Cultural Appropriation for Improved Knowledge Acquisition in Medical Education.

Background: Culture is an essential component that governs all aspects of human behavior. Superstition is an irrational belief observed in almost all cultures. It is linked to one or more factors like supernatural powers, good luck, bad omen, fiction, illegitimate activity, absurd narration, folk tales, or practice without any rational basis. Methods: A cross-sectional social experiment was conducted to evaluate the effect of cultural appropriation as a tool to enhance medical knowledge acquisition and attitudinal development in medical education. The experiment was designed to target a non-medical population. Four superstition-oriented videos were developed with 20 scientific pieces of information related to forensic medicine. A data collection sheet was developed on Microsoft form with 16 questions was distributed on the participants. Results: Out of the 986 participants, 763 (77.5%) watched the whole set of videos. About 55-95% of responders demonstrated knowledge acquisition of all the questions. There was a statistically significant difference between those who watched the videos and those who did not. When participants were asked about the most important information they remember from the videos, their answers fell into two main categories; information related to core scientific knowledge (80% of participants) and information not related to the core knowledge (16% of respondents). The top three areas for the reasons why people wanted to watch the videos were curiosity, knowledge, and career. A change in attitudes was reported among the participants where 80% of responders demonstrated curiosity to know more about this world, 46% responders reported developing more respect for the forensic physician and 43% revealed their ignorance about this great hidden world. Conclusion: Cultural appropriation could be a needed strategy to accommodate for upscale in education. Learners might validate that learning happens through a door that adopts not only honours their culture and adapts to it.

Rest the Brain to Learn New Gait Patterns after Stroke.

Background: The ability to relearn a lost skill is critical to motor recovery after a stroke. Previous studies indicate that stroke typically affects the processes underlying motor control and execution but not the learning of those skills. However, these prior studies could have been confounded by the presence of significant motor impairments and/or have not focused on motor acuity tasks (i.e., tasks focusing on the quality of executed actions) that have direct functional relevance to rehabilitation. Methods: Twenty-five participants (10 stroke; 15 controls) were recruited for this prospective, case-control study. Participants learned a novel foot-trajectory tracking task on two consecutive days while walking on a treadmill. On day 1, participants learned a new gait pattern by performing a task that necessitated greater hip and knee flexion during the swing phase of the gait. On day 2, participants repeated the task with their training leg to test retention. An average tracking error was computed to determine online and offline learning and was compared between stroke survivors and uninjured controls. Results: Stroke survivors were able to improve their tracking performance on the first day (p=0.033); however, the amount of learning in stroke survivors was lower in comparison with the control group on both days (p≤0.05). Interestingly, the offline gains in motor learning were higher in stroke survivors when compared with uninjured controls (p=0.011). Conclusions: The results suggest that even high-functioning stroke survivors may have difficulty acquiring new motor skills related to walking, which may be related to the underlying neural damage caused at the time of stroke. Furthermore, it is likely that stroke survivors may require longer training with adequate rest to acquire new motor skills, and rehabilitation programs should target motor skill learning to improve outcomes after stroke.

Midwives' experiences of professional learning when practicing collegial midwifery assistance during the active second stage of labour: data from the oneplus trial.

BACKGROUND: Learning is a lifelong process and the workplace is an essential arena for professional learning. Workplace learning is particularly relevant for midwives as essential knowledge and skills are gained through clinical work. A clinical practice known as 'Collegial Midwifery Assistance' (CMA), which involves two midwives being present during the active second stage of labour, was found to reduce severe perineal trauma by 30% in the Oneplus trial. Research regarding learning associated with CMA, however, is lacking. The aim was to investigate learning experiences of primary and second midwives with varying levels of work experience when practicing CMA, and to further explore possible factors that influence their learning. METHODS: The study uses an observational design to analyse data from the Oneplus trial. Descriptive statistics and proportions were calculated with 95% confidence intervals. Stratified univariable and multivariable logistic regression analysis were performed. RESULTS: A total of 1430 births performed with CMA were included in the study. Less experienced primary midwives reported professional learning to a higher degree (< 2 years, 76%) than the more experienced (> 20 years, 22%). A similar but less pronounced pattern was seen for the second midwives. Duration of the intervention ≥ 15 min improved learning across groups, especially for the least experienced primary midwives. The colleague's level of experience was found to be of importance for primary midwives with less than five years' work experience, whereas for second midwives it was also important in their mid to late career. Reciprocal feedback had more impact on learning for the primary midwife than the second midwife. CONCLUSIONS: The study provides evidence that CMA has the potential to contribute with professional learning both for primary and second midwives, for all levels of work experience. We found that factors such as the colleague's work experience, the duration of CMA and reciprocal feedback influenced learning, but the importance of these factors were different for the primary and second midwife and varied depending on the level of work experience. The findings may have implications for future implementation of CMA and can be used to guide the practice.

Insights into the alleviation of cadmium toxicity in rice by nano-zinc and Serendipita indica: Modulation of stress-responsive gene expression and antioxidant defense system activation.

The adversities of cadmium (Cd) contamination are quite distinguished among other heavy metals (HMs), and so is the efficacy of zinc (Zn) nutrition in mitigating Cd toxicity. Rice (Oryza sativa) crop, known for its ability to absorb HMs, inadvertently facilitates the bioaccumulation of Cd, posing a significant risk to both the plant itself and to humans consuming its edible parts, and damaging the environment as well. The use of nanoparticles, such as nano-zinc oxide (nZnO), to improve the nutritional quality of crops and combat the harmful effects of HMs, have gained substantial attention among scientists and farmers. While previous studies have explored the individual effects of nZnO or Serendipita indica (referred to as S.i) on Cd toxicity, the synergistic action of these two agents has not been thoroughly investigated. Therefore, the gift of nature, i.e., S. indica, was incorporated alongside nZnO (50 mg L-1) against Cd stress (15 µM L-1) and their alliance manifested as phenotypic level modifications in two rice genotypes (Heizhan43; Hz43 and Yinni801; Yi801). Antioxidant activities were enhanced, specifically peroxidase (61.5 and 122.5% in Yi801 and Hz43 roots, respectively), leading to a significant decrease in oxidative burst; moreover, Cd translocation was reduced (85% for Yi801 and 65.5% for Hz43 compared to Cd alone treatment). Microstructural study showed a decrease in number of vacuoles and starch granules with ameliorative treatments. Overall, plants treated with nZnO displayed gene expression pattern (particularly of ZIP genes), different from the ones with alone or combined S.i and Cd. Inferentially, the integration of nZnO and S.i holds great promise as an effective strategy for alleviating Cd toxicity in rice plants. By immobilizing Cd ions in the soil and promoting their detoxification, this novel approach contributes to environmental restoration and ensures food safety worldwide.

Learning verbs in English and Korean: The roles of word order and argument drop.

To learn new words, particularly verbs, child learners have been shown to benefit from the linguistic contexts in which the words appear. However, cross-linguistic differences affect how this process unfolds. One previous study found that children's abilities to learn a new verb differed across Korean and English as a function of the sentence in which the verb occurred (Arunachalam et al., 2013). The authors hypothesized that the properties of word order and argument drop, which vary systematically in these two languages, were driving the differences. In the current study, we pursued this finding to ask if the difference persists later in development, or if children acquiring different languages come to appear more similar as their linguistic knowledge and learning capacities increase. Preschool-aged monolingual English learners (N = 80) and monolingual Korean learners (N = 64) were presented with novel verbs in contexts that varied in word order and argument drop and accompanying visual stimuli. We assessed their learning by measuring accuracy in a forced-choice pointing task, and we measured eye gaze during the learning phase as an indicator of the processes by which they mapped the novel verbs to meaning. Unlike previous studies which identified differences between English and Korean learning 2-year-olds in a similar task, our results revealed similarities between the two language groups with these older preschoolers. We interpret our results as evidence that over the course of early childhood, children become adept at learning from a larger variety of contexts, such that differences between learners of different languages are attenuated.

Incidental durotomy resulting in a postoperative lumbosacral nerve root with eventration into the adjacent facet joint: illustrative cases.

BACKGROUND: Radicular pain after lumbar decompression surgery can result from epidural hematoma/seroma, recurrent disc herniation, incomplete decompression, or other rare complications. A less recognized complication is postoperative nerve root herniation, resulting from an initially unrecognized intraoperative or, more commonly, a spontaneous postoperative durotomy. Rarely, this nerve root herniation can become entrapped within local structures, including the facet joint. The aim of this study was to illustrate our experience with three cases of lumbosacral nerve root eventration into an adjacent facet joint and to describe our diagnostic and surgical approach to this rare complication. OBSERVATIONS: Three patients who had undergone lumbar decompression surgery with or without fusion experienced postoperative radiculopathy. Exploratory revision surgery revealed all three had a durotomy with nerve root eventration into the facet joint. Significant symptom improvement was achieved in all patients following liberation of the neural elements from the facet joints. LESSONS: Entrapment of herniated nerve roots into the facet joint may be a previously underappreciated complication and remains quite challenging to diagnose even with the highest-quality advanced imaging. Thus, clinicians must have a high index of suspicion to diagnose this issue and a low threshold for surgical exploration.

Evaluating the Impact of Practical Training: A Study on Satisfaction and Drug Knowledge among Pharmacy Students.

Practical training stands as a crucial component in shaping pharmacy students, bridging the gap between classroom-based theoretical knowledge and its application in real-world contexts. This study investigates the correlation between the satisfaction levels experienced during practical training and the acquisition of knowledge, particularly focusing on drug names. Drawing from the National DataBase (NDB) open data provided by Japan's Ministry of Health, Labour and Welfare, a survey centered on the top 100 dispensed drugs was crafted. A correlation analysis was conducted between the satisfaction scores gathered from students and their depth of knowledge on drug names. Intriguingly, despite observing a significantly high satisfaction level during the practical training, there was no marked correlation between this satisfaction and the proficiency in recalling drug names after the training. Furthermore, the volume of daily prescriptions handled did not significantly impact this knowledge. The findings underscore the notion that high satisfaction during training does not necessarily guarantee a thorough understanding of the subject matter. This sheds light on the importance of not solely relying on satisfaction metrics in training programs and ensuring a holistic, in-depth educational approach.

Metabolic causes of liver disease among adults living with HIV from low- and middle-income countries: a cross-sectional study.

INTRODUCTION: Liver disease is a leading cause of morbidity and mortality among persons living with HIV (PLHIV). While chronic viral hepatitis has been extensively studied in low- and middle-income countries (LMICs), there is limited information about the burden of metabolic disorders on liver disease in PLHIV. METHODS: We conducted a cross-sectional analysis of baseline data collected between October 2020 and July 2022 from the IeDEA-Sentinel Research Network, a prospective cohort enrolling PLHIV ≥40 years on antiretroviral treatment (ART) for ≥6 months from eight clinics in Asia, Americas, and central, East, southern and West Africa. Clinical assessments, laboratory testing on fasting blood samples and liver stiffness measurement (LSM)/controlled attenuation parameter (CAP) by vibration-controlled transient elastography were performed. Multivariable logistic regression models assessed factors associated with liver fibrosis (LSM ≥7.1 kPa) and steatosis (CAP ≥248 dB/m). Population attributable fraction (PAF) of each variable associated with significant liver fibrosis was estimated using Levin's formula. RESULTS: Overall, 2120 PLHIV (56% female, median age 50 [interquartile range: 45-56] years) were included. The prevalence of obesity was 19%, 12% had type 2 diabetes mellitus (T2DM), 29% had hypertension and 53% had dyslipidaemia. The overall prevalence of liver fibrosis and steatosis was 7.6% (95% confidence interval [CI] 6.1-8.4) and 28.4% (95% CI 26.5-30.7), respectively, with regional variability. Male sex at birth (odds ratio [OR] 1.62, CI 1.10-2.40), overweight/obesity (OR = 2.50, 95% CI 1.69-3.75), T2DM (OR 2.26, 95% CI 1.46-3.47) and prolonged exposure to didanosine (OR 3.13, 95% CI 1.46-6.49) were associated with liver fibrosis. Overweight/obesity and T2DM accounted for 42% and 11% of the PAF for liver fibrosis, while HBsAg and anti-HCV accounted for 3% and 1%, respectively. Factors associated with steatosis included overweight/obesity (OR 4.25, 95% CI 3.29-5.51), T2DM (OR 2.06, 95% CI 1.47-2.88), prolonged exposure to stavudine (OR 1.69, 95% CI 1.27-2.26) and dyslipidaemia (OR 1.68, 95% CI 1.31-2.16). CONCLUSIONS: Metabolic disorders were significant risk factors for liver disease among PLHIV in LMICs. Early recognition of metabolic disorders risk factors might be helpful to guide clinical and lifestyle interventions. Further prospective studies are needed to determine the causative natures of these findings.

Plant communication with rhizosphere microbes can be revealed by understanding microbial functional gene composition.

Understanding rhizosphere microbial ecology is necessary to reveal the interplay between plants and associated microbial communities. The significance of rhizosphere-microbial interactions in plant growth promotion, mediated by several key processes such as auxin synthesis, enhanced nutrient uptake, stress alleviation, disease resistance, etc., is unquestionable and well reported in numerous literature. Moreover, rhizosphere research has witnessed tremendous progress due to the integration of the metagenomics approach and further shift in our viewpoint from taxonomic to functional diversity over the past decades. The microbial functional genes corresponding to the beneficial functions provide a solid foundation for the successful establishment of positive plant-microbe interactions. The microbial functional gene composition in the rhizosphere can be regulated by several factors, e.g., the nutritional requirements of plants, soil chemistry, soil nutrient status, pathogen attack, abiotic stresses, etc. Knowing the pattern of functional gene composition in the rhizosphere can shed light on the dynamics of rhizosphere microbial ecology and the strength of cooperation between plants and associated microbes. This knowledge is crucial to realizing how microbial functions respond to unprecedented challenges which are obvious in the Anthropocene. Unraveling how microbes-mediated beneficial functions will change under the influence of several challenges, requires knowledge of the pattern and composition of functional genes corresponding to beneficial functions such as biogeochemical functions (nutrient cycle), plant growth promotion, stress mitigation, etc. Here, we focus on the molecular traits of plant growth-promoting functions delivered by a set of microbial functional genes that can be useful to the emerging field of rhizosphere functional ecology.

To what extent do children's expressions of time actually refer to time? An investigation into the temporal and discursive usages of temporal adverbs in family interaction.

Many studies have explored children's acquisition of temporal adverbs. However, the extent to which children's early temporal language has discursive instead of solely temporal meanings has been largely ignored. We report two corpus-based studies that investigated temporal adverbs in Finnish child-parent interaction between the children's ages of 1;7 and 4;11. Study 1 shows that the two corpus children used temporal adverbs to construe both temporal and discursive meanings from their early adverb production and that the children's usage syntactically broadly reflected the input received. Study 2 shows that the discursive uses of adverbs appeared to be learned from contextually anchored caregiver constructions that convey discourse functions like urging and reassuring, and that the usage is related to the children's and caregivers' interactional roles. Our study adds to the literature on the acquisition of temporal adverbs by demonstrating that these items are learned also with additional discursive meanings in family interaction.

Babbling opens the sensory phase for imitative vocal learning.

Zebra finches, a species of songbirds, learn to sing by creating an auditory template through the memorization of model songs (sensory learning phase) and subsequently translating these perceptual memories into motor skills (sensorimotor learning phase). It has been traditionally believed that babbling in juvenile birds initiates the sensorimotor phase while the sensory phase of song learning precedes the onset of babbling. However, our findings challenge this notion by demonstrating that testosterone-induced premature babbling actually triggers the onset of the sensory learning phase instead. We reveal that juvenile birds must engage in babbling and self-listening to acquire the tutor song as the template. Notably, the sensory learning of the template in songbirds requires motor vocal activity, reflecting the observation that prelinguistic babbling in humans plays a crucial role in auditory learning for language acquisition.

A Comprehensive Examination of Prediction-Based Error as a Mechanism for Syntactic Development: Evidence From Syntactic Priming.

Prediction-based accounts of language acquisition have the potential to explain several different effects in child language acquisition and adult language processing. However, evidence regarding the developmental predictions of such accounts is mixed. Here, we consider several predictions of these accounts in two large-scale developmental studies of syntactic priming of the English dative alternation. Study 1 was a cross-sectional study (N = 140) of children aged 3-9 years, in which we found strong evidence of abstract priming and the lexical boost, but little evidence that either effect was moderated by age. We found weak evidence for a prime surprisal effect; however, exploratory analyses revealed a protracted developmental trajectory for verb-structure biases, providing an explanation as for why prime surprisal effects are more elusive in developmental populations. In a longitudinal study (N = 102) of children in tightly controlled age bands at 42, 48, and 54 months, we found priming effects emerged on trials with verb overlap early but did not observe clear evidence of priming on trials without verb overlap until 54 months. There was no evidence of a prime surprisal effect at any time point and none of the effects were moderated by age. The results relating to the emergence of the abstract priming and lexical boost effects are consistent with prediction-based models, while the absence of age-related effects appears to reflect the structure-specific challenges the dative presents to English-acquiring children. Overall, our complex pattern of findings demonstrates the value of developmental data sets in testing psycholinguistic theory.

Acquisition Duration Optimization Using Visual Grading Regression in [68Ga]FAPI-46 PET Imaging of Oncologic Patients.

Fibroblast activation protein is a promising target for oncologic molecular imaging with radiolabeled fibroblast activation protein inhibitors (FAPI) in a large variety of cancers. However, there are yet no published recommendations on how to set up an optimal imaging protocol for FAPI PET/CT. It is important to optimize the acquisition duration and strive toward an acquisition that is sufficiently short while simultaneously providing sufficient image quality to ensure a reliable diagnosis. The aim of this study was to evaluate the feasibility of reducing the acquisition duration of [68Ga]FAPI-46 imaging while maintaining satisfactory image quality, with certainty that the radiologist's ability to make a clinical diagnosis would not be affected. Methods: [68Ga]FAPI-46 PET/CT imaging was performed on 10 patients scheduled for surgical resection of suspected pancreatic cancer, 60 min after administration of 3.6 ± 0.2 MBq/kg. The acquisition time was 4 min/bed position, and the raw PET data were statistically truncated and reconstructed to represent images with an acquisition duration of 1, 2, and 3 min/bed position, additional to the reference images of 4 min/bed position. Four image quality criteria that focused on the ability to distinguish specific anatomic details, as well as perceived image noise and overall image quality, were scored on a 4-point Likert scale and analyzed with mixed-effects ordinal logistic regression. Results: A trend toward increasing image quality scores with increasing acquisition duration was observed for all criteria. For the overall image quality, there was no significant difference between 3 and 4 min/bed position, whereas 1 and 2 min/bed position were rated significantly (P < 0.05) lower than 4 min/bed position. For the other criteria, all images with a reduced acquisition duration were rated significantly inferior to images obtained at 4 min/bed position. Conclusion: The acquisition duration can be reduced from 4 to 3 min/bed position while maintaining satisfactory image quality. Reducing the acquisition duration to 2 min/bed position or lower is not recommended since it results in inferior-quality images so noisy that clinical interpretation is significantly disrupted.

Radiation dose reduction of 50% in dynamic myocardial CT perfusion with skipped beat acquisition: a retrospective study.

BACKGROUND: Dynamic myocardial computed tomography perfusion (CTP) is a novel imaging technique that increases the applicability of CT for cardiac imaging; however, the scanning requires a substantial radiation dose. PURPOSE: To investigate the feasibility of dose reduction in dynamic CTP by comparing all-heartbeat acquisitions to periodic skipping of heartbeats. MATERIAL AND METHODS: We retrieved imaging data of 38 dynamic CTP patients and created new datasets with every fourth, third or second beat (Skip1:4, Skip1:3, Skip1:2, respectively) removed. Seven observers evaluated the resulting images and perfusion maps for perfusion deficits. The mean blood flow (MBF) in each of the 16 myocardial segments was compared per skipped-beat level, normalized by the respective MBF for the full dose, and averaged across patients. The number of segments/cases whose MBF was <1.0 mL/g/min were counted. RESULTS: Out of 608 segments in 38 cases, the total additional number of false-negative (FN) segments over those present in the full-dose acquisitions and the number of additional false-positive cases were shown as acquisition (segment [%], case): Skip1:4: 7 (1.2%, 1); Skip1:3: 12 (2%, 3), and Skip1:2: 5 (0.8%, 2). The variability in quantitative MBF analysis in the repeated analysis for the reference condition resulted in 8 (1.3%) additional FN segments. The normalized results show a comparable MBF across all segments and patients, with relative mean MBFs as 1.02 ± 0.16, 1.03 ± 0.25, and 1.06 ± 0.30 for the Skip1:4, Skip1:3, and Skip1:2 protocols, respectively. CONCLUSION: Skipping every second beat acquisition during dynamic myocardial CTP appears feasible and may result in a radiation dose reduction of 50%. Diagnostic performance does not decrease after removing 50% of time points in dynamic sequence.

Inserting Pre-analytical Chromatographic Priming Runs Significantly Improves Targeted Pathway Proteomics with Sample Multiplexing.

GoDig, a platform for targeted pathway proteomics without the need for manual assay scheduling or synthetic standards, is a powerful, flexible, and easy-to-use method that uses tandem mass tags to increase sample throughput up to 18-fold relative to label-free methods. Though the protein-level success rates of GoDig are high, the peptide-level success rates are more limited, hampering assays of harder-to-quantify proteins and site-specific phenomena. To guide the optimization of GoDig assays as well as improvements to the GoDig platform, we created GoDigViewer, a new stand-alone software that provides detailed visualizations of GoDig runs. GoDigViewer guided the implementation of "priming runs," an acquisition mode with significantly higher success rates. In this mode, two or more chromatographic priming runs are automatically performed to improve the accuracy and precision of target elution orders, followed by analytical runs which quantify targets. Using priming runs, success rates exceeded 97% for a list of 400 peptide targets and 95% for a list of 200 targets that are usually not quantified using untargeted mass spectrometry. We used priming runs to establish a quantitative assay of 125 macroautophagy proteins that had a >95% success rate and revealed differences in macroautophagy expression profiles across four human cell lines.

Concomitant investigation of crustacean amphipods lipidome and metabolome during the molting cycle by Zeno SWATH data-independent acquisition coupled with electron activated dissociation and machine learning.

BACKGROUND: DIA (Data-Independent Acquisition) is a powerful technique in Liquid Chromatography coupled with high-resolution tandem Mass Spectrometry (LC-MS/MS) initially developed for proteomics studies and recently emerging in metabolomics and lipidomics. It provides a comprehensive and unbiased coverage of molecules with improved reproducibility and quantitative accuracy compared to Data-Dependent Acquisition (DDA). Combined with the Zeno trap and Electron-Activated Dissociation (EAD), DIA enhances data quality and structural elucidation compared to conventional fragmentation under CID. These tools were applied to study the lipidome and metabolome of the freshwater amphipod Gammarus fossarum, successfully discriminating stages and highlighting significant biological features. Despite being underused, DIA, along with the Zeno trap and EAD, holds great potential for advancing research in the omics field. RESULTS: DIA combined with the Zeno trap enhances detection reproducibility compared to conventional DDA, improving fragmentation spectra quality and putative identifications. LC coupled with Zeno-SWATH-DIA methods were used to characterize molecular changes in reproductive cycle of female gammarids. Multivariate data analysis including Principal Component Analysis and Partial Least Square Discriminant Analysis successfully identified significant features. EAD fragmentation helped to identify unknown features and to confirm their molecular structure using fragmentation spectra database annotation or machine learning. EAD database matching accurately annotated five glycerophospholipids, including the position of double bonds on fatty acid chain moieties. SIRIUS database predicted structures of unknown features based on experimental fragmentation spectra to compensate for database incompleteness. SIGNIFICANCE: Reproducible detection of features and confident identification of putative compounds are pivotal stages within analytical pipelines. The DIA approach combined with Zeno pulsing enhances detection sensitivity and targeted fragmentation with EAD in positive polarity provides orthogonal fragmentation information. In our study, Zeno-DIA and EAD thereby facilitated a comprehensive and insightful exploration of pertinent biological molecules associated with the reproductive cycle of gammarids. The developed methodology holds great promises for identifying informative biomarkers on the health status of an environmental sentinel species.

[Deciphering cellular processes responding to lethality of 17ß-estradiol by quantitative phosphoproteomics].

17ß-Estradiol (E2), an important endocrine hormone in the mammalian body, participates in the regulation of the physiological functions of the reproductive system, mammary glands, bone, and cardiovascular system, among others. Paradoxically, despite the physiological actions of endogenous E2 (0.2-1.0 nmol/L), numerous clinical and experimental studies have demonstrated that high-dose E2 treatment can cause tumor regression and exert pro-apoptotic actions in multiple cell types; however, the underlying mechanism remains undescribed. In particular, little information of the cellular processes responding to the lethality of E2 is available. In the present study, we attempted to characterize the cellular processes responding to high-dose (µmol/L) E2 treatment using quantitative phosphoproteomics to obtain a better understanding of the regulatory mechanism of E2-induced cell death. First, the cell phenotype induced by high-dose E2 was determined by performing Cell Counting Kit-8 assay (CCK8), cell cytotoxicity analysis by trypan blue staining, and microscopic imaging on HeLa cells treated with 1-10 µmol/L E2 or dimethyl sulfoxide (DMSO) for 1-3 d. E2 inhibited cell proliferation and induced cell death in a dose- and time-dependent manner. Compared with the DMSO-treated HeLa cells, the cells treated with 5 µmol/L E2 for 2 d demonstrated >74% growth inhibition and approximately 50% cell death. Thus, these cells were used for quantitative phosphoproteomic analysis. Next, a solid-phase extraction (SPE)-based immobilized titanium ion affinity chromatography (Ti4+-IMAC) phosphopeptide-enrichment method coupled with data-independent acquisition (DIA)-based quantitative proteomics was employed for the in-depth screening of high-dose E2-regulated phosphorylation sites to investigate the intracellular processes responding to high-dose E2 treatment. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) identified over 10000 phosphorylation sites regulated by E2 and DMSO in HeLa cells. In comparison with the DMSO-treated cells, the cells treated with 5 µmol/L E2 showed 537 upregulated phosphorylation sites and 387 downregulated phosphorylation sites, with a threshold of p<0.01 and |log2(fold change)|≥1. A total of 924 phosphorylation sites on 599 proteins were significantly regulated by high-dose E2, and these sites were subjected to enrichment analysis. In addition, 453 differently regulated phosphorylation sites on 325 proteins were identified only in the E2- or DMSO-treated cell samples. These phosphorylation sites may be phosphorylated or dephosphorylated in response to high-dose E2 stimulation and were subjected to parallel enrichment analyses. Taken together, 1218 phosphorylation sites on 741 proteins were significantly regulated by high-dose E2 treatment. The functional phosphoproteins in these two groups were then analyzed using Gene Ontology (GO) and Gene Set Enrichment Analysis (GSEA) to determine the biological processes in which they participate and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway database. Consistent with the cell-phenotype data, cell cycle-related proteins were highly enriched in the two groups of E2-regulated phosphoproteins (p<0.05), indicating that high-dose E2 treatment can regulate cell proliferation. In addition, E2-regulated phosphoproteins were highly enriched in the cellular processes of ribosome biogenesis, nucleocytoplasmic transport, and messenger ribonucleic acid (mRNA) processing/splicing (p<0.05), indicating that the activation of these processes may contribute to high-dose E2-induced cell death. These results further confirm that high-dose E2 treatment inhibits protein translation and induces cell death. Furthermore, the significant upregulation of multiple phosphorylation sites associated with epidermal growth factor receptor (EGFR) and mitogen-activated protein kinases (MAPKs) MAPK1, MAPK4, and MAPK14 by high-dose E2 indicates that the EGFR and MAPK signaling pathways are likely involved in the regulation of E2-induced cell death. These phosphorylation sites likely play vital roles in E2-induced cell death in HeLa cells. Overall, our phosphoproteomic data could be a valuable resource for uncovering the regulatory mechanisms of E2 in the micromolar range.

Attention-sensitive signalling by 7- to 20-month-old infants in a comparative perspective.

Attention-sensitive signalling is the pragmatic skill of signallers who adjust the modality of their communicative signals to their recipient's attention state. This study provides the first comprehensive evidence for its onset and development in 7-to 20-month-olds human infants, and underlines its significance for language acquisition and evolutionary history. Mother-infant dyads (N = 30) were studied in naturalistic settings, sampled according to three developmental periods (in months); [7-10], [11-14], and [15-20]. Infant's signals were classified by dominant perceptible sensory modality and proportions compared according to their mother's visual attention, infant-directed speech and tactile contact. Maternal visual attention and infant-directed speech were influential on the onset and steepness of infants' communicative adjustments. The ability to inhibit silent-visual signals towards visually inattentive mothers (unimodal adjustment) predated the ability to deploy audible-or-contact signals in this case (cross-modal adjustment). Maternal scaffolding of infant's early pragmatic skills through her infant-directed speech operates on the facilitation of infant's unimodal adjustment, the preference for oral over gestural signals, and the audio-visual combinations of signals. Additionally, breakdowns in maternal visual attention are associated with increased use of the audible-oral modality/channel. The evolutionary role of the sharing of attentional resources between parents and infants into the emergence of modern language is discussed.

Effects of ChatGPT's AI capabilities and human-like traits on spreading information in work environments.

The rapid proliferation and integration of AI chatbots in office environments, specifically the advanced AI model ChatGPT, prompts an examination of how its features and updates impact knowledge processes, satisfaction, and word-of-mouth (WOM) among office workers. This study investigates the determinants of WOM among office workers who are users of ChatGPT. We adopted a quantitative approach, utilizing a stratified random sampling technique to collect data from a diverse group of office workers experienced in using ChatGPT. The hypotheses were rigorously tested through Structural Equation Modeling (SEM) using the SmartPLS 4. The results revealed that system updates, memorability, and non-language barrier attributes of ChatGPT significantly enhanced knowledge acquisition and application. Additionally, the human-like personality traits of ChatGPT significantly increased both utilitarian value and satisfaction. Furthermore, the study showed that knowledge acquisition and application led to a significant increase in utilitarian value and satisfaction, which subsequently increased WOM. Age had a positive influence on WOM, while gender had no significant impact. The findings provide theoretical contributions by expanding our understanding of AI chatbots' role in knowledge processes, satisfaction, and WOM, particularly among office workers.