This retrospective observational study incorporated ultrasound images of children who underwent emergency ultrasonography for suspected ileocolic intussusception. After excluding video clips, Doppler images, and annotated images, 40,765 images from two tertiary hospitals were included (positive-to-negative ratio: hospital A, 2,775:35,373; hospital B, 140:2,477). Images from hospital A were split into a training set, a tuning set, and an internal test set (ITS) at a ratio of 7:1.5:1.5. Images from hospital B comprised an external test set (ETS). For each image indicating intussusception, two radiologists provided a bounding box as the ground-truth label. If intussusception was suspected in the input image, the model generated a bounding box with a confidence score (0-1) at the estimated lesion location. Average precision (AP) was used to evaluate overall model performance. The performance of practical thresholds for the modelgenerated confidence score, as determined from the ITS, was verified using the ETS. RESULTS: The AP values for the ITS and ETS were 0.952 and 0.936, respectively. Two confidence thresholds, CTopt and CTprecision, were set at 0.557 and 0.790, respectively. For the ETS, the perimage precision and recall were 95.7% and 80.0% with CTopt, and 98.4% and 44.3% with CTprecision. For per-patient diagnosis, the sensitivity and specificity were 100.0% and 97.1% with CTopt, and 100.0% and 99.0% with CTprecision. The average number of false positives per patient was 0.04 with CTopt and 0.01 for CTprecision. CONCLUSION: The feasibility of using an AI model to diagnose ileocolic intussusception on ultrasonography was demonstrated. However, further study involving bias-free data is warranted for robust clinical validation.

Bone Age Assessment Using Artificial Intelligence in Korean Pediatric Population: A Comparison of Deep-Learning Models Trained With Healthy Chronological and Greulich-Pyle Ages as Labels.

OBJECTIVE: To develop a deep-learning-based bone age prediction model optimized for Korean children and adolescents and evaluate its feasibility by comparing it with a Greulich-Pyle-based deep-learning model. MATERIALS AND METHODS: A convolutional neural network was trained to predict age according to the bone development shown on a hand radiograph (bone age) using 21036 hand radiographs of Korean children and adolescents without known bone development-affecting diseases/conditions obtained between 1998 and 2019 (median age [interquartile range {IQR}], 9 [7-12] years; male:female, 11794:9242) and their chronological ages as labels (Korean model). We constructed 2 separate external datasets consisting of Korean children and adolescents with healthy bone development (Institution 1: n = 343; median age [IQR], 10 [4-15] years; male: female, 183:160; Institution 2: n = 321; median age [IQR], 9 [5-14] years; male: female, 164:157) to test the model performance. The mean absolute error (MAE), root mean square error (RMSE), and proportions of bone age predictions within 6, 12, 18, and 24 months of the reference age (chronological age) were compared between the Korean model and a commercial model (VUNO Med-BoneAge version 1.1; VUNO) trained with Greulich-Pyle-based age as the label (GP-based model). RESULTS: Compared with the GP-based model, the Korean model showed a lower RMSE (11.2 vs. 13.8 months; P = 0.004) and MAE (8.2 vs. 10.5 months; P = 0.002), a higher proportion of bone age predictions within 18 months of chronological age (88.3% vs. 82.2%; P = 0.031) for Institution 1, and a lower MAE (9.5 vs. 11.0 months; P = 0.022) and higher proportion of bone age predictions within 6 months (44.5% vs. 36.4%; P = 0.044) for Institution 2. CONCLUSION: The Korean model trained using the chronological ages of Korean children and adolescents without known bone development-affecting diseases/conditions as labels performed better in bone age assessment than the GP-based model in the Korean pediatric population. Further validation is required to confirm its accuracy.

Biportal endoscopic discectomy versus tubular microscopic discectomy for treating single-level lumbar disc herniation in obese patients: a multicenter, retrospective analysis.

PURPOSE: In microscopic lumbar discectomy in obese patients, a correlation is found between the operation time and increase in estimated blood loss according to the increase in body mass index; however, no studies have investigated the outcomes of biportal endoscopic lumbar discectomy in obese patients. Therefore, this study aimed to compare the clinical and radiographic outcomes of microscopic and endoscopic discectomy in obese patients with lumbar herniated discs. METHODS: In this multicenter, retrospective study, clinical and radiological data were compared and analyzed in 73 obese patients with a body mass index of > 30 kg/m2 who underwent microscopic or biportal endoscopic lumbar discectomy. Clinical data on the visual analog scale (VAS), Oswestry disability index (ODI), and EuroQol-5D (EQ-5D) scores were measured, and radiological data were obtained using magnetic resonance imaging (MRI). RESULTS: This study enrolled 43 patients who underwent microscopic discectomy and 30 who underwent biportal endoscopic discectomy. The VAS, ODI, and EQ-5D scores in both groups improved after surgery compared with those before surgery, although there was no difference between the two groups. Although there was a difference in the incidence of recurrent disc herniation confirmed by MRI after surgery, no difference was found in the number of patients requiring surgery between the two groups. CONCLUSION: In obese patients with lumbar disc herniation that was not improved with conservative treatment, no significant clinical or radiological differences in outcomes were noted between microscopic and biportal endoscopic surgery methods. In contrast, minor complications were less common in the biportal group.

Clinical characteristics of tetralogy of Fallot with left pulmonary artery acute angulation on computed tomography.

Left pulmonary artery (LPA) stenosis with acute angulation commonly necessitates surgical revision in the treatment of tetralogy of Fallot (TOF). We investigated the clinical characteristics of acute angulation of the LPA in patients with TOF via computed tomography (CT). Between 2011 and 2022, 160 patients were diagnosed with TOF using CT. After excluding 28 patients due to insufficient records or age, 132 patients were included in the present analysis. The patients were divided into two groups according to the presence or absence of acute angulation of the LPA: group I (TOF with an acute angle of the LPA, n = 53) and group II (TOF without an acute angle of the LPA, n = 79). We retrospectively collected clinical data from electronic medical records. T-tests were used to analyze continuous variables (i.e., age, sex, weight, right ventricular outflow tract [RVOT] pressure on echocardiography, and distance to bifurcation), and Fisher's exact and chi-square tests were used to analyze categorical data (i.e., presence of the right aortic arch, pulmonary arterial atresia/hypoplasia, atrial septal defect [ASD], patent ductus arteriosus [PDA], and pulmonary valve). The groups did not differ significantly in terms of sex, weight, presence of the right aortic arch, pulmonary arterial atresia/hypoplasia, ASD, or distance to the bifurcation. Moreover, there was no significant difference between the presence and absence of PDA (P = 0.057); however, patients in group I were significantly older (143.2 ± 97.8 days) than those in group II (91.1 ± 76.0 days, P = 0.002). Furthermore, RVOT pressure was significantly higher among patients in group I (45.1 ± 22.5 mmHg) than in group II (25.0 ± 12.4 mmHg, P < 0.001). In the current study, acute angulation of the LPA in patients with TOF, as observed on CT, was associated with older age and higher RVOT pressure on echocardiography.

Cardiac CTA image quality of adaptive statistical iterative reconstruction-V versus deep learning reconstruction "TrueFidelity" in children with congenital heart disease.

BACKGROUND: Several recent studies have reported that deep learning reconstruction "TrueFidelity" (TF) improves computed tomography (CT) image quality. However, no study has compared adaptive statistical repeated reconstruction (ASIR-V) using TF in pediatric cardiac CT angiography (CTA) with a low peak kilovoltage. OBJECTIVE: This study aimed to determine whether ASIR-V or TF CTA image quality is superior in children with congenital heart disease (CHD). MATERIALS AND METHODS: Fifty children (median age, 2 months; interquartile range, 0-5 months; 28 men) with CHD who underwent CTA were enrolled between June and September 2020. Images were reconstructed using 2 ASIR-V blending factors (80% and 100% [AV-100]) and 3 TF settings (low, medium, and high [TF-H] strength levels). For the quantitative analyses, 3 objective image qualities (attenuation, noise, and signal-to-noise ratio [SNR]) were measured of the great vessels and heart chambers. The contrast-to-noise ratio (CNR) was also evaluated between the left ventricle and the dial wall. For the qualitative analyses, the degree of quantum mottle and blurring at the upper level to the first branch of the main pulmonary artery was assessed independently by 2 radiologists. RESULTS: When the ASIR-V blending factor level and TF strength were higher, the noise was lower, and the SNR was higher. The image noise and SNR of TF-H were significantly lower and higher than those of AV-100 (P < .01), except for noise in the right atrium and left pulmonary artery and SNR of the right ventricle. Regarding CNR, TF-H was significantly better than AV-100 (P < .01). In addition, in the objective assessment of the degree of quantum mottle and blurring, TF-H had the best score among all examined image sets (P < .01). CONCLUSION: TF-H is superior to AV-100 in terms of objective and subjective image quality. Consequently, TF-H was the best image set for cardiac CTA in children with CHD.

A Case Report of Postinfectious Bronchiolitis Obliterans After Coronavirus Disease 2019 in a 10-Year-Old Child.

Coronavirus disease 2019 (COVID-19) is usually less severe in children and adolescents than in adults. However, it can cause severe respiratory illness in a small proportion of children with risk factors. Here, we report a rare case of a 10-year-old boy with postinfectious bronchiolitis obliterans that developed after pneumonia caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). This patient was previously healthy apart from a high body mass index (BMI, 30.13; 99.6th percentile for the age bracket), history of preterm birth (35 weeks), and low birth weight (1,850 g). He had persistent exertional dyspnea after recovering from SARS-CoV-2-related pneumonia. Spirometry revealed obstructive lung disease with the following results: predicted forced vital capacity (FVC%pred), 71%; forced expiratory volume in 1 second (FEV1%pred), 63%; FEV1/FVC, 0.81; and forced expiratory flow25-75%pred, 55%. Chest computed tomography showed multifocal areas of parenchymal hyperlucency and mosaic attenuation in both lungs. This case suggests that careful observation of children with obesity and low birth weight is necessary after recovery from SARS-CoV-2-related pneumonia.

Comparison of a Deep Learning-Based Reconstruction Algorithm with Filtered Back Projection and Iterative Reconstruction Algorithms for Pediatric Abdominopelvic CT.

OBJECTIVE: To compare a deep learning-based reconstruction (DLR) algorithm for pediatric abdominopelvic computed tomography (CT) with filtered back projection (FBP) and iterative reconstruction (IR) algorithms. MATERIALS AND METHODS: Post-contrast abdominopelvic CT scans obtained from 120 pediatric patients (mean age ± standard deviation, 8.7 ± 5.2 years; 60 males) between May 2020 and October 2020 were evaluated in this retrospective study. Images were reconstructed using FBP, a hybrid IR algorithm (ASiR-V) with blending factors of 50% and 100% (AV50 and AV100, respectively), and a DLR algorithm (TrueFidelity) with three strength levels (low, medium, and high). Noise power spectrum (NPS) and edge rise distance (ERD) were used to evaluate noise characteristics and spatial resolution, respectively. Image noise, edge definition, overall image quality, lesion detectability and conspicuity, and artifacts were qualitatively scored by two pediatric radiologists, and the scores of the two reviewers were averaged. A repeated-measures analysis of variance followed by the Bonferroni post-hoc test was used to compare NPS and ERD among the six reconstruction methods. The Friedman rank sum test followed by the Nemenyi-Wilcoxon-Wilcox all-pairs test was used to compare the results of the qualitative visual analysis among the six reconstruction methods. RESULTS: The NPS noise magnitude of AV100 was significantly lower than that of the DLR, whereas the NPS peak of AV100 was significantly higher than that of the high- and medium-strength DLR (p < 0.001). The NPS average spatial frequencies were higher for DLR than for ASiR-V (p < 0.001). ERD was shorter with DLR than with ASiR-V and FBP (p < 0.001). Qualitative visual analysis revealed better overall image quality with high-strength DLR than with ASiR-V (p < 0.001). CONCLUSION: For pediatric abdominopelvic CT, the DLR algorithm may provide improved noise characteristics and better spatial resolution than the hybrid IR algorithm.

Re-Assessment of Applicability of Greulich and Pyle-Based Bone Age to Korean Children Using Manual and Deep Learning-Based Automated Method.

PURPOSE: To evaluate the applicability of Greulich-Pyle (GP) standards to bone age (BA) assessment in healthy Korean children using manual and deep learning-based methods. MATERIALS AND METHODS: We collected 485 hand radiographs of healthy children aged 2-17 years (262 boys) between 2008 and 2017. Based on GP method, BA was assessed manually by two radiologists and automatically by two deep learning-based BA assessment (DLBAA), which estimated GP-assigned (original model) and optimal (modified model) BAs. Estimated BA was compared to chronological age (CA) using intraclass correlation (ICC), Bland-Altman analysis, linear regression, mean absolute error, and root mean square error. The proportion of children showing a difference >12 months between the estimated BA and CA was calculated. RESULTS: CA and all estimated BA showed excellent agreement (ICC ≥0.978, p<0.001) and significant positive linear correlations (R²≥0.935, p<0.001). The estimated BA of all methods showed systematic bias and tended to be lower than CA in younger patients, and higher than CA in older patients (regression slopes ≤-0.11, p<0.001). The mean absolute error of radiologist 1, radiologist 2, original, and modified DLBAA models were 13.09, 13.12, 11.52, and 11.31 months, respectively. The difference between estimated BA and CA was >12 months in 44.3%, 44.5%, 39.2%, and 36.1% for radiologist 1, radiologist 2, original, and modified DLBAA models, respectively. CONCLUSION: Contemporary healthy Korean children showed different rates of skeletal development than GP standard-BA, and systemic bias should be considered when determining children's skeletal maturation.

Capsule Endoscopy versus Magnetic Resonance Enterography for Evaluation of Pediatric Small Bowel Crohn's Disease: Prospective Study.

BACKGROUND: Magnetic resonance enterography (MRE) and capsule endoscopy (CE) are currently used for the evaluation of small bowel involvement in pediatric Crohn's disease (CD). Several studies have been conducted to investigate the usefulness and diagnostic accuracy of each test. However, only a few studies have been conducted to compare the performance of both tests in the assessment of pediatric small bowel CD upon diagnosis and during follow-up. Therefore, the purpose of this study was to assess the diagnostic accuracy and diagnostic consistency of CE and MRE for the evaluation of pediatric small bowel CD at the time of diagnosis and during follow-up. METHODS: Fifteen patients with pediatric CD were recruited for this study. They underwent MRE and CE concomitantly at the time of diagnosis and 10-12 weeks and one year after induction therapy for CD. MRE was interpreted using MRE global score (MEGS) and bowel wall inflammation severity diffusion-weighted imaging score (BWI-DWIS), whereas CE was interpreted using Lewis's score (LS). The two diagnostic modalities were then compared. RESULTS: Eleven patients completed MRE and CE at the time of diagnosis. Analysis of the results showed that LS had a strong correlation with MEGS and BIS-DWIS (ρ = 0.633, p = 0.037, and ρ = 0.629, p = 0.038, respectively). Nine patients completed three MREs and three CEs. LS significantly decreased throughout the sessions (p = 0.044), whereas MEGS and BIS-DWIS did not show any statistically significant changes. When LS was compared with MEGS and BIS-DWIS, both MRE indicators showed statistically significant differences throughout the sessions. CONCLUSIONS: At the time of diagnosis, the severity indexes of MRE and CE showed very good agreement. However, throughout management, MRE and CE did not show consistent changes.

Radiologic placement of Hickman catheters using intravenous sedation in pediatric patients under 20 kg.

ABSTRACT: Surgeons generally perform Hickman catheter insertion in children under general anesthesia. At times, it is difficult to perform procedures with an anesthesiologist for an interventional radiologist. Several diagnostic and therapeutic procedures are efficiently and safely conducted using intravenous (IV) sedation in children with a pediatrician. This study aims to evaluate the efficacy and safety of radiologically placed Hickman catheters using IV sedation in children under 20 kg.Fifty-nine catheters were inserted in 45 children under IV sedation. With continuous monitoring of vital signs, IV midazolam and ketamine were slowly infused by a pediatrician. Mean age and body weights were 3.2 years and 15.2 kg, respectively. Acute leukemia was the most common disease for the procedure (72.9%). The location of the catheter tip was evaluated by measuring the height of the thoracic vertebra.Technical success rate was 100%, and IV sedation-related complications did not occur. The right internal jugular vein was accessed for 51 catheters (86.4%), and the mean procedure time was 21.5 minutes. The 2 vertebral body units below the carina were the cavoatrial junction on a fluoroscopy image. Mean catheter life was 285 days, and catheters were removed post-treatment (35.6%). During follow-up, complications occurred in 29 cases (1.72 per 1000 catheter-days). Catheter-related infections were suspected in 4 patients (6.8%), with 1 positive result.Radiological Hickman catheter placement in children under 20 kg using IV sedation by pediatricians is effective and safe, with minimal complications. The carina is a landmark to estimate the cavoatrial junction in pediatric patients.

Image quality and diagnostic accuracy of reduced-dose computed tomography enterography with model-based iterative reconstruction in pediatric Crohn's disease patients.

This study assessed the image quality and diagnostic accuracy in determining disease activity of the terminal ileum of the reduced-dose computed tomography enterography using model-based iterative reconstruction in pediatric patients with Crohn's disease (CD). Eighteen patients were prospectively enrolled and allocated to the standard-dose (SD) and reduced-dose (RD) computed tomography enterography (CTE) groups (n = 9 per group). Image quality, reader confidence in interpreting bowel findings, accuracy in determining active CD in the terminal ileum, and radiation dose were evaluated. Objective image quality did not show intergroup differences, except for image sharpness. Although reader confidence in detecting mural stratification, ulcer, and perienteric fat stranding of the RD-CTE were inferior to SD-CTE, RD-CTE correctly diagnosed active disease in all patients. The mean values of radiation dose metrics (SD-CTE vs. RD-CTE) were 4.3 versus 0.74 mGy, 6.1 versus 1.1 mGy, 211.9 versus 34.5 mGy∙cm, and 4.4 versus 0.7 mSv mGy∙cm for CTDIvol, size-specific dose estimation, dose-length product, and effective dose, respectively. RD-CTE showed comparable diagnostic accuracy to SD-CTE in determining active disease of the terminal ileum in pediatric CD patients. However, image quality and reader confidence in detecting ulcer and perienteric fat stranding was compromised.

MS4A3 promotes differentiation in chronic myeloid leukemia by enhancing common ß-chain cytokine receptor endocytosis.

The chronic phase of chronic myeloid leukemia (CP-CML) is characterized by the excessive production of maturating myeloid cells. As CML stem/progenitor cells (LSPCs) are poised to cycle and differentiate, LSPCs must balance conservation and differentiation to avoid exhaustion, similar to normal hematopoiesis under stress. Since BCR-ABL1 tyrosine kinase inhibitors (TKIs) eliminate differentiating cells but spare BCR-ABL1-independent LSPCs, understanding the mechanisms that regulate LSPC differentiation may inform strategies to eliminate LSPCs. Upon performing a meta-analysis of published CML transcriptomes, we discovered that low expression of the MS4A3 transmembrane protein is a universal characteristic of LSPC quiescence, BCR-ABL1 independence, and transformation to blast phase (BP). Several mechanisms are involved in suppressing MS4A3, including aberrant methylation and a MECOM-C/EBPε axis. Contrary to previous reports, we find that MS4A3 does not function as a G1/S phase inhibitor but promotes endocytosis of common ß-chain (ßc) cytokine receptors upon GM-CSF/IL-3 stimulation, enhancing downstream signaling and cellular differentiation. This suggests that LSPCs downregulate MS4A3 to evade ßc cytokine-induced differentiation and maintain a more primitive, TKI-insensitive state. Accordingly, knockdown (KD) or deletion of MS4A3/Ms4a3 promotes TKI resistance and survival of CML cells ex vivo and enhances leukemogenesis in vivo, while targeted delivery of exogenous MS4A3 protein promotes differentiation. These data support a model in which MS4A3 governs response to differentiating myeloid cytokines, providing a unifying mechanism for the differentiation block characteristic of CML quiescence and BP-CML. Promoting MS4A3 reexpression or delivery of ectopic MS4A3 may help eliminate LSPCs in vivo.

Chirality-matched catalyst-controlled macrocyclization reactions.

Macrocycles, formally defined as compounds that contain a ring with 12 or more atoms, continue to attract great interest due to their important applications in physical, pharmacological, and environmental sciences. In syntheses of macrocyclic compounds, promoting intramolecular over intermolecular reactions in the ring-closing step is often a key challenge. Furthermore, syntheses of macrocycles with stereogenic elements confer an additional challenge, while access to such macrocycles are of great interest. Herein, we report the remarkable effect peptide-based catalysts can have in promoting efficient macrocyclization reactions. We show that the chirality of the catalyst is essential for promoting favorable, matched transition-state relationships that favor macrocyclization of substrates with preexisting stereogenic elements; curiously, the chirality of the catalyst is essential for successful reactions, even though no new static (i.e., not "dynamic") stereogenic elements are created. Control experiments involving either achiral variants of the catalyst or the enantiomeric form of the catalyst fail to deliver the macrocycles in significant quantity in head-to-head comparisons. The generality of the phenomenon, demonstrated here with a number of substrates, stimulates analogies to enzymatic catalysts that produce naturally occurring macrocycles, presumably through related, catalyst-defined peripheral interactions with their acyclic substrates.

Rosai-Dorfman disease in the spleen of a pediatric patient: A case report.

BACKGROUND: Rosai-Dorfman disease (RDD) is a rare histiocytic proliferation of unknown etiology commonly found in children and adolescents. The common manifestation of RDD is massive and painless bilateral cervical lymphadenopathy with extranodal disease. While extranodal involvement in RDD is common, the spleen is an infrequent site of disease. CASE SUMMARY: We report a 10-mo-old female infant with RDD presenting multiple splenic masses without cervical lymphadenopathy. She had fever, and blood tests showed leukocytosis, anemia, and elevated erythrocyte sedimentation rate and C-reactive protein. Ultrasound, computed tomography, and magnetic resonance images demonstrated multiple splenic masses. Despite antibiotic therapy, her symptoms were not relived. She underwent diagnostic splenectomy and was discharged with recovery. CONCLUSION: In pediatric patients with refractory infectious symptoms or hematological abnormalities, clinicians should suspect RDD, even in patients without significant lymphadenopathy.

Loss of N1-methylation of G37 in tRNA induces ribosome stalling and reprograms gene expression.

N1-methylation of G37 is required for a subset of tRNAs to maintain the translational reading-frame. While loss of m1G37 increases ribosomal +1 frameshifting, whether it incurs additional translational defects is unknown. Here, we address this question by applying ribosome profiling to gain a genome-wide view of the effects of m1G37 deficiency on protein synthesis. Using E coli as a model, we show that m1G37 deficiency induces ribosome stalling at codons that are normally translated by m1G37-containing tRNAs. Stalling occurs during decoding of affected codons at the ribosomal A site, indicating a distinct mechanism than that of +1 frameshifting, which occurs after the affected codons leave the A site. Enzyme- and cell-based assays show that m1G37 deficiency reduces tRNA aminoacylation and in some cases peptide-bond formation. We observe changes of gene expression in m1G37 deficiency similar to those in the stringent response that is typically induced by deficiency of amino acids. This work demonstrates a previously unrecognized function of m1G37 that emphasizes its role throughout the entire elongation cycle of protein synthesis, providing new insight into its essentiality for bacterial growth and survival.

Radiological manifestation of familial acute necrotizing encephalopathy with RANBP2 mutation in a Far-East Asian family: Case report.

RATIONALE: Acute necrotizing encephalopathy (ANE) is a specific type of encephalopathy usually followed by febrile infection. It has an aggressive clinical course; however, it usually does not recur after recovery in cases of spontaneous ANE. Nevertheless, there are several studies reporting recurrences in familial ANE with RAN-binding protein 2 (RANBP2) mutation. There are few cases of familial ANE with RANBP2 mutation in Asian populations. PATIENTS CONCERNS: A 21-month-old Korean boy who was previously healthy, presented with seizure following parainfluenza - a virus and bocavirus infection, followed by 2 recurrent seizure episodes and encephalitis after febrile respiratory illnesses. Meanwhile, his 3-year-old sister had focal brain lesions on neuroimaging studies when evaluated for head trauma. The siblings also had an older brother who presented status epilepticus after febrile respiratory illness at the age of 10 months old. DIAGNOSIS: Brain magnetic resonance imaging was performed to evaluate the seizure and neurologic symptoms. Imaging findings showed variable spectrum - from non-specific diffuse white matter injury pattern to typical "tricolor pattern" of the ANE on diffusion-weighted images. The other 2 siblings showed focal lesions in both external capsules and severe diffuse brain edema. Genetic tests identified a heterozygous missense mutation in the RANBP2 [c.1754C>T (p.Thr585Met)] in 2 siblings and their mother. INTERVENTIONS: Patients were treated conservatively with anticonvulsive agents, intravascular immunoglobulin, and steroids. OUTCOMES: Among the 3 siblings, 2 male siblings died from familial ANE, whereas the female sibling was asymptomatic. LESSONS: These cases highlight the radiological aspects of familial ANE with incomplete penetrance of the RANBP2 gene in 3 family members, showing variable involvements of the brain and natural history on magnetic resonance images. Radiologists should be aware of the typical and atypical imaging findings of familial ANE for prompt management of affected patients.