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Negative symptoms in schizophrenia, particularly motivational deficits, pose significant challenges to treatment and recovery. Despite their profound impact on functional outcomes, these symptoms remain poorly understood and inadequately addressed by current interventions.
Aims
The CHANSS (Characterising Negative Symptoms in Schizophrenia) study aims to dissect the cognitive mechanisms underlying motivational impairments by focusing on three interconnected domains: executive cognition, motivational cognition and meta-cognition.
Method
This large, international, cross-sectional study recruits a heterogeneous sample of patients across illness stages – from first-episode psychosis to treatment-resistant schizophrenia – and uses a comprehensive cognitive battery, clinical scales, self-report measures and computerised cognitive tasks. Four novel tasks assess key processes in motivated behaviour: option generation, reward-based decision-making, risk sensitivity and performance self-evaluation. By incorporating control for secondary influences like depression, psychosis, sedation and illness chronicity, the study seeks to identify distinct cognitive and behavioural subtypes within motivational dysfunction.
Results
CHANSS tests the hypothesis that specific patient profiles exhibit predominant impairments in one or more cognitive domains, which may differentially affect goal-directed behaviour. The study’s design allows exploration of hierarchical relationships between cognitive processes, such as how neurocognitive deficits may cascade to impair motivation and self-evaluation.
Conclusions
Ultimately, CHANSS aims to advance mechanistic understanding of motivational deficits in schizophrenia and pave the way for personalised, targeted interventions. Its findings may inform future clinical trials and contribute to a shift away from one-size-fits-all approaches towards more effective, stratified treatment strategies in schizophrenia.
Observational studies suggested an association between childhood maltreatment and neuropsychiatric disorders; however, mediators remain disputed.
Aims
We aimed to confirm the relationship between childhood maltreatmen and neuropsychiatric disorders, and to identify addiction-related, biological, behavioural, cognitive, socioeconomic and epigenetic mediators.
Method
We used two-sample Mendelian randomisation and publicly available genome-wide association data to evaluate the effect of genetically predicted childhood maltreatment (N = 143 473) on the risk of six neuropsychiatric disorders (up to N = 500 199). We used two-step Mendelian randomisation to determine the proportion of the effect of childhood maltreatment on disorders that was mediated by mediators. We used multivariable Mendelian randomisation to determine the direct effect of childhood maltreatment on disorders accounting for mediators. We used epigenetic Mendelian randomisation to determine the effect of DNA methylation at childhood maltreatment-associated CpG sites on disorders.
Results
Childhood maltreatment was significantly associated with higher risk of attention-deficit/hyperactivity disorder (ADHD) (odds ratio 10.09, 95% CI: 4.76–21.40), major depressive disorder (MDD) (odds ratio 1.89, 95% CI: 1.32–2.70) and schizophrenia (odds ratio: 5.89, 95% CI: 1.46–23.78). We determined that 4.14–22.17% of the effect of childhood maltreatment was mediated by addiction-related behaviours (smoking initiation, leisure screen time and substance abuse), cognitive traits (executive functioning, intelligence and risk tolerance) and educational attainment. We found that the direct effects of childhood maltreatment on ADHD (odds ratio 2.57) and schizophrenia (odds ratio 5.10) were less than the total effects, while the direct effect on MDD (odds ratio 1.95) remained relatively unchanged. We found altered DNA methylation levels at 3, 4 and 19 CpG sites to be significantly associated with ADHD, MDD and schizophrenia, respectively.
Conclusions
These results emphasise the need for preventative strategies to reduce childhood maltreatment prevalence, including strengthening support for high-risk families and responsive strategies to mitigate consequences for victims, with clinical screening for childhood maltreatment history and holistic approaches addressing addiction-related, cognitive and socioeconomic mediators.
Data on the distribution of iodine in the urine and breast milk of lactating women are limited. This study aimed to establish a formula to assess iodine status in lactating women by evaluating the fractional iodine excretion in urine and breast milk. A 3-d 24-h iodine metabolism survey in 2021–2023 was conducted on fifty-four pairs of lactating women and infants in Tianjin and Luoyang, China. We used the 24-h dietary record and salt weighing method to assess daily iodine intake (DII). Iodine excretion in breast milk and urine was measured. The median 24-h urinary iodine concentration and breast milk iodine concentration were 135·06 μg/L and 150·26 µg/L, respectively. When the DII was between 240 μg/d and 600 μg/d, the predicted value of fractional breast milk iodine excretion was 31·48 % (95 % CI: 27·16 %, 36·22 %). When the daily iodine excretion was between 258 μg/d and 476 μg/d, the fractional urine iodine excretion (59·09 %) and fractional breast milk iodine excretion (40·91 %) were stable. DII can be derived from the spot urinary iodine concentration as follows: urinary iodine concentration (μg/L) × (0·0009 L/h/kg × 24 h/d) × body weight (kg) ÷ 0·59 ÷ 0·94 = DII (μg/d). In conclusion, lactating women with adequate iodine delivered approximately 31·48 % of the DII to their infants. A stable proportion (59·09 %) of iodine excretion was discharged through urine, which was used to assess the iodine status based on the spot urinary iodine concentration of lactating women. This study was registered at ClinicalTrials.gov (NCT04492657).
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.
Posttraumatic stress disorder (PTSD) has been associated with advanced epigenetic age cross-sectionally, but the association between these variables over time is unclear. This study conducted meta-analyses to test whether new-onset PTSD diagnosis and changes in PTSD symptom severity over time were associated with changes in two metrics of epigenetic aging over two time points.
Methods
We conducted meta-analyses of the association between change in PTSD diagnosis and symptom severity and change in epigenetic age acceleration/deceleration (age-adjusted DNA methylation age residuals as per the Horvath and GrimAge metrics) using data from 7 military and civilian cohorts participating in the Psychiatric Genomics Consortium PTSD Epigenetics Workgroup (total N = 1,367).
Results
Meta-analysis revealed that the interaction between Time 1 (T1) Horvath age residuals and new-onset PTSD over time was significantly associated with Horvath age residuals at T2 (meta β = 0.16, meta p = 0.02, p-adj = 0.03). The interaction between T1 Horvath age residuals and changes in PTSD symptom severity over time was significantly related to Horvath age residuals at T2 (meta β = 0.24, meta p = 0.05). No associations were observed for GrimAge residuals.
Conclusions
Results indicated that individuals who developed new-onset PTSD or showed increased PTSD symptom severity over time evidenced greater epigenetic age acceleration at follow-up than would be expected based on baseline age acceleration. This suggests that PTSD may accelerate biological aging over time and highlights the need for intervention studies to determine if PTSD treatment has a beneficial effect on the aging methylome.
Depression has been linked to disruptions in resting-state networks (RSNs). However, inconsistent findings on RSN disruptions, with variations in reported connectivity within and between RSNs, complicate the understanding of the neurobiological mechanisms underlying depression.
Methods
A systematic literature search of PubMed and Web of Science identified studies that employed resting-state functional magnetic resonance imaging (fMRI) to explore RSN changes in depression. Studies using seed-based functional connectivity analysis or independent component analysis were included, and coordinate-based meta-analyses were performed to evaluate alterations in RSN connectivity both within and between networks.
Results
A total of 58 studies were included, comprising 2321 patients with depression and 2197 healthy controls. The meta-analysis revealed significant alterations in RSN connectivity, both within and between networks, in patients with depression compared with healthy controls. Specifically, within-network changes included both increased and decreased connectivity in the default mode network (DMN) and increased connectivity in the frontoparietal network (FPN). Between-network findings showed increased DMN–FPN and limbic network (LN)–DMN connectivity, decreased DMN–somatomotor network and LN–FPN connectivity, and varied ventral attention network (VAN)–dorsal attentional network (DAN) connectivity. Additionally, a positive correlation was found between illness duration and increased connectivity between the VAN and DAN.
Conclusions
These findings not only provide a comprehensive characterization of RSN disruptions in depression but also enhance our understanding of the neurobiological mechanisms underlying depression.
The maser instability associated with the loss-cone distribution has been widely invoked to explain the radio bursts observed in the astrophysical plasma environment, such as aurora and corona. In the laboratory plasma of a tokamak, events reminiscent of these radio bursts have also been frequently observed as an electron cyclotron emission (ECE) burst in the microwave range ($\mathrm{\sim }2{f_{\textrm{ce}}}$ near the last closed flux surface) during transient magnetohydrodynamic events. These bursts have a short duration of ~10 μs and display a radiation spectrum corresponding to a radiation temperature ${T_{e,\textrm{rad}}}$ of over $30\ \textrm{keV}$ while the edge thermal electron temperature ${T_e}$ is only in the range of $1\ \textrm{keV}$. Suprathermal electrons can be generated through magnetic reconnection, and a loss-cone distribution can be generated through open stochastic field lines in the magnetic mirror of the near-edge region of a tokamak plasma. Radiation modelling shows that a sharp distribution gradient $\partial f/\partial {v_ \bot } > 0$ at the loss-cone boundary can cause a negative absorption of ECE radiation through the maser instability. The negative absorption then amplifies the radiation so that the microwave intensity is significantly stronger than the thermal value. The significant ${T_{e,\textrm{rad}}}$ from the simulations suggests the potential role of the loss-cone maser instability in generating the ECE burst in a tokamak.
In this paper, we investigate a sink-driven three-layer flow in a radial Hele-Shaw cell. The three fluids are of different viscosities, with one fluid occupying an annulus-like domain, forming two interfaces with the other two fluids. Using a boundary integral method and a semi-implicit time stepping scheme, we alleviate the numerical stiffness in updating the interfaces and achieve spectral accuracy in space. The interaction between the two interfaces introduces novel dynamics leading to rich pattern formation phenomena, manifested by two typical events: either one of the two interfaces reaches the sink faster than the other (forming cusp-like morphology), or they come very close to each other (suggesting a possibility of interface merging). In particular, the inner interface can be wrapped by the other to have both scenarios. We find that multiple parameters contribute to the dynamics, including the width of the annular region, the location of the sink, and the mobilities of the fluids.
In this paper, a high-level Green–Naghdi (HLGN) model for large-amplitude internal waves in a two-layer fluid system, where the upper-fluid layer is of finite depth and the lower-fluid layer is of infinite depth, is developed under the rigid-lid free-surface approximation. The equations of the present HLGN model follow Euler's equations under the sole assumption that the horizontal and vertical velocity distributions along the vertical column are presented by known shape functions for each layer. The linear dispersion relations of the HLGN model for different levels are presented and compared with those obtained by other strongly nonlinear models for deep water, including the fully nonlinear models that include the dispersion effects $O(\mu )$ (where $\mu$ is the ratio of the upper-fluid layer depth to a typical wavelength) derived by Choi & Camassa (Phys. Rev. Lett., vol. 77, 1996, pp. 1759–1762) and $O(\mu ^2)$ derived by Debsarma et al. (J. Fluid Mech., vol. 654, 2010, pp. 281–303). It is shown that the HLGN model has a wider application range than other models. Solutions of travelling large-amplitude internal solitary waves in the absence and presence of background shear-current are then investigated by using the HLGN model. For the no-current cases, results obtained by the HLGN model show better agreement with Euler's solution on wave profile, velocity profile at the maximum interface displacement and wave speed compared with those obtained by other models. For the background shear-current cases, results obtained by the HLGN model also show good agreement with those obtained by solving the Dubreil-Jacotin–Long equation.
As an important component of prehistoric subsistence, an understanding of bone-working is essential for interpreting the evolution of early complex societies, yet worked bones are rarely systematically collected in China. Here, the authors apply multiple analytical methods to worked bones from the Longshan site of Pingliangtai, in central China, showing that Neolithic bone-working in this area, with cervid as the main raw material, was mature but localised, household-based and self-sufficient. The introduction of cattle in the Late Neolithic precipitated a shift in bone-working traditions but it was only later, in the Bronze Age, that cattle bones were utilised in a specialised fashion and dedicated bone-working industries emerged in urban centres.
To meet the demands of laser-ion acceleration at a high repetition rate, we have developed a comprehensive diagnostic system for real-time and in situ monitoring of liquid sheet targets (LSTs). The spatially resolved rapid characterizations of an LST’s thickness, flatness, tilt angle and position are fulfilled by different subsystems with high accuracy. With the help of the diagnostic system, we reveal the dependence of thickness distribution on collision parameters and report the 238-nm liquid sheet generated by the collision of two liquid jets. Control methods for the flatness and tilt angle of LSTs have also been provided, which are essential for applications of laser-driven ion acceleration and others.
Here, we report the generation of MeV alpha-particles from H-11B fusion initiated by laser-accelerated boron ions. Boron ions with maximum energy of 6 MeV and fluence of 109/MeV/sr@5 MeV were generated from 60 nm-thick self-supporting boron nanofoils irradiated by 1 J femtosecond pulses at an intensity of 1019 W/cm2. By bombarding secondary hydrogenous targets with the boron ions, 3 × 105/sr alpha-particles from H-11B fusion were registered, which is consistent with the theoretical yield calculated from the measured boron energy spectra. Our results demonstrated an alternative way toward ultrashort MeV alpha-particle sources employing compact femtosecond lasers. The ion acceleration and product measurement scheme are referential for the studies on the ion stopping power and cross section of the H-11B reaction in solid or plasma.
With the advantages of short duration and extreme brightness, laser proton accelerators (LPAs) show great potential in many fields for industrial, medical, and research applications. However, the quality of current laser-driven proton beams, such as the broad energy spread and large divergence angle, is still a challenge. We use numerical simulations to study the propagation of such proton bunches in the plasma. Results show the bunch will excite the wakefield and modulate itself. Although a small number of particles at the head of the bunch cannot be manipulated by the wakefield, the total energy spread is reduced. Moreover, while reducing the longitudinal energy spread, the wakefield will also pinch the beam in the transverse direction. The space charge effect of the bunch is completely offset by the wakefield, and the transverse momentum of the bunch decreases as the bunch transports in the plasma. For laser-driven ion beams, our study provides a novel idea about the optimization of these beams.
The global transition towards diets high in calories has contributed to 2.1 billion people becoming overweight, or obese, which damages male reproduction and harms offspring. Recently, more and more studies have shown that paternal exposure to stress closely affects the health of offspring in an intergenerational and transgenerational way. SET Domain Containing 2 (SETD2), a key epigenetic gene, is highly conserved among species, is a crucial methyltransferase for converting histone 3 lysine 36 dimethylation (H3K36me2) into histone 3 lysine 36 trimethylation (H3K36me3), and plays an important regulator in the response to stress. In this study, we compared patterns of SETD2 expression and the H3K36me3 pattern in pre-implantation embryos derived from normal or obese mice induced by high diet. The results showed that SETD2 mRNA was significantly higher in the high-fat diet (HFD) group than the control diet (CD) group at the 2-cell, 4-cell, 8-cell, and 16-cell stages, and at the morula and blastocyst stages. The relative levels of H3K36me3 in the HFD group at the 2-cell, 4-cell, 8-cell, 16-cell, morula stage, and blastocyst stage were significantly higher than in the CD group. These results indicated that dietary changes in parental generation (F0) male mice fed a HFD were traceable in SETD2/H3K36me3 in embryos, and that a paternal high-fat diet brings about adverse effects for offspring that might be related to SETD2/H3K36me3, which throws new light on the effect of paternal obesity on offspring from an epigenetic perspective.
Galls function as provide shelter for gall inducers, guarding them against their natural enemies. Previous research has illuminated the interactions between galls, gall inducers, and their corresponding parasitoids within various caltrop plants. However, less is known about these relationships within Nitraria sibirica, particularly regarding the efficacy of parasitism. Therefore, this study aimed to identify the morphometric relationships among the swollen galls, gall inducers, and their parasitoids. Two species of gall inducers and three species of parasitoids were obtained from the swollen galls of N. sibirica. The correlations of the parasitization indexes, the lifespan of gall inhabitants, and temperature and the morphometric relationships between the galls and their inhabitants were analyzed. The dominant gall inducer identified was Contarinia sp. (Diptera: Cecidomyiidae). Furthermore, it was observed that three solitary parasitoids attacked Contarinia sp. in the swollen galls, with only Eupelmus gelechiphagus acting as an idiobiont ectoparasitoid. The dominant parasitoids were Platygaster sp. and Cheiloneurus elegans at sites 1 and 2, respectively, with Platygaster sp. displaying greater abundance than C. elegans in the swollen galls. The lifespan of the gall inhabitants shortened gradually as the temperature increased. Moreover, the optimal number of gall chambers ranged from two to four per swollen gall with maximized fitness, which can be considered the optimal population density for the gall inducer Contarinia sp. Morphometric analysis exhibited a strong linear correlation between gall size and chamber number or the number of gall inhabitants, as well as a weak correlation between gall size and body size of the primary inhabitants of swollen galls. Our results highlight the importance of the biological investigation of parasitoids and gall inducers living in closed galls with multiple chambers and may pave the way for potential application in biological control.
Post-acceleration of protons in helical coil targets driven by intense, ultrashort laser pulses can enhance ion energy by utilizing the transient current from the targets’ self-discharge. The acceleration length of protons can exceed a few millimeters, and the acceleration gradient is of the order of GeV/m. How to ensure the synchronization between the accelerating electric field and the protons is a crucial problem for efficient post-acceleration. In this paper, we study how the electric field mismatch induced by current dispersion affects the synchronous acceleration of protons. We propose a scheme using a two-stage helical coil to control the current dispersion. With optimized parameters, the energy gain of protons is increased by four times. Proton energy is expected to reach 45 MeV using a hundreds-of-terawatts laser, or more than 100 MeV using a petawatt laser, by controlling the current dispersion.
In recent years, the incidence of teratospermia has been increasing, and it has become a very important factor leading to male infertility. The research on the molecular mechanism of teratospermia is also progressing rapidly. This article briefly summarizes the clinical incidence of teratozoospermia, and makes a retrospective summary of related studies reported in recent years. Specifically discussing the relationship between gene status and spermatozoa, the review aims to provide the basis for the genetic diagnosis and gene therapy of teratozoospermia.
Electronic skin (e-skin) is playing an increasingly important role in health detection, robotic teleoperation, and human-machine interaction, but most e-skins currently lack the integration of on-site signal acquisition and transmission modules. In this paper, we develop a novel flexible wearable e-skin sensing system with 11 sensing channels for robotic teleoperation. The designed sensing system is mainly composed of three components: e-skin sensor, customized flexible printed circuit (FPC), and human-machine interface. The e-skin sensor has 10 stretchable resistors distributed at the proximal and metacarpal joints of each finger respectively and 1 stretchable resistor distributed at the purlicue. The e-skin sensor can be attached to the opisthenar, and thanks to its stretchability, the sensor can detect the bent angle of the finger. The customized FPC, with WiFi module, wirelessly transmits the signal to the terminal device with human-machine interface, and we design a graphical user interface based on the Qt framework for real-time signal acquisition, storage, and display. Based on this developed e-skin system and self-developed robotic multi-fingered hand, we conduct gesture recognition and robotic multi-fingered teleoperation experiments using deep learning techniques and obtain a recognition accuracy of 91.22%. The results demonstrate that the developed e-skin sensing system has great potential in human-machine interaction.