Immune Response following FLASH and Conventional Radiation in Diffuse Midline Glioma.

PURPOSE: Diffuse midline glioma (DMG) is a fatal tumor traditionally treated with radiation therapy (RT) and previously characterized as having a noninflammatory tumor immune microenvironment (TIME). FLASH is a novel RT technique using ultra-high dose rate that is associated with decreased toxicity and effective tumor control. However, the effect of FLASH and conventional (CONV) RT on the DMG TIME has not yet been explored. METHODS AND MATERIALS: Here, we performed single-cell RNA sequencing (scRNA-seq) and flow cytometry on immune cells isolated from an orthotopic syngeneic murine model of brainstem DMG after the use of FLASH (90 Gy/sec) or CONV (2 Gy/min) dose-rate RT and compared to unirradiated tumor (SHAM). RESULTS: At day 4 post-RT, FLASH exerted similar effects as CONV in the predominant microglial (MG) population, including the presence of two activated subtypes. However, at day 10 post-RT, we observed a significant increase in the type 1 interferon α/ß receptor (IFNAR+) in MG in CONV and SHAM compared to FLASH. In the non-resident myeloid clusters of macrophages (MACs) and dendritic cells (DCs), we found increased type 1 interferon (IFN1) pathway enrichment for CONV compared to FLASH and SHAM by scRNA-seq. We observed this trend by flow cytometry at day 4 post-RT in IFNAR+ MACs and DCs, which equalized by day 10 post-RT. DMG control and murine survival were equivalent between RT dose rates. CONCLUSIONS: Our work is the first to map CONV and FLASH immune alterations of the DMG TIME with single-cell resolution. Although DMG tumor control and survival were similar between CONV and FLASH, we found that changes in immune compartments differed over time. Importantly, although both RT modalities increased IFN1, we found that the timing of this response was cell-type and dose-rate dependent. These temporal differences, particularly in the context of tumor control, warrant further study.

Comparison of first-line radiosurgery for small-cell and non-small cell lung cancer brain metastases (CROSS-FIRE).

INTRODUCTION: Historical reservations regarding stereotactic radiosurgery (SRS) for small-cell lung cancer (SCLC) brain metastases include concerns for short-interval and diffuse central nervous system (CNS) progression, poor prognoses, and increased neurological mortality specific to SCLC histology. We compared SRS outcomes for SCLC and non-small cell lung cancer (NSCLC) where SRS is well established. METHODS: Multicenter first-line SRS outcomes for SCLC and NSCLC from 2000 to 2022 were retrospectively collected (n = 892 SCLC, n = 4785 NSCLC). Data from the prospective Japanese Leksell Gamma Knife Society (JLGK0901) clinical trial of first-line SRS were analyzed as a comparison cohort (n = 98 SCLC, n = 814 NSCLC). Overall survival (OS) and CNS progression were analyzed using Cox proportional hazard and Fine-Gray models, respectively, with multivariable adjustment for cofactors including age, sex, performance status, year, extracranial disease status, and brain metastasis number and volume. Mutation-stratified analyses were performed in propensity score-matched retrospective cohorts of epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) positive NSCLC, mutation-negative NSCLC, and SCLC. RESULTS: OS was superior for patients with NSCLC compared to SCLC in the retrospective dataset (median OS = 10.5 vs 8.6 months; P < .001) and in the JLGK0901 dataset. Hazard estimates for first CNS progression favoring NSCLC were similar in both datasets but reached statistical significance in the retrospective dataset only (multivariable hazard ratio = 0.82, 95% confidence interval = 0.73 to 0.92, P = .001). In the propensity score-matched cohorts, there were continued OS advantages for NSCLC patients (median OS = 23.7 [EGFR and ALK positive NSCLC] vs 13.6 [mutation-negative NSCLC] vs 10.4 months [SCLC], pairwise P values < 0.001), but no statistically significant differences in CNS progression were observed in the matched cohorts. Neurological mortality and number of lesions at CNS progression were similar for NSCLC and SCLC patients. Leptomeningeal progression was increased in patients with NSCLC compared to SCLC in the retrospective dataset only (multivariable hazard ratio = 1.61, 95% confidence interval = 1.14 to 2.26, P = .007). CONCLUSIONS: After SRS, SCLC histology was associated with shorter OS compared to NSCLC. CNS progression occurred earlier in SCLC patients overall but was similar in patients matched on baseline factors. SCLC was not associated with increased neurological mortality, number of lesions at CNS progression, or leptomeningeal progression compared to NSCLC. These findings may better inform clinical expectations and individualized decision making regarding SRS for SCLC patients.

Parent Perception of Child's Behavior during the Initial Dental Visit among Children with Autism Spectrum Disorder: A Cross Sectional Study.

(1) Background: The purpose of this study was to evaluate parent perception of behavior and level of cooperation to determine the success of a dental appointment with a child with autism spectrum disorder (ASD). (2) Methods: pre-treatment form, task analysis (TAS), and Frankl scale scores were extracted from patient charts. Values were calculated for patient demographics and other health characteristics (N = 235). Regression models were constructed to examine the success level during the first dental appointment (measured by TAS and Frankl scores) by several factors. (3) Results: The model to test patient characteristics: age, gender, ethnicity, and verbal communication, Hispanic ethnicity significantly predicted the TAS score, F (4, 191) = 2.45, p = 0.03 [95% CI -17.18, -3.53], and age significantly predicted the Frankl score, F (4, 194) = 5.17, p = 0.00 [95% CI 0.04, 0.12]. There was a significant association between parent perception of behavior and Frankl scores, F (2, 202) = 7.68, p = 0.00 [ 95% CI -0.11, -0.02]. (4) Conclusion: The results indicate that ethnicity and age play a role in successful outcomes during the dental appointment. Additionally, parent perception of their child's behavior significantly predicted the Frankl score, thus coordinating with parents during the dental appointment can be a key factor in treatment planning for productive dental visits.

A naturalistic study of brushing patterns using powered toothbrushes.

Dental caries and periodontal disease are very common chronic diseases closely linked to inadequate removal of dental plaque. Powered toothbrushes are viewed as more effective at removing plaque; however, the conflicting evidence and considerable unexplained heterogeneity in their clinical outcomes does not corroborate the relative merits of powered tooth brushing. To explain the heterogeneity of brushing patterns with powered toothbrushes, we conducted a observational study of tooth brushing practices of 12 participants in their naturalistic setting. Integrated brush sensors and a digital data collection platform allowed unobtrusive and accurate capture of habitual brushing patterns. Annotated brushing data from 10 sessions per participant was chosen for scrutiny of brushing patterns. Analysis of brushing patterns from the total 120 sessions revealed substantial between- and within-participant variability in brushing patterns and efficiency. Most participants (91.67%) brushed for less than the generally prescribed two minutes; individual participants were also inconsistent in brushing duration across sessions. The time devoted to brushing different dental regions was also quite unequal. Participants generally brushed their buccal tooth surfaces more than twice as long as the occlusal (2.18 times longer (95% CI 1.42, 3.35; p < 0.001)) and lingual surfaces (2.22 times longer (95% CI 1.62, 3.10; p < 0.001); the lingual surfaces of the maxillary molars were often neglected (p < 0.001). Participants also varied in the epochs of excessive brushing pressure and the regions to which they were applied. In general, the occlusal surfaces were more likely to be brushed with excessive pressure (95% CI 0.10, 0.98; p = 0.015). Our study reveals that users of powered toothbrushes vary substantially in their use of the toothbrushes and diverge from recommended brushing practices. The inconsistent brushing patterns, between and within individuals, can affect effective plaque removal. Our findings underscore the limited uptake of generic oral self-care recommendations and emphasize the need for personalized brushing recommendations that derive from the objective sensor data provided by powered toothbrushes.

Extensions to the Proximal Distance Method of Constrained Optimization.

The current paper studies the problem of minimizing a loss f(x) subject to constraints of the form Dx ∈ S, where S is a closed set, convex or not, and D is a matrix that fuses parameters. Fusion constraints can capture smoothness, sparsity, or more general constraint patterns. To tackle this generic class of problems, we combine the Beltrami-Courant penalty method of optimization with the proximal distance principle. The latter is driven by minimization of penalized objectives f(x)+ρ2dist(Dx,S)2 involving large tuning constants ρ and the squared Euclidean distance of Dx from S. The next iterate xn+1 of the corresponding proximal distance algorithm is constructed from the current iterate xn by minimizing the majorizing surrogate function f(x)+ρ2‖Dx-𝒫S(Dxn)‖2. For fixed ρ and a subanalytic loss f(x) and a subanalytic constraint set S, we prove convergence to a stationary point. Under stronger assumptions, we provide convergence rates and demonstrate linear local convergence. We also construct a steepest descent (SD) variant to avoid costly linear system solves. To benchmark our algorithms, we compare their results to those delivered by the alternating direction method of multipliers (ADMM). Our extensive numerical tests include problems on metric projection, convex regression, convex clustering, total variation image denoising, and projection of a matrix to a good condition number. These experiments demonstrate the superior speed and acceptable accuracy of our steepest variant on high-dimensional problems. Julia code to replicate all of our experiments can be found at https://github.com/alanderos91/ProximalDistanceAlgorithms.jl.

Developing a Descriptive Sensory Characterization of Flour Tortilla Applying Flash Profile.

For any food, it is important to know consumption, preference, and the characteristics as quality parameters that are important to consumers of a product. The descriptive methodologies are an important tool to know the quality attributes of the products. Within these methodologies is the flash profile (FP), which is based on the generation of the distinctive attributes of the products without any expensive and time-consuming training sessions. The aim of this research was to study the consumption and preference of flour tortillas by consumers and to develop the descriptive characterization of the tortillas by using the flash profile method. The wheat flour tortillas used were two commercial and two handcrafted samples. Ten experienced panelists participated as the FP panel. The panelists generated 22 descriptors, six for texture, seven for appearance, five for odor, and four for flavor. These descriptors differentiate the samples of the flour tortillas. The panelists' performance was assessed using the consensus index (Rc = 0.508). The first two dimensions of the Generalized Procrustes Analysis represent 83.78% of the data variability. Flash profile proved to be an easy and rapid technique that allowed the distinctive attributes of flour tortillas to be obtained.

Exploiting Radiation Therapy to Restore Immune Reactivity of Glioblastoma.

Glioblastoma (GBM) is among the most aggressive of brain tumors and confers a dismal prognosis despite advances in surgical technique, radiation delivery methods, chemotherapy, and tumor-treating fields. While immunotherapy (IT) has improved the care of several adult cancers with previously dismal prognoses, monotherapy with IT in GBM has shown minimal response in first recurrence. Recent discoveries in lymphatics and evaluation of blood brain barrier offer insight to improve the use of ITs and determine the best combinations of therapies, including radiation. We highlight important features of the tumor immune microenvironment in GBM and potential for combining radiation and immunotherapy to improve prognosis in this devastating disease.

Extending Shelf-Life and Quality of Minimally Processed Golden Delicious Apples with Three Bioactive Coatings Combined with Cinnamon Essential Oil.

The application of coatings with essential oils for food preservation is an alternative way to keep minimally processed apple slices fresh, nutritious, safe, sensory palatable, and accessible for consumers. In the present study, the effect of three bioactive coatings on quality variables of minimally processed Golden Delicious apple slices for 25-days at 4 °C was evaluated. The coatings were CT1-chitosan-based, CT2-guar gum-based, and CT3-composite guar gum-starch-based; all three coatings contained cinnamon essential oil and were compared with UCT0-uncoated apple slices. The quality variables evaluated were weight-loss, firmness, browning index, total phenolic content, total soluble solids, titratable acidity, respiration rate, microbial analysis, and sensory evaluation. All coatings improved the preservation and sensorial quality variables of Golden Delicious apples; however, although the CT1-chitosan-based coating was capable of extending the shelf-life of minimally processed apple, it demonstrated less sensorially favorable scores for flavor, odor, and overall acceptance attributes.

Bioactive Protecting Coating of Guar Gum with Thyme Oil to Extend Shelf Life of Tilapia (Oreoschromis niloticus) Fillets.

Edible coatings are safe, legal, and sensory acceptable for food applications and they can be incorporated as natural additives due to their antimicrobial activity, thickening capacity, nutrient content, and bioactive agents for protecting seafood from physical, chemical, and microbiological damage that affects its shelf-life. This study aimed to evaluate the effect of the guar gum bioactive coating with thyme oil on the quality of tilapia fish fillets for 15 days of storage at 4 °C, as a means to extend shelf-life. pH, moisture, ash, fat, color, thiobarbituric acid reactive substances (TBARS), total volatile basic nitrogen (TVB-N), microbiological, and sensory examinations were investigated, and the results were analyzed by analysis of variance. The treatments were control (uncoated, UC), GGC (coated with guar gum, GGC), and guar gum combined with thyme oil (GGCTH). Tilapia fillets were stored at 4 °C, the safe temperature for refrigerated storage for 15 days. GGCTH had a slower increase of pH after 15 days of storage in comparison with GGC and UC (p < 0.05). GGC and GGCTH resulted in lower and lowest lightness (L*; p < 0.05) values, lower and lowest redness (a*; p < 0.01) values, and greater and greatest yellowness (b*; p < 0.05) values compared to UC, respectively. UC reduced shear force at 5 (0.37 kgf), 10 (0.32 kgf), and 15 (0.30 kgf) days post-storage in comparison with GGC (0.43, 0.43, and 0.43 kgf) and GGCTH (0.43, 0.44, and 0.44 kgf), respectively. There was less (p < 0.05) deterioration, as well as differences in textural and sensorial variables between uncoated and coated fish fillets. The microbiological analyses demonstrated that there was greater microbial growth in the uncoated fillets than in the coated ones. It was concluded that this bioactive coating with thyme oil retards microbial colonization of fish and reduces degradability of quality variables, therefore, it is a reliable and effective alternative to extend the shelf-life of tilapia fillets.

Modelado estadístico y matemático en la epidemia del coronavirus: algunas consideraciones para minimizar los sesgos en los resultados / Statistical and Mathematical Modeling in the Coronavirus Epidemic: Some Considerations to Minimize Biases in the Results

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Modelado estadístico y matemático en la epidemia del coronavirus: algunas consideraciones para minimizar los sesgos en los resultados / Statistical and Mathematical Modeling in the Coronavirus Epidemic: Some Considerations to Minimize Biases in the Result

No disponible

Adaptive nonparametric regression with the K-nearest neighbour fused lasso.

The fused lasso, also known as total-variation denoising, is a locally adaptive function estimator over a regular grid of design points. In this article, we extend the fused lasso to settings in which the points do not occur on a regular grid, leading to a method for nonparametric regression. This approach, which we call the [Formula: see text]-nearest-neighbours fused lasso, involves computing the [Formula: see text]-nearest-neighbours graph of the design points and then performing the fused lasso over this graph. We show that this procedure has a number of theoretical advantages over competing methods: specifically, it inherits local adaptivity from its connection to the fused lasso, and it inherits manifold adaptivity from its connection to the [Formula: see text]-nearest-neighbours approach. In a simulation study and an application to flu data, we show that excellent results are obtained. For completeness, we also study an estimator that makes use of an [Formula: see text]-graph rather than a [Formula: see text]-nearest-neighbours graph and contrast it with the [Formula: see text]-nearest-neighbours fused lasso.

The development and implementation of a training program for pediatric dentistry residents working with patients diagnosed with ASD in a special needs dental clinic.

Oral health care is the most prevalent unmet health care need among all U.S. children age 17 and under in the U.S., and this includes those with special health care needs (SHCN). Children with SHCN experience unique barriers to receiving oral care including challenging behaviors, inadequate insurance coverage, and a lack of trained dentists. Despite the need for specialized training to successfully provide dental care to children with SHCN, few dental programs offer the necessary educational preparation. The Nova Southeastern University College of Dentistry was funded by the Health Resources and Services Administration to prepare pediatric and Advanced Education in General Dentistry (AEGD) dental residents in the care of children, adolescents, and adults with SHCN. The purpose of this paper is to describe the didactic and clinical training program and to provide data on the program's impact.

Stereotactic body radiotherapy with periprostatic hydrogel spacer for localized prostate cancer: toxicity profile and early oncologic outcomes.

BACKGROUND: Multiple phase I-II clinical trials have reported on the efficacy and safety of prostate stereotactic body radiotherapy (SBRT) for the treatment of prostate cancer. However, few have reported outcomes for prostate SBRT using periprostatic hydrogel spacer (SpaceOAR; Augmenix). Herein, we report safety and efficacy outcomes from our institutional prostate SBRT experience with SpaceOAR placement. METHODS: Fifty men with low- or intermediate-risk prostate cancer treated at a single institution with linear accelerator-based SBRT to 3625 cGy in 5 fractions, with or without androgen deprivation therapy (ADT) were included. All patients underwent SpaceOAR and fiducial marker placement followed by pre-treatment MRI. Toxicity assessments were conducted at least weekly while on treatment, 1 month after treatment, and every follow-up visit thereafter. Post-treatment PSA measurements were obtained 4 months after SBRT, followed by every 3-6 months thereafter. Acute toxicity was documented per RTOG criteria. RESULTS: Median follow up time was 20 (range 4-44) months. Median PSA at time of diagnosis was 7.4 (2.7-19.5) ng/ml. Eighteen men received 6 months of ADT for unfavorable intermediate risk disease. No PSA failures were recorded. Median PSA was 0.9 ng/mL at 20 months; 0.08 and 1.32 ng/mL in men who did and did not receive ADT, respectively. Mean prostate-rectum separation achieved with SpaceOAR was 9.6 ± 4 mm at the prostate midgland. No grade ≥ 3 GU or GI toxicity was recorded. During treatment, 30% of men developed new grade 2 GU toxicity (urgency or dysuria). These symptoms were present in 30% of men at 1 month and in 12% of men at 1 year post-treatment. During treatment, GI toxicity was limited to grade 1 symptoms (16%), although 4% of men developed grade 2 symptoms during the first 4 weeks after SBRT. All GI symptoms were resolving by the 1 month post-treatment assessment and no acute or late rectal toxicity was reported > 1 month after treatment. CONCLUSIONS: Periprostatic hydrogel placement followed by prostate SBRT resulted in minimal GI toxicity, and favorable early oncologic outcomes. These results indicate that SBRT with periprostatic spacer is a well-tolerated, safe, and convenient treatment option for localized prostate cancer.

Travel distance and stereotactic body radiotherapy for localized prostate cancer.

BACKGROUND: Definitive stereotactic body radiotherapy (SBRT) represents an emerging and debated treatment option for patients with prostate cancer, with potential economic savings and reports of short-term efficacy since 2006. The current study sought to define national trends in definitive prostate SBRT use and determine whether patterns vary by travel distance for treatment. METHODS: The National Cancer Data Base identified 181,544 men with localized prostate cancer who were treated with definitive external beam radiotherapy from 2004 through 2012. Joinpoint regression analyzed definitive prostate SBRT trends over time, whereas multivariable logistic regression defined the odds for its receipt by travel distance for treatment. RESULTS: Definitive prostate SBRT use increased from 1.8% in 2004 to 5.9% in 2012 (P for trend <.0001), with a joinpoint for increased use noted in 2006 (P<.0001). Higher SBRT use was found to be associated with longer travel distance for treatment, younger age, white race, more affluent zip code of residence, academic treatment center, favorable disease characteristics, and fewer comorbidities (all P<.0001). Compared with travel distances <25 miles for treatment, travel distances of 25 to 50 miles and >50 miles were associated with increasing adjusted odds of receipt of definitive prostate SBRT (1.63 [95% confidence interval, 1.51-1.76] and 2.35 [95% confidence interval, 2.14-2.57], respectively; both P < .0001). CONCLUSIONS: Definitive prostate SBRT use increased more than 3-fold since 2004, with a significant increase in use coinciding with early reports of short-term efficacy. Long-distance travel for treatment was associated with greater than twice the odds of receipt of definitive prostate SBRT compared with short-distance travel, suggesting that treatment decisions with unknown long-term clinical implications may be strongly driven by sociodemographic factors. Cancer 2018;124:1141-9. © 2017 American Cancer Society.

A side-by-side comparison of T cell reactivity to fifty-nine Mycobacterium tuberculosis antigens in diverse populations from five continents.

We compared T cell recognition of 59 prevalently recognized Mycobacterium tuberculosis (MTB) antigens in individuals latently infected with MTB (LTBI), and uninfected individuals with previous BCG vaccination, from nine locations and populations with different HLA distribution, MTB exposure rates, and standards of TB care. This comparison revealed similar response magnitudes in diverse LTBI and BCG-vaccinated cohorts and significant correlation between responses in LTBIs from the USA and other locations. Many antigens were uniformly recognized, suggesting suitability for inclusion in vaccines targeting diverse populations. Several antigens were similarly immunodominant in LTBI and BCG cohorts, suggesting applicability for vaccines aimed at boosting BCG responses. The panel of MTB antigens will be valuable for characterizing MTB-specific CD4 T cell responses irrespective of ethnicity, infecting MTB strains and BCG vaccination status. Our results illustrate how a comparative analysis can provide insight into the relative immunogenicity of existing and novel vaccine candidates in LTBIs.

Loss of parietal cell superoxide dismutase leads to gastric oxidative stress and increased injury susceptibility in mice.

Mitochondrial superoxide dismutase (SOD2) prevents accumulation of the superoxide that arises as a consequence of oxidative phosphorylation. However, SOD2 is a target of oxidative/nitrosative inactivation, and reduced SOD2 activity has been demonstrated to contribute to portal hypertensive gastropathy. We investigated the consequences of gastric parietal cell-specific SOD2 deficiency on mitochondrial function and gastric injury susceptibility. Mice expressing Cre recombinase under control of the parietal cell Atpase4b gene promoter were crossed with mice harboring loxP sequences flanking the sod2 gene (SOD2 floxed mice). Cre-positive mice and Cre-negative littermates (controls) were used in studies of SOD2 expression, parietal cell function (ATP synthesis, acid secretion, and mitochondrial enzymatic activity), increased oxidative/nitrosative stress, and gastric susceptibility to acute injury. Parietal cell SOD2 deficiency was accompanied by a 20% (P < 0.05) reduction in total gastric SOD activity and a 93% (P < 0.001) reduction in gastric SOD2 activity. In SOD2-deficient mice, mitochondrial aconitase and ATP synthase activities were impaired by 36% (P < 0.0001) and 44% (P < 0.005), respectively. Gastric tissue ATP content was reduced by 34% (P < 0.002). Basal acid secretion and peak secretagogue (histamine)-induced acid secretion were reduced by 43% (P < 0.0001) and 40% (P < 0.0005), respectively. There was a fourfold (P < 0.02) increase in gastric mucosal apoptosis and 41% (P < 0.001) greater alcohol-induced gastric damage in the parietal cell SOD2-deficient mice. Our findings indicate that loss of parietal cell SOD2 leads to mitochondrial dysfunction, resulting in perturbed energy metabolism, impaired parietal cell function, and increased gastric mucosal oxidative stress. These alterations render the gastric mucosa significantly more susceptible to acute injury.