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Purpose: The tonsoku-like DNA repair protein (TONSL) encoded by the TONSL gene, located on chromosome 8q24.3, is crucial for repairing DNA double-strand breaks through homologous recombination. However, TONSL overexpression in lung adenocarcinoma (LUAD) promotes tumor development, leading to a poor prognosis., Methods: TONSL was verified as a reliable prognostic marker for LUAD using bioinformatics, and clinical features related to LUAD prognosis were screened from the TCGA database to establish the relationship between risk factors and TONSL expression. In addition, TONSL expression in normal and LUAD tissues was verified using real-time quantitative polymerase chain reaction and immunohistochemistry. To elucidate the possible functions of TONSL, TONSL-related differentially expressed genes were screened, and functional enrichment analysis was performed. Subsequently, siRNA was used to knock down TONSL expression in lung cancer cells for cytobehavioral experiments. The effects of TONSL expression on tumor immune escape were analyzed using the ESTIMATE algorithm and tumor immune-infiltration analysis. In addition, the half-maximal inhibitory concentration of LUAD with varying TONSL expression levels in response to first-line chemotherapeutic drugs and epidermal growth factor receptor-tyrosine kinase inhibitors was analyzed for drug sensitivity., Results: Up-regulation of TONSL in LUAD promotes the proliferation, migration, and invasion of lung cancer cells, thereby contributing to a poor prognosis. Furthermore, TONSL overexpression promotes immune escape and drug sensitivity in LUAD., Conclusion: TONSL serves as a reliable prognostic marker for LUAD, and its up-regulation is associated with increased immune escape and drug sensitivity. These findings suggest that TONSL holds potential as a novel therapeutic target for LUAD., (© 2024. The Author(s), under exclusive licence to Federación de Sociedades Españolas de Oncología (FESEO).)

Developing superporous hemostatic sponges with simultaneously enhanced permeability and mechanical properties remains challenging but highly desirable to achieve rapid hemostasis for non-compressible hemorrhage. Typical approaches to improve the permeability of hemostatic sponges by increasing porosity sacrifice mechanical properties and yield limited pore interconnectivity, thereby undermining the hemostatic efficacy and subsequent tissue regeneration. Herein, we propose a temperature-assisted secondary network compaction strategy following the phase separation-induced primary compaction to fabricate the superporous chitosan sponge with highly-interconnected porous structure, enhanced blood absorption rate and capacity, and fatigue resistance. The superporous chitosan sponge exhibits rapid shape recovery after absorbing blood and maintains sufficient pressure on wounds to build a robust physical barrier to greatly improve hemostatic efficiency. Furthermore, the superporous chitosan sponge outperforms commercial gauze, gelatin sponges, and chitosan powder by enhancing hemostatic efficiency, cell infiltration, vascular regeneration, and in-situ tissue regeneration in non-compressible organ injury models, respectively. We believe the proposed secondary network compaction strategy provides a simple yet effective method to fabricate superporous hemostatic sponges for diverse clinical applications., (© 2024. The Author(s).)

Background: Neural Precursor Cell Expressed Developmentally Down-Regulated Protein 1 (NEDD1) serves as a crucial factor in promoting cellular mitosis by directly facilitating wheel assembly and daughter centriole biogenesis at the lateral site of parent centrioles, ultimately driving centrosome replication. The amplification of centrosomes and the abnormal expression of centrosome-associated proteins contribute to the invasion and metastasis of non-small cell lung cancer cells. However, the specific mechanism by which NEDD1 contributes to the progression of lung adenocarcinoma (LUAD) remains unexplored. Therefore, the objective of this study is to uncover the role played by NEDD1 in LUAD. Methods: To verify the expression of NEDD1 in pan-carcinoma. The feasibility of NEDD1 as a prognostic marker for LUAD in TCGA and GEO databases was verified. Subsequently, Cox proportional hazard regression analysis was used to screen the prognostic factors of LUAD, so as to analyze the correlation between prognostic factors and NEDD1 expression. For another, NEDD1-related genes were screened for pathway enrichment analysis to verify their possible functions. In addition, the expression of NEDD1 in LUAD was verified by qPCR and IHC, then siRNA was used to construct NEDD1-knocked lung cancer cells for subsequent cytobehavioral experiments. Finally, the distribution of NEDD1 in single-cell samples was revealed, and then the correlation between its overexpression and LUAD immune escape and drug resistance was analyzed. Results: LUAD exhibits upregulation of NEDD1, which in turn promotes the proliferation, migration, invasion, and epithelial-mesenchymal transition of lung cancer cells, thereby contributing to a poor prognosis. Furthermore, the overexpression of NEDD1 is closely associated with immune escape and drug resistance in LUAD. Conclusion: NEDD1 serves as a reliable prognostic marker for LUAD, and its upregulation is associated with increased immune escape and drug resistance. Given these findings, NEDD1 holds potential as a novel therapeutic target for the treatment of LUAD., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Effective and easy regulation of hydrogel surface properties without changing the overall chemical composition is important for their diverse applications but remains challenging to achieve. We report a generalizable strategy to reconfigure hydrogel surface networks based on hydrogel-substrate interface dynamics for manipulation of hydrogel surface wettability and bioadhesion. We show that the grafting of hydrophobic yet flexible polymeric chains on mold substrates can significantly elevate the content of hydrophobic polymer backbones and reduce the presence of polar groups in hydrogel surface networks, thereby transforming the otherwise hydrophilic hydrogel surface into a hydrophobic surface. Experimental results show that the grafted highly dynamic hydrophobic chains achieved with optimal grafting density, chain length, and chain structure are critical for such substantial hydrogel surface network reconfiguration. Molecular dynamics simulations further reveal the atomistic details of the hydrogel network reconfiguration induced by the dynamic interface interactions. The hydrogels prepared using our strategy show substantially enhanced bioadhesion and transdermal delivery compared with the hydrogels of the same chemical composition but fabricated via the conventional method. Our findings provide important insights into the dynamic hydrogel-substrate interactions and are instrumental to the preparation of hydrogels with custom surface properties., (© 2024. The Author(s).)

Background: Diabetic foot ulcers (DFU) are among the fastest-growing diseases worldwide. Recent evidence has emphasized the critical role of microRNA (miRNA)-mRNA networks in various chronic wounds, including DFU. In this study, we aimed to clarify the miRNA-mRNA axes associated with the occurrence of DFU., Methods: Expression profiles of miRNAs and mRNAs were extracted from the Gene Expression Omnibus. Differentially expressed genes and differentially expressed miRNAs were identified, and miRNA-mRNA regulatory axes were constructed through integrated bioinformatics analyses. We validated the miRNA-mRNA axes using quantitative real-time PCR (qPCR) and dual-luciferase reporter assays. We conducted an immune infiltration analysis and confirmed the bioinformatics results using immunofluorescence staining. Single-sample gene set enrichment analysis (ssGSEA) was used to analyze the metabolic mechanisms., Results: miR-182-5p-CHL1/MITF and miR-338-3p-NOVA1 interactions were identified using in silico analysis. The qPCR results showed apparent dysregulation of these miRNA-mRNA axes in DFU. The dual-luciferase reporter assay confirmed that miR-182-5p targeted CHL1 and MITF, and miR-338-3p targeted NOVA1. We conducted an immune infiltration analysis and observed that key genes correlated with decreased infiltration of M1 macrophages and resting mast cells in DFU. Immunofluorescence staining verified the co-localization of CHL1 and tryptase, while MITF and CD68 showed weak positive correlations. Metabolic pathways related to these three genes were identified using ssGSEA., Conclusions: In summary, the miR-182-5p-CHL1/MITF and miR-338-3p-NOVA1 pathway interactions and decreased infiltration of M1 macrophages and resting mast cells may provide novel clues to the pathogenesis of DFU., Trial Registration: The clinical trial included in this study was registered in the Chinese Clinical Trial Registry ( ChiCTR2200066660 ) on December 13, 2022., (© 2023. The Author(s).)

Ideal Plant Architecture 1 (IPA1) is a key regulator of plant architecture. However, knowledge of downstream genes applicable for improving rice plant architecture is very limited. We identified the plant architecture regulatory gene NARROW LEAF 11 (NAL11), which encodes a heat-shock protein (HSP) containing a DnaJ domain. A promising rare allele of NAL11 (NAL11 -923del-1552 ) positively selected in Aus cultivars was identified; this allele exhibited increased expression and generated relatively few tillers, thick stems, and large panicles, components of the ideal plant architecture (IPA). NAL11 is involved in regulating the cell cycle and cell proliferation. NAL11 loss-of-function mutants present impaired chloroplast development and gibberellin (GA) defects. Biochemical analyses show that IPA1 directly binds to elements in the missing fragment of the NAL11 -923del-1552 promoter and negatively regulates NAL11 expression. Genetic analyses support the hypothesis that NAL11 acts downstream of IPA1 to regulate IPA by modulating GA homeostasis, and NAL11 may be an essential complement for IPA1. Our work revealed that avoidance of the inhibition of NAL11 -923del-1552 caused by IPA1 represents a positive strategy for rescuing GA defects accompanied by the upregulation of IPA1 in breeding high-yield rice., (© 2022 The Authors. New Phytologist © 2022 New Phytologist Foundation.)

Objectives: The current study aimed to examine the neurodegenerative implication of isolated REM sleep without atonia (RSWA) among first-degree relatives of patients with REM sleep behaviour disorder (RBD)., Methods: This cross-sectional case-control study recruited three groups of subjects: First-degree relatives of RBD patients with isolated RSWA (n = 17), first-degree relatives of RBD patients without isolated RSWA (n = 18), and normal controls who did not have any RWSA and family history of RBD (n = 15). Prodromal Parkinson's Disease likelihood ratio by the updated MDS Research Criteria and striatal dopaminergic transmission function of the subjects as assessed by triple-tracer (18F-DOPA, 11C-Raclopride, and 18F-FDG) PET/CT scan were used as proxy markers of neurodegeneration., Results: In contrary to our hypothesis, the three groups did not differ in their pre- or post-striatal dopaminergic transmission function, and their Prodromal Parkinson's Disease likelihood ratio. However, they differed significantly in their frequency of a having first-degree relatives with Parkinson's disease or dementia of Lewy body (first-degree relativess with RSWA vs first degree relatives without RSWA vs normal controls = 58.8% vs 22.2% vs 0%, p = 0.001)., Conclusion: FDRs of RBD patients with isolated RSWA did not have increased neurodegenerative markers compared to FDRs of RBD patients without isolated RSWA and normal control, despite an paradoxical increase in frequency of Parkinson's disease or dementia of Lewy body among their family compared to FDRs of RBD patients without isolated RSWA. Further longitudinal follow-up study will be needed to ascertain their long-term prognosis., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Early diagnosis of rheumatoid arthritis with the initiation of disease-modifying antirheumatic drugs is important to prevent future disability. Seronegative rheumatoid arthritis lacks the classical immunological markers, thus imposing clinical diagnostic difficulty. In this case, we reported 68  Ga-FAPI PET/CT findings of seronegative rheumatoid arthritis in a 60-year-old lady. This case illustrates how 68  Ga-FAPI PET/CT aids in the diagnosis of seronegative rheumatoid arthritis., Competing Interests: Conflict of InterestShing Kee Cheung, Sirong Chen, Yuet Hung Wong, Kwan Kit Wu, and Chi Lai Ho declare no conflict of interest., (© The Author(s), under exclusive licence to Korean Society of Nuclear Medicine 2022.)

Growing evidence shows that there is an increased risk of cardiovascular diseases among gout patients, especially coronary heart disease (CHD). Screening for CHD in gout patients based on simple clinical factors is still challenging. Here we aim to build a diagnostic model based on machine learning so as to avoid missed diagnoses or over exaggerated examinations as much as possible. Over 300 patient samples collected from Jiangxi Provincial People's Hospital were divided into two groups (gout and gout+CHD). The prediction of CHD in gout patients has thus been modeled as a binary classification problem. A total of eight clinical indicators were selected as features for machine learning classifiers. A combined sampling technique was used to overcome the imbalanced problem in the training dataset. Eight machine learning models were used including logistic regression, decision tree, ensemble learning models (random forest, XGBoost, LightGBM, GBDT), support vector machine (SVM) and neural networks. Our results showed that stepwise logistic regression and SVM achieved more excellent AUC values, while the random forest and XGBoost models achieved more excellent performances in terms of recall and accuracy. Furthermore, several high-risk factors were found to be effective indices in predicting CHD in gout patients, which provide insights into the clinical diagnosis.

NLRP3, the sensor protein of the NLRP3 inflammasome, plays central roles in innate immunity. Over-activation of NLRP3 inflammasome contributes to the pathogenesis of a variety of inflammatory diseases, while gain-of-function mutations of NLRP3 cause cryopyrin-associated periodic syndromes (CAPS). NLRP3 inhibitors, particularly those that inhibit inflammasome assembly and activation, are being intensively pursued, but alternative approaches for targeting NLRP3 would be highly desirable. During priming NLRP3 protein is synthesized on demand and becomes attached to the membranes of ER and mitochondria. Here, we show that fatty acid amide hydrolase (FAAH), the key integral membrane enzyme in the endocannabinoid system, unexpectedly served the critical membrane-anchoring and stabilizing role for NLRP3. The specific interaction between NLRP3 and FAAH, mediated by the NACHT and LRR domains of NLRP3 and the amidase signature sequence of FAAH, was essential for preventing CHIP- and NBR1-mediated selective autophagy of NLRP3. Heterozygous knockout of FAAH, resulting in ~50% reduction in both FAAH and NLRP3 expression, was sufficient to substantially inhibit the auto-inflammatory phenotypes of the NLRP3-R258W knock-in mice, while homozygous FAAH loss almost completely abrogates these phenotypes. Interestingly, select FAAH inhibitors, in particular URB597 and PF-04457845, disrupted NLRP3-FAAH interaction and induced autophagic NLRP3 degradation, leading to diminished inflammasome activation in mouse macrophage cells as well as in peripheral blood mononuclear cells isolated from CAPS patients. Our results unraveled a novel NLRP3-stabilizing mechanism and pinpointed NLRP3-FAAH interaction as a potential drug target for CAPS and other NLRP3-driven diseases., (© 2022. The Author(s), under exclusive licence to ADMC Associazione Differenziamento e Morte Cellulare.)

Purpose: To determine an optimal setting for functional contouring and quantification of prostate cancer lesions with minimal variation by evaluating metabolic parameters on 18F-PSMA-1007 PET/CT measured by threshold-based and gradient-based methods under the influence of varying uptake time., Methods and Materials: Dual time point PET/CT was chosen to mimic varying uptake time in clinical setting. Positive lesions of patients who presented with newly diagnosed disease or biochemical recurrence after total prostatectomy were reviewed retrospectively. Gradient-based and threshold-based tools at 40%, 50% and 60% of lesion SUVmax (MIM 6.9) were used to create contours on PET. Contouring was considered completed if the target lesion, with its hottest voxel, was delineated from background tissues and nearby lesions under criteria specific to their operations. The changes in functional tumour volume (FTV) and metabolic tumour burden (MTB, defined as the product of SUVmean and FTV) were analysed. Lesion uptake patterns (increase/decrease/stable) were determined by the percentage change in tumour SUVmax at ±10% limit., Results: A total of 275 lesions (135 intra-prostatic lesions, 65 lymph nodes, 45 bone lesions and 30 soft tissue lesions in pelvic region) in 68 patients were included. Mean uptake time of early and delayed imaging were 94 and 144 minutes respectively. Threshold-based method using 40% to 60% delineated only 85 (31%), 110 (40%) and 137 (50%) of lesions which all were contoured by gradient-based method. Although the overall percentage change using threshold at 50% was the smallest among other threshold levels in FTV measurement, it was still larger than gradient-based method (median: 50%=-7.6% vs gradient=0%). The overall percentage increase in MTB of gradient-based method (median: 6.3%) was compatible with the increase in tumour SUVmax. Only a small proportion of intra-prostatic lesions (<2%), LN (<4%), bone lesions (0%) and soft tissue lesions (<4%) demonstrated decrease uptake patterns., Conclusions: With a high completion rate, gradient-based method is reliable for prostate cancer lesion contouring on 18F-PSMA-1007 PET/CT. Under the influence of varying uptake time, it has smaller variation than threshold-based method for measuring volumetric parameters. Therefore, gradient-based method is recommended for tumour delineation and quantification on 18F-PSMA-1007 PET/CT., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Lau, Chen, Ho and Cai.)

Rationale: How striatal dopamine synthesis capacity (DSC) contributes to the pathogenesis of negative symptoms in first-episode schizophrenia (SZ) and delusional disorder (DD) has seldom been explored. As negative symptoms during active psychotic episodes can be complicated by secondary influences, such as positive symptoms, longitudinal investigations may help to clarify the relationship between striatal DSC and negative symptoms and differentiate between primary and secondary negative symptoms., Objective: A longitudinal study was conducted to examine whether baseline striatal DSC would be related to negative symptoms at 3 months in first-episode SZ and DD patients., Methods: Twenty-three first-episode age- and gender-matched patients (11 DD and 12 SZ) were consecutively recruited through an early intervention service for psychosis in Hong Kong. Among them, 19 (82.6%) patients (9 DD and 10 SZ) were followed up at 3 months. All patients received an 18 F-DOPA PET/MR scan at baseline., Results: Baseline striatal DSC (K occ;30-60 ) was inversely associated with negative symptoms at 3 months in first-episode SZ patients (r s  =  - 0.80, p = 0.010). This association remained in SZ patients even when controlling for baseline negative, positive, and depressive symptoms, as well as cumulative antipsychotic dosage (β =  - 0.69, p = 0.012). Such associations were not observed in first-episode DD patients. Meanwhile, the severity of negative symptoms at 3 months was associated with more positive symptoms in DD patients (r s  = 0.74, p = 0.010) and not in SZ patients., Conclusions: These findings highlight the role of striatal DSC in negative symptoms upon resolution of active psychotic episodes among first-episode SZ patients. Baseline striatal dopamine activity may inform future symptom expression with important treatment implications., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Alzheimer’s disease (AD) was recently defined as a biological construct to reflect neuropathologic status, and both abnormal amyloid and tau are required for a diagnosis of AD. We aimed to determine the proton MR spectroscopic (1H-MRS) patterns of the posterior cingulate in biologically defined AD. A total of 68 participants were included in this study, comprising 37 controls, 16 early AD, and 15 late AD, who were classified according to their amyloid and tau status and presence of hippocampal atrophy. Compared with controls, early AD showed lower N-acetylaspartate (NAA)/creatine (Cr) (p = 0.003), whereas late AD showed lower NAA/Cr and higher myoInositol (mI)/Cr (all with p < 0.05). Lower NAA/Cr correlated with a greater global amyloid load (r = −0.47, p < 0.001) and tau load (r = −0.51, p < 0.001) and allowed a discrimination of early AD from controls (p < 0.001). Subgroup analysis showed that NAA/Cr also allowed a differentiation of early AD from controls in the cognitively unimpaired subjects, with an area under the receiver operating characteristics curve, sensitivity, and specificity of 0.96, 100%, and 83.8%, respectively. Lower posterior cingulate NAA levels may help to inform underlying neuropathologic changes in the early stage of AD.

The spread of COVID-19 and large-scale travel restrictions has caused serious damage to the global tourism industry. Tourists pay additional attention to public health services and their health during travel, but studies on tourism public health service quality (TPHSQ) are limited. Therefore, this study aims to define TPHSQ and revise and validate its scale. The result of exploratory factor analysis (EFA) indicates that TPHSQ includes two dimensions "overall environmental image" and "public health facilities and management." And based on 456 valid samples, the relationship among TPHSQ, tourists' trust, satisfaction, and loyalty was validated using the multiple linear regression models. Results revealed the importance of the TPHSQ in improving tourists' satisfaction and recovering their trust and loyalty. These results provided several implications for research, practice, and society that can benefit diverse stakeholders, which could accelerate the recovery of the tourism industry., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Han, Zuo, Law, Chen and Zhang.)

Background: The fimbria is a small white matter bundle that connects the hippocampus to the rest of the brain. Damage to the hippocampal gray matter is established in Alzheimer's disease (AD), but the hippocampal fimbrial status in the pathogenesis of AD is unclear. AD-related demyelination and iron deposition alter the diamagnetic and paramagnetic composition of tissues, which can be measured by quantitative susceptibility mapping (QSM)., Hypothesis: AD is associated with microstructural changes in the fimbria that might be detected by QSM., Study Type: Retrospective cross-sectional study., Subjects: In all, 53 adults comprised of controls (n = 30), subjects with early stage AD (n = 13), and late stage AD (n = 10) who were classified according to their amyloid and tau status and presence of hippocampal atrophy., Field Strength / Sequence: 3T; 3D fast-field echo sequence for QSM analysis and 3D T 1 -weighted MP-RAGE sequence for anatomical analysis., Assessment: Segmentation of the left hippocampal fimbria subfield was performed on T 1 -weighted images and was applied to the coregistered QSM map for extraction of the mean, median, minimum, and maximum values of QSM., Statistical Tests: Group comparison of QSM values using analysis of variance (ANOVA) with post-hoc Tukey's test, accuracy of binary differentiation using receiver operating characteristic (ROC), and individual classification using discriminant analysis., Results: QSM mean and QSM median values were significantly different among the three groups (P < 0.05) and showed a shifting from negative in the control group to positive in the AD group. The control and early AD subjects, who have normal hippocampal volumes, were differentiated by the QSM mean value (area under the curve [AUC] 0.744, P < 0.05) and the QSM median value (AUC 0.782, P < 0.05). Up to 76% of subjects (inclusive of 26 controls and six with early AD) were correctly classified using a model incorporating clinical and radiologic data., Data Conclusion: The fimbria showed higher magnetic susceptibility in AD compared with controls., Level of Evidence: 2 TECHNICAL EFFICACY STAGE: 3., (© 2020 International Society for Magnetic Resonance in Medicine.)

Alzheimer's Disease-resemblance atrophy index (AD-RAI) is an MRI-based machine learning derived biomarker that was developed to reflect the characteristic brain atrophy associated with AD. Recent study showed that AD-RAI (≥0.5) had the best performance in predicting conversion from mild cognitive impairment (MCI) to dementia and from cognitively unimpaired (CU) to MCI. We aimed to validate the performance of AD-RAI in detecting preclinical and prodromal AD. We recruited 128 subjects (MCI=50, CU=78) from two cohorts: CU-SEEDS and ADNI. Amyloid (A+) and tau (T+) status were confirmed by PET ( 11 C-PIB, 18 F-T807) or CSF analysis. We investigated the performance of AD-RAI in detecting preclinical and prodromal AD (i.e. A+T+) among MCI and CU subjects and compared its performance with that of hippocampal measures. AD-RAI achieved the best metrics among all subjects (sensitivity 0.74, specificity 0.91, accuracy 85.94%) and among MCI subjects (sensitivity 0.92, specificity 0.81, accuracy 86.00%) in detecting A+T+ subjects over other measures. Among CU subjects, AD-RAI yielded the best specificity (0.95) and accuracy (85.90%) over other measures, while hippocampal volume achieved a higher sensitivity (0.73) than AD-RAI (0.47) in detecting preclinical AD. These results showed the potential of AD-RAI in the detection of early AD, in particular at the prodromal stage.

There have been few studies performed to examine the pathophysiological differences between different types of psychosis, such as between delusional disorder (DD) and schizophrenia (SZ). Notably, despite the different clinical characteristics of DD and schizophrenia (SZ), antipsychotics are deemed equally effective pharmaceutical treatments for both conditions. In this context, dopamine dysregulation may be transdiagnostic of the pathophysiology of psychotic disorders such as DD and SZ. In this study, an examination is made of the dopamine synthesis capacity (DSC) of patients with SZ, DD, other psychotic disorders, and the DSC of healthy subjects. Fifty-four subjects were recruited to the study, comprising 35 subjects with first-episode psychosis (11 DD, 12 SZ, 12 other psychotic disorders) and 19 healthy controls. All received an 18 F-DOPA positron emission tomography (PET)/magnetic resonance (MR) scan to measure DSC (K occ;30-60 value) within 1 month of starting antipsychotic treatment. Clinical assessments were also made, which included Positive and Negative Syndrome Scale (PANSS) measurements. The mean K occ;30-60 was significantly greater in the caudate region of subjects in the DD group (ES = 0.83, corrected p = 0.048), the SZ group (ES = 1.40, corrected p = 0.003) and the other psychotic disorder group (ES = 1.34, corrected p = 0.0045), compared to that of the control group. These data indicate that DD, SZ, and other psychotic disorders have similar dysregulated mechanisms of dopamine synthesis, which supports the utility of abnormal dopamine synthesis in transdiagnoses of these psychotic conditions.

The past decade has witnessed the rising popularity and acceptance of molecular definitions on disease management. Prostate-specific membrane antigen (PSMA), in light of its molecular nature and cytokinetic properties, has rapidly become the target for development of a variety of functional tracers for PET/CT evaluation of prostate cancer. The most commonly used PSMA-binding analog is 68 Ga-labeled PSMA-11, which is now widely applied in both research and clinical settings. Literature data in the recent years have been enriched by a number of meta-analyses and systemic reviews on the evolving role of PSMA PET in primary diagnosis, staging, detection of biochemical recurrence after primary cancer treatment, identification, and significance of oligometastasis, as well as in restaging and treatment monitoring. Being a highly sensitive and reasonably specific molecular tracer, PSMA-binding analogs have a high potential to possess the majority of imaging characteristics required for a variety of management decisions in prostate malignancy., (© 2020 John Wiley & Sons Australia, Ltd.)

Blue light extensively regulates multiple physiological processes and secondary metabolism of plants. Although blue light quantity (fluence rate) is important for plant life, few studies have focused on the effects of different blue light intensity on plant secondary metabolism regulation, including tea plants. Here, we performed transcriptomic and metabolomic analyses of young tea shoots (one bud and two leaves) under three levels of supplemental blue light, including low-intensity blue light (LBL, 50 μmol m -2 s -1 ), medium-intensity blue light (MBL, 100 μmol m -2 s -1 ), and high-intensity blue light (HBL, 200 μmol m -2 s -1 ). The total number of differentially expressed genes (DEGs) in LBL, MBL and HBL was 1, 7 and 1097, respectively, indicating that high-intensity blue light comprehensively affects the transcription of tea plants. These DEGs were primarily annotated to the pathways of photosynthesis, lipid metabolism and flavonoid synthesis. In addition, the most abundant transcription factor (TF) families in DEGs were bHLH and MYB, which have been shown to be widely involved in the regulation of plant flavonoids. The significantly changed metabolites that we detected contained 15 lipids and 6 flavonoid components. Further weighted gene co-expression network analysis (WGCNA) indicated that CsMYB (TEA001045) may be a hub gene for the regulation of lipid and flavonoid metabolism by blue light. Our results may help to establish a foundation for future research investigating the regulation of woody plants by blue light.

Triptolide (TP), a principal bioactive component extracted from traditional Chinese medicine Tripterygium wilfordii Hook. F. (TWHF), has attracted wide attention of its therapeutic effects on inflammation and autoimmune diseases. However, the therapeutic application of TP is hindered by severe cardiomyocyte toxicity and narrow therapeutic window. We previously identified that the p53 was an indispensable contributor in TP-induced myocardial injury. p53 has an inhibitory effect on IKKβ-NF-κB pathway that regulates glucose transporters (GLUT) expression. Based on these evidences, we speculate that p53 mediates TP-disturbed glucose uptake by blocking IKKβ-NF-κB signaling. This study focused on the effect of TP on cardiac glucose uptake and the role of p53 in glucose metabolism in cardiomyocytes, and p53 -/- mice. TP treatment depressed glucose consumption and ATP production resulting in myocardial damage. Incubation with ATP (5 mM) remarkably decreased the cellular damage. Immunoblotting and immunofluorescence identified that TP suppressed glucose uptake by restricting IKKβ-NF-κB signaling activation, GLUT1 and GLUT4 expression. p53 inhibition alleviated the cell damage and the compromise of glucose uptake. Mechanistically, p53 antagonist PFTα abolished TP-induced the inhibition of IKKβ, IκBα phosphorylation, p65 nuclear translocation, and GLUT1, GLUT4 expression. Consistently, in acute heart injury models, p53 deficiency upregulated IKKβ-NF-κB activation and GLUT1, GLUT4 protein levels which was also indicated as amelioration of heart histological injury after 1.2 mg kg -1 TP administration. The present findings indicate that TP-induced p53 overactivation suppresses glucose uptake by inhibiting IKKβ-NF-κB pathway and downregulating NF-κB-dependent GLUT1 and GLUT4 expression., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Pretreatment dual-tracer ( 18 F-fluorodeoxyglucose and 11 C-acetate) PET/computed tomography (CT) has potential to predict treatment response for 90 Y microsphere radioembolization (RE) in patients with inoperable hepatocellular carcinoma (HCC). Patients with 11 C-acetate-avid HCC have a better response to 90 Y microsphere RE, and possibly better survival. Pretreatment dual-tracer PET/CT has a significant theranostic value on 90 Y microsphere RE in determining target tumor dose for HCCs with different cellular differentiation, metabolic tumor volume, and functioning liver volume, and can be used to prescribe individual injected activity of 90 Y microspheres., (Copyright © 2019 Elsevier Inc. All rights reserved.)

A patient was found incidentally on dual-tracer (C-acetate [ACT] and F-FDG [FDG]) PET/CT for having crossed fused renal ectopia and 2 types of malignant tumors, colonic carcinoma and renal cell carcinoma (RCC), each having its own characteristic tracer avidity. Multiple liver metastases were also mutually exclusive, with a purely ACT-avid group of metastatic lesions from RCC and another FDG-avid group from colonic carcinoma. Bone and lung metastases, however, could not be readily distinguishable in terms of primary origins. Crossed fused renal ectopia is a rare anomaly, even rarer to have RCC coexisting with a second primary malignancy.

Purpose: The aim of this study was to establish an algorithm for the prescription of 90 Y glass microsphere radioembolization ( 90 Y-GMRE) of HCC in individual patients based on the relationship between tumour dose (TD) and response validated by 90 Y PET/CT dosimetry and dual-tracer PET/CT metabolic parameters., Methods: The study group comprised 62 HCC patients prospectively recruited for 90 Y-GMRE who underwent pretreatment dual-tracer ( 11 C-acetate and 18 F-FDG) PET/CT as surrogate markers of HCC cellular differentiation. Pretreatment tumour-to-nontumour ratio on 99m Tc-MAA SPECT/CT (T/NT MAA ) was correlated with posttreatment 90 Y PET/CT T/NT 90Y after quantification validation. The TD-response relationship for HCC of different tracer groups was assessed on follow-up PET/CT 2 months after treatment., Results: 90 Y PET/CT was accurate in the measurement of recovery of injected 90 Y activity (81.9-99.9%, median 94.8%). Pretreatment SPECT/CT T/NT MAA was strongly correlated with posttreatment 90 Y PET/CT T/NT 90Y (5.6 ± 3.2 versus 5.9 ± 3.5, T/NT 90Y 1.01 × T/NT MAA  + 0.161, r = 0.918, P < 0.05). The response rates were 72.4% (21/29), 70.6% (12/17) and 25% (4/16) for well, moderately and poorly differentiated HCC, respectively. The cut-off TD for a good response was significantly different between poorly differentiated and well/moderately differentiated HCC (262 Gy versus 152/174 Gy) with 89.2% sensitivity and 88% specificity. At a limiting tolerated liver dose of 70 Gy, the T/NT MAA thresholds for predicting a good response in poorly differentiated and well/moderately differentiated HCC were 3.5 and 2.0/2.3. Disregarding HCC cellular differentiation, the cut-off TD became 170 Gy, with lower sensitivity (70.3%) and specificity (76%)., Conclusion: 90 Y PET/CT can provide accurate dosimetry for 90 Y-GMRE. Pretreatment T/NT MAA predicts posttreatment T/NT 90Y . The TD thresholds for a good response are tracer-dependent, with a strong correlation between HCC radiosensitivity and cellular differentiation and other PET-based parameters. These cytokinetic factors improve treatment efficacy while minimizing organ damage for the prescription of personalized 90 Y-GMRE.

Background: A liver transplant recipient developed hospital-acquired symptomatic hepatitis C virus (HCV) genotype 6a infection 14 months post transplant., Objective: Standard outbreak investigation., Methods: Patient chart review, interviews of patients and staff, observational study of patient care practices, environmental surveillance, blood collection simulation experiments, and phylogenetic study of HCV strains using partial envelope gene sequences (E1-E2) of HCV genotype 6a strains from the suspected source patient, the environment, and the index patient were performed., Results: Investigations and data review revealed no further cases of HCV genotype 6a infection in the transplant unit. However, a suspected source with a high HCV load was identified. HCV genotype 6a was found in a contaminated reusable blood-collection tube holder with barely visible blood and was identified as the only shared item posing risk of transmission to the index case patient. Also, 14 episodes of sequential blood collection from the source patient and the index case patient were noted on the computerized time log of the laboratory barcoding system during their 13 days of cohospitalization in the liver transplant ward. Disinfection of the tube holders was not performed after use between patients. Blood collection simulation experiments showed that HCV and technetium isotope contaminating the tip of the sleeve capping the sleeved-needle can reflux back from the vacuum-specimen tube side to the patient side., Conclusions: A reusable blood-collection tube holder without disinfection between patients can cause a nosocomial HCV infection. Single-use disposable tube holders should be used according to the recommendations by Occupational Safety and Health Administration and World Health Organization.

A bedridden 90-year-old man with fever and elevated prostate-specific antigen (PSA) (49 ng/mL) was referred for differentiation between infection and tumor. F-FDG PET/CT was negative for infection, but Ga-PSMA PET/CT showed multiple lesions in prostate gland with infiltration to bladder wall and seminal vesicle, consistent with locally advanced prostate cancer. The lesion with the highest Ga-PSMA uptake was strongly avid for Ga-DOTATOC, suggesting neuroendocrine tumor differentiation. After hormonal therapy, PSA normalized, but chromogranin-A increased (from 251 to 398 ng/mL), inferring progression of neuroendocrine tumor differentiation. Advanced prostate cancer may require investigation for pathological neuroendocrine transformation, although PSA may suggest improvement.

Introduction: Patients surviving stroke without immediate dementia are at high risk of delayed-onset dementia. Mechanisms underlying delayed-onset dementia are complex and may involve vascular and/or neurodegenerative diseases., Methods: Dementia-free patients with stroke and/or transient ischemic attack (TIA; n = 919) were studied for 3 years prospectively, excluding those who developed dementia 3 to 6 months after stroke and/or TIA., Results: Forty subjects (4.4%) developed dementia during the study period. Imaging markers of severe small vessel disease (SVD), namely presence of ≥3 lacunes and confluent white matter changes; history of hypertension and diabetes mellitus independently predicted delayed-onset dementia after adjustment for age, gender, and education. Only 6 of 31 (19.4%) subjects with delayed cognitive decline harbored Alzheimer's disease-like Pittsburg compound B (PiB) retention. Most PiB cases (16/25, 64%) had evidence of severe SVD., Discussion: Severe SVD contributes importantly to delayed-onset dementia after stroke and/or TIA. Future clinical trials aiming to prevent delayed-onset dementia after stroke and/or TIA should target this high-risk group., (Copyright © 2016 The Alzheimer's Association. Published by Elsevier Inc. All rights reserved.)

Background and Purpose: We hypothesized that comorbid amyloid-beta (Aβ) deposition played a key role in long-term cognitive decline in subjects with stroke/transient ischemic attack., Methods: We recruited 72 subjects with cognitive impairment after stroke/transient ischemic attack to receive Carbon-11-labeled Pittsburgh compound B positron emission tomography. We excluded subjects with known clinical Alzheimer's disease. Those with and without Alzheimer's disease-like Aβ deposition were classified as mixed vascular cognitive impairment (mVCI, n=14) and pure VCI (pVCI, n=58), respectively. We performed Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment to evaluate global cognition and cognitive domains (memory, visuospatial function, language, attention, and executive function) at 3 to 6 months (baseline) and annually for 3 years after the index event. We compared cognitive changes between mVCI and pVCI using linear mixed models and analysis of covariance adjusted for age and education., Results: Over 3 years, there were significant differences between mVCI and pVCI on change of MMSE score over time (group×time interaction, P=0.007). We observed a significant decline on MMSE score (P=0.020) in the mVCI group but not in the pVCI group (P=0.208). The annual rates of decline on MMSE (P=0.023) and Montreal Cognitive Assessment score (P=0.003) were greater in the mVCI group than in the pVCI group. Memory, visuospatial, and executive function domain scores on the Montreal Cognitive Assessment were related to Aβ deposition., Conclusions: Compared with subjects without Alzheimer's disease-like Aβ deposition, those with Aβ deposition experienced a more severe and rapid cognitive decline over 3 years after stroke/transient ischemic attack. Aβ was associated with changes in multiple cognitive domains., (© 2015 American Heart Association, Inc.)

Objective: To investigate dopamine transmission in patients with comorbid REM sleep behavior disorder (RBD) and major depressive disorder (MDD)., Methods: This is a case-control study including 11 medicated patients with comorbid RBD and MDD (mean age 47.5 ± 8.2), 8 medicated patients with MDD only (mean age 47.9 ± 8.4), and 10 healthy participants (mean age 46.5 ± 10.6 years). They underwent clinical assessment, video-polysomnography, olfactory tests, and neuroimaging studies ((18)F-DOPA, (11)C-raclopride, and (18)F-FDG PET neuroimaging)., Results: Compared with the 2 control groups, patients with comorbid RBD and MDD had significantly lower (18)F-DOPA uptake at 60 minutes in the putamen and caudate after controlling for age and sex effect (p < 0.05). There were no significant differences for the (11)C-raclopride and (18)F-FDG-PET. The (18)F-DOPA uptake in putamens had significant inverse correlation with severity of RBD symptoms (p < 0.01) and REM-related tonic muscle activity (p < 0.01). The comorbid RBD and MDD group had more impairment in olfactory function., Conclusion: Patients with comorbid RBD and MDD had presynaptic dopamine dysfunction and impaired olfactory function. There is a distinct possibility that the development of RBD symptoms among patients with MDD may represent an early phase of α-synucleinopathy neurodegeneration instead of a merely antidepressant-induced condition., (© 2015 American Academy of Neurology.)

Background: We hypothesized that chronic brain changes are important substrates for incident dementia after stroke and transient ischemic attack (TIA)., Methods: We compared clinical and imaging features between patients with consecutive stroke/TIA with (n = 88) and without (n = 925) incident dementia at 3 to 6 months after a stroke/TIA. Pittsburg compound B (PiB) positron emission tomography was performed in 50 patients, including those with (n = 37) and without (n = 13) incident dementia., Results: Age, history of diabetes mellitus, severity of white matter changes (WMCs), and medial temporal lobe atrophy (MTLA) were associated with incident dementia. Alzheimer's disease (AD)--like PiB retention was found in 29.7% and 7.7% (P = .032) of patients with and without incident dementia, respectively., Conclusions: Chronic brain changes including WMCs, MTLA, and AD pathology are associated with incident dementia after stroke/TIA. Interventions targeting these chronic brain changes may reduce burden of vascular cognitive impairment., (Copyright © 2015 The Alzheimer's Association. Published by Elsevier Inc. All rights reserved.)

Unlabelled: We prospectively compared (11)C-acetate with (18)F-FDG in a PET/CT evaluation of multiple myeloma (MM), specifically on diagnostic accuracy, identification of high-risk patients, and monitoring of treatment response., Methods: Dual-tracer PET/CT was performed on 35 pathologically and clinically confirmed and untreated patients (26 with symptomatic MM, 5 with smoldering MM, and 4 with monoclonal gammopathy of unknown significance) and 20 individuals with normal marrow., Results: (11)C-acetate showed significant incremental value over (18)F-FDG (84.6% vs. 57.7%) for positively identifying patients with diffuse and focal symptomatic MM, and was negative in patients with indolent smoldering MM and monoclonal gammopathy of unknown significance. Three functional parameters-number of (11)C-acetate-avid and (18)F-FDG-avid focal bone lesions and (11)C-acetate general marrow activity-strongly correlated with β-2-microglobulin as surrogate imaging markers of tumor burden. After induction chemotherapy, the metabolic change in (11)C-acetate general marrow activity correlated with clinical response., Conclusion: Metabolic characterization of MM in diagnosis, risk stratification, and treatment monitoring can be done more accurately by assessing lipid metabolism with (11)C-acetate than by assessing glucose metabolism with (18)F-FDG.

Intracranial hemangiopericytoma (IHPC) is a rare tumor representing less than 1% of all CNS tumors and is often indistinguishable from meningioma on structural imaging alone. Unlike meningioma, IHPC is an aggressive tumor with the propensity for early locoregional recurrence and distant metastases. Hence, its management strategies differ greatly from that of meningioma. Some investigators have reported the potential role of multitracers (F-FDG, C-methionine, and O-H2O) PET imaging in distinguishing IHPC from meningioma. We described the findings of dual-tracer (C-acetate and F-FDG) PET/CT imaging in a histopathologically proven case of IHPC with extensive extracranial osseous metastases that showed significantly greater C-acetate avidity.

Unlabelled: The success of liver transplantation (LT) for hepatocellular carcinoma (HCC) is enhanced by careful patient selection on the basis of the Milan criteria. The criteria are traditionally assessed by contrast CT, which is known to be affected by structural or architectural changes in cirrhotic livers. We aimed to compare dual-tracer ((11)C-acetate and (18)F-FDG) PET/CT with contrast CT for patient selection on the basis of the Milan criteria., Methods: Patients who had HCC and had undergone both preoperative dual-tracer PET/CT and contrast CT within a 1-mo interval were retrospectively studied. They then underwent either LT (n = 22) or partial hepatectomy (PH) (n = 21; HCC of ≤ 8 cm). Imaging data were compared with data from postoperative pathologic analysis for accuracy in assessment of parameters specified by the Milan criteria (tumor size and extent, vascular invasion, and metastasis), TNM staging, and patient selection for LT., Results: Dual-tracer PET/CT performed equally well in both LT and PH groups for HCC detection (94.1% vs. 95.8%) and TNM staging (90.9% vs. 90.5%). Contrast CT performed reasonably well in the LT group but not in the PH group for HCC detection (67.6% vs. 37.5%) and TNM staging (54.5% vs. 28.6%). In the LT group, the sensitivity and specificity of contrast CT for patient selection on the basis of the Milan criteria were 43.8% and 66.7%, respectively (comparable to values in the literature); the sensitivity and specificity of dual-tracer PET/CT were 93.8% and 100%, respectively (both Ps < 0.05). From the surgeon's perspective, we tended to perform transplantation for patients with higher diagnostic certainty (stricter CT criteria) because of a shortage of donor grafts. Patients who were not transplant candidates usually underwent up-front hepatectomy without the benefit of reassessment contrast CT, resulting in lower accuracies for the PH group. The overall sensitivity (96.8%) and specificity (91.7%) of dual-tracer PET/CT for patient selection for LT were significantly higher than those of contrast CT (41.9% and 33.0%, respectively) (both Ps < 0.05). Sources of error for contrast CT were related to cirrhosis or previous treatment and included difficulty in differentiating cirrhotic nodules from HCC (39%) and estimation of tumor size (14%). Overstaging of vascular invasion (4.6%) and extrahepatic metastases (4.6%) was infrequent. The rate of false-negative results of dual-tracer PET/CT was 4.7%., Conclusion: Dual-tracer PET/CT was significantly less affected by cirrhotic changes than contrast CT for HCC staging and patient selection for LT on the basis of the Milan criteria. The inclusion of dual-tracer PET/CT in pretransplant workup may warrant serious consideration.

Unlabelled: We studied the metabolic characteristics of RCC subtypes and angiomyolipoma with 18F-FDG and 11C-acetate PET/CT., Methods: Fifty-eight patients with both baseline CT and dual-tracer PET/CT were recruited: 10 angiomyolipoma (16 lesions) and 48 RCC (50 lesions). Each lesion was assessed for SUVmax ratio (lesion-to-normal kidney) on 11C-acetate/18F-FDG PET and attenuation density on CT. Receiver operating characteristic (ROC) curve was analyzed to define the threshold of 11C-acetate SUVmax ratio for differentiating angiomyolipoma from RCC. Thirty-nine RCC patients were selected for 3-year disease-free survival analysis., Results: All angiomyolipoma showed negative 18F-FDG but markedly increased 11C-acetate metabolism, significantly higher than RCC (11C-acetate SUVmax ratio = 4.11 ± 0.53 vs 2.00 ± 0.71; P < 0.05). 11C-acetate SUVmax ratio = 3.71 could differentiate angiomyolipoma including "fat-poor angiomyolipoma" (n = 10) from RCC with sensitivity of 93.8% (15/16) and specificity of 98.0% (49/50). Different RCC subtypes/grades (25 low- and 11 high-grade clear cell [CC], 7 chromophobe, 4 papillary, and 1 collecting duct) were found to have different dual-tracer metabolic pattern (P < 0.05), with overall RCC detection sensitivity of 90% (45/50). All chromophobe RCC were avid only for C-acetate but not 18F-FDG, whereas papillary RCC were primarily the opposite. RCC-CC showed variable dual-tracer uptake: high-grade more avid for F-FDG, low-grade more for 11C-acetate. Four RCC cases negative by dual-tracers were of low-grade RCC-CC. "Primary RCC being 18F-FDG-avid" was the only independent predictor of RCC recurrence in 3 years (P < 0.05), with a median disease-free survival of 22 months., Conclusion: 11C-acetate PET/CT helps in differentiating "fat-poor angiomyolipoma" from RCC. Dual-tracer PET/CT has value in diagnosis of RCC subtypes and predicting survival.

Background: Although patients harboring confluent white matter hyperintensities (WMH) are at high risk of cognitive decline, this risk varies among individuals. We investigated the predictors for cognitive decline in stroke patients with confluent WMH., Methods: We followed up 100 stroke patients with confluent WMH who were participants of the VITAmins TO Prevent Stroke study for 2 years. We investigated the association between clinical features, apolipoprotein E status, imaging measures (infarcts, microbleeds, volumes of WMH, cortical gray matter [cGM], lateral ventricles, and hippocampi), and B vitamins with changes in cognitive measures (clinical dementia rating scale, Mini-Mental State Examination, Mattis dementia rating scale--initiation/perseveration subscale). We performed Pittsburgh compound B imaging among dementia converters., Results: Multivariate regression analysis showed that increase in clinical dementia rating scale grade was associated with cGM atrophy, absence of hyperlipidemia, and lower diastolic blood pressure at baseline. cGM atrophy and absence of hyperlipidemia were also associated with deterioration in Mini-Mental State Examination and Mattis dementia rating scale--initiation/perseveration subscale scores. Pittsburgh compound B retention typical of Alzheimer's disease was found only in 10% of dementia converters. Incident stroke and B vitamins were not associated with cognitive decline., Conclusions: Among stroke patients with confluent WMH, cGM atrophy and absence of hyperlipidemia are important predictors for cognitive decline. Significant cognitive decline can occur in the absence of incident stroke or Alzheimer's pathology., (Copyright © 2012 The Alzheimer's Association. Published by Elsevier Inc. All rights reserved.)

[11C]Acetate (ACT) positron emission tomography/computed tomography (PET/CT) is useful in the detection of hepatocellular carcinoma (HCC). This study aimed to evaluate whether [18F]fluoroacetate (FAC) could be an alternative analogue of [11C]ACT for the diagnosis of HCC. [18F]FAC was synthesized using the precursor t-butyl 2-(methanesulfonyloxy)ethanoate. Five volunteer patients with known HCC were recruited after consent. Whole-body [18F]FAC PET/CT was performed at 20 minutes and 1 hour postinjection and compared to [11C]ACT PET/CT at 20 minutes postinjection to assess biodistribution and tumor uptake characteristics. Qualitative and semiquantitative analyses were performed with statistical correlations on the physiologic organs of accumulation and HCC lesions for both tracers. [18F]FAC was obtained with 99% radiochemical purity, and the reaction yield was 16.0% with 1-hour synthesis time. The biodistribution of [18F]FAC on PET/CT was significantly different from that of [11C]ACT (p < .05) by the lack of preferential uptake in any specific organ, particularly the pancreas, resembling the pattern of blood-pool retention although partly metabolized via the bowel. There was no significant defluorination, and none of the [11C]ACT-avid HCC lesions showed increased [18F]FAC activity. These were different from the results reported on other species. [18F]FAC may not be a potential alternative tracer for [11C]ACT in PET/CT evaluation of HCC in human subjects.

Purpose: To compare the prognostic implications and positron emission tomography (PET)/computed tomography (CT) characteristics of isolated bone metastasis secondary to hepatocellular carcinoma (HCC) with those of HCC metastases to bone and other sites., Materials and Methods: This study was approved by the institutional ethics committee, and informed consent was obtained from all patients. Extrahepatic metastases were diagnosed in 257 patients with HCC by using dual-tracer (carbon 11 [(11)C] acetate and fluorine 18 fluorodeoxyglucose [FDG]) PET/CT. Metastatic bone lesions were identified with visual inspection and semiquantitative assessment and confirmed with histopathologic examination and/or supported by findings at other radiologic examinations or serial PET/CT., Results: The frequency of bone metastasis from HCC was 19% (49 of 257 patients; eight patients had histopathologic proof and 41 had imaging proof). Metastasis isolated to bone (group 1, 30 of 257 patients [12%]) was more common than metastasis to bone and other sites (group 2, 19 of 257 patients [7%]). At lesion-based analysis of group 1 (71 index lesions; mean lesion size ± standard deviation, 3.25 cm ± 1.88), (11)C acetate PET was more sensitive than FDG PET (93% [66 of 71 lesions] vs 62% [44 of 71 lesions], respectively; P < .05). The combined sensitivity was 97% (69 of 71 lesions) with dual-tracer PET and 72% (51 of 71 lesions) with CT. At patient-based analysis, (11)C acetate PET had an incremental value of 23% (seven of 30 patients) over FDG PET. At lesion-based analysis of group 2, FDG PET was more sensitive than (11)C acetate PET (87% [33 of 38 lesions] vs 50% [19 of 38 lesions], respectively; P < .05). Tracer avidities of metastatic bone lesions were closely correlated with that of their corresponding primary HCC tumors. The median survival time was longer in group 1 than in group 2 (18 months vs 11 months, respectively; P < .05)., Conclusion: Isolated bone metastasis from HCC may not be as uncommon as previously believed. The detection of these metastases can be significantly enhanced with (11)C acetate PET compared with FDG PET alone. Identification of this group of patients also seems to have prognostic importance., (© RSNA, 2010.)

Objective: Although age-related confluent white-matter lesion (WML) is an important substrate for cognitive impairment, the mechanisms whereby WML induces cognitive impairment are uncertain. The authors investigated cognitive predictors in patients with confluent WML., Methods: Among 100 patients with ischaemic stroke with confluent WML on MRI, the authors assessed executive function and global cognition by the Mattis Dementia Rating Scale--Initiation/Perseveration Subscale (MDRS I/P) and Mini-Mental State Examination (MMSE), respectively. All volumetric measures were corrected for intracranial volume. The authors investigated the association between basic demography, vascular risk factors, APOE status, WML volume, infarct measures (volume, number, location), microbleed number, atrophy measures (global, central, regional) and cognitive performance. The authors also performed Pittsburgh Compound B (PIB) imaging among seven cognitive impaired patients with stroke., Results: WML was no longer related to cognitive performance after adding atrophy into regression equations. Multivariate regression models showed that cortical grey matter volume independently accounted for performance on both the MDRS I/P (β=0.241, p=0.045) and MMSE (β=0.243, p=0.032). Models examining frontal subregions revealed that volumes of both left (β=0.424, p<0.001) and right (β=0.219, p=0.045) lateral frontal orbital gyri predicted MDRS I/P, whereas education (β=0.385, p<0.001) and left lateral frontal orbital gyrus (β=0.222, p=0.037) predicted MMSE. Volumes of WML and cognitively relevant brain regions were significantly associated. Seven patients with PIB imaging showed no uptake pattern typical of Alzheimer's disease, suggesting a predominantly vascular aetiology for the cognitive impairment and brain changes in these patients., Conclusions: Cognitive impairment in patients with confluent WML is mediated by global and frontal cortical atrophy.

An adult patient presented with acute severe pelvic and low-back pain. Evaluations with CT and MRI were negative/inconclusive. F-18 FDG PET/CT localized the site of pathology in right sacroiliac-joint by demonstrating hypermetabolic activities conformal with the joint's outline, signifying infectious/inflammatory sacroiliitis. Blood culture was positive for Group B streptococcus (GBS). Antibiotic treatment was started within 24 hours from onset of symptoms, and there was almost immediate partial pain relief. GBS sacroiliitis is a rare form of septic sacroiliitis requiring prompt diagnosis and urgent treatment. This is the first report of F-18 FDG PET/CT for diagnosing GBS sacroiliitis in adults with no predisposing factors.

We hypothesize that Pittsburgh compound B (PIB) binding is common in poststroke dementia (PSD) and that cognitive decline may be faster in PIB positive patients. We performed PIB positron emission tomography (PET) among 17 subjects: 10 PSD patients, 4 Alzheimer's disease (AD) patients, and 3 healthy controls. We also compared the rate of change in mini-mental state examination (MMSE) between PIB positive and negative patients. We detected AD-like PIB binding in 4 PSD patients (40%), all the AD patients, and 1 healthy control. The global PIB retention standardized uptake value (SUV) at 35-45 min for PIB positive stroke patients was 1.67 (range 1.56-1.82), which was similar to the AD patients (1.65; range 1.46-1.88) and was lower than PIB negative patients (1.29, range 1.24-1.34). Mean annual MMSE decline for the 4 PIB positive patients was 2.9 and that for the 6 PIB negative patients was 1. This pilot study suggests that PIB PET is feasible for the evaluation of PSD and PIB binding may be common in PSD. Whether presence of PIB binding is associated with a more rapid cognitive decline in PSD requires further study to confirm.

Unlabelled: We have reported previously that (11)C-acetate ((11)C-ACT) PET was complementary to (18)F-FDG PET in the evaluation of primary hepatocellular carcinoma (HCC) in relation to the degree of tumor cellular differentiation. In this retrospective study, our goals were to further explore the complementary role of (11)C-ACT and (18)F-FDG PET in the detection of metastatic HCC disease, to evaluate the tracer characteristics of individual organ metastasis, to identify the risk factors of metastasis, and to evaluate how these results could affect patient management., Methods: One hundred twenty-one patients were selected for this study. All patients had undergone a "dual-tracer" PET/CT same-day protocol with (11)C-ACT PET/CT followed by (18)F-FDG PET/CT. Sets of criteria were chosen to define "metastasis" and "no metastasis" on a patient basis. The patients considered as true-positive (n = 97) were then divided into 4 groups on the basis of their primary HCC tracer avidity: (18)F-FDG-avid group, (11)C-ACT-avid group, (18)F-FDG- and (11)C-ACT-avid group, and a posttreatment group with metastasis but no baseline dual-tracer PET characterization of the primary tumor and no hepatic recurrence., Results: On a patient basis, dual-tracer PET/CT had a sensitivity of 98%, a specificity of 86%, a positive predictive value of 97%, a negative predictive value of 90%, and an accuracy of 96% in the detection of HCC metastasis. On a lesion basis, 273 metastatic HCC lesions considered as true-positive were detected and categorized according to the organ or site of metastasis: lymph node (abdominal and thoracic, 49%), lung (32%), bone (8%), and others (10%). The lesion-based and patient-based detection sensitivities were 60% and 64%, respectively, by (11)C-ACT and 77% and 79%, respectively, by (18)F-FDG, and they were complementary. In analyzing lesion tracer avidity, there was a positive statistical correlation between primary HCC avidity with the general tendency of metastasis. Clinically significant changes in management were found in patients with true-positive metastasis, of whom 19% were affected by (11)C-ACT PET alone. Dual-tracer PET/CT was more effective than single-tracer PET/CT in identifying candidates for curative therapy (negative predictive value of dual-tracer, (18)F-FDG, and (11)C-ACT PET/CT: 90%, 49%, and 37%, respectively)., Conclusion: This study confirmed that (18)F-FDG PET/CT is useful in the evaluation of HCC metastasis, although its role in the diagnosis of primary HCC is more limited. Dual-tracer PET/CT had an incremental value and complementary advantage when compared with single-tracer imaging in the evaluation of HCC metastasis.

The successful investigation of 11C-acetate in positron emission tomography (PET) imaging for marking hepatocellular carcinoma (HCC) has been validated by both clinical and quantitative modeling studies. In the previous quantitative studies, all the individual model parameters were estimated by the weighted nonlinear least squares (NLS) algorithm. However, five parameters need to be estimated simultaneously, therefore, the computational time-complexity is high and some estimates are not quite reliable, which limits its application in clinical environment. In addition, liver system modeling with dual-input function is very different from the widespread single-input system modeling. Therefore, most of the currently developed estimation techniques are not applicable. In this paper, two parameter estimation techniques: graphed NLS (GNLS) and graphed dual-input generalized linear least squares (GDGLLS) algorithms were presented for 11C-acetate dual-input liver model. Clinical and simulated data were utilized to test the proposed algorithms by a systematic statistical analysis. Compared to NLS fitting, these two novel methods achieve better estimation reliability and are computationally efficient, and they are extremely powerful for the estimation of the two potential HCC indicators: local hepatic metabolic rate-constant of acetate and relative portal venous contribution to the hepatic blood flow.

Medical parametric imaging with dynamic positron emission tomography (PET) plays an increasingly potential role in modern biomedical research and clinical diagnosis. The key issue in parametric imaging is to estimate parameters based on sampled data at the pixel-by-pixel level from certain dynamic processes described by valid mathematical models. Classic nonlinear least squares (NLS) algorithm requires a "good" initial guess and the computational time-complexity is high, which is impractical for image-wide parameter estimation. Although a variety of fast parametric imaging techniques have been developed, most of them focus on single input systems, which do not provide an optimal solution for dual-input biomedical system parameter estimation, which is the case of liver metabolism. In this study, a dual-input-generalized linear least squares (D-I-GLLS) algorithm was proposed to identify the model parameters including the parameter in the dual-input function. Monte Carlo simulation was conducted to examine this novel fast algorithm. The results of the quantitative analysis suggested that the proposed technique could provide comparable reliability of the parameter estimation with NLS fitting and accurately identify the parameter in the dual-input function. This method may be potentially applicable to other dual-input biomedical system parameter estimation as well.

Our recent research has demonstrated that 11C-acetate could be a complementary tracer to 18F-fluorodeoxyglucose (FDG) in positron emission tomography (PET) imaging of hepatocellular carcinoma (HCC). In our previous modeling study, a three-compartment four-parameter model with a fixed contribution ratio of the liver's two blood supplies was proposed to characterize the kinetic behavior of 11C-acetate in liver. However, in real pathology, both tumor and nontumor liver tissue can be heterogeneous in the distribution and proportion of the two blood supplies. To further improve the accuracy of quantitative analysis, the actual proportion of the hepatic artery and portal vein (PV) in different regions of interest (ROIs) was investigated in this study. An extra parameter av was included in the model input function to describe the contribution of PV to the liver. Ten ROIs extracted from six patients were used to test the models with fixed/nonfixed weighted dual-input function. The weighted nonlinear least squares algorithm was used to estimate all of the parameters. Evaluation of the adequacy of the two models was conducted and the computer simulation was performed to test the estimation accuracy of the new model. The forward clearance K was also estimated by the linear Patlak method. The results show that the model with parameter av in the input function was more suitable for mapping the tracer time activity curves. Moreover, the estimated av value fits the practical physiological and pathological conditions well and could be a potential candidate to provide useful additional diagnostic information for the early detection of hepatic metastases.

It is well known that 40%-50% of hepatocellular carcinoma (HCC) do not show increased 18F-fluorodeoxyglucose (FDG) uptake. Recent research studies have demonstrated that 11C-acetate may be a complementary tracer to FDG in positron emission tomography (PET) imaging of HCC in the liver. Quantitative dynamic modeling is, therefore, conducted to evaluate the kinetic characteristics of this tracer in HCC and nontumor liver tissue. A three-compartment model consisting of four parameters with dual inputs is proposed and compared with that of five parameters. Twelve regions of dynamic datasets of the liver extracted from six patients are used to test the models. Estimation of the adequacy of these models is based on Akaike Information Criteria (AIC) and Schwarz Criteria (SC) by statistical study. The forward clearance K = K1 * k3/(k2 + k3) is estimated and defined as a new parameter called the local hepatic metabolic rate-constant of acetate (LHMRAct) using both the weighted nonlinear least squares (NLS) and the linear Patlak methods. Preliminary results show that the LHMRAct of the HCC is significantly higher than that of the nontumor liver tissue. These model parameters provide quantitative evidence and understanding on the kinetic basis of C-acetate for its potential role in the imaging of HCC using PET.