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Neuropsychiatric symptoms (NPSs) are prevalent in Alzheimer’s disease (AD), yet their neurobiological etiology remains elusive. We investigated relationships between NPS subsyndromes, plasma neurofilament light chain (NFL), AD-vulnerable brain atrophy, and cognition.
Methods
We included 146 participants from a Chinese cohort. NPSs were assessed using the Neuropsychiatric Inventory Questionnaire and clustered into four subsyndromes (hyperactivity, psychosis, affective, apathy), each graded by severity (none, mild, severe). Sequential mediation analyses examined whether NPSs influence cognition through NFL and atrophy. Additionally, 1534 ADNI participants were enrolled to (1) replicate mediation effects; (2) examine longitudinal relationships of NPSs with incident cognitive decline; and (3) evaluate cognitive discrimination of NPSs and NFL and onset hazards of NPS subsyndromes.
Results
In the discovery cohort, global NPSs burden and three subsyndromes (hyperactivity, affective, apathy) were associated with elevated plasma NFL, poorer global cognition and memory, and reduced brain volumes (all P < 0.05). Sequential mediation revealed that plasma NFL and atrophy mediated the cross-sectional NPSs–cognition relationship, replicated in ADNI. Adding NPSs and NFL improved cognitive discrimination (AUC: 0.6754 to 0.8210, P < 0.001). Additionally, apathy and psychosis showed lower onset hazards than affective and hyperactivity (both P < 0.001).
Conclusions
Baseline NPSs were cross-sectionally associated with elevated NFL, brain atrophy, and poorer cognition. Sequential mediation models supported a pathway linking NPSs to cognition via NFL and atrophy, though longitudinal evidence did not fully confirm temporal directionality. These hypothesis-generating findings require prospective validation.
Blended-wing-body (BWB) aircraft with distributed propulsion offers significant potential for aerodynamic efficiency. However, this tightly integrated configuration inherently operates under boundary layer ingestion (BLI) conditions. The ingested thick fuselage boundary layer, coupled with the strong aerodynamic interactions between the S-shaped intake and wing, generates adverse pressure gradients at the inlet alongside low total pressure recovery coefficients and high outlet distortion. This study investigates integrated flow control under high-altitude flight conditions using a BWB aerofoil integrated with a semi-embedded S-shaped intake model, incorporating energy analysis. During cruise, strong adverse pressure gradients between the wing shock wave and intake cause distinct lip separation, resulting in a low total pressure recovery coefficient and high distortion. Distributed dual-row suction generates secondary flow generates distributed secondary flow near the separation point with equivalent energy consumption. This enhances fuselage boundary layer mixing, reduces near-wall adverse pressure gradients and improves the total pressure recovery coefficient. The integration of internal jet control synergistically augments the benefits of external wing suction via distinct spatial mechanisms: central jets replenish core flow kinetic energy to suppress separation and improve the total pressure recovery coefficient, while side jets enhance mixing between separation zones and mainstream flow, mitigating secondary swirl losses and substantially reducing distortion at the aerodynamic interface plane (AIP). Energy analysis confirms that a modest energy input (equivalent to 7.4% of the mainstream kinetic energy) yields a significant increase in intake thrust, while simultaneously reducing total pressure and swirl distortion.
Gambling disorder (GD) involves persistent risky choices despite losses, suggesting impaired impulse control. While static paradigms reveal inhibition deficits in GD, they cannot model dynamic risk-reward escalations during real gambling. This study aims to investigate whether GD involves impaired dynamic impulse control during escalating stakes and to dissociate contributions of subjective risk evaluation and trait impulsivity to this deficit.
Methods
Using a sequential gambling task with 83 male patients with GD and 62 matched healthy controls (HCs), this study investigated dynamic impulse control deficits under escalating stakes. We quantified dynamic impulse control via the reward–reaction time (RT) coupling for ‘continue’ choices (dynamic impulse control index [DICI]) using Bayesian modeling. Risk sensitivity and risk preference were derived from stop/continue decisions. Trait impulsivity was assessed with the Barratt Impulsiveness Scale (BIS-11). Regression analyses examined the modulation of DICI by risk sensitivity and trait impulsivity.
Results
Patients with GD exhibited significantly attenuated DICI versus HCs, reflecting failure to increase deliberation with escalating stakes. Computational modeling revealed markedly reduced risk sensitivity in GD despite comparable risk preference. Critically, trait impulsivity positively modulated DICI in HCs but not in GD, indicating pathological decoupling. Risk sensitivity positively predicted DICI in both groups, though significantly weaker in GD.
Conclusions
These findings establish a triadic impairment in GD: (1) attenuated adaptive impulse control during escalation (impaired DICI), (2) deficient subjective risk weighting (reduced sensitivity), and (3) breakdown of impulsivity-based modulation of control. This reveals a dynamic, mechanism-focused pathology beyond static trait models.
We investigate the onset of transient natural convection in fluid layers subject to volumetric radiative heating and surface cooling. Linear stability analysis reveals a non-monotonic evolution of stability in deep layers, where the flow undergoes successive stages of initial destabilisation, intermediate suppression and eventual restabilisation. This complex temporal behaviour necessitates the definition of dual critical Rayleigh numbers: a lower bound marking the onset of initial instability and an upper bound required for sustained convection. To efficiently predict these thresholds, we develop a local Rayleigh number model that depends solely on the instantaneous conductive temperature profile. When the Rayleigh number exceeds the lower bound, the critical time $t_c$ for flow onset is determined through transient linear stability analysis, and scaling laws are derived to characterise the dependence of $t_c$ on the Rayleigh number $\textit{Ra}$, Prandtl number $\textit{Pr}$, cooling parameter $\phi$ and layer depth $H$. Two distinct instability triggering mechanisms are identified: a top-triggered regime, where $t_c \sim [\textit{Ra} \textit{Pr} \phi /(2+\textit{Pr})]^{-1/2}$, and a bottom-triggered regime, where $t_c \sim [\textit{Ra} \textit{Pr} \exp (-H)/(2+\textit{Pr})]^{-1/2}$. All theoretical predictions are rigorously validated against direct numerical simulations, providing a unified predictive framework for convective onset in systems governed by coupled effects of radiation absorption and surface cooling.
Pandemics, unlike other disasters, extend over prolonged periods, requiring continuous responses from both public and private sectors. The term “dual disaster” describes the occurrence of a pandemic alongside other emergencies. However, little research has explored how COVID-19 impacted non-pandemic emergencies.
Methods:
This study analyzed emergency data from Taiwan’s Emergency Medical Resources Management System (EMRMS) between 2018 and 2023. EMRMS is a web-based platform where hospitals report details such as date, age, sex, transport mode, triage level, disposition, and diagnosis during emergencies. We examined COVID-19-related policies from 2020 to 2023, categorizing them into four phases: Imported COVID (IC), Regional Epidemic (RE), Regulatory Relaxation (RR), and Extensive Community Transmission (ERT). Pre-pandemic data served as the non-COVID (NC) baseline. To compare emergency trends, annualized emergency rates were calculated for each phase, and casualty data, including triage levels, ICU needs, and mortality, were reviewed.
Results:
A total of 734 emergencies involving 6,734 casualties were reported. The annualized emergency incidences were 172.8 (NC), 154.8 (IC), 85.9 (RE), 78.2 (RR), and 105.2 (ERT). Emergencies declined during the pandemic phases, though the proportion of patients transported by EMS remained stable. However, casualty severity increased, with more ICU admissions, surgeries, and deaths observed.
Conclusion:
COVID-19 shifted emergency patterns, reducing incidence but increasing severity. Infection control and crowd management lowered emergency numbers, but resource-limited periods heightened the burden on healthcare systems. Preparedness for severe emergencies remains critical in dual disaster scenarios.
We investigate the role of slippery boundaries, quantified by the Navier boundary friction coefficient $\beta$, in regulating heat transport and flow structures in rotating Rayleigh–Bénard convection. Owing to the Ekman pumping effect arising from viscous boundary layers that is intensified with increasing boundary friction, it is found that the properties of global heat transport exhibit two distinct parameter regimes separated by a transitional Rayleigh number ($ \textit{Ra}_t$). In the rotation-dominated regime ($ \textit{Ra} \lt \textit{Ra}_t$), enhanced viscous friction increases the efficiency of Ekman pumping, significantly elevating the Nusselt number and lowering the convection onset threshold. Conversely, in the buoyancy-dominated regime ($ \textit{Ra} \gt \textit{Ra}_t$), boundary-induced viscous dissipation suppresses convective motions, thereby reducing heat transport. Large-scale vortices (LSVs), prevalent under free-slip conditions, progressively dissipate as $\beta$ increases, revealing that viscous friction disrupts the inverse energy cascade from baroclinic to barotropic modes. Through kinetic energy partitioning analysis, the transition between quasi-two-dimensional and three-dimensional turbulent states is identified, with the parameter $\beta _{\textit{cr}}$ following a generic scaling relation on the Prandtl (Pr) and Ekman (Ek) numbers $\beta _{\textit{cr}}\sim \textit{Pr}^{-0.67}\textit{Ek}^{-1.18}$. This relation enables us to predict LSV emergence across different parameter spaces. Furthermore, it is reported that the heat-transport scaling exponent, the convection onset and the partitioning of kinetic energy between barotropic and baroclinic components undergo a smooth flow transition at $\beta _{\textit{cr}}$. These results also indicate a direct correlation between Ekman pumping efficacy and the friction coefficient $\beta$, demonstrating that controlling boundary friction can modulate global transport properties and reshape flow structures.
This study aimed to determine the optimal Biological Effective Dose (BED)-based compensation strategy for treatment interruptions in left-sided breast cancer radiotherapy, with a focus on evaluating cardiac substructures to address a previously unmet clinical need.
Methods:
Twenty patients with left-sided breast cancer who had received radiotherapy were retrospectively enrolled.
Simulations assumed treatment interruptions (number of interruption days) occurred after the first week, ranging from 1 to 10 days. Three BED-based compensation strategies were evaluated: (A) maintaining total fractions and days while delivering twice-daily treatments; (B) maintaining total days while increasing the dose per fraction; and (C) keeping the dose per fraction constant while extending the overall treatment course. Original uninterrupted plans served as the baseline. BEDs for the planning target volume (PTV), simultaneous integrated boost (SIB), cardiac substructures and other organs at risk (OARs) were calculated. Physical and BED differences among the schemes were systematically compared.
Results:
Compared to the original scheme, physical doses to PTV and SIB were lower in Scheme B but higher in Scheme C. As interruptions increased from 1 to 10 days, PTV and SIB doses in Scheme B decreased to minimum values of 42.71 Gy and 50.58 Gy, respectively, while Scheme C resulted in maximum values of 58.60 Gy and 67.15 Gy. Analysis of BED changes (ΔBED) in OARs revealed that the left anterior descending artery (LAD) was the most affected cardiac substructure, with ΔBED values of 0.41, –1.20 and 0.60 for Schemes A, B and C, respectively, at 10 interruption days. Among other OARs, the left lung showed the highest ΔBED changes (0.39, –0.30 and 0.32, respectively). Most OAR comparisons reached statistical significance (ANOVA, p < 0.05).
Conclusion:
Compensation strategies for radiotherapy interruptions significantly influence the BED of OARs, particularly in the LAD and left lung. Scheme B most effectively reduced the BED of OARs but requires replanning. Schemes A and C offer clinical convenience at the cost of a higher BED of OARs. The choice of compensation strategy should be individualised based on clinical priorities and patient-specific anatomy.
This paper presents an experimental and analytical investigation of the turbulent transport and flame geometric characteristics of free turbulent buoyant diffusion flames under different fuel mass fluxes and burner boundary conditions (i.e. with/without a flush floor). The stereo particle image velocimetry technique was utilised to measure the three-dimensional instantaneous velocity fields of the free methane buoyant flames with a burner diameter (d) of 0.30 m and dimensionless heat release rates ($\dot{Q}^{*}$) of 0.50–0.90. The results showed that, compared with the configuration without a floor, the time-averaged axial velocity fluctuations squared and the time-averaged radial velocity fluctuations squared decreased, and the peak values of the time-averaged radial velocity, the time-averaged radial velocity fluctuations squared and the time-averaged axial and radial fluctuation product shifted towards the burner centreline in the configuration with a flush floor. Based on the dimensional analysis and the gradient transport assumption, the mean turbulent viscosity within the mean flame height ($\nu _{t}^{=}$) was scaled. Compared with the configuration without a floor of under equal $\dot{Q}^{*}$, the turbulent viscosity decreased in the configuration with a flush floor, resulting in an increase in mean flame height and a reduction in mean flame width. Based on the concepts of turbulent mixing and equal axial convection and radial diffusion times, semi-physical models were derived for the mean flame height and the mean flame width, respectively. The two correlations agreed well with the experimental data of this work for the two burner configurations with and without a flush floor.
The COVID-19 pandemic exacerbated psychological distress, but limited information is available on the shifts in mental health symptoms and their associated factors across different stages. This study was conducted to more reliably estimate shifts in mental health impacts and to identify factors associated with symptoms at different pandemic stages.
Methods
We performed a national repeated cross-sectional study at stable (2021), recurrence (2022), and end-of-emergency (2023) stages based on representative general national population with extensive geographic coverage. Anxiety, depression, post-traumatic stress disorder (PTSD) and insomnia symptoms were evaluated by GAD-7, PHQ-9, IES-R and ISI scales, respectively, and their associated factors were identified via multivariable linear regression.
Results
Generally, 42,000 individuals were recruited, and 36,218, 36,097 and 36,306 eligible participants were included at each stage. The prevalence of anxiety, depression and insomnia symptoms increased from 13.7–16.4% at stable to 17.3–22.2% at recurrence and decreased to 14.5–18.6% at end of emergency, while PTSD symptom continuously increased from 5.1% to 7.6% and 9.2%, respectively (all significant, P < 0.001). Common factors associated with mental health symptoms across all stages included centralized quarantine, frontline work and residence in initially widely infected areas. Centralized quarantine was linked to anxiety, depression, PTSD and insomnia during the stable, recurrence and end-of-emergency stages. Frontline workers exhibited higher risks of anxiety, depression and insomnia throughout these stages. Individuals in initially widely infected areas were more likely to experience depression and PTSD, particularly during the stable and recurrence stages. Stage-specific risk factors were also identified. Lack of outdoor activity was associated with anxiety, depression and insomnia during the stable and recurrence stages. Residents in high-risk areas during the recurrence stage correlated with increased anxiety and insomnia. Suspected infection was tied to anxiety and insomnia in the recurrence and end-of-emergency stages, while the death of family or friends was linked to PTSD during recurrence and to depression, PTSD and insomnia at the end-of-emergency stage.
Conclusions
Mental health symptoms increased when pandemic recurred, and could remain after end-of-emergency, requiring prolonged interventions. Several key factors associated with mental symptoms and their variations were identified at different pandemic stages, suggesting different at-risk populations.
To explore the longitudinal associations between a Chinese healthy diet and the progression of cardiometabolic multimorbidity (CMM) development among Chinese adults. A prospective analysis was conducted utilising data from 18 720 participants in the China Health and Nutrition Survey, spanning from 1997 to 2018. Dietary data were collected by three consecutive 24-h dietary recalls combined with the weighing method. A Chinese healthy diet score was developed by assigning scores to various food components. CMM was defined as the coexistence of two or more cardiometabolic diseases (CMD), including myocardial infarction, stroke and type 2 diabetes, diagnosed through blood indicators and clinical diagnosis. We employed a multistate model to examine the associations between the Chinese healthy diet and the longitudinal progression from being free of CMD to first CMD and then to CMM. Quantile G-computation was utilised to evaluate the relative contribution of each food component. Over a median follow-up period of 7·3 years, 2214 (11·8 %) participants developed first CMD, and 156 (0·83 %) progressed to CMM. Comparing participants in the highest quintile of dietary scores with those in the lowest, we observed a 55 % lower risk of transitioning from baseline to CMM (HR = 0·45, 95 % CI: 0·23, 0·87) and a 60 % lower risk of transition from first CMD to CMM (HR = 0·40, 95 % CI: 0·20, 0·81). Fresh fruits contributed to 42·8 and 43·0 % for delaying CMM and transition from first CMD to CMM, respectively. Our study revealed that greater adherence to the Chinese healthy diet is negatively associated with the risk of CMM.
DNA methylation plays a crucial role in gene regulation and has been implicated in various neuropsychiatric disorders, including alcohol use disorder (AUD). The rs27072 polymorphism within the SLC6A3 gene has been studied in addictive disorders; however, its role in epigenetic modifications remains unclear. This study investigates the methylation levels of CpG sites near rs27072 and their potential associations with AUD, personality traits, and environmental stressors.
Materials and methods
One hundred twenty-four male participants (66 patients with AUD and 58 controls) were analyzed for DNA methylation at CpG islands proximal to the rs27072 locus. The personality traits and life stress events were assessed in all participants.
Results
AUD patients had a lower methylation level than healthy controls (p = 0.003 for total average). However, the results changed to borderline significance after adjusting for clinical covariates in the analysis (p = 0.042), and the genotype at rs27072 did not modulate the methylation levels. There is high novelty seeking (p < 0.001), and more bad life events in patients with AUD than healthy controls (p < 0.001). Additionally, no significant correlations were found between methylation levels and personality traits or life stress scores (p > 0.05).
Conclusions
The methylation of the SLC6A3 gene may be marginally associated with AUD; however, the rs27072 genotype, personality, and life stress may not be directly linked to epigenetic modifications. Cross-sectional epigenetic studies may not establish causality; future studies with larger, more diverse cohorts and longitudinal designs are warranted to elucidate the complex interplay in AUD pathophysiology.
High-order harmonic generation (HHG) in noble gases driven by femtosecond lasers is currently a feasible solution to obtain ultrafast pulses in the extreme ultraviolet (EUV) wavelength range. Implementation of high-flux EUV sources requires driving HHG using an ultrafast laser source in the visible wavelength range with MHz repetition rate. In this paper, we employ a multi-pass cell followed by chirped mirrors to compress 1-MHz, 200-W, 300-fs pulses at 1.03 μm to a duration of 35 fs. The resulting 186-W compressed pulses are focused onto 0.5-mm thick beta barium borate crystal to drive second-harmonic generation and produce positively chirped pulses at 520 nm. These green pulses are de-chirped to 26 fs in duration with an average power of 64 W, which, to the best of our knowledge, represents the highest average power of green pulses with a duration below 100 fs.
High-power 808 nm vertical-cavity surface-emitting laser (VCSEL) chips have unique characteristics for neodymium-doped yttrium aluminum garnet (Nd:YAG) laser pumping compared with conventional edge-emitting laser bars, including a chip surface with high reflectivity, near flat top distribution in the near field, larger emitting width and smaller divergence. A novel symmetrical pump cavity with an inter-reflective chamber was invented by introducing even-numbered pumping geometry and removing the conventional internal reflector. Several optical tuning measures were taken to improve the uniformity of the pumping distribution, including power and spectrum balancing in the cross-section and the long axis of the laser rod, a diffuse mechanism in the pump chamber by a frosted flow tube and optional eccentric pumping geometry. A series of VCSEL pumping experiments were conducted and optical tuning measures were evaluated through distribution profiles and efficiencies. A new design philosophy for the VCSEL side-pumped Nd:YAG laser cavity was finally developed.
A dual-beam platform is developed for all-optical Thomson/Compton scattering, with versatile parameter tuning capabilities including electron energy, radiation energy, radiation polarization, etc. By integrating this platform with a 200 TW Ti:sapphire laser system, we demonstrate the generation of inverse Compton scattering X-/gamma-rays with tunable energies ranging from tens of keV to MeV. The polarization of X-/gamma-rays is manipulated by adjusting the polarization of the scattering laser. In the near future, by combining this platform with multi-PW laser facilities, our goal is to explore the transition from nonlinear Thomson scattering to nonlinear Compton scattering, ultimately verifying theories related to strong-field quantum electrodynamics effects induced by extreme scattering.
Rare earth elements (REEs) preserved in speleothems have garnered increasing attention as ideal proxies for the paleoenvironmental reconstruction. However, due to their typically low contents in stalagmites, the availability of stalagmite-based REE records remains limited. Here we present high-resolution REEs alongside oxygen isotope (δ18O) records in stalagmite SX15a from Sanxing Cave, southwestern China (110.1–103.3 ka). This study demonstrates that REE records could provide useful information for the provenance and formation process of the stalagmite, due to consistent distribution pattern across different periods indicating stable provenance. More interestingly, the total REE (ΣREE) record could serve as an effective indicator to reflect local hydrological processes associated with monsoonal precipitation. During Marine Isotopic Stage (MIS) 5d, a relatively low ΣREE content is consistent with the positive SX15a δ18O and negative NGRIP δ18O, reflecting a dry-cold environment; while during MIS 5c, a generally high ΣREE content suggests a humid-warm circumstance. Furthermore, the ΣREE record captured four prominent sub-millennial fluctuations within the Greenland interstadial 24 event, implying a combined influence by the regional climate and local soil redox conditions. Our findings indicate that the stalagmite-based REE records would be a useful proxy for better understanding of past climate and environment changes.
Hand, foot, and mouth disease (HFMD) shows spatiotemporal heterogeneity in China. A spatiotemporal filtering model was constructed and applied to HFMD data to explore the underlying spatiotemporal structure of the disease and determine the impact of different spatiotemporal weight matrices on the results. HFMD cases and covariate data in East China were collected between 2009 and 2015. The different spatiotemporal weight matrices formed by Rook, K-nearest neighbour (KNN; K = 1), distance, and second-order spatial weight matrices (SO-SWM) with first-order temporal weight matrices in contemporaneous and lagged forms were decomposed, and spatiotemporal filtering model was constructed by selecting eigenvectors according to MC and the AIC. We used MI, standard deviation of the regression coefficients, and five indices (AIC, BIC, DIC, R2, and MSE) to compare the spatiotemporal filtering model with a Bayesian spatiotemporal model. The eigenvectors effectively removed spatial correlation in the model residuals (Moran’s I < 0.2, p > 0.05). The Bayesian spatiotemporal model’s Rook weight matrix outperformed others. The spatiotemporal filtering model with SO-SWM was superior, as shown by lower AIC (92,029.60), BIC (92,681.20), and MSE (418,022.7) values, and higher R2 (0.56) value. All spatiotemporal contemporaneous structures outperformed the lagged structures. Additionally, eigenvector maps from the Rook and SO-SWM closely resembled incidence patterns of HFMD.
Sepiolite is considered a suitable substrate for Maya blue pigment. However, the interaction between sepiolite and indigo dye has not been fully understood. Previous studies have demonstrated that pre-treatment of sepiolite by heating or acid was useful in identifying the sepiolite–indigo interaction. The purpose of the present study was to prepare a series of hybrid sepiolite–indigo pigments after modifying the sepiolite using various alkali treatments (NaOH), then to evaluate their properties with respect to color, chemical resistance, and photostability. Samples were characterized using reflectance spectroscopy, X-ray diffraction, Fourier-transform infrared spectroscopy, Raman spectroscopy, transmission electron microscopy, and N2 adsorption-desorption. Under alkaline conditions, Si4+ and Mg2+ ions in sepiolite partially dissolved, disrupting the coordinated water associated with them. Mg2+ ions precipitated and blocked the structural channels of the sepiolite. The impact of the alkali treatment on the microporous structure and coordinated water of sepiolite significantly influenced the color properties and stability of the hybrid pigments. Proper alkaline treatment enhanced the greenish hue and chemical stability of the pigment, while severe treatments apparently compromised the structural integrity of the sepiolite, thus diminishing the quality of the hybrid pigment. Results from this study provide new insights into the color-causing and stabilizing mechanisms of sepiolite-based Maya blue pigment and also provide guidance for developing hybrid pigments based on clay minerals and organic dyes.