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Abstract Objective White matter hyperintensities (WMH) on brain MRI images are the most common feature of cerebral small vessel disease (CSVD). Studies have yielded divergent findings on the modifiable risk factors for WMH and WMH’s impact on cognitive decline. Mounting evidence suggests sex differences in WMH burden and subsequent effects on cognition. Thus, we aimed to identify sex-specific modifiable risk factors for WMH. We then explored whether there were sex-specific associations of WMH to longitudinal clinical dementia outcomes. Methods Participants aged 49–89 years were recruited at memory clinics and underwent a T2-weighted fluid-attenuated inversion recovery (FLAIR) 3T MRI scan to measure WMH volume. Participants were then recruited for two additional follow-up visits, 1–2 years apart, where clinical dementia rating sum of boxes (CDR-SB) scores were measured. We first explored which known modifiable risk factors for WMH were significant when tested for a sex-interaction effect. We additionally tested which risk factors were significant when stratified by sex. We then tested to see whether WMH is longitudinally associated with clinical dementia that is sex-specific. Results The study utilized data from 713 participants (241 males, 472 females) with a mean age of 72.3 years and 72.8 years for males and females, respectively. 57.3% and 59.5% of participants were diagnosed with mild cognitive impairment (MCI) for males and females, respectively. 40.7% and 39.4% were diagnosed with dementia for males and females, respectively. Of the 713 participants, 181 participants had CDR-SB scores available for three longitudinal time points. Compared to males, females showed stronger association of age to WMH volume. Type 2 Diabetes was associated with greater WMH burden in females but not males. Finally, baseline WMH burden was associated with worse clinical dementia outcomes longitudinally in females but not in males. Discussion Older females have an accelerated increase in cerebrovascular burden as they age, and subsequently are more vulnerable to clinical dementia decline due to CSVD. Additionally, females are more susceptible to the cerebrovascular consequences of diabetes. These findings emphasize the importance of considering sex when examining the consequences of CSVD. Future research should explore the underlying mechanisms driving these sex differences and personalized prevention and treatment strategies. Clinical trial registration The BICWALZS is registered in the Korean National Clinical Trial Registry (Clinical Research Information Service; identifier, KCT0003391). Registration Date 2018/12/14.

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.

PurposeTo evaluate the effects of clear corneal incision (CCI) location and morphology on corneal surgically induced astigmatism (SIA) and higher-order aberrations (HOAs) in patients receiving implantable collamer lens (ICL V4c) implantation.MethodsThis retrospective study classified right eyes that underwent ICL implantation into two groups based on temporal or superior CCI. The Pentacam HR analyzer was used to measure the corneal astigmatism and HOAs. Analysis of the clear corneal incision (CCI) morphology, including incision width (Angle-W), incision length (IL), incision angles (Angle-En/Ex), and distance from the incision to corneal apex (Dis-En/Ex), was conducted using anterior segment optical coherence tomography (AS-OCT).ResultsThere were 75 eyes in the temporal CCI group and 47 eyes in the superior CCI group. Both groups showed satisfactory safety and efficacy postoperatively. In the temporal CCI group, Dis-En and Dis-Ex were considerably longer, whereas the superior CCI group displayed a significantly wider Angle-W. The anterior and posterior corneal SIA were comparable in both groups. Anterior corneal SIA was significantly correlated to Dis-En and Dis-Ex in the superior CCI group. Superior CCI caused a notable rise in corneal Z (3, 3), while temporal CCI led to increased Z (3, 1). CCI morphology was correlated to corneal Z (4, −4) and Z (4, 4) in the superior CCI group.ConclusionCCI locations caused slight variations in postoperative corneal SIA and HOAs following ICL implantation. Optimal postoperative visual outcomes may be better achieved with a CCI design featuring an increased distance from the corneal centroid and a decreased Angle-W.