A library for innovative category exemplars (ALICE) database: Streamlining research with printable 3D novel objects.

This paper introduces A Library for Innovative Category Exemplars (ALICE) database, a resource that enhances research efficiency in cognitive and developmental studies by providing printable 3D objects representing 30 novel categories. Our research consists of three experiments to validate the novelty and complexity of the objects in ALICE. Experiment 1 assessed the novelty of objects through adult participants' subjective familiarity ratings and agreement on object naming and descriptions. The results confirm the general novelty of the objects. Experiment 2 employed multidimensional scaling (MDS) to analyze perceived similarities between objects, revealing a three-dimensional structure based solely on shape, indicative of their complexity. Experiment 3 used two clustering techniques to categorize objects: k-means clustering for creating nonoverlapping global categories, and hierarchical clustering for allowing global categories that overlap and have a hierarchical structure. Through stability tests, we verified the robustness of each clustering method and observed a moderate to good consensus between them, affirming the strength of our dual approach in effectively and accurately delineating meaningful object categories. By offering easy access to customizable novel stimuli, ALICE provides a practical solution to the challenges of creating novel physical objects for experimental purposes.

A Randomized, Multi-Center, Open Label Study to Compare the Safety and Efficacy between Afatinib Monotherapy and Combination Therapy with HAD-B1 for the Locally Advanced or Metastatic NSCLC Patients with EGFR Mutations.

BACKGROUND: Lung cancer, especially non-small cell lung cancer (NSCLC), poses a significant health challenge globally due to its high mortality. Afatinib, a second-generation epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI), has shown superior efficacy over traditional chemotherapy in NSCLC treatment. However, issues like secondary resistance and adverse effects call for alternative therapies. HAD-B1, comprising 4 herbal medicines, has shown promise in lung cancer treatment in both preclinical and clinical settings. This study assesses the combination of HAD-B1 and Afatinib in advanced NSCLC patients to potentially improve outcomes by addressing the limitations of current EGFR-TKI therapies. METHOD: A randomized, open-label trial evaluated the efficacy and safety of HAD-B1 with Afatinib in 90 EGFR-mutation-positive NSCLC patients. Participants were divided into treatment and control groups, receiving Afatinib with or without HAD-B1. The study focused on the initial dose maintenance rate and disease control rate (DCR) of Afatinib, alongside secondary outcomes like survival rates and quality of life, under continuous safety monitoring. RESULTS: Among the 90 participants, no significant difference was found in initial dose maintenance (60.98% in the treatment group vs 52.50% in the control, P = .4414) or DCR (80.49% vs 90.00%, P = .2283). Secondary outcomes like PFS, TTP, and OS showed no notable differences. However, physical functioning significantly improved in the treatment group (P = .0475, PPS group). The control group experienced higher rates of adverse events of special interest and adverse drug reactions (P = .01), suggesting HAD-B1 with Afatinib might enhance physical function without increasing adverse effects. CONCLUSION: Combining HAD-B1 with Afatinib potentially improves quality of life and reduces adverse events in advanced NSCLC patients. Further research is necessary to confirm the long-term benefits of this combination therapy, aiming to advance NSCLC treatment outcomes. TRIAL REGISTRATION: Clinical Research Information Service (CRIS) of the Republic of Korea, https://cris.nih.go.kr/ (ID: KCT0005414).

Watching hands move enhances learning from concrete and dynamic visualizations.

This article explores the role of sensorimotor engagement in students' learning of a challenging science, technology, engineering, and math-related concept. Previous research has failed to distinguish two features commonly associated with embodiment: sensorimotor engagement and visuospatial concreteness. In the current research, we ask whether sensorimotor engagement-operationalized as watching a video of hands manipulating paper representations-offers unique benefits beyond the visuospatial concreteness of a dynamic visualization of the same process. Participants were randomly assigned to one of three conditions to learn about the shuffle() function in R: a Watch Hands Moving Objects group, which watched a video with hands; a Watch Moving Objects group, which watched a video with a dynamic visualization in which objects moved without hands; or a control group, which watched a live-coding video that did not include either hands or visuospatial representations. Results revealed that only participants in the Watch Hands Moving Objects group demonstrated significantly superior performance compared with both the Watch Moving Objects group and control groups. These findings highlight the unique benefit of sensorimotor engagement for learning, contributing to a deeper understanding of how embodiment can enhance the learning process. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Development of Non-Invasive miRNA Markers for Assessing the Quality of Human Induced Pluripotent Stem Cell-Derived Retinal Organoids.

Human retinal organoids (ROs) have emerged as valuable tools for studying retinal development, modeling human retinal diseases, and screening drugs. However, their application is limited primarily due to time-intensive generation, high costs, and low reproducibility. Quality assessment of RO differentiation is crucial for their application in research. However, traditional methods such as morphological evaluation and immunohistochemical analysis have limitations due to their lack of precision and invasiveness, respectively. This study aims to identify non-invasive biomarkers for RO differentiation quality using exosomal microRNAs (miRNAs), which are known to reflect cell-specific functions and development in the retina. We differentiated ROs from human induced pluripotent stem cells (hiPSCs) and classified them into 'superior' and 'inferior' groups based on morphological and immunohistochemical criteria. Exosomes from the conditioned media were isolated and analyzed for miRNA content. Our findings revealed distinct miRNA profiles between superior and inferior ROs, with superior ROs exhibiting higher miRNA diversity and specifically up- or down-regulated miRNAs. Gene ontology and pathway enrichment analyses indicated that the target genes of these miRNAs are involved in neuron proliferation and differentiation. The study suggests the potential of exosomal hsa-miR-654-3p and hsa-miR-451a as non-invasive biomarkers for real-time monitoring of RO quality, facilitating the development of standardized, efficient, and cost-effective culture methods.

Disparities in exposure to concentrated animal feeding operations (CAFOs) and risk of adverse birth outcomes in Pennsylvania, USA.

Background: Previous studies have linked exposure to concentrated animal feeding operations (CAFOs) with various health outcomes. However, relatively few studies evaluated the impacts of CAFOs on adverse birth outcomes, despite significant public health concerns regarding maternal and child health. Objectives: This cross-sectional study investigated the risk of adverse birth outcomes associated with CAFOs exposure and evaluated disparities in exposure to CAFOs and associated health outcomes. Methods: We obtained individual-level birth records from 2003 to 2020 from the Pennsylvania Department of Health. We considered two adverse birth outcomes: (1) preterm birth (PTB); and (2) low birth weight (LBW). Exposure was considered as a binary indicator (presence or absence of CAFO) and as categories based on level of exposure. Logistic regression was applied to estimate the association between CAFOs exposure and adverse birth outcomes. Models were adjusted for infant's sex, maternal demographics (age, race/ethnicity, education), prenatal BMI, prenatal care, smoking status, marital status, plurality, WIC status, and urban/rural indicator. We examined both disparities in exposure and in health response. Results: Presence of CAFOs was associated with higher risk of PTB, with an increasing trend with higher levels of CAFOs exposure. Compared to the no CAFO exposure group, the odds ratios for PTB were 1.022 (95 % confidence interval 1.003, 1.043), 1.066 (1.034, 1.100), 1.069 (1.042, 1.097) for low, medium, and high CAFOs exposure groups, respectively. Some maternal characteristics were associated with a higher CAFO-related risk of PTB. Similar associations were observed for LBW for some characteristics such as mother's race/ethnicity, education, WIC status, and urbanicity, although some findings were not statistically significant. Conclusions: Our findings suggest that presence of CAFOs increases risk of preterm birth. Our results indicate that some maternal characteristics may be associated with higher risk of CAFO-related PTB or LBW. This study can inform future research on disparities in CAFO exposure and associated health burden.

Associations between gestational residential radon exposure and term low birthweight in Connecticut, USA.

BACKGROUND: Studies suggest biologic mechanisms for gestational exposure to radiation and impaired fetal development. We explored associations between gestational radon exposure and term low birthweight, for which evidence is limited. METHODS: We examined data for 68,159 singleton full-term births in Connecticut, USA, 2016-2018. Using a radon spatiotemporal model, we estimated ZIP code-level basement and ground-level exposures during pregnancy and trimesters for each participant's address at birth or delivery. We used logistic regression models, including confounders, to estimate odds ratios (ORs) for term low birth weight in four exposure quartiles (Q1 to Q4) with the lowest exposure group (Q1) as the reference. RESULTS: Exposure levels to basement radon throughout pregnancy (0.27-3.02 pCi/L) were below the guideline level set by the US Environmental Protection Agency (4 pCi/L). The ORs for term low birth weight in the second-highest (Q3; 1.01-1.33 pCi/L) exposure group compared to the reference (<0.79 pCi/L) group for basement radon during the first trimester was 1.22 (95% confidence interval [CI]: 1.02, 1.45). The OR in the highest (Q4; 1.34-4.43 pCi/L) quartile group compared to the reference group during the first trimester was 1.26 (95% CI: 1.05, 1.50). Risks from basement radon were higher for participants with lower income, lower maternal education levels, or living in urban regions. CONCLUSION: This study found increased term low birth weight risks for increases in basement radon. Results have implications for infants' health for exposure to radon at levels below the current national guideline for indoor radon concentrations and building remediations.

The Relationship between High-Intensity Physical Activity and Traumatic Dental Injury among Young Adults in South Korea.

Materials and Methods: This study analyzed data collected from the 5th National Health and Nutrition Examination Survey (KNHANES V:2010-2012). The total number of participants in the 5th KNAHANES was 5,383 young adults aged 19-39 years, selected from 25,534 participants. Logistic regression analysis was performed using socioeconomic status (sex, age, education level, and income), physical activity intensity (vigorous and moderate), frequency of vigorous and moderate physical activity (days per week), and traumatic dental injuries due to exercise. Results: A total of 5,383 participants were included in the analysis. High-intensity exercisers had a statistically different association with traumatic dental injuries due to exercise. In all models, high-intensity exercisers had more traumatic dental injuries than moderate-intensity exercisers, and participants who exercised vigorously 4 or more days per week had a significantly higher prevalence experience of traumatic dental injuries. Among adults in their 20s, men, college attendees, and those with higher incomes, the prevalence of exercising vigorously 4 or more days per week was higher. Conclusions: Among young adults, a higher frequency of high-intensity physical activity was associated with a higher prevalence experience of traumatic tooth injury due to exercise compared with no physical activity.

A systematic review of animal feeding operations including concentrated animal feeding operations (CAFOs) for exposure, health outcomes, and environmental justice.

BACKGROUND: Despite growing literature on animal feeding operations (AFOs) including concentrated animal feeding operations (CAFOs), research on disproportionate exposure and associated health burden is relatively limited and shows inconclusive findings. OBJECTIVE: We systematically reviewed previous literature on AFOs/CAFOs, focusing on exposure assessment, associated health outcomes, and variables related to environmental justice (EJ) and potentially vulnerable populations. METHODS: We conducted a systematic search of databases (MEDLINE/PubMed and Web of Science) and performed citation screening. Screening of titles, abstracts, and full-text articles and data extraction were performed independently by pairs of reviewers. We summarized information for each study (i.e., study location, study period, study population, study type, study design, statistical methods, and adjusted variables (if health association was examined), and main findings), AFO/CAFO characteristics and exposure assessment (i.e., animal type, data source, measure of exposure, and exposure assessment), health outcomes or symptoms (if health association was examined), and information related to EJ and potentially vulnerable populations (in relation to exposure and/or health associations, vulnerable populations considered, related variables, and main findings in relation to EJ and vulnerable populations). RESULTS: After initial screening of 10,963 papers, we identified 76 eligible studies. This review found that a relatively small number of studies (20 studies) investigated EJ and vulnerability issues related to AFOs/CAFOs exposure and/or associated health outcomes (e.g., respiratory diseases/symptoms, infections). We found differences in findings across studies, populations, the metrics used for AFO/CAFO exposure assessment, and variables related to EJ and vulnerability. The most commonly used metric for AFO/CAFO exposure assessment was presence of or proximity to facilities or animals. The most investigated variables related to disparities were race/ethnicity and socioeconomic status. CONCLUSION: Findings from this review provide suggestive evidence that disparities exist with some subpopulations having higher exposure and/or health response in relation to AFO/CAFO exposure, although results varied across studies.

Exosomal miR-196b secreted from bronchial epithelial cells chronically exposed to low-dose PM2.5 promotes invasiveness of adjacent and lung cancer cells.

Fine particulate matter (PM2.5) is a risk factor for pulmonary diseases and lung cancer, and inhaled PM2.5 is mainly deposited in the bronchial epithelium. In this study, we investigated the effect of long-term exposure to low-dose PM2.5 on BEAS-2B cells derived from the normal bronchial epithelium. BEAS-2B cells chronically exposed to a concentration of 5 µg/ml PM2.5 for 30 passages displayed the phenotype promoting epithelial-mesenchymal transition (EMT) and cell invasion. Cellular internalization of exosomes (designated PM2.5 Exo) extracted from BEAS-2B cells chronically exposed to low-dose PM2.5 promoted cell invasion in vitro and metastatic potential in vivo. Hence, to identify the key players driving phenotypic alterations, we analyzed microRNA (miRNA) expression profiles in PM2.5 Exo. Five miRNAs with altered expression were selected: miRNA-196b-5p, miR-135a-2-5p, miR-3117-3p, miR-218-5p, and miR-497-5p. miR-196b-5p was the most upregulated in both BEAS-2B cells and isolated exosomes after PM2.5 exposure. In a functional validation study, genetically modified exosomes overexpressing a miR-196b-5p mimic induced an enhanced invasive phenotype in BEAS-2B cells. Conversely, miR-196b-5p inhibition diminished the PM2.5-enhanced EMT and cell invasion. These findings indicate that exosomal miR-196b-5p may be a candidate biomarker for predicting the malignant behavior of the bronchial epithelium and a therapeutic target for inhibiting PM2.5-triggered pathogenesis.

Value addition of MXenes as photo-/electrocatalysts in water splitting for sustainable hydrogen production.

The energy transition from fossil fuel-based to renewable energy is a global agenda. At present, a major concern in the green hydrogen economy is the demand for clean fuels and non-noble materials to produce hydrogen through water splitting. Researchers are focusing on addressing this concern with the help of the development of appropriate non-noble-based photo-/electrocatalytic materials. A new class of two-dimensional materials, MXenes, have recently shown tremendous potential for water splitting to produce H2via a photoelectrochemical process. The unique properties of emerging 2D MXene materials, such as hydrophilic surface functionalities, higher surface-to-volume ratios, and inherent flexibility, present these materials as appropriate photo-/electrocatalytic materials. Unique value addition and innovative strategies such as the introduction of end-group modification, heterojunctions, and nanostructure engineering have shown the potential of MXene materials as emerging photo-/electrocatalysts for water splitting. When integrated with conventional noble metal catalysts, MXene-based catalysts demonstrated a lower overpotential for hydrogen and oxygen evolution reactions and a remarkable boost in performance for enhanced H2 production rates surpassing those of pristine noble metal-based catalysts. These promote future perspectives for the utilization of chemically synthesized MXenes as alternative photo-/electrocatalysts. Future research direction should focus on MXene synthesis and utilization for surface modification, composite formation, stabilization, and optimization in synthesis methods and post-synthesis treatments. This review highlights the progress in the understanding of fundamental mechanisms and issues associated with water splitting, influencing factors of MXenes, their value addition role, and application strategies for water splitting, including performance, challenges, and outlook of MXene-based photo-/electrocatalysts, in the last five years.

Lytic transglycosylase repertoire diversity enables intrinsic antibiotic resistance and daughter cell separation in Escherichia coli under acidic stress.

Peptidoglycan (PG) is an important architectural element that imparts physical toughness and rigidity to the bacterial envelope. It is also a dynamic structure that undergoes continuous turnover or autolysis. Escherichia coli possesses redundant PG degradation enzymes responsible for PG turnover; however, the advantage afforded by the existence of numerous PG degradation enzymes remains incompletely understood. In this study, we elucidated the physiological roles of MltE and MltC, members of the lytic transglycosylase (LTG) family that catalyze the cleavage of glycosidic bonds between disaccharide subunits within PG strands. MltE and MltC are acidic LTGs that exhibit increased enzymatic activity and protein levels under acidic pH conditions, respectively, and deletion of these two LTGs results in a pronounced growth defect at acidic pH. Furthermore, inactivation of these two LTGs induces increased susceptibility at acidic pH against various antibiotics, particularly vancomycin, which seems to be partially caused by elevated membrane permeability. Intriguingly, inactivation of these LTGs induces a chaining morphology, indicative of daughter cell separation defects, only under acidic pH conditions. Simultaneous deletion of PG amidases, known contributors to daughter cell separation, exacerbates the chaining phenotype at acidic pH. This suggests that the two LTGs may participate in the cleavage of glycan strands between daughter cells under acidic pH conditions. Collectively, our findings highlight the role of LTG repertoire diversity in facilitating bacterial survival and antibiotic resistance under stressful conditions.

Usefulness of the heart rate variability test in predicting intradialytic hypotension in patients undergoing chronic haemodialysis.

Background: Intradialytic hypotension (IDH) is the primary complication of haemodialysis (HD); however, its diverse pathophysiology and inconsistent definitions complicate its prediction. Despite attempts using the heart rate variability (HRV) test for IDH prediction, studies on its usefulness for predicting IDH diagnosed per the nadir 90 criterion are lacking. We aimed to evaluate HRV test efficacy and reproducibility in predicting IDH based on the nadir 90 criterion. Methods: Seventy patients undergoing HD participated in this multicentre prospective observational study. The HRV test was performed during non-HD periods and IDH was monitored during 12 HD sessions. IDH was diagnosed according to the nadir 90 criterion, defined as a decrease in systolic blood pressure of ≤90 mmHg during HD. After monitoring, the HRV test was repeated. An HRV-IDH index was developed using multivariate logistic regression analysis employing HRV test parameters. The predictive power of the HRV-IDH index was analysed using the area under the receiver operating characteristics curve (AUROC). Reproducibility was evaluated using correlation analysis of two HRV tests on the same patient. Results: There were 37 and 33 patients in the IDH and non-IDH groups, respectively. The HRV-IDH index predicted IDH occurrence with AUROCs of 0.776 and 0.803 for patients who had experienced at least one or repeated IDH episodes, respectively. Spearman's correlation coefficient for HRV-IDH indices was 0.859 for the first and second HRV tests. Conclusions: The HRV test holds promise for predicting IDH, particularly for patients with recurring IDH diagnosed based on the nadir 90 criterion.

Effect of 3D-printed polycaprolactone/osteolectin scaffolds on the odontogenic differentiation of human dental pulp cells.

Cell-based tissue engineering often requires the use of scaffolds to provide a three-dimensional (3D) framework for cell proliferation and tissue formation. Polycaprolactone (PCL), a type of polymer, has good printability, favorable surface modifiability, adaptability, and biodegradability. However, its large-scale applicability is hindered by its hydrophobic nature, which affects biological properties. Composite materials can be created by adding bioactive materials to the polymer to improve the properties of PCL scaffolds. Osteolectin is an odontogenic factor that promotes the maintenance of the adult skeleton by promoting the differentiation of LepR+ cells into osteoblasts. Therefore, the aim of this study was to evaluate whether 3D-printed PCL/osteolectin scaffolds supply a suitable microenvironment for the odontogenic differentiation of human dental pulp cells (hDPCs). The hDPCs were cultured on 3D-printed PCL scaffolds with or without pores. Cell attachment and cell proliferation were evaluated using EZ-Cytox. The odontogenic differentiation of hDPCs was evaluated by alizarin red S staining and alkaline phosphatase assays. Western blot was used to evaluate the expression of the proteins DSPP and DMP-Results: The attachment of hDPCs to PCL scaffolds with pores was significantly higher than to PCL scaffolds without pores. The odontogenic differentiation of hDPCs was induced more in PCL/osteolectin scaffolds than in PCL scaffolds, but there was no statistically significant difference. 3D-printed PCL scaffolds with pores are suitable for the growth of hDPCs, and the PCL/osteolectin scaffolds can provide a more favorable microenvironment for the odontogenic differentiation of hDPCs.

Oral habits and temporomandibular joint disorders according to stress levels among military personnel in South Korea: A cross-sectional study.

BACKGROUND: Military personnel suffer from stress-induced temporomandibular joint disorders (TMD). No previous studies have evaluated the oral habits and TMD in military personnel based on their stress levels. OBJECTIVES: To examine the correlation between oral habits and TMD based on stress levels. In addition, we assessed the relationship between stress levels and TMD by military rank as well as the impact of oral habits on TMD. METHOD: This cross-sectional survey included 89 military personnel who visited the Armed Forces Medical Center in Korea with discomfort in the temporomandibular joint (TMJ) discomfort. Oral habits, stress level, TMD and general characteristics of the subjects were investigated. A questionnaire was distributed to the subjects who agreed to the study, and they were asked to respond in a self-written form. Multiple linear regression analysis was performed to examine the factors that affect oral habits and TMJ symptoms. RESULTS: Stress scores and oral habits were highest in the 'Private' rank. In contrast, temporomandibular joint symptoms were highest in the 'Corporal' rank. Additionally, the high-risk stress group exhibited higher scores in oral habits and TMD compared to the potential stress group. Furthermore, there was a positive correlation between an increase in high-risk stress scores and a rise in oral habits. And individuals with more oral habits are at an increased likelihood of experiencing TMD. CONCLUSION: Our study findings suggest that military personnel with prevent TMD and improve oral habits by addressing stress levels.

Short tandem repeat expansions in cortical layer-specific genes implicate in phenotypic severity and adaptability of autism spectrum disorder.

AIM: Short tandem repeats (STRs) are repetitive DNA sequences and highly mutable in various human disorders. While the involvement of STRs in various genetic disorders has been extensively studied, their role in autism spectrum disorder (ASD) remains largely unexplored. In this study, we aimed to investigate genetic association of STR expansions with ASD using whole genome sequencing (WGS) and identify risk loci associated with ASD phenotypes. METHODS: We analyzed WGS data of 634 ASD families and performed genome-wide evaluation for 12,929 STR loci. We found rare STR expansions that exceeded normal repeat lengths in autism cases compared to unaffected controls. By integrating single cell RNA and ATAC sequencing datasets of human postmortem brains, we prioritized STR loci in genes specifically expressed in cortical development stages. A deep learning method was used to predict functionality of ASD-associated STR loci. RESULTS: In ASD cases, rare STR expansions predominantly occurred in early cortical layer-specific genes involved in neurodevelopment, highlighting the cellular specificity of STR-associated genes in ASD risk. Leveraging deep learning prediction models, we demonstrated that these STR expansions disrupted the regulatory activity of enhancers and promoters, suggesting a potential mechanism through which they contribute to ASD pathogenesis. We found that individuals with ASD-associated STR expansions exhibited more severe ASD phenotypes and diminished adaptability compared to non-carriers. CONCLUSION: Short tandem repeat expansions in cortical layer-specific genes are associated with ASD and could potentially be a risk genetic factor for ASD. Our study is the first to show evidence of STR expansion associated with ASD in an under-investigated population.

Clinical and Genomic Landscape of RAS Mutations in Gynecologic Cancers.

PURPOSE: We aimed to describe RAS mutations in gynecologic cancers as they relate to clinicopathologic and genomic features, survival, and therapeutic implications. EXPERIMENTAL DESIGN: Gynecologic cancers with available somatic molecular profiling data at our institution between February 2010 and August 2022 were included and grouped by RAS mutation status. Overall survival was estimated by the Kaplan-Meier method, and multivariable analysis was performed using the Cox proportional hazard model. RESULTS: Of 3,328 gynecologic cancers, 523 (15.7%) showed any RAS mutation. Patients with RAS-mutated tumors were younger (57 vs. 60 years nonmutated), had a higher prevalence of endometriosis (27.3% vs. 16.9%), and lower grades (grade 1/2, 43.2% vs. 8.1%, all P < 0.0001). The highest prevalence of KRAS mutation was in mesonephric-like endometrial (100%, n = 9/9), mesonephric-like ovarian (83.3%, n = 5/6), mucinous ovarian (60.4%), and low-grade serous ovarian (44.4%) cancers. After adjustment for age, cancer type, and grade, RAS mutation was associated with worse overall survival [hazard ratio (HR) = 1.3; P = 0.001]. Specific mutations were in KRAS (13.5%), NRAS (2.0%), and HRAS (0.51%), most commonly KRAS G12D (28.4%) and G12V (26.1%). Common co-mutations were PIK3CA (30.9%), PTEN (28.8%), ARID1A (28.0%), and TP53 (27.9%), of which 64.7% were actionable. RAS + MAPK pathway-targeted therapies were administered to 62 patients with RAS-mutated cancers. While overall survival was significantly higher with therapy [8.4 years [(95% confidence interval (CI), 5.5-12.0) vs. 5.5 years (95% CI, 4.6-6.6); HR = 0.67; P = 0.031], this effect did not persist in multivariable analysis. CONCLUSIONS: RAS mutations in gynecologic cancers have a distinct histopathologic distribution and may impact overall survival. PIK3CA, PTEN, and ARID1A are potentially actionable co-alterations. RAS pathway-targeted therapy should be considered.

Identification and validation of PCDHGA12 and PRRX1 methylation for detecting lung cancer in bronchial washing sample.

Bronchoscopy is a frequently used initial diagnostic procedure for patients with suspected lung cancer (LC). Cytological examinations of bronchial washing (BW) samples obtained during bronchoscopy often yield inconclusive results regarding LC diagnosis. The present study aimed to identify molecular biomarkers as a non-invasive method for LC diagnosis. Aberrant DNA methylation is used as a useful biomarker for LC. Therefore, microarray-based methylation profiling analyses on 13 patient-matched tumor tissues at stages I-III vs. non-tumor tissues were performed, and a group of highly differentially methylated genes was identified. A subsequent analysis using bisulfite-pyrosequencing with additional tissues and cell lines revealed six methylated genes [ADAM metallopeptidase with thrombospondin type 1 motif 20, forkhead box C2 (mesenchyme forkhead 1), NK2 transcription factor related, locus 5 (Drosophila), oligodendrocyte transcription factor 3, protocadherin γ subfamily A 12 (PCDHGA12) and paired related homeobox 1 (PRRX1)] associated with LC. Next, a highly sensitive and accurate detection method, linear target enrichment-quantitative methylation-specific PCR in a single closed tube, was applied for clinical validation using BW samples from patients with LC (n=68) and individuals with benign diseases (n=33). PCDHGA12 and PRRX1 methylation were identified as the best-performing biomarkers to detect LC. The two-marker combination showed a sensitivity of 82.4% and a specificity of 87.9%, with an area under the curve of 0.891. Notably, the sensitivity for small cell LC was 100%. The two-marker combination had a positive predictive value of 93.3% and a negative predictive value of 70.7%. The sensitivity was higher than that of cytology, which only had a sensitivity of 50%. The methylation status of the two-marker combination showed no association with sex, age or stage, but was associated with tumor location and histology. In conclusion, the present study showed that the regulatory regions of PCDHGA12 and PRRX1 are highly methylated in LC and can be used to detect LC in BW specimens as a diagnostic adjunct to cytology in clinical practice.

Associations between traumatic dental injuries due to violence and various drinking behaviors in Korea: A cross-sectional study.

BACKGROUND AND AIM: Various patterns of alcohol consumption are associated with trauma and violence. The aim of this study was to assess the association between traumatic dental injuries (TDI) due to violence and different patterns of alcohol consumption in Korean adults. MATERIALS AND METHODS: A cross-sectional study was conducted with representative sample of Korean adults. Among the total participants, 11.8% (6489/58,999) experienced TDI, and 0.9% (520/58,999) experienced TDI due to violence. The associations between various types of alcohol consumption (frequency of drinking, frequency of binge drinking, age of first drinking) and TDI due to violence were assessed using logistic regression analyses. We confirmed differences in the prevalence experience of TDI due to violence with various types of alcohol consumption by confounders (socioeconomic status). RESULTS: All types of drinking (frequency of drinking, frequency of binge drinking, age of first drinking) were strongly associated with TDI due to violence. After adjusting for confounders, those who started drinking at the age of 18 or younger and drank 4 or more days a week (OR: 2.86, 95% CI: 1.68-4.88), those who started drinking at the age of 18 or younger and drank 3 days or less a week (OR: 2.37, 95% CI: 1.40-4.02), and those who started drinking at the age of 18 or younger and binge drinking at least once a week (OR: 3.18, 95% CI: 1.79-5.65) had higher prevalence of TDI due to violence compared to those with no alcohol drinking. CONCLUSIONS: This study presents evidence of an association between various types of alcohol consumption and TDI due to violence in Korean adults. These findings suggest the necessity for policies aimed at reducing alcohol consumption, frequency of drinking, and access to drinking especially in adolescent to reduce the prevalence experience of TDI due to violence.

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.

Clinical outcomes of colistin methanesulfonate sodium in correlation with pharmacokinetic parameters in critically ill patients with multi-drug resistant bacteria-mediated infection: A systematic review and meta-analysis.

BACKGROUND: Colistin is a viable option for multidrug resistant gram-negative bacteria emerged from inappropriate antibiotic use. Nonetheless, suboptimal colistin concentrations and nephrotoxicity risks hinder its clinical use. Thus, the aim of this study is to investigate clinical outcomes in correlation with pharmacokinetic differences and infection types in critically ill patients on intravenous colistin methanesulfornate sodium (CMS). METHODS: A systematic literature search of Embase, Google Scholars, and PubMed was performed to identify clinical trials evaluating pharmacokinetic parameters along with clinical outcomes of CMS treatment from inception to July 2023. The pooled analyses of clinical impact of CMS on nephrotoxicity, mortality, clinical cure, and colistin concentration at steady state (Css,avg) were performed. This study was registered in the PROSPERO (CRD 42023456120). RESULTS: Total of 695 critically ill patients from 17 studies were included. The mortality was substantially lower in clinically cured patients (OR 0.05; 95% CI 0.02 - 0.14), whereas the mortality rate was statistically insignificant between nephrotoxic and non-nephrotoxic patients. Inter-patient variability of pharmacokinetic parameters of CMS and colistin was observed in critically ill patients. The standard mean differences of Css,avg were statistically insignificant between clinically cure and clinically failure groups (standard mean difference (SMD) -0.25; 95% CI -0.69 - 0.19) and between nephrotoxic and non-nephrotoxic groups (SMD 0.67; 95% CI -0.27-1.61). The clinical cure rate is substantially lower in pneumonia patients (OR 0.09; 95% CI 0.01 - 0.56), and pharmacokinetic parameters pertaining to microbiological cure were different among strains. CONCLUSION: The mortality rate was substantially lower in clinically cured patients with CMS. However, no significant differences in Css,avg of colistin were examined to determine the impact of pharmacokinetic differences on clinical outcomes including mortality rate and nephrotoxicity risk. Nevertheless, the clinical cure rate is substantially lower in patients with respiratory infection than patients with urinary tract infection.