School Connectedness and Adolescent E-cigarette Susceptibility in an Urban Sample of Middle and High School Students.

Adolescent school connectedness generally protects from risk behaviors such as tobacco use; however, its relationship to e-cigarette use is unclear. This study examines the relationship between adolescent school connectedness and e-cigarette susceptibility in a diverse longitudinal sample. This secondary analysis of a school-based intervention surveyed 608 middle (66%) and high school (34%) students from 10 schools at 3 time points over 1 year. At baseline, respondents had a mean age of 14 years, 54% were female, and 71% were BIPOC (Black, Indigenous, People of Color). Logistic regression models examined unadjusted and adjusted associations between school connectedness (both baseline and concurrent) and e-cigarette susceptibility over time. E-cigarettes represented the most prevalent form of current nicotine-containing product use in spring 2019 (2.3%), and most respondents reported no e-cigarette susceptibility (69%). E-cigarette susceptibility remained relatively stable during the study. Higher baseline school connectedness levels were associated with lower odds of e-cigarette susceptibility over time. Similarly, higher concurrent school connectedness scores were associated with lower odds of e-cigarette susceptibility over time: spring 2019 (OR, 0.39; 95% CI, 0.32, 0.47), fall 2019 (OR, 0.49; 95% CI, 0.34, 0.72), and spring 2020 (OR, 0.64; 95% CI, 0.47, 0.87). Findings were similar for middle and high school students and did not differ significantly after adjusting for other covariates. Adolescents' school connectedness appears to protect from e-cigarette susceptibility over time, underscoring the importance of promoting positive school experiences to reduce adolescent risk e-cigarette use.

Clinical and Histopathologic Characteristics of Pediatric Patients With Primary Membranous Nephropathy.

Introduction: Primary membranous nephropathy (PMN) is uncommon in children. Therefore, data on the clinical course of affected children are scarce. In recent years, several novel antigens have been implicated in the pathogenesis of PMN. However, the histopathologic characteristics of pediatric patients with PMN remain poorly represented in the literature. Methods: We have retrospectively analyzed the clinical presentation and outcomes data of 21 children with PMN from 3 centers in the United States. In addition, we have identified novel antigens in biopsy specimens from these patients and correlated their presence or absence to clinical outcomes. Finally, we compared the results of the novel antigen staining from our clinical cohort to a validation cohort of 127 biopsy specimens from children with PMN at Arkana Laboratories. Results: The data from the 2 cohorts demonstrated similar overall antigen positivity rates of 62% to 63%, with phospholipase A2 receptor (PLA2R) and exostosin 1 (EXT1) being the most commonly found antigens. Results from the clinical cohort showed that overall, the kidney prognosis for children with PMN was good, with 17 of 21 patients entering a complete or partial remission. Children who were positive for PLA2R or EXT1 were significantly more likely to enter remission than those in the antigen negative group. Conclusion: Approximately 60% of pediatric membranous cases are positive for a novel antigen on kidney biopsy and the clinical prognosis is generally favorable. More studies are needed to understand the clinical implications of each specific novel antigen.

Predictors of adverse safety events and unscheduled care among an outpatient parenteral antimicrobial therapy (OPAT) patient cohort.

Background: Select circumstances require outpatient parenteral antimicrobial therapy (OPAT). The potency of OPAT agents presents an increased risk of adverse events and unscheduled medical care. We analyzed these outcomes among OPAT recipients as part of the implementation of a collaborative OPAT program. Methods: Adult patients discharged home from an academic hospital with OPAT between January 2019 and June 2021 were included in this retrospective cohort; participants discharged between June 2020 and June 2021 were part of the collaborative OPAT program. Patients with cystic fibrosis were excluded. Data on patient characteristics and outcomes were collected from electronic medical records by two reviewers. Multivariable analysis was conducted to identify predictors of vascular access device (VAD) complications, adverse drug events (ADEs), and OPAT-related emergency department (ED) visits and rehospitalizations. Results: Among 265 patients included in the cohort, 57 (21.5%) patients experienced a VAD complication; obesity [odds ratio (OR): 3.32; 95% confidence interval (CI): 1.38-8.73; p = 0.01) and multi-drug therapy (OR: 2.56; 95% CI: 1.21-5.39; p = 0.01) were associated with an increased odds of VAD complication. Eighty-two (30.9%) participants experienced an ADE; 30 (11.3%) experienced a severe/serious ADE. Lipo/glycopeptide receipt, (OR: 5.28; 95% CI: 1.89-15.43; p < 0.01) and Black/African American race (OR: 4.85; 95% (CI): 1.56-15.45; p < 0.01) were associated with an increased odds of severe/serious ADE. Inclusion in the OPAT collaborative was associated with a decreased odds of severe/serious ADE (OR: 0.26; 95% CI: 0.08-0.77; p = 0.01). Fifty-eight (21.9%) patients experienced an OPAT-related ED visit and 53 (20.0%) experienced an OPAT-related rehospitalization. VAD complication (OR: 2.37; 95% (CI): 1.15-4.86, p = 0.02) and ADEs (OR: 2.19; CI: 1.13-4.22; p = 0.02) were associated with OPAT-related ED visits. ADE was associated with 90-day OPAT-related rehospitalization (OR: 3.21; (CI): 1.59-6.58; p < 0.01). Conclusion: Adverse safety events and OPAT-related unscheduled care occurred often in our cohort. A structured OPAT program that includes ID pharmacist antibiotic reconciliation may reduce rates of ADEs.

Evaluation of Dosimetry Formalisms in Intraoperative Radiation Therapy of Glioblastoma.

PURPOSE: The intraoperative radiotherapy in newly diagnosed glioblastoma multiforme (INTRAGO) clinical trial assesses survival in patients with glioblastoma treated with intraoperative radiation therapy (IORT) using the INTRABEAM. Treatment planning for INTRABEAM relies on vendor-provided in-water depth dose curves obtained according to the TARGeted Intraoperative radioTherapy (TARGIT) dosimetry protocol. However, recent studies have shown discrepancies between the estimated TARGIT and delivered doses. This work evaluates the effect of the choice of dosimetry formalism on organs at risk (OAR) doses. METHODS AND MATERIALS: A treatment planning framework for INTRABEAM was developed to retrospectively calculate the IORT dose in 8 INTRAGO patients. These patients received an IORT prescription dose of 20 to 30 Gy in addition to external beam radiation therapy. The IORT dose was obtained using (1) the TARGIT method; (2) the manufacturer's V4.0 method; (3) the CQ method, which uses an ionization chamber Monte Carlo (MC) calculated factor; (4) MC dose-to-water; and (5) MC dose-to-tissue. The IORT dose was converted to 2 Gy fractions equivalent dose. RESULTS: According to the TARGIT method, the OAR dose constraints were respected in all cases. However, the other formalisms estimated a higher mean dose to OARs and revealed 1 case where the constraint for the brain stem was exceeded. The addition of the external beam radiation therapy and TARGIT IORT doses resulted in 10 cases of OARs exceeding the dose constraints. The more accurate MC calculation of dose-to-tissue led to the highest dosimetric differences, with 3, 3, 2, and 2 cases (out of 8) exceeding the dose constraint to the brain stem, optic chiasm, optic nerves, and lenses, respectively. Moreover, the mean cumulative dose to brain stem exceeded its constraint of 66 Gy with the MC dose-to-tissue method, which was not evident with the current INTRAGO clinical practice. CONCLUSIONS: The current clinical approach of calculating the IORT dose with the TARGIT method may considerably underestimate doses to nearby OARs. In practice, OAR dose constraints may have been exceeded, as revealed by more accurate methods.

Prolonged Elevations of Factor VIII and von Willebrand Factor Antigen After Multisystem Inflammatory Syndrome in Children.

Multisystem Inflammatory Syndrome in Children (MIS-C) is a late systemic inflammatory response to a recent mild or asymptomatic coronavirus disease of 2019 infection. The pathophysiology is incompletely understood but it often features significant coagulopathy along with cardiac and endothelial dysfunction. Endothelial inflammation has been primarily described in acute coronavirus disease of 2019 infection, with less characterization in MIS-C. Here we describe novel findings of nearly universal severe and prolonged factor VIII (FVIII) and von Willebrand factor antigen elevations in an institutional cohort of patients with MIS-C ages younger than or 21 years old (N=31). All patients had elevated acute phase reactants and D-dimer at presentation and met published criteria for MIS-C. FVIII was high at presentation in 97% of patients but continued to rise during the ensuing weeks of treatment to a mean 429%, peaking on median day 17 of illness as an outpatient. FVIII levels were >600% in multiple patients. von Willebrand factor antigen was measured less frequently but showed similar trends. These escalations occurred amidst resolving cardiac dysfunction and acute phase reactant normalization and despite patients receiving multimodal anti-inflammatory treatments and aspirin and enoxaparin thromboprophylaxis. No thrombotic events occurred. Endothelial dysfunction represented by very elevated FVIII levels may persist longer than other acute phase reactants may reflect.

The mixed spongiotic and interface reaction pattern: A study of clinical and histopathologic findings.

BACKGROUND: Categorization of biopsy specimens into inflammatory reaction patterns is central to dermatopathologic assessment. Mixed inflammatory patterns are poorly characterized and may represent clinicopathologic challenges. The purpose of this study was to identify clinical and histopathologic findings associated with the mixed spongiotic-interface dermatitis (SID) histopathologic pattern. METHODS: Fifty-one institutional biopsy specimens of SID were identified over a 2-year period by retrospective natural language search. Histopathologic and clinical features were identified. RESULTS: The most common histopathologic features associated with SID were mild spongiosis (51%), focal vacuolar interface change (72%), lymphocytic exocytosis (92%), and superficial-dermal lymphocytic infiltrate (94%) with variable eosinophils (61%). Clinically, 80% of subjects presented with a symmetric morbilliform eruption. Polypharmacy (94%), immunosuppression (47%), and history of malignancy (47%) were common. The most common diagnoses were drug reaction (37%), possible drug reaction (12%), and viral exanthem (12%). Drug reaction with eosinophilia and systemic symptoms represented 25% of all confirmed cutaneous adverse drug reactions (CADR). Average time from drug initiation to symptom initiation was 20 days (SD: 22.3, range: 0-90); median disease duration was 25.5 days. Spongiotic vesicles and Langerhans cells were less common in patients with a strong clinicopathologic diagnosis of drug reaction compared to non-drug eruptions (p = 0.04). CONCLUSIONS: The mixed SID pattern is commonly encountered in CADR but may represent a more subacute course, implying consideration for inciting medication(s) started before the typical 7- to 14-day window.

Health Information Technology Use among Chronic Disease Patients: An Analysis of the United States Health Information National Trends Survey.

BACKGROUND: Chronic disease is the leading cause of mortality in the United States. Health information technology (HIT) tools show promise for improving disease management. OBJECTIVES: This study aims to understand the following: (1) how self-perceptions of health compare between those with and without disease; (2) how HIT usage varies between chronic disease profiles (diabetes, hypertension, cardiovascular disease, pulmonary disease, depression, cancer, and comorbidities); (3) how HIT trends have changed in the past 6 years; and (4) the likelihood that a given chronic disease patient uses specific HIT tools. METHODS: The Health Information National Trends Survey (HINTS) inclusive of 2014 to 2020 served as the primary data source with statistical analysis completed using Stata. Bivariate analyses and two-tailed t-tests were conducted to compare self-perceived health and HIT usage to chronic disease. Logistic regression models were created to examine the odds of a specific patient using various forms of HIT, controlling for demographics and comorbidities. RESULTS: Logistic regression models controlling for sociodemographic factors and comorbidities showed that pulmonary disease, depression, and cancer patients had an increased likelihood of using HIT tools, for example, depression patients had an 81.1% increased likelihood of looking up health information (p < 0.0001). In contrast, diabetic, high blood pressure, and cardiovascular disease patients appeared to use HIT tools at similar rates to patients without chronic disease. Overall HIT usage has increased during the timeframe examined. CONCLUSION: This study demonstrates that certain chronic disease cohorts appear to have greater HIT usage than others. Further analysis should be done to understand what factors influence patients to utilize HIT which may provide additional insights into improving design and user experience for other populations with the goal of improving management of disease. Such analyses could also establish a new baseline to account for differences in HIT usage as a direct consequence of the novel coronavirus disease 2019 (COVID-19) pandemic.

Brief Motivational Interviewing: Evaluation of a skills-based education program.

Purpose: Oral health care providers have been charged with recommending the human papillomavirus (HPV) vaccine for the prevention of HPV oropharyngeal cancers (OPC). The purpose of this study was to determine dental hygiene student competency of the application of brief motivational interviewing (BMI) and the accuracy of HPV vaccine information for the prevention of HPV OPC.Methods: A convenience sample of 59 senior dental hygiene (DH) students from the class of 2020 (n=31) and the class of 2021 (n=28) participated in the HPV OPC curriculum and skills-based BMI training at the University of Minnesota School of Dentistry. Students completed two audio-recorded patient interactions and one Objective Structured Clinical Examination (OSCE). Student self-assessment and faculty evaluation scores were determined by a standardized BMI HPV rubric. Descriptive statistics were used to analyze the data.Results: Class of 2021 self-assessment ratings were higher than the class of 2020 in all components of the BMI HPV rubric at all three time points. Faculty evaluation achieved statistically significant improvement for the class of 2021 from patient Interaction 1 (evocation p<0.01; summary p<0.01) to the OSCE (evocation p<0.05; summary p<0.01). Both classes rated themselves as competent (≥70%) for most BMI subcategories.Conclusion: Dental hygiene student competence in demonstrating the components of the Spirit of MI to the accuracy of HPV and HPV vaccine information was achieved through the implementation of the skills-based BMI HPV training. Outcomes of student self-assessment and faculty evaluation highlighted the Kirkpatrick Model as a framework to evaluate BMI skills-based training.

Dental Hygiene Students' Perceptions Regarding the Importance of and Confidence with Using Brief Motivational Interviewing during HPV Patient Counseling.

Purpose: Human papillomavirus (HPV), a sexually transmitted virus that has been identified in over two-thirds of all oropharyngeal cancers. Oral health care professionals play a key role in educating the public regarding HPV and the role of vaccinations. The purpose of this study was to examine dental hygiene and dental therapy students' perceptions of the importance of and their confidence with applying brief motivational interviewing (BMI) during patient counseling regarding the human papilloma virus (HPV).Methods: A convenience sample of dental hygiene and dual degree dental hygiene/dental therapy students (n=32) participated in an enhanced BMI curriculum that included a 90-minute HPV BMI coaching and role-playing session on the use of eight MI strategies and the technique of elicit-provide-elicit. Questionnaires assessing participants' perceptions were disseminated at three time points; prior to the HPV BMI training (pre-test), immediately after the coaching and role-playing session (post-test 1) and after the participants had applied their HPV BMI skills during two patient interactions that included self-assessment and faculty feedback (post-test 2).Results: All the students in the sample (n=32) completed the three questionnaires. While participants' perception of the importance of BMI increased for three of the eight strategies (pre-test to post-test 2), it was not statistically significant. Perceptions of confidence in applying of BMI increased for seven of the strategies (pre-test to post-test 1). Statistical significance was achieved for the "Use of the Importance Ruler" strategy (p=0.003) from pretest to posttest 1 and pre-test to post-test 2 (p=0.003).Conclusion: Results indicate that an enhanced HPV BMI coaching curriculum in addition and two HPV BMI sessions with patients is not enough training to retain confidence overtime. Future research should investigate strategies, such as additional coaching and role-playing sessions, for retaining confidence with applying BMI for HPV discussions during patient care.

Monte Carlo calculation of the TG-43 dosimetry parameters for the INTRABEAM source with spherical applicators.

OBJECTIVE: The relative TG-43 dosimetry parameters of the INTRABEAM (Carl Zeiss Meditec AG, Jena, Germany) bare probe were recently reported by Ayala Alvarezet al(2020Phys. Med. Biol.65245041). The current study focuses on the dosimetry characterization of the INTRABEAM source with the eight available spherical applicators according to the TG-43 formalism using Monte Carlo (MC) simulations. APPROACH: This report includes the calculated dose-rate conversion coefficients that determine the absolute dose rate to water at a reference point of 10 mm from the applicator surface, based on calibration air-kerma rate measurements at 50 cm from the source on its transverse plane. Since the air-kerma rate measurements are not yet provided from a standards laboratory for the INTRABEAM, the values in the present study were calculated with MC. This approach is aligned with other works in the search for standardization of the dosimetry of electronic brachytherapy sources. As a validation of the MC model, depth dose calculations along the source axis were compared with calibration data from the source manufacturer. MAIN RESULTS: The calculated dose-rate conversion coefficients were 434.0 for the bare probe, and 683.5, 548.3, 449.9, 376.5, 251.0, 225.6, 202.8, and 182.6 for the source with applicators of increasing diameter from 15 to 50 mm, respectively. The radial dose and the 2D anisotropy functions of the TG-43 formalism were also obtained and tabulated in this document. SIGNIFICANCE: This work presents the data required by a treatment planning system for the characterization of the INTRABEAM system in the context of intraoperative radiotherapy applications.

Monte Carlo calculation of the relative TG-43 dosimetry parameters for the INTRABEAM electronic brachytherapy source.

The INTRABEAM system (Carl Zeiss Meditec AG, Jena, Germany) is an electronic brachytherapy (eBT) device designed for intraoperative radiotherapy applications. To date, the INTRABEAM x-ray source has not been characterized according to the AAPM TG-43 specifications for brachytherapy sources. This restricts its modelling in commercial treatment planning systems (TPSs), with the consequence that the doses to organs at risk are unknown. The aim of this work is to characterize the INTRABEAM source according to the TG-43 brachytherapy dosimetry protocol. The dose distribution in water around the source was determined with Monte Carlo (MC) calculations. For the validation of the MC model, depth dose calculations along the source longitudinal axis were compared with measurements using a soft x-ray ionization chamber (PTW 34013) and two synthetic diamond detectors (microDiamond PTW TN60019). In our results, the measurements in water agreed with the MC model calculations within uncertainties. The use of the microDiamond detector yielded better agreement with MC calculations, within estimated uncertainties, compared to the ionization chamber at points of steeper dose gradients. The radial dose function showed a steep fall-off close to the INTRABEAM source ([Formula: see text]10 mm) with a gradient higher than that of commonly used brachytherapy radionuclides (192Ir, 125I and 103Pd), with values of 2.510, 1.645 and 1.232 at 4, 6 and 8 mm, respectively. The radial dose function partially flattens at larger distances with a fall-off comparable to that of the Xoft Axxent® (iCAD, Inc., Nashua, NH) eBT system. The simulated 2D polar anisotropy close to the bare probe walls showed deviations from unity of up to 55% at 10 mm and 155°. This work presents the MC calculated TG-43 parameters for the INTRABEAM, which constitute the necessary data for the characterization of the source as required by a TPS used in clinical dose calculations.

Predictors of Survival After Liver Transplantation in Patients With the Highest Acuity (MELD ≥40).

OBJECTIVE: To identify factors that accurately predict 1-year survival for liver transplant recipients with a MELD score ≥40. BACKGROUND: Although transplant is beneficial for patients with the highest acuity (MELD ≥40), mortality in this group is high. Predicting which patients are likely to survive for >1 year would be medically and economically helpful. METHODS: The Scientific Registry of Transplant Recipients database was reviewed to identify adult liver transplant recipients from 2002 through 2016 with MELD score ≥40 at transplant. The relationships between 44 recipient and donor factors and 1-year patient survival were examined using random survival forests methods. Variable importance measures were used to identify the factors with the strongest influence on survival, and partial dependence plots were used to determine the dependence of survival on the target variable while adjusting for all other variables. RESULTS: We identified 5309 liver transplants that met our criteria. The overall 1-year survival of high-acuity patients improved from 69% in 2001 to 87% in 2016. The strongest predictors of death within 1 year of transplant were patient on mechanical ventilator before transplantation, prior liver transplant, older recipient age, older donor age, donation after cardiac death, and longer cold ischemia. CONCLUSIONS: Liver transplant outcomes continue to improve even for patients with high medical acuity. Applying ensemble learning methods to recipient and donor factors available before transplant can predict survival probabilities for future transplant cases. This information can be used to facilitate donor/recipient matching and to improve informed consent.

Preliminary evaluation of dental hygiene curriculum: Assessment and management of peri-implant conditions and diseases.

OBJECTIVE: The purpose of this study was to investigate dental hygiene (DH) educational programs' didactic and clinical curriculum in the management of peri-implant diseases and conditions. The specific aims were (1) assess if evidence-based content for peri-implant diseases and conditions are currently included in didactic and clinical DH curriculum and (2) determine if DH education programs are currently preparing students at a level of clinical competency for the assessment and management of peri-implant diseases and conditions. DESIGN: A cross-sectional study of DH faculty member(s) from 331 United States entry-level programs responsible for didactic and clinical curriculum for peri-implant diseases and conditions were surveyed. The survey was disseminated electronically via Qualtricsxm August 2019 for a response rate of 26%. RESULTS: The results showed didactic courses taught DH students the etiology of peri-mucositis and peri-implantitis (98%), clinical characteristics (98%), and risk factors contributing to these implant diseases (96%). Evaluation methods to determine student level of competency in a didactic setting included quizzes/examinations (98%), case-based examinations (63%), and written essays (6%). Eighty-five percent reported DH students are not required in a clinical setting to provide care for patients with peri-implant diseases and conditions. CONCLUSIONS: Study results suggest DH education programs may need to revise didactic and clinical curriculum to ensure students graduate at a level of clinical competency for assessing and managing peri-implant conditions and diseases. DH educational programs should consider requiring clinical patient experiences for the assessment and management of peri-mucositis and peri-implantitis to prepare students for their professional role.

Club Cell TRPV4 Serves as a Damage Sensor Driving Lung Allergic Inflammation.

Airway epithelium is the first body surface to contact inhaled irritants and report danger. Here, we report how epithelial cells recognize and respond to aeroallergen alkaline protease 1 (Alp1) of Aspergillus sp., because proteases are critical components of many allergens that provoke asthma. In a murine model, Alp1 elicits helper T (Th) cell-dependent lung eosinophilia that is initiated by the rapid response of bronchiolar club cells to Alp1. Alp1 damages bronchiolar cell junctions, which triggers a calcium flux signaled through calcineurin within club cells of the bronchioles, inciting inflammation. In two human cohorts, we link fungal sensitization and/or asthma with SNP/protein expression of the mechanosensitive calcium channel, TRPV4. TRPV4 is also necessary and sufficient for club cells to sensitize mice to Alp1. Thus, club cells detect junction damage as mechanical stress, which signals danger via TRPV4, calcium, and calcineurin to initiate allergic sensitization.

Regulation of Osteoclast Differentiation at Multiple Stages by Protein Kinase D Family Kinases.

Balanced osteoclast and osteoblast activity is necessary for skeletal health, whereas unbalanced osteoclast activity causes bone loss in many skeletal conditions. A better understanding of pathways that regulate osteoclast differentiation and activity is necessary for the development of new therapies to better manage bone resorption. The roles of Protein Kinase D (PKD) family of serine/threonine kinases in osteoclasts have not been well characterized. In this study we use immunofluorescence analysis to reveal that PKD2 and PKD3, the isoforms expressed in osteoclasts, are found in the nucleus and cytoplasm, the mitotic spindle and midbody, and in association with the actin belt. We show that PKD inhibitors CRT0066101 and CID755673 inhibit several distinct aspects of osteoclast formation. Treating bone marrow macrophages with lower doses of the PKD inhibitors had little effect on M-CSF + RANKL-dependent induction into committed osteoclast precursors, but inhibited their motility and subsequent differentiation into multinucleated mature osteoclasts, whereas higher doses of the PKD inhibitors induced apoptosis of the preosteoclasts. Treating post-fusion multinucleated osteoclasts with the inhibitors disrupted the osteoclast actin belts and impaired their resorptive activity. In conclusion, these data implicate PKD kinases as positive regulators of osteoclasts, which are essential for multiple distinct processes throughout their formation and function.

Cord Blood-Derived Exosomal CNTN2 and BDNF: Potential Molecular Markers for Brain Health of Neonates at Risk for Iron Deficiency.

Maternal iron deficiency anemia, obesity, and diabetes are prevalent during pregnancy. All are associated with neonatal brain iron deficiency (ID) and neurodevelopmental impairment. Exosomes are extracellular vesicles involved in cell-cell communication. Contactin-2 (CNTN2), a neural-specific glycoprotein, and brain-derived neurotrophic factor (BDNF) are important in neurodevelopment and found in exosomes. We hypothesized that exosomal CNTN2 and BDNF identify infants at risk for brain ID. Umbilical cord blood samples were measured for iron status. Maternal anemia, diabetes, and body mass index (BMI) were recorded. Cord blood exosomes were isolated and validated for the exosomal marker CD81 and the neural-specific exosomal marker CNTN2. Exosomal CNTN2 and BDNF levels were quantified by ELISA. Analysis of CNTN2 and BDNF levels as predictors of cord blood iron indices showed a direct correlation between CNTN2 and ferritin in all neonates (n = 79, ß = 1.75, p = 0.02). In contrast, BDNF levels inversely correlated with ferritin (ß = -1.20, p = 0.03), with stronger association in female neonates (n = 37, ß = -1.35, p = 0.06), although there is no evidence of a sex-specific effect. Analysis of maternal risk factors for neonatal brain ID as predictors of exosomal CNTN2 and BDNF levels showed sex-specific relationships between infants of diabetic mothers (IDMs) and CNTN2 levels (Interaction p = 0.0005). While male IDMs exhibited a negative correlation (n = 42, ß = -0.69, p = 0.02), female IDMs showed a positive correlation (n = 37, ß = 0.92, p = 0.01) with CNTN2. A negative correlation between BNDF and maternal BMI was found with stronger association in female neonates (per 10 units BMI, ß = -0.60, p = 0.04). These findings suggest CNTN2 and BNDF are respective molecular markers for male and female neonates at risk for brain ID. This study supports the potential of exosomal markers to assess neonatal brain status in at-risk infants.

Deep convolutional neural networks with multiplane consensus labeling for lung function quantification using UTE proton MRI.

BACKGROUND: Ultrashort echo time (UTE) proton MRI has gained popularity for assessing lung structure and function in pulmonary imaging; however, the development of rapid biomarker extraction and regional quantification has lagged behind due to labor-intensive lung segmentation. PURPOSE: To evaluate a deep learning (DL) approach for automated lung segmentation to extract image-based biomarkers from functional lung imaging using 3D radial UTE oxygen-enhanced (OE) MRI. STUDY TYPE: Retrospective study aimed to evaluate a technical development. POPULATION: Forty-five human subjects, including 16 healthy volunteers, 5 asthma, and 24 patients with cystic fibrosis. FIELD STRENGTH/SEQUENCE: 1.5T MRI, 3D radial UTE (TE = 0.08 msec) sequence. ASSESSMENT: Two 3D radial UTE volumes were acquired sequentially under normoxic (21% O2 ) and hyperoxic (100% O2 ) conditions. Automated segmentation of the lungs using 2D convolutional encoder-decoder based DL method, and the subsequent functional quantification via adaptive K-means were compared with the results obtained from the reference method, supervised region growing. STATISTICAL TESTS: Relative to the reference method, the performance of DL on volumetric quantification was assessed using Dice coefficient with 95% confidence interval (CI) for accuracy, two-sided Wilcoxon signed-rank test for computation time, and Bland-Altman analysis on the functional measure derived from the OE images. RESULTS: The DL method produced strong agreement with supervised region growing for the right (Dice: 0.97; 95% CI = [0.96, 0.97]; P < 0.001) and left lungs (Dice: 0.96; 95% CI = [0.96, 0.97]; P < 0.001). The DL method averaged 46 seconds to generate the automatic segmentations in contrast to 1.93 hours using the reference method (P < 0.001). Bland-Altman analysis showed nonsignificant intermethod differences of volumetric (P ≥ 0.12) and functional measurements (P ≥ 0.34) in the left and right lungs. DATA CONCLUSION: DL provides rapid, automated, and robust lung segmentation for quantification of regional lung function using UTE proton MRI. LEVEL OF EVIDENCE: 2 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2019;50:1169-1181.

RapidBrachyMCTPS: a Monte Carlo-based treatment planning system for brachytherapy applications.

Despite being considered the gold standard for brachytherapy dosimetry, Monte Carlo (MC) has yet to be implemented into a software for brachytherapy treatment planning. The purpose of this work is to present RapidBrachyMCTPS, a novel treatment planning system (TPS) for brachytherapy applications equipped with a graphical user interface (GUI), optimization tools and a Geant4-based MC dose calculation engine, RapidBrachyMC. Brachytherapy sources and applicators were implemented in RapidBrachyMC and made available to the user via a source and applicator library in the GUI. To benchmark RapidBrachyMC, TG-43 parameters were calculated for the microSelectron v2 (192Ir) and SelectSeed (125I) source models and were compared against previously validated MC brachytherapy codes. The performance of RapidBrachyMC was evaluated for a prostate high dose rate case. To assess the accuracy of RapidBrachyMC in a heterogeneous setup, dose distributions with a cylindrical shielded/unshielded applicator were validated against film measurements in a Solid WaterTM phantom. TG-43 parameters calculated using RapidBrachyMC generally agreed within 1%-2% of the results obtained in previously published work. For the prostate case, clinical dosimetric indices showed general agreement with Oncentra TPS within 1%. Simulation times were on the order of minutes on a single core to achieve uncertainties below 2% in voxels within the prostate. The calculation time was decreased further using the multithreading features of Geant4. In the comparison between MC-calculated and film-measured dose distributions, at least 95% of points passed the 3%/3 mm gamma index criteria in all but one case. RapidBrachyMCTPS can be used as a post-implant dosimetry toolkit, as well as for MC-based brachytherapy treatment planning. This software is especially well suited for the development of new source and applicator models.

Pulmonary ventilation imaging in asthma and cystic fibrosis using oxygen-enhanced 3D radial ultrashort echo time MRI.

BACKGROUND: A previous study demonstrated the feasibility of using 3D radial ultrashort echo time (UTE) oxygen-enhanced MRI (UTE OE-MRI) for functional imaging of healthy human lungs. The repeatability of quantitative measures from UTE OE-MRI needs to be established prior to its application in clinical research. PURPOSE: To evaluate repeatability of obstructive patterns in asthma and cystic fibrosis (CF) with UTE OE-MRI with isotropic spatial resolution and full chest coverage. STUDY TYPE: Volunteer and patient repeatability. POPULATION: Eighteen human subjects (five asthma, six CF, and seven normal subjects). FIELD STRENGTH/SEQUENCE: Respiratory-gated free-breathing 3D radial UTE (80 µs) sequence at 1.5T. ASSESSMENT: Two 3D radial UTE volumes were acquired sequentially under normoxic and hyperoxic conditions. A subset of subjects underwent repeat acquisitions on either the same day or ≤15 days apart. Asthma and CF subjects also underwent spirometry. A workflow including deformable registration and retrospective lung density correction was used to compute 3D isotropic percent signal enhancement (PSE) maps. Median PSE (MPSE) and ventilation defect percent (VDP) of the lung were measured from the PSE map. STATISTICAL TESTS: The relations between MPSE, VDP, and spirometric measures were assessed using Spearman correlations. The test-retest repeatability was evaluated using Bland-Altman analysis and intraclass correlation coefficients (ICC). RESULTS: Ventilation measures in normal subjects (MPSE = 8.0%, VDP = 3.3%) were significantly different from those in asthma (MPSE = 6.0%, P = 0.042; VDP = 21.7%, P = 0.018) and CF group (MPSE = 4.5%, P = 0.0006; VDP = 27.2%, P = 0.002). MPSE correlated significantly with forced expiratory lung volume in 1 second percent predicted (ρ = 0.72, P = 0.017). The ICC of the test-retest VDP and MPSE were both ≥0.90. In all subject groups, an anterior/posterior gradient was observed with higher MPSE and lower VDP in the posterior compared to anterior regions (P ≤ 0.0021 for all comparisons). DATA CONCLUSION: 3D radial UTE OE-MRI supports quantitative differentiation of diseased vs. healthy lungs using either whole lung VDP or MPSE with excellent test-retest repeatability. LEVEL OF EVIDENCE: 2 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2018;47:1287-1297.