Heterogeneous Brain Abnormalities in Schizophrenia Converge on a Common Network Associated With Symptom Remission.

BACKGROUND AND HYPOTHESIS: There is a huge heterogeneity of magnetic resonance imaging findings in schizophrenia studies. Here, we hypothesized that brain regions identified by structural and functional imaging studies of schizophrenia could be reconciled in a common network. STUDY DESIGN: We systematically reviewed the case-control studies that estimated the brain morphology or resting-state local function for schizophrenia patients in the literature. Using the healthy human connectome (n = 652) and a validated technique "coordinate network mapping" to identify a common brain network affected in schizophrenia. Then, the specificity of this schizophrenia network was examined by independent data collected from 13 meta-analyses. The clinical relevance of this schizophrenia network was tested on independent data of medication, neuromodulation, and brain lesions. STUDY RESULTS: We identified 83 morphological and 60 functional studies comprising 7389 patients with schizophrenia and 7408 control subjects. The "coordinate network mapping" showed that the atrophy and dysfunction coordinates were functionally connected to a common network although they were spatially distant from each other. Taking all 143 studies together, we identified the schizophrenia network with hub regions in the bilateral anterior cingulate cortex, insula, temporal lobe, and subcortical structures. Based on independent data from 13 meta-analyses, we showed that these hub regions were specifically connected with regions of cortical thickness changes in schizophrenia. More importantly, this schizophrenia network was remarkably aligned with regions involving psychotic symptom remission. CONCLUSIONS: Neuroimaging abnormalities in cross-sectional schizophrenia studies converged into a common brain network that provided testable targets for developing precise therapies.

Linking Personalized Brain Atrophy to Schizophrenia Network and Treatment Response.

BACKGROUND AND HYPOTHESIS: Schizophrenia manifests with marked heterogeneity in both clinical presentation and underlying biology. Modeling individual differences within clinical cohorts is critical to translate knowledge reliably into clinical practice. We hypothesized that individualized brain atrophy in patients with schizophrenia may explain the heterogeneous outcomes of repetitive transcranial magnetic stimulation (rTMS). STUDY DESIGN: The magnetic resonance imaging (MRI) data of 797 healthy subjects and 91 schizophrenia patients (between January 1, 2015, and December 31, 2020) were retrospectively selected from our hospital database. The healthy subjects were used to establish normative reference ranges for cortical thickness as a function of age and sex. Then, a schizophrenia patient's personalized atrophy map was computed as vertex-wise deviations from the normative model. Each patient's atrophy network was mapped using resting-state functional connectivity MRI from a subgroup of healthy subjects (n = 652). In total 52 of the 91 schizophrenia patients received rTMS in a randomized clinical trial (RCT). Their longitudinal symptom changes were adopted to test the clinical utility of the personalized atrophy map. RESULTS: The personalized atrophy maps were highly heterogeneous across patients, but functionally converged to a putative schizophrenia network that comprised regions implicated by previous group-level findings. More importantly, retrospective analysis of rTMS-RCT data indicated that functional connectivity of the personalized atrophy maps with rTMS targets was significantly associated with the symptom outcomes of schizophrenia patients. CONCLUSIONS: Normative modeling can aid in mapping the personalized atrophy network associated with treatment outcomes of patients with schizophrenia.

Neuroplasticity-Related Genes and Dopamine Receptors Associated with Regional Cortical Thickness Increase Following Electroconvulsive Therapy for Major Depressive Disorder.

Electroconvulsive therapy (ECT) is an effective neuromodulatory therapy for major depressive disorder (MDD). Treatment is associated with regional changes in brain structure and function, indicating activation of neuroplastic processes. To investigate the underlying neurobiological mechanism of macroscopic reorganization following ECT, we longitudinally (before and after ECT in two centers) collected magnetic resonance images for 96 MDD patients. Similar patterns of cortical thickness (CT) changes following ECT were observed in two centers. These CT changes were spatially colocalized with a weighted combination of genes enriched for neuroplasticity-related ontology terms and pathways (e.g., synaptic pruning) as well as with a higher density of D2/3 dopamine receptors. A multiple linear regression model indicated that the region-specific gene expression and receptor density patterns explained 40% of the variance in CT changes after ECT. In conclusion, these findings suggested that dopamine signaling and neuroplasticity-related genes are associated with the ECT-induced morphological reorganization.

Efficacy of twice-daily high-frequency repetitive transcranial magnetic stimulation on associative memory.

Objectives: Several studies have examined the effects of repetitive transcranial magnetic stimulation (rTMS) on associative memory (AM) but findings were inconsistent. Here, we aimed to test whether twice-daily rTMS could significantly improve AM. Methods: In this single-blind, sham-controlled experiment, 40 participants were randomized to receive twice-daily sham or real rTMS sessions for five consecutive days (a total of 16,000 pulses). The stimulation target in left inferior parietal lobule (IPL) exhibiting peak functional connectivity to the left hippocampus was individually defined for each participant. Participants completed both a picture-cued word association task and Stroop test at baseline and 1 day after the final real or sham rTMS session. Effects of twice-daily rTMS on AM and Stroop test performance were compared using two-way repeated measures analysis of variance with main factors Group (real vs. sham) and Time (baseline vs. post-rTMS). Results: There was a significant Group × Time interaction effect. AM score was significantly enhanced in the twice-daily real group after rTMS, but this difference could not survive the post hoc analysis after multiple comparison correction. Further, AM improvement in the twice-daily real group was not superior to a previously reported once-daily rTMS group receiving 8,000 pulses. Then, we combined the twice- and once-daily real groups, and found a significant Group × Time interaction effect. Post hoc analysis indicated that the AM score was significantly enhanced in the real group after multiple comparisons correction. Conclusion: Our prospective experiment did not show significant rTMS effect on AM, but this effect may become significant if more participants could be recruited as revealed by our retrospective analysis.

Minimal scanning duration for producing individualized repetitive transcranial magnetic stimulation targets.

This study aimed to determine the minimal scanning duration of functional magnetic resonance imaging (fMRI) for producing individualized repetitive transcranial magnetic stimulation (rTMS) targets that are superior to the group-level targets. This study included 30 healthy subjects and 20 depressive patients with high-sampled fMRI data (> 69 min). We computed suboptimal targets by gradually increasing the scanning duration beginning at 6 min. The suboptimal target connectivity and spatial distance to the optimal target (based on the full-duration scanning data) were compared to an anatomically fixed target from a group analysis (termed as the group target). These analyses were repeated for healthy subjects and depressive patients, as well as for target masks in the dorsolateral prefrontal cortex (DLPFC) and inferior parietal lobule (IPL). As the scanning duration increased, the suboptimal targets gradually approached the optimal targets in the healthy subjects. Compared with the group targets, the suboptimal targets in the DLPFC showed higher connectivity strength after 10 min of data collection and shorter spatial distance after 40 min. Similar results were found in major depressive patients. In the IPL, the minimal scanning duration decreased to 6 and 8 min for connectivity strength and distance, respectively. These findings provide an important reference for individualized target definition in terms of scanning duration, which may standardize connectivity-based personalized studies. Future research is needed to further validate the therapeutic effects of the approach.

A landmark-based approach to locate symptom-specific transcranial magnetic stimulation targets of depression.

Objective: Two subregions of the dorsolateral prefrontal cortex have been identified as effective repetitive transcranial magnetic stimulation (rTMS) targets for the "anxiosomatic" and "dysphoric" symptoms, respectively. We aimed to develop a convenient approach to locate these targets on the scalp. Materials and methods: In a discovery experiment, the two personalized targets were precisely identified on 24 subjects using a neuronavigation system. Then, a localized approach was developed based on individual scalp landmarks. This "landmark-based approach" was replicated and validated in an independent cohort (N = 25). Reliability of the approach was tested by calculating the correlation of both the inter-rater and intra-rater results. Validity was tested by comparing the mean distance between the personalized and landmark-based targets to the TMS spatial resolution (i.e., 5 mm). We further conducted a total of 24 sham rTMS sessions to estimate the misplacement between the coil center and target during a 10-min stimulation without neuronavigation. Results: The parameters of the "landmark-based approach" in the discovery experiment were replicated well in an independent cohort. Using discovery parameters, we successfully identified the symptom-specific targets in the independent cohort. Specifically, the mean distance between the personalized and landmark-based targets on the cortex was not significantly larger than 5 mm. However, the personalized and landmark-based targets distance exceeded 5 mm in more than 50% of subjects. During the 10-min sham rTMS session, the average coil misplacement was significantly larger than 5 mm. Conclusion: The "landmark-based approach" can conveniently and reliably locate the two symptom-specific targets at group level. However, the accuracy was highly varied at individual level and further improvement is needed.

Inverse micelle fabrication of ordered mesoporous manganese oxide and degradation of tetracycline hydrochloride.

Ordered mesoporous manganese oxides (MnOx) were synthesized using the modified inverse micelle method. The crystal structure and surface morphology were characterized by X-ray diffraction (XRD), scanning electron microscopy (SEM) and transmission electron microscopy (TEM). The element content and changes in surface valence of catalysts were analyzed by X-ray photoelectron spectroscopy (XPS). The MnOx were used to activate peroxymonosulfate (PMS) to degrade tetracycline hydrochloride (TCH). The catalytic activity of MnOx was enhanced at a calcination temperature of 350 °C (MM-3). The degradation efficiency of TCH in MM-3/PMS system was 87.89% in 180 min. Appropriate dosages of catalyst and PMS improve the degradation efficiency of TCH. This system showed a wide range of pH application (3-9). In the presence of coexisting ions and humic acid, the degradation efficiency of TCH was still above 80%. The results of free radical capture experiment and electron paramagnetic resonance (EPR) test proved that the system activates PMS to produce three types of free radicals: SO4-, OH and 1O2. Therefore, MM-3 is a promising catalyst for the degradation of TCH in practical wastewater treatment.

In-situ micro-Raman study of SnSe single crystals under atmosphere: Effect of laser power and temperature.

Single crystal of tin selenide (SnSe) was studied by micro-Raman spectroscopy under atmosphere conditions. The effect of varying the incident laser power on the sample up to 2 mW was analyzed. The Raman spectra showed that the number of all vibrational modes have not decreased or increased, but all peaks red-shifted and softened obviously as the laser power increased to the threshold value. The temperature-dependent micro-Raman study of the single crystal was carried out for illustrating thermal effect due to the high incident laser power. A new SnSe2 phase appeared at high temperature without vacuum and become the dominant phase at the surface of the crystal gradually because of oxidation. Detecting few amounts of SnSe2 crystals on the surface of single crystal shows the high sensitivity of Raman spectroscopy. High resolution transmission electron microscopy (HRTEM) was also used to confirm that the newly generated SnSe2 phase is precipitated by SnSe under high temperature oxidation conditions. To study the Raman spectra of low thermal conductivity materials under high temperature and non-vacuum conditions, lower incident laser power should be used to avoid the influence of additional thermal effects.

Podoplanin promotes cancer-associated thrombosis and contributes to the unfavorable overall survival in an ectopic xenograft mouse model of oral cancer.

BACKGROUND: Podoplanin (PDPN) is a transmembrane glycoprotein that mediates tumor cell-induced platelets aggregation in different cancer types. Emerging data indicate that PDPN is a marker for poor prognosis of human oral squamous cell carcinoma (OSCC). However, the functional impacts of PDPN on cancer formation and disease progression of OSCC remain to be elucidated. METHODS: The sublines of the OECM-1 oral cancer cells with PDPN knockdown or overexpression were established. The cellular characteristics and the ability to induce platelet aggregation of these cells lines were analyzed. An ectopic xenograft animal model by inoculating cancer cells into the anterior neck region of nude mice was established to investigate the functional impact of PDPN on disease progression and cancer-associated thrombosis of OSCC. RESULTS: PDPN promoted OSCC cell migration and invasion, but had no effect on cell proliferation in vitro and tumor growth in vivo. Co-incubation of PDPN-positive (PDPN+) OSCC cells with platelets induced platelet activation and aggregation. The mice bearing PDPN+ tumor had a decrease in overall survival despite that there was no gross appearance of distant metastasis. A speckled immunofluorescence staining pattern of platelet marker mCD41 was defined in the PDPN+ tumor sections and the intensity was greater than in the PDPN-low or negative tumor sections. Co-immunofluorescence staining of the tumor sections with mCD41 and the endothelial cell marker mCD31 further demonstrated that platelet aggregates were located in the lumen of blood vessel and were also distributed intratumorally in the mice bearing PDPN+ tumors. CONCLUSIONS: These data demonstrated that PDPN expression in the cancer cells is associated with high risk of thrombosis, leading to unfavorable overall survival of the mice. This study provides new insights into the functions of PDPN in cancer-associated thrombosis and in the pathophysiology of OSCC.

Facile inverse micelle fabrication of magnetic ordered mesoporous iron cerium bimetal oxides with excellent performance for arsenic removal from water.

In this study, magnetic ordered mesoporous Fe/Ce bimetal oxides (OMICs) were successfully synthesized via the modified sol-gel-based inverse micelle method. The textural/structure properties, surface chemistry and adsorption behavior of OMICs could be easily adjusted by using the calcination temperature. The sintering of samples would decrease the surface area, while expand the pore and crystallite size, which resulted in the formation of highly ordered inner-connected structure. Compared with pure mesoporous iron oxides (MI) and mesoporous cerium oxides (MC), this ordered mesoporous iron-cerium bimetal oxides (OMIC-3, 450 °C) exhibited remarkable arsenic adsorption performance. The maximum adsorption capacities of As(III) and As(V) for OMIC-3 were 281.34 and 216.72 mg/g, respectively, and both As(III)/As(V) adsorption kinetics were well described by the pseudo-second order. The ionic strength and coexisting ions (except SiO32- and PO43-) did not affect arsenic removal, while humic acid (HA) significantly influenced on the arsenic removal even at a lower concentration. The adsorption mechanism study revealed that both the surface charge and surface M-OH groups of OMIC-3 were played the key roles in arsenic removal. The reusable property suggested that this magnetic OMIC-3 was a promising excellent adsorbent for decontamination of arsenic-polluted (especially As(III)-polluted) wastewater.

Simultaneous removal of As(V)/Cr(VI) and acid orange 7 (AO7) by nanosized ordered magnetic mesoporous Fe-Ce bimetal oxides: Behavior and mechanism.

In this study, nanosized ordered magnetic mesoporous Fe-Ce bimetal oxides (Nanosized-MMIC) with highly well-ordered inner-connected mesostructure were successfully synthesized through the KIT-6 template method. This Nanosized-MMIC displayed excellent adsorption capacities for As(V), Cr(VI) and AO7, and the corresponding calculated maximum adsorption capacities of material were 111.17, 125.28 and 156.52 mg/g, respectively. As(V) and Cr(VI) removal by Nanosized-MMIC were slightly dependent on the ionic strength but highly solution pH-dependent, the coexistent silicate and phosphate ions competed remarkably with both As(V) and Cr(VI) for the adsorption active site. Mechanisms indicated As(V) and Cr(VI) formed inner-sphere complexes on Nanosized-MMIC interface via the electrostatic interaction and surface complexation, while the total organic carbon (TOC) change demonstrated that AO7 could be removed completely and no organic intermediates formed through the adsorption process. In addition, Nanosized-MMIC also possessed superior adsorption performance in As(V)/Cr(VI)-AO7 binary systems, and the reusable and regeneration properties indicated that the obtained nanomaterials could maintain at a comparatively high level after several recycling. Finally, fixed-bed experiments suggested the Nanosized-MMIC was expected to have a promising excellent nano-adsorbent with high application potential for co-existed toxic heavy metals and organic dyes removal in practical wastewater treatment.

Short-term prediction of extremely hot days in summer due to climate change and ENSO and related attributable mortality.

Summer days with extremely hot temperatures in Taiwan have been increasing for the past few decades, and this continuing trend is expected to worsen heat-related mortality. To mitigate the corresponding health impacts, in this study, we developed a statistical state-space model to predict the number of extremely hot days in June-September for the next year. Based on historical data from 1951 to 2017, we estimated the climate change trend after adjusting for the nonlinear lagged effect of the Niño 3.4 index. We then developed a predictive state-space model using these two primary factors and adjusting for residual autocorrelations. Validation results comparing the extremely hot days observed over 2015-2017 with predictions showed that 86% of the average prediction errors were within 4 days of the observations. To assess the health impacts, we applied the model to the projection of heat-attributable mortality (AM) in 2018 by adopting a comparative risk assessment (CRA) approach with the reference period of 2001-2010. The results showed that the Taipei metropolitan area in northern Taiwan is the most affected region with AM of 1501 deaths from all-causes, followed by Taichung in central Taiwan with 490 deaths. The prediction model and the CRA projection provide both a tool and guidance for public health administrators to address the imminent threat posed by climate change.

Circulating Epithelial Cell Characterization and Correlation with Remission and Survival in Patients with Thyroid Cancer.

BACKGROUND: Thyroid cancer is the most common endocrine tumor and generally has relatively good clinical outcomes. However, 15-20% of patients ultimately develop recurrence or disease-related death. The appropriate prognostic factors for thyroid cancer are still elusive. This study evaluated whether the number of circulating tumor cells/circulating epithelial cells (CECs) expressing either epithelial cell adhesion molecule (EpCAM), podoplanin (PDPN), or thyrotropin receptor (TSHR) is related to remission and disease-specific mortality (DSM) of patients with thyroid cancer. METHODS: Blood samples were collected from patients (n = 128) after thyroidectomy or radioactive iodide therapy. CECs were enriched by lysis of red blood cells and depletion of leukocytes. Subtyping and quantification of the enriched cells were performed with immunofluorescence staining using antibodies against EpCAM, TSHR, and PDPN, respectively. Whether the number of a specific subtype of CECs is related to remission and DSM of patients was determined by univariate and multivariate analyses. RESULTS: The EpCAM+-CECs, TSHR+-CECs, and PDPN+-CECs counts for patients in the non-remission group (n = 43) were significantly higher when compared to the remission group (n = 85; p < 0.001). Receiver operating characteristic analysis showed that the number of EpCAM+-CECs, TSHR+-CECs, and PDPN+-CECs was able to distinguish the status of remission from non-remission. The cutoff point for EpCAM+-CECs, TSHR+-CECs, and PDPN+-CECs was 40, 47, and 14 (cells/mL), with the accuracy of the assay equivalent to 80.4%, 76.6%, and 77.3%, respectively. On the other hand, the number of EpCAM+-CECs (p < 0.001), PDPN+-CECs (p = 0.013), and TSHR+-CECs (p < 0.001) for patients in the DSM group (n = 17) was significantly higher when compared to the patients who survived (n = 111). Receiver operating characteristic analysis showed that EpCAM+-CECs, TSHR+-CECs, and PDPN+-CECs counts were able to distinguish mortality from survival status. The cutoff point for EpCAM+-CECs, TSHR+-CECs, and PDPN+-CECs was 27, 25, and 9 (cells/mL), with the accuracy of the assay equivalent to 69.5%, 67.2%, and 68.5%, respectively. CONCLUSIONS: CEC testing is a useful tool for analysis of overall survival and remission status of patients with thyroid cancer. Implementation of CEC testing into routine clinical test may be worthy to consider for patient clinical care.

Study on the Effect of the Three-Dimensional Electrode in Degradation of Methylene Blue by Lithium Modified Rectorite.

This study presents the electrochemical degradation of methylene blue (MB) wastewater in a synthetic solution using three-dimensional particle electrodes. The novel particle electrodes were fabricated in this work using the lithium modified rectorite (Li-REC). The adsorption property of the fabricated particle electrodes was studied in a series of experiments. The optimum electrochemical operating conditions of plate distance, cell voltage, and concentration of electrolyte were 2 cm, 9 V, and 0.06 mol L-1, respectively. It was also found that microwave irradiation can effectively improve the adsorption property and electrical property of the fabricated electrodes. In addition, the scanning electron microscope (SEM) of the fabricated electrodes was investigated. The experimental results revealed the order of adsorption property and electrical property of the fabricated electrodes. So, fabricated electrodes are not only of low cost and mass produced, but also efficient to achieve decolorization of MB solution.

Study on the effect of electrochemical dechlorination reduction of hexachlorobenzene using different cathodes.

Hexachlorobenzene (HCB) is a persistent organic pollutant and poses great threat on ecosystem and human health. In order to investigate the degradation law of HCB, a RuO2/Ti material was used as the anode, meanwhile, zinc, stainless steel, graphite, and RuO2/Ti were used as the cathode, respectively. The gas chromatography (GC) was used to analyze the electrochemical products of HCB on different cathodes. The results showed that the cathode materials significantly affected the dechlorination efficiency of HCB, and the degradation of HCB was reductive dechlorination which occurred only on the cathode. During the reductive process, chlorine atoms were replaced one by one on various intermediates such as pentachlorobenzene, tetrachlorobenzene, and trichlorobenzene occurred; the trichlorobenzene was obtained when zinc was used as cathode. The rapid dechlorination of HCB suggested that the electrochemical method using zinc or stainless steel as cathode could be used for remediation of polychlorinated aromatic compounds in the environment. The dechlorination approach of HCB by stainless steel cathode could be proposed.