Inactivation of Cronobacter sakazakii in powdered infant formula with probiotics and metagenomic analysis.

In the present study, proper manual for powdered infant formula with probiotics (PIF-P) to prevent the contamination of Cronobacter sakazakii was investigated. First, the population of C. sakazakii and LAB in three different PIF-P samples were quantitatively analyzed after reconstituted with hydrothermal treatments. When C. sakazakii was inoculated into reconstituted infant formula with probiotics (RIF-P), it was immediately reduced below the detection limit by 60-65 °C hydrothermal treatment whereas reduction levels of LAB was 1-2 log CFU/g. When heat resistance of C. sakazakii inoculated to PIF-P with 4 h drying was compared with that inoculated to RIF-P samples, the heat resistance of C. sakazakii increased significantly after the inoculation in PIF-P with drying. Metagenomic analysis revealed that Lactobacillus and Bifidobacterium were dominant genus in all three groups and there was no significant difference in the microbial community of untreated PIF sample and hydrothermal treated samples. Supplementary Information: The online version contains supplementary material available at 10.1007/s10068-023-01503-x.

MASCC 2023 Patient-Centered Antiemetic Guidelines and Education Statements: an evidence-based and consensus resource for patients.

PURPOSE: The Multinational Association of Supportive Care in Cancer (MASCC)/European Society of Medical Oncology (ESMO) Patient Antiemetic Guideline Committee aimed to (1) adapt the updated evidence-based, clinical guidelines to patient-centered antiemetic guidelines and (2) develop patient education materials and statements. METHODS: The MASCC 2023 Patient Antiemetic Guidelines were created and reviewed by antiemetic experts and patient advocates by incorporating the 2023 MASCC/ESMO antiemetic guidelines into patient-friendly language. Patient Education Statements were developed based on current literature and by utilizing an expert modified Delphi consensus (≥ 75% agreement). Patient advocate/focus group input and patient survey results were further integrated into Patient-Centered Antiemetic Guidelines and Education Statements. RESULTS: Patient-Centered Antiemetic Guidelines were created using patient-friendly language and visual slides. Patient-friendly language was also utilized to communicate the Educational Statements. Key content categories identified for the Educational Statements included the following: nausea/vomiting definitions, causes, risk factors, categories, complications, accompanying symptoms, prophylactic antiemetic treatment, general management, when to call/what to ask the healthcare team, what caregivers can do, and available resources. All identified content met the ≥ 75% expert agreement threshold. Fifteen (15) items demonstrated 100% agreement, 11 items achieved ≥ 90% agreement, and three content items demonstrated 80 ~ 82% agreement. CONCLUSIONS: The inaugural MASCC 2023 Patient Antiemetic Guidelines can help patients and caregivers understand the prevention of nausea and vomiting related to their cancer treatment. Educational Statements provide further patient information. Educating patients on how to utilize guideline antiemetics and the education statements can contribute improvements in the control of anticancer treatment-related nausea and vomiting.

The changes in biethnic acceptance across daily settings and biethnic adolescents' psychological well-being during middle school transition.

INTRODUCTION: Patterns of biethnic adolescents' perceived biethnic acceptance across families, peers, and school contexts were examined during the transition from elementary to middle school in South Korea. We also examined how the transition patterns were related to their psychological outcomes during this period. METHODS: Utilizing 2-wave data (2017 and 2019) from the Panel Survey of Korean Multicultural Youth Adjustment, a latent transition analysis was conducted. Participants were biethnic adolescents who were in 5th or 6th grade at Wave 1 (N = 245; 51.02% female; Mage = 11.38). Their fathers were Korean, and mothers were immigrants from neighboring countries. Familial ethnic socialization, peer discrimination, and school multicultural climate scores were used as indicators of biethnic acceptance. Outcomes of self-esteem, depression, and biethnic affirmation were also examined. RESULTS: Latent profile and transition analyses yielded two groups (i.e., high acceptance and low acceptance) at each wave and four transition patterns (i.e., high-high, low-high, low-low, and high-low). Compared to high-high group, which was the most prevalent group, low-low and high-low groups reported lower self-esteem and ethnic affirmation, and greater depression at Wave 3. CONCLUSIONS: While for the majority of participants, their daily settings continued to be high in biethnic acceptance across the transition period, most at risk were those who perceived a decrease in biethnic acceptance in their daily settings. Results shed light on the need for support to maintain the context of high biethnic acceptance surrounding biethnic adolescents for their psychological well-being in school transitions.

SNPs in microRNA seed region and impact of miR-375 in concurrent regulation of multiple lipid accumulation-related genes.

Bovine intramuscular fat (IMF), commonly referred to as marbling, is regulated by lipid metabolism, which includes adipogenesis, lipogenesis, glycerolipid synthesis, and lipolysis. In recent years, breeding researchers have identified single nucleotide polymorphisms (SNPs) as useful marker-assisted selection tools for improving marbling scores in national breeding programs. These included causal SNPs that induce phenotypic variation. MicroRNAs (miRNAs) are small highly conserved non-coding RNA molecules that bind to multiple non-coding regions. They are involved in post-transcriptional regulation. Multiple miRNAs may regulate a given target. Previously, three SNPs in the GPAM 3' UTR and four miRNAs were identified through in silico assays. The aim of this study is to verify the binding ability of the four miRNAs to the SNPs within the 3'UTR of GPAM, and to identify the regulatory function of miR-375 in the expression of genes related to lipid metabolism in mammalian adipocytes. It was verified that the four miRNAs bind to the GPAM 3'UTR, and identified that the miR-375 sequence is highly conserved. Furthermore, it was founded that miR-375 upregulated the GPAM gene, C/EBPα, PPARγ and lipid metabolism-related genes and promoted lipid droplet accumulation in 3T3-L1 cells. In conclusion, these results suggest that miR-375 is a multifunctional regulator of multiple lipid metabolism-related genes and may aid in obesity research as a biomarker.

The Risk of Venous Thromboembolism and Ischemic Stroke Stratified by VTE Risk Following Multiple Myeloma: A Korean Population-Based Cohort Study.

Background: Multiple myeloma (MM) is associated with high morbidity and mortality, with elevated rates of arterial thrombosis and venous thromboembolism (VTE) and ischemic stroke (IS). We aimed to estimate the incidence of VTE and IS categorized by the VTE risk grade among individuals with MM in Korea. Additionally, we explored the potential of the IMPEDE VTE score as a tool for assessing IS risk in patients with MM. Methods: This retrospective cohort study comprised 37,168 individuals aged ≥ 18 years newly diagnosed with MM between January 2008 and December 2021 using the representative claims database of the Korean population. The risk of the incidence of VTE and IS within 6 months after MM diagnosis was stratified based on high-risk (IMPEDE VTE score ≥ 8) and low-risk (<8) categories. The hazard ratios (HRs) were estimated using Cox proportional hazard models. Results: The VTE incidence was 120.4 per 1000 person-years and IS incidence was 149.3 per 1000 person-years. Statistically significant differences were observed in the cumulative incidence rates of VTE between groups with high and low VTE scores (p < 0.001) and between individuals aged ≤ 65 years (p < 0.001) and those with a Charlson comorbidity index (CCI) ≥ 3 compared to lower scores (p < 0.001). Additionally, the cumulative incidence rate of IS differed significantly across all groups (p < 0.001). The HR for the high-risk group in VTE and IS occurrence was 1.59 (95% CI, 1.26-2.00) and 3.47 (95% CI, 2.99-4.02), respectively. Conclusions: It is important to screen and manage high-risk groups for the early development of VTE or IS in patients with newly diagnosed MM.

Orthodontic diagnosis rates based on panoramic radiographs in children aged 6-8 years: A retrospective study.

Objective: This study aimed to retrospectively analyze the prevalence of orthodontic problems and the proportion of patients who underwent orthodontic diagnosis among children aged 6 (n = 300), 7 (n = 400), and 8 (n = 400) years who had undergone panoramic radiography. Methods: Children were divided into five groups according to their chief complaint and consultation: conservative dentistry, oral and maxillofacial surgery, orthodontics, periodontics, and prosthodontics). Chief complaints investigated included first molar eruption, lack of space for incisor eruption, frequency of eruption problems, lack of space, impaction, supernumerary teeth (SNT), missing teeth, and ectropion eruption. The number of patients whose chief complaint was not related to orthodontics but had dental problems requiring orthodontic treatment was counted. The proportion of patients with orthodontic problems who received an orthodontic diagnosis was also examined. Results: Dental trauma and SNT were the most frequent chief complaints among the children. The proportion of patients with orthodontic problems increased with age. However, the orthodontic diagnosis rates based on panoramic radiographs among children aged 6, 7, 8 years were only 1.5% (6 years) and 23% (7 and 8 years). Conclusions: Accurate information should be provided to patient caregivers to correct misconceptions regarding the appropriateness of delaying orthodontic examination until permanent dentition is established.

The needs for digital health and eHeath literacy of cancer patients, caregivers, and healthcare providers: A multicenter, descriptive correlational study.

PURPOSE: Digital health is an indispensable tool, but its use depends on the eHealth literacy (eHL) of end-users. This study aimed to understand the need for digital health and eHL among cancer patients, caregivers, and healthcare providers and to identify differences in digital health needs related to the eHL of cancer patients. METHODS: A multicenter, descriptive correlational study was conducted and included a total of 209 patients, 150 caregivers and 150 healthcare providers. Digital health needs were identified, and eHL was measured using the Korean version of the eHealth Literacy Scale. Differences in digital health needs in relation to the eHL of patients were analyzed. RESULTS: The most necessary digital health functions among cancer patients and caregivers were 'information and education on symptom management after cancer treatment' and 'education on coping methods for each type of cancer' (87.1-94.0%). Healthcare providers reported the need for a digital health function for 'medication information' and assisting in 'medical appointments' (96.7-98.0%). The preferred types of digital health were telemonitoring, mobile services, and telemedicine by telephone (81.3-90.5%). The mean eHL score of the cancer patients was 28.84 ± 6.75. Differences existed in the need for digital health functions and preferences for digital health types between cancer patients with high and low eHL. CONCLUSIONS: Cancer patients and caregivers expressed strong needs for digital health that provide information and education about symptom management and coping with cancer. Digital health interventions for cancer care need to be developed to reflect the identified needs and preferences and eHL of end-users.

A multimodal machine learning model for predicting dementia conversion in Alzheimer's disease.

Alzheimer's disease (AD) accounts for 60-70% of the population with dementia. Mild cognitive impairment (MCI) is a diagnostic entity defined as an intermediate stage between subjective cognitive decline and dementia, and about 10-15% of people annually convert to AD. We aimed to investigate the most robust model and modality combination by combining multi-modality image features based on demographic characteristics in six machine learning models. A total of 196 subjects were enrolled from four hospitals and the Alzheimer's Disease Neuroimaging Initiative dataset. During the four-year follow-up period, 47 (24%) patients progressed from MCI to AD. Volumes of the regions of interest, white matter hyperintensity, and regional Standardized Uptake Value Ratio (SUVR) were analyzed using T1, T2-weighted-Fluid-Attenuated Inversion Recovery (T2-FLAIR) MRIs, and amyloid PET (αPET), along with automatically provided hippocampal occupancy scores (HOC) and Fazekas scales. As a result of testing the robustness of the model, the GBM model was the most stable, and in modality combination, model performance was further improved in the absence of T2-FLAIR image features. Our study predicts the probability of AD conversion in MCI patients, which is expected to be useful information for clinician's early diagnosis and treatment plan design.

Prevalence and Associated Factors of Depression and Anxiety Among Healthcare Workers During the Coronavirus Disease 2019 Pandemic: A Nationwide Study in Korea.

BACKGROUND: A healthcare system's collapse due to a pandemic, such as the coronavirus disease 2019 (COVID-19), can expose healthcare workers (HCWs) to various mental health problems. This study aimed to investigate the impact of the COVID-19 pandemic on the depression and anxiety of HCWs. METHODS: A nationwide questionnaire-based survey was conducted on HCWs who worked in healthcare facilities and public health centers in Korea in December 2020. Patient Health Questionnaire-9 (PHQ-9) and Generalized Anxiety Disorder-7 (GAD-7) were used to measure depression and anxiety. To investigate factors associated with depression and anxiety, stepwise multiple logistic regression analysis was performed. RESULTS: A total of 1,425 participating HCWs were included. The mean depression score (PHQ-9) of HCWs before and after COVID-19 increased from 2.37 to 5.39, and the mean anxiety score (GAD-7) increased from 1.41 to 3.41. The proportion of HCWs with moderate to severe depression (PHQ-9 ≥ 10) increased from 3.8% before COVID-19 to 19.5% after COVID-19, whereas that of HCWs with moderate to severe anxiety (GAD-7 ≥ 10) increased from 2.0% to 10.1%. In our study, insomnia, chronic fatigue symptoms and physical symptoms after COVID-19, anxiety score (GAD-7) after COVID-19, living alone, and exhaustion were positively correlated with depression. Furthermore, post-traumatic stress symptoms, stress score (Global Assessment of Recent Stress), depression score (PHQ-9) after COVID-19, and exhaustion were positively correlated with anxiety. CONCLUSION: In Korea, during the COVID-19 pandemic, HCWs commonly suffered from mental health problems, including depression and anxiety. Regularly checking the physical and mental health problems of HCWs during the COVID-19 pandemic is crucial, and social support and strategy are needed to reduce the heavy workload and psychological distress of HCWs.

A Janus carbaporphyrin pseudo-dimer.

Carbaporphyrin dimers, investigated for their distinctive electronic structures and exceptional properties, have predominantly consisted of systems containing identical subunits. This study addresses the associated knowledge gap by focusing on asymmetric carbaporphyrin dimers with Janus-like characteristics. The synthesis of a Janus-type carbaporphyrin pseudo-dimer 5 is presented. It displays antiaromatic characteristics on the fused side and nonaromatic behavior on the unfused side. A newly synthesized tetraphenylene (TPE) linked bis-dibenzihomoporphyrin 8 and a previously reported dibenzo[g,p]chrysene (DBC) linked bis-dicarbacorrole 9 were prepared as controls. Comprehensive analyses, including 1H NMR spectral studies, single crystal X-ray diffraction analyses, and DFT calculations, validate the mixed character of 5. A further feature of the Janus pseudo-dimer 5 is that it may be transformed into a heterometallic complex, with one side coordinating a Cu(III) center and the other stabilizing a BODIPY complex. This disparate regiochemical reactivity underscores the potential of carbaporphyrin dimers as versatile frameworks, with electronic features and site-specific coordination chemistry controlled through asymmetry. These findings position carbaporphyrin dimers as promising candidates for advances in electronic structure studies, coordination chemistry, materials science, and beyond.

Impact of scleral tunnel length on the position of IOLs in flanged intrascleral haptic fixation.

PURPOSE: To investigate the effect of scleral tunnel length on the effective lens position and tilt of the intraocular lens (IOL) in flanged intrascleral haptic fixation (ISHF) using anterior segment optical coherence tomography (AS-OCT). SETTING: Tertiary institution. DESIGN: Retrospective case-control study. METHODS: This study included 55 and 42 eyes that underwent ISHF with 1.0- and 2.0-mm scleral tunnels, respectively. Twenty-three eyes that underwent sutured fixation were used as a control. The anterior chamber depth (ACD), scleral tunnel length, incident angle of haptic, and tilting of optic were analyzed using AS-OCT. RESULTS: The mean postoperative ACD, vertical tilt angle, and spherical equivalent of the 1.0-mm were 5.27 ± 0.39 mm, 6.04 ± 4.87°, and 0.38 ± 1.03 D, respectively. The ACD and vertical tilt angle of the 1.0-mm were larger than those of the others (p<0.001 and p<0.05, respectively), and the postoperative spherical equivalent was more hyperopic (p<0.05). The 2.0-mm exhibited a lower frequency of tilting greater than 7°. The inter-eye difference in ACD between in-the-bag fixation and ISHF of the1.0-mm tunnel was significantly greater than that in the 2.0-mm tunnel (p<0.05). The 1.0 mm tunnel had a significantly larger incident angle and a longer tunnel length (p<0.001, respectively) and showed a greater difference in the tunnel length on both sides (p<0.05). CONCLUSION: A shorter tunnel yielded a more unstable IOL position, greater variation in angle and tunnel length, and longer ACD during ISHF. An exact 2.0-mm tunnel must be created on both sides to achieve a stable and predictable IOL position.

Metalla-Carbaporphyrinoids Consisting of an Acyclic N-Confused Tetrapyrrole Analogue Served as Stable Near-Infrared-II Dyes.

We present herein the synthesis of novel pseudo-metalla-carbaporphyrinoid species (1M: M=Pd and Pt) achieved through the inner coordination of palladium(II) and platinum(II) with an acyclic N-confused tetrapyrrin analogue. Despite their tetrapyrrole frameworks being small, akin to well-known porphyrins, these species exhibit an unusually narrow HOMO-LUMO gap, resulting in an unprecedentedly low-energy absorption in the second near-infrared (NIR-II) region. Density functional theory (DFT) calculations revealed unique dπ-pπ-conjugated electronic structures involving the metal dπ-ligand pπ hybridized molecular orbitals of 1M. Magnetic circular dichroism (MCD) spectroscopy confirmed distinct electronic structures. Remarkably, the complexes feature an open-metal coordination site in the peripheral NN dipyrrin site, forming hetero-metal complexes (1Pd-BF2 and 1Pt-BF2) through boron difluoride complexation. The resulting hetero metalla-carbaporphyrinoid species displayed further redshifted NIR-II absorption, highly efficient photothermal conversion efficiencies (η; 62-65 %), and exceptional photostability. Despite the challenges associated with the theoretical and experimental assessment of dπ-pπ-conjugated metalla-aromaticity in relatively larger (more than 18π electrons) polycyclic ring systems, these organometallic planar tetrapyrrole systems could serve as potential molecular platforms for aromaticity-relevant NIR-II dyes.

Maximization strategies in relationship and career enhances life satisfaction through meaning making among established adults in South Korea.

BACKGROUND: Choosing a partner and job have long been regarded as important developmental milestones to reach in adulthood. In a collective cultural context with high familial and societal expectations to commit to a relationship and job by age 30, maximizing on such life decisions might potentially harm one's well-being. The literature on maximization-well-being association is complex, and recent research suggests that this relationship might differ by its dimensions and cultural context. In the present study, we examined how engaging in a maximization strategy in relationship and career domains predicts life satisfaction and whether this pathway is mediated by a meaning-making process (search-to-presence of meaning) among established adults in South Korea. METHODS: Survey data on measures of relational maximization strategy, career maximization strategy, search for meaning, presence of meaning, and life satisfaction was collected from 264 South Korean unmarried, working adults in their 30 s to 40 s. A two-step structural equation modeling method was applied to test the hypothesized serial mediation model. RESULTS: Tests of the measurement and structural model showed good fit with the data (CFI = .96, TLI = .95, RMSEA = .07, SRMR = .05). Further bootstrapping results supported significant indirect effects of the serial mediation model in the paths between maximization strategy and life satisfaction via a search-to-presence of meaning in both relational (b = .16, 95% CI [.01, -.16], p < .05) and career (b = .26, 95% CI [.11, -.26], p < .01) domains. CONCLUSIONS: Our findings suggest that for established adults in a collectivist culture who may experience familial and social pressure on these life choices, searching for alternative options to make the best relationship and career decisions could potentially lead to higher life satisfaction, when done through an intentional meaning-making process.

Priming Sentence Production in Older Adults: Evidence for Preserved Implicit Learning.

Purpose: Structural priming- speakers' unconscious tendency to echo previously encountered message-structure mappings - is thought to reflect the processes of implicit language learning that occur throughout the lifespan. Recently, structural priming has also been used as a means to facilitate language re-learning in age-related language disorders such as aphasia. However, little evidence is available on whether structural priming remains effective in healthy aging, limiting clinical translation of the structural priming paradigm. This study examined the impact of aging on the strength and longevity of abstract structural priming and lexical boost effects. Method: Twenty-four young and 24 older adults participated in a collaborative picture-matching task where the participant and experimenter took turns describing picture cards using transitive and dative sentences. In Experiment 1, a target was elicited immediately following a prime (0-lag), whereas two filler items were embedded between a prime and a target sentence in Experiment 2 (2-lag) to examine longer-term priming effects. In both experiments, the verb was repeated for half of the prime-target pairs to examine lexical boost on structural priming. Results: At immediate priming, older adults showed both abstract structural priming and lexical boost in transitives and datives, similar to young adults. At longer-term priming, only abstract priming effects were significant in both groups of participants, with no evidence of age-related reduction in priming. Conclusions: Both lexically-specific and independent mechanisms of structural priming remain resilient in older adults, supporting the view that structural priming reflects life-long language learning. Further, the findings provide empirical basis for applying structural priming to elderly clinical populations.

Interruption of p38MAPK-MSK1-CREB-MITF-M pathway to prevent hyperpigmentation in the skin.

Background: Melanocortin 1 receptor (MC1R), a receptor of α-melanocyte-stimulating hormone (α-MSH), is exclusively present in melanocytes where α-MSH/MC1R stimulate melanin pigmentation through microphthalmia-associated transcription factor M (MITF-M). Toll-like receptor 4 (TLR4), a receptor of endotoxin lipopolysaccharide (LPS), is distributed in immune and other cell types including melanocytes where LPS/TLR4 activate transcriptional activity of nuclear factor (NF)-κB to express cytokines in innate immunity. LPS/TLR4 also up-regulate MITF-M-target melanogenic genes in melanocytes. Here, we propose a molecular target of antimelanogenic activity through elucidating inhibitory mechanism on α-MSH-induced melanogenic programs by benzimidazole-2-butanol (BI2B), an inhibitor of LPS/TLR4-activated transcriptional activity of NF-κB. Methods: Ultraviolet B (UV-B)-irradiated skins of HRM-2 hairless mice and α-MSH-activated melanocyte cultures were employed to examine melanogenic programs. Results: Topical treatment with BI2B ameliorated UV-B-irradiated skin hyperpigmentation in mice. BI2B suppressed the protein or mRNA levels of melanogenic markers, such as tyrosinase (TYR), MITF-M and proopiomelanocortin (POMC), in UV-B-exposed and pigmented skin tissues. Moreover, BI2B inhibited melanin pigmentation in UV-B-irradiated co-cultures of keratinocyte and melanocyte cells and that in α-MSH-activated melanocyte cultures. Mechanistically, BI2B inhibited the activation of cAMP response element-binding protein (CREB) in α-MSH-induced melanogenic programs and suppressed the expression of MITF-M at the promoter level. As a molecular target, BI2B primarily inhibited mitogen-activated protein kinase (MAPK) kinase 3 (MKK3)-catalyzed kinase activity on p38MAPK. Subsequently, BI2B interrupted downstream pathway of p38MAPK-mitogen and stress-activated protein kinase-1 (MSK1)-CREB-MITF-M, and suppressed MITF-M-target melanogenic genes, encoding enzymes TYR, TYR-related protein-1 (TRP-1) and dopachrome tautomerase (DCT) in melanin biosynthesis, and encoding proteins PMEL17 and Rab27A in the transfer of pigmented melanosomes to the overlaying keratinocytes in the skin. Conclusion: Targeting the MKK3-p38MAPK-MSK1-CREB-MITF-M pathway was suggested as a rationale to inhibit UV-B- or α-MSH-induced facultative melanogenesis and as a strategy to prevent acquired pigmentary disorders in the skin.

Isomerism of Cyclodextrin Tetramer Induced by Alkali Halide Cluster Ions Observed by Ion Mobility Spectrometry-Mass Spectrometry.

Cyclodextrins (CDs) exhibit versatile self-assembly properties due to their hydrophilic and hydrophobic components, with applications such as drug delivery and selective binding. While research on CD self-assembly is extensive, limited studies have explored their aggregation behavior, particularly in interactions with small ionic guests. The present work investigates the structure of ß-CD tetramers aggregated with alkali metal chloride clusters using ion mobility spectrometry-mass spectrometry (IMS-MS). The results revealed that diverse structures emerge in the tetramer depending on the alkali metal cluster size. Notably, the doubly charged tetramer exhibits distinct aggregation trends with specific numbers of MCl clusters for Na+ and K+ ions. After initially adopting a bucket-wheel structure with two internal cations, the structure transforms into a new isomer with a tetrahedral configuration upon cluster addition. The formation of the new isomer structure is closely linked to filling the cavity volume with MCl clusters and ionic interactions, which possibly compensate for the weakened hydrogen bonds between CDs. Theoretical calculations further support the structures, showing well-matched collision cross-section (CCS) values compared with the experimental CCS values. This study highlights the role of alkali metal chloride clusters as potential templates, leading to the formation of novel CD assemblies.

RFX4 is an intrinsic factor for neuronal differentiation through induction of proneural genes POU3F2 and NEUROD1.

Proneural genes play a crucial role in neuronal differentiation. However, our understanding of the regulatory mechanisms governing proneural genes during neuronal differentiation remains limited. RFX4, identified as a candidate regulator of proneural genes, has been reported to be associated with the development of neuropsychiatric disorders. To uncover the regulatory relationship, we utilized a combination of multi-omics data, including ATAC-seq, ChIP-seq, Hi-C, and RNA-seq, to identify RFX4 as an upstream regulator of proneural genes. We further validated the role of RFX4 using an in vitro model of neuronal differentiation with RFX4 knock-in and a CRISPR-Cas9 knock-out system. As a result, we found that RFX4 directly interacts with the promoters of POU3F2 and NEUROD1. Transcriptomic analysis revealed a set of genes associated with neuronal development, which are highly implicated in the development of neuropsychiatric disorders, including schizophrenia. Notably, ectopic expression of RFX4 can drive human embryonic stem cells toward a neuronal fate. Our results strongly indicate that RFX4 serves as a direct upstream regulator of proneural genes, a role that is essential for normal neuronal development. Impairments in RFX4 function could potentially be related to the development of various neuropsychiatric disorders. However, understanding the precise mechanisms by which the RFX4 gene influences the onset of neuropsychiatric disorders requires further investigation through human genetic studies.

Communicating uncertainties regarding COVID-19 vaccination: Moderating roles of trust in science, government, and society.

This study examined how uncertainty affects information seeking and avoidance behaviors via information insufficiency in the COVID-19 vaccination context. It also investigated how trust in science, government, and society moderate the effects of information insufficiency. An online experiment with 131 Korean adults showed that uncertainty indirectly affects information seeking intentions via information insufficiency, which is moderated by science trust and governmental trust. It also showed that uncertainty indirectly affects information avoidance intentions via information insufficiency, which is moderated by social trust.