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Myelin development during adolescence is becoming an area of growing interest in view of its potential relationship to cognition, behavior, and learning. While recent investigations suggest that both white matter (WM) and gray matter (GM) undergo protracted myelination during adolescence, quantitative relations between myelin development in WM and GM have not been previously studied. We quantitatively characterized the dependence of cortical GM, WM, and subcortical myelin density across the brain on age, gender, and puberty status during adolescence with the use of a novel macromolecular proton fraction (MPF) mapping method. Whole-brain MPF maps from a cross-sectional sample of 146 adolescents (age range 9–17 years) were collected. Myelin density was calculated from MPF values in GM and WM of all brain lobes, as well as in subcortical structures. In general, myelination of cortical GM was widespread and more significantly correlated with age than that of WM. Myelination of GM in the parietal lobe was found to have a significantly stronger age dependence than that of GM in the frontal, occipital, temporal and insular lobes. Myelination of WM in the temporal lobe had the strongest association with age as compared to WM in other lobes. Myelin density was found to be higher in males as compared to females when averaged across all cortical lobes, as well as in a bilateral subcortical region. Puberty stage was significantly correlated with myelin density in several cortical areas and in the subcortical GM. These findings point to significant differences in the trajectories of myelination of GM and WM across brain regions and suggest that cortical GM myelination plays a dominant role during adolescent development.

Lung cancer screening (LCS) can reduce lung cancer mortality; however, poor understanding of results may impact patient experience and follow-up. We sought to determine whether an informational handout accompanying LCS results can improve patient-reported outcomes and adherence to follow-up. This was a prospective alternating intervention pilot trial of a handout to accompany LCS results delivery. Patients undergoing LCS in a multisite program over a 6-month period received a mailing containing either: 1) a standardized form letter of LCS results (control) or 2) the LCS results letter and the handout (intervention). A two-sided informational handout on commonly asked questions after LCS created through iterative mixed-methods evaluation with both LCS patients and providers. The primary outcomes of 1)patient understanding of LCS results, 2)correct identification of next steps in screening, and 3)patient distress were measured through survey. Adherence to recommended follow-up after LCS was determined through chart review. Outcomes were compared between the intervention and control group using generalized estimating equations. 389 patients were eligible and enrolled with survey responses from 230 participants (59% response rate). We found no differences in understanding of results, identification of next steps in follow-up or distress but did find higher levels of knowledge and understanding on questions assessing individual components of LCS in the intervention group. Follow-up adherence was overall similar between the two arms, though was higher in the intervention group among those with positive findings (p = 0.007). There were no differences in self-reported outcomes between the groups or overall follow-up adherence. Those receiving the intervention did report greater understanding and knowledge of key LCS components, and those with positive results had a higher rate of follow-up. This may represent a feasible component of a multi-level intervention to address knowledge and follow-up for LCS. ClinicalTrials.gov NCT05265897.

Background Diffusion-weighted imaging (DWI) can increase breast MRI diagnostic specificity due to the tendency of malignancies to restrict diffusion. Diffusion tensor imaging (DTI) provides further information over conventional DWI regarding diffusion directionality and anisotropy. Our study evaluates DTI features of suspicious breast lesions detected on MRI to determine the added diagnostic value of DTI for breast imaging . Methods With IRB approval, we prospectively enrolled patients over a 3-year period who had suspicious (BI-RADS category 4 or 5) MRI-detected breast lesions with histopathological results. Patients underwent multiparametric 3 T MRI with dynamic contrast-enhanced (DCE) and DTI sequences. Clinical factors (age, menopausal status, breast density, clinical indication, background parenchymal enhancement) and DCE-MRI lesion parameters (size, type, presence of washout, BI-RADS category) were recorded prospectively by interpreting radiologists. DTI parameters (apparent diffusion coefficient [ADC], fractional anisotropy [FA], axial diffusivity [ λ 1 ], radial diffusivity [( λ 2  +  λ 3 )/2], and empirical difference [ λ 1  −  λ 3 ]) were measured retrospectively. Generalized estimating equations (GEE) and least absolute shrinkage and selection operator (LASSO) methods were used for univariate and multivariate logistic regression, respectively. Diagnostic performance was internally validated using the area under the curve (AUC) with bootstrap adjustment. Results The study included 238 suspicious breast lesions (95 malignant, 143 benign) in 194 women. In univariate analysis, lower ADC, axial diffusivity, and radial diffusivity were associated with malignancy (OR = 0.37–0.42 per 1-SD increase, p  < 0.001 for each), as was higher FA (OR = 1.45, p  = 0.007). In multivariate analysis, LASSO selected only ADC (OR = 0.41) as a predictor for a DTI-only model, while both ADC (OR = 0.41) and FA (OR = 0.88) were selected for a model combining clinical and imaging parameters. Post-hoc analysis revealed varying association of FA with malignancy depending on the lesion type. The combined model (AUC = 0.81) had a significantly better performance than Clinical/DCE-MRI-only (AUC = 0.76, p  < 0.001) and DTI-only (AUC = 0.75, p  = 0.002) models. Conclusions DTI significantly improves diagnostic performance in multivariate modeling. ADC is the most important diffusion parameter for distinguishing benign and malignant breast lesions, while anisotropy measures may help further characterize tumor microstructure and microenvironment.

Objectives Interstitial lung disease (ILD) impacts mortality in antisynthetase syndrome (ASyS). Computed tomographic (CT) patterns and evolution in ASyS ILD are not well described. We report longitudinal CT patterns in ASyS-ILD and their impact on survival. Methods This is a monocentric retrospective study of 47 patients with ASyS-ILD. Longitudinal CT patterns and fibrosis severity (severity of radiographic features indicating fibrosis) were analyzed by two radiologists in consensus. The association between imaging features and survival was examined using univariate Cox regression analysis. Results In total, 211 CT scans were analyzed with an average of 4 ± 2 CT scans/patient with a median follow-up of 79 months in 47 patients. Non-fibrotic patterns were present initially in 63.8% ( n  = 30) of patients, while fibrotic patterns occurred in 36.2% ( n  = 17). The initial non-fibrotic patterns/abnormalities resolved in 23.3% ( n  = 7), evolved in 6.7% ( n  = 2), persisted in 13.3% ( n  = 4), and progressed in 56.7% ( n  = 17), while initial fibrotic patterns persisted in 82.4% ( n  = 14) and progressed in 17.6% ( n  = 3). Radiographic progression of ILD (progression in CT pattern or increased fibrosis severity) occurred in 53.2% ( n  = 25) of patients. Advanced age and radiographic progression were associated with decreased survival (all p  < 0.05). The presence of ground-glass opacities (GGO) and predominant lower lung distribution of abnormalities on initial CTs were associated with increased survival (all p  < 0.05). Conclusion Progression occurred in 56.7% of ASyS-ILD patients presenting with non-fibrotic patterns. Fibrotic patterns tended to persist. Age and radiographic progression were associated with reduced survival while the initial presence of GGO and predominant lower lobe distribution were associated with increased survival. Key Points • In ASyS-ILD, initial non-fibrotic patterns such as OP, cNSIP, or OP-cNSIP tended to progress to fNSIP . • Fibrotic patterns such as fNSIP or UIP in ASyS-ILD tended to persist without pattern changes . • GGO and lower lung predominance on initial CT were associated with better survival while advanced baseline age and radiographic ILD progression during follow-up were associated with decreased survival .

Angiogenesis is a critical component of breast cancer development, and identification of imaging-based angiogenesis assays has prognostic and treatment implications. We evaluated the association of semi-quantitative kinetic and radiomic breast cancer features on dynamic contrast-enhanced (DCE)-MRI with microvessel density (MVD), a marker for angiogenesis. Invasive breast cancer kinetic features (initial peak percent enhancement [PE], signal enhancement ratio [SER], functional tumor volume [FTV], and washout fraction [WF]), radiomics features (108 total features reflecting tumor morphology, signal intensity, and texture), and MVD (by histologic CD31 immunostaining) were measured in 27 patients (1/2016–7/2017). Lesions with high MVD levels demonstrated higher peak SER than lesions with low MVD (mean: 1.94 vs. 1.61, area under the receiver operating characteristic curve [AUC] = 0.79, p  = 0.009) and higher WF (mean: 50.6% vs. 22.5%, AUC = 0.87, p  = 0.001). Several radiomics texture features were also promising for predicting increased MVD (maximum AUC = 0.84, p  = 0.002). Our study suggests DCE-MRI can non-invasively assess breast cancer angiogenesis, which could stratify biology and optimize treatments.

ObjectiveTo assess the impact of mobile virtual reality (VR) simulations using electronic Helping Babies Breathe (eHBB) or video for the maintenance of neonatal resuscitation skills in healthcare workers in resource-scarce settings.DesignRandomised controlled trial with 6-month follow-up (2018–2020).SettingSecondary and tertiary healthcare facilities.Participants274 nurses and midwives assigned to labour and delivery, operating room and newborn care units were recruited from 20 healthcare facilities in Nigeria and Kenya and randomised to one of three groups: VR (eHBB+digital guide), video (video+digital guide) or control (digital guide only) groups before an in-person HBB course.Intervention(s)eHBB VR simulation or neonatal resuscitation video.Main outcome(s)Healthcare worker neonatal resuscitation skills using standardised checklists in a simulated setting at 1 month, 3 months and 6 months.ResultsNeonatal resuscitation skills pass rates were similar among the groups at 6-month follow-up for bag-and-mask ventilation (BMV) skills check (VR 28%, video 25%, control 22%, p=0.71), objective structured clinical examination (OSCE) A (VR 76%, video 76%, control 72%, p=0.78) and OSCE B (VR 62%, video 60%, control 49%, p=0.18). Relative to the immediate postcourse assessments, there was greater retention of BMV skills at 6 months in the VR group (−15% VR, p=0.10; −21% video, p<0.01, –27% control, p=0.001). OSCE B pass rates in the VR group were numerically higher at 3 months (+4%, p=0.64) and 6 months (+3%, p=0.74) and lower in the video (−21% at 3 months, p<0.001; −14% at 6 months, p=0.066) and control groups (−7% at 3 months, p=0.43; −14% at 6 months, p=0.10). On follow-up survey, 95% (n=65) of respondents in the VR group and 98% (n=82) in the video group would use their assigned intervention again.ConclusioneHBB VR training was highly acceptable to healthcare workers in low-income to middle-income countries and may provide additional support for neonatal resuscitation skills retention compared with other digital interventions.

Background Metastatic uveal melanoma (mUM) is an uncommon melanoma subtype, poorly immunogenic with low objective response rates (ORR) to immune checkpoint inhibitors (ICI). Liver-directed therapies (LDT) are commonly used given the strong predilection for hepatic metastases. Transarterial immunoembolization (TAIE) with granulocyte–macrophage colony stimulating factor (GM-CSF) can potentially synergize with concurrent systemic ICI to overcome immune evasion. Methods This single-center, retrospective study includes mUM patients with liver-predominant metastases who received TAIE, with/without concurrent systemic ICI (≤ 3 months before/during TAIE). Endpoints included ORR, progression-free survival (PFS), overall survival (OS), and adverse events (AEs). Results Between 2016 and 2023, 18 mUM patients (median age 64 years) received TAIE (median 4 procedures/patient). Fourteen patients (78%) received concurrent ICI. ORR was 17% (3/18), all in patients receiving ICI, with partial responses lasting 4.2, 35 + and 46 months. Disease control rate (stable disease or better) was 56% (10/18). Median time to next systemic therapy or death was 19.5 months (range 1.6- 46). Median PFS and OS from first TAIE treatment were 4.9 months (range 0.7–46) and 35 months (range 1.7- 46). Immune-related AEs (IRAE) during concurrent therapy occurred in seven of 10 patients receiving anti-CTLA-4/PD-1 combination, including hepatitis (n = 5; grade 2 in 1, grade 3 in 4). Four of seven patients resumed anti-PD-1 monotherapy without recurrent IRAE. Conclusions Concurrent LDT with GM-CSF TAIE and ICI, including anti-CTLA-4/PD-1 combination, is feasible, safe, and can lead to sustained clinical benefit in a subset of mUM patients. OS with this combination compares favorably to published outcomes for systemic therapy or LDT alone.

Over the past two decades, there has been an increase in the use of simulation-based education for training healthcare providers in technical and non-technical skills. Simulation education and research programs have mostly focused on the impact on clinical knowledge and improvement of technical skills rather than on cost. To study and characterize existing evidence to inform multi-stakeholder investment decisions, we performed a systematic review of the literature on costs in simulation-based education in medicine in general and in neonatal resuscitation as a particular focus. We conducted a systematic literature search of the PubMed database using two targeted queries. The first searched for cost analyses of healthcare simulation-based education more broadly, and the second was more narrowly focused on cost analyses of neonatal resuscitation training. The more general query identified 47 qualified articles. The most common specialties for education interventions were surgery (51%); obstetrics, gynecology, or pediatrics (11%); medicine, nursing, or medical school (11%); and urology (9%), accounting for over 80% of articles. The neonatal resuscitation query identified five qualified articles. The two queries identified seven large-scale training implementation studies, one in the United States and six in low-income countries. There were two articles each from Tanzania and India and one article each from Zambia and Ghana. Methods, definitions, and reported estimates varied across articles, implying interpretation, comparison, and generalization of program effects are challenging. More work is needed to understand the costs, processes, and outcomes likely to make simulation-based education programs cost-effective and scalable. To optimize return on investments in training, assessing resource requirements, associated costs, and subsequent outcomes can inform stakeholders about the potential sustainability of SBE programs. Healthcare stakeholders and decision makers will benefit from more transparent, consistent, rigorous, and explicit assessments of simulation-based education program development and implementation costs in low- and high-income countries.

Most women with breast cancer in sub-Saharan Africa (SSA) are diagnosed with late-staged disease. The current study assesses patient-related barriers among women from a general SSA population to better understand how patient-related barriers contribute to diagnostic delays. Using convenience-based sampling, 401 Ugandan women without breast cancer were surveyed to determine how prior participation in cancer detection practices correlate with patient-related barriers to prompt diagnosis. In a predominantly poor (76%) and rural population (75%), the median age of the participants was 38. Of the women surveyed, 155 (46%) had prior exposure to breast cancer education, 92 (27%) performed breast self-examination (BSE) and 68 (20%) had undergone a recent clinical breast examination (CBE), breast ultrasound or breast biopsy. The most commonly identified barriers to prompt diagnosis were knowledge deficits regarding early diagnosis (79%), economic barriers to accessing care (68%), fear (37%) and poor social support (24%). However, only women who reported knowledge deficits-a modifiable barrier-were less likely to participate in cancer detection practices (p<0.05). Women in urban and rural areas were similarly likely to report economic barriers, knowledge deficits and/or poor social support, but rural women were less likely than urban women to have received breast cancer education and/or perform BSE (p<0.001). Women who have had prior breast cancer education (p<0.001) and/or who perform BSE (p = 0.02) were more likely to know where she can go to receive a diagnostic breast evaluation. These findings suggest that SSA countries developing early breast cancer detection programs should specifically address modifiable knowledge deficits among women less likely to achieve a diagnostic work-up to reduce diagnostic delays and improve breast cancer outcomes.

Abstract BACKGROUND Spinal cord dose limits are critically important for the safe practice of spine stereotactic body radiotherapy (SBRT). However, the effect of inherent spinal cord motion on cord dose in SBRT is unknown. OBJECTIVE To assess the effects of cord motion on spinal cord dose in SBRT. METHODS Dynamic balanced fast field echo (BFFE) magnetic resonance imaging (MRI) was obtained in 21 spine metastasis patients treated with SBRT. Planning computed tomography (CT), conventional static T2-weighted MRI, BFFE MRI, and dose planning data were coregistered. Spinal cord from the dynamic BFFE images (corddyn) was compared with the T2-weighted MRI (cordstat) to analyze motion of corddyn beyond the cordstat (Dice coefficient, Jaccard index), and beyond cordstat with added planning organ at risk volume (PRV) margins. Cord dose was compared between cordstat, and corddyn (Wilcoxon signed-rank test). RESULTS Dice coefficient (0.70-0.95, median 0.87) and Jaccard index (0.54-0.90, median 0.77) demonstrated motion of corddyn beyond cordstat. In 62% of the patients (13/21), the dose to corddyn exceeded that of cordstat by 0.6% to 13.8% (median 4.3%). The corddyn spatially excursed outside the 1-mm PRV margin of cordstat in 9 patients (43%); among these dose to corddyn exceeded dose to cordstat >+ 1-mm PRV margin in 78% of the patients (7/9). Corddyn did not excurse outside the 1.5-mm or 2-mm PRV cord cordstat margin. CONCLUSION Spinal cord motion may contribute to increases in radiation dose to the cord from SBRT for spine metastasis. A PRV margin of at least 1.5 to 2 mm surrounding the cord should be strongly considered to account for inherent spinal cord motion.