Slingshot homolog-1 amplifies mitochondrial abnormalities by distinctly impairing health and clearance of mitochondria.

Accumulating toxic protein assemblies, including Aß and tau, and dysfunctional mitochondria are associated with synaptic and neuronal loss in Alzheimer's disease (AD). Such accumulations are thought to be owing to clearance defects in the autophagy-lysosome pathway. Mitochondrial dysfunction is evident in AD brains and animal models at multiple levels, such as mitochondrial genomic mutations, disrupted bioenergetics, deregulated mitochondrial dynamics and impaired clearance of damaged mitochondria (mitophagy). Slingshot homolog-1 (SSH1) is a phosphatase activated by oxidative stress, high intracellular levels of Ca2+ and Aß42 oligomers (Aß42O), known for its function to dephosphorylate/activate cofilin through the N-terminal region. SSH1-mediated cofilin dephosphorylation results in Ab42O-induced severing of F-actin and translocation of cofilin to mitochondria, which promotes mitochondria-mediated apoptosis, synaptic loss and synaptic deficits. On the other hand, SSH1-mediated dephosphorylation/deactivation of the autophagy-cargo receptor p62 (SQSTM1), through its C-terminal region, inhibits p62 autophagy flux. However, the interplay between these two different activities of SSH1 in Aß42O-induced mitochondrial toxicity remains unclear. In this study, we assessed the role of endogenous SSH1 and different regions of SSH1 in regulating mitochondrial health, mitochondrial respiration, clearance of damaged mitochondria and synaptic integrity in vitro and in vivo. Our results indicate that SSH1 suppresses mitochondrial health and respiration through the cofilin-binding N-terminal region, whereas SSH1 impairs mitophagy through a newly identified ~ 100 residue p62-binding domain in the C-terminal region. These results indicate that both N-terminal and C-terminal regions negatively impact mitochondria by distinct and independent modalities to amplify mitochondrial abnormalities, making SSH1 an excellent target to mitigate AD pathogenesis.

Programmable Optoelectronic Synaptic Transistors Based on MoS2/Ta2NiS5 Heterojunction for Energy-Efficient Neuromorphic Optical Operation.

The optoelectronic synaptic transistors with various functions, broad spectral perception, and low power consumption are an urgent need for the development of advanced optical neural network systems. However, it remains a great challenge to realize the functional diversification of the systems on a single device. 2D van der Waals (vdW) materials can combine unique properties by stacking with each other to form heterojunctions, which may provide a strategy for solving this problem. Herein, an all-2D vdW heterojunction-based programmable optoelectronic synaptic transistor based on MoS2/Ta2NiS5 heterojunctions is demonstrated. The device implements reconfigurable, multilevel non-volatile memory (NVM) states through sequential modulation of multiple optical and electrical stimuli to achieve broadband (532-808 nm), energy-efficient (17.2 fJ), hetero-synaptic functionality in a bionic manner. The intrinsic working mechanisms of the photogating effect caused by band alignment and the interfacial trapping defect modulation induced by gate voltage are revealed by Kelvin-probe force microscopy (KPFM) measurements and carrier transport analysis. Overall, the (opto)electronic synaptic weight controllability for combined in-sensor and in-memory logic processors is realized by the heterojunction properties. The proposed findings facilitate the technical realization of generic all 2D hetero-synapses for future artificial vision systems, opto-logical systems, and Internet of Things (IoT) entities.

Aging Increases Global Annual Food Greenhouse Gas Emissions up to 300 Million Tonnes by 2100.

The dietary preferences of the elderly population exhibit distinct variations from the overall averages in most countries, gaining increasing significance due to aging demographics worldwide. These dietary preferences play a crucial role in shaping global food systems, which will result in changed environmental impacts in the future such as greenhouse gas (GHG) emissions. We present a quantitative evaluation of the influence of population aging on the changes in GHG emissions from global food systems. To achieve this, we developed regional dietary coefficients (DCs) of the elderly based on the Global Dietary Database (GDD). We then reconciled the GDD with the dataset from the Food and Agriculture Organization of the United Nations (FAO) to calculate the food GHG emissions of the average population in each of the countries. By applying the DCs, we estimated the national food GHG emissions and obtained the variations between the emissions from aged and average populations. We employed a modified version of the regional integrated model of climate and the economy model (RICE) to forecast the emission trends in different countries based on FAO and GDD data. This integrated approach allowed us to evaluate the dynamic relationships among aging demographics, food consumption patterns, and economic developments within regions. Our results indicate that the annual aging-embodied global food GHG emissions will reach 288 million tonnes of CO2 equivalent (Mt CO2e) by 2100. This estimation is crucial for policymakers, entrepreneurs, and researchers as it provides insights into a potential future environmental challenge and emphasizes the importance of sustainable food production and consumption strategies to GHG emission mitigations associated with aging dietary patterns.

miR-590-5p/Tiam1-mediated glucose metabolism promotes malignant evolution of pancreatic cancer by regulating SLC2A3 stability.

BACKGROUND: T lymphoma invasion and metastasis 1 (Tiam1) is a tumor related gene that specifically activates Rho-like GTPases Rac1 and plays a critical role in the progression of various malignancies. Glycolysis plays an important role in cancer progression, it is crucial for supplying energy and producing metabolic end products, which can maintain the survival of tumor cells. As yet, however, the mechanism of Tiam1 in glycolysis reprogramming of pancreatic cancer (PC) remains to be clarified. Here, we investigated the functional role of Tiam1 in PC cell proliferation, metastasis and glycolysis reprogramming. It is expected to provide a new direction for clinical treatment. METHODS: The clinical relevance of Tiam1 was evaluated in 66 patients with PC, the effect of Tiam1 on cell proliferation was detected via 5-Ethynyl-2'-deoxyuridine (EdU) and colony formation. The ability of cell migration was detected by the wound healing and Transwell. Quantitative real time polymerase chain reaction (qRT-PCR) and luciferase reporter gene experiments clarify the regulatory relationship of miR-590-5p inhibiting Tiam1. Detection of the molecular mechanism of Tiam1 regulating glucose metabolism reprogramming in PC by glucose metabolism kit. RNA sequencing and Co-Immunoprecipitation (CoIP) have identified glucose transporter protein 3 (SLC2A3) as a key downstream target gene for miR-590-5p/Tiam1. RESULTS: We found that Tiam1 expression increased in PC tissues and was associated with lymph node metastasis. The silencing or exogenous overexpression of Tiam1 significantly altered the proliferation, invasion, and angiogenesis of PC cells through glucose metabolism pathway. In addition, Tiam1 could interact with the crucial SLC2A3 and promote the evolution of PC in a SLC2A3-dependent manner. Moreover, miR-590-5p was found to exacerbate the PC cell proliferation, migration and invasion by targeting Tiam1. Furthermore, the reversing effects on proliferation, migration and invasion were found in PC cells with miR-590-5p/Tiam1 overexpression after applying glucose metabolism inhibition. CONCLUSIONS: Our findings demonstrate the critical role of Tiam1 in PC development and the miR-590-5p/Tiam1/SLC2A3 signaling pathway may serve as a target for new PC therapeutic strategies.

Ellagic acid inhibits human colon cancer HCT-116 cells by regulating long noncoding RNAs.

The natural phenolic compound ellagic acid exerts anti-cancer effects, including activity against colorectal cancer (CRC). Previously, we reported that ellagic acid can inhibit the proliferation of CRC, and can induce cell cycle arrest and apoptosis. This study investigated ellagic acid-mediated anticancer effects using the human colon cancer HCT-116 cell line. After 72 h of ellagic acid treatment, a total of 206 long noncoding RNAs (lncRNAs) with differential expression greater than 1.5-fold were identified (115 down-regulated and 91 up-regulated). Furthermore, the co-expression network analysis of differentially expressed lncRNA and mRNA showed that differential expressed lncRNA might be the target of ellagic acid activity in inhibiting CRC.

ß-Arrestin2 oligomers impair the clearance of pathological tau and increase tau aggregates.

Multiple G protein-coupled receptors (GPCRs) are targets in the treatment of dementia, and the arrestins are common to their signaling. ß-Arrestin2 was significantly increased in brains of patients with frontotemporal lobar degeneration (FTLD-tau), a disease second to Alzheimer's as a cause of dementia. Genetic loss and overexpression experiments using genetically encoded reporters and defined mutant constructs in vitro, and in cell lines, primary neurons, and tau P301S mice crossed with ß-arrestin2-/- mice, show that ß-arrestin2 stabilizes pathogenic tau and promotes tau aggregation. Cell and mouse models of FTLD showed this to be maladaptive, fueling a positive feedback cycle of enhanced neuronal tau via non-GPCR mechanisms. Genetic ablation of ß-arrestin2 markedly ablates tau pathology and rescues synaptic plasticity defects in tau P301S transgenic mice. Atomic force microscopy and cellular studies revealed that oligomerized, but not monomeric, ß-arrestin2 increases tau by inhibiting self-interaction of the autophagy cargo receptor p62/SQSTM1, impeding p62 autophagy flux. Hence, reduction of oligomerized ß-arrestin2 with virus encoding ß-arrestin2 mutants acting as dominant-negatives markedly reduces tau-laden neurofibrillary tangles in FTLD mice in vivo. Reducing ß-arrestin2 oligomeric status represents a new strategy to alleviate tau pathology in FTLD and related tauopathies.

Curcumin suppressed the proliferation and apoptosis of HPV-positive cervical cancer cells by directly targeting the E6 protein.

Most human papillomavirus (HPV) types, including HPV16 and HPV18, are closely related to the occurrence of cervical cancer, predominantly through the action of viral oncoproteins E6 and E7. Curcumin, the active ingredient of the turmeric plant, has been gaining attention over the past two decades as an antioxidant, anti-inflammatory, and anticancer agent. In the present study, the HPV-positive cervical cancer cells HeLa and CaSki were treated with curcumin, and the results showed that curcumin has a dose-dependent and time-dependent inhibitory effect on cell viability. In addition, apoptosis induction was further quantitatively confirmed through flow cytometric analysis. Furthermore, the influence of different concentrations of curcumin on the mitochondrial membrane potential was evaluated through JC-1 staining and found to dramatically decrease the membrane potential in treated HeLa and CaSki cells, suggesting the critical role of the mitochondrial pathway in their apoptosis-inducing effect. This study also demonstrated the wound-healing potential of curcumin, and the results of transwell assays showed that curcumin treatment inhibited HeLa and CaSki cell invasion and migration in a dose-dependent manner compared with the control treatment. Curcumin also downregulated the expression of Bcl-2, N-cadherin, and Vimentin and upregulated the expression of Bax, C-caspase-3, and E-cadherin in both cell lines. Further research showed that curcumin also selectively inhibited the expression of the viral oncoproteins E6 and E7, as demonstrated by western blot analysis; moreover, the downregulation of E6 was more significant than that of E7. Our research also showed that coculture with cells infected with siE6 lentivirus (siE6 cells) can inhibit the proliferation, invasion, and metastasis of HPV-positive cells. While the siE6 cells were also treated with curcumin, the effect of curcumin monotherapy was offset. In summary, our research shows that curcumin regulates the apoptosis, migration, and invasion of cervical cancer cells, and the mechanism may be related to its ability to downregulate E6. This study provides a foundation for future research on the prevention and treatment of cervical cancer.

Prevention of Pregabalin-Related Side Effects Using Slow Dose Escalation Before Surgery: A Trial in Primary Total Joint Arthroplasty Within the Enhanced Recovery After Surgery Pathway.

BACKGROUND: The side effects of pregabalin likely occur after the first dose. We aimed to evaluate the effect of 75 milligrams (mg) of pregabalin prescribed as an initial dose with a slow dose escalation for primary total joint arthroplasty within the enhanced recovery after surgery pathway. METHODS: Participants were randomly assigned to two groups. Fifty-eight patients were enrolled, and twenty-nine were assigned to each group. Group 1 (G1) received pregabalin (37.5 mg) twice on the day before surgery, as well as pregabalin 75 mg two hours pre-operatively; Group 2 (G2) received none on the day before surgery and the same dose of pregabalin at two hours pre-operatively. The primary outcome was dizziness assessed by severity; secondary outcomes included nausea, vomiting, sedation, opioid consumption, independent transfer at six hours post-operatively, time to readiness for independent transfers, time to readiness for discharge, and pain. RESULTS: At two, four, and six hours post-operatively, the proportion of patients experiencing dizziness and nausea was significantly greater in G2 than in G1, and opioid consumption was significantly greater in G2 than in G1 (P = .012). The proportion of independent transfers at six hours post-operatively was significantly greater in G1 than in G2 (P = .010). The time to readiness for independent transfers was significantly shorter in G1 than in G2 (P = .016). CONCLUSION: Prescription of pregabalin 37.5 mg twice on the day before surgery was effective in reducing early postoperative dizziness and nausea after receiving pregabalin 75 mg two hours pre-operatively. It also promoted early independent transfers and reduced opioid consumption.

Improving Blueberry Anthocyanins' Stability Using a Ferritin Nanocarrier.

Blueberries are fruits known for their high level of anthocyanins, which have high nutritional value and several biological properties. However, the chemical instability of anthocyanins is one of the major limitations of their application. The stability of blueberry anthocyanin extracts (BAEs) encapsulated in a ferritin nanocarrier was investigated in this study for several influencing parameters, including pH, temperature, UV-visible light, redox agents, and various metal ions. The outcomes supported the positive role of protein nanoparticles in enhancing the stability of blueberry anthocyanins by demonstrating that the stability of encapsulated BAE nanoparticles with ferritin carriers was significantly higher than that of free BAEs and a mixture of BAEs and ferritin carriers. This study provides an alternative approach for enhancing blueberry anthocyanin stability using ferritin nanocarrier encapsulation.

MRI-Based Multiple Instance Convolutional Neural Network for Increased Accuracy in the Differentiation of Borderline and Malignant Epithelial Ovarian Tumors.

BACKGROUND: Preoperative differentiation of borderline from malignant epithelial ovarian tumors (BEOT vs. MEOT) is challenging and can significantly impact surgical management. PURPOSE: To develop a multiple instance convolutional neural network (MICNN) that can differentiate BEOT from MEOT, and to compare its diagnostic performance with that of radiologists. STUDY TYPE: Retrospective study of eight clinical centers. SUBJECTS: Between January 2010 and June 2018, a total of 501 women (mean age, 48.93 ± 14.05 years) with histopathologically confirmed BEOT (N = 165) or MEOT (N = 336) were divided into the training (N = 342) and validation cohorts (N = 159). FIELD STRENGTH/SEQUENCE: Three axial sequences from 1.5 or 3 T scanner were used: fast spin echo T2-weighted imaging with fat saturation (T2WI FS), echo planar diffusion-weighted imaging, and 2D volumetric interpolated breath-hold examination of contrast-enhanced T1-weighted imaging (CE-T1WI) with FS. ASSESSMENT: Three monoparametric MICNN models were built based on T2WI FS, apparent diffusion coefficient map, and CE-T1WI. Based on these monoparametric models, we constructed an early multiparametric (EMP) model and a late multiparametric (LMP) model using early and late information fusion methods, respectively. The diagnostic performance of the models was evaluated using the receiver operating characteristic (ROC) curve and compared to the performance of six radiologists with varying levels of experience. STATISTICAL TESTS: We used DeLong test, chi-square test, Mann-Whitney U-test, and t-test, with significance level of 0.05. RESULTS: Both EMP and LMP models differentiated BEOT from MEOT, with an area under the ROC curve (AUC) of 0.855 (95% CI, 0.795-0.915) and 0.884 (95% CI, 0.831-0.938), respectively. The AUC of the LMP model was significantly higher than the radiologists' pooled AUC (0.884 vs. 0.797). DATA CONCLUSION: The developed MICNN models can effectively differentiate BEOT from MEOT and the diagnostic performances (AUCs) were more superior than that of the radiologists' assessments. LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY STAGE: 2.

CT-based radiomics signatures can predict the tumor response of non-small cell lung cancer patients treated with first-line chemotherapy and targeted therapy.

OBJECTIVES: The goal of this study was to evaluate the effectiveness of radiomics signatures on pre-treatment computed tomography (CT) images of lungs to predict the tumor responses of non-small cell lung cancer (NSCLC) patients treated with first-line chemotherapy, targeted therapy, or a combination of both. MATERIALS AND METHODS: This retrospective study included 322 NSCLC patients who were treated with first-line chemotherapy, targeted therapy, or a combination of both. Of these patients, 224 were randomly assigned to a cohort to help develop the radiomics signature. A total of 1946 radiomics features were obtained from each patient's CT scan. The top-ranked features were selected by the Minimum Redundancy Maximum Relevance (MRMR) feature-ranking method and used to build a lightweight radiomics signature with the Random Forest (RF) classifier. The independent predictive (IP) features (AUC > 0.6, p value < 0.05) were further identified from the top-ranked features and used to build a refined radiomics signature by the RF classifier. Its prediction performance was tested on the validation cohort, which consisted of the remaining 98 patients. RESULTS: The initial lightweight radiomics signature constructed from 15 top-ranked features had an AUC of 0.721 (95% CI, 0.619-0.823). After six IP features were further identified and a refined radiomics signature was built, it had an AUC of 0.746 (95% CI, 0.646-0.846). CONCLUSIONS: Radiomics signatures based on pre-treatment CT scans can accurately predict tumor response in NSCLC patients after first-line chemotherapy or targeted therapy treatments. Radiomics features could be used as promising prognostic imaging biomarkers in the future. KEY POINTS: The radiomics signature extracted from baseline CT images in patients with NSCLC can predict response to first-line chemotherapy, targeted therapy, or both treatments with an AUC = 0.746 (95% CI, 0.646-0.846). The radiomics signature could be used as a new biomarker for quantitative analysis in radiology, which might provide value in decision-making and to define personalized treatments for cancer patients.

Pushing the Length Limit of Dihydrodiboraacenes: Synthesis and Characterizations of Boron-Embedded Heptacene and Nonacene.

Boron-embedded heteroacenes (boraacenes) have attracted enormous interest in organic chemistry and materials science. However, extending the skeleton of boraacenes to higher acenes (N≥6) is synthetically challenging because of their limited stability under ambient conditions. Herein, we report the synthesis of boron-embedded heptacene (DBH) and nonacene (DBN) as the hitherto longest boraacenes. The former is highly stable (even after 240 h in tetrahydrofuran), while the latter is air-sensitive with the half-life (t1/2 ) of 11.8 min. The structures of both compounds are verified by single-crystal X-ray diffraction, revealing a linear backbone with an antiaromatic C4 B2 core. Photophysical characterizations associated with theoretical calculations indicate that both compounds exhibit highly efficient anti-Kasha emissions. Remarkably, the air-stable DBH manifests an ultrahigh photoluminescence quantum yield (PLQY) of 98±2 % and can be chemically reduced to its radical anion and dianion states, implying the value of boron-doped higher acenes as novel functional materials.

POLR2A blocks osteoclastic bone resorption and protects against osteoporosis by interacting with CREB1.

Bone-resorbing osteoclasts significantly contribute to osteoporosis, and understanding the mechanisms of osteoclastogenesis is crucial for developing new drugs to treat diseases associated with bone loss. Here, we report that POLR2A is upregulated during osteoclastogenesis. Functional analyses showed that the inhibition of POLR2A decreased osteoclastogenesis, whereas the overexpression of POLR2A had completely opposite effects in vitro. Notably, the osteoclast-specific deletion of POLR2A blocks bone resorption in vivo. Furthermore, POLR2A loss-of-function suppresses estrogen deficiency-induced bone resorption. Mechanistically, POLR2A regulates the assembly of CREB1 on the regulatory elements of its target genes. Collectively, using genetic, pharmacological, and disease mouse models, we have identified a previously undescribed protein that interacts with CREB1 to regulate osteoclastic bone resorption.

Focus calibration method based on the illumination beam scanning angle modulation in a grating alignment system.

A focus calibration method is developed to determine the focus position of a grating alignment system. An illumination beam scanning module is utilized to generate a circular motion for the beam, which forms an angular modulation interference image on the reference mark. A theoretical model is presented to determine the focus by determining the alignment grating z-position, at which the alignment offset is independent of the incident beam tilt. The standard uncertainty of the focus calibration results is estimated to be better than 150 nm. This technique may improve the measurement performance for lithography systems and precision machine applications.

Multiparametric Magnetic Resonance Imaging-Based Peritumoral Radiomics for Preoperative Prediction of the Presence of Extracapsular Extension With Prostate Cancer.

BACKGROUND: Preoperative prediction of extracapsular extension (ECE) of prostate cancer (PCa) is important to guide clinical decision-making and improve patient prognosis. PURPOSE: To investigate the value of multiparametric magnetic resonance imaging (mpMRI)-based peritumoral radiomics for preoperative prediction of the presence of ECE. STUDY TYPE: Retrospective. POPULATION: Two hundred eighty-four patients with PCa from two centers (center 1: 226 patients; center 2: 58 patients). Cases from center 1 were randomly divided into training (158 patients) and internal validation (68 patients) sets. Cases from center 2 were assigned to the external validation set. FIELD STRENGTH/SEQUENCE: A 3.0 T MRI scanners (three vendors). Sequence: Pelvic T2-weighted turbo/fast spin echo sequence and diffusion weighted echo planar imaging sequence. ASSESSMENT: The peritumoral region (PTR) was obtained by 3-12 mm (half of the tumor length) 3D dilatation of the intratumoral region (ITR). Single-MRI radiomics signatures, mpMRI radiomics signatures, and integrated models, which combined clinical characteristics with the radiomics signatures were built. The discrimination ability was assessed by area under the receiver operating characteristic curve (AUC) in the internal and external validation sets. STATISTICAL TESTS: Fisher's exact test, Mann-Whitney U-test, DeLong test. RESULTS: The PTR radiomics signatures demonstrated significantly better performance than the corresponding ITR radiomics signatures (AUC: 0.674 vs. 0.554, P < 0.05 on T2-weighted, 0.652 vs. 0.546, P < 0.05 on apparent diffusion coefficient, 0.682 vs. 0.556 on mpMRI in the external validation set). The integrated models combining the PTR radiomics signature with clinical characteristics performed better than corresponding radiomics signatures in the internal validation set (eg. AUC: 0.718 vs. 0.671, P < 0.05 on mpMRI) but performed similar in the external validation set (eg. AUC: 0.684, vs. 0.682, P = 0.45 on mpMRI). DATA CONCLUSION: The peritumoral radiomics can better predict the presence of ECE preoperatively compared with the intratumoral radiomics and may have better generalization than clinical characteristics. EVIDENCE LEVEL: 4 TECHNICAL EFFICACY: 2.

CHCHD10-regulated OPA1-mitofilin complex mediates TDP-43-induced mitochondrial phenotypes associated with frontotemporal dementia.

Mutations in CHCHD10, a gene coding for a mitochondrial protein, are implicated in ALS-FTD spectrum disorders, which are pathologically characterized by transactive response DNA binding protein 43 kDa (TDP-43) accumulation. While both TDP-43 and CHCHD10 mutations drive mitochondrial pathogenesis, mechanisms underlying such phenotypes are unclear. Moreover, despite the disruption of the mitochondrial mitofilin protein complex at cristae junctions in patient fibroblasts bearing the CHCHD10S59L mutation, the role of CHCHD10 variants in mitofilin-associated protein complexes in brain has not been examined. Here, we utilized novel CHCHD10 transgenic mouse variants (WT, R15L, & S59L), TDP-43 transgenic mice, FTLD-TDP patient brains, and transfected cells to assess the interplay between CHCHD10 and TDP-43 on mitochondrial phenotypes. We show that CHCHD10 mutations disrupt mitochondrial OPA1-mitofilin complexes in brain, associated with impaired mitochondrial fusion and respiration. Likewise, CHCHD10 levels and OPA1-mitofilin complexes are significantly reduced in brains of FTLD-TDP patients and TDP-43 transgenic mice. In cultured cells, CHCHD10 knockdown results in OPA1-mitofilin complex disassembly, while TDP-43 overexpression also reduces CHCHD10, promotes OPA1-mitofilin complex disassembly via CHCHD10, and impairs mitochondrial fusion and respiration, phenotypes that are rescued by wild type (WT) CHCHD10. These results indicate that disruption of CHCHD10-regulated OPA1-mitofilin complex contributes to mitochondrial abnormalities in FTLD-TDP and suggest that CHCHD10 restoration could ameliorate mitochondrial dysfunction in FTLD-TDP.

MR image-based radiomics to differentiate type Ι and type ΙΙ epithelial ovarian cancers.

OBJECTIVES: Epithelial ovarian cancers (EOC) can be divided into type I and type II according to etiology and prognosis. Accurate subtype differentiation can substantially impact patient management. In this study, we aimed to construct an MR image-based radiomics model to differentiate between type I and type II EOC. METHODS: In this multicenter retrospective study, a total of 294 EOC patients from January 2010 to February 2019 were enrolled. Quantitative MR imaging features were extracted from the following axial sequences: T2WI FS, DWI, ADC, and CE-T1WI. A combined model was constructed based on the combination of these four MR sequences. The diagnostic performance was evaluated by ROC-AUC. In addition, an occlusion test was carried out to identify the most critical region for EOC differentiation. RESULTS: The combined radiomics model exhibited superior diagnostic capability over all four single-parametric radiomics models, both in internal and external validation cohorts (AUC of 0.806 and 0.847, respectively). The occlusion test revealed that the most critical region for differential diagnosis was the border zone between the solid and cystic components, or the less compact areas of solid component on direct visual inspection. CONCLUSIONS: MR image-based radiomics modeling can differentiate between type I and type II EOC and identify the most critical region for differential diagnosis. KEY POINTS: • Combined radiomics models exhibited superior diagnostic capability over all four single-parametric radiomics models, both in internal and external validation cohorts (AUC of 0.834 and 0.847, respectively). • The occlusion test revealed that the most crucial region for differentiating type Ι and type ΙΙ EOC was the border zone between the solid and cystic components, or the less compact areas of solid component on direct visual inspection on T2WI FS. • The light-combined model (constructed by T2WI FS, DWI, and ADC sequences) can be used for patients who are not suitable for contrast agent use.

Predicting the Outcome of Transcatheter Arterial Embolization Therapy for Unresectable Hepatocellular Carcinoma Based on Radiomics of Preoperative Multiparameter MRI.

BACKGROUND: In unresectable hepatocellular carcinoma (HCC), methods to predict patients at increased risk of progression are required. PURPOSE: To investigate the feasibility of radiomics model in predicting early progression of unresectable HCC after transcatheter arterial chemoembolization (TACE) therapy using preoperative multiparametric magnetic resonance imaging (MP-MRI). STUDY TYPE: Retrospective. POPULATION: A total of 84 patients with BCLC B stage HCC from one medical center. According to the modified response evaluation criteria in solid tumors, patients who progressed at 6 months after TACE therapy were assigned as the progressive disease (PD) group (n = 32). Patients whose MRI was performed on four devices were divided into a training cohort (n = 67). Patients whose MRI was performed on other than the previous four devices were used as the testing set (n = 17). FIELD STRENGTH/SEQUENCE: 3.0T, 1.5T axial T2 -weighted imaging (T2 WI), diffusion-weighted imaging (DWI, b = 0, 500 s/mm2 ), and apparent diffusion coefficient (ADC) ASSESSMENT: PD was confirmed via imaging studies with MRI. Risk factors, including age, alpha fetoprotein (AFP), size, and radiomic-related features of PD were assessed. In addition, the discrimination ability of each radiomics signature was tested on an independent testing set. STATISTICAL TESTS: The area under the receiver-operator characteristic (ROC) curve (AUC) was used to evaluate the predictive accuracy of the radiomic signature in both the training and testing sets. The results indicated that the MP-MRI model achieved the greatest benefit. RESULTS: In the testing set, the model based on DWI features presented an AUC of (b = 0, 0.786; b = 500, 0.729), followed by T2 WI features (0.729) and ADC (0.714). The AUC of the MP-MRI signature was increased to 0.800 compared to any single MRI signature. The multivariate logistic analysis identified the radiomics signature as independent parameters of PD, while clinical information such as age, AFP, size, etc., had no significance in the PD group. DATA CONCLUSION: Preoperative MP-MRI has the potential to predict the outcome of TACE therapy for unresectable HCC. In addition, these image features may be complementary to the current staging systems of HCC patients. LEVEL OF EVIDENCE: 2. TECHNICAL EFFICACY STAGE: 3. J. Magn. Reson. Imaging 2020;52:1083-1090.

MRI-Based Machine Learning for Differentiating Borderline From Malignant Epithelial Ovarian Tumors: A Multicenter Study.

BACKGROUND: Preoperative differentiation of borderline from malignant epithelial ovarian tumors (BEOT from MEOT) can impact surgical management. MRI has improved this assessment but subjective interpretation by radiologists may lead to inconsistent results. PURPOSE: To develop and validate an objective MRI-based machine-learning (ML) assessment model for differentiating BEOT from MEOT, and compare the performance against radiologists' interpretation. STUDY TYPE: Retrospective study of eight clinical centers. POPULATION: In all, 501 women with histopathologically-confirmed BEOT (n = 165) or MEOT (n = 336) from 2010 to 2018 were enrolled. Three cohorts were constructed: a training cohort (n = 250), an internal validation cohort (n = 92), and an external validation cohort (n = 159). FIELD STRENGTH/SEQUENCE: Preoperative MRI within 2 weeks of surgery. Single- and multiparameter (MP) machine-learning assessment models were built utilizing the following four MRI sequences: T2 -weighted imaging (T2 WI), fat saturation (FS), diffusion-weighted imaging (DWI), apparent diffusion coefficient (ADC), and contrast-enhanced (CE)-T1 WI. ASSESSMENT: Diagnostic performance of the models was assessed for both whole tumor (WT) and solid tumor (ST) components. Assessment of the performance of the model in discriminating BEOT vs. early-stage MEOT was made. Six radiologists of varying experience also interpreted the MR images. STATISTICAL TESTS: Mann-Whitney U-test: significance of the clinical characteristics; chi-square test: difference of label; DeLong test: difference of receiver operating characteristic (ROC). RESULTS: The MP-ST model performed better than the MP-WT model for both the internal validation cohort (area under the curve [AUC] = 0.932 vs. 0.917) and external validation cohort (AUC = 0.902 vs. 0.767). The model showed capability in discriminating BEOT vs. early-stage MEOT, with AUCs of 0.909 and 0.920, respectively. Radiologist performance was considerably poorer than both the internal (mean AUC = 0.792; range, 0.679-0.924) and external (mean AUC = 0.797; range, 0.744-0.867) validation cohorts. DATA CONCLUSION: Performance of the MRI-based ML model was robust and superior to subjective assessment of radiologists. If our approach can be implemented in clinical practice, improved preoperative prediction could potentially lead to preserved ovarian function and fertility for some women. LEVEL OF EVIDENCE: Level 4. TECHNICAL EFFICACY: Stage 2. J. Magn. Reson. Imaging 2020;52:897-904.

Coating film and asymmetric amplitude difference effects on measurement performance in phase grating interference-based metrology.

In this study, the effects of the coating film thickness on a grating interferometry system were analyzed. The asymmetry-induced error of the deformed phase grating varied periodically with the coating film thickness, due to the spurious interference of multiple reflections in the film layer and asymmetry in the amplitudes of the diffraction orders, which led to phase offsets (and thus position errors). The average error obtained with a multiorder interferometer was compared to that simulated by atomic force microscopy. The simulation and measurement results were consistent with the theoretical analysis, which will facilitate accurate measurement error analysis.