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Effective recruitment and retention strategies of teachers remain elusive for school districts. This study examines the pilot implementation of a year-long teacher residency program throughout four high-needs districts. This program embeds eight residents in these schools and provides various teacher preparation supports to support these beginning professionals to sustain within the classroom. We interview district administrators about their recruitment and retention efforts, and then document how the teacher residents experienced these structures throughout their residency year. Findings have implications for improving this innovative and increasingly implemented teacher pipeline structure towards raising the quality and diversifying the workforce.

Purpose: This study explored the relation between therapy group size and language outcomes for children receiving school-based language therapy through an implementation science lens. Method: Data for the current study were gathered as part of the Speech-Language Therapy Experiences in Public Schools study. Participants included 273 English-speaking kindergarten through second-grade children with language impairment receiving business-as-usual therapy on the caseloads of 75 speech-language pathologists. Data were collected over an academic year, including weekly therapy logs, speech-language pathology questionnaires, and pre-- and post--language measures. Results: Descriptive analysis revealed that children primarily experienced small-group therapy sessions (two to four children); however, there was considerable variability in group size. Hierarchical general linear modeling indicated that caseload size did not explain group size variability. However, the number of student cancellations was positively associated with receipt of large-group sessions. Notably, a significant negative association was found between receipt of large-group sessions (i.e., five to 10 children) and language outcomes. Children who received more than the average number of sessions in large groups (i.e., more than 5% of total sessions) experienced 0.18 SD less language gain over the academic year compared to the mean (0.54 SD). No other group size configurations (i.e., individual, small group, and extra large) yielded significant associations with language outcomes. Conclusions: The findings suggest that young children receiving language-based therapy in large groups make substantially fewer language gains over an academic year. These results have considerable implications for educational policy and clinical practice, which are discussed through an implementation science frame.

Parenting and family environment have significant impact on child development, including development of executive function, attention, and self-regulation, and may affect the risk of developmental disorders including attention-deficit/hyperactivity disorder (ADHD). This paper examines the relationship of parenting and family environment factors with ADHD. A systematic review of the literature was conducted in 2014 and identified 52 longitudinal studies. A follow-up search in 2021 identified 7 additional articles, for a total of 59 studies that examined the association of parenting factors with ADHD outcomes: ADHD overall (diagnosis or symptoms), ADHD diagnosis specifically, or presence of the specific ADHD symptoms of inattention and hyperactivity/impulsivity. For parenting factors that were present in three or more studies, pooled effect sizes were calculated separately for dichotomous or continuous ADHD outcomes, accounting for each study's conditional variance. Factors with sufficient information for analysis were parenting interaction quality (sensitivity/warmth, intrusiveness/reactivity, and negativity/harsh discipline), maltreatment (general maltreatment and physical abuse), parental relationship status (divorce, single parenting), parental incarceration, and child media exposure. All factors showed a significant direct association with ADHD outcomes, except sensitivity/warmth which had an inverse association. Parenting factors predicted diagnosis and overall symptoms as well as inattentive and hyperactive symptoms when measured, but multiple factors showed significant heterogeneity across studies. These findings support the possibility that parenting and family environment influences ADHD symptoms and may affect a child's likelihood of being diagnosed with ADHD. Prevention strategies that support parents, such as decreasing parenting challenges and increasing access to parent training in behavior management, may improve children's long-term developmental health.

ABSTRACT: Innovation around cheese is constant in attempts to meet ever-increasing consumer demands. Retail packaging provides a canvas to communicate to consumers added value from innovations or inherent properties of cheese. Packaging itself may also be the subject of cheese-related innovation. This systematic review of literature organizes research over the past 10 years related to cheese packaging innovation that consumers experience in the marketplace and during consumption of cheese products. The review discusses shipping, displaying cheese at grocery stores, the value of branding, purchasing preferences by demographics, health and nutrition claims, opportunities to highlight protein in cheese, marketing to children, issues of obesity and cheese, diet cheeses, allergens and nondairy or vegan cheese, opening cheese packaging, cutting of cheese, cooking with cheese, eating cheese, the growing trend of snacking and convenience, and flavor preferences. This review provides helpful insights to cheese producers applying findings from research of various styles of cheeses, cheese marketers communicating effectively to consumers, cheese developers designing new products relevant to recent consumer demands, smaller or specialized companies seeking to differentiate their cheese product through available technology and strategy, and cheese lovers or those with hobbies surrounding food wanting to know recent advancements in cheese packaging. This review is a tool for discovering relevant articles related to cheese packaging in a marketplace and consumption setting to guide cheese and cheese packaging and labeling innovation in the United States.

Children may not yet understand political issues or be engaged in politics, but identification with social groups emerges early; indeed, nearly a third of first-graders report identification with a political party. As a result, it is likely that ingroup favoritism (or preference for members of one's own political group) and outgroup derogation (or animus toward members of other political groups) appear sooner than previously assumed. In this article, the author reports on a study that examined whether these attitudes appear as early as pre-adolescence, and if so, how youth affective polarization levels compare to adult levels.

This paper provides an experience report on a co-design approach with teachers to co-create learning analytics-based technology to support problem-based learning in middle school science classrooms. We have mapped out a workflow for such applications and developed design narratives to investigate the implementation, modifications and temporal roles of the participants in the design process. Our results provide precedent knowledge on co-designing with experienced and novice teachers and co-constructing actionable insight that can help teachers engage more effectively with their students' learning and problem-solving processes during classroom PBL implementations.

Recent policy efforts have attempted to increase the number of dual enrollment courses offered within Career and Technical Education (CTE) pathways, and there is evidence to suggest that this practice is widespread. However, there is very little research on student participation in CTE dual enrollment and on its impacts. This study examines participation in the CTE Dual Enrollment Pathway in North Carolina, finding that about 9 percent of North Carolina students participated in CTE dual enrollment courses in eleventh or twelfth grade and disparities in participation among subgroups were less than for college transfer dual enrollment courses. Using a propensity-score weighing approach that compared outcomes for participating students with a weighted group of nonparticipants, the study found that participation in CTE dual enrollment was positively associated with college credits earned in high school, graduation from high school, and overall enrollment in college within one year after high school. The study also examined results by subgroup.

Abstract Background Anopheles melas is an understudied malaria vector with a potential role in malaria transmission on the Bijagós Archipelago of Guinea-Bissau. This study presents the first whole-genome sequencing and population genetic analysis for this species from the Bijagós. To our knowledge, this also represents the largest population genetic analysis using WGS data from non-pooled An. melas mosquitoes. Methods WGS was conducted for 30 individual An. melas collected during the peak malaria transmission season in 2019 from six different islands on the Bijagós Archipelago. Bioinformatics tools were used to investigate the population structure and prevalence of insecticide resistance markers in this mosquito population. Results Insecticide resistance mutations associated with pyrethroid resistance in Anopheles gambiae s.s. from the Bijagós were absent in the An. melas population, and no signatures of selective sweeps were identified in insecticide resistance-associated genes. Analysis of structural variants identified a large duplication encompassing the cytochrome-P450 gene cyp9k1. Phylogenetic analysis using publicly available mitochondrial genomes indicated that An. melas from the Bijagós split into two phylogenetic groups because of differentiation on the mitochondrial genome attributed to the cytochrome C oxidase subunits COX I and COX II and the NADH dehydrogenase subunits 1, 4, 4L and 5. Conclusions This study identified an absence of insecticide-resistant SNPs common to An. gambiae in the An. melas population, but did identify structural variation over insecticide resistance-associated genes. Furthermore, this study presents novel insights into the population structure of this malaria vector using WGS analysis. Additional studies are required to further understand the role of this vector in malaria transmission. Graphical abstract

Unprecedented rates of biodiversity loss and ecosystem function necessitate the use of rapid, efficacious, and cost-effective biomonitoring tools. The combination of autonomous samplers and high throughput sequencing (i.e., “metabarcoding”) of environmental DNA (eDNA) samples enables characterization of entire communities at high frequency and can be an important tool for conservation and management, allowing researchers to track fluctuations in biodiversity. We deployed two autonomous samplers at two U.S. Geological Survey streamgage sites in the upper Snake River (Wyoming and Idaho, USA) to collect eDNA samples from July-September 2021 and 2022 to characterize fish diversity. We used a probabilistic approach to evaluate the effects of water temperature, water discharge, filter pore size, water volume filtered, number of samples collected, timing, and primers on the probability of detecting eDNA from fish species known to be present. We detected eDNA from 13/15 species present in these areas of the Snake River. Overall, we did not find evidence that filter pore size, water volume filtered, water discharge, and water temperature affected the probability of detecting fish species’ eDNA. By contrast, primers and sampling day affected fish detection probabilities, indicating that primer choice and sampling day can either over- or under- estimate species diversity. These results indicate that users would ideally consider sampling on non-consecutive days and which primer set will maximize species detections.

Abstract PTPN2 (protein tyrosine phosphatase non-receptor type 2, or TC-PTP) and PTPN1 are attractive immuno-oncology targets, with the deletion of Ptpn1 and Ptpn2 improving response to immunotherapy in disease models. Targeted protein degradation has emerged as a promising approach to drug challenging targets including phosphatases. We developed potent PTPN2/N1 dual heterobifunctional degraders (Cmpd-1 and Cmpd-2) which facilitate efficient complex assembly with E3 ubiquitin ligase CRL4CRBN, and mediate potent PTPN2/N1 degradation in cells and mice. To provide mechanistic insights into the cooperative complex formation introduced by degraders, we employed a combination of structural approaches. Our crystal structure reveals how PTPN2 is recognized by the tri-substituted thiophene moiety of the degrader. We further determined a high-resolution structure of DDB1-CRBN/Cmpd-1/PTPN2 using single-particle cryo-electron microscopy (cryo-EM). This structure reveals that the degrader induces proximity between CRBN and PTPN2, albeit the large conformational heterogeneity of this ternary complex. The molecular dynamic (MD)-simulations constructed based on the cryo-EM structure exhibited a large rigid body movement of PTPN2 and illustrated the dynamic interactions between PTPN2 and CRBN. Together, our study demonstrates the development of PTPN2/N1 heterobifunctional degraders with potential applications in cancer immunotherapy. Furthermore, the developed structural workflow could help to understand the dynamic nature of degrader-induced cooperative ternary complexes.

The neural crest is a stem cell population that originates from the ectoderm during the initial steps of nervous system development. Neural crest cells delaminate from the neuroepithelium by undergoing a spatiotemporally regulated epithelial-mesenchymal transition (EMT) that proceeds in a coordinated wave head-to-tail to exit from the neural tube. While much is known about the transcriptional programs and membrane changes that promote EMT, there are additional levels of gene expression control that neural crest cells exert at the level of RNA to control EMT and migration. Yet, the role of post-transcriptional regulation, and how it drives and contributes to neural crest EMT, is not well understood. In this mini-review, we explore recent advances in our understanding of the role of post-transcriptional regulation during neural crest EMT.

ABSTRACT Vulvovaginal candidiasis (VVC) is a common vaginal infectious disease caused by Candida. The high recurrence rate of VVC is a great clinical challenge, with recurrent VVC (RVVC) defined as four or more episodes within a year. In this study, we recruited 31 RVVC patients, 28 VVC patients, and 29 healthy women. Vaginal samples were collected for metagenomic and metabolic analysis. RVVC and VVC groups presented similar clinical symptoms, with only a significantly increased incidence of swelling in the VVC group. Vaginal microbiota in VVC/RVVC exhibited a decreased abundance of Lactobacillus and increased bacterial vaginosis-associated bacteria, such as Gardnerella, Prevotella, and Atopobium. Notably, Lactobacillus iners was higher in RVVC, suggesting not all Lactobacillus species are protective. Healthy women showed lower overall microbiota diversity, emphasizing single-species dominance for stability. Glycogen metabolism pathways were enriched in RVVC/VVC, and were correlated with Atopobium vaginae, Prevotella bivia, and Lactobacillus jensenii. Peptidoglycan synthesis pathways, associated with P. bivia, were enriched, with the substrate L-glutamate elevated in RVVC, possibly promoted by L. iners. These findings shed light on potential therapeutic targets for recurrent VVC, contributing to the understanding of the intricate interplay between the metabolism of vaginal microbiome and disease.IMPORTANCEThis study enhances our knowledge of the vaginal microbiota dynamics and the role of associated metabolites in individuals with vulvovaginal candidiasis (VVC) and recurrent vulvovaginal candidiasis through shotgun sequencing and multi-omics analysis. The relationship between metabolites and vaginal microbiota and disease state was revealed. The accumulation of L-glutamate generated in glycogen metabolism, which is governed by Lactobacillus iners or bacterial vaginosis-associated bacteria, may contribute to the incidence and recurrence of VVC. Such insights have the potential to impact the treatment and prevention strategies for these common yet distressing conditions, potentially leading to targeted therapies and improved patient outcomes.

“AI ethics” has become a popular term for signaling concerns with the development and application of artificial intelligence, and a hot-button issue in both academic and public discourse. The current work tends to center adult-oriented, adult-generated, and issues-based conceptions of ethics. This paper reports on an alternative model for “doing ethics” via co-design with young people, highlighting the need for students to engage in AI ethics work, especially as AI is increasingly used in their education and social lives. In particular, we focus on developing a rights-based approach, using the White House Blueprint for an AI Bill of Rights as a starting point for redesigning core AI ethics principles and their conveyance to be accessible and relevant to young people, in collaboration with young people. In this manuscript, we describe our empirical work in a series of three studies on AI ethics teaching and learning with middle and high school students, which culminated in redesigning pieces of the AI Bill of Rights. We present lessons learned, implications for responsible AI in education from student perspectives, and conclude with our suggested principles for integrating student insight and perspectives into the ethics frameworks that guide AI applications.

Abstract Despite its great scientific and technological importance, wall-bounded turbulence is an unresolved problem in classical physics that requires new perspectives to be tackled. One of the key strategies has been to study interactions among the energy-containing coherent structures in the flow. Such interactions are explored in this study using an explainable deep-learning method. The instantaneous velocity field obtained from a turbulent channel flow simulation is used to predict the velocity field in time through a U-net architecture. Based on the predicted flow, we assess the importance of each structure for this prediction using the game-theoretic algorithm of SHapley Additive exPlanations (SHAP). This work provides results in agreement with previous observations in the literature and extends them by revealing that the most important structures in the flow are not necessarily the ones with the highest contribution to the Reynolds shear stress. We also apply the method to an experimental database, where we can identify structures based on their importance score. This framework has the potential to shed light on numerous fundamental phenomena of wall-bounded turbulence, including novel strategies for flow control.

Abstract Background Health-related quality of life (HRQOL) is related to body composition, which is also related to resting metabolic rate (RMR). RMR can be increased by exercise and diet interventions that are not dependent on changes in body composition, so a link between RMR and HRQOL may provide interventions that directly improve HRQOL in women. Methods One hundred twenty women (median age 63.5 [IQR: 53.0–71.0] years) completed one-time measurement of body composition (multi-frequency bioelectrical impedance), RMR (handheld calorimetry), and HRQOL (RAND-36). Physical (PCS) and mental (MCS) composite scores were calculated for the RAND-36. Pearson correlations were used to identify relationships between RMR, body composition, and HRQOL. Variables at the p

The Foundational Data Initiative for Parkinson Disease (FOUNDIN-PD) is an international collaboration producing fundamental resources for Parkinson disease (PD). FOUNDIN-PD generated a multi-layered molecular dataset in a cohort of induced pluripotent stem cell (iPSC) lines differentiated to dopaminergic (DA) neurons, a major affected cell type in PD. The lines were derived from the Parkinson's Progression Markers Initiative study, which included participants with PD carrying monogenic PD variants, variants with intermediate effects, and variants identified by genome-wide association studies and unaffected individuals. We generated genetic, epigenetic, regulatory, transcriptomic, and longitudinal cellular imaging data from iPSC-derived DA neurons to understand molecular relationships between disease-associated genetic variation and proximate molecular events. These data reveal that iPSC-derived DA neurons provide a valuable cellular context and foundational atlas for modeling PD genetic risk. We have integrated these data into a FOUNDIN-PD data browser as a resource for understanding the molecular pathogenesis of PD.

While motor and cortical neurons are affected in C9orf72 amyotrophic lateral sclerosis and frontotemporal dementia (ALS/FTD), it remains largely unknown if and how non-neuronal cells induce or exacerbate neuronal damage. We differentiated C9orf72 ALS/FTD patient-derived induced pluripotent stem cells into microglia (iPSC-MG) and examined their intrinsic phenotypes. Similar to iPSC motor neurons, C9orf72 ALS/FTD iPSC-MG mono-cultures form G4C2 repeat RNA foci, exhibit reduced C9orf72 protein levels, and generate dipeptide repeat proteins. Healthy control and C9orf72 ALS/FTD iPSC-MG equally express microglial specific genes and perform microglial functions, including inflammatory cytokine release and phagocytosis of extracellular cargos, such as synthetic amyloid beta peptides and healthy human brain synaptoneurosomes. RNA sequencing analysis revealed select transcriptional changes of genes associated with neuroinflammation or neurodegeneration in diseased microglia yet no significant differentially expressed microglial-enriched genes. Moderate molecular and functional differences were observed in C9orf72 iPSC-MG mono-cultures despite the presence of C9orf72 pathological features suggesting that a diseased microenvironment may be required to induce phenotypic changes in microglial cells and the associated neuronal dysfunction seen in C9orf72 ALS/FTD neurodegeneration.

Background Chimeric antigen receptor T-cell (CAR-T) therapy has achieved remarkable remission in patients with B-cell malignancies. However, its efficacy in treating solid tumors remains limited. Here, we investigated a combination therapy approach using an engineered long-acting interleukin (IL)-7 (rhIL-7-hyFc or NT-I7) and CAR-T cells targeting three antigens, glypican-2 (GPC2), glypican-3 (GPC3), and mesothelin (MSLN), against multiple solid tumor types including liver cancer, neuroblastoma, ovarian cancer, and pancreatic cancer in mice.Methods CAR-T cells targeting GPC2, GPC3, and MSLN were used in combination with NT-I7 to assess the anticancer activity. Xenograft tumor models, including the liver cancer orthotopic model, were established using NOD scid gamma mice engrafted with cell lines derived from hepatocellular carcinoma, neuroblastoma, ovarian cancer, and pancreatic cancer. The mice were monitored by bioluminescence in vivo tumor imaging and tumor volume measurement using a caliper. Immunophenotyping of CAR-T cells on NT-I7 stimulation was evaluated for memory markers, exhaust markers, and T-cell signaling molecules by flow cytometry and western blotting.Results Compared with the IL-2 combination, preclinical evaluation of NT-I7 exhibited regression of solid tumors via enhanced occupancy of CD4+ CAR-T, improved T-cell expansion, reduced exhaustion markers (programmed cell death protein 1 or PD-1 and lymphocyte-activation gene 3 or LAG-3) expression, and increased generation of stem cell-like memory CAR-T cells. The STAT5 pathway was demonstrated to be downstream of NT-I7 signaling, mediated by increased expression of the IL-7 receptor expression in CAR-T cells. Furthermore, CAR-T cells improved efficacy against tumors with low antigen density when combined with NT-I7 in mice, presenting an avenue for patients with heterogeneous antigenic profiles.Conclusion This study provides a rationale for NT-I7 plus CAR-T cell combination therapy for solid tumors in humans.

Abstract Soluble angiotensin‐converting enzyme 2 (ACE2) can act as a decoy molecule that neutralizes severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) by blocking spike (S) proteins on virions from binding ACE2 on host cells. Based on structural insights of ACE2 and S proteins, we designed a “muco‐trapping” ACE2‐Fc conjugate, termed ACE2‐(G4S)6‐Fc, comprised of the extracellular segment of ACE2 (lacking the C‐terminal collectrin domain) that is linked to mucin‐binding IgG1‐Fc via an extended glycine‐serine flexible linker. ACE2‐(G4S)6‐Fc exhibits substantially greater binding affinity and neutralization potency than conventional full length ACE2‐Fc decoys or similar truncated ACE2‐Fc decoys without flexible linkers, possessing picomolar binding affinity and strong neutralization potency against pseudovirus and live virus. ACE2‐(G4S)6‐Fc effectively trapped fluorescent SARS‐CoV‐2 virus like particles in fresh human airway mucus and was stably nebulized using a commercial vibrating mesh nebulizer. Intranasal dosing of ACE2‐(G4S)6‐Fc in hamsters as late as 2 days postinfection provided a 10‐fold reduction in viral load in the nasal turbinate tissues by Day 4. These results strongly support further development of ACE2‐(G4S)6‐Fc as an inhaled immunotherapy for COVID‐19, as well as other emerging viruses that bind ACE2 for cellular entry.