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A new reading curriculum incorporating the principles of concept-based instruction and reading strategy instruction was designed and implemented for a previous study. Concept-based instruction was compared with reading strategy instruction to determine the impact of the new curriculum on language learners' reading and reflective thinking skills. The data revealed that the concept-based group performed better in reflective reading and thinking skills. The new curriculum involves the creation of a Schema of a Complete Orienting Basis of an Action (SCOBA) during reflection sessions. To explore the necessity of SCOBA creation, an experimental study with two groups was conducted, where only one group created a SCOBA. Both groups received concept-based reading instruction and were compared based on their reading, reflective reading, and reflective thinking skills. The data revealed that the groups performed similarly in reading and reflective reading skills, but the SCOBA group performed better in reflective thinking skills. The study sheds light on the importance of incorporating reflective thinking activities, such as SCOBA creation, in concept-based reading instruction.

Although research has consistently highlighted the importance of school adjustment for high school students, validated tools for assessing this construct are currently lacking. To address this gap, our study aimed to develop and validate a scale to measure school adjustment among high school students. Employing a two-stage approach, we first examined the concept of adjustment and generated scale items. Subsequently, we surveyed 1121 high school students, and randomly split the data into two groups for subsequent analyses. Through exploratory in the first stage and confirmatory factor analyses in the second stage, we identified two higher-order factors within the scale: social adjustment and academic adjustment, with academic adjustment consisting of two sub-factors, academic performance and, academic engagement. The results indicated that the scale has an excellent model fit, as well as adequate reliability and high construct validity. Overall, our study provides a valuable tool for assessing school adjustment in high school students.

Researchers may have at their disposal the raw data of the studies they wish to meta-analyze. The goal of this study is to identify, illustrate, and compare a range of possible analysis options for researchers to whom raw data are available, wanting to fit a structural equation model (SEM) to these data. This study illustrates techniques that directly analyze the raw data, such as multilevel and multigroup SEM, and techniques based on summary statistics, such as correlation-based meta-analytical structural equation modeling (MASEM), discussing differences in procedures, capabilities, and outcomes. This is done by analyzing a previously published collection of datasets using open source software. A path model reflecting the theory of planned behavior is fitted to these datasets using different techniques involving SEM. Apart from differences in handling of missing data, the ability to include study-level moderators, and conceptualization of heterogeneity, results show differences in parameter estimates and standard errors across methods. Further research is needed to properly formulate guidelines for applied researchers looking to conduct individual participant data MASEM.

BackgroundMicroglia play a critical role in neurodegenerative disorders, such as Alzheimer's disease, where alterations in microglial function may result in pathogenic amyloid-β (Aβ) accumulation, chronic neuroinflammation, and deleterious effects on neuronal function. However, studying these complex factors in vivo, where numerous confounding processes exist, is challenging, and until recently, in vitro models have not allowed sustained culture of critical cell types in the same culture.ObjectiveWe employed a rat primary tri-culture (neurons, astrocytes, and microglia) model and compared it to co-culture (neurons and astrocytes) and mono-culture (microglia) to study microglial function (i.e., motility and Aβ clearance) and proteomic response to exogenous Aβ.MethodsThe cultures were exposed to fluorescently-labeled Aβ (FITC-Aβ) particles for varying durations. Epifluorescence microscopy images were analyzed to quantify the number of FITC-Aβ particles and assess cytomorphological features. Cytokine profiles from conditioned media were obtained. Live-cell imaging was employed to extract microglia motility parameters.ResultsFITC-Aβ particles were more effectively cleared in the tri-culture compared to the co-culture. This was attributed to microglia engulfing FITC-Aβ particles, as confirmed via epifluorescence and confocal microscopy. FITC-Aβ treatment significantly increased microglia size, but had no significant effect on neuronal surface coverage or astrocyte size. Upon FITC-Aβ treatment, there was a significant increase in proinflammatory cytokines in tri-culture, but not in co-culture. Aβ treatment altered microglia motility evident as a swarming-like motion.ConclusionsThe results suggest that neuron-astrocyte-microglia interactions influence microglia function and highlight the utility of the tri-culture model for studies of neuroinflammation, neurodegeneration, and cell-cell communication.

BackgroundSubstance use is a public crisis in the U.S. Substance use can be understood as a series of events in the life course, from initiation to mortality. Social Determinants of Health (SDoH) have increasingly been recognized as essential contributors to individuals' health. This scoping review aims to examine available evidence of SDoH impact on the life course of substance use disorder (SUD).MethodsThis study identified peer-reviewed articles that reported longitudinal studies with SDoH factors as independent variables and substance use and disorders as dependent variables from PubMed, Embase, and Web of Science. The reported associations between SDoH and substance use stages over the life course were narratively and graphically summarized.ResultsAmong the 50 studies identified, ten revealed parental monitoring/support and early childhood education as protective factors, while negative peer influences and neighborhood instability were risk factors of substance use initiation. Nineteen articles reported factors associated with escalation in substance use, including unemployment, neighborhood vulnerability, negative peer influence, violence/trauma, and criminal justice system (CJS) involvement. Ten articles suggested that employment, social support, urban living, and low-barrier medication treatment facilitated treatment participation, while stigma and CJS involvement had negative impact on treatment trajectory. Social support and employment could foster progress in recovery and CJS involvement and unstable housing deterred recovery. Four studies suggested that unemployment, unstable housing, CJS involvement, and lack of social support were associated with overdose and mortality.ConclusionsThis review underscores the influence of social networks and early life experiences on the life course of SUD. Future SDoH research should investigate overdose and mortality and the impact of broader upstream SDoH on SUD. Interventions addressing these social factors are needed to mitigate their detrimental effects on the trajectories of SUD over the life course.

This paper investigates the effects of large language model (LLM) based feedback on the essay writing proficiency of university students in Hong Kong. It focuses on exploring the potential improvements that generative artificial intelligence (AI) can bring to student essay revisions, its effect on student engagement with writing tasks, and the emotions students experience while undergoing the process of revising written work. Utilizing a randomized controlled trial, it draws comparisons between the experiences and performance of 918 language students at a Hong Kong university, some of whom received generated feedback (GPT-3.5-turbo LLM) and some of whom did not. The impact of AI-generated feedback is assessed not only through quantifiable metrics, entailing statistical analysis of the impact of AI feedback on essay grading, but also through subjective indices, student surveys that captured motivational levels and emotional states, as well as thematic analysis of interviews with participating students. The incorporation of AI-generated feedback into the revision process demonstrated significant improvements in the caliber of students' essays. The quantitative data suggests notable effect sizes of statistical significance, while qualitative feedback from students highlights increases in engagement and motivation as well as a mixed emotional experience during revision among those who received AI feedback.

Background: Pediatric lower urinary tract symptoms (LUTS) are a set of common childhood problems. Community-level interventions that target behavioral change among children with LUTS can improve symptoms outside of the clinic environment. Parents, navigating the home and school environments, are key in supporting healthy bladder behaviors. Thus, we asked parents about their perceptions and barriers related to pediatric bladder health. Methods: English-speaking parents (n = 30) of children ages 5-10 years with and without LUTS were interviewed. Transcripts were coded iteratively by two independent coders using deductive and inductive approaches that emphasized consensus coding and peer debriefing. Results: Ninety-three percent of participants were women, 50% were 30-39 years old, and 60% held a graduate degree. Parents identified school-, classroom-, and child-based barriers to bladder health. These included the bathroom environment, restrictive policies for bathroom use, and anxiety on how and when to use the bathroom. Conclusions: Addressing school-, classroom-, and child-based barriers is necessary to promote healthy bladder habits among children in the school environment and beyond. Recommended school-based interventions include bathroom use and sanitation policies that support students' voiding needs, teachers' professional development, and school readiness initiatives. Limitations include participation of English-speaking parents only.

The interest in Computational Thinking (CT) development among young learners increases with the number of studies located in literature. In this study, a meta-analysis was conducted to address two main objectives: (a) the effectiveness of empirical interventions on the development of CT in children aged of 3-8 years; and (b) the variables that influence the effectiveness of the interventions. Following PRISMA procedures, we identified 17 empirical studies with 34 effect sizes and 1665 participants meeting the inclusion criteria from Web of Science database. Overall, we found a statistically significant large effect size (d = 0.83 [95% CI: 730, 0.890]; p < 0.001) on the CT development of 3-8 years old children, which provides empirical support for having young children to engage in CT experiences. The effect size was significantly influenced by moderating variables including gender, scaffolding, and education level. Intervention length showed a marginally significant effect. Therefore, educators could refer to the significant moderators when designing tailored interventions for CT development in early childhood education while a call for more empirical studies of CT development in young children is proposed.

Salmonella translocate to the gut epithelium via microfold cells lining the follicle-associated epithelium (FAE). How Salmonella localize to the FAE is not well characterized. Here we use live imaging and competitive assays between wild-type and chemotaxis-deficient mutants to show that Salmonella enterica serotype Typhimurium (S. Typhimurium) localize to the FAE independently of chemotaxis in an ex vivo mouse caecum infection model. Electrical recordings revealed polarized FAE with sustained outward current and small transepithelial potential, while the surrounding villus is depolarized with inward current and large transepithelial potential. The distinct electrical potentials attracted S. Typhimurium to the FAE while Escherichia coli (E. coli) localized to the villi, through a process called galvanotaxis. Chloride flux involving the cystic fibrosis transmembrane conductance regulator (CFTR) generated the ionic currents around the FAE. Pharmacological inhibition of CFTR decreased S. Typhimurium FAE localization but increased E. coli recruitment. Altogether, our findings demonstrate that bioelectric cues contribute to S. Typhimurium targeting of specific gut epithelial locations, with potential implications for other enteric bacterial infections.

INTRODUCTION: Opioid and alcohol use disorders are increasingly being addressed in primary care, yet how medications to treat these disorders are prescribed in rural regions is unknown. METHODS: We determined prevalence, types, and duration of medication prescription for opioid and/or alcohol use disorder among adult patients in rural primary clinics. The sample included 1874 adult patients who visited one of six rural primary care sites in the Northeastern and Northwestern United States at least once from October 2019 to January 2021 and had a diagnosis code for opioid use disorder (OUD), alcohol use disorder (AUD), or co-occurring opioid and alcohol use disorder (OUD + AUD) during that time. RESULTS: Patients with OUD + AUD were more likely to be prescribed medication for at least one of these disorders (85.3 %) than patients with OUD only (63.7 %) or AUD only (10.3 %). Further, the OUD + AUD group had the highest number of days on medication (M = 264.7), followed by OUD only (M = 220.5), then the AUD only group (M = 62.5). Only 8.8 % of patients with OUD + AUD were prescribed naltrexone or medication for OUD + AUD to treat both substance use disorders. CONCLUSIONS: Medications for treating AUD as well as OUD are available, but few patients with OUD + AUD and even fewer with AUD received pharmacological treatment for AUD. The current work highlights the need for rural clinicians to consider medications for AUD as an important treatment method for patients with AUD only or OUD + AUD.

BACKGROUND: In the phase 3 EMPOWER-Cervical 1/GOG-3016/ENGOT-cx9 study, cemiplimab significantly improved overall survival (OS) versus chemotherapy for patients with recurrent or metastatic cervical cancer who progressed after first-line platinum-based chemotherapy. We present a post hoc subgroup analysis of patients enrolled in Japan. METHODS: Patients were enrolled regardless of programmed cell death-ligand 1 status and randomized 1:1 to cemiplimab 350 mg intravenously every 3 weeks or investigators choice  single-agent chemotherapy for up to 96 weeks. Primary endpoint was OS. Key secondary endpoints were progression-free survival (PFS) and objective response rate (ORR). RESULTS: Overall, 608 patients were randomized, of whom 56 (9.2%) were in Japan (cemiplimab, n = 29; chemotherapy, n = 27). The median (range) duration of follow-up was 13.6 (6.0-25.3) versus 18.2 (6.0-38.2) months for patients in Japan and for the overall population, respectively. Median OS (95% confidence interval [CI]) was 8.4 (7.0-not evaluable) and 9.4 (5.4-14.9) months for cemiplimab versus chemotherapy (hazard ratio [HR]: 0.86; 95% CI: 0.43-1.68). Median PFS (95% CI) was 4.0 (1.4-8.2) versus 3.7 (1.8-4.2) months with cemiplimab and chemotherapy (HR: 0.90; 95% CI: 0.50-1.61), respectively. ORR was 17.2% for cemiplimab and 7.4% for chemotherapy (odds ratio, 2.47; 95% CI, 0.44-13.99). Incidence of treatment-emergent adverse events at any grade was 79.3% for cemiplimab and 100% for chemotherapy. Grade ≥3 adverse events were 37.9% versus 66.7% with cemiplimab and chemotherapy, respectively. DISCUSSION: While acknowledging limitations inherent to a small subgroup analysis, the HR of 0.86 observed in Japanese patients suggests an emerging survival benefit despite a 4.6-month shorter median duration of follow-up versus the overall study population.

Inhibition of histone lysine acetyltransferases (KATs) KAT6A and KAT6B has shown antitumor activity in estrogen receptor-positive (ER+) breast cancer preclinical models. PF-07248144 is a selective catalytic inhibitor of KAT6A and KAT6B. In the present study, we report the safety, pharmacokinetics (PK), pharmacodynamics, efficacy and biomarker results from the first-in-human, phase 1 dose escalation and dose expansion study (n = 107) of PF-07248144 monotherapy and fulvestrant combination in heavily pretreated ER+ human epidermal growth factor receptor-negative (HER2-) metastatic breast cancer (mBC). The primary objectives of assessing the safety and tolerability and determining the recommended dose for expansion of PF-07248144, as monotherapy and in combination with fulvestrant, were met. Secondary endpoints included characterization of PK and evaluation of antitumor activity, including objective response rate (ORR) and progression-free survival (PFS). Common treatment-related adverse events (any grade; grades 3-4) included dysgeusia (83.2%, 0%), neutropenia (59.8%, 35.5%) and anemia (48.6%, 13.1%). Exposure was approximately dose proportional. Antitumor activity was observed as monotherapy. For the PF-07248144-fulvestrant combination (n = 43), the ORR (95% confidence interval (CI)) was 30.2% (95% CI = 17.2-46.1%) and the median PFS was 10.7 (5.3-not evaluable) months. PF-07248144 demonstrated a tolerable safety profile and durable antitumor activity in heavily pretreated ER+HER2- mBC. These findings establish KAT6A and KAT6B as druggable cancer targets, provide clinical proof of concept and reveal a potential avenue to treat mBC. clinicaltrial.gov registration: NCT04606446 .