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Engaging ecological resource users in intervention to protect resources is challenging for governments due to the self-interest of users and uncertainty about intervention consequences. Focusing on a case of forest insect infestations, we addressed questions of resource protection and environmentally responsible behavior promotion with a conceptual model. We coupled a forest infestation model with a social model in which a governing agent applies a mechanism for the recognition and promotion of environmentally responsible behavior among several user agents. We ran the coupled model in various scenarios with a reinforcement-learning algorithm for the governing agent as well as best-case, worst-case, and random baselines. Results showed that a proper recognition policy facilitates emergence of environmentally responsible behavior. However, ecosystem health may deteriorate due to temporal differences between the social and ecological systems. Our work shows it is possible to gain insight about complexities of social–ecological systems with conceptual models through scenario analysis.

The shift to online learning has highlighted significant gaps in how students' emotional and social needs are supported (Bao, 2020). This paper explores innovative pedagogical feedback mechanisms designed to enhance emotional and social support in online settings. It introduces frameworks for delivering feedback that are both academically relevant and sensitive to students' well-being. This paper advocates for more empathetic and socially aware practices in providing feedback, especially in online discussion boards. Key mechanisms include AI-driven tools, social network analytics, multimodal tools, and sentiment analysis. These tools aim to create a more inclusive and supportive online learning community, boosting student engagement, retention, and satisfaction.

Research into instructed pragmatics mainly comparing implicit and explicit instruction has gained salience in language teaching research in the last two decades. The present study was designed to investigate the effect of cognitive and interpersonal task-based instruction on EFL Learners' production of two speech acts of apology and request. To this end, 125 intermediate EFL learners were conveniently sampled, and randomly assigned to four experimental groups (EG) and one control group (CG). The four experimental groups received task-based instruction on the two speech acts of apology and request (three 30-minute sessions on each), though instruction varied in terms of general tasks types (cognitive or interpersonal) and their specific variants (cognitive: predicting (EG1; N=25) and inducing (EG2; N=25); interpersonal: co-operating (EG3; N=25) and role-play (EG4; N=25)). The control group (N=25) did not receive any speech act-specific treatment. The participants' speech act production was measured through a 16-item written discourse completion test (WDCT) as both the pretest and the posttest. The findings showed the significant effect of both cognitive and interpersonal tasks, but also the greater effectiveness of the latter for speech act production. The study has implications for pragmatic task design and classroom practice. More specifically, it shows the potential of task-based instruction and interaction for EFL learners' pragmatic development.

Abstract Background While COVID-19 has been controlled and deaths have decreased, the long-term consequences of COVID-19 remain a challenge we face today. This study was conducted to determine the relationship between the apoptosis of lymphocyte cells with DNA damage and oxidative stress and the therapeutic and clinical outcomes of elderly patients with COVID-19. Methods This study was conducted from April 2020 to May 2021 (the period of severe attacks of the epidemic peak of COVID-19) and September 2022 (the post-COVID-19 period). The study groups included elderly patients with COVID-19 hospitalized in the ICU and normal wards of the hospital as well as elderly patients with influenza. A polymerase chain reaction was used to check the validity of the studied diseases. The Annexin V/Propidium Iodide method was used to evaluate the level of apoptosis. Genotoxic effects and DNA damage were assessed by the comet assay method. Total antioxidant status (TAS), total oxidant status (TOS), and myeloperoxidase activity (MPO) were measured by photometric methods. Results The highest level of apoptosis in peripheral blood lymphocytes and the highest level of DNA damage were observed at both times in the intubated-ICU and non-intubated-ICU groups. In all groups, there was a significant increase in peripheral blood lymphocyte apoptosis levels and DNA damage levels compared to the healthy control group (p

Creatine transporter deficiency (CTD) is an inborn error of creatine (Cr) metabolism in which Cr is not properly distributed to the brain due to a mutation in the Cr transporter (CrT) SLC6A8 gene. CTD is associated with developmental delays and with neurological disability in children. Dodecyl creatine ester (DCE), as a Cr prodrug, is a promising drug to treat CTD after administration by the nasal route, taking advantage of the nose-to-brain pathway. In this study, the potential adaptive response to energy imbalance in glucose metabolism was investigated in CTD using both SLC6A8-deficient mice (CrT KO) and brain organoids derived from CTD patient cells. Longitudinal brain [18F]FDG PET imaging in CrT KO mice compared to wild-type mice demonstrated that CTD was associated with a significant loss and decline in brain glucose metabolism. In CrT KO mice, intranasal supplementation with DCE for a month significantly mitigated the decline in brain glucose metabolism compared to untreated (vehicle) animals. Mechanistic investigations in CrT KO mice and cerebral organoids derived from CTD patient cells suggest that intracellular trafficking of glucose transporter (Glut) may be altered by lack of activation of AMP-activated protein kinase (AMPK). Consistency between observations in the CrT KO mouse model and cerebral organoids derived from CTD patient cells supports the value of this new model for drug discovery and development. In addition, these results suggest that [18F]FDG PET imaging may offer a unique and minimally-invasive biomarker to monitor the impact of investigational treatment on CTD pathophysiology, with translational perspectives.

Human induced pluripotent stem cell (iPSC)-derived macrophages (IDMs) present a valuable substitute for monocyte-derived macrophages (MDMs) in order to study inflammation pathways in vitro. Through optimization of an IDM differentiation protocol, a six-fold increase in the production yield of myeloid progenitors was achieved. The derived IDMs were further characterized with respect to nucleotide-binding oligomerization domain (NOD) and receptor-interacting serine/threonine-protein kinase 2 (RIPK2) signaling, a key regulatory pathway for autoimmune diseases. The IDM cells recapitulated MDM biology with respect to the proinflammatory chemokine and inflammatory cytokine fingerprint more closely than THP-1 cells. When assessing RIPK2 modulation effect on tumor necrosis factor α (TNF-α), a cardinal mediator of inflammation, a similar pharmacological effect of RIPK2 inhibitors was observed in IDMs and MDMs. Additionally, IDMs and MDMs displayed a similar transcription and pathway profile in response to NOD1/2 stimulation and pharmacological inhibition of RIPK2. In summary, the enhanced myeloid production yield in the improved IDM differentiation protocol offers new opportunities for utilizing physiologically relevant macrophage models in the context of inflammatory diseases.

This study introduces an advanced community-level resilience analysis methodology integrating 3D fragility surfaces for combined successive earthquake-tsunami hazard and analysis. The methodology facilitates comprehensive evaluations of spatial damage, economic loss, and risk under multi-hazard conditions. This study compares earthquake-only analysis results to the successive earthquake-tsunami analysis at the community level to reveal – and quantify - significant disparities in damage and loss estimations between the analyses, emphasizing the need to consider both hazards in community planning even at lower seismic intensities. Critical assessment of the FEMA combinational rule demonstrates its limitations in accurately predicting losses and damage patterns at higher hazard intensities, highlighting the necessity for refined models that accurately account for hazard interactions. This research advances multi-hazard community-level resilience analysis by offering a robust framework for earthquake and tsunami assessment, underscoring the need for integration of detailed multi-hazard analyses into resilience planning. Finally, it suggests future directions for enhancing framework applicability across diverse community settings and structural types, aiming to improve community resilience.

Background: To our knowledge, there is scant research on the use of rehabilitative ultrasound imaging (RUSI) method for evaluating bladder base displacement in pregnant women. The RUSI is a non-invasive and simple method that assesses the function of pelvic floor muscles (PFM) based on the movement of the bladder base. Objectives: This study aims to assess the reliability of the RUSI for the assessment of PFM function in pregnant women during voluntary muscle contractions. Materials & Methods: In this cross-sectional study, 18 pregnant women with different gestational ages participated. The amount of bladder base displacement during PFM contraction was assessed in all women and considered an indicator of PFM function. The test re-test reliability was evaluated using the intraclass correlation coefficient (ICC) and Bland-Altman plot. The percentages of standard error of measurement (SEM%) and minimal detectable change (MDC%) were also calculated. Results: The mean amount of bladder base displacement during PFM contraction at time points 1 and 2 was 4.89±1.43 and 4.81±1.41, respectively. The ICC was 0.989 (95% CI, 0.969%, 0.996%), which indicates excellent reliability. The Bland-Altman plot showed that all the points were within the 95% limits of agreement with no considerable trend or bias. The SEM% and MDC% were 3.09% and 8.41%, respectively. Conclusion: The intra-rater reliability of the RUSI to assess PFM function in pregnant women is high, and can be useful for further studies on the PFMs in pregnant women.

BackgroundThere is an expanding unregulated market for a psychotropic compound called ∆8-Tetrahydrocannabinol (delta-8-THC) that is being derived from hemp, but a summary of adverse events related to delta-8-THC has not been publicly reported.MethodsThis case series assessed adverse events reported by delta-8-THC users on the Reddit forum r/Delta8 and compared these to delta-8-THC AEs in the US Food and Drug Administration Adverse Event Reporting System (FAERS). Delta-8-THC and cannabis AEs reported in FAERS were also compared. The r/Delta8 forum was selected because it includes a large sample of 98,700 registered individuals who publicly discuss their experiences using delta-8-THC. All r/Delta8 posts were obtained from August 20, 2020, through September 25, 2022. A random sample of r/Delta8 posts was drawn (n = 10,000) and filtered for posts in which delta-8-THC users reported an adverse event (n = 335). FAERS reports that listed delta-8-THC (N = 326) or cannabis (N = 7076) as a suspect product active ingredient were obtained. Adverse events claimed to result from delta-8-THC use were coded using Medical Dictionary for Regulatory Activities to system organ class and preferred term categories.ResultsThe absolute number of delta-8-THC adverse event reports (N = 2184, 95% CI = 1949-2426) and serious adverse event reports (N = 437; 95% CI = 339-541) on r/Delta 8 were higher than the adverse event reports (N = 326) and serious adverse event reports (N = 289) to FAERS. Psychiatric disorders were the most frequently cited system organ class in r/Delta8 adverse event reports, mentioned in 41.2% (95% CI = 35.8%-46.3%) of reports, followed by respiratory, thoracic and mediastinal disorders (29.3%, 95% CI = 25.1%-34.0%) and nervous system disorders (23.3%, 95% CI = 18.5%-27.5%). Anxiety (16.4%, 95% CI = 12.8-20.6), Cough (15.5%, 95% CI = 11.9-20.0) and Paranoia (9.3%, 95% CI = 6.3-12.5) were the most frequently cited preferred terms in adverse event reports. The overall prevalence of AEs reported for cannabis and delta-8-THC on FAERS were also similar when analyzed by system organ class (Pearson's r = 0.88).ConclusionsThe findings of this case series suggest that most of the adverse events reported by delta-8-THC users are like those reported during acute cannabis intoxication. This finding suggests that health care professionals follow similar treatment and management protocols, and that jurisdictions should clarify whether delta-8-THC can be sold as a hemp product.

Adaptive learning is an educational method that uses computer algorithms and artificial intelligence (AI) to customize learning materials and activities based on each user's model. Adaptive learning has been used for more than 20 years. However, it is still unique, and no other system could bring more or even similar capabilities than the ones adaptive technology offers, including the application of AI, psychology, psychometrics, machine learning, and providing a personalized learning environment. However, there are not many studies on its practicality, usefulness, improving students' learning skills, students' perception, etc., due to the limited number of institutes investing in this new technology. This paper presents the results of administering the newly developed Adaptive Self-regulated Learning Questionnaire (ASRQ) in an adaptive learning course equipped with the ALEKS (Assessment and Learning in Knowledge Spaces) system to study the amount of Self-regulated Learning Skills (SRL) score change, if any, of the students. The ASRQ was administered at the beginning and end of the semester as a pretest and posttest. Then, the quantitative Sample Paired t Test was run to measure the students' SRL score change between the beginning and end of the semester. The results showed a significant decline in students' SRL skills score while working with ALEKS. This paper also discusses the reasons for the considerable drop in SRL skills based on students' perception and feedback collected through administering an open-ended survey at the end of the semester. The survey's qualitative analysis showed various possible factors contributing to the decline of the SRL skills score, including lack of motivation, system complexity, hard penalty, lack of social presence, and lack of system practicality.

Abstract The optimal interval between the first and second doses of COVID-19 mRNA vaccines has not been thoroughly evaluated. Employing a target trial emulation approach, we compared the effectiveness of different interdose intervals among >6 million mRNA vaccine recipients in Georgia, USA, from December 2020 to March 2022. We compared three protocols defined by interdose interval: recommended by the Food and Drug Administration (FDA) (17-25 days for Pfizer-BioNTech; 24-32 days for Moderna), late-but-allowable (26-42 days for Pfizer-BioNTech; 33-49 days for Moderna), and late ( ≥ 43 days for Pfizer-BioNTech; ≥50 days for Moderna). In the short-term, the risk of SARS-CoV-2 infection was lowest under the FDA-recommended protocol. Longer-term, the late-but-allowable protocol resulted in the lowest risk (risk ratio on Day 120 after the first dose administration compared to the FDA-recommended protocol: 0.83 [95% confidence interval: 0.82-0.84]). Here, we showed that delaying the second dose by 1-2 weeks may provide stronger long-term protection.

Background: While dishonesty is considered unethical, its occurrence within the healthcare system is not rare; therefore, addressing and controlling this behavior requires targeted interventions to address its root causes. This study investigates the encounters of patients with COVID-19, their families, and healthcare workers with white lies during the COVID-19 pandemic in Iran. Materials and Methods: In this qualitative study, we employed a content analysis approach. Semi-structured interviews were conducted with 50 participants, including healthcare workers, individuals diagnosed with COVID-19, and their families. The research was carried out at teaching hospitals affiliated with the Tehran University of Medical Sciences in 2020. For data analysis, the methodology proposed by Graneheim and Lundman was used. In addition, the management and analysis of data were facilitated through MAXQDA software, version 12. Results: This study included 23 female and 27 male participants, with a mean age of 35±6.3 years. Through data analysis, a total of 3201 codes were identified and subsequently organized into 5 main categories as follows: social stigma, media inconsistencies, fear and uncertainty, negligence, and breaking free from quarantine. These categories further branched into 11 sub-categories. Conclusion: Employing white lies as a means to sidestep social stigma and discrimination, along with grappling with fear and xenophobia, emerged as prevalent experiences. The articulation of transparent and truthful information at the community level plays a crucial role in priming public perceptions to acknowledge factual circumstances. To achieve this, healthcare authorities and the media bear the responsibility of disseminating coherent and honest information, thereby mitigating and managing the proliferation of rumors within the community amidst the ongoing pandemic.

COVID-19 has emphasized the importance of holistic education with fostering stu- dents' multiple intelligences through effective social and emotional learning (SEL). Understanding students' SEL not only supports students' learning performance, it's also beneficial to inform teachers to provide more adequate social-communicative, metacognitive, and affective learning. This study examined: How does Data-Informed Learning Design (DILD) support online teaching on students' social and emotional learning? The study concluded that DILD is an effective design model to support teachers to probe students' socio-communicative, metacognitive, and affective learnings. The findings inform the educators to set high expectations for teaching and provide appropriate personal, social, data, and instructional support to enable teachers to regulate and support students to achieve ideal social and emotional learning.

Creatine transporter deficiency (CTD) is an X-linked disease caused by mutations in the Slc6a8 gene. The impaired creatine uptake in the brain leads to developmental delays with intellectual disability. We hypothesized that deficient creatine uptake in CTD cerebral cells impact methylation balance leading to alterations of genes and proteins expression by epigenetic mechanism. In this study, we determined the status of nucleic acid methylation in both Slc6a8 knockout mouse model and brain organoids derived from CTD patients’ cells. We also investigated the effect of dodecyl creatine ester (DCE), a promising prodrug that increases brain creatine content in the mouse model of CTD. The level of nucleic acid methylation was significantly reduced compared to healthy controls in both in vivo and in vitro CTD models. This hypo-methylation tended to be regulated by DCE treatment in vivo. These results suggest that increased brain creatine after DCE treatment restores normal levels of DNA methylation, unveiling the potential of using DNA methylation as a marker to monitor the drug efficacy.

Background & Aims: Particulate hepatitis B core antigen (HBcoreAg) is a potent immunogen used as a vaccine carrier platform. HBcoreAg produced in E. coli encapsidates random bacterial RNA (bRNA). Using the heterologous protein-prime, viral-vector-boost therapeutic hepatitis B vaccine TherVacB, we compared the properties of different HBcoreAg forms. We explored how the content of HBcoreAg modulates antigen stability, immunogenicity, and antiviral efficacy. Methods: bRNA was removed from HBcoreAg by capsid disassembly, followed by reassembly in the absence or presence of specific nucleic acid-based adjuvants poly I:C or CpG. The morphology and structure of empty, bRNA-containing and adjuvant-loaded HBcoreAg were monitored by electron microscopy and nuclear magnetic resonance spectroscopy. Empty, bRNA-containing or adjuvant-loaded HBcoreAg were applied together with HBsAg and with or without nucleic acid-based external adjuvants within the TherVacB regimen in both wild-type and HBV-carrier mice. Results: While HBcoreAg retained its structure upon bRNA removal, its stability and immunogenicity decreased significantly. Loading HBcoreAg with nucleic acid-based adjuvants re-established stability of the capsid-like antigen. Immunization with poly I:C- or CpG-loaded HBcoreAg induced high antibody titers against co-administered HBsAg. When applied within the TherVacB regimen, they activated vigorous HBcoreAg- and HBsAg-specific T-cell responses in wild-type and HBV-carrier mice, requiring a significantly lower dose of adjuvant compared to externally added adjuvant. Finally, immunization with adjuvant-loaded HBcoreAg mixed with HBsAg led to long-term control of persistent HBV replication in the HBV-carrier mice. Conclusion: Adjuvant-loaded HBcoreAg retained capsid integrity and stability, was as immunogenic in vivo as externally adjuvanted HBcoreAg, requiring lower adjuvant levels, and supported immunity against co-administered, non-adjuvanted HBsAg. Thus, adjuvant-loaded HBcoreAg represents a promising novel platform for vaccine development. Impact and implications: Hepatitis B core antigen (HBcoreAg) recapitulates the capsid of the HBV that hosts the viral genome. Produced recombinantly, it is not infectious but emerges as a potent immunogen in vaccine development. In this preclinical study, we show that loading HBcoreAg with defined nucleic-acid-based adjuvants on the one hand stabilizes the HBcoreAg with standardized capsid content and, on the other hand, efficiently promotes the immunity of HBcoreAg and a co-administered antigen, allowing for reduced adjuvant doses. Therefore, adjuvant-loaded HBcoreAg not only serves as an encouraging option for therapeutic hepatitis B vaccines, but could also act as an efficient adjuvant delivery system for other types of vaccine.

Abstract Improving the quantum coherence of solid-state systems is a decisive factor in realizing solid-state quantum technologies. The key to optimize quantum coherence lies in reducing the detrimental influence of noise sources such as spin noise and charge noise. Here we demonstrate that we can utilize highly-excited Rydberg excitons to neutralize charged impurities in the semiconductor Cuprous Oxide - an effect we call purification. Purification reduces detrimental electrical stray fields drastically. We observe that the absorption of the purified crystal increases by up to 25% and that the purification effect is long-lived and may persist for hundreds of microseconds or even longer. We investigate the interaction between Rydberg excitons and impurities and find that it is long-ranged and based on charge-induced dipole interactions. Using a time-resolved pump-probe technique, we can discriminate purification from Rydberg blockade, which has been a long-standing goal in excitonic Rydberg systems.