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Prior observational studies have reported conflicting results regarding whether antidepressant treatment reduces long-term dementia risk, likely due to confounding by indication and reverse causation. We aimed to investigate the association between baseline antidepressant use and incident dementia, incorporating cognitive and neuroimaging outcomes.
Methods
We conducted a prospective cohort study using UK Biobank participants free of dementia at baseline. Antidepressant use was self-reported at baseline (2006–2010). Incident dementia was identified through linked electronic health records until December 19, 2022. Cox proportional hazards models estimated hazard ratios (HRs) for all-cause dementia, Alzheimer’s disease (AD), and vascular dementia (VD), adjusting for sociodemographic, lifestyle, health-related, antidepressant indication factors, and co-medication of other anticholinergics. In subsamples, cognitive performance (n = 57,330) and structural brain imaging (n = 42,276) were examined as intermediate outcomes.
Results
Among 461,464 participants, 33,721 (7.3%) reported baseline antidepressant use. Over a mean follow-up of 13.4 years, 7,922 (1.7%) developed incident dementia. Baseline antidepressant use was associated with higher risks of all-cause dementia (adjusted HR: 1.47, 95% CI 1.36–1.60), AD (1.53, 1.36–1.73), and VD (1.44, 1.23–1.70). Users performed worse on fluid intelligence and prospective memory tasks and showed lower total and gray matter volume, regional reductions in the hippocampal gray matter and basal nucleus, and greater white matter hyperintensity volume.
Conclusions
Baseline antidepressant use was linked to a higher risk of dementia, poorer cognitive performance, and adverse brain structural changes. These findings underscore the importance of judicious prescribing, regular cognitive monitoring, and consideration of non-pharmacological approaches in clinical care.
Glymphatic system dysfunction has been increasingly implicated in Alzheimer’s disease (AD), yet its relationships with cerebral small vessel disease (CSVD), plasma biomarkers, and cognitive impairment across the AD remain incompletely understood.
Methods
We prospectively recruited 216 participants from Hainan General Hospital, including healthy controls (HC), individuals with subjective cognitive decline (SCD), mild cognitive impairment (MCI), and AD dementia. All participants underwent brain magnetic resonance imaging, plasma biomarker testing, and neuropsychological assessments. White matter hyperintensity (WMH) volume from T2-weighted fluid-attenuated inversion recovery images served as a marker of CSVD. The diffusion tensor image analysis along the perivascular space (DTI-ALPS) index assessed glymphatic function. Plasma amyloid β-protein (Aβ) concentrations measured peripheral Aβ levels as a surrogate indicator of amyloid pathology.
Results
The ALPS index was significantly lower in AD patients compared with HC, SCD, and MCI groups (all P < 0.01) and tended to be lower in the MCI group relative to SCD. After controlling for demographics and APOE4 status, ALPS positively correlated with the plasma Aβ42/Aβ40 ratio (r = 0.16, P = 0.038). ALPS index showed significant negative correlations with log-transformed juxtaventricular and juxtacortical WMH volumes (r = −0.32, P < 0.001; r = −0.19, P = 0.010), with marginal correlation for periventricular WMH (r = −0.13, P = 0.052).
Conclusion
Plasma Aβ levels and regional WMH burden are associated with glymphatic dysfunction as indicated by reduced ALPS. Impaired glymphatic clearance also correlates with cognitive impairment, providing theoretical support for novel pathophysiological hypotheses and potential therapeutic targets in AD pathogenesis.
The present study establishes a general theory for fluid-element rotation and intrinsic vorticity decompositions within the framework of vorticity kinematics. We propose two direction-dependent vorticity decompositions (DVDs) based on the analysis of rotation of directed material line and surface elements, with the rigid-rotation and spin modes of vorticity being explicitly defined. Intrinsic coupling relations are then derived for a pair of orthogonal line and surface elements, demonstrating their complementary roles in both kinematics and geometry. Notably, the surface-element-based spin mode is shown to coincide with the relative vorticity in the generalized Caswell formula, thereby providing a faithful representation of surface shear stress in Newtonian fluids. Correspondingly, another two DVDs are constructed based on the geometry of streamlines and streamsurfaces in the field description. Furthermore, within the characteristic algebraic description, in terms of the rotational invariants $(\psi ,\gamma )$ in the real Schur form of the velocity gradient tensor, two invariant vorticity decompositions (IVDs) are formulated. The first IVD with positive spin aligns with the Liutex-shear decomposition, which corresponds to the Klein–Kaden–Betz (KKB) mechanism by which wrapping shear layers form axial vortices. The second IVD is indispensable for understanding unidirectional swirling motion around a point on the rotation-axis-normal plane ${\mathcal{P}}$, corresponding to an anti-KKB mechanism/phenomenon characterized by the negative spin. Importantly, it is proved that the DVD vorticity modes are rigorously bounded by the IVD vorticity modes $(R_{N}^{\pm },s_{N}^{\pm })=(2\psi ^{\pm },\gamma ^{\pm })$ on ${\mathcal{P}}$. Finally, distinctive features and applicability of these kinematic tools are demonstrated with representative examples. The results indicate that a coupled IVD–DVD approach provides a powerful diagnostic tool for unravelling the subtle structures and fundamental physics inherent to complex flow fields.
The traditional design of laser drivers for inertial confinement fusion (ICF) is highly dependent on coherent laser light fields, which have significant advantages in achieving harmonic conversion and enhancing amplification efficiency. However, they also bring the core challenge of achieving uniform irradiation. This paper investigates the dynamic evolution process of uniform irradiation of multi-mode spatiotemporal light fields and analyzes the influence mechanism of spatiotemporal coherence on irradiation uniformity with different integration times. By balancing the relationship between the spatiotemporal coherence of the light field and uniform irradiation, we explore a possible scheme to alleviate the beam smoothing problem while satisfying the basic requirements of laser amplification and high-efficiency harmonic conversion. Based on this scheme, the overall architecture of the ICF laser driver is constructed.
Multi-plane light conversion (MPLC) is a versatile technique that enables arbitrary manipulation of optical fields, and is numerically investigated as a novel avenue for coherent beam combining (CBC) applications. The optical parameters have been investigated to guide the MPLC design, indicating that the number of phase planes and plane spacing serve as pivotal factors. The channel scalability is simulated, revealing that the plane spacing should be increased in a larger array to maintain high performance under a few-plane limit. CBC of up to 1027 lasers has been numerically demonstrated with near-diffraction-limited beam quality (M2 of 1.16 and combining efficiency close to 100%) with only seven phase plates. Beam steering is investigated, revealing that steering capability is related to both the number of multiplexed modes in MPLC and their mode fidelities, and the main-lobe power ratio of 87.1% at one divergence angle is achieved in a 10-mode MPLC with five phase plates.
In the field of parafoil airdrop path planning, the inherent complexity and time-sensitive nature of mission requirements necessitate rapid path generation through low-order mathematical models that approximate the system’s true dynamics. This study presents a novel sparse identification framework for constructing a parafoil path planning approximate model. Leveraging high-fidelity 9-degree-of-freedom (9 DOF) dynamic simulation data as training inputs, our method identifies simple nonlinear relationships between 3D positional coordinates (for spatial targeting) and yaw angle (for directional control), which are critical path planning parameters. Compared to conventional 4 DOF models, experimental validation using field airdrop data reveals that the proposed sparse model achieves enhanced predictive accuracy while maintaining computational efficiency. Quantitative analysis demonstrates reductions in root mean square error (RMSE) by approximately 12.96% (horizontal position), 54.44% (height) and 37.96% (yaw angle). The efficacy is further confirmed through successful fixed-point homing across diverse initial deployment scenarios, underscoring its potential for parafoil path planning.
Loneliness is a common public health concern, particularly among mid- to later-life adults. However, its impact on early mortality (deaths occurring before reaching the oldest old age of 85 years) remains underexplored. This study examined the predictive role of loneliness on early mortality across different age groups using data from the Health and Retirement Study (HRS).
Methods
A retrospective cohort study was conducted using data from the 2010–2020 waves of the HRS, restricted to participants aged 50–84 years at baseline. Loneliness was measured using the 11-item UCLA Loneliness Scale, categorized into four levels: low/no loneliness (scores 11–13), mild loneliness (14–16), moderate loneliness (17–20) and severe loneliness (21–33). Cox proportional hazards models and time-varying Cox regression models with age as the time scale were created to evaluate the relationship between loneliness and early mortality, adjusting for sociodemographic, lifestyle, and physical and mental health factors.
Results
Among 6,392 participants, the overall mortality rate before the age of 85 years was 19.1 per 1,000 person-years. A dose–response relationship was observed, with moderate and severe loneliness associated with 23% (adjusted hazard ratio [aHR]: 1.23, 95% confidence interval [CI] = 1.02–1.48) and 36% (aHR: 1.36, 95% CI = 1.13–1.65) higher mortality risk, respectively. Significant associations existed for the 65–74-year-old (aHR = 1.37, 95% CI = 1.03–1.83) and 75–84-year-old (aHR = 1.77, 95% CI = 1.23–2.56) age groups in the fully-adjusted models, but not for the 50–64-year-old age group. Time-varying Cox models showed a stronger association for severe loneliness (aHR = 1.65, 95% CI = 1.37–1.99).
Conclusions
Loneliness is a significant predictor of mortality among older adults. Preventive and interventional programs targeting loneliness may promote healthy ageing.
Tumour immunotherapy holds great promise as a treatment for cancer, which ranks as the second highest cause of mortality worldwide. This therapeutic approach can be broadly categorized into two main types: active immunotherapy and passive or adoptive immunotherapy. Active immunotherapy, such as cancer vaccines, stimulates the patients’ immune system to target tumour cells. On the other hand, adoptive immunotherapy involves supplying in vitro activated immune cells, such as T cells, natural killer cells and macrophages, to the patient to combat the tumour. Induced pluripotent stem cells are extensively utilized in both active and adoptive tumour immunotherapy due to their pluripotency and ease of gene editing. They can be differentiated into various types of immune cells for direct cancer treatment and can also function as tumour vaccines to elicit an immune response against the tumour. Importantly, iPSCs can be leveraged to develop off-the-shelf allogenic immunotherapy products.
Conclusion
This article provides a comprehensive review of the application of iPSCs in tumor immunotherapy, along with a discussion of the opportunities and challenges in this evolving field.
The incorporation of trace metals into land snail shells may record the ambient environmental conditions, yet this potential remains largely unexplored. In this study, we analyzed modern snail shells (Cathaica sp.) collected from 16 sites across the Chinese Loess Plateau to investigate their trace metal compositions. Our results show that both the Sr/Ca and Ba/Ca ratios exhibit minimal intra-shell variability and small inter-shell variability at individual sites. A significant positive correlation is observed between the shell Sr/Ca and Ba/Ca ratios across the plateau, with higher values being recorded in the northwestern sites where less monsoonal rainfall is received. We propose that shell Sr/Ca and Ba/Ca ratios, which record the composition of soil solution, may be controlled by the Rayleigh distillation in response to prior calcite precipitation. Higher rainfall amounts may lead to a lower degree of Rayleigh distillation and thus lower shell Sr/Ca and Ba/Ca ratios. This is supported by the distinct negative correlation between summer precipitation and shell Sr/Ca and Ba/Ca ratios, enabling us to reconstruct summer precipitation amounts using the Sr/Ca and Ba/Ca ratios of Cathaica sp. shells. The potential application of these novel proxies may also be promising for other terrestrial mollusks living in the loess deposits globally.
Machine learning has already shown promising potential in tiled-aperture coherent beam combining (CBC) to achieve versatile advanced applications. By sampling the spatially separated laser array before the combiner and detuning the optical path delays, deep learning techniques are incorporated into filled-aperture CBC to achieve single-step phase control. The neural network is trained with far-field diffractive patterns at the defocus plane to establish one-to-one phase-intensity mapping, and the phase prediction accuracy is significantly enhanced thanks to the strategies of sin-cos loss function and two-layer output of the phase vector that are adopted to resolve the phase discontinuity issue. The results indicate that the trained network can predict phases with improved accuracy, and phase-locking of nine-channel filled-aperture CBC has been numerically demonstrated in a single step with a residual phase of λ/70. To the best of our knowledge, this is the first time that machine learning has been made feasible in filled-aperture CBC laser systems.
The COVID-19 pandemic has impacted patient’s visits to general practitioners (GPs). However, it is unclear what the impact of COVID-19 has been on the interaction among the local primary care clinics, the GP Department within the hospital and specialists.
Methods:
The interaction among GPs referring to hospital-based specialists and specialists to local doctors was determined, comparing pre-pandemic 2019 and 2020 during the pandemic.
Results:
Reduced referrals from GPs to specialists were consistent with the reduction in specialist referrals back to the local doctors, which dropped by approximately 50% in 2020, particularly in the two most common chronic conditions (hypertension and diabetes mellitus).
Discussion:
Reduced referral of patients from local clinics to Tongren Hospital is probably due to the extensive online training provided to the local GPs to become more competent in handling local patients via telehealth. Our data provide some insight to assist in combatting the pandemic of COVID-19, offering objective evidence of the impact of COVID-19 on patient management by GPs.
Typical ophiolitic rock assemblages such as siliciclastic rocks, basalts and gabbros, together with the subduction-related intermediate-acidic intrusive rocks, are newly discovered in the Tongjiang-Fuyuan area of the Heilongjiang Provence, NE China. To determine the formation age and genesis of the mafic rocks (basalts and gabbros) and intermediate-acidic intrusive rocks (granodiorites) in the area, as well as their geodynamic settings, the whole-rock geochemical analysis and zircon LA-ICP-MS U-Pb dating were carried out. Zircon U-Pb results suggest that the granodiorites are 93–95 Ma and gabbro is 95 Ma, respectively. Geochemical results show that the gabbros and basalts exhibit characteristics of ocean island basalt (OIB) affinity and are typically related to having originated from mantle plumes. While the granodiorites show the nature of the island-arc magmatic rocks and may originate from the lower crust. Based on the coeval igneous rock associations and regional tectonic evolution, we conclude that the late Cretaceous magmatic rocks in the Tongjiang-Fuyuan area are the product of continuous subduction of the Palaeo-Pacific plate and reflect the subduction rollback process of the Palaeo-Pacific plate.
All-fiber coherent beam combiners based on the self-imaging effect can achieve a near-perfect single laser beam, which can provide a promising way to overcome the power limitation of a single-fiber laser. One of the key points is combining efficiency, which is determined by various mismatches during fabrication. A theoretical model has been built, and the mismatch error is analyzed numerically for the first time. The mismatch errors have been numerically studied with the beam quality and combining efficiency being chosen as the evaluation criteria. The tolerance of each mismatch error for causing 1% loss is calculated to guide the design of the beam combiners. The simulation results are consistent with the experimental results, which show that the mismatch error of the square-core fiber is the main cause of the efficiency loss. The results can provide useful guidance for the fabrication of all-fiber coherent beam combiners.
The development of high-brightness X-ray free electron lasers (XFELs), such as hard X-ray self-seeding free electron lasers and XFEL oscillators (XFELOs), brings a severe challenge to the crystal monochromator due to a strong non-uniform thermal load. The distortion caused by spatial temperature gradients can severely affect the optical performance of crystals. Therefore, this paper presents a model to estimate the performance of non-uniform thermally distorted crystals. The model not only takes into account thermal strain, slope error and incident angle deviation, but also considers temperature-dependent factors such as the Debye–Waller factor and electric susceptibility. Our investigation indicates that the Debye–Waller factor reduces the height and bandwidth of rocking curves, and the impact of the electric susceptibility is tiny. The proposed model can describe the distortion of the reflectivity and transmissivity curves of non-uniform thermally loaded crystals and can be applied in the design of crystal monochromators, crystal splitters, crystal compressors and XFELOs.
Although ethanol treatment is widely used to activate oocytes, the underlying mechanisms are largely unclear. Roles of intracellular calcium stores and extracellular calcium in ethanol-induced activation (EIA) of oocytes remain to be verified, and whether calcium-sensing receptor (CaSR) is involved in EIA is unknown. This study showed that calcium-free ageing (CFA) in vitro significantly decreased intracellular stored calcium (sCa) and CaSR expression, and impaired EIA, spindle/chromosome morphology and developmental potential of mouse oocytes. Although EIA in oocytes with full sCa after ageing with calcium does not require calcium influx, calcium influx is essential for EIA of oocytes with reduced sCa after CFA. Furthermore, the extremely low EIA rate in oocytes with CFA-downregulated CaSR expression and the fact that inhibiting CaSR significantly decreased the EIA of oocytes with a full complement of CaSR suggest that CaSR played a significant role in the EIA of ageing oocytes. In conclusion, CFA impaired EIA and the developmental potential of mouse oocytes by decreasing sCa and downregulating CaSR expression. Because mouse oocytes routinely treated for activation (18 h post hCG) are equipped with a full sCa complement and CaSR, the present results suggest that, while calcium influx is not essential, CaSR is required for the EIA of oocytes.
We firstly report a 2-μm all-fiber nonlinear pulse compressor based on two pieces of normal dispersion fiber (NDF), which enables a high-power scaling ability of watt-level and a high pulse compression ratio of 13.7. With the NDF-based all-fiber nonlinear pulse compressor, the 450-fs laser pulses with a repetition rate of 101.4 MHz are compressed to 35.1 fs, corresponding to a 5.2 optical oscillation cycle at the 2-μm wavelength region. The output average power reaches 1.28 W, which is believed to be the highest value never achieved from the previous 2-μm all-fiber nonlinear pulse compressors with a high pulse repetition rate above 100 MHz. The dynamic evolution of the ultrafast pulse inside the all-fiber nonlinear pulse compressor is numerically analyzed, matching well with the experimental results.
Sepsis is a clinical syndrome characterised by a severe disorder of pathophysiology caused by infection of pathogenic micro-organisms. The addition of antioxidant micronutrient therapies such as thiamine to sepsis treatment remains controversial. This study explored the effect of thiamine on the prognosis of patients with sepsis. This study was a retrospective study involving patients with sepsis from the Medical Information Mart for Intensive Care IV. Patients were divided into two groups, the thiamine received group (TR) and the thiamine unreceived group (TUR), according to whether they were supplemented with thiamin via intravenous while in the intensive care unit (ICU). The primary outcome was ICU mortality. The association between thiamine and outcome was analysed using the Cox proportional hazards regression model, propensity score matching (PSM), generalised boosted model-based inverse probability of treatment weighting (IPTW) and doubly robust estimation. A total of 11 553 sepsis patients were enrolled in this study. After controlling for potential confounders using Cox regression models, the TR group had a statistically significantly lower ICU mortality risk than the TUR group. The hazard ratio of ICU mortality for the TR group was 0·80 (95 % CI 0·70, 0·93). We obtained the same results after using PSM, IPTW and doubly robust estimation. Supplementation with thiamine has a beneficial effect on the prognosis of patients with sepsis. More randomised controlled trials are needed to confirm the effectiveness of thiamine supplementation in the treatment of sepsis.
The relationship of a diet low in fibre with mortality has not been evaluated. This study aims to assess the burden of non-communicable chronic diseases (NCD) attributable to a diet low in fibre globally from 1990 to 2019.
Design:
All data were from the Global Burden of Disease (GBD) Study 2019, in which the mortality, disability-adjusted life-years (DALY) and years lived with disability (YLD) were estimated with Bayesian geospatial regression using data at global, regional and country level acquired from an extensively systematic review.
Setting:
All data sourced from the GBD Study 2019.
Participants:
All age groups for both sexes.
Results:
The age-standardised mortality rates (ASMR) declined in most GBD regions; however, in Southern sub-Saharan Africa, the ASMR increased from 4·07 (95 % uncertainty interval (UI) (2·08, 6·34)) to 4·60 (95 % UI (2·59, 6·90)), and in Central sub-Saharan Africa, the ASMR increased from 7·46 (95 % UI (3·64, 11·90)) to 9·34 (95 % UI (4·69, 15·25)). Uptrends were observed in the age-standardised YLD rates attributable to a diet low in fibre in a number of GBD regions. The burden caused by diabetes mellitus increased in Central Asia, Southern sub-Saharan Africa and Eastern Europe.
Conclusions:
The burdens of disease attributable to a diet low in fibre in Southern sub-Saharan Africa and Central sub-Saharan Africa and the age-standardised YLD rates in a number of GBD regions increased from 1990 to 2019. Therefore, greater efforts are needed to reduce the disease burden caused by a diet low in fibre.