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Recent studies have increasingly utilized gradient metrics to investigate the spatial transitions of brain organization, enabling the conversion of macroscale brain features into low-dimensional manifold representations. However, it remains unclear whether alterations exist in the cortical morphometric similarity (MS) network gradient in patients with schizophrenia (SCZ). This study aims to examine potential differences in the principal MS gradient between individuals with SCZ and healthy controls and to explore how these differences relate to transcriptional profiles and clinical phenomenology.
Methods
MS network was constructed in this study, and its gradient of the network was computed in 203 patients with SCZ and 201 healthy controls, who shared the same demographics in terms of age and gender. To examine irregularities in the MS network gradient, between-group comparisons were carried out, and partial least squares regression analysis was used to study the relationships between the MS network gradient-based variations in SCZ, and gene expression patterns and clinical phenotype.
Results
In contrast to healthy controls, the principal MS gradient of patients with SCZ was primarily significantly lower in sensorimotor areas, and higher in more areas. In addition, the aberrant gradient pattern was spatially linked with the genes enriched for neurobiologically significant pathways and preferential expression in various brain regions and cortical layers. Furthermore, there were strong positive connections between the principal MS gradient and the symptomatologic score in SCZ.
Conclusions
These findings showed changes in the principal MS network gradient in SCZ and offered potential molecular explanations for the structural changes underpinning SCZ.
Matching-adjusted indirect comparison (MAIC) has been increasingly applied in health technology assessments (HTA). By reweighting subjects from a trial with individual participant data (IPD) to match the summary statistics of covariates in another trial with aggregate data (AgD), MAIC enables a comparison of the interventions for the AgD trial population. However, when there are imbalances in effect modifiers with different magnitudes of modification across treatments, contradictory conclusions may arise if MAIC is performed with the IPD and AgD swapped between trials. This can lead to the “MAIC paradox,” where different entities reach opposing conclusions about which treatment is more effective, despite analyzing the same data. In this paper, we use synthetic data to illustrate this paradox and emphasize the importance of clearly defining the target population in HTA submissions. Additionally, we recommend making de-identified IPD available to HTA agencies, enabling further indirect comparisons that better reflect the overall population represented by both IPD and AgD trials, as well as other relevant target populations for policy decisions. This would help ensure more accurate and consistent assessments of comparative effectiveness.
Network meta-analysis (NMA), also known as mixed treatment comparison meta-analysis or multiple treatments meta-analysis, extends conventional pairwise meta-analysis by simultaneously synthesizing multiple interventions in a single integrated analysis. Despite the growing popularity of NMA within comparative effectiveness research, it comes with potential challenges. For example, within-study correlations among treatment comparisons are rarely reported in the published literature. Yet, these correlations are pivotal for valid statistical inference. As demonstrated in earlier studies, ignoring these correlations can inflate mean squared errors of the resulting point estimates and lead to inaccurate standard error estimates. This article introduces a composite likelihood-based approach that ensures accurate statistical inference without requiring knowledge of the within-study correlations. The proposed method is computationally robust and efficient, with substantially reduced computational time compared to the state-of-the-science methods implemented in R packages. The proposed method was evaluated through extensive simulations and applied to two important applications including an NMA comparing interventions for primary open-angle glaucoma, and another comparing treatments for chronic prostatitis and chronic pelvic pain syndrome.
The emotion regulation network (ERN) in the brain provides a framework for understanding the neuropathology of affective disorders. Although previous neuroimaging studies have investigated the neurobiological correlates of the ERN in major depressive disorder (MDD), whether patients with MDD exhibit abnormal functional connectivity (FC) patterns in the ERN and whether the abnormal FC in the ERN can serve as a therapeutic response signature remain unclear.
Methods
A large functional magnetic resonance imaging dataset comprising 709 patients with MDD and 725 healthy controls (HCs) recruited across five sites was analyzed. Using a seed-based FC approach, we first investigated the group differences in whole-brain resting-state FC of the 14 ERN seeds between participants with and without MDD. Furthermore, an independent sample (45 MDD patients) was used to evaluate the relationship between the aforementioned abnormal FC in the ERN and symptom improvement after 8 weeks of antidepressant monotherapy.
Results
Compared to the HCs, patients with MDD exhibited aberrant FC between 7 ERN seeds and several cortical and subcortical areas, including the bilateral middle temporal gyrus, bilateral occipital gyrus, right thalamus, calcarine cortex, middle frontal gyrus, and the bilateral superior temporal gyrus. In an independent sample, these aberrant FCs in the ERN were negatively correlated with the reduction rate of the HAMD17 score among MDD patients.
Conclusions
These results might extend our understanding of the neurobiological underpinnings underlying unadaptable or inflexible emotional processing in MDD patients and help to elucidate the mechanisms of therapeutic response.
Rhopalosiphum padi is an important grain pest, causing severe losses during crop production. As a systemic insecticide, flonicamid can control piercing-sucking pests efficiently. In our study, the lethal effects of flonicamid on the biological traits of R. padi were investigated via a life table approach. Flonicamid is highly efficiently toxic to R. padi, with an LC50 of 9.068 mg L−1. The adult longevity and fecundity of the R. padi F0 generation were markedly reduced under the LC25 and LC50 concentrations of flonicamid exposure. In addition, negative transgenerational effects on R. padi were observed under exposure to lethal concentrations of flonicamid, with noticeable decreases in the reproductive period, adult longevity, total longevity, and total fecundity of the F1 generation under the LC25 concentration of flonicamid. Furthermore, the third nymph stage (N3), preadult stage, duration of the adult pre-reproductive period, duration of the total pre-reproductive period, reproductive period, adult longevity, total longevity, and total fecundity of the F1 generation were significantly lower under treatment with the LC50 concentration of flonicamid. The life table parameters were subsequently analysed, revealing that the intrinsic rate of increase (rm) and the net reproductive rate (R0) were significantly lower but that the finite rate of increase (λ) and the mean generation time (T) were not significantly different under the LC25 and LC50 concentrations of flonicamid. These data are beneficial for grain aphid control and are critical for exploring the role of flonicamid in the integrated management of this key pest.
An increasing number of observational studies have reported associations between frailty and mental disorders, but the causality remains ambiguous.
Aims
To assess the bidirectional causal relationship between frailty and nine mental disorders.
Method
We conducted a bidirectional two-sample Mendelian randomisation on genome-wide association study summary data, to investigate causality between frailty and nine mental disorders. Causal effects were primarily estimated using inverse variance weighted method. Several secondary analyses were applied to verify the results. Cochran's Q-test and Mendelian randomisation Egger intercept were applied to evaluate heterogeneity and pleiotropy.
Results
Genetically determined frailty was significantly associated with increased risk of major depressive disorder (MDD) (odds ratio 1.86, 95% CI 1.36–2.53, P = 8.1 × 10−5), anxiety (odds ratio 2.76, 95% CI 1.56–4.90, P = 5.0 × 10−4), post-traumatic stress disorder (PTSD) (odds ratio 2.56, 95% CI 1.69–3.87, P = 9.9 × 10−6), neuroticism (β = 0.25, 95% CI 0.11–0.38, P = 3.3 × 10−4) and insomnia (β = 0.50, 95% CI 0.25–0.75, P = 1.1 × 10−4). Conversely, genetic liability to MDD, neuroticism, insomnia and suicide attempt significantly increased risk of frailty (MDD: β = 0.071, 95% CI 0.033–0.110, P = 2.8 × 10−4; neuroticism: β = 0.269, 95% CI 0.173–0.365, P = 3.4 × 10−8; insomnia: β = 0.160, 95% CI 0.141–0.179, P = 3.2 × 10−61; suicide attempt: β = 0.056, 95% CI 0.029–0.084, P = 3.4 × 10−5). There was a suggestive detrimental association of frailty on suicide attempt and an inverse relationship of subjective well-being on frailty.
Conclusions
Our findings show bidirectional causal associations between frailty and MDD, insomnia and neuroticism. Additionally, higher frailty levels are associated with anxiety and PTSD, and suicide attempts are correlated with increased frailty. Understanding these associations is crucial for the effective management of frailty and improvement of mental disorders.
Broadband frequency-tripling pulses with high energy are attractive for scientific research, such as inertial confinement fusion, but are difficult to scale up. Third-harmonic generation via nonlinear frequency conversion, however, remains a trade-off between bandwidth and conversion efficiency. Based on gradient deuterium deuterated potassium dihydrogen phosphate (KDxH2-xPO4, DKDP) crystal, here we report the generation of frequency-tripling pulses by rapid adiabatic passage with a low-coherence laser driver facility. The efficiency dependence on the phase-matching angle in a Type-II configuration is studied. We attained an output at 352 nm with a bandwidth of 4.4 THz and an efficiency of 36%. These results, to the best of our knowledge, represent the first experimental demonstration of gradient deuterium DKDP crystal in obtaining frequency-tripling pulses. Our research paves a new way for developing high-efficiency, large-bandwidth frequency-tripling technology.
Knowledge is growing on the essential role of neural circuits involved in aberrant cognitive control and reward sensitivity for the onset and maintenance of binge eating.
Aims
To investigate how the brain's reward (bottom-up) and inhibition control (top-down) systems potentially and dynamically interact to contribute to subclinical binge eating.
Method
Functional magnetic resonance imaging data were acquired from 30 binge eaters and 29 controls while participants performed a food reward Go/NoGo task. Dynamic causal modelling with the parametric empirical Bayes framework, a novel brain connectivity technique, was used to examine between-group differences in the directional influence between reward and executive control regions. We explored the proximal risk factors for binge eating and its neural basis, and assessed the predictive ability of neural indices on future disordered eating and body weight.
Results
The binge eating group relative to controls displayed fewer reward-inhibition undirectional and directional synchronisations (i.e. medial orbitofrontal cortex [mOFC]–superior parietal gyrus [SPG] connectivity, mOFC → SPG excitatory connectivity) during food reward_nogo condition. Trait impulsivity is a key proximal factor that could weaken the mOFC–SPG connectivity and exacerbate binge eating. Crucially, this core mOFC–SPG connectivity successfully predicted binge eating frequency 6 months later.
Conclusions
These findings point to a particularly important role of the bottom-up interactions between cortical reward and frontoparietal control circuits in subclinical binge eating, which offers novel insights into the neural hierarchical mechanisms underlying problematic eating, and may have implications for the early identification of individuals suffering from strong binge eating-associated symptomatology in the general population.
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.
In contemporary neuroimaging studies, it has been observed that patients with major depressive disorder (MDD) exhibit aberrant spontaneous neural activity, commonly quantified through the amplitude of low-frequency fluctuations (ALFF). However, the substantial individual heterogeneity among patients poses a challenge to reaching a unified conclusion.
Methods
To address this variability, our study adopts a novel framework to parse individualized ALFF abnormalities. We hypothesize that individualized ALFF abnormalities can be portrayed as a unique linear combination of shared differential factors. Our study involved two large multi-center datasets, comprising 2424 patients with MDD and 2183 healthy controls. In patients, individualized ALFF abnormalities were derived through normative modeling and further deconstructed into differential factors using non-negative matrix factorization.
Results
Two positive and two negative factors were identified. These factors were closely linked to clinical characteristics and explained group-level ALFF abnormalities in the two datasets. Moreover, these factors exhibited distinct associations with the distribution of neurotransmitter receptors/transporters, transcriptional profiles of inflammation-related genes, and connectome-informed epicenters, underscoring their neurobiological relevance. Additionally, factor compositions facilitated the identification of four distinct depressive subtypes, each characterized by unique abnormal ALFF patterns and clinical features. Importantly, these findings were successfully replicated in another dataset with different acquisition equipment, protocols, preprocessing strategies, and medication statuses, validating their robustness and generalizability.
Conclusions
This research identifies shared differential factors underlying individual spontaneous neural activity abnormalities in MDD and contributes novel insights into the heterogeneity of spontaneous neural activity abnormalities in MDD.
In a two-dimensional plane, entire solutions of the Allen–Cahn type equation with a finite Morse index necessarily have finite ends. In the case that the nonlinearity is a sine function, all the finite-end solutions have been classified. However, for the classical Allen–Cahn nonlinearity, the structure of the moduli space of these solutions remains unknown. We construct in this paper new finite-end solutions to the Allen–Cahn equation, which will be called fence of saddle solutions, by gluing saddle solutions together. Our construction can be generalized to the case of gluing multiple four-end solutions, with some of their ends being almost parallel.
Compacted bentonite, used as an engineering barrier for permanent containment of high-level radioactive waste, is susceptible to mineral evolution resulting in compromise of the expected barrier performance due to alkaline–thermal chemical interaction in the near-field. To elucidate the mineral-evolution mechanisms within bentonite and the transformation of the nuclide adsorption properties during that period, experimental evolution of bentonite was conducted in a NaOH solution with a pH of 14 at temperatures ranging from 60 to 120°C. The results showed that temperature significantly affects the stability of minerals in bentonite under alkali conditions. The dissolution rate of fine-grained cristobalite in bentonite exceeds that of smectite, with the phase-transition products of smectite being temperature-dependent. As the temperature rises, smectite experiences a three-stage transformation: initially, at 60°C, the lattice structure thins due to the collapse of the octahedral sheets; at 80°C, the lattice disintegrates and reorganizes into a loose framework akin to albite; and by 100°C, it further reorganizes into a denser framework resembling analcime. The adsorption properties of bentonite exhibit a peak inflection point at 80°C, where the dissolution of the smectite lattice eliminates interlayer pores and exposes numerous polar or negatively charged sites which results in a decrease in specific surface area and an increase in cation exchange capacity and adsorption capacity of Eu3+. This research provides insights into the intricate evolution of bentonite minerals and the associated changes in radionuclide adsorption capacity, contributing to a better understanding of the stability of bentonite barriers and the effective long-term containment of nuclear waste.
First-episode schizophrenia (FES) is a progressive psychiatric disorder influenced by genetics, environmental factors, and brain function. The functional gradient deficits of drug-naïve FES and its relationship to gene expression profiles and treatment outcomes are unknown.
Methods
In this study, we engaged a cohort of 116 FES and 100 healthy controls (HC), aged 7 to 30 years, including 15 FES over an 8-week antipsychotic medication regimen. Our examination focused on primary-to-transmodal alterations in voxel-based connection gradients in FES. Then, we employed network topology, Neurosynth, postmortem gene expression, and support vector regression to evaluate integration and segregation functions, meta-analytic cognitive terms, transcriptional patterns, and treatment predictions.
Results
FES displayed diminished global connectome gradients (Cohen's d = 0.32–0.57) correlated with compensatory integration and segregation functions (Cohen's d = 0.31–0.36). Predominant alterations were observed in the default (67.6%) and sensorimotor (21.9%) network, related to high-order cognitive functions. Furthermore, we identified notable overlaps between partial least squares (PLS1) weighted genes and dysregulated genes in other psychiatric conditions. Genes linked with gradient alterations were enriched in synaptic signaling, neurodevelopment process, specific astrocytes, cortical layers (layer II and IV), and developmental phases from late/mid fetal to young adulthood. Additionally, the onset age influenced the severity of FES, with discernible differences in connection gradients between minor- and adult-FES. Moreover, the connectivity gradients of FES at baseline significantly predicted treatment outcomes.
Conclusions
These results offer significant theoretical foundations for elucidating the intricate interplay between macroscopic functional connection gradient changes and microscopic transcriptional patterns during the onset and progression of FES.
The inverse dynamics model of an industrial robot can predict and control the robot’s motion and torque output, improving its motion accuracy, efficiency, and adaptability. However, the existing inverse rigid body dynamics models still have some unmodelled residuals, and their calculation results differ significantly from the actual industrial robot conditions. The bootstrap aggregating (bagging) algorithm is combined with a long short-term memory network, the linear layer is introduced as the network optimization layer, and a compensation method of hybrid inverse dynamics model for robots based on the BLL residual prediction algorithm is proposed to meet the above needs. The BLL residual prediction algorithm framework is presented. Based on the rigid body inverse dynamics of the Newton–Euler method, the BLL residual prediction network is used to perform error compensation on the inverse dynamics model of the Franka robot. The experimental results show that the hybrid inverse dynamics model based on the BLL residual prediction algorithm can reduce the average residuals of the robot joint torque from 0.5651 N·m to 0.1096 N·m, which improves the accuracy of the inverse dynamics model compared with those of the rigid body inverse dynamics model. This study lays the foundation for performing more accurate operation tasks using industrial robots.
As a member of the Scathophagidae family, Scathophaga stercoraria (S. stercoraria) is widely distributed globally and is closely associated with animal feces. It is also a species of great interest to many scientific studies. However, its phylogenetic relationships are poorly understood. In this study, S. stercoraria was found in plateau pikas for the first time. The potential cause of its presence in the plateau pikas was discussed and it was speculated that the presence of S. stercoraria was related to the yak feces. In addition, 2 nuclear genes (18SrDNA and 28SrDNA), 1 mitochondrial gene (COI), and the complete mitochondrial genome of S. stercoraria were sequenced. Phylogenetic trees constructed based on 13 Protein coding genes (13PCGs), 18S and 28S rDNA showed that S. stercoraria is closely related to the Calliphoridae family; phylogenetic results based on COI suggest that within the family Scathophagidae, S. stercoraria is more closely related to the genus Leptopa, Micropselapha, Parallelomma and Americina. Divergence times estimated using the COI gene suggest that the divergence formation of the genus Scathophaga is closely related to changes in biogeographic scenarios and potentially driven by a combination of uplift of the Qinghai-Tibetan Plateau (QTP) and dramatic climate changes. These results provide valuable information for further studies on the phylogeny and differentiation of the Scathophaga genus in the future.
China is still among the 30 high-burden tuberculosis (TB) countries in the world. Few studies have described the spatial epidemiological characteristics of pulmonary TB (PTB) in Jiangsu Province. The registered incidence data of PTB patients in 95 counties of Jiangsu Province from 2011 to 2021 were collected from the Tuberculosis Management Information System. Three-dimensional spatial trends, spatial autocorrelation, and spatial–temporal scan analysis were conducted to explore the spatial clustering pattern of PTB. From 2011 to 2021, a total of 347,495 newly diagnosed PTB cases were registered. The registered incidence rate of PTB decreased from 49.78/100,000 in 2011 to 26.49/100,000 in 2021, exhibiting a steady downward trend (χ2 = 414.22, P < 0.001). The average annual registered incidence rate of PTB was higher in the central and northern regions. Moran’s I indices of the registered incidence of PTB were all >0 (P< 0.05) except in 2016, indicating a positive spatial correlation overall. Local autocorrelation analysis showed that ‘high–high’ clusters were mainly distributed in northern Jiangsu, and ‘low–low’ clusters were mainly concentrated in southern Jiangsu. The results of this study assist in identifying settings and locations of high TB risk and inform policy-making for PTB control and prevention.
This research communication reports the effects of a compound enzyme preparation consisting of fibrolytic (cellulase 3500 CU/g, xylanase 2000 XU/g, β-glucanase 17 500 GU/g) and amylolytic (amylase 37 000 AU/g) enzymes on nutrient intake, rumen fermentation, serum parameters and production performance in primiparous early-lactation (47 ± 2 d) dairy cows. Twenty Holstein–Friesian cows in similar body condition scores were randomly divided into control (CON, n = 10) and experimental (EXP, n = 10) groups in a completely randomized single-factor design. CON was fed a basal total mixed ration diet and EXP was dietary supplemented with compound enzyme preparation at 70 g/cow/d. The experiment lasted 4 weeks, with 3 weeks for adaptation and then 1 week for measurement. Enzyme supplementation significantly increased diet non-fibrous carbohydrates (NFC) content as well as dry matter intake (DMI) and NFC intake (P < 0.05). EXP had increased ruminal butyrate and isobutyrate percentages (P < 0.01) but decreased propionate and valerate percentages (P < 0.05), as well as increased serum alkaline phosphatase activity and albumin concentration (P ≤ 0.01). Additionally, EXP had increased milk yield (0.97 kg/d), 4% fat corrected milk yield and energy corrected milk yield, as well as milk fat and protein yield (P < 0.01). In conclusion, dietary supplementation with a fibrolytic and amylolytic compound enzyme preparation increased diet NFC content, DMI and NFC intake, affected rumen fermentation by increasing butyrate proportion at the expense of propionate, and enhanced milk performance in primiparous early-lactation dairy cows.
We introduce the notion of completed $F$-crystals on the absolute prismatic site of a smooth $p$-adic formal scheme. We define a functor from the category of completed prismatic $F$-crystals to that of crystalline étale $\mathbf {Z}_p$-local systems on the generic fiber of the formal scheme and show that it gives an equivalence of categories. This generalizes the work of Bhatt and Scholze, which treats the case of a mixed characteristic complete discrete valuation ring with perfect residue field.