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Abstract Psychological help-seeking for suicidal ideation is a critical aspect of effective suicide prevention. Past research has documented low help-seeking amongst rural residents in China. This study investigates the patterns and predictors of help-seeking intentions for suicidal ideation versus mental (depression) and physical (heart disease) health conditions among Chinese rural residents using General Help-Seeking Questionnaire Vignette version. A total of 143 rural participants from sixteen villages in Hubei province of China completed the survey via home-visiting interviews. Results revealed a general trend that the help-seeking intentions decreased as the helping sources shifted from close others (spouses, family, etc.) to professional helpers and online sources. Additionally, rural residents with higher educational levels, high self-efficacy, and more severe suicide ideations were more willing to seek help; and suicide literacy was found to be negatively associated with help-seeking intentions. The implications of the research findings are discussed.

Abstract Background Cytosolic calcium overload contributes to muscle degradation in Duchenne muscular dystrophy (DMD). The sarcoplasmic reticulum (SR) is the primary calcium storage organelle in muscle. The sarco-endoplasmic reticulum ATPase (SERCA) pumps cytosolic calcium to the SR during muscle relaxation. Calcium is kept in the SR by calcium-binding proteins. Methods Given the importance of the canine DMD model in translational studies, we examined transcriptional changes of SERCA (SERCA1 and SERCA2a), SERCA regulators (phospholamban, sarcolipin, myoregulin, and dwarf open reading frame), and SR calcium-binding proteins (calreticulin, calsequestrin 1, calsequestrin 2, and sarcalumenin) in skeletal muscle (diaphragm and extensor carpi ulnaris) and heart (left ventricle) in normal and affected male dogs by droplet digital PCR before the onset (≤ 2-m-old), at the active stage (8 to 16-m-old), and at the terminal stage (30 to 50-m-old) of the disease. Since many of these proteins are expressed in a fiber type-specific manner, we also evaluated fiber type composition in skeletal muscle. Results In affected dog skeletal muscle, SERCA and its regulators were down-regulated at the active stage, but calcium-binding proteins (except for calsequestrin 1) were upregulated at the terminal stage. Surprisingly, nominal differences were detected in the heart. We also examined whether there exists sex-biased expression in 8 to 16-m-old dogs. Multiple transcripts were significantly downregulated in the heart and extensor carpi ulnaris muscle of female dogs. In fiber type analysis, we found significantly more type I fiber in the diaphragm of 8 to 16-m-old affected dogs, and significantly more type II fibers in the extensor carpi ulnaris of 30 to 50-m-old affected dogs. However, no difference was detected between male and female dogs. Conclusions Our study adds new knowledge to the understanding of muscle calcium regulation in normal and dystrophic canines.

Abstract Background Respiratory syncytial virus (RSV) is the leading cause of severe respiratory infections in infants worldwide, significantly affecting their health and contributing to the global healthcare burden. We aimed to examine healthcare resource utilisation patterns and costs for infants under one year old with confirmed RSV infection across subgroups of different gestational ages and health conditions and the cost implications of RSV infections over time, thereby demonstrating the economic burden of the disease. Methods This retrospective cohort study utilised nationwide claims data from the Korea Health Insurance Review and Assessment Service for infants under one year of age with confirmed RSV infection in the first year of life from January 2017 to April 2022. The infants were stratified into three subgroups based on their gestational age and health status: unhealthy preterm, healthy preterm, and full-term infants. A descriptive analysis was conducted to estimate healthcare utilization by type of resource and costs related to the treatment of RSV. Results Out of 93,585 RSV infections identified, 31,206 patients met the inclusion criteria; these included 963 unhealthy preterm, 1,768 healthy preterm and 28,475 full-term infants. In our study, 76.3% of the infants with confirmed RSV infection required intensive care, including hospitalisation and more critical interventions such as intensive care unit (ICU) or mechanical ventilation (MV). The total average cost of RSV management was notably higher for unhealthy preterm infants ($ 6,325; 95% confidence interval (CI): $ 5,484-7,165) than for healthy preterm ($ 1,134; 95% CI: $ 1,006 − 1,261) and full-term infants ($ 606; 95% CI: 583–630). Our findings confirmed a significant epidemiological and economic burden, with infants at greater risk–shorter gestational age and poorer health conditions. Furthermore, we observed a marked increase in the total average cost of RSV management during COVID-19, reflecting the complex interplay between RSV and pandemic-related healthcare dynamics. Conclusion Our findings provide evidence for the significant economic burden of RSV infection among infants, with considerable disparities based on gestational age and health status subgroups. However, RSV prevention policies should also recognise that healthy preterm or full-term infants who receive intensive care face a significant disease burden.

Abstract Preventive treatments for unruptured intracranial aneurysms (UIAs) are used worldwide. However, the long-term effects to cognition have been underestimated. Using representative sample data from the National Health Insurance Service-Senior Cohort database, we compared cumulative risk of incident dementia between two groups: (1) treatment versus observation group, and (2) within the treatment group (surgical versus endovascular treatment). Cox proportional hazard ratios were estimated after applying one-to-one propensity score matching. Subgroup analyses were conducted to investigate interactions between treatment effects and sex, age and history of stroke, respectively. After matching, 3,763 participants were included in each group. The 10-year incidence rates of dementia were 9.82 and 8.68 per 1,000 person-years in the treatment and observation groups, respectively (HR: 1.11, 95% CI: 0.90–1.38, P = 0.33). Furthermore, the risk of incident dementia was not different between the surgical and endovascular treatment groups (HR: 0.98, 95% CI: 0.70–1.37, P = 0.91). In the subgroup analysis, surgical treatment was associated with an increased risk of developing dementia, particularly among male patient (HR: 2.34, 95% CI: 1.04–5.28). Preventive treatment of UIAs appears acceptable in terms of long-term effects to cognition. However, further researches are strongly required to identify the high risk patients of development of dementia.

Abstract Rechargeable batteries with high durability over wide temperature is needed in aerospace and submarine fields. Unfortunately, Current battery technologies suffer from limited operating temperatures due to the rapid performance decay at extreme temperatures. A major challenge for wide-temperature electrolyte design lies in restricting the parasitic reactions at elevated temperatures while improving the reaction kinetics at low temperatures. Here, we demonstrate a temperature-adaptive electrolyte design by regulating the dipole-dipole interactions at various temperatures to simultaneously address the issues at both elevated and subzero temperatures. This approach prevents electrolyte degradation while endowing it with the ability to undergo adaptive changes as temperature varies. Such electrolyte favors to form solvation structure with high thermal stability with rising temperatures and transits to one that prevents salt precipitation at lower temperatures. This ensures stably within a wide temperature range of ‒60 −55 °C. This temperature-adaptive electrolyte opens an avenue for wide-temperature electrolyte design, highlighting the significance of dipole-dipole interactions in regulating solvation structures.

This study aimed to obtain a lentinan-specific fluorescent probe for the in situ visualization of lentinan. A carbohydrate-binding module with potential lentinan-binding capacity was discovered in a β-1,3-D-glucanase by using the bioinformatics techniques, and further recombinantly expressed. The binding specificity of the expressed protein, which was named as LBM was determined by the microtiter plate assays. The results indicated that LBM displayed a desired specificity for lentinan. The protein exhibited positive binding signals to lentinan, while could not bind to several examined polysaccharides including barley β-glucan, curdlan, or konjac glucomannan. Furthermore, the first lentinan-specific fluorescent probe was successfully constructed by fusing LBM with a green fluorescent protein EmGFP, based on which the in situ visualization of lentinan in Lentinula edodes was realized. It was shown that lentinan was not only presented in the mycelial cell wall, but also amorphously distributed in the interstitial space and inside the cell. The construction of the EmGFP-LBM provided a promising tool for the in situ visualization of lentinan.

The human leukocyte antigen (HLA) system, which is part of the major histocompatibility complex (MHC) plays a vital role in immune responses by differentiating between itself and foreign cells and antigens. The significant diversity of alleles affects disease susceptibility and immune responses within different populations. Specifically, the HLA-A and HLA-DRB1 alleles are associated with various immune-related diseases, and understanding the frequency and haplotype associations of these alleles is vital for genetic and immunological research. To investigate the distribution of these characteristics in Koreans, we isolated peripheral blood mononuclear cells (PBMCs) from blood samples donated by volunteers at the Seoul Central Blood Bank and performed HLA typing on 790 samples. Our study found that the HLA-A and HLA-DRB1 alleles are widely distributed within the Korean population, with HLA-A*24:02 (21.7%) and HLA-DRB1*09:01 (9.9%) being the most frequent. Significant haplotype associations between specific HLA-A and HLA-DRB1 alleles were identified using the Chi-square test, suggesting that certain genetic combinations may influence disease onset. This insight could contribute to the development of predictive and preventative strategies for various diseases. The unique genetic characteristics of the Korean population highlight the importance of studying the HLA allele and the haplotype distributions in this group as key indicators for understanding disease susceptibility.

Abstract Background Right aortic arch (RAA) is a common congenital aortic arch abnormality. Fetuses with RAA frequently have good outcomes after birth. However, chromosomal abnormalities and genetic syndromes suggest poor prognosis for these patients. So far the underlying genetic etiology is still not identified in most RAA patients based on traditional genetic techniques and a problem is still debated whether fetuses with isolated RAA should be referred for CMA. Our study aims to investigate the genetic etiology of fetuses with right aortic arch (RAA) by chromosomal microarray analysis (CMA) and whole exome sequencing (WES) and evaluate the efficacy of CMA in fetal isolated RAA. Results Among these 153 fetuses, 99 (64.7%) with isolated RAA and 54 (35.3%) with non-isolated RAA; 25.5% (39/153) with additional intracardiac anomalies (ICA), and 19.0% (29/153) with extracardiac anomalies (ECA). Tetralogy of Fallot (n = 10) and persistent left superior vena cava (n = 11) are the most common ICA and ECA, respectively. CMA detected 15 clinically significant copy number variations (CNVs) in 14 cases (9.2%); microdeletion of 22q11.21 was the most common pathogenic CNVs (7.8%). The chromosomal abnormalities rate was higher in non-isolated RAA and RAA with ICA groups than in isolated RAA group (16.7% vs. 5.1%; 20% vs. 5.1%, both p < 0.05). From five cases further undergoing WES, a diagnostic variant in MTOR gene (c.7255G > A, de novo) was first reported in prenatal, extending the prenatal manifestation of Smith–Kingsmore syndrome (OMIM: 616638); a clinically relevant variant c.3407A > T in STAG2 was identified, being inherited from the healthy mother. Moreover, the premature birth and termination rates were higher in non-isolated RAA group than in isolated RAA group (11.1% vs. 1.0%; 37.0% vs. 2.0%, both p < 0.01). Conclusions We demonstrate that CMA and WES are useful diagnostic tools for fetal RAA, particularly non-isolated RAA, and all fetuses with RAA should be referred for CMA. The data probably aids in prenatal diagnosis and prenatal counseling of fetal RAA.

Abstract Background Determining the impact of somatic mutations requires understanding the functional relationship of genes acquiring mutations; however, it is largely unknown how mutations in functionally related genes influence each other. Methods We employed non-synonymous-to-synonymous or dNdS ratios to evaluate the evolutionary dependency (ED) of gene pairs, assuming a mutation in one gene of a gene pair can affect the evolutionary fitness of mutations in its partner genes as mutation context. We employed PanCancer- and tumor type-specific mutational profiles to infer the ED of gene pairs and evaluated their biological relevance with respect to gene dependency and drug sensitivity. Results We propose that dNdS ratios of gene pairs and their derived cdNS (context-dependent dNdS) scores as measure of ED distinguishing gene pairs either as synergistic (SYN) or antagonistic (ANT). Mutation contexts can induce substantial changes in the evolutionary fitness of mutations in the paired genes, e.g., IDH1 and IDH2 mutation contexts lead to substantial increase and decrease of dNdS ratios of ATRX indels and IDH1 missense mutations corresponding to SYN and ANT relationship with positive and negative cdNS scores, respectively. The impact of gene silencing or knock-outs on cell viability (genetic dependencies) often depends on ED, suggesting that ED can guide the selection of candidates for synthetic lethality such as TCF7L2-KRAS mutations. Using cell line-based drug sensitivity data, the effects of targeted agents on cell lines are often associated with mutations of genes exhibiting ED with the target genes, informing drug sensitizing or resistant mutations for targeted inhibitors, e.g., PRSS1 and CTCF mutations as resistant mutations to EGFR and BRAF inhibitors for lung adenocarcinomas and melanomas, respectively. Conclusions We propose that the ED of gene pairs evaluated by dNdS ratios can advance our understanding of the functional relationship of genes with potential biological and clinical implications.

Abstract In this paper, we systematically investigate the general dark matter-electron interactions within the framework of effective field theories (EFTs). We consider both the non-relativistic (NR) EFT and the relativistic EFT descriptions of the interactions with the spin of dark matter (DM) up to one, i.e., the scalar (ϕ), fermion (χ), and vector (X) DM scenarios. We first collect the leading-order NR EFT operators describing the DM-electron interactions, and construct especially the NR operators for the vector DM case. Next, we consider all possible leading-order relativistic EFT operators including those with a photon field and perform the NR reduction to match them onto the NR EFT. Then we rederive the DM-bound-electron scattering rate within the NR EFT framework and find that the matrix element squared, which is the key input that encodes the DM and atomic information, can be compactly decomposed into three terms. Each term is a product of a DM response function (a 0,1,2), which is essentially a factor of Wilson coefficients squared, and its corresponding generalized atomic response function W ~ 0 , 1 , 2 $$ \left({\overset{\sim }{W}}_{0,1,2}\right) $$ . Lastly, we employ the electron recoil data from the DM direct detection experiments (including XENON10, XENON1T, and PandaX-4T) to constrain all the non-relativistic and relativistic operators in all three DM scenarios. We set strong bounds on the DM-electron interactions in the sub-GeV region. Particularly, we find that the latest PandaX-4T S2-only data provide stringent constraints on dark matter with a mass greater than approximately 20 MeV, surpassing those from the previous XENON10 and XENON1T experiments.

Abstract Lithium batteries with solid-state electrolytes are an appealing alternative to state-of-the-art non-aqueous lithium-ion batteries with liquid electrolytes because of safety and energy aspects. However, engineering development at the cell level for lithium batteries with solid-state electrolytes is limited. Here, to advance this aspect and produce high-energy lithium cells, we introduce a cell design based on advanced parametrization of microstructural and architectural parameters of electrode and electrolyte components. To validate the cell design proposed, we assemble and test (applying a stack pressure of 3.74 MPa at 45 °C) 10-layer and 4-layer solid-state lithium pouch cells with a solid polymer electrolyte, resulting in an initial specific energy of 280 Wh kg−1 (corresponding to an energy density of 600 Wh L−1) and 310 Wh kg−1 (corresponding to an energy density of 650 Wh L−1) respectively.

Abstract Topological materials confined in 1D can transform computing technologies, such as 1D topological semimetals for nanoscale interconnects and 1D topological superconductors for fault-tolerant quantum computing. As such, understanding crystallization of 1D-confined topological materials is critical. Here, we demonstrate 1D template-assisted nanowire synthesis where we observe diameter-dependent phase selectivity for tungsten phosphides. A phase bifurcation occurs to produce tungsten monophosphide and tungsten diphosphide at the cross-over nanowire diameter regime of 35–70 nm. Four-dimensional scanning transmission electron microscopy is used to identify the two phases and to map crystallographic orientations of grains at a few nm resolution. The 1D-confined phase selectivity is attributed to the minimization of the total surface energy, which depends on the nanowire diameter and chemical potentials of precursors. Theoretical calculations are carried out to construct the diameter-dependent phase diagram, which agrees with experimental observations. Our findings suggest a crystallization route to stabilize topological materials confined in 1D.

Abstract Background More than 50% of people who die by suicide have not been in contact with formal mental health services. The rate of people who fly ‘under the radar’ of mental health services is higher among men than women, indicating a need to improve engagement strategies targeted towards men who experience suicidal thoughts and/or behaviours. In Australia, a range of mental health support services exist, designed specifically for men, yet, a substantial proportion of men do not use these services. The aim of this study is to evaluate whether a brief online video-based messaging intervention is an effective approach for encouraging men with suicidal thoughts and/or behaviours to engage with existing support services. Methods Informed by a literature review, surveys, and consultation with men with a lived experience of suicidal thoughts and/or behaviours, we designed five video-based messages that will be used in this five-arm randomised controlled trial. A total of 380 (76 per arm) men aged 18 years or older with suicidal thoughts who are not currently accessing formal mental health services will be recruited online and randomly assigned to watch one of the five web-based video messages. After viewing the video, men will be presented with information about four existing Australian support services, along with links to these services. The primary outcome will be help-seeking, operationalised as a click on any one of the four support service links, immediately after viewing the video. Secondary outcomes include immediate self-reported help-seeking intentions in addition to self-reported use of the support services during a 1-week follow-up period. We will also use the Discrete Choice Experiment methodology to determine what aspects of support services (e.g. low cost, short appointment wait times) are most valued by this group of men. Discussion This study is the first to evaluate the effectiveness of a brief web-based video messaging intervention for promoting engagement with existing support services among men with suicidal thoughts who are not currently receiving formal help. If found to be effective, this would represent a scalable, cost-effective approach to promote help-seeking for this at-risk population. Limitations and strengths of this study design are discussed.

BackgroundCoenzyme Q10 (CoQ10) plays an important role in the electron transport chain within the human mitochondrial respiratory chain. The manifestations of this deficiency exhibit a diverse range. This study investigates the clinical manifestations of primary coenzyme Q10 deficiency in neonates with the COQ4 mutation to improve the diagnosis of the disease and the prognosis through targeted treatment.MethodsWe report 4 patients with primary coenzyme Q10 deficiency by COQ4 variants in neonates. A comprehensive literature search and review for original articles and case reports with COQ4 mutation published from January 1989 to November 2023 was performed through Pubmed. We review clinical manifestations, diagnostic approaches, and treatment monitoring in these and 20 previously reported patients.ResultsWithin the cohort of four cases examined, three females and one male were identified from two distinct families. Specifically, case 1 and 2 consisted of monoamniotic twins. Cases 3 and 4 were siblings. A comprehensive review of 20 cases involving neonatal-onset COQ4 mutation was conducted. Half of the cases are Chinese. There was no statistically significant difference in the mortality between Chinese (9/12, 75%) and other regions (11/12, 91.7%) (P = 0.27). The survival time for the 24 cases was 60.0 ± 98.0 days (95% confidence interval CI: 0–252.0 days). The incidence of prenatal abnormalities in preterm infants was significantly higher than that in full-term infants (66.7% vs. 16.7%, P = 0.02). Hyperlactatemia was one of the most common manifestations, accounting for 75% of cases (18/24). Twenty of the 24 cases were diagnosed by whole exome sequencing. Only 9 patients received exogenous coenzyme Q10 treatment, and all the 4 surviving patients received coenzyme Q10 supplementation.ConclusionThe prognosis of COQ4 mutation in the neonatal period indicates a low survival rate and an poor prognosis. This may be due to the incomplete understanding of the mechanism of how COQ4 gene defects lead to coenzyme Q10 deficiency and why CoQ10 supplementation does not respond well to treatment. To improve the diagnostic rate, in addition to genetic testing, mitochondrial functional verification should be prioritized in southern China, where the incidence is relatively high. It will facilitate more in-depth mechanistic studies.

Purpose: 17q12 copy number variants (CNVs) have variable presentations and incomplete penetrance, challenging prenatal counseling and management. This study aims to investigate the intrauterine phenotype. Methods: We included 48 fetuses diagnosed with 17q12 microdeletion or microduplication by chromosomal microarray analysis. Results: For 17q12 deletion, renal anomalies were found in 35 fetuses (35/37, 94.6 %), with hyperechogenic kidneys (HEK, 28/37, 75.7 %) and multicystic dysplastic kidneys (17/37, 45.9 %) being the most common findings. Duodenal obstruction (DO) was most frequently combined in 17q12 duplication fetuses. In addition, cardiac abnormalities were the first reported prenatal phenotype in 17q12 duplication fetuses. Conclusion: Our study shows that HEK and DO are the most predominant presentations of 17q12 deletion and duplication, respectively, and cardiac structural abnormalities may be associated with the latter. Although 17q12 CNVs have incomplete penetrance and variable expressivity and may be mainly involved in neurodevelopmental disorders, their short-term prognosis appears positive.

Abstract Background Noonan syndrome (NS) is a rare genetic disease, and patients who suffer from it exhibit a facial morphology that is characterized by a high forehead, hypertelorism, ptosis, inner epicanthal folds, down-slanting palpebral fissures, a highly arched palate, a round nasal tip, and posteriorly rotated ears. Facial analysis technology has recently been applied to identify many genetic syndromes (GSs). However, few studies have investigated the identification of NS based on the facial features of the subjects. Objectives This study develops advanced models to enhance the accuracy of diagnosis of NS. Methods A total of 1,892 people were enrolled in this study, including 233 patients with NS, 863 patients with other GSs, and 796 healthy children. We took one to 10 frontal photos of each subject to build a dataset, and then applied the multi-task convolutional neural network (MTCNN) for data pre-processing to generate standardized outputs with five crucial facial landmarks. The ImageNet dataset was used to pre-train the network so that it could capture generalizable features and minimize data wastage. We subsequently constructed seven models for facial identification based on the VGG16, VGG19, VGG16-BN, VGG19-BN, ResNet50, MobileNet-V2, and squeeze-and-excitation network (SENet) architectures. The identification performance of seven models was evaluated and compared with that of six physicians. Results All models exhibited a high accuracy, precision, and specificity in recognizing NS patients. The VGG19-BN model delivered the best overall performance, with an accuracy of 93.76%, precision of 91.40%, specificity of 98.73%, and F1 score of 78.34%. The VGG16-BN model achieved the highest AUC value of 0.9787, while all models based on VGG architectures were superior to the others on the whole. The highest scores of six physicians in terms of accuracy, precision, specificity, and the F1 score were 74.00%, 75.00%, 88.33%, and 61.76%, respectively. The performance of each model of facial recognition was superior to that of the best physician on all metrics. Conclusion Models of computer-assisted facial recognition can improve the rate of diagnosis of NS. The models based on VGG19-BN and VGG16-BN can play an important role in diagnosing NS in clinical practice.

Background: Lifestyle changes, such as those related to the COVID-19 pandemic, including alterations in physical activity and dietary habits, are known to affect pregnancy outcomes. In particular, suboptimal intrauterine conditions during pregnancy are known to influence not only fetal growth but also growth during infancy. However, research on the impact of the environmental changes caused by the COVID-19 pandemic on the growth of infants and children during their early years is lacking. To address this issue, this study evaluated the effect of the COVID-19 pandemic on obesity in infants. Methods: This retrospective cohort study used the data collected from the Korea National Health Insurance (KNHI) claims database. The data of 1985,678 women who delivered infants between 2015 and 2021 were collected. Women who delivered during the pandemic and those who delivered during the pre-pandemic period were matched in a 1:1 frequency-matched pair procedure for factors such as age, hypertension, diabetes mellitus, preeclampsia, gestational diabetes mellitus, mode of delivery, gestational age at delivery, offspring sex, and birth weight. Finally, 197,580 women were enrolled. The weight and head circumference of infants (4–6 months of age) of the COVID-19 pandemic group were compared with those of the pre-pandemic group. Results: The COVID-19 pandemic group infants exhibited significantly higher weight and prevalence of obesity at 4–6 months of age compared to infants in the pre-pandemic group. After adjustment for covariates, pandemic group infants had a higher risk of obesity (odds ratio: 1.54, 95% confidence interval: 1.51–1.57) compared to the pre-pandemic group infants. Conclusion: The COVID-19 pandemic has had a notable impact on the weight of infants aged 4–6 months. This suggests that pandemic conditions may influence the growth of newborns, underscoring the importance of monitoring and assessing trends in the growth of infants born during such crises.

Abstract Background The molecular mechanism of fetal cystic hygroma (CH) is still unclear, and no study has previously reported the transcriptome changes of single cells in CH. In this study, single-cell transcriptome sequencing (scRNA-seq) was used to investigate the characteristics of cell subsets in the lesion tissues of CH patients. Methods Lymphoid tissue collected from CH patients and control donors for scRNA-seq analysis. Differentially expressed gene enrichment in major cell subpopulations as well as cell-cell communication were analyzed. At the same time, the expression and interactions of important VEGF signaling pathway molecules were analyzed, and potential transcription factors that could bind to KDR (VEGFR2) were predicted. Results The results of scRNA-seq showed that fibroblasts accounted for the largest proportion in the lymphatic lesions of CH patients. There was a significant increase in the proportion of lymphatic endothelial cell subsets between the cases and controls. The VEGF signaling pathway is enriched in lymphatic endothelial cells and participates in the regulation of cell-cell communication between lymphatic endothelial cells and other cells. The key regulatory gene KDR in the VEGF signaling pathway is highly expressed in CH patients and interacts with other differentially expressed EDN1, TAGLN, and CLDN5 Finally, we found that STAT1 could bind to the KDR promoter region, which may play an important role in promoting KDR up-regulation. Conclusion Our comprehensive delineation of the cellular composition in tumor tissues of CH patients using single-cell RNA-sequencing identified the enrichment of lymphatic endothelial cells in CH and highlighted the activation of the VEGF signaling pathway in lymphoid endothelial cells as a potential modulator. Simple summary The molecular and cellular pathogenesis of fetal cystic hygroma (CH) remains largely unknown. This study examined the distribution and gene expression signature of each cell subpopulation and the possible role of VEGF signaling in lymphatic endothelial cells in regulating the progression of CH by single-cell transcriptome sequencing. The enrichment of lymphatic endothelial cells in CH and the activation of the VEGF signaling pathway in lymphatic endothelial cells provide some clues to the pathogenesis of CH from the perspective of cell subpopulations.

Background/Aims Metabolic dysfunction-associated steatotic liver disease (MASLD) is characterized by fat accumulation in the liver. MASLD encompasses both steatosis and MASH. Since MASH can lead to cirrhosis and liver cancer, steatosis and MASH must be distinguished during patient treatment. Here, we investigate the genomes, epigenomes, and transcriptomes of MASLD patients to identify signature gene set for more accurate tracking of MASLD progression. Methods Biopsy-tissue and blood samples from patients with 134 MASLD, comprising 60 steatosis and 74 MASH patients were performed omics analysis. SVM learning algorithm were used to calculate most predictive features. Linear regression was applied to find signature gene set that distinguish the stage of MASLD and to validate their application into independent cohort of MASLD. Results After performing WGS, WES, WGBS, and total RNA-seq on 134 biopsy samples from confirmed MASLD patients, we provided 1,955 MASLD-associated features, out of 3,176 somatic variant callings, 58 DMRs, and 1,393 DEGs that track MASLD progression. Then, we used a SVM learning algorithm to analyze the data and select the most predictive features. Using linear regression, we identified a signature gene set capable of differentiating the various stages of MASLD and verified it in different independent cohorts of MASLD and a liver cancer cohort. Conclusions We identified a signature gene set (i.e., CAPG, HYAL3, WIPI1, TREM2, SPP1, and RNASE6) with strong potential as a panel of diagnostic genes of MASLD-associated disease.

Abstract Background Lung cancer (LC) is an important comorbidity of interstitial lung disease (ILD) and has a poor prognosis. The clinical characteristics and outcome of each ILD subtype in LC patients have not been sufficiently investigated. Therefore, this study aimed to evaluate the difference between idiopathic pulmonary fibrosis (IPF) and non-IPF ILD as well as prognostic factors in patients with ILD-LC. Methods The medical records of 163 patients diagnosed with ILD-LC at Asan Medical Center from January 2018 to May 2023 were retrospectively reviewed. Baseline characteristics and clinical outcomes were compared between the IPF-LC and non-IPF ILD-LC groups, and prognostic factors were analyzed using the Cox proportional-hazard model. Results The median follow-up period was 11 months after the cancer diagnosis. No statistically significant differences were observed in clinical characteristics and mortality rates (median survival: 26 vs. 20 months, p = 0.530) between the groups. The independent prognostic factors in patients with ILD-LC were higher level of Krebs von den Lungen-6 (≥ 1000 U/mL, hazard ratio [HR] 1.970, 95% confidence interval [CI] 1.026-3.783, p = 0.025) and advanced clinical stage of LC (compared with stage I, HR 3.876 for stage II, p = 0.025, HR 5.092 for stage III, p = 0.002, and HR 5.626 for stage IV, p = 0.002). In terms of treatment, surgery was the significant factor for survival (HR 0.235; 95% CI 0.106-0.520; p

AbstractObjective Both oral contraceptive pills (OCPs) and cyclic medroxyprogesterone acetate (MPA) are widely used to control menstrual abnormalities in women with polycystic ovary syndrome (PCOS). We aimed to evaluate the chance of ovulation resumption after cessation of OCPs and MPA in women with PCOS.Methods A retrospective study was conducted of women with PCOS who were treated with OCPs or cyclic MPA from September 2015 to March 2019. After cessation of medication, ovulation was assessed using basal body temperature and/or measurement of serum progesterone. The odds ratio for ovulation resumption was assessed with multivariable logistic regression. Additionally, doubly robust analysis was performed with inverse-probability-weighted analysis and regression adjustment based on the covariate balancing propensity score to adjust for the effect of covariates on the treatment assignment.Results Among 272 women with PCOS, 136 were prescribed OCPs and 136 were prescribed cyclic MPA. Ovulation resumed in 18.4% of women (n = 25) after cessation of MPA and in 24.3% of women (n = 33) after cessation of OCPs. The odds of ovulation resumption in MPA users were comparable with those in OCP users (adjusted odds ratio (aOR) 1.00, 95% confidence interval (CI) 0.89–1.12). After multiple imputation due to missing values, the results did not change substantially (aOR 0.99, 95% CI 0.89–1.10).Conclusions Among women with PCOS, MPA users have a similar chance of ovulation resumption as OCP users after cessation of medication. Cyclic MPA can be a good alternative to OCPs in women for whom OCPs are contraindicated or who decline to take OCPs.

IntroductionUniversity students are particularly susceptible to developing high levels of stress, which occur when environmental demands outweigh an individual’s ability to cope. The growing advent of mental health smartphone apps has led to a surge in use by university students seeking ways to help them cope with stress. Use of these apps has afforded researchers the unique ability to collect extensive amounts of passive sensing data including GPS and step detection. Despite this, little is known about the relationship between passive sensing data and stress. Further, there are no established methodologies or tools to predict stress from passive sensing data in this group.MethodsIn this study, we establish a clear machine learning-based methodological pipeline for processing passive sensing data and extracting features that may be relevant in the context of mental health.ResultsWe then use this methodology to determine the relationship between passive sensing data and stress in university students.DiscussionIn doing so, we offer the first proof-of-principle data for the utility of our methodological pipeline and highlight that passive sensing data can indeed digitally phenotype stress in university students.Clinical trial registrationAustralia New Zealand Clinical Trials Registry (ANZCTR), identifier ACTRN12621001223820.

Garnet-type Li7La3Zr2O12 (LLZO) Li-ion solid electrolytes are promising candidates for safe, next-generation solid-state batteries. In this study, we synthesize Ga-doped LLZO (Ga–LLZO) electrolytes using a microwave-assisted solvothermal method followed by low-temperature heat treatment. The nanostructured precursor (

Digital phenotyping is a promising method for advancing scalable detection and prediction methods in mental health research and practice. However, little is known about how digital phenotyping data are used to make inferences about youth mental health. We conducted a scoping review of 35 studies to better understand how passive sensing (e.g., Global Positioning System, microphone etc) and electronic usage data (e.g., social media use, device activity etc) collected via smartphones are used in detecting and predicting depression and/or anxiety in young people between 12 and 25 years-of-age. GPS and/or Wifi association logs and accelerometers were the most used sensors, although a wide variety of low-level features were extracted and computed (e.g., transition frequency, time spent in specific locations, uniformity of movement). Mobility and sociability patterns were explored in more studies compared to other behaviours such as sleep, phone use, and circadian movement. Studies used machine learning, statistical regression, and correlation analyses to examine relationships between variables. Results were mixed, but machine learning indicated that models using feature combinations (e.g., mobility, sociability, and sleep features) were better able to predict and detect symptoms of youth anxiety and/or depression when compared to models using single features (e.g., transition frequency). There was inconsistent reporting of age, gender, attrition, and phone characteristics (e.g., operating system, models), and all studies were assessed to have moderate to high risk of bias. To increase translation potential for clinical practice, we recommend the development of a standardised reporting framework to improve transparency and replicability of methodology.

Key Clinical Message In previous reports, hypothyroidism, hypopituitrism, and hypogonadism were common endocrine causes of SCFE, but this is the first time that congenital adrenal hyperplasia has been observed. As such, patients who have undergone long‐term endocrine treatment for congenital adrenal hyperplasia could potentially be subjected to a higher risk for SCFE.

Objective: To investigate the prevalence of subthreshold depression among Chinese college students and to explore the related factors. Methods: The research subjects were Chinese college students participating in the “2022 Psychology and Behavior Investigation of Chinese Residents (PBICR-2022)''. Data on respondents' general characteristics, quality of life, perceived pressure, family communication, perceived social support, self-efficacy, and depression status were gathered. To investigate the association between each variable and the risk of subthreshold depression, statistical analyses, including chi-square tests and rank sum tests were conducted. Furthermore, a binary stepwise logistic regression was employed to establish the regression model of the factors related to subthreshold depression among Chinese college students. Results: A prevalence of subthreshold depression of about 39.7 % was found among the 8934 respondents. Logistic regression analysis revealed that respondents who are female, have chronic diseases, are in debt, experience significant impacts from epidemic control policies, have lower self-assessed quality of life, experience challenges in family communication, perceive lower social support, have lower self-efficacy, and feel higher perceived pressure are more likely to develop subthreshold depression compared to the control group. (P

Pyruvate kinase M2 (PKM2), a rate limiting enzyme in glycolysis, is a cellular regulator that has received extensive attention and regards as a metabolic regulator of cellular metabolism and energy. Kidney is a highly metabolically active organ, and glycolysis is the important energy resource for kidney. The accumulated evidences indicates that the enzymatic activity of PKM2 is disturbed in kidney disease progression and treatment, especially diabetic kidney disease and acute kidney injury. Modulating PKM2 post-translational modification determines its enzymatic activity and nuclear translocation that serves as an important interventional approach to regulate PKM2. Emerging evidences show that PKM2 and its post-translational modification participate in kidney disease progression and treatment through modulating metabolism regulation, podocyte injury, fibroblast activation and proliferation, macrophage polarization, and T cell regulation. Interestingly, PKM2 activators (TEPP-46, DASA-58, mitapivat, and TP-1454) and PKM2 inhibitors (shikonin, alkannin, compound 3k and compound 3h) have exhibited potential therapeutic property in kidney disease, which indicates the pleiotropic effects of PKM2 in kidney. In the future, the deep investigation of PKM2 pleiotropic effects in kidney is urgently needed to determine the therapeutic effect of PKM2 activator/inhibitor to benefit patients. The information in this review highlights that PKM2 functions as a potential biomarker and therapeutic target for kidney diseases.

Dual immunoglobulin domain-containing cell adhesion molecule (DICAM) is a type I transmembrane protein that presents in various cells including renal tubular cells. This study evaluated the expression and protective role of DICAM in renal tubular cell injury. HK-2 cells were incubated and treated with lipopolysaccharide (LPS, 30 μg/mL) or hydrogen peroxide (H2O2, 100 μM) for 24 h. To investigate the effect of the gene silencing of DICAM, small interfering RNA of DICAM was used. Additionally, to explain its role in cellular response to injury, DICAM was overexpressed using an adenoviral vector. DICAM protein expression levels significantly increased following treatment with LPS or H2O2 in HK-2 cells. In response to oxidative stress, DICAM showed an earlier increase (2–4 h following treatment) than neutrophil gelatinase-associated lipocalin (NGAL) (24 h following treatment). DICAM gene silencing increased the protein expression of inflammation-related markers, including IL-1β, TNF-α, NOX4, integrin β1, and integrin β3, in H2O2-induced HK-2 cell injury. Likewise, in the LPS-induced HK-2 cell injury, DICAM knockdown led to a decrease in occludin levels and an increase in integrin β3, IL-1β, and IL-6 levels. Furthermore, DICAM overexpression followed by LPS-induced HK-2 cell injury resulted in an increase in occludin levels and a decrease in integrin β1, integrin β3, TNF-α, IL-1β, and IL-6 levels, suggesting an alleviating effect on inflammatory responses. DICAM was elevated in the early stage of regular tubular cell injury and may protect against renal tubular injury through its anti-inflammatory properties. DICAM has a potential as an early diagnostic marker and therapeutic target for renal cell injury.

Objectives: Adjusting for potential confounders is crucial for producing valuable evidence in outcome studies. Although numerous studies have been published using the Korea National Health Insurance Claim Database, no study has critically reviewed the methods used to adjust for confounders. This study aimed to review these studies and suggest methods and applications to adjust for confounders. Methods: We conducted a literature search of electronic databases, including PubMed and Embase, from January 1, 2021 to December 31, 2022. In total, 278 studies were retrieved. Eligibility criteria were published in English and outcome studies. A literature search and article screening were independently performed by 2 authors and finally, 173 of 278 studies were included. Results: Thirty-nine studies used matching at the study design stage, and 171 adjusted for confounders using regression analysis or propensity scores at the analysis stage. Of these, 125 conducted regression analyses based on the study questions. Propensity score matching was the most common method involving propensity scores. A total of 171 studies included age and/or sex as confounders. Comorbidities and healthcare utilization, including medications and procedures, were used as confounders in 146 and 82 studies, respectively. Conclusions: This is the first review to address the methods and applications used to adjust for confounders in recently published studies. Our results indicate that all studies adjusted for confounders with appropriate study designs and statistical methodologies; however, a thorough understanding and careful application of confounding variables are required to avoid erroneous results.

Abstract We introduce the effective field theory of two different light dark particles interacting with the standard model (SM) light states in a single vertex, termed dark sector effective field theory (DSEFT). We focus on the new light particles with spin up to 1 and being real in essence, namely, new real scalars ϕ and S, Majorana fermions χ and ψ, and real vectors X μ and V μ . In the framework of low energy effective field theory with QED and QCD symmetry, the DSEFT can be classified into six categories, including the scalar-scalar-SM (ϕS-SM), fermion-fermion-SM (χψ-SM), vector-vector-SM (XV-SM), scalar-fermion-SM (ϕχ-SM), scalar-vector-SM (ϕX-SM), and fermion-vector-SM (χX-SM) cases. For each case, we construct the effective operator basis up to canonical dimension 7, which will cover most interesting phenomenology at low energy. As a phenomenological example, we investigate the longstanding neutron lifetime anomaly through the neutron dark decay modes n → χϕ or χX from the effective interactions in the fermion-scalar-SM or fermion-vector-SM case. When treating the light fermion as a dark matter candidate, we also explore the constraints from DM-neutron annihilation signal at Super-Kamiokande. We find the neutron dark decay in each scenario can accommodate the anomaly, at the same time, without contradicting with the Super-Kamiokande limit.

Abstract Teleost fishes, which are the largest and most diverse group of living vertebrates, have a rich history of ancient and recent polyploidy. Previous studies of allotetraploid common carp and goldfish (cyprinids) reported a dominant subgenome, which is more expressed and exhibits biased gene retention. However, the underlying mechanisms contributing to observed ‘subgenome dominance’ remains poorly understood. Here we report high-quality genomes of twenty-one cyprinids to investigate the origin and subsequent subgenome evolution patterns following three independent allopolyploidy events. We identify the closest extant relatives of the diploid progenitor species, investigate genetic and epigenetic differences among subgenomes, and conclude that observed subgenome dominance patterns are likely due to a combination of maternal dominance and transposable element densities in each polyploid. These findings provide an important foundation to understanding subgenome dominance patterns observed in teleost fishes, and ultimately the role of polyploidy in contributing to evolutionary innovations.

ABSTRACTAutoimmune diseases are conditions in which the immune system mistakenly targets and damages healthy tissue in the body. In recent decades, the incidence of autoimmune diseases has increased, resulting in a significant disease burden. The current autoimmune therapies focus on targeting inflammation or inducing immunosuppression rather than addressing the underlying cause of the diseases. The activity of metabolic pathways is elevated in autoimmune diseases, and metabolic changes are increasingly recognized as important pathogenic processes underlying these. Therefore, metabolically targeted therapies may represent an important strategy for treating autoimmune diseases. This review provides a comprehensive overview of the evidence surrounding glucose metabolic reprogramming and its potential applications in drug discovery and development for autoimmune diseases, such as type 1 diabetes, multiple sclerosis, systemic lupus erythematosus, rheumatoid arthritis, and systemic sclerosis.

Members of the Malvaceae family, including Corchorus spp., Gossypium spp., Bombax spp., and Ceiba spp., are important sources of natural fibers. In the past decade, the genomes of several Malvaceae species have been assembled; however, the evolutionary history of Malvaceae species and the differences in their fiber development remain to be clarified. Here, we report the genome assembly and annotation of two natural fiber plants from the Malvaceae, Bombax ceiba and Ceiba pentandra, whose assembled genome sizes are 783.56 Mb and 1575.47 Mb, respectively. Comparative analysis revealed that whole-genome duplication and Gypsy long terminal repeat retroelements have been the major causes of differences in chromosome number (2n = 14 to 2n = 96) and genome size (234 Mb to 2676 Mb) among Malvaceae species. We also used comparative genomic analyses to reconstruct the ancestral Malvaceae karyotype with 11 proto-chromosomes, providing new insights into the evolutionary trajectories of Malvaceae species. MYB-MIXTA-like 3 is relatively conserved among the Malvaceae and functions in fiber cell-fate determination in the epidermis. It appears to perform this function in any tissue where it is expressed, i.e. in fibers on the endocarp of B. ceiba and in ovule fibers of cotton. We identified a structural variation in a cellulose synthase gene and a higher copy number of cellulose synthase-like genes as possible causes of the finer, less spinnable, weaker fibers of B. ceiba. Our study provides two high-quality genomes of natural fiber plants and offers insights into the evolution of Malvaceae species and differences in their natural fiber formation and development through multi-omics analysis.

Abstract Soft robots require soft actuators for mobility and functionality. To integrate multiple functions in a limited space, researchers are developing multifunctional soft actuators with several functions integrated in one device. This study successfully demonstrates an electroluminescent (EL) soft actuator, a single device with both light‐emitting and actuating capabilities, using liquid dielectric and uniformly dispersed EL phosphor particles. EL phosphor particles are copper‐doped zinc sulfide (ZnS) particles doped with copper. The work is able to disperse the ZnS particles uniformly in the oil by coating the ZnS particles with silica, ensuring consistent luminescence across the device's active area. The performance of the soft actuator is notable, with a strain of 25% and a maximum EL intensity of 23 cd m−2 for a single actuator. When stacking multiple actuators, the intensity exceeds 29 cd m−2. The findings suggest that EL actuator devices will be valuable smart components for soft robots and interactive sensors. They can effectively represent external stimuli through color signals, expanding the capabilities of these systems.

IntroductionAryl hydrocarbon receptor (AhR) is a transcription factor that performs various functions upon ligand activation. Several studies have explored the role of AhR expression in tumor progression and immune surveillance. Nevertheless, investigations on the distribution of AhR expression, specifically in cancer or immune cells in the tumor microenvironment (TME), remain limited. Examining the AhR expression and distribution in the TME is crucial for gaining insights into the mechanism of action of AhR-targeting anticancer agents and their potential as biomarkers.MethodsHere, we used multiplexed immunohistochemistry (mIHC) and image cytometry to investigate the AhR expression and distribution in 513 patient samples, of which 292 are patients with one of five solid cancer types. Additionally, we analyzed the nuclear and cytosolic distribution of AhR expression.ResultsOur findings reveal that AhR expression was primarily localized in cancer cells, followed by stromal T cells and macrophages. Furthermore, we observed a positive correlation between the nuclear and cytosolic expression of AhR, indicating that the expression of AhR as a biomarker is independent of its localization. Interestingly, the expression patterns of AhR were categorized into three clusters based on the cancer type, with high AhR expression levels being found in regulatory T cells (Tregs) in non-small cell lung cancer (NSCLC).DiscussionThese findings are anticipated to serve as pivotal evidence for the design of clinical trials and the analysis of the anticancer mechanisms of AhR-targeting therapies.

Abstract High‐capacity silicon (Si) materials hold a position at the forefront of advanced lithium‐ion batteries. The inherent potential offers considerable advantages for substantially increasing the energy density in batteries, capable of maximizing the benefit by changing the paradigm from nano‐ to micron‐sized Si particles. Nevertheless, intrinsic structural instability remains a significant barrier to its practical application, especially for larger Si particles. Here, a covalently interconnected system is reported employing Si microparticles (5 µm) and a highly elastic gel polymer electrolyte (GPE) through electron beam irradiation. The integrated system mitigates the substantial volumetric expansion of pure Si, enhancing overall stability, while accelerating charge carrier kinetics due to the high ionic conductivity. Through the cost‐effective but practical approach of electron beam technology, the resulting 500 mAh‐pouch cell showed exceptional stability and high gravimetric/volumetric energy densities of 413 Wh kg−1, 1022 Wh L−1, highlighting the feasibility even in current battery production lines.

Background: Previous studies have reported that genes highly expressed in leukemic stem cells (LSC) may dictate the survival probability of patients and expression-based cellular deconvolution may be informative in forecasting prognosis. However, whether the prognosis of acute myeloid leukemia (AML) can be predicted using gene expression and deconvoluted cellular abundances is debatable.Methods: Nine different cell-type abundances of a training set composed of the AML samples of 422 patients, were used to build a model for predicting prognosis by least absolute shrinkage and selection operator Cox regression. This model was validated in two different validation sets, TCGA-LAML and Beat AML (n = 179 and 451, respectively).Results: We introduce a new prognosis predicting model for AML called the LSC activity (LSCA) score, which incorporates the abundance of 5 cell types, granulocyte-monocyte progenitors, common myeloid progenitors, CD45RA + cells, megakaryocyte-erythrocyte progenitors, and multipotent progenitors. Overall survival probabilities between the high and low LSCA score groups were significantly different in TCGA-LAML and Beat AML cohorts (log-rank p-value = 3.3×10−4 and 4.3×10−3, respectively). Also, multivariate Cox regression analysis on these two validation sets shows that LSCA score is independent prognostic factor when considering age, sex, and cytogenetic risk (hazard ratio, HR = 2.17; 95% CI 1.40–3.34; p < 0.001 and HR = 1.20; 95% CI 1.02–1.43; p < 0.03, respectively). The performance of the LSCA score was comparable to other prognostic models, LSC17, APS, and CTC scores, as indicated by the area under the curve. Gene set variation analysis with six LSC-related functional gene sets indicated that high and low LSCA scores are associated with upregulated and downregulated genes in LSCs.Conclusion: We have developed a new prognosis prediction scoring system for AML patients, the LSCA score, which uses deconvoluted cell-type abundance only.

IntroductionTo understand the immune system within the tumor microenvironment (TME) of non-small cell lung cancer (NSCLC), it is crucial to elucidate the characteristics of molecules associated with T cell activation.MethodsWe conducted an in-depth analysis using single-cell RNA sequencing data obtained from tissue samples of 19 NSCLC patients. T cells were classified based on the Tumor Proportion Score (TPS) within the tumor region, and molecular markers associated with activation and exhaustion were analyzed in T cells from high TPS areas.ResultsNotably, tetraspanins CD81 and CD82, belonging to the tetraspanin protein family, were found to be expressed in activated T cells, particularly in cytotoxic T cells. These tetraspanins showed strong correlations with activation and exhaustion markers. In vitro experiments confirmed increased expression of CD81 and CD82 in IL-2-stimulated T cells. T cells were categorized into CD81highCD82high and CD81lowCD82low groups based on their expression levels, with CD81highCD82high T cells exhibiting elevated activation markers such as CD25 and CD69 compared to CD81lowCD82low T cells. This trend was consistent across CD3+, CD8+, and CD4+ T cell subsets. Moreover, CD81highCD82high T cells, when stimulated with anti-CD3, demonstrated enhanced secretion of cytokines such as IFN-γ, TNF-α, and IL-2, along with an increase in the proportion of memory T cells. Bulk RNA sequencing results after sorting CD81highCD82high and CD81lowCD82low T cells consistently supported the roles of CD81 and CD82. Experiments with overexpressed CD81 and CD82 showed increased cytotoxicity against target cells.DiscussionThese findings highlight the multifaceted roles of CD81 and CD82 in T cell activation, cytokine production, memory subset accumulation, and target cell cytolysis. Therefore, these findings suggest the potential of CD81 and CD82 as promising candidates for co-stimulatory molecules in immune therapeutic strategies for cancer treatment within the intricate TME.

Abstract Background The factors that influence transition from suicidal ideation to a suicide attempt or remission of suicidal thoughts are poorly understood. Despite an abundance of research on risk factors for suicidal ideation, no large-scale longitudinal population-based studies have specifically recruited people with suicidal ideation to examine the mechanisms underlying critical transitions to either suicide attempt or recovery from suicidal ideation. Without longitudinal data on the psychological, behavioural, and social determinants of suicide attempt and the remission of suicidal ideation, we are unlikely to see major gains in the prevention of suicide. Aim The LifeTrack Project is a population-based longitudinal cohort study that aims to identify key modifiable risk and protective factors that predict the transition from suicidal ideation to suicide attempt or remission of suicidal ideation. We will assess theory-informed risk and protective factors using validated and efficient measures to identify distinct trajectories reflecting changes in severity of suicidal ideation and transition to suicide attempt over three years. Methods A three-year prospective population-based longitudinal cohort study will be conducted with adults from the general Australian population who initially report suicidal ideation (n = 842). Eligibility criteria include recent suicidal ideation (past 30 days), aged 18 years or older, living in Australia and fluent in English. Those with a suicide attempt in past 30 days or who are unable to participate in a long-term study will be excluded. Participants will be asked to complete online assessments related to psychopathology, cognition, psychological factors, social factors, mental health treatment use, and environmental exposures at baseline and every six months during this three-year period. One week of daily measurement bursts (ecological momentary assessments) at yearly intervals will also capture short-term fluctuations in suicidal ideation, perceived burdensomeness, thwarted belongingness, capability for suicide, and distress. Conclusion This study is intended to identify potential targets for novel and tailored therapies for people experiencing suicidal ideation and improve targeting of suicide prevention programs. Even modest improvements in current treatments may lead to important reductions in suicide attempts and deaths. Study Registration Australian New Zealand Clinical Trials Registry identifier: ACTRN12623000433606.

PURPOSE With the widespread of mitochondrial function, the need to accurately quantify and comprehend mitochondrial O2 respiration has gained prominence within the physiological and pathological spheres. Various in situ, in vitro, and in vivo approaches have been available to investigate numerous aspects of mitochondrial O2 consumption. This review aims to provide a specific method for researchers to consider in examining mitochondrial O2 respiration using permeabilized or homogenized tissues. These techniques allow direct access to mitochondrial O2 respiration, facilitating an exploration of mitochondrial bioenergetics under well-defined substrate conditions. METHODS Here, we present a method for measuring mitochondrial O2 consumption in permeabilized or homogenized tissues using high-resolution respirometry (Oroboros Oxygraph-2K, Oroboros Instrument). RESULTS A high-resolution respirometry provides the most direct way to assess mitochondrial O2 respiration with interpretations based on specific modeling approaches. CONCLUSIONS As many diseases are closely associated with mitochondrial dysfunction, ongoing advancements in this methodology may provide researchers with exciting and novel opportunities for finding the potential role of mitochondria in the etiology and treatment of various diseases.

Abstract Background Although acute exacerbation (AE) after treatment for lung cancer (LC) is a poor prognostic factor in patients with interstitial lung disease associated with lung cancer (ILD‐LC), the risk of AE according to cancer treatment type remains unclear. Therefore, in the present study, we aimed to investigate the association between AE and treatment received for LC in patients with ILD‐LC. Methods We conducted a retrospective study of patients with ILD‐LC who had undergone treatment for LC between January 2018 and December 2022. The primary study outcome was the incidence of AE within 12 months of treatment for LC according to treatment type. The association between AE and all‐cause mortality was evaluated as a secondary outcome. Results Among a total of 137 patients, 23 (16.8%) developed AE within 12 months of treatment for LC. The incidence of AE according to treatment type was 4.3% for surgery, 16.2% for radiotherapy, 15.6% for chemotherapy, and 54.5% for concurrent chemoradiation therapy (CCRT). Patients who received CCRT were more likely to develop AE, even after adjustment for covariables (hazard ratio [HR], 15.39; 95% confidence interval [CI]: 4.00–59.19; p

Purpose This study aimed to assess the variability of transrectal shear wave elastography (SWE) using a designed phantom. Materials and Methods In a phantom, the SWE values were examined by two radiologists using agarose and emulsion silicone of different sizes (1, 2, and 3 cm) and shapes (round, cubic) at three depths (1, 2, and 3 cm), two region of interest (ROI) and locations (central, peripheral) using two ultrasound machines (A, B from different vendors). Variability was evaluated using the coefficient of variation (CV). Results The CVs decreased with increasing phantom size. Significant changes in SWE values included; agarose phantom at 3 cm depth (p < 0.001; machine A), 1 cm depth (p = 0.01; machine B), emulsion silicone at 2 cm depth (p = 0.047, p = 0.020; both machines). The CVs increased with increasing depth. Significant changes in SWE values included; 1 cm agarose (p = 0.037, p = 0.021; both machines) and 2 cm agarose phantom (p = 0.047; machine A). Significant differences in SWE values were observed between the shapes for emulsion silicone phantom (p = 0.032; machines A) and between ROI locations on machine B (p ≤ 0.001). The SWE values differed significantly between the two machines (p < 0.05). The intra-/inter-operator agreements were excellent (intraclass correlation coefficient > 0.9). Conclusion The phantom size, depth, and different machines affected the variability of transrectal SWE.

Abstract In the view of the situation where great economic loss often occurs during mining deep coal seams in Feicheng coal field due to water inrush from the floor Ordovician limestone aquifer, the floor "lower four-zone" theory was used as a guide. 81006 working face of Caozhuang Coalmine in Feicheng coal field was taken as the research background, and paste filling technology was proposed to inhibit or reduce the damaged floor depth caused by mine ground pressure in order to prevent water inrush from the floor Ordovician limestone aquifer. Glue material, coal gangue powder, and fly ash were selected as filling material, and a ground filling system, including a material production system, storage material system, power supply and water supply system, automatic control and measurement system, monitoring and control communications system, emergency response system, and underground filling system, including pipe conveyor system and working face blocking grout loss system, were established to achieve effective filling goaf. Field stress monitoring and floor damaged depth measurement showed that when reaching a steady state after a period of time, paste filling working face not only restored to the original stress state but also significantly reduced the floor's damaged depth caused by mine ground pressure. This verifies that working face with paste-like backfill technology is a very effective measure to prevent water-inrush from the floor.

Abstract Suppressing the oxidation of active-Ir(III) in IrOx catalysts is highly desirable to realize an efficient and durable oxygen evolution reaction in water electrolysis. Although charge replenishment from supports can be effective in preventing the oxidation of IrOx catalysts, most supports have inherently limited charge transfer capability. Here, we demonstrate that an excess electron reservoir, which is a charged oxygen species, incorporated in antimony-doped tin oxide supports can effectively control the Ir oxidation states by boosting the charge donations to IrOx catalysts. Both computational and experimental analyses reveal that the promoted charge transfer driven by excess electron reservoir is the key parameter for stabilizing the active-Ir(III) in IrOx catalysts. When used in a polymer electrolyte membrane water electrolyzer, Ir catalyst on excess electron reservoir incorporated support exhibited 75 times higher mass activity than commercial nanoparticle-based catalysts and outstanding long-term stability for 250 h with a marginal degradation under a water-splitting current of 1 A cm−2. Moreover, Ir-specific power (74.8 kW g−1) indicates its remarkable potential for realizing gigawatt-scale H2 production for the first time.

In structures manufactured using 3D concrete printing, cracks can easily propagate along the interface between printed layers. Therefore, it was necessary to determine the interlayer bond strength. In this study, direct shear and tensile tests were performed to determine the interlayer bond stability of the 3DCP members. To confirm the appropriateness of the mix proportion used to fabricate the specimens, the open time available for printing was identified via a mixing test, and the extrudability and buildability were verified via a printing test. In addition, direct shear and tensile tests were performed using the specimen manufacturing method (i.e., mold casting and 3D printing) and printing time gap (PTG) between the laminated layers as key test variables. The interlayer bond strengths of the specimens, according to the variables obtained from the test results, were compared and analyzed based on the interfacial shear strength standards presented in the current structural codes. In the direct shear test, failure occurred at the interlayers of all the specimens, and the interlayer bond strength tended to decrease with increasing PTG. In addition, the interlayer bond strength of the direct shear specimens exceeded the interfacial shear strength suggested by current structural codes. In contrast, in the direct tensile test, interlayer surface failure occurred only in some specimens, and there was no distinct change in the interlayer bond strength owing to PTG.

Gastric cancer is the fifth most common disease in the world and the fourth most common cause of death. It is diagnosed through esophagogastroduodenoscopy with biopsy; however, there are limitations in finding lesions in the early stages. Recently, research has been actively conducted to use liquid biopsy to diagnose various cancers, including gastric cancer. Various substances derived from cancer are reflected in the blood. By analyzing these substances, it was expected that not only the presence or absence of cancer but also the type of cancer can be diagnosed. However, the amount of these substances is extremely small, and even these have various variables depending on the characteristics of the individual or the characteristics of the cancer. To overcome these, we collected methylated DNA fragments using MeDIP and compared them with normal plasma to characterize gastric cancer tissue or patients’ plasma. We attempted to diagnose gastric cancer using the characteristics of cancer reflected in the blood through the cancer tissue and patients’ plasma. As a result, we confirmed that the consistency of common methylated fragments between tissue and plasma was approximately 41.2% and we found the possibility of diagnosing and characterizing cancer using the characteristics of the fragments through SFR and 5′end-motif analysis.

Macrophage activation syndrome (MAS) is potentially fatal; so, early diagnosis and timely treatment are essential. However, detecting MAS is sometimes challenging because its principal features can be observed in other pediatric diseases that cause severe inflammation. Cytokine storm due to immune dysregulation represents the clinical and laboratory features of MAS that are included in the diagnostic criteria. Most cases of MAS occur as an underlying condition worsens and progresses. Therefore, a patient with autoimmune or autoinflammatory disease who shows unexplained clinical deterioration despite appropriate management should be considered at high risk for MAS (i.e., occult MAS). The basic principles of treatment are control of triggering factors, supportive care, and relief of hyperinflammation. Systemic steroids and cyclosporine A are frequently used as a first-line treatment. For the treatment of refractory MAS, cytokine-specific biologic agents such as anakinra have recently become preferred over traditional immunosuppressive agents such as etoposide. MAS might be underrecognized in pediatric patients with infectious and inflammatory diseases due to its diverse clinical presentations. Clinical suspicion of MAS is of the utmost importance for early recognition of the disease.