IRF8-driven reprogramming of the immune microenvironment enhances anti-tumor adaptive immunity and reduces immunosuppression in murine glioblastoma.

Background: Glioblastoma (GBM) has a highly immunosuppressive tumor immune microenvironment (TIME), largely mediated by myeloid-derived suppressor cells (MDSCs). Here, we utilized a retroviral replicating vector (RRV) to deliver Interferon Regulatory Factor 8 (IRF8), a master regulator of type 1 conventional dendritic cell (cDC1) development, in a syngeneic murine GBM model. We hypothesized that RRV-mediated delivery of IRF8 could "reprogram" intratumoral MDSCs into antigen-presenting cells (APCs) and thereby restore T-cell responses. Methods: Effects of RRV-IRF8 on survival and tumor growth kinetics were examined in the SB28 murine GBM model. Immunophenotype was analyzed by flow cytometry and gene expression assays. We assayed functional immunosuppression and antigen presentation by ex vivo T-cell-myeloid co-culture. Results: Mice with RRV-IRF8 pre-transduced intracerebral tumors had significantly longer survival and slower tumor growth compared to controls. RRV-IRF8 treated tumors exhibited significant enrichment of cDC1s and CD8+ T-cells. Additionally, myeloid cells derived from RRV-IRF8 tumors showed decreased expression of the immunosuppressive markers Arg1 and IDO1 and demonstrated reduced suppression of naïve T-cell proliferation in ex vivo co-culture, compared to controls. Furthermore, DCs from RRV-IRF8 tumors showed increased antigen presentation compared to those from control tumors. In vivo treatment with azidothymidine (AZT), a viral replication inhibitor, showed that IRF8 transduction in both tumor and non-tumor cells is necessary for survival benefit, associated with a reprogrammed, cDC1- and CD8 T-cell-enriched TIME. Conclusions: Our results indicate that reprogramming of glioma-infiltrating myeloid cells by in vivo expression of IRF8 may reduce immunosuppression and enhance antigen presentation, achieving improved tumor control.

Crop cover and nutrient levels mediate the effects of land management type on aquatic invertebrate richness in prairie potholes.

Aquatic invertebrates provide important ecosystem services, including decomposition and nutrient cycling, and provide nutrition for birds, fish, amphibians, and bats. Thus, the effects of agricultural land management practices on aquatic invertebrates are relevant to farmers, wildlife biologists, and policymakers. Here, we used data on aquatic invertebrates (159 taxa, 73 to species, 75 to genus/family) collected in 40 wetlands in the Canadian prairies to test for direct and indirect relationships among land management types (perennial cover, organic, minimum tillage, conventional), landscape structure (cropland and wetland cover within the surrounding landscape), and water quality (total nutrient levels, turbidity) on species richness of invertebrates using structural equation modelling. Additionally, we assessed variation in community composition within and among wetlands in different land use management types using a direct gradient analysis and variance partitioning. The direct effects of land management type were not supported but we found strong supportive evidence that effects of land management on richness were significantly mediated through cropland cover, nutrient levels, and turbidity. After controlling for these indirect effects, aquatic invertebrate richness decreased along a gradient from the lowest to the highest farming intensity, i.e., richness decreased from perennial cover sites to organic to minimum tillage to conventional sites. Support was also found for negative effects of nutrient levels and turbidity on richness. We did not find significant support for differences in gamma diversity or a simple test (homogeneity of multivariate dispersions) of differences in turnover among land management types; however, land management had a significant effect in distance-based redundancy analysis. Taken together, these results suggest that focusing conservation efforts on reducing cropland erosion and nutrient inputs to wetlands and creating more permanent cover may be effective strategies for conserving richness of aquatic invertebrates in agricultural landscapes in this region.

On the Belatedness of Psychoanalytic Clinical Writing.

The belatedness of analytic writing and its effects on analytic processes are explored through the concepts of nachträglichkeit and thirdness. The temporal gap between being with and writing about functions as a meaningful pause filled with opportunities for investigating unconscious pathways to the analyst's countertransference. The significance of analytic narration in affecting specific psychoanalytic developments is explored. The theoretical framework utilizes the concept of après coup, which brings to light new meanings in an afterwardness of time. Aspects of analytical writing dynamics are discussed as equivalent to those of nachträglichkeit. Analysts also deploy thirdness in constructing presentations of clinical material. This could be an intrapsychic third or an external figure representing an internal introjected third. A clinical vignette demonstrates the enhanced understanding achieved by writing. It specifically assisted in exploring the analyst's enactment relating to change in the setting, the background for which was a move to online analysis. This evoked infantile anxieties and painful confusions about loss. Historically, the patient had to navigate a path through miasmic ambiguities between reality and phantasy, truths and lies. A conclusion is reached, arguing that analytic processes extend beyond the duration of sessions, and that the processes of clinical writing can provide a significant contribution.

Examining the Family-Centeredness of Speech-Language Pathologists Working With Children Who Use Augmentative and Alternative Communication.

PURPOSE: Family-professional partnerships are important for youth learning to use aided augmentative and alternative communication (AAC). This study examined the family-oriented beliefs and practices of speech-language pathologists (SLPs) working with preschool and school-aged children learning to use aided AAC (aged 3-21 years), specifically during the COVID-19 pandemic. METHOD: Participants were 25 SLPs who participated in an individual semistructured interview. Qualitative analysis was used to identify and describe groups of SLPs based on commonalities and differences in their beliefs and practices working with families. The characteristics of SLPs in each group was also explored descriptively (e.g., race/ethnicity, work setting, caseload). RESULTS: SLPs clustered into three groups based on their beliefs and practices: (a) professionally centered, (b) family-allied, and (c) family-focused. SLPs varied across these groups in how they planned services, offered training/coaching, communicated, shared resources, offered emotional support, and adapted to and with different families. CONCLUSIONS: Findings indicate the need to support greater family-centeredness in AAC services by building on the strengths of SLPs in the field. Promoting strong family-professional partnerships could in turn improve outcomes for students who use AAC. SUPPLEMENTAL MATERIAL: https://doi.org/10.23641/asha.25044125.

Associations between patient-reported functional disability and measures of physical ability in juvenile fibromyalgia.

ABSTRACT: Juvenile fibromyalgia (JFM) is a chronic condition characterized by symptoms of pain and fatigue and is associated with sedentary behavior and functional disability. Adults with fibromyalgia exhibit deficits in physical fitness as evidenced by lower aerobic capacity and physical endurance, but it is unknown whether these impairments are apparent in adolescents with JFM. Furthermore, the extent to which functional disability and pain interference relate to measures of physical fitness has not been investigated in a pediatric pain population. During a baseline assessment for a clinical trial, 321 adolescents with juvenile fibromyalgia (M age = 15.14, 85.2% female) completed measures of pain intensity, fatigue, JFM symptom severity, functional disability, and pain interference. They also completed 2 validated fitness tasks: (1) the Harvard step test, which assesses aerobic fitness, and (2) the 6-minute walk test, a simple submaximal test of endurance. We examined associations among self-report measures and fitness assessments using bivariate correlations. We then employed hierarchical regression analyses to determine the unique contributions of physical fitness assessments to self-reported functional disability and pain interference. Results indicated that youth with JFM exhibited deficits in aerobic capacity and physical endurance. However, physical fitness explained negligible variance in functional disability and pain interference beyond that accounted for by pain, fatigue, and JFM symptom severity. Scores on available functional disability measures may reflect perceived difficulties in coping with symptoms during physical tasks rather than actual physical capability. Rigorous and sensitive assessments of physical fitness and endurance are needed to determine whether rehabilitation interventions for pediatric pain improve physical functioning.

Augmentative and Alternative Communication Services During the COVID-19 Pandemic: Contextual Determinants of the Parent-Speech-Language Pathologist Partnership.

PURPOSE: The COVID-19 pandemic caused significant changes for family-professional interactions. Many services shifted to telepractice, with new opportunities for parents and speech-language pathologists (SLPs) to partner for service delivery. Parent-coached models of augmentative and alternative communication (AAC) intervention provide positive outcomes for children; however, SLPs have reported difficulty building strong partnerships with families. The shift to telepractice during the COVID-19 pandemic provided a unique context to examine factors influencing parent-SLP partnerships, particularly for parents with children who use aided AAC. METHOD: Twenty-five parents and 25 SLPs who engaged in services with children and youth from 3 to 21 years of age who used aided AAC during the initial stages of the COVID-19 pandemic in June 2020 participated. Semistructured interviews were conducted individually with parents and SLPs to understand perspectives on whether the change in service delivery facilitated or hindered family-oriented practice. Inductive qualitative analysis was used to analyze information about the factors impacting parent-SLP partnerships. RESULTS: The parent-SLP partnership was influenced by setting and systemic determinants, and intrinsic determinants to the parent and the SLP that included their history and rapport, beliefs about partnering, and knowledge and skills. These determinants served as barriers or facilitators to their partnership. CONCLUSIONS: It is essential to consider the relationship, expectations, and knowledge and skills that SLPs and parents bring to the partnership, along with extrinsic structural factors that can impact this partnership. Positive rapport, valued partnership, and an openness to sharing knowledge through teaming and collaboration provided for positive parent-SLP partnerships.

Field Resistance to Rose Rosette Disease as Determined by Multi-Year Evaluations in Tennessee and Delaware.

Rose rosette disease (RRD) caused by the rose rosette emaravirus (RRV) and transmitted by the eriophyid mite Phyllocoptes fructiphilus (Pf), both native to North America, has caused significant damage to roses over the last several decades. As cultural and chemical control of this disease is difficult and expensive, a field trial was established to systematically screen rose germplasm for potential sources of resistance. One hundred and eight rose accessions representing the diversity of rose germplasm were planted in Tennessee and Delaware, managed to encourage disease development, and evaluated for symptom development and viral presence for three years. All major commercial rose cultivars were susceptible to this viral disease to varying levels. The rose accessions with no or few symptoms were species accessions from the sections Cinnamomeae, Carolinae, Bracteatae, and Systylae or hybrids with these. Among these, some were asymptomatic; they displayed no symptoms but were infected by the virus. Their potential depends on their ability to serve as a source of viruses. The next step is to understand the mechanism of resistance and genetic control of the various sources of resistance identified.

Direct and indirect effects of agricultural land cover on avian biodiversity in eastern Canada.

Agriculture is one of the largest threats to global biodiversity. However, most studies have focused only on the direct effects of agriculture on biodiversity, and few have addressed the indirect effects, potentially over or under-estimating the overall impacts of agriculture on biodiversity. The indirect effect is the response not to the agricultural cover types or operations per se, but instead, to the way that agriculture influences the extent and configuration of different types of natural land cover in the landscape. We used structural equation modelling (SEM) to evaluate the direct, indirect, and total effects of agriculture on species richness of three bird guilds: forest birds, shrub-edge birds, and open country birds. We found that forest bird richness was driven by the negative indirect effect of cropland via forest loss. Shrub-edge and open country bird richness increased with the amount of agriculture land covers; however, importantly, we found negative indirect effects of agriculture on both guilds via a reduction in more natural land covers. This latter result highlights how we would have over-estimated the positive effects of agriculture on shrub-edge and open country bird richness had we not measured both direct and indirect effects (i.e., the total effect size is less than the direct effect size). Overall, our results suggest that a bird-friendly agricultural landscape in our region would have forest that is configured to maximize forest edge, and a high proportion of perennial forage within the agricultural portion of the landscape. Supplementary Information: The online version contains supplementary material available at 10.1007/s10531-023-02559-1.

Intrinsic and extrinsic factors contributing to running-related lower limb injuries among adolescent runners.

The purpose of this study was to assess which combination of intrinsic and extrinsic factors contribute to running-related injury (RRI)among adolescent cross-country, track, and long-distance runners. We conducted a retrospective study at a hospital-affiliated sports injury prevention centre of 130 adolescent runners (F: 62.1%, M: 37.9%; cross-country: 34.1%, track: 56.1%, long-distance running: 9.8%) who underwent an Injury Prevention Evaluation between 2013 and 2021. The evaluation included a questionnaire on personal and training factors, and standardised physical assessments. We used a binomial logistic regression to assess the influence of demographics, lower extremity strength and alignment, training (running volume and intensity, weight training), and dietary factors on RRIs. There were 38 adolescent runners who reported RRIs (ankle sprains: N = 16, shin splints: N = 9, stress fractures: N = 13). Female sex (odds ratio [OR]: 4.58 [1.37, 15.37]; p = 0.01), reduced weekday hours of sleep (OR: 1.75 [1.04, 2.95]; p = 0.04), reduced hip abduction strength (OR: 1.02 [1.00, 1.04]; p = 0.05), and intention to lose weight to improve athletic performance (OR: 4.58 [1.00, 21.28]; p = 0.05) were associated with RRIs. These intrinsic and extrinsic risk factors may represent targets for injury prevention for adolescent runners.

A Comparison of Factors Associated with Running-Related Injuries between Adult and Adolescent Runners.

Background: There are multiple personal and environmental factors that influence the risk of developing running-related injuries (RRIs). However, it is unclear how these key clinical factors differ between adult and adolescent runners. Purpose: The purpose of this study was to compare anthropometric, training, and self-reported outcomes among adult and adolescent runners with and without lower extremity musculoskeletal RRIs. Study Design: Cross-sectional study. Methods: Questionnaire responses and clinical assessment data were extracted from 38 adult runners (F: 25, M: 13; median age: 23 [range 18-36]) and 91 adolescent runners (F: 56, M: 35; median age: 15 [range 14-16]) who underwent a physical injury prevention evaluation at a hospital-affiliated sports injury prevention center between 2013 and 2021. Participants were sub-grouped into those with (adults: 25; adolescents: 38) and those without (adults: 13; adolescents: 53) a history of self-reported RRIs based on questionnaire responses. Multivariate analyses of covariance (MANCOVA) covarying for gender were conducted to compare outcomes across groups. Results: Adult runners had lower Functional Movement Screen™ (FMS™) scores (mean differences [MD]: -1.4, p=0.01), were more likely to report intentional weight-loss to improve athletic performance (% difference: 33.0%; p:<.001), and more frequently included resistance training into their training routines (% difference: 21.0%, p=0.01) compared to adolescents. Those with a history of RRIs were more likely to report intentional weight-loss compared to uninjured runners (% difference: 21.3; p=0.02) and had shorter single leg bridge durations than those without RRIs (RRI: 57.9±30, uninjured: 72.0±44, p=0.01). Conclusion: The findings indicate that addressing aspects of biomechanics identified by the FMS™ and behaviors of weight loss as an effort to improve performance may represent targets for the prevention of RRIs for adult and adolescent runners, given the association with history of RRIs. Level of Evidence: 3.

Augmentative and alternative communication services during the COVID-19 pandemic: impact on children, their families and service providers.

The closure of schools and healthcare facilities across the United States due to COVID-19 has dramatically changed the way that services are provided to children with disabilities. Little is known about how children who use augmentative and alternative communication (AAC), their families and their service providers have been impacted by these changes. This qualitative study sought to understand the perspectives of parents and speech-language pathologists (SLPs) on how COVID-19 has affected children, families, services providers and the delivery of AAC-related communication services. For the study, 25 parents and 25 SLPs of children who used aided AAC participated in semi-structured interviews, with data analyzed using qualitative thematic analysis. Parents and SLPs highlighted wide disparities in how children have been impacted, ranging from views of children making more progress with communication and language than before the pandemic to worries about regression. A complex system of factors and processes may explain these differences. COVID-19 will have lasting impacts on the lives of children with complex communication needs. This research highlights the crucial role of family-service provider partnerships and access to quality AAC services for children during the pandemic and into the future.

Rose Rosette Disease Resistance Loci Detected in Two Interconnected Tetraploid Garden Rose Populations.

Rose rosette disease (RRD), caused by the Rose rosette emaravirus (RRV), is a major threat to the garden rose industry in the United States. There has been limited work on the genetics of host plant resistance to RRV. Two interconnected tetraploid garden rose F1 biparental mapping populations were created to develop high-quality tetraploid rose linkage maps that allowed the discovery of RRD resistance quantitative trait loci (QTLs) on linkage groups (LGs) 5, 6, and 7. These QTLs individually accounted for around 18-40% of the phenotypic variance. The locus with the greatest effect on partial resistance was found in LG 5. Most individuals with the LG 5 QTL were in the simplex configuration; however, two individuals were duplex (likely due to double reduction). Identification of resistant individuals and regions of interest can help the development of diagnostic markers for marker-assisted selection in a breeding program.

Biomechanical running gait assessments across prevalent adolescent musculoskeletal injuries.

BACKGROUND: While there is substantial information available regarding expected biomechanical adaptations associated with adult running-related injuries, less is known about adolescent gait profiles that may influence injury development. RESEARCH QUESTIONS: Which biomechanical profiles are associated with prevalent musculoskeletal lower extremity injuries among adolescent runners, and how do these profiles compare across injury types and body regions? METHODS: We conducted a cross-sectional study of 149 injured adolescents (110 F; 39 M) seen at a hospital-affiliated injured runner's clinic between the years 2016-2021. Biomechanical data were obtained from 2-dimensional video analyses and an instrumented treadmill system. Multivariate analyses of variance covarying for gender and body mass index were used to compare continuous biomechanical measures, and Chi-square analyses were used to compare categorical biomechanical variables across injury types and body regions. Spearman's rho correlation analyses were conducted to assess the relationship of significant outcomes. RESULTS: Patients with bony injuries had significantly higher maximum vertical ground reaction forces (bony: 1.87 body weight [BW] vs. soft tissue: 1.79BW, p = 0.05), and a higher proportion of runners with contralateral pelvic drop at midstance (χ2 =5.3, p = 0.02). Maximum vertical ground reaction forces and pelvic drop were significantly yet weakly correlated (ρ = 0.20, p = 0.01). Foot strike patterns differed across injured body regions, with a higher proportion of hip and knee injury patients presenting with forefoot strike patterns (χ2 =22.0, p = 0.01). SIGNIFICANCE: These biomechanical factors may represent risk factors for injuries sustained by young runners. Clinicians may consider assessing these gait adaptations when treating injured adolescent patients.

Identification of QTLs for Reduced Susceptibility to Rose Rosette Disease in Diploid Roses.

Resistance to rose rosette disease (RRD), a fatal disease of roses (Rosa spp.), is a high priority for rose breeding. As RRD resistance is time-consuming to phenotype, the identification of genetic markers for resistance could expedite breeding efforts. However, little is known about the genetics of RRD resistance. Therefore, we performed a quantitative trait locus (QTL) analysis on a set of inter-related diploid rose populations phenotyped for RRD resistance and identified four QTLs. Two QTLs were found in multiple years. The most consistent QTL is qRRV_TX2WSE_ch5, which explains approximately 20% and 40% of the phenotypic variation in virus quantity and severity of RRD symptoms, respectively. The second, a QTL on chromosome 1, qRRD_TX2WSE_ch1, accounts for approximately 16% of the phenotypic variation for severity. Finally, a third QTL on chromosome 3 was identified only in the multiyear analysis, and a fourth on chromosome 6 was identified in data from one year only. In addition, haplotypes associated with significant changes in virus quantity and severity were identified for qRRV_TX2WSE_ch5 and qRRD_TX2WSE_ch1. This research represents the first report of genetic determinants of resistance to RRD. In addition, marker trait associations discovered here will enable better parental selection when breeding for RRD resistance and pave the way for marker-assisted selection for RRD resistance.

Augmentative and Alternative Communication Supports for Language and Literacy in Preschool: Considerations for Down Syndrome and Autism Spectrum Disorder.

Children with Down syndrome and children with autism spectrum disorder have a range of speech abilities during preschool that impacts access to both language and literacy instruction. It is the responsibility of the speech-language pathologist to advocate for and provide intervention using augmentative and alternative communication (AAC) through individualized assessment. This article provides a review of the literature supporting the use of AAC during preschool for both language and literacy development in children with Down syndrome and children with autism spectrum disorder who have limited speech. A small scale exploratory report is discussed to highlight differences in early literacy skills found in children in each group. Implications for AAC intervention during preschool to support both language and literacy are discussed.

Clinical development of retroviral replicating vector Toca 511 for gene therapy of cancer.

INTRODUCTION: The use of tumor-selectively replicating viruses is a rapidly expanding field that is showing considerable promise for cancer treatment. Retroviral replicating vectors (RRV) are unique among the various replication-competent viruses currently being investigated for potential clinical utility, because they permanently integrate into the cancer cell genome and are capable of long-term persistence within tumors. RRV can mediate efficient tumor-specific delivery of prodrug activator genes, and subsequent prodrug treatment leads to synchronized cell killing of infected cancer cells, as well as activation of antitumor immune responses. AREAS COVERED: Here we review preclinical studies supporting bench-to-bedside translation of Toca 511, an optimized RRV for prodrug activator gene therapy, the results from Phase I through III clinical trials to date, and potential future directions for this therapy as well as other clinical candidate RRV. EXPERT OPINION: Toca 511 has shown highly promising results in early-stage clinical trials. This vector progressed to a registrational Phase III trial, but the results announced in late 2019 appeared negative overall. However, the median prodrug dosing schedule was not optimal, and promising possible efficacy was observed in some prespecified subgroups. Further clinical investigation, as well as development of RRV with other transgene payloads, is merited.

Comparative accuracy of non-invasive imaging versus right heart catheterization for the diagnosis of pulmonary hypertension: A systematic review and meta-analysis.

BACKGROUND: Right heart catheterization (RHC) is the gold-standard in the diagnosis of pulmonary hypertension (PH) but at the cost of procedure-related complications. We sought to determine the comparative accuracy of RHC versus non-invasive imaging techniques such as computed tomography (CT), magnetic resonance imaging (MRI), and transthoracic echocardiography (TTE). METHODS: Pulmonary hypertension was defined as a mean pulmonary artery pressure (mPAP) of>20 mmHg. Multiple databases were queried for relevant articles. Raw data were pooled using a bivariate model to calculate the measures of diagnostic accuracy and to estimate Hierarchical Summary Receiver Operating Characteristic (HSROC) on Stata 13. RESULTS: A total of 51 studies with a total patient population of 3947 were selected. The pooled sensitivity and specificity of MRI for diagnosing PH was 0.92(95% confidence interval (CI) 0.88-0.96) and 0.86 (95% CI, 0.77-0.95), respectively. The net sensitivities for CT scan and TTE were 0.79 (95% CI 0.72-0.89) and 0.85 (95% CI 0.83-0.91), respectively. The overall specificity was 0.82 (0.76-0.92) for the CT scan and 0.71 (95% CI 0.61-0.84) for TTE. The diagnostic odds ratio (DOR) for MRI was 124 (95% CI 36-433) compared to 30 (95% CI 11-78) and 24 (95% 11-38) for CT scan and TTE, respectively. Chi-squared (x2) test showed moderate heterogeneity on the test for equality of sensitivities and specificities. CONCLUSIONS: MRI has the highest sensitivity and specificity compared to CT and TTE. MRI can potentially serve as a surrogate technique to RHC for the diagnosis of PH.

Playback point counts and N-mixture models suggest higher than expected abundance of the critically endangered blond titi monkey in northeastern Brazil.

Effective management of threatened species requires accurate population size estimation and monitoring. However, reliable population size estimates are lacking for many endangered species. The critically endangered blond titi monkey (Callicebus barbarabrownae) is an endemic primate of the Caatinga biome in Northeastern Brazil. A previous assessment based on presence-only data estimated a minimum population size of 260 mature individuals in 2,636 km2 , and studies based on visual records suggested very low local relative abundance. However, this cryptic species is known to be difficult to visually detect. We played back recordings of C. barbarabrownae loud calls to count the number of responding groups in 34 sampling sites during 9 consecutive days in a 221-km2 study area. Repeated group counts at sites were used in N-mixture models, which account for imperfect detection, to estimate the number of groups in relation to dry forest area and distance to villages. We estimated a total of 91 groups in the study area. Considering the mean number of adults per group as three, we estimated a population of 273 adult individuals, resulting in a density of 2.3 individuals/km2 in the dry forest habitat. Detection probability was four times higher for surveys conducted between sunrise to midmorning than between midmorning to sunset. We also found that C. barbarabrownae abundance increases with increasing dry forest area and increasing distance to the nearest village, indicating the need to promote dry forest restoration in the Caatinga. As our results suggest a larger population of C. barbarabrownae than had been previously estimated for its entire distribution, our results suggest a need for similar assessments in other areas to reliably estimate the total population size. This study demonstrates how playback surveys coupled with N-mixture models can be used to estimate population sizes of acoustically-responsive primates, and thus contribute to more effective conservation management.