Structural brain abnormalities and aggressive behaviour in schizophrenia: Mega-analysis of data from 2095 patients and 2861 healthy controls via the ENIGMA consortium.

Background: Schizophrenia is associated with an increased risk of aggressive behaviour, which may partly be explained by illness-related changes in brain structure. However, previous studies have been limited by group-level analyses, small and selective samples of inpatients and long time lags between exposure and outcome. Methods: This cross-sectional study pooled data from 20 sites participating in the international ENIGMA-Schizophrenia Working Group. Sites acquired T1-weighted and diffusion-weighted magnetic resonance imaging scans in a total of 2095 patients with schizophrenia and 2861 healthy controls. Measures of grey matter volume and white matter microstructural integrity were extracted from the scans using harmonised protocols. For each measure, normative modelling was used to calculate how much patients deviated (in z-scores) from healthy controls at the individual level. Ordinal regression models were used to estimate the associations of these deviations with concurrent aggressive behaviour (as odds ratios [ORs] with 99% confidence intervals [CIs]). Mediation analyses were performed for positive symptoms (i.e., delusions, hallucinations and disorganised thinking), impulse control and illness insight. Aggression and potential mediators were assessed with the Positive and Negative Syndrome Scale, Scale for the Assessment of Positive Symptoms or Brief Psychiatric Rating Scale. Results: Aggressive behaviour was significantly associated with reductions in total cortical volume (OR [99% CI] = 0.88 [0.78, 0.98], p = .003) and global white matter integrity (OR [99% CI] = 0.72 [0.59, 0.88], p = 3.50 × 10-5) and additional reductions in dorsolateral prefrontal cortex volume (OR [99% CI] = 0.85 [0.74, 0.97], p =.002), inferior parietal lobule volume (OR [99% CI] = 0.76 [0.66, 0.87], p = 2.20 × 10-7) and internal capsule integrity (OR [99% CI] = 0.76 [0.63, 0.92], p = 2.90 × 10-4). Except for inferior parietal lobule volume, these associations were largely mediated by increased severity of positive symptoms and reduced impulse control. Conclusions: This study provides evidence that the co-occurrence of positive symptoms, poor impulse control and aggressive behaviour in schizophrenia has a neurobiological basis, which may inform the development of therapeutic interventions.

Immunogenic Extracellular Vesicles Derived from Endoplasmic Reticulum-Stressed Tumor Cells: Implications as the Therapeutic Cancer Vaccine.

Tumor-derived extracellular vesicles (TDEs) have potential for therapeutic cancer vaccine applications since they innately possess tumor-associated antigens, mediate antigen presentation, and can incorporate immune adjuvants for enhanced vaccine efficacy. However, the original TDEs also contain immune-suppressive proteins. To address this, we proposed a simple yet powerful preconditioning method to improve the overall immunogenicity of the TDEs. This approach involved inducing endoplasmic reticulum (ER) stress on parental tumor cells via N-glycosylation inhibition with tunicamycin. The generated immunogenic TDEs (iTDEs) contained down-regulated immunosuppressive proteins and up-regulated immune adjuvants, effectively activating dendritic cells (DCs) in vitro. Furthermore, in vivo evidence from a tumor-bearing mouse model showed that iTDEs activated DCs, enabling cytotoxic T lymphocytes (CTLs) to target tumors, and eventually established a systemic antitumor immune response. Additionally, iTDEs significantly delayed tumor recurrence in a postsurgery model compared with control groups. These findings highlight the immense potential of our strategy for utilizing TDEs to develop effective cancer vaccines.

Beyond verbal fluency in the verbal fluency task: semantic clustering as a predictor of remission in individuals at clinical high risk for psychosis.

BACKGROUND: There have been conflicting reports on whether conventional verbal fluency measures can predict the prognosis of individuals at clinical high risk (CHR) for psychosis. We aimed to investigate whether verbal fluency task measures that represent semantic processing more directly than conventional measures could be more reliable predictors of later remission in CHR individuals. METHODS: We recruited CHR individuals and healthy controls to participate in a baseline verbal fluency assessment. We identified semantic clusters within the verbal fluency task responses based on cosine similarity between consecutive words, calculated from the word embedding model. Binomial logistic regression was performed to test whether average semantic cluster size and number of words produced could be predictors of remission in CHR individuals. RESULTS: Our study sample included 96 CHR individuals and 178 healthy controls. According to clinical assessment at the last follow-up, 23 CHR individuals were classified as remitters and 73 as nonremitters, including 29 individuals who converted to psychosis. The CHR remitters showed larger average and maximum semantic cluster sizes than CHR nonremitters and healthy controls. Average semantic cluster size, but not the number of words, was a significant predictor of later remission in CHR individuals. LIMITATIONS: Our sample included only native Korean speakers. CONCLUSION: A verbal fluency task measure that more specifically represents semantic processing may be a better neurocognitive predictive marker for remission in CHR individuals than conventional verbal fluency measures. Our results provide an explanation for heterogeneous reports on whether verbal fluency can predict prognosis in CHR individuals and suggest that semantic processing is a putative cognitive predictor of their prognosis.

Aberrant cortico-thalamo-cerebellar network interactions and their association with impaired cognitive functioning in patients with schizophrenia.

Evidence indicating abnormal functional connectivity (FC) among the cortex, thalamus, and cerebellum in schizophrenia patients has increased. However, the role of the thalamus and cerebellum when integrated into intrinsic networks and how those integrated networks interact in schizophrenia patients are largely unknown. We generated an integrative network map by merging thalamic and cerebellar network maps, which were parcellated using a winner-take-all approach, onto a cortical network map. Using cognitive networks, the default mode network (DMN), the dorsal attention network (DAN), the salience network (SAL), and the central executive network (CEN) as regions of interest, the FC of 48 schizophrenia patients was compared with that of 57 healthy controls (HCs). The association between abnormal FC and cognitive impairment was also investigated in patients. FC was lower between the SAL-CEN, SAL-DMN, and DMN-CEN and within-CEN in schizophrenia patients than in HCs. Hypoconnectivity between the DMN-CEN was correlated with impaired cognition in schizophrenia patients. Our findings broadly suggest the plausible role of the thalamus and cerebellum in integrative intrinsic networks in patients, which may contribute to the disrupted triple network and cognitive dysmetria in schizophrenia.

Catalytic ozonation of methylethylketone over porous Mn-Cu/HZSM-5.

The catalytic ozonation of methylethylketone (MEK) was performed at the room temperature (25 °C) using the synthesized Mn and Cu-loaded zeolite (ZSM-5, SiO2/Al2O3 = 80) catalysts. The ZSM-5 zeolite was used as a porous support material due to the large surface area and high capacity for adsorption of volatile organic compounds. Since Mn and Cu-loaded zeolite catalysts were effective for the catalytic ozonation of VOCs such as MEK, according to the loaded concentration of Mn and Cu, there are four types of metal loaded ZSM5 catalysts synthesized [5 wt% Mn/ZSM-5, 5 wt% Cu/ZSM-5, 5 wt% Mn-1 wt% Cu/ZSM-5 (5Mn1CuZSM), and 5 wt% Cu-1 wt% Mn/ZSM-5]. The catalytic efficiency for the removal of MEK and ozonation using the different catalysts was also studied. Based on various experimental analysis processes, the characteristics of the synthesized catalysts were explored and the removal efficiencies of MEK and O3 together with the COx concentration generated from the destruction of MEK and O3 were explored. The results for the decomposition of MEK and O3 at the room temperature indicated that the Mn dominant ZSM-5 catalysts showed better efficiency for the conversion of MEK and O3. The 5 wt% Mn/ZSM-5 outweighed the rest of them for the removal of MEK while the 5Mn1CuZSM showed the best catalytic reactivity for the conversion of O3 and the CO2 selectivity. It was ascertained that during the reaction time of catalyst and reactants of 120 min the Mn dominantly deposited bimetallic catalyst, 5Mn1CuZSM, was determined as the most effective for the removal of MEK and O3 due to the high capability of production of Mn3+ species and more available adsorbed oxygen sites compared to the other catalysts. Finally, the durability measurement for the 5Mn1CuZSM catalyst was performed together with the produced CO and CO2 concentration for 420 min.

Altered intrinsic cerebellar-cerebral functional connectivity is related to negative symptoms in patients with first-episode psychosis.

BACKGROUND: Negative symptoms in schizophrenia include cognitive and affective dysfunction, such as diminished expression and amotivation. Although the cerebellar posterior hemisphere and vermis are involved in cognitive and affective functioning, previous studies on the neural mechanism of negative symptoms have mostly been confined to the cerebral cortex. This study aimed to investigate whether resting-state cerebellar-cerebral functional connectivity (FC) is altered in first-episode psychosis (FEP) patients and whether this connectivity is related to negative symptoms. METHODS: Resting-state functional magnetic resonance images were obtained from 38 FEP patients and 100 healthy controls (HCs). Using the posterior hemisphere and vermis of the cerebellum as seeds, whole-brain FC was compared between FEP patients and HCs. As cerebellar-parietal cortex connectivity is associated with negative symptoms and sociocognitive dysfunctions in schizophrenia patients, its correlation with negative symptoms was explored in FEP patients. RESULTS: FEP patients showed hyperconnectivity between the cerebellum and bilateral frontal pole (FP), occipital pole, fusiform gyrus, right lingual gyrus, central opercular cortex, anterior middle temporal gyrus, precuneus, and subcallosal cortex. Hypoconnectivity was found between the cerebellum and left FP, right anterior supramarginal gyrus (aSMG), and cerebellum crus I. FC between the left crus II and right aSMG was negatively correlated with the severity of negative symptoms and diminished expression. CONCLUSIONS: Altered FC between the cerebellum and cerebral regions related to cognitive, affective, and sensory processing was found in FEP patients and was connected to negative symptoms. These results suggest that the cerebellum plays a role in the pathophysiology of negative symptoms in schizophrenia.

Bridging Big Data: Procedures for Combining Non-equivalent Cognitive Measures from the ENIGMA Consortium.

Investigators in neuroscience have turned to Big Data to address replication and reliability issues by increasing sample sizes, statistical power, and representativeness of data. These efforts unveil new questions about integrating data arising from distinct sources and instruments. We focus on the most frequently assessed cognitive domain - memory testing - and demonstrate a process for reliable data harmonization across three common measures. We aggregated global raw data from 53 studies totaling N = 10,505 individuals. A mega-analysis was conducted using empirical bayes harmonization to remove site effects, followed by linear models adjusting for common covariates. A continuous item response theory (IRT) model estimated each individual's latent verbal learning ability while accounting for item difficulties. Harmonization significantly reduced inter-site variance while preserving covariate effects, and our conversion tool is freely available online. This demonstrates that large-scale data sharing and harmonization initiatives can address reproducibility and integration challenges across the behavioral sciences.

Cortical gyrification differences between early- and late-onset obsessive-compulsive disorder: neurobiological evidence for neurodevelopmentally distinct subtypes.

BACKGROUND: Identifying more homogenous subtypes of patients with obsessive-compulsive disorder (OCD) using biological evidence is critical for understanding complexities of the disorder in this heterogeneous population. Age of onset serves as a useful subtyping scheme for distinguishing OCD into two subgroups that aligns with neurodevelopmental perspectives. The underlying neurobiological markers for these distinct neurodevelopmental differences can be identified by investigating gyrification changes to establish biological evidence-based homogeneous subtypes. METHODS: We compared whole-brain cortical gyrification in 84 patients with early-onset OCD, 84 patients with late-onset OCD, and 152 healthy controls (HCs) to identify potential markers for early neurodevelopmental deficits using the local gyrification index (lGI). Then, the relationships between lGI in clusters showing significant differences and performance in visuospatial memory and verbal fluency, which are considered trait-related neurocognitive impairments in OCD, were further examined in early-onset OCD patients. RESULTS: The early-onset OCD patients exhibited significantly greater gyrification than those with late-onset OCD patients and HCs in frontoparietal and cingulate regions, including the bilateral precentral, postcentral, precuneus, paracentral, posterior cingulate, superior frontal, and caudal anterior cingulate gyri. Moreover, impaired neurocognitive functions in early-onset OCD patients were correlated with increased gyrification. CONCLUSIONS: Our findings provide a neurobiological marker to distinguish the OCD population into more neurodevelopmentally homogeneous subtypes, which may contribute to the understanding of the neurodevelopmental underpinnings of an etiology in early-onset OCD consistent with the accumulated phenotypic evidence of greater neurodevelopmental deficits in early-onset OCD than in late-onset OCD.

Large-Scale Thalamocortical Triple Network Dysconnectivities in Patients With First-Episode Psychosis and Individuals at Risk for Psychosis.

BACKGROUND AND HYPOTHESIS: Aberrant thalamocortical connectivity and large-scale network interactions among the default mode network (DMN), salience network (SN), and executive control network (ECN) (ie, triple networks) have been regarded as critical in schizophrenia pathophysiology. Despite the importance of network properties and the role of the thalamus as an integrative hub, large-scale thalamocortical triple network functional connectivities (FCs) in different stages of the psychotic disorder have not yet been reported. STUDY DESIGN: Thirty-nine first-episode psychosis (FEP) patients, 75 individuals at clinical high risk (CHR) for psychosis, 46 unaffected relatives (URs) of schizophrenia patients with high genetic loading, and 110 healthy controls (HCs) underwent resting-state functional magnetic resonance imaging (rs-fMRI). Modular community detection was used to identify cortical and thalamic resting-state networks, and thalamocortical network interactions were compared across the groups. STUDY RESULTS: Thalamic triple networks included higher-order thalamic nuclei. Thalamic SN-cortical ECN FC was greater in the FEP group than in the CHR, UR, and HC groups. Thalamic DMN-cortical DMN and thalamic SN-cortical DMN FCs were greater in FEP and CHR participants. Thalamic ECN-cortical DMN and thalamic ECN-cortical SN FCs were greater in FEP patients and URs. CONCLUSIONS: These results highlight critical modulatory functions of thalamic triple networks and the shared and distinct patterns of thalamocortical triple network dysconnectivities across different stages of psychotic disorders. The current study findings suggest that large-scale thalamocortical triple network dysconnectivities may be used as an integrative biomarker for extending our understanding of the psychosis pathophysiology and for targeting network-based neuromodulation therapeutics.

Brain ageing in schizophrenia: evidence from 26 international cohorts via the ENIGMA Schizophrenia consortium.

Schizophrenia (SZ) is associated with an increased risk of life-long cognitive impairments, age-related chronic disease, and premature mortality. We investigated evidence for advanced brain ageing in adult SZ patients, and whether this was associated with clinical characteristics in a prospective meta-analytic study conducted by the ENIGMA Schizophrenia Working Group. The study included data from 26 cohorts worldwide, with a total of 2803 SZ patients (mean age 34.2 years; range 18-72 years; 67% male) and 2598 healthy controls (mean age 33.8 years, range 18-73 years, 55% male). Brain-predicted age was individually estimated using a model trained on independent data based on 68 measures of cortical thickness and surface area, 7 subcortical volumes, lateral ventricular volumes and total intracranial volume, all derived from T1-weighted brain magnetic resonance imaging (MRI) scans. Deviations from a healthy brain ageing trajectory were assessed by the difference between brain-predicted age and chronological age (brain-predicted age difference [brain-PAD]). On average, SZ patients showed a higher brain-PAD of +3.55 years (95% CI: 2.91, 4.19; I2 = 57.53%) compared to controls, after adjusting for age, sex and site (Cohen's d = 0.48). Among SZ patients, brain-PAD was not associated with specific clinical characteristics (age of onset, duration of illness, symptom severity, or antipsychotic use and dose). This large-scale collaborative study suggests advanced structural brain ageing in SZ. Longitudinal studies of SZ and a range of mental and somatic health outcomes will help to further evaluate the clinical implications of increased brain-PAD and its ability to be influenced by interventions.

Thalamic Connectivity System Across Psychiatric Disorders: Current Status and Clinical Implications.

The thalamic connectivity system, with the thalamus as the central node, enables transmission of the brain's neural computations via extensive connections to cortical, subcortical, and cerebellar regions. Emerging reports suggest deficits in this system across multiple psychiatric disorders, making it a unique network of high translational and transdiagnostic utility in mapping neural alterations that potentially contribute to symptoms and disturbances in psychiatric patients. However, despite considerable research effort, it is still debated how this system contributes to psychiatric disorders. This review characterizes current knowledge regarding thalamic connectivity system deficits in psychiatric disorders, including schizophrenia, bipolar disorder, major depressive disorder, and autism spectrum disorder, across multiple levels of the system. We identify the presence of common and distinct patterns of deficits in the thalamic connectivity system in major psychiatric disorders and assess their nature and characteristics. Specifically, this review assembles evidence for the hypotheses of 1) thalamic microstructure, particularly in the mediodorsal nucleus, as a state marker of psychosis; 2) thalamo-prefrontal connectivity as a trait marker of psychosis; and 3) thalamo-somatosensory/parietal connectivity as a possible marker of general psychiatric illness. Furthermore, possible mechanisms contributing to thalamocortical dysconnectivity are explored. We discuss current views on the contributions of cerebellar-thalamic connectivity to the thalamic connectivity system and propose future studies to examine its effects at multiple levels, from the molecular (e.g., glutamatergic) to the behavioral (e.g., cognition), to gain a deeper understanding of the mechanisms that underlie the disturbances observed in psychiatric disorders.

Relationship between meibomian gland loss in infrared meibography and meibum quality in dry eye patients.

BACKGROUND: In the present study, we evaluated the correlation between meibomian gland dropout and meibum quality in the same central 8 meibomian glands of the eyelid. METHODS: Ninety-nine eyes of 91 patients with dry eye were included in the study. Dropout of the 8 central meibomian glands of the eyelids was graded as 0, 1, 2, or 3, according to the dropout area. The meibum quality was graded as follows: grade 0, no secretion; 1, inspissated/toothpaste consistency; 2, cloudy liquid secretion; and 3, clear liquid secretion. For 68 eyes of 68 patients, correlation analysis between dropout and meibum quality was performed. To precisely analyze the direct correlation between meibomian gland dropout in meibography and meibum quality, we evaluated 31 eyes of 23 patients with focal dropout in meibography. RESULTS: The median (interquartile range) meiboscore was 1.0 (2.0) in the upper eyelids and 0.0 (1.0) in the lower eyelids. The median (interquartile range) meibum quality grade was 3.0 (1.0) in the upper eyelids and 1.0 (1.0) in the lower eyelids. No significant correlation between the meiboscore and meibum quality grade was detected in the upper (p =0.746) or lower (p =0.551) eyelids. Analysis of the direct correlation between meibomian gland dropout in meibography and meibum quality in patients with focal dropout (loss of 1 or 2 adjacent meibomian glands), however, indicated that meibomian glands with dropout secreted little to no meibum. CONCLUSIONS: Overall analysis revealed no relationship between meibomian gland dropout and meibum quality, but more detailed investigation of each meibomian gland alone revealed that meibomian glands with dropout secrete little to no meibum.

Hyaluronic acid hydrogels crosslinked via blue light-induced thiol-ene reaction for the treatment of rat corneal alkali burn.

To assess corneal inflammation from alkali chemical burns, we examined the therapeutic effects of in situ-forming hyaluronic acid (HA) hydrogels crosslinked via blue light-induced thiol-ene reaction on a rat corneal alkali burn model. Animals were divided into three groups (n = 7 rats per group): untreated, treated with 0.1% HA eye drops, and treated with crosslinked HA hydrogels. Crosslinking of HA hydrogel followed by the administration of HA eye drops and crosslinked HA hydrogels were carried out once a day from days 0-4. Corneal re-epithelialization, opacity, neovascularization, thickness, and histology were evaluated to compare the therapeutic effects of the three groups. Further investigation was conducted on the transparency of HA hydrogels to acquire the practical capabilities of hydrogel as a reservoir for drug delivery. Compared to untreated animals, animals treated with crosslinked HA hydrogels exhibited greater corneal re-epithelialization on days 1, 2, 4, and 7 post-injury (p = 0.004, p = 0.007, p = 0.008, and p = 0.034, respectively) and the least corneal neovascularization (p = 0.008). Histological analysis revealed lower infiltration of stromal inflammatory cells and compact collagen structure in crosslinked HA hydrogel-treated animals than in untreated animals. These findings corresponded with immunohistochemical analyses indicating that the expression of inflammatory markers such as α-SMA, MMP9, and IL1-ß was lower in animals treated with crosslinked HA hydrogels than untreated animals and animals treated only with 0.1% HA eye drops. With beneficial pharmacological effects such as re-epithelization and anti-inflammation, in situ-forming hyaluronic acid (HA) hydrogels may be a promising approach to effective drug delivery in cases of corneal burn injuries.

Evaluation of the meibomian glands using the tear interferometer wearing orthokeratology lenses.

BACKGROUND: To investigate the impact of orthokeratology wear on meibomian glands in Korean pediatric population using the tear interferometer. METHODS: Fifty-three orthokeratology wearers and 79 non-lens wearers were evaluated using the LipiView® II ocular surface interferometer which shows incomplete blink rate, average lipid layer thickness, and meiboscores. RESULTS: No significant differences in the incomplete blink rate and meiboscores for upper eyelids, but the lipid layer thickness and meiboscores for lower eyelids were significantly higher in the Ortho-K group than in the control group (p = 0.024 and 0.007, respectively). Correlation analysis showed no significant correlation between the duration of orthokeratology wear and the parameters measured by LipiView® (p > 0.05 for all). Among subgroups based on average duration of lens wear, the longer duration (≥ 24 months) subgroup showed higher meiboscores of lower eyelids (p = 0.011), but no other significant differences. CONCLUSIONS: Ortho-K wearers showed no significant differences in the incomplete blink rate and meiboscores of upper eyelids, but they were associated with increased LLT and higher meiboscores of lower eyelids. Thorough examination and close monitoring of orthokeratology wearers is necessary. Prospective and observational studies are needed to further elucidate the relationship between Orthokeratology and meibomian glands.

A Novel Intraocular Lens Simulator that Allows Patients to Experience the World Through Multifocal Intraocular Lenses Before Surgeries.

Purpose: The purpose of this study was to investigate whether the intraocular lens (IOL) simulator can simulate how the world appears to patients with multifocal IOLs by allowing the patients to see far and near objects through the IOL simulator. Methods: Twenty eyes from 20 patients (age = 50-70 years old) were included in the study. The IOL simulator we developed consists of a trial lens frame adapter, a lens tube, a concave lens, a spacer, a wet cell, and an IOL. We used two IOLs: Tecnis monofocal and Tecnis bifocal IOL (add +3.25 diopter [D]). Patients wore a trial lens frame with an IOL simulator on distant corrected trial lenses and underwent the following tests: defocus curve, satisfaction with distance and near vision, halo around the light, and near point accommodation (NPA). To check how the world appears to the patients through this simulator, a machine vision lens and a scientific camera were attached to the simulator, and far and near objects were photographed. Results: In the defocus curve of multifocal IOL, the visual acuity showed the second peak at -4 D. Compared to monofocal IOL, satisfaction with distant vision was slightly worse, more halos were felt, satisfaction with near vision was higher, and the NPA was shorter in multifocal IOL. In the scientific camera test, through the multifocal IOL, the waiting room was blurry, the halo around the ceiling light was prominent, and the characteristics on the near visual acuity chart were clear. Conclusion: Subjects could experience the functions of multifocal IOLs with our newly developed IOL simulator. Translational Relevance: This IOL simulator using geometric optics allows patients to experience the function of multifocal IOLs before cataract surgery.

Triple-Network Dysconnectivity in Patients With First-Episode Psychosis and Individuals at Clinical High Risk for Psychosis.

OBJECTIVE: In the triple-network model, the salience network (SN) plays a crucial role in switching between the default-mode network (DMN) and the central executive network (CEN). Aberrant patterns of triple-network connectivity have been reported in schizophrenia patients, while findings have been less consistent for patients in the early stages of psychotic disorders. Thus, the present study examined the connectivity among the SN, DMN, and CEN in first-episode psychosis (FEP) patients and individuals at clinical high risk (CHR) for psychosis. METHODS: Thirty-nine patients with FEP, 78 patients with CHR for psychosis, and 110 healthy controls (HCs) underwent resting-state functional magnetic resonance imaging. We compared the SN, DMN, and CEN connectivity patterns of the three groups. The role of the SN in networks with significant connectivity differences was examined by mediation analysis. RESULTS: FEP patients showed lower SN-DMN and SN-CEN (cluster-level F=5.83, false discovery rate [FDR] corrected-p=0.001) connectivity than HCs. There was lower SN-DMN connectivity (cluster-level F=3.06, FDR corrected-p=0.053) at a trend level in CHR subjects compared to HCs. Between HCs and FEP patients, mediation analysis showed that SN-DMN connectivity was a mediator between group and SN-CEN connectivity. Additionally, SN-CEN connectivity functioned as a mediator between group and SN-DMN connectivity. CONCLUSION: Aberrant connectivity between the SN and DMN/CEN suggests disrupted network switching in FEP patients, although CHR subjects showed trend-level SN-DMN dysconnectivity. Our findings suggest that dysfunctional triple-network dynamics centered on the SN can appear in patients in the early stages of psychotic disorders.

Intrinsic cerebellar functional connectivity of social cognition and theory of mind in first-episode psychosis patients.

Neuroimaging studies have revealed how intrinsic dysconnectivity among cortical regions of the mentalizing network (MENT) and the mirror neuron system (MNS) could explain the theory of mind (ToM) deficit in schizophrenia patients. However, despite the concurrent involvement of the cerebellum with the cortex in social cognition, the dysfunction in intrinsic interplay between the cerebellar nodes of MENT/MNS and the cortex in schizophrenia patients remains unknown. Thus, we aimed to investigate whether resting-state cerebello-cortical dysconnectivity exists in first-episode psychosis (FEP) patients in relationship with their ToM deficit. A total of 37 FEP patients and 80 healthy controls (HCs) underwent resting-state functional magnetic resonance imaging. Using a priori-defined cerebellar seeds that functionally connect to the MENT (right crus II) and MNS (right crus I), we compared cerebello-cortical functional connectivities (FCs) in FEP patients and HCs. Correlations between cerebello-parietal connectivities and ToM performance were investigated in FEP patients. FEP patients showed hyperconnectivity between the right crus II and anterior cingulate gyrus and between the right crus I and supplementary motor area, bilateral postcentral gyrus, and right central/parietal operculum (CO/PO). Hypoconnectivity was found between the right crus II and left supramarginal gyrus (SMG) in FEP patients. FCs between the right crus II and left SMG and between the right crus I and right CO/PO were significantly correlated with ToM scores in FEP patients. In accordance with the "cognitive dysmetria" hypothesis, our results highlight the importance of cerbello-cortical dysconnectivities in understanding social cognitive deficits in schizophrenia patients.

Polysorbate- and DNA-Mediated Synthesis and Strong, Stable, and Tunable Near-Infrared Photoluminescence of Plasmonic Long-Body Nanosnowmen.

Direct photoluminescence (PL) from metal nanoparticles (NPs) without chemical dyes is promising for sensing and imaging applications since this offers a highly tunable platform for controlling and enhancing the signals in various conditions and does not suffer from photobleaching or photoblinking. It is, however, difficult to synthesize metal NPs with a high quantum yield (QY), particularly in the near-infrared (NIR) region where deep penetration and reduced light scattering are advantageous for bioimaging. Herein, we designed and synthesized Au-Ag long-body nanosnowman structures (LNSs), facilitated by polysorbate 20 (Tween 20). The DNA-engineered conductive junction between the head and body parts results in a charge transfer plasmon (CTP) mode in the NIR region. The junction morphology can be controlled by the DNA sequence on the Au core, and polythymine and polyadenine induced thick and thin junctions, respectively. We found that the LNSs with a thicker conductive junction generates the stronger CTP peak and PL signal than the LNSs with a thinner junction. The Au-Ag LNSs showed much higher intensities in both PL and QY than widely studied Au nanorods with similar localized surface plasmon resonance wavelengths, and notably, the LNSs displayed high photostability and robust, sustainable PL signals under continuous laser exposure for >15 h. Moreover, the PL emission from Au-Ag LNSs could be imaged in a deeper scattering medium than fluorescent silica NPs. Finally, highly robust PL-based cell images can be obtained using Au-Ag LNSs without significant signal change while repetitively imaging cells. The results offer the insights in plasmonic NIR probe design, and show that chemical dye-free LNSs can be a very promising candidate with a high QY and a robust, reliable NIR PL signal for NIR sensing and imaging applications.

Mapping thalamocortical functional connectivity with large-scale brain networks in patients with first-episode psychosis.

Abnormal thalamocortical networks involving specific thalamic nuclei have been implicated in schizophrenia pathophysiology. While comparable topography of anatomical and functional connectivity abnormalities has been reported in patients across illness stages, previous functional studies have been confined to anatomical pathways of thalamocortical networks. To address this issue, we incorporated large-scale brain network dynamics into examining thalamocortical functional connectivity. Forty patients with first-episode psychosis and forty healthy controls underwent T1-weighted and resting-state functional magnetic resonance imaging. Independent component analysis of voxelwise thalamic functional connectivity maps parcellated the cortex into thalamus-related networks, and thalamic subdivisions associated with these networks were delineated. Functional connectivity of (1) networks with the thalamus and (2) thalamic subdivision seeds were examined. In patients, functional connectivity of the salience network with the thalamus was decreased and localized to the ventrolateral (VL) and ventroposterior (VP) thalamus, while that of a network comprising the cerebellum, temporal and parietal regions was increased and localized to the mediodorsal (MD) thalamus. In patients, thalamic subdivision encompassing the VL and VP thalamus demonstrated hypoconnectivity and that encompassing the MD and pulvinar regions demonstrated hyperconnectivity. Our results extend the implications of disrupted thalamocortical networks involving specific thalamic nuclei to dysfunctional large-scale brain network dynamics in schizophrenia pathophysiology.

Comparison of surgically induced astigmatism between anterior and total cornea in 2.2 mm steep meridian incision cataract surgery.

BACKGROUND: This study aimed to compare surgically induced astigmatism (SIA) on the anterior and total cornea during cataract surgery through a 2.2 mm steep meridian incision. METHODS: The study included 69 left eyes of 69 patients who had undergone cataract surgery. The 69 eyes were classified into three subgroups according to the preoperative steep meridian. Following phacoemulsification, an intraocular lens was inserted into the bag. The keratometric measurements were taken 12 months postoperatively, on the anterior cornea (automated keratometer and anterior keratometry [K] from a rotating Scheimpflug camera) and total cornea (equivalent K reading [EKR] 3.0 mm, EKR 4.5 mm, total corneal refractive power (TCRP) 2.0 mm ring, TCRP 3.0 mm zone, TCRP 4.0 mm zone). The SIA was analyzed for each parameter. RESULTS: On the double-angle polar plot, the summated vector mean values of SIA determined by the automated keratometer and Scheimpflug anterior K were 0.28 diopter (axis: 177°) and 0.37 diopter (axis: 175°) in with-the-rule (WTR) astigmatism; 0.03 diopter (axis: 156°) and 0.18 diopter (axis: 177°) in oblique astigmatism; 0.15 diopter (axis: 96°) and 0.17 diopter (axis: 73°) in against-the-rule (ATR) astigmatism. The mean SIAs on the total cornea ranged from 0.31 to 0.42 diopter in WTR astigmatism; from 0.16 to 0.27 diopter in oblique astigmatism; from 0.04 to 0.11 diopter in ATR astigmatism. Mean magnitude SIA ranged from 0.41 to 0.46 diopter on anterior corneal surface and 0.50 to 0.62 diopter on total cornea. J0 and J45 of the posterior cornea showed no significant changes after cataract surgery, and the changes in J0 and J45 did not show any statistical differences between the anterior and total cornea (all p > 0.05). CONCLUSIONS: There were no differences in the summed vector mean values of SIA between the anterior cornea and the total cornea.