MACTFusion: Lightweight Cross Transformer for Adaptive Multimodal Medical Image Fusion.

Multimodal medical image fusion aims to integrate complementary information from different modalities of medical images. Deep learning methods, especially recent vision Transformers, have effectively improved image fusion performance. However, there are limitations for Transformers in image fusion, such as lacks of local feature extraction and cross-modal feature interaction, resulting in insufficient multimodal feature extraction and integration. In addition, the computational cost of Transformers is higher. To address these challenges, in this work, we develop an adaptive cross-modal fusion strategy for unsupervised multimodal medical image fusion. Specifically, we propose a novel lightweight cross Transformer based on cross multi-axis attention mechanism. It includes cross-window attention and cross-grid attention to mine and integrate both local and global interactions of multimodal features. The cross Transformer is further guided by a spatial adaptation fusion module, which allows the model to focus on the most relevant information. Moreover, we design a special feature extraction module that combines multiple gradient residual dense convolutional and Transformer layers to obtain local features from coarse to fine and capture global features. The proposed strategy significantly boosts the fusion performance while minimizing computational costs. Extensive experiments, including clinical brain tumor image fusion, have shown that our model can achieve clearer texture details and better visual quality than other state-of-the-art fusion methods.

Hemodynamics and arrhythmia disorder caused by lithium poisoning: A case report. / 锂中毒导致心律失常、血流动力学障碍1例.

Bipolar affective disorder refers to a category of mood disorders characterized clinically by the presence of both manic or hypomanic episodes and depressive episodes. Lithium stands out as the primary pharmacological intervention for managing bipolar affective disorder. However, its therapeutic dosage closely approaches toxic levels. Toxic symptoms appear when the blood lithium concentration surpasses 1.4 mmol/L, typically giving rise to gastrointestinal and central nervous system reactions. Cardiac toxicity is rare but serious in cases of lithium poisoning. The study reports a case of a patient with bipolar affective disorder who reached a blood lithium concentration of 6.08 mmol/L after the patient took lithium carbonate sustained-release tablets beyond the prescribed dosage daily and concurrently using other mood stabilizers. This resulted in symptoms such as arrhythmia, shock, impaired consciousness, and coarse tremors. Following symptomatic supportive treatment, including blood dialysis, the patient's physical symptoms gradually improved. It is necessary for clinicians to strengthen the prevention and recognition of lithium poisoning.

Glutamatergic basis of antipsychotic response in first-episode psychosis: a dual voxel study of the anterior cingulate cortex.

A subgroup of patients with schizophrenia is believed to have aberrant excess of glutamate in the frontal cortex; this subgroup is thought to show poor response to first-line antipsychotic treatments that focus on dopamine blockade. If we can identify this subgroup early in the course of illness, we can reduce the repeated use of first-line antipsychotics and potentially stratify first-episode patients to intervene early with second-line treatments such as clozapine. The use of proton magnetic resonance spectroscopy (1H-MRS) to measure glutamate and Glx (glutamate plus glutamine) may provide a means for such a stratification. We must first establish if there is robust evidence linking elevations in anterior cingulate cortex (ACC) glutamate metabolites to poor response, and determine if the use of antipsychotics worsens the glutamatergic excess in eventual nonresponders. In this study, we estimated glutamate levels at baseline in 42 drug-naive patients with schizophrenia. We then treated them all with risperidone at a standard dose range of 2-6 mg/day and followed them up for 3 months to categorize their response status. We expected to see baseline "hyperglutamatergia" in nonresponders, and expected this to worsen over time at the follow-up. In line with our predictions, nonresponders had higher glutamate than responders, but patients as a group did not differ in glutamate and Glx from the healthy control (HC) group before treatment-onset (F1,79 = 3.20, p = 0.046, partial η2 = 0.075). Glutamatergic metabolites did not change significantly over time in both nonresponders and responders over the 3 months of antipsychotic exposure (F1,31 = 1.26, p = 0.270, partial η2 = 0.039). We conclude that the use of antipsychotics without prior knowledge of later response delays symptom relief in a subgroup of first-episode patients, but does not worsen the glutamatergic excess seen at the baseline. Given the current practice of nonstratified use of antipsychotics, longer-time follow-up MRS studies are required to see if improvement in symptoms accompanies a dynamic shift in glutamate profile.

The month of walking alone and BDNF level differ between drug-naive first-episode schizophrenia patients and healthy controls.

Introduction: Schizophrenia is a neurodevelopmental disorder, characterized by impairment in reasoning, affectivity, and social relationships. Previous studies have shown delayed motor development and Brain-Derived Neurotrophic Factor (BDNF) level change in individuals with schizophrenia. We researched the month of walking alone (MWA) and BDNF level between drug-naive first-episode schizophrenia patients (FEP) and healthy control (HC), as well as how they behave in neurocognitive function and severity of symptoms. Predictors of schizophrenia were further explored too. Methods: We researched the MWA and BDNF levels between FEP and HCs in the Second Xiangya Hospital of Central South University from August 2017 to January 2020, as well as how they behave in neurocognitive function and the severity of symptoms. A binary logistic regression analysis was used to examine the risk factors affecting the onset and treatment outcome of schizophrenia. Results: We find that FEP showed a walking delay and lower BDNF levels compared to HCs, which were associated with cognitive impairment and severity of symptoms. According to the difference and correlation analysis results, and combined with the appropriate application conditions for binary logistic regression, Wechsler Intelligence Scale Picture completion, Hopkins Verbal Learning Test-Revised, and Trail Making Test: part A were added to the binary logistic regression analysis to distinguish FEP and HCs. Conclusion: Our study has shown delayed motor development and changes in BDNF levels in schizophrenia, extending insight into the early identification of patients with schizophrenia versus healthy populations.

Neuronal dysfunction in individuals at early stage of schizophrenia, A resting-state fMRI study.

Schizophrenia has been associated with abnormal intrinsic brain activity, involving various cognitive impairments. Qualitatively similar abnormalities are seen in individuals at ultra-high risk (UHR) for psychosis. In this study, resting-state fMRI (rs-fMRI) data were collected from 44 drug-naïve first-episode schizophrenia (Dn-FES) patients, 48 UHR individuals, and 40 healthy controls (HCs). The fractional amplitude of low-frequency fluctuations (fALFF), regional homogeneity (ReHo), and functional connectivity (FC), were performed to evaluate resting brain function. A support vector machine (SVM) was applied for classification analysis. Compared to HCs, both clinical groups showed increased fALFF in the central executive network (CEN), decreased ReHo in the ventral visual pathway (VVP) and decreased FC in temporal-sensorimotor regions. Excellent performance was achieved by using fALFF value in distinguishing both FES (sensitivity=83.21%, specificity=80.58%, accuracy=81.37%, p=0.009) and UHR (sensitivity=75.88%, specificity=85.72%, accuracy=80.72%, p<0.001) from HC group. Moreover, the study highlighted the importance of frontal and temporal alteration in the pathogenesis of schizophrenia. However, no fMRI features were observed that could well distinguish Dn-FES from UHR group. To conclude, fALFF in the CEN may provide potential power for identifying individuals at the early stage of schizophrenia and the alteration in the frontal and temporal lobe may be important to these individuals.

Short-chain fatty acids in patients with schizophrenia and ultra-high risk population.

Background: Individuals who experience the prodromal phase of schizophrenia (SCZ), a common and complex psychiatric disorder, are referred to as ultra-high-risk (UHR) individuals. Short-chain fatty acid (SCFA) is imperative in the microbiota-gut-brain axis and brain function. Accumulating amount of evidence shows the connections between psychiatric disorders and SCFAs. This study aims to explore the underlying roles SCFAs play in SCZ by investigating the association of alterations in SCFAs concentrations with common cognitive functions in both the SCZ and UHR populations. Methods: The study recruited 59 SCZ patients (including 15 participants converted from the UHR group), 51 UHR participants, and 40 healthy controls (HC) within a complete follow-up of 2 years. Results of cognitive functions, which were assessed by utilizing HVLT-R and TMT, and serum concentrations of SCFAs were obtained for all participants and for UHR individuals at the time of their conversion to SCZ. Results: Fifteen UHR participants converted to SCZ within a 2-year follow-up. Valeric acid concentration levels were lower in both the baseline of UHR individuals whom later converted to SCZ (p = 0.046) and SCZ patients (p = 0.036) than the HC group. Additionally, there were lower concentrations of caproic acid in the baseline of UHR individuals whom later transitioned to SCZ (p = 0.019) and the UHR group (p = 0.016) than the HC group. Furthermore, the caproic acid levels in the UHR group are significantly positively correlated with immediate memory (r = 0.355, p = 0.011) and negatively correlated with TMT-B (r = -0.366, p = 0.009). Significant differences in levels of acetic acid, butyric acid and isovaleric acid were absent among the three groups and in UHR individuals before and after transition to SCZ. Conclusion: Our study suggests that alterations in concentrations of SCFAs may be associated with the pathogenesis and the cognitive impairment of schizophrenia. Further researches are warranted to explore this association. The clinical implications of our findings were discussed.

Alteration of a brain network with stable and strong functional connections in subjects with schizophrenia.

It is widely accepted that there are some common network patterns in the human brain. However, the existence of stable and strong functional connections in the human brain and whether they change in schizophrenia is still a question. By setting 1% connections with the smallest coefficient of variation, we found a widespread brain functional network (frame network) in healthy people(n = 380, two datasets from public databases). We then explored the alterations in a medicated group (60 subjects with schizophrenia vs 71 matched controls) and a drug-naive first-episode group (68 subjects with schizophrenia vs 45 matched controls). A linear support vector classifier (SVC) was constructed to distinguish patients and controls using the medicated patients' frame network. We found most frame connections of healthy people had high strength, which were symmetrical and connected the left and right hemispheres. Conversely, significant differences in frame connections were observed in both patient groups, which were positively correlated with negative symptoms (mainly language dysfunction). Additionally, patients' frame network were more left-lateralized, concentrating on the left frontal lobe, and was quite accurate at distinguishing medicated patients from controls (classifier accuracy was 78.63%, sensitivity was 86.67%, specificity was 76.06%, and the area under the curve (AUC) was 0.83). Furthermore, the results were repeated in the drug-naive set (accuracy was 84.96%, sensitivity was 85.29%, specificity was 88.89%, and AUC was 0.93). These findings indicate that the abnormal pattern of frame network in subjects with schizophrenia might provide new insights into the dysconnectivity in schizophrenia.

Abnormal Brain Network Interaction Associated With Positive Symptoms in Drug-Naive Patients With First-Episode Schizophrenia.

Positive symptoms are marked features of schizophrenia, and emerging evidence has suggested that abnormalities of the brain network underlying these symptoms may play a crucial role in the pathophysiology of the disease. We constructed two brain functional networks based on the positive and negative correlations between positive symptom scores and brain connectivity in drug-naive patients with first-episode schizophrenia (FES, n = 45) by using a machine-learning approach (connectome-based predictive modeling, CPM). The accuracy of the model was r = 0.47 (p = 0.002). The positively and negatively associated network strengths were then compared among FES subjects, individuals at genetic high risk (GHR, n = 41) for schizophrenia, and healthy controls (HCs, n = 48). The results indicated that the positively associated network contained more cross-subnetwork connections (96.02% of 176 edges), with a focus on the default-mode network (DMN)-salience network (SN) and the DMN-frontoparietal task control (FPT) network. The negatively associated network had fewer cross-subnetwork connections (71.79% of 117 edges) and focused on the sensory/somatomotor hand (SMH)-Cingulo opercular task control (COTC) network, the DMN, and the visual network with significantly decreased connectivity in the COTC-SMH network in FES (FES < GHR, p = 0.01; FES < HC, p = 0.01). Additionally, the connectivity strengths of the right supplementary motor area (SMA) (p < 0.001) and the right precentral gyrus (p < 0.0001) were reduced in FES. To the best of our knowledge, this is the first study to generate two brain networks associated with positive symptoms by utilizing CPM in FES. Abnormal segregation, interactions of brain subnetworks, and impaired SMA might lead to salience attribution abnormalities and, thus, as a result, induce positive symptoms in schizophrenia.

Fire Performance of FRP-RC Flexural Members: A Numerical Study.

Fiber-reinforced polymer (FRP) bars are increasingly used as a substitute for steel reinforcements in the construction of concrete structures, mainly due to their excellent durability characteristics. When FRP bar-reinforced concrete (referred to as FRP-RC for simplicity) members are used in indoor applications (e.g., in buildings), the fire performance of FRP-RC members needs to be appropriately designed to satisfy safety requirements. The bond behavior between the FRP bar and the surrounding concrete governs the composite action between the two materials and the related structural performance of the FRP-RC flexural member that will be affected when exposed to fire. However, there is a lack of reliable numerical models in the literature to quantify the effect of bond degradations of the FRP bar-to-concrete interface at high temperatures on the fire performance of FRP-RC flexural members. This paper presents a three-dimensional (3D) finite element (FE) model of FRP-RC flexural members exposed to fire and appropriately considers the temperature-dependent bond degradations of the FRP bar-to-concrete interface at high temperatures. In addition, the thermal properties of concrete and FRP bars are considered in the heat transfer analysis to predict the cross-sectional temperatures of the FRP-RC members under fire exposure. In the FE model, the mechanical properties and constitutive laws of concrete and FRP bars at high temperatures in addition to the bond degradations between them have been properly defined, thereby accurately predicting the global and local structural responses of the FRP-RC members under fire exposure. The proposed FE model has been validated by comparing the FE predictions (both temperature and midspan deflection responses during fire exposure) and the full-scale fire test results reported in the literature. The validated FE model is then used to study the effects of bond degradations on the global and local structural responses of the FRP-RC members under fire exposure. It is proved that the temperature-dependent bond degradations need to be considered to achieve accurate predictions of the failure mode and deflection responses.

IL-17 and TNF-ß: Predictive biomarkers for transition to psychosis in ultra-high risk individuals.

Background: Dysregulation of immunity, such as levels of inflammatory factors, has been regarded as a sign of schizophrenia. Changes in cytokine levels are not only described in the early onset of disease, but also observed in ultra-high risk (UHR) individuals. This study aimed to investigate the potential of cytokines as biomarkers for psychotic disorders and in individuals at UHR of developing a psychotic disorder in the future. Methods: The Luminex liquid chip technology was used to detect the concentrations of Interferon-gamma (INF-γ), Interleukin (IL)-2, Interleukin (IL)-4, Interleukin (IL)-6, Interleukin (IL)-17, Interleukin-1beta (IL-1ß), and Tumor Necrosis Factor-beta (TNF-ß) in the plasma of all subjects. Meanwhile, the plasma level of Tumor Necrosis Factor-Alpha (TNF-α) was measured with the enzyme-linked immunosorbent assay (ELISA) kits. Then, the levels of these cytokines were compared among patients with Drug-naïve first-episode schizophrenia (FES; n = 40), UHR population (UHR; n = 49), and healthy controls (HCs; n = 30). Baseline cytokine levels were compared among UHR individuals who later transitioned (UHR-T; n = 14), those who did not transition (UHR-NT; n = 35), and HCs (n = 30). Results: Our analysis results showed that IL-1ß levels were significantly higher in UHR group than HC group (p = 0.015). Meanwhile, TNF-α concentration was significantly increased in FES group compared with HC group (p = 0.027). IL-17 (p = 0.04) and TNF-ß (p = 0.008) levels were significantly higher in UHR-T group compared with UHR-NT group. Conclusion: In conclusion, our findings suggest that the immuno-inflammatory activation level is increased in the early stage of psychosis before psychotic conversion and the Drug-naïve FES. IL-1ß and TNF-α are the representatives of the specific biomarkers for UHR and FES, respectively. IL-17 and TNF-ß may be the potential selective predictive biomarkers for future transition in UHR individuals.

Abnormal neurobiochemical metabolites in the first- episode schizophrenia and clinical high-risk population. / 首发精神分裂症及临床高危人群脑神经生化代谢物异常.

OBJECTIVES: To explore the metabolite characteristics in medial prefrontal cortex (mPFC) by 1H magnetic resonance spectroscopy (1H-MRS) in the first-episode schizophrenia (FES) and clinical high-risk (CHR) people. METHODS: A total of 46 patients with the first-episode schizophrenia (FES), 49 people with clinical high risk (CHR), 61 people with genetic high risk (GHR), and 58 healthy controls (HC) were enrolled. The levels of N-acetylaspartylglutamate+N-acetylaspartate (tNAA), choline-containing compounds (Cho) and myo-inositol (MI), glutamate+glutamine (Glx) in medial prefrontal cortex were measured by single-voxel 1H-MRS. The clinical symptoms were evaluated in the FES group and the CHR group. Continuous performance test (CPT) were carried out to assess the visual and auditory accuracy and reaction time in the 4 groups. RESULTS: There were significant differences in Glx, tNAA, and MI concentrations among 4 groups (all P<0.05). Compared with the HC group, the FES group showed lower level of MI and Glx. The levels of Glx and tNAA in the CHR group were significantly lower than those in the GHR group (all P<0.05). The visual and auditory accuracies of CPT in the FES group were significantly lower than those in the HC group (P<0.05). In the FES group, Glx was negatively correlated with the reaction time of vision (r=-0.41, P=0.05). CONCLUSIONS: The decreased levels of MI and Glx in the FES patients suggest that there may be glial functional damage and glutamatergic transmitter dysfunction in the early stage of the disease. The compensatory increase of metabolites may be a protective factor for schizophrenia in the genetic individuals.

Anterior Cingulate Cortex Glutamate Levels Are Related to Response to Initial Antipsychotic Treatment in Drug-Naive First-Episode Schizophrenia Patients.

The glutamatergic system has previously been shown to be involved in the pathophysiology of schizophrenia and the mechanisms of action of antipsychotic treatment. The present study aimed to investigate the relationship between the levels of glutamate (Glu) or Glu/total creatine (Glu/Cr+PCr) in the anterior cingulate cortex (ACC) and psychiatric symptoms as well as the response to antipsychotic treatment. We performed proton magnetic resonance spectroscopy (1H-MRS) to measure Glu and Glu/Cr+PCr in the ACC of 35 drug-naïve first-episode schizophrenia (FES) patients and 40 well-matched healthy controls (HCs). After scanning, we treated the patients with risperidone for eight weeks. Remission status was based on the Positive and Negative Syndrome Scale (PANSS) scores at week 8. At baseline, there were no significant differences in the levels of Glu or Glu/Cr+PCr in the ACC between drug-naïve FES patients and HCs. Lower baseline levels of Glu/Cr+PCr but not Glu in the ACC were associated with more severe negative symptoms of schizophrenia. Compared to the remission group (RM), the non-remission group (NRM) had lower baseline ACC Glu levels (P < 0.05). Our results suggest that ACC Glu levels may be related to the severity of symptoms in the early stages of schizophrenia and therefore may be a marker with which to evaluate the treatment effect of antipsychotics in schizophrenia patients.

Decreased regional homogeneity and increased functional connectivity of default network correlated with neurocognitive deficits in subjects with genetic high-risk for schizophrenia: A resting-state fMRI study.

The complex symptoms of schizophrenia (SCZ) have been associated with dysfunction of the default mode network (DMN). Subjects at genetic high risk (GHR) for SCZ exhibit similar but milder brain abnormalities. This study aimed to investigate functional alterations of DMN from the local to the whole and their relationships with cognitive deficits in GHR subjects. 42 GHR subjects and 38 matched healthy controls (HC) were studied by resting-state functional magnetic resonance imaging (rs-fMRI). Regional homogeneity (ReHo) analysis was performed to measure the local brain function of the DMN, derived by the group independent component analysis, and areas with aberrant ReHo were used as seeds in functional connectivity (FC). Compared with the HC group, the GHR group exhibited significantly decreased ReHo and increased FC in the fronto-limbic-striatal system within the DMN. Furthermore, a significant negative correlation was found between decreased ReHo in the right superior frontal gyrus and the delayed recall in GHR subjects. Our findings revealed decreased local function and hyper-connectivity in the fronto-limbic-striatal system of the DMN in GHR subjects, which is associated with cognitive deficits. This may improve our understanding of the neurophysiological endophenotypes of SCZ and the neural substrate underlying the cognitive deficits of the disease.

Olfactory and cognitive functions in Chinese individuals at clinical high risk for psychosis.

The abnormal olfactory function has been regarded as a sign in psychosis. To confirm the theory that olfactory and cognitive functions are deficient in Chinese cohort with clinical high risk state of psychosis, 19 individuals at clinical high risk for psychosis (CHRs) and 37 healthy controls (HCs) were recruited. The CHRs scored significantly lower than the HCs in the olfactory identification test and all other cognitive tests. Our findings suggest that olfactory dysfunction may be an early change of psychosis.