Advancements and Future Directions in Prevention Based on Evaluation for Individuals With Clinical High Risk of Psychosis: Insights From the SHARP Study.

BACKGROUND AND HYPOTHESIS: This review examines the evolution and future prospects of prevention based on evaluation (PBE) for individuals at clinical high risk (CHR) of psychosis, drawing insights from the SHARP (Shanghai At Risk for Psychosis) study. It aims to assess the effectiveness of non-pharmacological interventions in preventing psychosis onset among CHR individuals. STUDY DESIGN: The review provides an overview of the developmental history of the SHARP study and its contributions to understanding the needs of CHR individuals. It explores the limitations of traditional antipsychotic approaches and introduces PBE as a promising framework for intervention. STUDY RESULTS: Three key interventions implemented by the SHARP team are discussed: nutritional supplementation based on niacin skin response blunting, precision transcranial magnetic stimulation targeting cognitive and brain functional abnormalities, and cognitive behavioral therapy for psychotic symptoms addressing symptomatology and impaired insight characteristics. Each intervention is evaluated within the context of PBE, emphasizing the potential for tailored approaches to CHR individuals. CONCLUSIONS: The review highlights the strengths and clinical applications of the discussed interventions, underscoring their potential to revolutionize preventive care for CHR individuals. It also provides insights into future directions for PBE in CHR populations, including efforts to expand evaluation techniques and enhance precision in interventions.

The role of gonadal hormones in regulating opioid antinociception.

Opioids are the most prescribed drugs for the alleviation of pain. Both clinical and preclinical studies have reported strong evidence for sex-related divergence regarding opioid analgesia. There is an increasing amount of evidence indicating that gonadal hormones regulate the analgesic efficacy of opioids. This review presents an overview of the importance of gonadal steroids in modulating opioid analgesic responsiveness and focuses on elaborating what is currently known regarding the underlyingmechanism. We sought to identify the link between gonadal hormones and the effect of oipiod antinociception.

Gonadal hormones contribute to the sexual dimorphism of opioid antinociception.Generally, oestradiol is a negative modulator of opioid analgesia via both non-genomic and genomic effects.Testosterone facilitates opioid analgesia mainly through the transcriptional activities of androgen receptors.Under normal physiological conditions, progestin and oestrogen exist in parallel and have a combined effect. However, progestin alone could promote opioid analgesia by increasing the expression of opioid receptors.

Grandmother-grandchild physiological synchrony in Chinese three-generation families: Links with child emotion regulation.

The current study examined the characteristics of physiological synchrony between grandmothers and grandchildren in Chinese three-generation families, and the associations between physiological synchrony and child emotion regulation. The participants included 92 children (age 8-10-year old) and their grandmothers. Respiratory sinus arrhythmia (RSA) was collected from both grandmothers and their grandchildren throughout a collaborative drawing task and a conflict discussion task. Child emotion regulation was measured using the Children's Emotional Management Scale. We found no evidence for an overall pattern of concordant or discordant synchrony within dyads. Instead, there was great variability in patterns of synchrony across dyads. During the collaborative drawing task, concordance in grandmother's RSA and grandchildren's subsequent RSA was linked with better emotion regulation. During the conflict discussion, concordance in grandmother's RSA and grandchildren's simultaneous RSA was linked with poorer emotion regulation. These results suggest that grandmother-grandchild synchrony in different directions, time lags, and contexts has different influences on children's emotion regulation. The findings of this study highlight the importance of contextual physiological co-regulation between Chinese children and their grandmothers for children's social-emotional development.

Crohn's disease treatment and memory T-cell subset changes: insights from a case series.

Background: Crohn's disease (CD) is a chronic inflammatory bowel disease with significant morbidity, affecting millions worldwide. The intricacies of immune responses in CD, especially post-treatment, remain a vital area of exploration. While memory T (Tm)-cell subsets play a pivotal role in adaptive immunity, their specific function in patients with CD after treatment is not well-understood. This study aims to investigate the effect and function of Tm-cell subsets in these patients, addressing a crucial knowledge gap in the context of CD therapeutics. Methods: A total of eight patients diagnosed with CD were selected based on predefined inclusion criteria. All patients were treated with either anti-inflammatory agents, immunosuppressive drugs, or a combination of both. For comparison, healthy donors were enrolled based on exclusion of autoimmune or inflammatory diseases. Peripheral blood mononuclear cells (PBMCs) and lymphocytes were isolated from blood and lymph node tissue respectively. The phenotype and cytokine production of T lymphocytes from both CD patients and healthy donors were analyzed using flow cytometry. Statistical comparisons of the outcomes between CD patients and healthy donors were made using Mann-Whitney test (two-tailed) and Student t-test. Results: Post-treatment CD patients exhibited an altered T cell distribution with a notable increase in CD8+ T cells in PBMCs (P=0.0005), and altered frequencies of CD4+ and CD8+ T cells in mesenteric lymph nodes (MLNs). Tm cells showed decreased interferon-γ (IFN-γ) and tumor necrosis factor-α (TNF-α) production, with significant alterations in the frequency of IFN-γ-producing CD8+ stem cell-like Tm (Tscm) cells in lesions of the MLNs from patients with CD (CD-M-Lys) compared to healthy MLNs from patients with CD (N-M-Lys) (P=0.0152). Differences in tissue-resident Tm (Trm)-cell subset frequencies were observed between the MLNs and small intestinal mucosa in CD patients. Conclusions: The treatments with anti-inflammatory agents and/or immunosuppressive drugs have a significant effect on the frequency and function of Tm-cell subsets. Clinically, these findings suggest a potential therapeutic avenue in modulating Tm-cell responses, which might be particularly beneficial for conditions where immune response modulation is crucial. Further clinical studies are warranted to explore the full therapeutic implications of these findings.

Cognitive functions following initiation of antipsychotic medication in adolescents and adults at clinical high risk for psychosis: a naturalistic sub group analysis using the MATRICS consensus cognitive battery.

BACKGROUND: The effects of antipsychotic (AP) medications on cognitive functions in individuals at clinical high-risk (CHR) of psychosis are poorly understood. This study compared the effects of AP treatment on cognitive improvement in CHR adolescents and adults. METHODS: A total of 327 CHR participants, with an age range of 13 to 45 years, who underwent baseline neuropsychological assessments and a 1-year clinical follow-up were included. Participants with CHR were categorized into four groups based on their age: adolescents (aged < 18) and adults (aged ≥ 18), as well as their antipsychotic medication status (AP+ or AP-). Therefore, the four groups were defined as Adolescent-AP-, Adolescent-AP+, Adult-AP-, and Adult-AP+. RESULTS: During the follow-up, 231 CHR patients received AP treatment, 94 converted to psychosis, and 161 completed the 1-year follow-up. The Adolescent-AP+ group had more positive symptoms, lower general functions, and cognitive impairments than the Adolescent-AP- group at baseline, but no significant differences were observed among adults. The Adolescent-AP+ group showed a significant increase in the risk of conversion to psychosis (p < 0.001) compared to the Adolescent-AP- group. The Adult-AP+ group showed a decreasing trend in the risk of conversion (p = 0.088) compared to the Adult-AP- group. The Adolescent-AP- group had greater improvement in general functions (p < 0.001), neuropsychological assessment battery mazes (p = 0.025), and brief visuospatial memory test-revised (p = 0.020), as well as a greater decrease in positive symptoms (p < 0.001) at follow-up compared to the Adolescent-AP+ group. No significant differences were observed among adults. CONCLUSIONS: Early use of AP was not associated with a positive effect on cognitive function in CHR adolescents. Instead, the absence of AP treatment was associated with better cognitive recovery, suggesting that AP exposure might not be the preferred choice for cognitive recovery in CHR adolescents, but may be more reasonable for use in adults.

Tumor cell-intrinsic epigenetic dysregulation shapes cancer-associated fibroblasts heterogeneity to metabolically support pancreatic cancer.

The tumor microenvironment (TME) in pancreatic ductal adenocarcinoma (PDAC) involves a significant accumulation of cancer-associated fibroblasts (CAFs) as part of the host response to tumor cells. The origins and functions of transcriptionally diverse CAF populations in PDAC remain poorly understood. Tumor cell-intrinsic genetic mutations and epigenetic dysregulation may reshape the TME; however, their impacts on CAF heterogeneity remain elusive. SETD2, a histone H3K36 trimethyl-transferase, functions as a tumor suppressor. Through single-cell RNA sequencing, we identify a lipid-laden CAF subpopulation marked by ABCA8a in Setd2-deficient pancreatic tumors. Our findings reveal that tumor-intrinsic SETD2 loss unleashes BMP2 signaling via ectopic gain of H3K27Ac, leading to CAFs differentiation toward lipid-rich phenotype. Lipid-laden CAFs then enhance tumor progression by providing lipids for mitochondrial oxidative phosphorylation via ABCA8a transporter. Together, our study links CAF heterogeneity to epigenetic dysregulation in tumor cells, highlighting a previously unappreciated metabolic interaction between CAFs and pancreatic tumor cells.

Mechanism of Xing 9 ling tablet candy for alcoholic liver disease based on network pharmacology.

Xing 9 Ling tablet candy (X9LTC) effectively treats alcoholic liver disease (ALD), but its potential mechanism and molecular targets remain unstudied. We aimed to address this gap using network pharmacology. Furthermore, high-performance liquid chromatography (HPLC) and database analysis revealed a total of 35 active ingredients and 311 corresponding potential targets of X9LTC. Protein interaction analysis revealed PTGS2, JUN, and FOS as its core targets. Enrichment analysis indicated that chemical carcinogenesis-receptor activation, IL-17 and TNF signaling pathway were enriched by multiple core targets, which might be the main pathway of action. Further molecular docking validation showed that the core targets had good binding activities with the identified compounds. Animal experiments showed that X9LTC could reduce the high expression of ALT, AST and TG in the serum of ALD mice, alleviate the lesions in liver tissues, and reverse the high expression of PTGS2, JUN, and FOS proteins in the liver tissues. In this study, we established a method for the determination of X9LTC content for the first time, and predicted its active ingredient and mechanism of action in treating ALD, providing theoretical basis for further research.

Repetitive transcranial magnetic stimulation can improve negative symptoms and/or neurocognitive impairments in the first psychosis episode: A randomized controlled trial.

OBJECTIVE: Negative symptoms and neurocognitive impairments in psychosis correlate with their severity. Currently, there is no satisfactory treatment. We aimed to evaluate and compare the effects of repetitive transcranial magnetic stimulation(rTMS) on negative symptoms and neurocognitive impairments in patients in first-episode of psychosis(FEP) in a randomized controlled trial(RCT). METHOD: This is a single-site RCT of 85 patients with FEP. Patients were randomized to receive a 4-week course of active(n = 45) or sham rTMS(n = 40). Factor analysis was applied to a cross-sectional dataset of 744 FEP patients who completed negative symptom evaluation and neurocognitive battery tests. Two independent dimensions were generated and used for the K-means cluster analysis to produce sub-clusters. rTMS of 1-Hz was delivered to the right orbitofrontal(OFC) cortex. RESULTS: Two distinct dimensional factors of neurocognitive functions(factor-1) and negative symptoms(factor-2), and three clusters with distinctive features were generated. Significant improvements in factor-1 and factor-2 were observed after 4-weeks of rTMS treatment in both the active and sham rTMS groups. The repeated-measures analysis of variance revealed a significant effect of time×group(F = 5.594, p = 0.021, η2 = 0.073) on factor-2, but no effect of time×group on factor-1. Only improvements in negative symptoms were significantly different between the active and sham rTMS groups(p = 0.028). Patients in cluster-3 characterized by extensive negative symptoms, showed greater improvement in the active rTMS group than in the sham rTMS group. CONCLUSIONS: The 1-Hz right OFC cortex rTMS is more effective in reducing negative symptoms than neurocognitive impairments. It is especially effective in patients with dominantly negative symptoms in FEP.

Magnetic Seizure Therapy vs Modified Electroconvulsive Therapy in Patients With Bipolar Mania: A Randomized Clinical Trial.

Importance: Bipolar mania is a common disabling illness. Electroconvulsive therapy (ECT) is an effective treatment for patients with severe mania, though it is limited by the risk of cognitive adverse effects. Magnetic seizure therapy (MST) as an alternative treatment to ECT for bipolar mania has not yet been reported. Objective: To compare the effectiveness and cognitive adverse effects of MST and ECT in bipolar mania. Design, Setting, and Participants: This randomized clinical trial was conducted at the Shanghai Mental Health Center from July 1, 2017, through April 26, 2021. Forty-eight patients with bipolar mania were recruited and randomly allocated to receive MST or ECT. The data analysis was performed from June 5, 2021, through August 30, 2023. Interventions: Patients completed 2 or 3 sessions of MST or ECT per week for a total of 8 to 10 sessions. The MST was delivered at 100% device output with a frequency of 75 Hz over the vertex. Main Outcomes and Measures: The primary outcomes were reduction of total Young Manic Rating Scale (YMRS) score and response rate (more than 50% reduction of the total YMRS score compared with baseline). An intention-to-treat (ITT) analysis and repeated-measures analyses of variance were conducted for the primary outcomes. Results: Twenty patients in the ECT group (mean [SD] age, 31.6 [8.6] years; 12 male [60.0%]) and 22 patients in the MST group (mean [SD] age, 34.8 [9.8] years; 15 male [68.2%]) were included in the ITT analysis. The response rates were 95.0% (95% CI, 85.4%-100%) in the ECT group and 86.4% (95% CI, 72.1%-100%) in the MST group. The YMRS reduction rate (z = -0.82; 95% CI, -0.05 to 0.10; P = .41) and response rate (χ2 = 0.18; 95% CI, -0.13 to 0.31; P = .67) were not significantly different between the groups. The time-by-group interaction was significant for the language domain (F1,24 = 7.17; P = .01), which was well preserved in patients receiving MST but worsened in patients receiving ECT. No serious adverse effects were reported in either group. Conclusions and Relevance: These findings suggest that MST is associated with a high response rate and fewer cognitive impairments in bipolar mania and that it might be an alternative therapy for the treatment of bipolar mania. Trial Registration: ClinicalTrials.gov Identifier: NCT03160664.

Models of mild cognitive deficits in risk assessment in early psychosis.

BACKGROUND: Mild cognitive deficits (MCD) emerge before the first episode of psychosis (FEP) and persist in the clinical high-risk (CHR) stage. This study aims to refine risk prediction by developing MCD models optimized for specific early psychosis stages and target populations. METHODS: A comprehensive neuropsychological battery assessed 1059 individuals with FEP, 794 CHR, and 774 matched healthy controls (HCs). CHR subjects, followed up for 2 years, were categorized into converters (CHR-C) and non-converters (CHR-NC). The MATRICS Consensus Cognitive Battery standardized neurocognitive tests were employed. RESULTS: Both the CHR and FEP groups exhibited significantly poorer performance compared to the HC group across all neurocognitive tests (all p < 0.001). The CHR-C group demonstrated poorer performance compared to the CHR-NC group on three sub-tests: visuospatial memory (p < 0.001), mazes (p = 0.005), and symbol coding (p = 0.023) tests. Upon adjusting for sex and age, the performance of the MCD model was excellent in differentiating FEP from HC, as evidenced by an Area Under the Receiver Operating Characteristic Curve (AUC) of 0.895 (p < 0.001). However, when applied in the CHR group for predicting CHR-C (AUC = 0.581, p = 0.008), the performance was not satisfactory. To optimize the efficiency of psychotic risk assessment, three distinct MCD models were developed to distinguish FEP from HC, predict CHR-C from CHR-NC, and identify CHR from HC, achieving accuracies of 89.3%, 65.6%, and 80.2%, respectively. CONCLUSIONS: The MCD exhibits variations in domains, patterns, and weights across different stages of early psychosis and diverse target populations. Emphasizing precise risk assessment, our findings highlight the importance of tailored MCD models for different stages and risk levels.

Shared and differing functional connectivity abnormalities of the default mode network in mild cognitive impairment and Alzheimer's disease.

Alzheimer's disease (AD) and mild cognitive impairment (MCI) both show abnormal resting-state functional connectivity (rsFC) of default mode network (DMN), but it is unclear to what extent these abnormalities are shared. Therefore, we performed a comprehensive meta-analysis, including 31 MCI studies and 20 AD studies. MCI patients, compared to controls, showed decreased within-DMN rsFC in bilateral medial prefrontal cortex/anterior cingulate cortex (mPFC/ACC), precuneus/posterior cingulate cortex (PCC), right temporal lobes, and left angular gyrus and increased rsFC between DMN and left inferior temporal gyrus. AD patients, compared to controls, showed decreased rsFC within DMN in bilateral mPFC/ACC and precuneus/PCC and between DMN and left inferior occipital gyrus and increased rsFC between DMN and right dorsolateral prefrontal cortex. Conjunction analysis showed shared decreased rsFC in mPFC/ACC and precuneus/PCC. Compared to MCI, AD had decreased rsFC in left precuneus/PCC and between DMN and left inferior occipital gyrus and increased rsFC in right temporal lobes. MCI and AD share a decreased within-DMN rsFC likely underpinning episodic memory deficits and neuropsychiatric symptoms, but differ in DMN rsFC alterations likely related to impairments in other cognitive domains such as language, vision, and execution. This may throw light on neuropathological mechanisms in these two stages of dementia.

Polygonum ciliinerve (Nakai) Ohwi: a review of its botany, traditional uses, phytochemistry, pharmacology, pharmacokinetics and toxicology.

Polygonum ciliinerve (Nakai) Ohwi is a perennial twining vine plant from the Polygonaceae family, which is a Chinese herbal medicine with great value for development and utilization. The purpose of this paper is to provide a systematic review of the botany, traditional uses, phytochemistry, pharmacology, pharmacokinetics, and toxicology of Polygonum ciliinerve (Nakai) Ohwi, as well as an outlook on the future research directions and development prospects of the plant. Data on Polygonum ciliinerve (Nakai) Ohwi were obtained from different databases, including China National Knowledge Infrastructure, Baidu Academic, Wanfang Database, Google Academic, PubMed, Web of Science, SpringerLink, Wiley; books; standards; and Ph.D. and MSc theses. So far, 86 compounds have been identified from Polygonum ciliinerve (Nakai) Ohwi, including anthraquinones, stilbenes, flavonoids, tannins, chromogenic ketones, organic acids and esters, lignans, isobenzofurans, alkaloids, naphthols, and others. Studies have found that Polygonum ciliinerve (Nakai) Ohwi has a wide range of pharmacological effects, including antiviral, antibacterial, anti-inflammatory and analgesic, antitumor, immunomodulatory, hypoglycemic, and antioxidant effects. Clinically, Polygonum ciliinerve (Nakai) Ohwi is very effective in the treatment of gastritis and chronic gastritis. Based on its traditional use, chemical composition, and pharmacological activity, Polygonum ciliinerve (Nakai) Ohwi is a promising source of natural medicine in drug development.

Electrocatalytic denitrification biofilter for advanced purification of chlorophenols via ceramsite-based Ti/SnO2-Sb particle electrode: Performance, microbial community structure and mechanism.

In response to the demand for advanced purification of industrial secondary effluent, a new method has been developed for treating chlorophenol wastewater using the novel ceramsite-based Ti/SnO2-Sb particle electrodes (Ti/SnO2-Sb/CB) enhanced electrocatalytic denitrification biofilter (EDNBF-P) to achieve removal of chlorophenols (CPs), denitrification, and reduction of effluent toxicity. The results showed that significantly improved CPs and TN removal efficiency at low COD/N compared to conventional denitrification biofilter, with CPs removal rates increasing by 0.33%-59.27% and TN removal rates increasing by 12.53%-38.92%. Under the conditions of HRT = 2h, 3V voltage, charging times = 12h, and 25 °C, the concentrations of the CPs in the effluent of EDNBF-P were all below 1 mg/L, the TN concentration was below 15 mg/L, while the effluent toxicity reached the low toxicity level. Additionally, the Ti/SnO2-Sb/CB particle electrodes effectively alleviated the accumulation of NO2--N caused by applied voltage. The Silanimonas, Pseudomonas and Rhodobacter was identified as the core microorganism for denitrification and toxicity reduction. This study validated that EDNBF-P could achieve synergistic treatment of CPs and TN through electrocatalysis and microbial degradation, providing a methodological support for achieving advanced purification of chlorophenol wastewater with low COD/N in industrial applications.

Sambucus williamsii Hance: A comprehensive review of traditional uses, processing specifications, botany, phytochemistry, pharmacology, toxicology, and pharmacokinetics.

OBJECTIVE: Sambucus williamsii Hance, belonging to the Sambucus L. family (Viburnaceae), possesses medicinal properties in its roots, stems, leaves, flowers, and fruits. It is recognized for its ability to facilitate bone reunion, enhance blood circulation, remove stasis, and dispel wind and dampness. This traditional Chinese medicine holds significant potential for development and practical use. Hence, this paper offers an in-depth review of S. williamsii, covering traditional uses, processing guidelines, botany, phytochemistry, pharmacology, toxicology, and pharmacokinetics, aiming to serve as a reference for its further development and utilization. MATERIALS AND METHODS: Information for this study was gathered from various books, bibliographic databases, and literature sources such as Google Scholar, Web of Science, PubMed, Chinese National Knowledge Infrastructure, Baidu Scholar, VIP Database for Chinese Technical Periodicals, and Wanfang Data. RESULTS: Phytochemical investigations have identified approximately 238 compounds within the root bark, stem branches, leaves, and fruits of S. williamsii. These compounds encompass flavonoids, sugars, glycosides, terpenoids, phenylpropanoids, alkaloids, phenols, phenolic glycosides, and other chemical constituents, with phenylpropanoids being the most prevalent. S. williamsii exhibits a wide range of pharmacological effects, particularly in promoting osteogenesis and fracture healing. CONCLUSION: This comprehensive review delves into the traditional uses, processing guidelines, botany, phytochemistry, pharmacology, toxicology, and pharmacokinetics of S. williamsii. It provides valuable insights into this plant, which will prove beneficial for future research involving S. williamsii.

Asymmetrical cortical surface area decrease in epilepsy patients with postictal generalized electroencephalography suppression.

Postictal generalized electroencephalographic suppression is a possible electroencephalographic marker for sudden unexpected death in epilepsy. We aimed to investigate the cortical surface area abnormalities in epilepsy patients with postictal generalized electroencephalographic suppression. We retrospectively included 30 epilepsy patients with postictal generalized electroencephalographic suppression (PGES+), 21 epilepsy patients without postictal generalized electroencephalographic suppression (PGES-), and 30 healthy controls. Surface-based analysis on high-resolution T1-weighted images was conducted and cortical surface areas were compared among the three groups, alongside correlation analyses with seizure-related clinical variables. Compared with PGES- group, we identified reduced surface area in the bilateral insula with more extensive distribution in the right hemisphere in PGES+ group. The reduced right insular surface area was associated with younger seizure-onset age. When compared with healthy controls, PGES- group presented reduced surface area in the left caudal middle frontal gyrus; PGES+ group presented more widespread surface area reductions in the right posterior cingulate gyrus, left postcentral gyrus, middle frontal gyrus, and middle temporal gyrus. Our results suggested cortical microstructural impairment in patients with postictal generalized electroencephalographic suppression. The significant surface area reductions in the insular cortex supported the autonomic network involvement in the pathology of postictal generalized electroencephalographic suppression, and its right-sided predominance suggested the potential shared abnormal brain network for postictal generalized electroencephalographic suppression and sudden unexpected death in epilepsy.

Eye Movement Characteristics for Predicting a Transition to Psychosis: Longitudinal Changes and Implications.

BACKGROUND AND HYPOTHESIS: Substantive inquiry into the predictive power of eye movement (EM) features for clinical high-risk (CHR) conversion and their longitudinal trajectories is currently sparse. This study aimed to investigate the efficiency of machine learning predictive models relying on EM indices and examine the longitudinal alterations of these indices across the temporal continuum. STUDY DESIGN: EM assessments (fixation stability, free-viewing, and smooth pursuit tasks) were performed on 140 CHR and 98 healthy control participants at baseline, followed by a 1-year longitudinal observational study. We adopted Cox regression analysis and constructed random forest prediction models. We also employed linear mixed-effects models (LMMs) to analyze longitudinal changes of indices while stratifying by group and time. STUDY RESULTS: Of the 123 CHR participants who underwent a 1-year clinical follow-up, 25 progressed to full-blown psychosis, while 98 remained non-converters. Compared with the non-converters, the converters exhibited prolonged fixation durations, decreased saccade amplitudes during the free-viewing task; larger saccades, and reduced velocity gain during the smooth pursuit task. Furthermore, based on 4 baseline EM measures, a random forest model classified converters and non-converters with an accuracy of 0.776 (95% CI: 0.633, 0.882). Finally, LMMs demonstrated no significant longitudinal alterations in the aforementioned indices among converters after 1 year. CONCLUSIONS: Aberrant EMs may precede psychosis onset and remain stable after 1 year, and applying eye-tracking technology combined with a modeling approach could potentially aid in predicting CHRs evolution into overt psychosis.

Effect of Evaluation of Various Emission Control Policies on PM2.5 Reduction.

In previous work, a methodology was developed to discuss the influence of meteorological factors, policies, and surrounding cities on PM2.5 concentrations in a city. Two models were constructed using Zibo City, Shandong Province, as the target city. Initially, we improved the established PM2.5-Meteorological-Policy (PMP) model and applied it to six other target cities in Shandong Province. Concurrently, a novel model named the PM2.5-Interregional (PI) model was further developed in each city to directly express the influence of surrounding cities on the target cities. The model construction period was from January 2014 to August 2022, with the extended prediction period until November 2022. The results confirmed that disparities in the spatial distribution in seasons became smaller after the implementation of environmental policies. Moreover, two models in each city revealed good interpretation with high adjusted R2 values (>0.7) and lower MAPE and RMSE values (the lowest was 5.53% and 2.57), suggesting reasonable short-term prediction. Additionally, meteorological factors and the combined implementation of different policy types played crucial roles in reducing PM2.5 concentrations in all cities. Specifically, the temperature and wind speed were negatively correlated with PM2.5 concentrations in all models, with temperature having a stronger influence. The Law of the People's Republic of China on the Prevention and Control of Atmospheric Pollution (LAPAP), implemented in 2016, had a clear influence on reducing PM2.5 concentrations, with the highest absolute fitted coefficient in most cities (-0.166 to -0.344). On the contrary, the influence of temperature seemed to be more significant compared to policies, due to the larger standardized coefficient in each city (-0.606 to -0.864).

Duration of Untreated Prodromal Psychosis and Cognitive Impairments.

Importance: The possible association between the duration of untreated prodromal symptoms (DUPrS) and cognitive functioning in individuals at clinical high risk (CHR) for psychosis remains underexplored. Objective: To investigate the intricate interplay between DUPrS, cognitive performance, and conversion outcomes, shedding light on the potential role of DUPrS in shaping cognitive trajectories and psychosis risk in individuals at CHR for psychosis. Design, Setting, and Participants: This cohort study of individuals at CHR for psychosis was conducted at the Shanghai Mental Health Center in China from January 10, 2016, to December 29, 2021. Participants at CHR for psychosis typically exhibit attenuated positive symptoms; they were identified according to the Structured Interview for Prodromal Syndromes, underwent baseline neuropsychological assessments, and were evaluated at a 3-year clinical follow-up. Data were analyzed from August 25, 2021, to May 10, 2023. Exposure: Duration of untreated prodromal symptoms and cognitive impairments in individuals at CHR for psychosis. Main Outcomes and Measures: The primary study outcome was conversion to psychosis. The DUPrS was categorized into 3 groups based on percentiles (33rd percentile for short [≤3 months], 34th-66th percentile for median [4-9 months], and 67th-100th percentile for long [≥10 months]). The DUPrS, cognitive variables, and the risk of conversion to psychosis were explored through quantile regression and Cox proportional hazards regression analyses. Results: This study included 506 individuals (median age, 19 [IQR, 16-21] years; 53.6% [n = 271] women). The mean (SD) DUPrS was 7.8 (6.857) months, and the median (IQR) was 6 (3-11) months. The short and median DUPrS groups displayed poorer cognitive performance than the long DUPrS group in the Brief Visuospatial Memory Test-Revised (BVMT-R) (Kruskal-Wallis χ2 = 8.801; P = .01) and Category Fluency Test (CFT) (Kruskal-Wallis χ2 = 6.670; P = .04). Quantile regression analysis revealed positive correlations between DUPrS rank and BVMT-R scores (<90th percentile of DUPrS rank) and CFT scores (within the 20th-70th percentile range of DUPrS rank). Among the 506 participants, 20.8% (95% CI, 17.4%-24.5%) converted to psychosis within 3 years. Cox proportional hazards regression analysis identified lower educational attainment (hazard ratio [HR], 0.912; 95% CI, 0.834-0.998), pronounced negative symptoms (HR, 1.044; 95% CI, 1.005-1.084), and impaired performance on the Neuropsychological Assessment Battery: Mazes (HR, 0.961; 95% CI, 0.924-0.999) and BVMT-R (HR, 0.949; 95% CI, 0.916-0.984) tests as factors associated with conversion. Conclusions and Relevance: The finding of this cohort study suggest the intricate interplay between DUPrS, cognitive performance, and conversion risk in individuals at CHR for psychosis. The findings emphasize the importance of considering both DUPrS and cognitive functioning in assessing the trajectory of these individuals.

Spatial and Temporal Abnormalities of Spontaneous Fixational Saccades and Their Correlates With Positive and Cognitive Symptoms in Schizophrenia.

BACKGROUND AND HYPOTHESIS: Visual fixation is a dynamic process, with the spontaneous occurrence of microsaccades and macrosaccades. These fixational saccades are sensitive to the structural and functional alterations of the cortical-subcortical-cerebellar circuit. Given that dysfunctional cortical-subcortical-cerebellar circuit contributes to cognitive and behavioral impairments in schizophrenia, we hypothesized that patients with schizophrenia would exhibit abnormal fixational saccades and these abnormalities would be associated with the clinical manifestations. STUDY DESIGN: Saccades were recorded from 140 drug-naïve patients with first-episode schizophrenia and 160 age-matched healthy controls during ten separate trials of 6-second steady fixations. Positive and negative symptoms were assessed using the Positive and Negative Syndrome Scale (PANSS). Cognition was assessed using the Measurement and Treatment Research to Improve Cognition in Schizophrenia Consensus Cognitive Battery (MCCB). STUDY RESULTS: Patients with schizophrenia exhibited fixational saccades more vertically than controls, which was reflected in more vertical saccades with angles around 90° and a greater vertical shift of horizontal saccades with angles around 0° in patients. The fixational saccades, especially horizontal saccades, showed longer durations, faster peak velocities, and larger amplitudes in patients. Furthermore, the greater vertical shift of horizontal saccades was associated with higher PANSS total and positive symptom scores in patients, and the longer duration of horizontal saccades was associated with lower MCCB neurocognitive composite, attention/vigilance, and speed of processing scores. Finally, based solely on these fixational eye movements, a K-nearest neighbors model classified patients with an accuracy of 85%. Conclusions: Our results reveal spatial and temporal abnormalities of fixational saccades and suggest fixational saccades as a promising biomarker for cognitive and positive symptoms and for diagnosis of schizophrenia.

Direct and indirect effects of error monitoring on social functioning in a cohort with high-risk and first-episode psychosis.

Error monitoring plays a key role in people's adjustment to social life. This study aimed to examine the direct (DE) and indirect effects (IDE) of error monitoring, as indicated by error-related negativity (ERN), on social functioning in a clinical cohort from high-risk (APS) to first-episode psychosis (FEP). This study recruited 100 outpatients and 49 healthy controls (HC). ERN was recorded during a modified flanker task; social functioning was evaluated using the social scale of global functioning. The path analysis was executed using the "lavaan" package. When controlling for age and education, the clinical cohort had a smaller ERN than the HC group (F1, 145 = 19.58, p < 0.001, partial η2 = 0.12, 95%CI: 0.04-0.22). ERN demonstrated no substantial direct impact on current social functioning; however, it manifested indirect influences on social functioning via the disorganization factor of the Positive and Negative Syndrome Scale, both with (standardized IDE: -0.139, p = 0.009) and without (standardized IDE: -0.087, p = 0.018) accounting for the diagnosis, defined as a dummy variable (FEP = 1 and APS = 0) and included as a covariate. These findings suggest that error monitoring, as indicated by ERN, may serve as a potential prognostic indicator of social functioning in patients with psychosis.