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This article explores student teachers' resilience during the COVID-19 pandemic and their ability to thrive in online teaching practice. Amid the pandemic's unprecedented challenges, student teachers exhibited remarkable adaptability in navigating the shift to remote teaching. Through qualitative research and thematic analysis, this article delves into student teachers' experiences, highlighting their positive encounters with online teaching methodologies and tools. The findings underscore the importance of resilience and adaptability in the dynamic field of education, emphasising the valuable skills student teachers attained through their engagement with online teaching. Furthermore, the article explores the advantages of online practical assessments, shedding light on innovative evaluation methods that may shape future educational practices. Overall, the insights gleaned from this research contribute to a deeper understanding of student teachers' experiences during times of educational transformation. Recommendations are also offered to integrate online teaching methods into teacher training programmes to enhance these students' resilience and adaptability in the face of adversity.

Macrophages sense pathogens and orchestrate specific immune responses. Stimulus specificity is thought to be achieved through combinatorial and dynamical coding by signaling pathways. While NFκB dynamics are known to encode stimulus information, dynamical coding in other signaling pathways and their combinatorial coordination remain unclear. Here, we established live-cell microscopy to investigate how NFκB and p38 dynamics interface in stimulated macrophages. Information theory and machine learning revealed that p38 dynamics distinguish cytokine TNF from pathogen-associated molecular patterns and high doses from low, but contributed little to information-rich NFκB dynamics when both pathways are considered. This suggests that immune response genes benefit from decoding immune signaling dynamics or combinatorics, but not both. We found that the heterogeneity of the two pathways is surprisingly uncorrelated. Mathematical modeling revealed potential sources of uncorrelated heterogeneity in the branched pathway network topology and predicted it to drive gene expression variability. Indeed, genes dependent on both p38 and NFκB showed high scRNAseq variability and bimodality. These results identify combinatorial signaling as a mechanism to restrict NFκB-AND-p38-responsive inflammatory cytokine expression to few cells.

Previous research has found that living in a disadvantaged neighborhood is associated with poor health outcomes. Living in disadvantaged neighborhoods may alter inflammation and immune response in the body, which could be reflected in epigenetic mechanisms such as DNA methylation (DNAm). We used robust linear regression models to conduct an epigenome-wide association study examining the association between neighborhood deprivation (Area Deprivation Index; ADI), and DNAm in brain tissue from 159 donors enrolled in the Emory Goizueta Alzheimers Disease Research Center (Georgia, USA). We found one CpG site (cg26514961, gene PLXNC1) significantly associated with ADI after controlling for covariates and multiple testing (p-value=5.0e-8). Effect modification by APOE ε4 was statistically significant for the top ten CpG sites from the EWAS of ADI, indicating that the observed associations between ADI and DNAm were mainly driven by donors who carried at least one APOE ε4 allele. Four of the top ten CpG sites showed a significant concordance between brain tissue and tissues that are easily accessible in living individuals (blood, buccal cells, saliva), including DNAm in cg26514961 (PLXNC1). Our study identified one CpG site (cg26514961, PLXNC1 gene) that was significantly associated with neighborhood deprivation in brain tissue. PLXNC1 is related to immune response, which may be one biological pathway how neighborhood conditions affect health. The concordance between brain and other tissues for our top CpG sites could make them potential candidates for biomarkers in living individuals.

Individual cell sensing of external cues has evolved through the temporal patterns in signaling. Since nuclear factor κB (NF-κB) signaling dynamics have been examined using a single subunit, RelA, it remains unclear whether more information might be transmitted via other subunits. Using NF-κB double-knockin reporter mice, we monitored both canonical NF-κB subunits, RelA and c-Rel, simultaneously in single macrophages by quantitative live-cell imaging. We show that signaling features of RelA and c-Rel convey more information about the stimuli than those of either subunit alone. Machine learning is used to predict the ligand identity accurately based on RelA and c-Rel signaling features without considering the co-activated factors. Ligand discrimination is achieved through selective non-redundancy of RelA and c-Rel signaling dynamics, as well as their temporal coordination. These results suggest a potential role of c-Rel in fine-tuning immune responses and highlight the need for approaches that will elucidate the mechanisms regulating NF-κB subunit specificity.

Abstract Background A novel anti-human epidermal growth factor receptor 2 (HER2) antibody–drug conjugate (ADC) GQ1001 was assessed in patients with previously treated HER2 positive advanced solid tumors in a global multi-center phase Ia dose escalation trial. Methods In this phase Ia trial, a modified 3 + 3 study design was adopted during dose escalation phase. Eligible patients were enrolled, and GQ1001 monotherapy was administered intravenously every 3 weeks. The starting dose was 1.2 mg/kg, followed by 2.4, 3.6, 4.8, 6.0, 7.2 and 8.4 mg/kg. Extra patients were enrolled into 6.0, 7.2, and 8.4 mg/kg cohorts as dose expansion phase. The primary endpoints were safety and to determine the maximum tolerated dose (MTD) based on dose limiting toxicities (DLTs). Pharmacokinetics and anti-tumor efficacy of GQ1001 were assessed. The plasma concentration of free DM1, the payload of GQ1001, was quantitated. Results A total of 32 patients were enrolled, predominantly in breast (9), gastric or gastro-esophageal junction (9) and salivary gland cancer (4). Median number of prior-line of therapies was 3 (0–11) and 37.5% patients received ≥ 2 lines of anti-HER2 therapies. No DLT was observed during dose escalation. MTD was not reached and dose recommended for dose expansion (DRDE) was determined as 8.4 mg/kg. Grade ≥ 3 treatment-related adverse events rate was 28.1% (9/32) and platelet count decreased (4/32, 12.5%) was the most common one. No drug-related death was observed. Objective response rate and disease control rate of 15 evaluable patients in 7.2 mg/kg and 8.4 mg/kg cohorts were 40.0% (6/15) and 60.0% (9/15). Pharmacokinetics analysis showed low exposure and accumulation of free DM1 in circulation. Conclusion GQ1001 is well tolerated and shows promising efficacy in previously treated HER2-positive advanced solid tumors. DRDE was determined as 8.4 mg/kg for following trials. Trial registration NCT, NCT04450732, Registered 23 June 2020, https://clinicaltrials.gov/study/NCT04450732

Background: The worldwide issue of stunting, which is prevalent up to 20.5%, can have an impact on future productivity and health Objectives: to determine the risk factors and prevalence of stunting in children aged 0-23 months in Palu City, Indonesia. Methods: This study used a cross-sectional analytical design in eight sub-districts of Palu City (January-June 2024), involving 516 pairs of mothers and children aged 0-23 months. Data were collected by 20 enumerators under the supervision of the Health Office, through interviews related to breastfeeding, complementary feeding, infection history, and other variables as well as anthropometric measurements using length Board Measuring calibrated tools. The data were analyzed using univariate analysis, chi-square test bivariate, and logistic regression. Data collection is carried out through the Cobocollect platform. Results: Logistic regression analysis shows several important findings. Children of mothers with low education (OR=1.9), male children (OR=2.2), low birth weight (OR=3.1), and families with more than 3 children (OR=2.1) have a higher risk of stunting. Of the 516 children, 20.5% experienced stunting. These findings highlight the importance of maternal education, gender, birth weight, and number of children as risk factors for stunting, as well as their implications for health policies. Conclusions: Factors such as low birth weight, male sex, the number of children over three, and mothers' education of less than 9 years significantly increased the risk of stunting in children. Targeted nutrition interventions for mothers with low education and families with many children are essential to reduce the prevalence of stunting in Palu City.

Background: Uterine myomas, or fibroids, are one of the most common benign tumors that occur in women of reproductive age, with a reasonably high prevalence worldwide. However, rarely, potentially malignant uterine myomas can cause a variety of health problems, including excessive menstruation, pelvic pain, fertility disorders, and pregnancy complications. Objective: This study aims to analyze the relationship between menarche age and parity with the incidence of uterine myoma. Methods: Types and design of research the plan used in this exploration is quantitative exploration with a case control approach. Sampel berjumlah 138 responden masing-masing 102 ibu yang mengalami mioma uteri dan 36 ibu yang tidak mengalami efek buruk mioma uteri. Results: The test results measured using the chi-square test were obtained with p-value menarche age = 0.004 and parity p-value = 0.000, meaning that there was a very large relationship between menarche age and parity with the incidence of uterine myomas. Conclusion: It can be concluded that the earlier the age of menarche increases the risk of uterine myoma later in life. In contrast, slower menarche may be associated with a reduced risk of myomas. Other factors such as genetic, environmental, and lifestyle factors also influence the incidence of uterine myomas, but menarche age is one of the significant hormonal indicators of risk

INTRODUCTION: Depression is one of the most common yet underdiagnosed perinatal complications and our understanding of its pathophysiology remains limited. Though perinatal depression is considered to have a multifactorial etiology, integrative approaches to investigation are minimal. This review takes an integrative approach to systematically evaluate determinants (e.g., biological, behavioral, environmental, social) and interactions among determinants of perinatal depression and the quality of methods applied. METHODS: Four databases (i.e., PubMed, CINAHL, APA PsycInfo, Web of Science) were systematically searched to identify studies examining determinants of perinatal depression in adult perinatal persons (≥ 18 years). Articles were excluded if the outcomes were not focused on perinatal persons and depression or depression symptoms, depression was examined in a specific subpopulation evidenced to have psychological consequences due to situational stressors (e.g., fetal/infant loss, neonatal intensive care unit admission), or was considered grey literature. The Critical Appraisal Skills Programme and AXIS tools were used to guide and standardize quality appraisal assessments and determine the level of risk of bias. RESULTS: Of the 454 articles identified, 25 articles were included for final review. A total of 14 categories of determinants were investigated: biological (5), behavioral (4), social and environmental (5). Though only 32% of studies simultaneously considered determinants under more than one domain, a pattern of interactions with the tryptophan pathway emerged. Concerns for risk of bias were noted or were unclear for three types of bias: 13 (52%) selection bias, 3 (12%) recall bias, and 24 (96%) measurement bias. CONCLUSIONS: Future research is needed to explore interactions among determinants and the tryptophan pathway; to strengthen the methods applied to this area of inquiry; and to generate evidence for best practices in reporting, selecting, and applying methods for measuring determinants and perinatal depression.

Acute gastrointestinal infection with intracellular pathogens like Salmonella Typhimurium triggers the release of the proinflammatory cytokine interleukin 1β (IL-1β). However, the role of IL-1β in intestinal defense against Salmonella remains unclear. Here, we show that IL-1β production is detrimental during Salmonella infection. Mice lacking IL-1β (IL-1β -/-) failed to recruit neutrophils to the gut during infection, which reduced tissue damage and prevented depletion of short-chain fatty acid (SCFA)-producing commensals. Changes in epithelial cell metabolism that typically support pathogen expansion, such as switching energy production from fatty acid oxidation to fermentation, were absent in infected IL-1β -/- mice which inhibited Salmonella expansion. Additionally, we found that IL-1β induces expression of complement anaphylatoxins and suppresses the complement-inactivator carboxypeptidase N (CPN1). Disrupting this process via IL-1β loss prevented mortality in Salmonella-infected IL-1β -/- mice. Finally, we found that IL-1β expression correlates with expression of the complement receptor in patients suffering from sepsis, but not uninfected patients and healthy individuals. Thus, Salmonella exploits IL-1β signaling to outcompete commensal microbes and establish gut colonization. Moreover, our findings identify the intersection of IL-1β signaling and the complement system as key host factors involved in controlling mortality during invasive Salmonellosis.

Background: This document updates previously published Clinical Practice Guidelines for the management of patients with acute respiratory distress syndrome (ARDS), incorporating new evidence addressing the use of corticosteroids, venovenous extracorporeal membrane oxygenation, neuromuscular blocking agents, and positive end-expiratory pressure (PEEP). Methods: We summarized evidence addressing four PICO questions (patient, intervention, comparison, and outcome). A multidisciplinary panel with expertise in ARDS used the Grading of Recommendations, Assessment, Development, and Evaluation framework to develop clinical recommendations. Results: We suggest the use of: 1) corticosteroids for patients with ARDS (conditional recommendation, moderate certainty of evidence), 2) venovenous extracorporeal membrane oxygenation in selected patients with severe ARDS (conditional recommendation, low certainty of evidence), 3) neuromuscular blockers in patients with early severe ARDS (conditional recommendation, low certainty of evidence), and 4) higher PEEP without lung recruitment maneuvers as opposed to lower PEEP in patients with moderate to severe ARDS (conditional recommendation, low to moderate certainty), and 5) we recommend against using prolonged lung recruitment maneuvers in patients with moderate to severe ARDS (strong recommendation, moderate certainty). Conclusions: We provide updated evidence-based recommendations for the management of ARDS. Individual patient and illness characteristics should be factored into clinical decision making and implementation of these recommendations while additional evidence is generated from much-needed clinical trials.

BACKGROUND: Racial and ethnic disparities in infant-feeding practices may negatively influence diet quality and health. OBJECTIVES: This study investigated the racial, ethnic, and language (English or Spanish) differences in infant diet quality, later diet quality, and weight status at 2-5 y, and whether these differences were explained through infant diet quality among participants in the Special Supplemental Nutrition Program for Women, Infants, and Children (WIC). METHODS: Using the WIC Infant and Toddler Feeding Practices Study-2 (unweighted n = 2663; weighted n = 362,712), relationships between the Infant Dietary Quality Index (IDQI; range 0-1) and Healthy Eating Index-2020 (HEI-2020; range 0-100) and BMI z-score (BMIz) at 2-5 y were analyzed by race, ethnicity, and language preference [Hispanic Spanish-speaking, Hispanic English-speaking, non-Hispanic (NH) White, and NH Black participants]. Statistical interaction between IDQI and each group was evaluated in multivariable models. The mediation of each group through the IDQI was assessed using causal mediation methods. RESULTS: Differences in IDQI [mean (standard deviation)] were observed between Hispanic Spanish-speaking participants [0.41 (0.10)], Hispanic English-speaking participants [0.37 (0.10)], NH White participants [0.36 (0.10)], and NH Black participants [0.35 (0.09)], P < 0.001. Differences in HEI-2020 occurred at 2-5 y, with the Hispanic Spanish-speaking participants having consistently higher HEI-2020 scores. Differences in BMIz were observed at 5 y, with higher scores among Hispanic Spanish-speaking participants. Interaction between race, ethnicity, and IDQI was observed for all outcomes except for BMIz at 3 y. Through mediation, IDQI explained 13%-20% of the difference in HEI-2020 scores between Hispanic Spanish-speaking and NH White participants at 2-5 y. IDQI explained 22%-25% of the difference in HEI-2020 scores between the Hispanic Spanish-speaking and NH Black participants at 4 y and 5 y. CONCLUSIONS: Higher infant diet quality scores observed in Hispanic Spanish-speaking participants explain some of the racial and ethnic differences observed in later diet quality, suggesting that improving infant diet quality may help reduce diet disparities during early childhood.

Introduction: Immune checkpoint inhibitors (ICIs) have substantially advanced the treatment of patients with malignant melanoma. However, improving therapeutic efficacy requires identifying drug combinations that elicit durable responses without inducing intolerable toxicity. Within that context, selinexor emerges as a possible combination option that has been shown in preclinical studies to enhance the efficacy of ICI therapy. Methods: In this phase 1b study, we investigated selinexor in combination with pembrolizumab in 25 patients with advanced non-uveal melanoma. Patients received selinexor at a dosage of 60 mg taken orally twice weekly, and pembrolizumab intravenously at a dosage of 200 mg every 3 weeks. Results: Despite the high incidence of adverse events (96%), most treatment-related toxicities were manageable with supportive care and dose reductions. The most common adverse events of any grade were nausea (n = 20; 80%), decreased white blood cell count (n = 15; 60%), vomiting (n = 14; 56%), anemia (n = 12; 48%), fatigue (n = 12; 48%), and decreased platelet count (n = 12; 48%). The 10 patients with treatment-naïve evaluable disease had an objective response rate (ORR) of 70% (n = 7, including three patients with complete response), which was significantly higher than that of the 14 patients with prior anti–programmed cell death protein 1 (anti-PD-1) therapy, whose ORR was 7% (n = 1; p = 0.002). Stable disease was observed in two patients (20%) with treatment-naïve disease and seven patients (50%) with prior anti-PD-1 therapy. Conclusion: Selinexor combined with pembrolizumab showed promising antitumor activity in patients with treatment-naïve metastatic melanoma. The toxicity profile of the combination was consistent with that reported for individual agents, with no additional safety concerns.

Background: Amyloid-β (Aβ) peptide accumulation in the brain is a pathological hallmark of Alzheimer disease (AD). Because of the relationship between the Aβ plaque formation and AD progression, targeting Aβ has been advocated as a treatment strategy for this disease. Several studies have focused on immunotherapy methods, such as different vaccination approaches. Materials & Methods: In this systematic review, we explored the main features of the vaccines used to date, including their efficiency in inducing anti-Aβ antibodies and removing Aβ plaques. We also summarized the reported clinical outcomes and mortality rates. A total of 29 articles written in English that describe human clinical trials using three different vaccines (AN1792, CAD106 and AADVac) were reviewed. Results: Based on these studies, most of the patients who received one of these vaccines showed a significant anti-Aβ antibody response at some point during the trial. Several studies reported a decline in Aβ plaque load and an increase in Aβ phagocytosis in different brain regions. The time intervals between the initial vaccination and the booster doses vary among studies, but a 30-day interval has been suggested as the most appropriate by most studies. Meningoencephalitis, microhemorrhages, amyloid encephalopathy, allergic dermatitis and atrial fibrillation have been reported as the most common adverse effects in vaccinated patients. Conclusion: Clinical investigations have shown improved functional and cognitive outcomes, such as the mini-mental state examination score (MMSE), for vaccinated patients compared to the control groups. However, more human clinical studies are needed for a more conclusive evaluation of the properties of different vaccines.