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This single center retrospective observational study of serial plasma metagenomic next-generation sequencing testing shows that >95% of serial testing was without meaningful clinical impact. Only 5/173 cases were adjudicated as having significant clinical impact.
Constant-force mechanisms (CFMs) are attractive for mechanical energy storage owing to their distinctive force–displacement characteristics, particularly under conditions with limited external load capacity and restricted space. However, conventional CFMs often suffer from short constant-force strokes and inefficient space utilization, which hinder their broader application. To address these limitations, this study exploits the buckling of compliant beams and increases the structural degrees of freedom by adopting a less constrained configuration, which extends the constant-force stroke and space utilization while reducing the required external load, thus improving energy storage efficiency for the same stored elastic energy. A novel catapult was developed through NSGA-II multi-objective optimization, achieving a high energy-to-cost ratio and an extended constant-force stroke. This work presents an effective design approach for motion mechanisms that demand high energy-storage efficiency and high-power output.
The treatment response for the negative symptoms of schizophrenia is not ideal, and the efficacy of antidepressant treatment remains a matter of considerable controversy. This systematic review and meta-analysis aimed to assess the efficacy of adjunctive antidepressant treatment for negative symptoms of schizophrenia under strict inclusion criteria.
Methods
A systematic literature search (PubMed/Web of Science) was conducted to identify randomized, double-blind, effect-focused trials comparing adjuvant antidepressants with placebo for the treatment of negative symptoms of schizophrenia from database establishment to April 16, 2025. Negative symptoms were examined as the primary outcome. Data were extracted from published research reports, and the overall effect size was calculated using standardized mean differences (SMD).
Results
A total of 15 articles, involving 655 patients, were included in this review. Mirtazapine (N = 2, n = 48, SMD −1.73, CI −2.60, −0.87) and duloxetine (N = 1, n = 64, SMD −1.19, CI −2.17, −0.21) showed significantly better efficacy for negative symptoms compared to placebo. In direct comparisons between antidepressants, mirtazapine showed significant differences compared to reboxetine, escitalopram, and bupropion, but there were no significant differences between other antidepressants or between antidepressants and placebo. No publication bias for the prevalence of this condition was observed.
Conclusions
These findings suggest that adjunctive use of mirtazapine and duloxetine can effectively improve the negative symptoms of schizophrenia in patients who are stably receiving antipsychotic treatment. Therefore, incorporating antidepressants into future treatment plans for negative symptoms of schizophrenia is a promising strategy that warrants further exploration.
This study aimed to compare the clinical outcomes of using refrigerated versus pre-warmed media for preparing time-lapse dishes in in vitro fertilization (IVF). Patients undergoing their first IVF/ICSI cycle were divided into two groups. The control group used pre-warmed culture media, while the experimental group used refrigerated culture media. The osmotic pressure of the culture droplets in both groups was tested. No statistical differences were found between the two groups’ basic data. The proportion of air microbubbles affecting imaging significantly decreased (4.55% vs. 37.97%, P < 0.001) when using pre-warmed media. However, the blastocyst formation rate (56.62% vs. 49.70%, P = 0.046) and total high-quality embryo rate (22.26% vs. 17.06%, P = 0.047) were significantly higher in the refrigerated media group compared to the pre-warmed media group. The higher rate of high-quality embryos in the refrigerated media group might result in a higher single embryo transfer rate (45.10% vs. 18.52%, P = 0.020) and implantation rate (58.23% vs. 34.69%, P = 0.010). From day –1 to day 1, osmolality increased, with the P-3.5 group showing a significant elevation compared to the other three groups. After 5 days of incubation, the osmotic pressure of group R-4.0 was significantly lower than that of groups P-3.5, P-4.0 and P-3.5. In conclusion, refrigerated culture media dishes helped stabilize the osmotic pressure of the culture microenvironment and reduce water evaporation. The refrigerated group showed a higher rate of high-quality embryos and live births, although pre-warmed culture media effectively reduced the occurrence of air microbubbles that affect embryo imaging in the next day’s dishes.
Ultra-thin liquid sheets generated by impinging two liquid jets are crucial high-repetition-rate targets for laser ion acceleration and ultra-fast physics, and serve widely as barrier-free samples for structural biochemistry. The impact of liquid viscosity on sheet thickness should be comprehended fully to exploit its potential. Here, we demonstrate experimentally that viscosity significantly influences thickness distribution, while surface tension primarily governs shape. We propose a thickness model based on momentum exchange and mass transport within the radial flow, which agrees well with the experiments. These results provide deeper insights into the behaviour of liquid sheets and enable accurate thickness control for various applications, including atomization nozzles and laser-driven particle sources.
An actively controllable cascaded proton acceleration driven by a separate 0.8 picosecond (ps) laser is demonstrated in proof-of-principle experiments. MeV protons, initially driven by a femtosecond laser, are further accelerated and focused into a dot structure by an electromagnetic pulse (EMP) on the solenoid, which can be tuned into a ring structure by increasing the ps laser energy. An electrodynamics model is carried out to explain the experimental results and show that the dot-structured proton beam is formed when the outer part of the incident proton beam is optimally focused by the EMP force on the solenoid; otherwise, it is overfocused into a ring structure by a larger EMP. Such a separately controlled mechanism allows precise tuning of the proton beam structures for various applications, such as edge-enhanced proton radiography, proton therapy and pre-injection in traditional accelerators.
It remains unclear which individuals with subthreshold depression benefit most from psychological intervention, and what long-term effects this has on symptom deterioration, response and remission.
Aims
To synthesise psychological intervention benefits in adults with subthreshold depression up to 2 years, and explore participant-level effect-modifiers.
Method
Randomised trials comparing psychological intervention with inactive control were identified via systematic search. Authors were contacted to obtain individual participant data (IPD), analysed using Bayesian one-stage meta-analysis. Treatment–covariate interactions were added to examine moderators. Hierarchical-additive models were used to explore treatment benefits conditional on baseline Patient Health Questionnaire 9 (PHQ-9) values.
Results
IPD of 10 671 individuals (50 studies) could be included. We found significant effects on depressive symptom severity up to 12 months (standardised mean-difference [s.m.d.] = −0.48 to −0.27). Effects could not be ascertained up to 24 months (s.m.d. = −0.18). Similar findings emerged for 50% symptom reduction (relative risk = 1.27–2.79), reliable improvement (relative risk = 1.38–3.17), deterioration (relative risk = 0.67–0.54) and close-to-symptom-free status (relative risk = 1.41–2.80). Among participant-level moderators, only initial depression and anxiety severity were highly credible (P > 0.99). Predicted treatment benefits decreased with lower symptom severity but remained minimally important even for very mild symptoms (s.m.d. = −0.33 for PHQ-9 = 5).
Conclusions
Psychological intervention reduces the symptom burden in individuals with subthreshold depression up to 1 year, and protects against symptom deterioration. Benefits up to 2 years are less certain. We find strong support for intervention in subthreshold depression, particularly with PHQ-9 scores ≥ 10. For very mild symptoms, scalable treatments could be an attractive option.
We develop the time-dependent regularised 13-moment equations for general elastic collision models under the linear regime. Detailed derivation shows the proposed equations have super-Burnett order for small Knudsen numbers, and the moment equations enjoy a symmetric structure. A new modification of Onsager boundary conditions is proposed to ensure stability as well as the removal of undesired boundary layers. Numerical examples of one-dimensional channel flows is conducted to verified our model.
The double-cone ignition scheme is a promising novel ignition method, which is expected to greatly save the driver energy and enhance the robustness of the implosion process. In this paper, ablation of the inner surface of the cone by the hard X-ray from coronal Au plasma is studied via radiation hydrodynamics simulations. It is found that the X-ray ablation of the inner wall will form strong pre-plasma, which will significantly affect the implosion process and cause the Au plasma to mix with the fuel, leading to ignition failure. The radiation and pre-ablation intensities in the system are estimated, and the evolutions of areal density, ion temperature and the distribution of Au ions are analysed. In addition, the mixing of Au in CH at collision is quantified. Then, a scheme to reduce the X-ray pre-ablation by replacing the gold cone with a tungsten cone is proposed, showing that it is effective in reducing high-Z mixing and improving collision results.
This study employs direct numerical simulations to examine the effects of varying backpressure conditions on the turbulent atomisation of impinging liquid jets. Using the incompressible Navier–Stokes equations, and a volume-of-fluid approach enhanced by adaptive mesh refinement and an isoface-based interface reconstruction algorithm, we analyse spray characteristics in the environments with ambient gas densities ranging from 1 to 40 times the atmospheric pressure under five different backpressure scenarios. We investigate the behaviour of turbulent jets, incorporate realistic orifice geometries and identify significant variations in the atomisation patterns depending on backpressure. Two distinct atomisation types emerge, namely jet-sheet-ligament-droplet at lower backpressures and jet-sheet-fragment-droplet at higher ones, alongside a transition from dilute to dense spray patterns. This variation affects the droplet size distribution and spray dynamics, with increased backpressure reducing the spray's spreading angle and breakup length, while increasing the droplet size variation. Furthermore, these conditions promote distributions that induce rapid, nonlinear wavy motion in liquid sheets. Topological analysis of the atomisation field using velocity-gradient tensor invariants reveals significant variations in topology volume fractions across different regions. Downstream, the droplet Sauter mean diameter increases and then stabilises, reflecting the continuous breakup and coalescence processes, notably under higher backpressures. This research underscores the substantial impact of backpressure on impinging-jet atomisation and provides essential insights for nozzle design to optimise droplet distributions.
Women with schizophrenia frequently discontinue antipsychotic medications during pregnancy. However, evidence on the risk of postpartum relapse associated with antipsychotic use during pregnancy is lacking.
Aims
To investigate the within-individual association between antipsychotic continuation during pregnancy and postpartum relapse in women with schizophrenia.
Method
This retrospective cohort study used data of women with schizophrenia who gave live birth between 2007 and 2018 identified from the National Health Information Database of South Korea. Women were classified according to antipsychotic use patterns during the 12 months before delivery as non-users, discontinuers and continuers. Relapse was defined as admission for psychosis (ICD-10, F20–29). The incidence rate ratio (IRR) for admission for psychosis in the 6-month postpartum period was estimated using conditional Poisson regression, with the reference period set between 2 and 1 years before delivery. Additionally, we calculated the relative risk ratios (RRRs) for the IRRs of different antipsychotic use patterns.
Results
Among the 3026 women included in the analysis (median age 34 years, interquartile range 31–37), the within-individual risk of admission for psychosis in the 6-month postpartum period was 0.56 times (RRR, 95% CI 0.36–0.87) lower in continuers (IRR = 1.31, 95% CI 0.89–1.72) than in discontinuers (IRR = 2.34, 95% CI 1.87–2.91). Among discontinuers, the IRRs of admission for psychosis in the 6-month postpartum period did not change significantly with the timing of discontinuation (trend P = 0.946).
Conclusions
Antipsychotic continuation during pregnancy was associated with a reduced risk of postpartum relapse in women with schizophrenia. Continuing antipsychotics during pregnancy would be recommended after a risk–benefit assessment.
This study aimed to explore the influence of laryngopharyngeal reflux on the features of vocal fold polyps and prognosis after office-based transnasal vocal fold polypectomy.
Methods
Eighty-four vocal fold polyp patients were retrospectively analysed. Patients were assigned to laryngopharyngeal reflux or non-laryngopharyngeal reflux groups using pre-operative Reflux Symptom Score-12.
Results
The laryngopharyngeal reflux group had significantly higher pre-operative Reflux Sign Assessment scores, worse lifestyle and worse eating habits than the non-laryngopharyngeal reflux group. After office-based transnasal vocal fold polypectomy, the Reflux Symptom Score-12 and Reflux Sign Assessment score decreased in both groups, although the laryngopharyngeal reflux group still had higher values. The non-laryngopharyngeal reflux group had better vocal fold morphology recovery than the laryngopharyngeal reflux group. Multivariate logistic regression analysis demonstrated that smoking and a higher pre-operative Reflux Symptom Score-12 score were independent risk factors for poor prognosis.
Conclusions
Laryngopharyngeal reflux is detrimental to vocal fold recovery of vocal fold polyp patients following office-based transnasal vocal fold polypectomy. For vocal fold polyp patients with laryngopharyngeal reflux, lifestyle and diet guidance should be focused.
A high-energy pulsed vacuum ultraviolet (VUV) solid-state laser at 177 nm with high peak power by the sixth harmonic of a neodymium-doped yttrium aluminum garnet (Nd:YAG) amplifier in a KBe2BO3F2 prism-coupled device was demonstrated. The ultraviolet (UV) pump laser is a 352 ps pulsed, spatial top-hat super-Gaussian beam at 355 nm. A high energy of a 7.12 mJ VUV laser at 177 nm is obtained with a pulse width of 255 ps, indicating a peak power of 28 MW, and the conversion efficiency is 9.42% from 355 to 177 nm. The measured results fitted well with the theoretical prediction. It is the highest pulse energy and highest peak power ever reported in the VUV range for any solid-state lasers. The high-energy, high-peak-power, and high-spatial-uniformity VUV laser is of great interest for ultra-fine machining and particle-size measurements using UV in-line Fraunhofer holography diagnostics.
Milk fat synthesis is tightly regulated by hormones and growth factors. Leptin is a versatile peptide hormone that exerts pleiotropic effects on metabolic pathways. In this study, we evaluated the expression and function of leptin and its long form receptor OB-Rb in dairy cow mammary tissues from different physiological stages and in cultured mammary epithelial cells. The results showed that the expression of leptin and OB-Rb were significantly higher in the mammary tissues of lactating cows as compared with dry cows, suggesting that they are related to milk component synthesis. In cultured dairy cow mammary epithelial cells, leptin treatment significantly increased OB-Rb expression and intracellular triacylglycerol content. Transcriptome analysis identified the difference in gene expression between leptin treated cells and control cells, and 317 differentially expressed genes were identified. Gene ontology and pathway mapping showed that lipid metabolism-related gene expression increased and signal transduction pathway-related genes were the most significantly enriched. Mechanistic studies showed that leptin stimulation enhanced sterol regulatory element-binding protein 1 expression via activating the phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/AKT/mTOR) signaling pathway, which in turn up-regulated the expression of genes related to milk fat synthesis. Moreover, we found that fatty acid synthesis precursors, acetate and β-hydroxybutyrate, could positively regulate the expression of leptin and OB-Rb in bovine mammary epithelial cells, thereby potentially increasing milk fat synthesis. Our study provided novel evidence in the regulation of leptin on milk fat production in mammary glands of dairy cows, as well as experimental basis for artificial regulation of milk fat
Recent studies of viscous dissipation mechanisms in impacting droplets have revealed distinct behaviours between the macroscale and nanoscale. However, the transition of these mechanisms from the macroscale to the nanoscale remains unexplored due to limited research at the microscale. This work addresses the gap using the many-body dissipative particle dynamics (MDPD) method. While the MDPD method omits specific atomic details, it retains crucial mesoscopic effects, making it suitable for investigating the impact dynamics at the microscale. Through the analysis of velocity contours within impacting droplets, the research identifies three primary contributors to viscous dissipation during spreading: boundary-layer viscous dissipation from shear flow; rim geometric head loss; and bulk viscous dissipation caused by droplet deformation. This prompts a re-evaluation of viscous dissipation mechanisms at both the macroscale and nanoscale. It reveals that the same three kinds of dissipation are present across all scales, differing only in their relative intensities at each scale. A model of the maximum spreading factor (βmax) incorporating all forms of viscous dissipation without adjustable parameters is developed to substantiate this insight. This model is validated against three distinct datasets representing the macroscale, microscale and nanoscale, encompassing a broad spectrum of Weber numbers, Ohnesorge numbers and contact angles. The satisfactory agreement between the model predictions and the data signifies a breakthrough in establishing a universal βmax model applicable across all scales. This model demonstrates the consistent nature of viscous dissipation mechanisms across different scales and underscores the importance of integrating microscale behaviours to understand macroscale and nanoscale phenomena.
Ridge B is one of the least studied areas in Antarctica but has been considered to be a potential location for the oldest ice on Earth. Among important parameters for calculating where very old ice may exist, geothermal heat flux (GHF) is critical but poorly understood. Here, GHF is determined by quantifying the transitions between dry and wet basal conditions using a radioglaciological method applied to airborne radio-echo sounding data. GHF is then constrained by a thermodynamic model matched to the transitions. The results show that GHF in Ridge B varies locally and ranges from 48.5 to 65.1 mW m−2, with an average value of 58.0 mW m−2, which is consistent with the current known GHF constrained by subglacial lakes and derived from Vostok ice core temperature measurements. Our work highlights the value of considering local GHF when locating the oldest ice in this potential region or other regions.
Dietary n-3 PUFA may have potential benefits in preventing peptic ulcer disease (PUD). However, data from observational epidemiological studies are limited. Thus, we conducted a Mendelian randomisation analysis to reveal the causal impact of n-3 PUFA on PUD. Genetic variants strongly associated with plasma levels of total or individual n-3 PUFA including plant-derived α-linolenic acid and marine-derived EPA, DPA and DHA were enrolled as instrumental variables. Effect size estimates of the n-3 PUFA-associated genetic variants with PUD were evaluated using data from the UK biobank. Per one sd increase in the level of total n-3 PUFA in plasma was significantly associated with a lower risk of PUD (OR = 0·91; 95 % CI 0·85, 0·99; P = 0·020). The OR were 0·81 (95 % CI 0·67, 0·97) for EPA, 0·72 (95 % CI 0·58, 0·91) for DPA and 0·87 (95 % CI 0·80, 0·94) for DHA. Genetically predicted α-linolenic acid levels in plasma had no significant association with the risk of PUD (OR = 5·41; 95 % CI 0·70, 41·7). Genetically predicted plasma levels of n-3 PUFA were inversely associated with the risk of PUD, especially marine-based n-3 PUFA. Such findings may have offered an effective and feasible strategy for the primary prevention of PUD.
Characterised by the extensive use of obsidian, a blade-based tool inventory and microblade technology, the late Upper Palaeolithic lithic assemblages of the Changbaishan Mountains are associated with the increasingly cold climatic conditions of Marine Isotope Stage 2, yet most remain poorly dated. Here, the authors present new radiocarbon dates associated with evolving blade and microblade toolkits at Helong Dadong, north-east China. At 27 300–24 100 BP, the lower cultural layers contain some of the earliest microblade technology in north-east Asia and highlight the importance of the Changbaishan Mountains in understanding changing hunter-gatherer lifeways in this region during MIS 2.
This paper retrospectively analysed the prevalence of macrolide-resistant Mycoplasma pneumoniae (MRMP) in some parts of China. Between January 2013 and December 2019, we collected 4,145 respiratory samples, including pharyngeal swabs and alveolar lavage fluid. The highest PCR-positive rate of M. pneumoniae was 74.5% in Beijing, the highest resistance rate was 100% in Shanghai, and Gansu was the lowest with 20%. The highest PCR-positive rate of M. pneumoniae was 74.5% in 2013, and the highest MRMP was 97.4% in 2019; the PCR-positive rate of M. pneumoniae for adults in Beijing was 17.9% and the MRMP was 10.48%. Among the children diagnosed with community-acquired pneumonia (CAP), the PCR-positive and macrolide-resistant rates of M. pneumoniae were both higher in the severe ones. A2063G in domain V of 23S rRNA was the major macrolide-resistant mutation, accounting for more than 90%. The MIC values of all MRMP to erythromycin and azithromycin were ≥ 64 μg/ml, and the MICs of tetracycline and levofloxacin were ≤ 0.5 μg/ml and ≤ 1 μg/ml, respectively. The macrolide resistance varied in different regions and years. Among inpatients, the macrolide-resistant rate was higher in severe pneumonia. A2063G was the common mutation, and we found no resistance to tetracycline and levofloxacin.