Genomic sequencing research in pediatric cancer care: Decision-making, attitudes, and perceived utility among adolescents and young adults and their parents.

PURPOSE: Professional guidelines recommend engaging adolescents and young adults (AYAs) in medical decision-making (DM), including whether to undergo genomic sequencing (GS). We explored DM around GS and attitudes after return of GS results among a diverse group of AYAs with cancer and their parents. METHODS: We surveyed AYAs with cancer (n=75) and their parents (n=52) six months after receiving GS results through the Texas KidsCanSeq Study. We analyzed AYAs' DM role in GS research enrollment and their satisfaction with that role. We compared AYAs' and parents' self-reported understanding of, attitudes toward, and perceived utility of the AYAs' GS results. RESULTS: Most AYAs reported equally sharing DM with their parents (55%) or leading DM (36%) about GS research. Compared to their cancer care DM role, 56% of AYAs reported the same level of involvement in GS research DM while 32% were more involved and 13% were less involved (p=0.011). AYAs were satisfied (99%) with their DM role regarding GS study participation. AYAs and parents had similar self-reported understanding of, attitudes toward, and perceived utility of the GS results. CONCLUSION: Our results support engaging AYAs in DM about GS research and provide insights into AYAs' DM preferences and positive attitudes toward GS.

Rapid preparation of binary mixtures of sodium carboxylates as anodes in sodium-ion batteries.

Sodium-ion batteries are emerging as a sustainable solution to tackle the growing global energy demands. In this context, organic electrode materials complement such technologies as they are composed of earth-abundant elements. As organic anodes, sodium carboxylates exhibit promising applicability in a wide range of molecules. To harness the advantages of individual systems and to minimise their limitations, in this work, an approach to form binary mixtures of sodium carboxylates using one-pot, microwave-assisted synthesis is presented. The target mixtures were synthesised in 30 min with disodium naphthalene-2,6-dicarboxylate (Na-NDC) as a common constituent in all. Both components in all mixtures were shown to participate in the charge storage and had a considerable effect on the performance characteristics, such as specific capacity and working voltage, in half and full cell formats. This approach opens a new avenue for enabling organic materials to be considered as more competitive candidates in sodium-ion batteries and promote their use in other material classes to overcome their limitations.

Association of urinary biomarkers of tobacco exposure with lung cancer risk in African American and White cigarette smokers in the Southern Community Cohort Study.

BACKGROUND: After accounting for smoking history lung cancer incidence is greater in African Americans than Whites. In the Multiethnic Cohort, total nicotine equivalents (TNE) are higher in African Americans than Whites at similar reported cigarettes per day (CPD). Greater toxicant uptake per cigarette may contribute to the greater lung cancer risk of African Americans. METHODS: In a nested case-control lung cancer study within the Southern Community Cohort, smoking-related biomarkers were measured in 259 cases and 503 controls (40% White, 56% African American). TNE, the trans-3-hydroxycotinine:cotinine ratio, 4-(methylnitrosamino)-1-3-(pyridyl)-1-butanol (NNAL), mercapturic acid metabolites of volatile organic compounds, phenanthrene metabolites, cadmium, and (Z)-7-(1R,2R,3R,5S)-3,5-dihydroxy-2-[(E,3S)-3-hydroxyoct-1-enyl]cyclopenyl]hept-5-enoic acid (8-iso-PGF2α) were quantified in urine. Unconditional logistic regression was used to estimate the odds ratios and 95% confidence intervals for each biomarker and lung cancer risk. RESULTS: TNE, NNAL and cadmium were higher in cases than controls (adjusted for age, race, sex, body mass index (BMI) and CPD). Among cases, these levels were higher in African Americans compared to Whites. After accounting for age, sex, BMI and pack-years, a one-SD increase in log-TNE (OR=1.30; 95% CI: 1.10-1.54) and log-NNAL (OR=1.27; 95% CI: 1.03-1.58 with TNE adjustment) were associated with lung cancer risk. In this study, where NNAL concentration is relatively high, the association for log-TNE was attenuated after adjustment for log-NNAL. CONCLUSION: Smoking-related biomarkers provide additional information for lung cancer risk in smokers beyond smoking pack-years. IMPACT: Urinary NNAL, TNE and cadmium concentrations in current smokers, particularly African American smokers, may be useful for predicting lung cancer risk.

Optimizing a mentorship program from the perspective of academic medicine leadership - a qualitative study.

BACKGROUND: Effective mentorship is an important contributor to academic success. Given the critical role of leadership in fostering mentorship, this study sought to explore the perspectives of departmental leadership regarding 1) current departmental mentorship processes; and 2) crucial components of a mentorship program that would enhance the effectiveness of mentorship. METHODS: Department Division Directors (DDDs), Vice-Chairs, and Mentorship Facilitators from the Department of Medicine at the University of Toronto Temerty Faculty of Medicine were interviewed between April and December 2021 using a semi-structured guide. Interviews were audio-recorded and transcribed verbatim, then coded. Analysis occurred in 2 steps: 1) codes were organized to identify emergent themes; then 2) the Social Ecological Model (SEM) was applied to interpret the findings. RESULTS: Nineteen interviews (14 DDDs, 3 Vice-Chairs, and 2 Mentorship Facilitator) were completed. Analysis revealed three themes: (1) a culture of mentorship permeated the department as evidenced by rigorous mentorship processes, divisional mentorship innovations, and faculty that were keen to mentor; (2) barriers to the establishment of effective mentoring relationships existed at 3 levels: departmental, interpersonal (mentee-mentor relationships), and mentee; and (3) strengthening the culture of mentorship could entail scaling up pre-existing mentorship processes and promoting faculty engagement. Application of SEM highlighted critical program features and determined that two components of interventions (creating tools to measure mentorship outcomes and systems for mentor recognition) were potential enablers of success. CONCLUSIONS: Establishing 'mentorship outcome measures' can incentivize and maintain relationships. By tangibly delineating departmental expectations for mentorship and creating systems that recognize mentors, these measures can contribute to a culture of mentorship.

An NMR crystallographic characterisation of solid (+)-usnic acid.

We use a combination of one- and two-dimensional solid-state nuclear magnetic resonance (NMR) spectroscopy and density functional theory (DFT) calculations to obtain a full assignment of the 1H and 13C signals for solid (+)-usnic acid, which contains two molecules in the asymmetric unit. By combining through-space 1H-1H correlation data with computation it is possible to assign signals not just to the same molecules (relative assignment) but to assign the signals to specific crystallographic molecules (absolute assignment). Variable-temperature measurements reveal that there is some variation in many of the 13C chemical shifts with temperature, likely arising from varying populations of different tautomeric forms of the molecule. The NMR spectrum of crystalline (+)-usnic acid is then compared with that of ground Usnea dasopoga lichen (the source material of the usnic acid). The abundance of usnic acid is so great in the lichen that this natural product can be observed directly in the NMR spectrum without further purification. This natural sample of usnic acid appears to have the same crystalline form as that in the pure commercial sample.

Disaster healthcare disparities solutions: Part 2-Response.

The purpose of this study was to explore the potential solutions for disaster healthcare disparities. This paper is the second of a three-part series that was written by the Disaster Healthcare Disparities Workgroup of the American College of Emergency Physicians Disaster Preparedness and Response Committee. The committee conducted a literature review and chose articles most representative and demonstrative of solutions to disaster healthcare disparities found in a past workgroup product. Many solutions for disaster healthcare disparities during disaster response were found. Some of these solutions have been successfully implemented and some are hypothetical. Solutions for disaster healthcare disparities seen during response are achievable but there is still much work to do. A variety of the proposed solutions can be advocated for by nondisaster specialists leading to better care for all our patients.

Glycemic control during TB treatment among Filipinos: The Starting Anti-Tuberculosis Treatment Cohort Study.

Poor TB treatment outcomes are observed in patients with type 2 diabetes mellitus (DM) comorbidity and glycemic control throughout treatment may play a role. The objective of this study was to investigate glycemic control longitudinally among Filipino adults undergoing TB treatment using mixed-effects linear and logistic regression. Analyses were conducted in 188 DM-TB patients out of 901 enrolled in the Starting Anti-TB Treatment (St-ATT) cohort, with a median baseline glycosylated hemoglobin (HbA1c) of 8.2% (range 4.5-13.3%). Previous versus new DM diagnosis was associated with higher mean HbA1c (worse glycemic control) during treatment, with a smaller effect amongst those with central obesity (coefficient 0.80, 95% confidence interval [CI] 0.26, 1.57, P = 0.043) than amongst those without central obesity (coefficient 3.48, 95% CI 2.16, 4.80, P<0.001). In those with a new DM diagnosis, central obesity was associated with higher blood glucose (coefficient 1.62, 95% CI 0.72, 2.53, P = 0.009). Of 177 participants with ≥2 HbA1c results, 40% had uncontrolled glycemia (≥2 HbA1c results ≥8%). Of 165 participants with ≥3 HbA1c results, 29.9% had consistently-controlled glycemia, 15.3% had initially-uncontrolled glycemia, and 18.6% had consistently-uncontrolled glycemia. Previous versus new DM diagnosis and glucose-lowering medication use versus no use were associated with having uncontrolled versus controlled glycemia (adjusted odds ratio [aOR] 2.50 95%CI 1.61, 6.05, P = 0.042; aOR 4.78 95% CI 1.61,14.23, P<0.001) and more likely to have consistently-uncontrolled versus consistently-controlled glycemia (adjusted relative risk ratio [aRRR] 5.14 95% CI 1.37, 19.20, P = 0.015; aRRR 10.24 95% CI 0.07, 0.95, P = 0.003). Relapse cases of TB were less likely than new cases to have uncontrolled (aOR 0.20 95%CI 0.06, 0.63, P = 0.031) or consistently-uncontrolled (aRRR 0.25 95%CI 0.07, 0.95, P = 0.042) versus controlled glycemia. Those with long-term DM, suggested by previous diagnosis, glucose-lowering medication use and possibly central obesity, may require additional support to manage blood glucose during TB treatment.

Lead Speciation, Bioaccessibility, and Sources for a Contaminated Subset of House Dust and Soils Collected from Similar United States Residences.

Residential lead (Pb) exposure is of critical concern to families globally as Pb promotes severe neurological effects in children, especially those less than 5 years old, and no blood lead level is deemed safe by the US Center for Disease Control. House dust and soils are commonly thought to be important sources of Pb exposure. Probing the relationship between house dust and soil Pb is critical to understanding residential exposure, as Pb bioavailability is highly influenced by Pb sources and/or species. We investigated paired house dust and soil collected from homes built before 1978 to determine Pb speciation, source, and bioaccessibility with the primary goal of assessing chemical factors driving Pb exposure in residential media. House dust was predominately found to contain (hydro)cerussite (i.e., Pb (hydroxy)carbonate) phases commonly used in Pb-based paint that, in-turn, promoted elevated bioaccessibility (>60%). Pb X-ray absorption spectroscopy, µ-XRF mapping, and Pb isotope ratio analysis for house dust and soils support house dust Pb as chemically unique compared to exterior soils, although paint Pb is expected to be a major source for both. Soil pedogenesis and increased protection from environmental conditions (e.g., weathering) in households is expected to greatly impact Pb phase differences between house dust and soils, subsequently dictating differences in Pb exposure.

Disaster healthcare disparities solutions: Part 3-Recovery and mitigation.

The purpose of this study was to explore the potential solutions for disaster healthcare disparities. This paper is the third of a three-part series that was written by the Disaster Healthcare Disparities Workgroup of the American College of Emergency Physicians Disaster Preparedness and Response Committee. The committee conducted a literature review and chose articles most representative and demonstrative of solutions to disaster healthcare disparities found in a past workgroup product. Many solutions for disaster healthcare disparities seen during recovery and mitigation were found. Some of these solutions have been successfully implemented and some remain theoretical. Solutions for disaster healthcare disparities seen during recovery and mitigation are achievable but there is still much work to do. Many of these solutions can be advocated for by nondisaster specialists.

Disaster healthcare disparities solutions: Part 1-Preparation.

The purpose of this study was to explore the potential solutions for disaster healthcare disparities. This paper is the first of a three-part series that was written by the Disaster Healthcare Disparities Workgroup of the American College of Emergency Physicians Disaster Preparedness and Response Committee. The committee workgroup conducted a literature review and chose articles most representative and demonstrative of solutions to disaster healthcare disparities found in a past workgroup product exploring disaster healthcare disparities seen in disaster. Many solutions for disaster healthcare disparities during preparation were found. Some of these solutions have been successfully implemented, while others are still theoretical. Solutions for disaster healthcare disparities seen in disaster preparation are achievable, but there is still much work to do. There are a variety of solutions that can be easily advocated for by disaster and nondisaster specialists, leading to better care for our patients.

Not feeling the heat? Effects of dietary protein on satiation and satiety in mice are not due to its impact on body temperature.

Dietary protein modulates food intake (FI) via unclear mechanism(s). One possibility is that higher protein leads to greater post-ingestive heat production (Specific dynamic action: SDA) leading to earlier meal termination (increased satiation), and inhibition of further intake (increased satiety). The influence of dietary protein on feeding behaviour in C57BL/6J mice was tested using an automated FI monitoring system (BioDAQ), simultaneous to body temperature (Tb). Total FI, inter meal intervals (IMI, satiety) and meal size (MS, satiation) were related to changes in Tb after consuming low (5%, LP), moderate (15%, MP) and high (30%, HP) protein diets. Diets were tested over three conditions: 1) room temperature (RT, 21 ± 1 °C), 2) room temperature and running wheels (RTRW) and 3) low temperature (10 °C) and running wheels (LTRW). The differences between diets and conditions were also compared using mixed models. Mice housed at RT fed HP diet, reduced total FI compared with LP and MP due to earlier meal termination (satiation effect). FI was lowered in RTRW conditions with no differences between diets. FI significantly increased under LTRW conditions for all diets, with protein content leading to earlier meal termination (satiation) but not the intervals between feeding bouts (satiety). Tb fell immediately after feeding in all conditions. Despite a reduction in total FI in mice fed HP, mediated via increased satiation, this effect was not linked to increased Tb during meals. We conclude effects of dietary protein on intake are not mediated via SDA and Tb.

Systematic large-scale application of ClinGen InSiGHT APC -specific ACMG/AMP variant classification criteria substantially alleviates the burden of variants of uncertain significance in ClinVar and LOVD databases.

Background: Pathogenic constitutional APC variants underlie familial adenomatous polyposis, the most common hereditary gastrointestinal polyposis syndrome. To improve variant classification and resolve the interpretative challenges of variants of uncertain significance (VUS), APC-specific ACMG/AMP variant classification criteria were developed by the ClinGen-InSiGHT Hereditary Colorectal Cancer/Polyposis Variant Curation Expert Panel (VCEP). Methods: A streamlined algorithm using the APC -specific criteria was developed and applied to assess all APC variants in ClinVar and the InSiGHT international reference APC LOVD variant database. Results: A total of 10,228 unique APC variants were analysed. Among the ClinVar and LOVD variants with an initial classification of (Likely) Benign or (Likely) Pathogenic, 94% and 96% remained in their original categories, respectively. In contrast, 41% ClinVar and 61% LOVD VUS were reclassified into clinically actionable classes, the vast majority as (Likely) Benign. The total number of VUS was reduced by 37%. In 21 out of 36 (58%) promising APC variants that remained VUS despite evidence for pathogenicity, a data mining-driven work-up allowed their reclassification as (Likely) Pathogenic. Conclusions: The application of APC -specific criteria substantially reduced the number of VUS in ClinVar and LOVD. The study also demonstrated the feasibility of a systematic approach to variant classification in large datasets, which might serve as a generalisable model for other gene-/disease-specific variant interpretation initiatives. It also allowed for the prioritization of VUS that will benefit from in-depth evidence collection. This subset of APC variants was approved by the VCEP and made publicly available through ClinVar and LOVD for widespread clinical use.

An updated review on the safety of N, N-diethyl-meta-toluamide insect repellent use in children and the efficacy of natural alternatives.

N, N-diethyl-meta-toluamide (DEET) has been considered the 'gold standard' for insect repellent use since the 1950s and constitutes most insect repellents on the market. However, conflicting data in the scientific literature and confusing information in the media are at the core of debates about the safety of DEET insect repellents for the protection of children against arthropod bites. The few fatal occurrences involving DEET insect repellents and complications of their use in the pediatric population are typically the result of accidental overdoses or misuse of insect repellents that disregard warnings on product labels. With appropriate application, the safety record of DEET insect repellents continues to be excellent with few side effects. The purpose of this review is to provide a summary of the literature on safety outcomes of DEET insect repellent use in children; outline the pediatric recommendations relating to DEET insect repellents; and provide an overview of EPA-approved and naturally derived alternatives to DEET that possess low toxicity while providing a similar level of protection to synthetic insect repellents.

Generating Clinical-Grade Gene-Disease Validity Classifications Through the ClinGen Data Platforms.

Clinical genetic laboratories must have access to clinically validated biomedical data for precision medicine. A lack of accessibility, normalized structure, and consistency in evaluation complicates interpretation of disease causality, resulting in confusion in assessing the clinical validity of genes and genetic variants for diagnosis. A key goal of the Clinical Genome Resource (ClinGen) is to fill the knowledge gap concerning the strength of evidence supporting the role of a gene in a monogenic disease, which is achieved through a process known as Gene-Disease Validity curation. Here we review the work of ClinGen in developing a curation infrastructure that supports the standardization, harmonization, and dissemination of Gene-Disease Validity data through the creation of frameworks and the utilization of common data standards. This infrastructure is based on several applications, including the ClinGen GeneTracker, Gene Curation Interface, Data Exchange, GeneGraph, and website.

Interventions on gender equity in the workplace: a scoping review.

BACKGROUND: Various studies have demonstrated gender disparities in workplace settings and the need for further intervention. This study identifies and examines evidence from randomized controlled trials (RCTs) on interventions examining gender equity in workplace or volunteer settings. An additional aim was to determine whether interventions considered intersection of gender and other variables, including PROGRESS-Plus equity variables (e.g., race/ethnicity). METHODS: Scoping review conducted using the JBI guide. Literature was searched in MEDLINE, Embase, PsycINFO, CINAHL, Web of Science, ERIC, Index to Legal Periodicals and Books, PAIS Index, Policy Index File, and the Canadian Business & Current Affairs Database from inception to May 9, 2022, with an updated search on October 17, 2022. Results were reported using Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension to scoping reviews (PRISMA-ScR), Sex and Gender Equity in Research (SAGER) guidance, Strengthening the Integration of Intersectionality Theory in Health Inequality Analysis (SIITHIA) checklist, and Guidance for Reporting Involvement of Patients and the Public (GRIPP) version 2 checklist. All employment or volunteer sectors settings were included. Included interventions were designed to promote workplace gender equity that targeted: (a) individuals, (b) organizations, or (c) systems. Any comparator was eligible. Outcomes measures included any gender equity related outcome, whether it was measuring intervention effectiveness (as defined by included studies) or implementation. Data analyses were descriptive in nature. As recommended in the JBI guide to scoping reviews, only high-level content analysis was conducted to categorize the interventions, which were reported using a previously published framework. RESULTS: We screened 8855 citations, 803 grey literature sources, and 663 full-text articles, resulting in 24 unique RCTs and one companion report that met inclusion criteria. Most studies (91.7%) failed to report how they established sex or gender. Twenty-three of 24 (95.8%) studies reported at least one PROGRESS-Plus variable: typically sex or gender or occupation. Two RCTs (8.3%) identified a non-binary gender identity. None of the RCTs reported on relationships between gender and other characteristics (e.g., disability, age, etc.). We identified 24 gender equity promoting interventions in the workplace that were evaluated and categorized into one or more of the following themes: (i) quantifying gender impacts; (ii) behavioural or systemic changes; (iii) career flexibility; (iv) increased visibility, recognition, and representation; (v) creating opportunities for development, mentorship, and sponsorship; and (vi) financial support. Of these interventions, 20/24 (83.3%) had positive conclusion statements for their primary outcomes (e.g., improved academic productivity, increased self-esteem) across heterogeneous outcomes. CONCLUSIONS: There is a paucity of literature on interventions to promote workplace gender equity. While some interventions elicited positive conclusions across a variety of outcomes, standardized outcome measures considering specific contexts and cultures are required. Few PROGRESS-Plus items were reported. Non-binary gender identities and issues related to intersectionality were not adequately considered. Future research should provide consistent and contemporary definitions of gender and sex. TRIAL REGISTRATION: Open Science Framework https://osf.io/x8yae .

Accelerated magnetocardiography in the evaluation of patients with suspected cardiac ischemia: The MAGNETO trial.

Background: Diagnosing ischemia in emergency department (ED) patients with suspected acute coronary syndrome (sACS) is challenging with equivocal disposition of intermediate risk patients. Objective: Compare sensitivity and specificity of magnetocardiography (MCG) versus standard of care (SOC) stress testing in diagnosing myocardial ischemia. Methods: Multicenter, prospective, observational cohort study. ED patients with sACS and HEART score ≥ 3 underwent 90 s noninvasive MCG to detect myocardial ischemia. Results were blinded to the patient's clinicians. MCGs were read independently by 3 physicians blinded to clinical data. Myocardial ischemia was ≥70 % epicardial coronary artery stenosis, revascularization within 30 days, or 30-day major adverse cardiac events (MACE). Time to first test (TTT) and patient satisfaction for MCG and SOC were compared. Results: Of enrolled patients (N = 390) (mean age 59 ± 12 years, 45 % female), 99 (25 %) underwent a non-invasive stress test: 42 (14 %) diagnosed with ischemia. MCG sensitivity was 66.7 % (50.5-80.4 %, 95 % CI) and specificity 57.1 % (50.0-63.3 %, 95 % CI) for detecting coronary ischemia. Noninvasive stress testing (stress echo, nuclear stress, and exercise stress) had the same sensitivity 66.7 % (95 % CI 29.9 % to 92.5 %) and a specificity of 89.9 % (95 % CI 81.7-95.3 %). Mean TTT was shorter for MCG, 3.18 h (SD 1.91) vs. SOC stress testing 22.71 (SD 15.23), p < 0.0001. Mean patient experience was MCG 4.7 versus 3.0 SOC stress testing (p < 0.0001). Conclusion: MCG provides similar sensitivity and lower specificity as non-invasive stress testing in ED sACS patients. Time to test is shorter for MCG with higher patient satisfaction scores.

Defining and Reducing Variant Classification Disparities.

Background: Multiplexed Assays of Variant Effects (MAVEs) can test all possible single variants in a gene of interest. The resulting saturation-style data may help resolve variant classification disparities between populations, especially for variants of uncertain significance (VUS). Methods: We analyzed clinical significance classifications in 213,663 individuals of European-like genetic ancestry versus 206,975 individuals of non-European-like genetic ancestry from All of Us and the Genome Aggregation Database. Then, we incorporated clinically calibrated MAVE data into the Clinical Genome Resource's Variant Curation Expert Panel rules to automate VUS reclassification for BRCA1, TP53, and PTEN . Results: Using two orthogonal statistical approaches, we show a higher prevalence ( p ≤5.95e-06) of VUS in individuals of non-European-like genetic ancestry across all medical specialties assessed in all three databases. Further, in the non-European-like genetic ancestry group, higher rates of Benign or Likely Benign and variants with no clinical designation ( p ≤2.5e-05) were found across many medical specialties, whereas Pathogenic or Likely Pathogenic assignments were higher in individuals of European-like genetic ancestry ( p ≤2.5e-05). Using MAVE data, we reclassified VUS in individuals of non-European-like genetic ancestry at a significantly higher rate in comparison to reclassified VUS from European-like genetic ancestry ( p =9.1e-03) effectively compensating for the VUS disparity. Further, essential code analysis showed equitable impact of MAVE evidence codes but inequitable impact of allele frequency ( p =7.47e-06) and computational predictor ( p =6.92e-05) evidence codes for individuals of non-European-like genetic ancestry. Conclusions: Generation of saturation-style MAVE data should be a priority to reduce VUS disparities and produce equitable training data for future computational predictors.

Evaluation of cytokine profiles related to Mycobacterium tuberculosis latent antigens using a whole-blood assay in the Philippines.

Introduction: There is no useful method to discriminate between latent tuberculosis infection (LTBI) and active pulmonary tuberculosis (PTB). This study aimed to investigate the potential of cytokine profiles to discriminate between LTBI and active PTB using whole-blood stimulation with Mycobacterium tuberculosis (MTB) antigens, including latency-associated antigens. Materials and methods: Patients with active PTB, household contacts of active PTB patients and community exposure subjects were recruited in Manila, the Philippines. Peripheral blood was collected from the participants and used for whole-blood stimulation (WBS) with either the early secretory antigenic target and the 10-kDa culture filtrate protein (ESAT-6/CFP-10), Rv3879c or latency-associated MTB antigens, including mycobacterial DNA-binding protein 1 (MDP-1), α-crystallin (Acr) and heparin-binding hemagglutinin (HBHA). Multiple cytokine concentrations were analyzed using the Bio-Plex™ multiplex cytokine assay. Results: A total of 78 participants consisting of 15 active PTB patients, 48 household contacts and 15 community exposure subjects were eligible. The MDP-1-specific IFN-γ level in the active PTB group was significantly lower than that in the household contact group (p < 0.001) and the community exposure group (p < 0.001). The Acr-specific TNF-α and IL-10 levels in the active PTB group were significantly higher than those in the household contact (TNF-α; p = 0.001, IL-10; p = 0.001) and community exposure (TNF-α; p < 0.001, IL-10; p = 0.01) groups. However, there was no significant difference in the ESAT-6/CFP-10-specific IFN-γ levels among the groups. Conclusion: The patterns of cytokine profiles induced by latency-associated MTB antigens using WBS have the potential to discriminate between LTBI and active PTB. In particular, combinations of IFN-γ and MDP-1, TNF-α and Acr, and IL-10 and Acr are promising. This study provides the first demonstration of the utility of MDP-1-specific cytokine responses in WBS.

Detecting High-Dose Methotrexate-Induced Brain Changes in Pediatric and Young Adult Cancer Survivors Using [18F]FDG PET/MRI: A Pilot Study.

Significant improvements in treatments for children with cancer have resulted in a growing population of childhood cancer survivors who may face long-term adverse outcomes. Here, we aimed to diagnose high-dose methotrexate-induced brain injury on [18F]FDG PET/MRI and correlate the results with cognitive impairment identified by neurocognitive testing in pediatric cancer survivors. Methods: In this prospective, single-center pilot study, 10 children and young adults with sarcoma (n = 5), lymphoma (n = 4), or leukemia (n = 1) underwent dedicated brain [18F]FDG PET/MRI and a 2-h expert neuropsychologic evaluation on the same day, including the Wechsler Abbreviated Scale of Intelligence, second edition, for intellectual functioning; Delis-Kaplan Executive Function System (DKEFS) for executive functioning; and Wide Range Assessment of Memory and Learning, second edition (WRAML), for verbal and visual memory. Using PMOD software, we measured the SUVmean, cortical thickness, mean cerebral blood flow (CBFmean), and mean apparent diffusion coefficient of 3 different cortical regions (prefrontal cortex, cingulate gyrus, and hippocampus) that are routinely involved during the above-specified neurocognitive testing. Standardized scores of different measures were converted to z scores. Pairs of multivariable regression models (one for z scores < 0 and one for z scores > 0) were fitted for each brain region, imaging measure, and test score. Heteroscedasticity regression models were used to account for heterogeneity in variances between brain regions and to adjust for clustering within patients. Results: The regression analysis showed a significant correlation between the SUVmean of the prefrontal cortex and cingulum and DKEFS-sequential tracking (DKEFS-TM4) z scores (P = 0.003 and P = 0.012, respectively). The SUVmean of the hippocampus did not correlate with DKEFS-TM4 z scores (P = 0.111). The SUVmean for any evaluated brain regions did not correlate significantly with WRAML-visual memory (WRAML-VIS) z scores. CBFmean showed a positive correlation with SUVmean (r = 0.56, P = 0.01). The CBFmean of the cingulum, hippocampus, and prefrontal cortex correlated significantly with DKEFS-TM4 (all P < 0.001). In addition, the hippocampal CBFmean correlated significantly with negative WRAML-VIS z scores (P = 0.003). Conclusion: High-dose methotrexate-induced brain injury can manifest as a reduction in glucose metabolism and blood flow in specific brain areas, which can be detected with [18F]FDG PET/MRI. The SUVmean and CBFmean of the prefrontal cortex and cingulum can serve as quantitative measures for detecting executive functioning problems. Hippocampal CBFmean could also be useful for monitoring memory problems.

Angiolymphoid hyperplasia with eosinophilia and Kimura disease: A case report and literature review.

Angiolymphoid hyperplasia with eosinophilia (ALHE) is a benign vascular proliferative condition, typically presenting as subcutaneous nodules in the head and neck region of middle-aged women. Kimura disease (KD) is a benign condition that presents with subcutaneous nodules in a similar distribution with lymphadenopathy and eosinophilia, typically in Asian adult males. These diseases are often discussed together, including whether they exist on a spectrum or if they represent separate disease entities. Both are very rare in the pediatric population; in this report we highlight the case of a 10-year-old Caucasian male presenting with ALHE and KD.