Phosphatidylserine enrichment in the nuclear membrane regulates key enzymes of phosphatidylcholine synthesis.

Phosphatidylserine (PS) is an important anionic phospholipid that is synthesized within the endoplasmic reticulum (ER). While PS shows the highest enrichment and serves important functional roles in the plasma membrane (PM) but its role in the nucleus is poorly explored. Using three orthogonal approaches, we found that PS is also uniquely enriched in the inner nuclear membrane (INM) and the nuclear reticulum (NR). Nuclear PS is critical for supporting the translocation of CCTα and Lipin1α, two key enzymes important for phosphatidylcholine (PC) biosynthesis, from the nuclear matrix to the INM and NR in response to oleic acid treatment. We identified the PS-interacting regions within the M-domain of CCTα and M-Lip domain of Lipin1α, and show that lipid droplet formation is altered by manipulations of nuclear PS availability. Our studies reveal an unrecognized regulatory role of nuclear PS levels in the regulation of key PC synthesizing enzymes within the nucleus.

Performance of LI-RADS category 5 vs combined categories 4 and 5: a systemic review and meta-analysis.

OBJECTIVE: Computed tomography (CT)/magnetic resonance imaging (MRI) Liver Imaging Reporting and Data System (LI-RADS, LR) category 5 has high specificity and modest sensitivity for diagnosis of hepatocellular carcinoma (HCC). The purpose of this study was to compare the diagnostic performance of LR-5 vs combined LR-4 and LR-5 (LR-4/5) for HCC diagnosis. METHODS: MEDLINE and EMBASE databases through January 03, 2023 were searched for studies reporting the performance of LR-5 and combined LR-4/5 for HCC diagnosis, using CT/MRI LI-RADS version 2014, 2017, or 2018. A bivariate random-effects model was used to calculate the pooled per-observation diagnostic performance. Subgroup analysis was performed based on imaging modalities and type of MRI contrast material. RESULTS: Sixty-nine studies (15,108 observations, 9928 (65.7%) HCCs) were included. Compared to LR-5, combined LR-4/5 showed significantly higher pooled sensitivity (83.0% (95% CI [80.3-85.8%]) vs 65.7% (95% CI [62.4-69.1%]); p < 0.001), lower pooled specificity (75.0% (95% CI [70.5-79.6%]) vs 91.7% (95% CI [90.2-93.1%]); p < 0.001), lower pooled positive likelihood ratio (3.60 (95% CI [3.06-4.23]) vs 6.18 (95% CI [5.35-7.14]); p < 0.001), and lower pooled negative likelihood ratio (0.22 (95% CI [0.19-0.25]) vs 0.38 (95% CI [0.35-0.41]) vs; p < 0.001). Similar results were seen in all subgroups. CONCLUSIONS: Our meta-analysis showed that combining LR-4 and LR-5 would increase sensitivity but decrease specificity, positive likelihood ratio, and negative likelihood ratio. These findings may inform management guidelines and individualized management. CLINICAL RELEVANCE STATEMENT: This meta-analysis estimated the magnitude of changes in the sensitivity and specificity of imaging criteria when LI-RADS categories 4 and 5 were combined; these findings can inform management guidelines and individualized management. KEY POINTS: There is no single worldwide reporting system for liver imaging, partly due to regional needs. Combining LI-RADS categories 4 and 5 increased sensitivity and decreased specificity and positive and negative likelihood ratios. Changes in the sensitivity and specificity of imaging criteria can inform management guidelines and individualized management.

Non-vesicular phosphatidylinositol transfer plays critical roles in defining organelle lipid composition.

Phosphatidylinositol (PI) is the precursor lipid for the minor phosphoinositides (PPIns), which are critical for multiple functions in all eukaryotic cells. It is poorly understood how phosphatidylinositol, which is synthesized in the ER, reaches those membranes where PPIns are formed. Here, we used VT01454, a recently identified inhibitor of class I PI transfer proteins (PITPs), to unravel their roles in lipid metabolism, and solved the structure of inhibitor-bound PITPNA to gain insight into the mode of inhibition. We found that class I PITPs not only distribute PI for PPIns production in various organelles such as the plasma membrane (PM) and late endosomes/lysosomes, but that their inhibition also significantly reduced the levels of phosphatidylserine, di- and triacylglycerols, and other lipids, and caused prominent increases in phosphatidic acid. While VT01454 did not inhibit Golgi PI4P formation nor reduce resting PM PI(4,5)P2 levels, the recovery of the PM pool of PI(4,5)P2 after receptor-mediated hydrolysis required both class I and class II PITPs. Overall, these studies show that class I PITPs differentially regulate phosphoinositide pools and affect the overall cellular lipid landscape.

Preoperative CT and MRI assessment of the longitudinal tumor extent of extrahepatic bile duct cancer after biliary drainage

PURPOSE: To examine the diagnostic performance for the longitudinal extent of extrahepatic bile duct (EHD) cancer on computed tomography (CT) after biliary drainage (BD) and investigate the appropriate timing of magnetic resonance imaging (MRI) acquisition. METHODS: This retrospective study included patients who underwent curative-intent surgery for EHD cancer and CT pre- and post-BD between November 2005 and June 2021. The biliary segment-wise longitudinal tumor extent was evaluated according to the 2019 Korean Society of Abdominal Radiology consensus recommendations, with pre-BD CT, post-BD CT, and both pre- and post-BD CT. The performance for tumor detectability was compared using generalized estimating equation (GEE) method. When preoperative MRI was performed, patients were divided into two subgroups according to the timing of MRI with respect to BD, and the performance of MRI obtained pre- and post-BD was compared. RESULTS: In 105 patients (mean age: 67 ± 8 years; 74 men and 31 women), the performance for tumor detectability was superior using both CT scans compared with using post-BD CT alone (reader 1: sensitivity, 72.6% vs. 64.6%, P < 0.001; specificity, 96.9% vs. 94.8%, P = 0.063; reader 2: sensitivity, 77.2% vs. 72.9%, P = 0.126; specificity, 97.5% vs. 94.2%, P = 0.003), and it was comparable with using pre-BD CT alone. In biliary segments with a catheter, higher sensitivity and specificity were observed using both CT scans than using post-BD CT (reader 1: sensitivity, 74.4% vs. 67.5%, P = 0.006; specificity, 92.4% vs. 88.0%, P = 0.068; reader 2: sensitivity, 80.5% vs. 74.4%, P = 0.013; specificity, 94.3% vs. 88.0%, P = 0.016). Post-BD MRI (n = 30) exhibited a comparable performance to pre-BD MRI (n = 55) (reader 1: sensitivity, 77.9% vs. 75.0%, P = 0.605; specificity, 97.2% vs. 94.9%, P = 0.256; reader 2: sensitivity, 73.2% vs. 72.6%, P = 0.926; specificity, 98.4% vs. 94.9%, P = 0.068). CONCLUSION: Pre-BD CT provided better diagnostic performance in the preoperative evaluation of EHD cancer. The longitudinal tumor extent could be accurately assessed with post-BD MRI, which was similar to pre-BD MRI. CLINICAL SIGNIFICANCE: The acquisition of pre-BD CT could be beneficial for the preoperative evaluation of EHD cancer when BD is planned. Post-BD MRI would not be significantly affected by BD in terms of the diagnostic performance of the longitudinal tumor extent.

Ultrasonographic findings of metabolic dysfunction-associated fatty liver disease: A comparative study with non-alcoholic fatty liver disease and clinical characteristics.

PURPOSE: Metabolic dysfunction-associated fatty liver disease (MAFLD) is a new term proposed to replace non-alcoholic fatty liver disease (NAFLD). We analyzed the ultrasonographic findings of MAFLD and NAFLD. METHODS: We conducted a retrospective cross-sectional study of subjects aged ≥19 years who underwent a health screening examination, including ultrasonography, (n = 17,066). Patients were separated into one of three groups; pure MAFLD (n = 5304), pure NAFLD (n = 579), and both NAFLD & MAFLD (n = 11,183). The outcomes were the degree of fatty liver disease and liver cirrhosis, defined by ultrasonography. In addition, the risk of ultrasonographic cirrhosis was assessed in the MAFLD group based on clinical characteristics. RESULTS: The pure NAFLD group had a lower risk of severe fatty liver disease than the both NAFLD & MAFLD groups (0.9 % vs. 4.4 %, p < 0.001). Cirrhosis was not diagnosed in the NAFLD group. Cirrhosis was more common in the pure MAFLD group than in the both NAFLD & MAFLD group (0.3 % vs. 0.0 %, p < 0.001). In the MAFLD group, multivariable analysis showed that diagnosis by hepatic steatosis index (Odds ratio [OR], 12.39; 95 % confidence interval [CI], 3.40-45.19; p < 0.001) or significant alcohol intake (OR, 9.58, 95 % CI, 1.93-47.61; p = 0.006) was independently associated with risk of liver cirrhosis on ultrasonography. CONCLUSION: Liver cirrhosis was more frequently identified on ultrasonography in patients with MAFLD than in NAFLD. MAFLD diagnosed using the hepatic steatosis index or significant alcohol intake is a risk factor for liver cirrhosis.

Liver Imaging Reporting and Data System version 2018 category 5 for diagnosing hepatocellular carcinoma: an updated meta-analysis.

OBJECTIVE: We performed an updated meta-analysis to determine the diagnostic performance of Liver Imaging Reporting and Data System (LI-RADS, LR) 5 category for hepatocellular carcinoma (HCC) using LI-RADS version 2018 (v2018), and to evaluate differences by imaging modalities and type of MRI contrast material. METHODS: The MEDLINE and Embase databases were searched for studies reporting the performance of LR-5 using v2018 for diagnosing HCC. A bivariate random-effects model was used to calculate the pooled per-observation sensitivity and specificity. Subgroup analysis was performed based on imaging modalities and type of MRI contrast material. RESULTS: Forty-eight studies qualified for the meta-analysis, comprising 9031 patients, 10,547 observations, and 7216 HCCs. The pooled per-observation sensitivity and specificity of LR-5 for diagnosing HCC were 66% (95% CI, 61-70%) and 91% (95% CI, 89-93%), respectively. In the subgroup analysis, MRI with extracellular agent (ECA-MRI) showed significantly higher pooled sensitivity (77% [95% CI, 70-82%]) than CT (66% [95% CI, 58-73%]; p = 0.023) or MRI with gadoxetate (Gx-MRI) (65% [95% CI, 60-70%]; p = 0.001), but there was no significant difference between ECA-MRI and MRI with gadobenate (gadobenate-MRI) (73% [95% CI, 61-82%]; p = 0.495). Pooled specificities were 88% (95% CI, 80-93%) for CT, 92% (95% CI, 86-95%) for ECA-MRI, 93% (95% CI, 91-95%) for Gx-MRI, and 91% (95% CI, 84-95%) for gadobenate-MRI without significant differences (p = 0.084-0.803). CONCLUSIONS: LI-RADS v2018 LR-5 provides high specificity for HCC diagnosis regardless of modality or contrast material, while ECA-MRI showed higher sensitivity than CT or Gx-MRI. CLINICAL RELEVANCE STATEMENT: Refinement of the criteria for improving sensitivity while maintaining high specificity of LR-5 for HCC diagnosis may be an essential future direction. KEY POINTS: • The pooled per-observation sensitivity and specificity of LR-5 for diagnosing HCC using LI-RADSv2018 were 66% and 91%, respectively. • ECA-MRI showed higher sensitivity than CT (77% vs 66%, p = 0.023) or Gx-MRI (77% vs 65%, p = 0.001). • LI-RADS v2018 LR-5 provides high specificity (88-93%) for HCC diagnosis regardless of modality or contrast material type.

Utility of fusion imaging for the evaluation of ultrasound quality in hepatocellular carcinoma surveillance.

PURPOSE: This study evaluated the quality of surveillance ultrasound (US) for hepatocellular carcinoma (HCC) utilizing fusion imaging. METHODS: This research involved a secondary analysis of a prospectively recruited cohort. Under institutional review board approval, participants referred for surveillance US who had undergone liver computed tomography (CT) or magnetic resonance imaging (MRI) within the past year were screened between August 2022 and January 2023. After patient consent was obtained, the US visualization score in the Liver Imaging Reporting and Data System was assessed with fusion imaging at the time of examination. This score was compared to that of conventional US using the extended McNemar test. Multivariable logistic regression analysis was used to identify factors independently associated with a US visualization score of B or C. Factors limiting visualization of focal lesions were recorded during fusion imaging. RESULTS: Among the 105 participants (mean age, 59±11 years; 66 men), US visualization scores of B and C were assigned to 57 (54.3%) and 17 (16.2%) participants, respectively, by conventional US and 54 (51.4%) and 32 (30.5%) participants, respectively, by fusion imaging. The score distribution differed significantly between methods (P=0.010). Male sex was independently associated with US visualization scores of B or C (adjusted odds ratio, 3.73 [95% confidence interval, 1.30 to 10.76]; P=0.015). The most common reason (64.5%) for lesion nondetection was a limited sonic window. CONCLUSION: Conventional US may underestimate the limitations of the sonic window relative to real-time fusion imaging with pre-acquired CT or MRI in the surveillance of HCC.

Interobserver Variability and Diagnostic Performance in Predicting Malignancy of Pancreatic Intraductal Papillary Mucinous Neoplasm with MRI.

Background The 2017 international consensus guidelines for intraductal papillary mucinous neoplasm (IPMN) of the pancreas are widely used. Purpose To evaluate the interobserver agreement and diagnostic performance of MRI assessment in predicting the malignant potential of IPMN according to radiologists' experience. Materials and Methods This multicenter retrospective study included 100 patients with pathologically proven pancreatic IPMN (77 patients with surgery, 23 patients with biopsy) who underwent contrast-enhanced MRI between 2016 and 2021. Eight post-fellowship radiologists (four more-experienced [8-20 years] and four less-experienced [1-4 years] reviewers) evaluated MRI for high-risk stigmata and worrisome features identified by the most recent 2017 guidelines. Interobserver agreement was determined using Fleiss κ statistics according to radiologist experience. The diagnostic performance for malignant IPMN was assessed using receiver operating characteristic curve analysis. Results Among 100 patients (mean age, 66 years ± 10 [SD]; 57 men), 52 (52%) had malignant IPMN. For high-risk stigmata, interobserver agreement was substantial for main pancreatic duct size of at least 10 mm (κ = 0.78; 95% CI: 0.75, 0.82), enhancing mural nodule of at least 5 mm (κ = 0.70: 95% CI: 0.66, 0.74), and at least one high-risk stigmata (κ = 0.73: 95% CI: 0.69, 0.76). The worrisome features showed fair to substantial interobserver agreement (κ range, 0.22-0.80). More-experienced reviewers demonstrated better agreement in the assessment of at least one high-risk stigmata than less-experienced reviewers (κ = 0.77 vs κ = 0.69, P < .001). The overall diagnostic performance of each reviewer was good for the prediction of malignant pancreatic IPMN (area under the receiver operating characteristic curve [AUC] range, 0.77-0.84; median AUC, 0.82), with substantial agreement (κ = 0.76). Conclusion The 2017 international consensus guidelines enabled good diagnostic performance and substantial interobserver agreement for high-risk stigmata but not worrisome features on the evaluation of the malignant pancreatic IPMN using MRI. Agreement tended to be better among more-experienced reviewers than among less-experienced reviewers. © RSNA, 2023 Supplemental material is available for this article.

BrainSuite BIDS App: Containerized Workflows for MRI Analysis.

There has been a concerted effort by the neuroimaging community to establish standards for computational methods for data analysis that promote reproducibility and portability. In particular, the Brain Imaging Data Structure (BIDS) specifies a standard for storing imaging data, and the related BIDS App methodology provides a standard for implementing containerized processing environments that include all necessary dependencies to process BIDS datasets using image processing workflows. We present the BrainSuite BIDS App, which encapsulates the core MRI processing functionality of BrainSuite within the BIDS App framework. Specifically, the BrainSuite BIDS App implements a participant-level workflow comprising three pipelines and a corresponding set of group-level analysis workflows for processing the participant-level outputs. The BrainSuite Anatomical Pipeline (BAP) extracts cortical surface models from a T1-weighted (T1w) MRI. It then performs surface-constrained volumetric registration to align the T1w MRI to a labeled anatomical atlas, which is used to delineate anatomical regions of interest in the MRI brain volume and on the cortical surface models. The BrainSuite Diffusion Pipeline (BDP) processes diffusion-weighted imaging (DWI) data, with steps that include coregistering the DWI data to the T1w scan, correcting for geometric image distortion, and fitting diffusion models to the DWI data. The BrainSuite Functional Pipeline (BFP) performs fMRI processing using a combination of FSL, AFNI, and BrainSuite tools. BFP coregisters the fMRI data to the T1w image, then transforms the data to the anatomical atlas space and to the Human Connectome Project's grayordinate space. Each of these outputs can then be processed during group-level analysis. The outputs of BAP and BDP are analyzed using the BrainSuite Statistics in R (bssr) toolbox, which provides functionality for hypothesis testing and statistical modeling. The outputs of BFP can be analyzed using atlas-based or atlas-free statistical methods during group-level processing. These analyses include the application of BrainSync, which synchronizes the time-series data temporally and enables comparison of resting-state or task-based fMRI data across scans. We also present the BrainSuite Dashboard quality control system, which provides a browser-based interface for reviewing the outputs of individual modules of the participant-level pipelines across a study in real-time as they are generated. BrainSuite Dashboard facilitates rapid review of intermediate results, enabling users to identify processing errors and make adjustments to processing parameters if necessary. The comprehensive functionality included in the BrainSuite BIDS App provides a mechanism for rapidly deploying the BrainSuite workflows into new environments to perform large-scale studies. We demonstrate the capabilities of the BrainSuite BIDS App using structural, diffusion, and functional MRI data from the Amsterdam Open MRI Collection's Population Imaging of Psychology dataset.

Roles of Phosphatidylinositol 4-Phosphorylation in Non-vesicular Cholesterol Trafficking.

Cholesterol (Chol) is an essential component of all eukaryotic cell membranes that affects the function of numerous peripheral as well as integral membrane proteins. Chol is synthesized in the ER, but it is selectively enriched within the plasma membrane (PM) and other endomembranes, which requires Chol to cross the aqueous phase of the cytoplasm. In addition to the classical vesicular trafficking pathways that are known to facilitate the bulk transport of membrane intermediates, Chol is also transported via non-vesicular lipid transfer proteins that work primarily within specialized membrane contact sites. Some of these transport pathways work against established concentration gradients and hence require energy. Recent studies highlight the unique role of phosphoinositides (PPIns), and phosphatidylinositol 4-phosphate (PI4P) in particular, for the control of non-vesicular Chol transport. In this chapter, we will review the emerging connection between Chol, PPIns, and lipid transfer proteins that include the important family of oxysterol-binding protein related proteins, or ORPs.

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The liver imaging reporting and data system (LI-RADS) has been developed with the support of the American College of Radiology to standardize the diagnosis and evaluation of treatment response of hepatocellular carcinoma (HCC). The CT/MRI LI-RADS version 2018 has been incorporated in the American Association for the Study of Liver Diseases guidance. This review examines the effect of CT/MRI LI-RADS on the standardized reporting of liver imaging, and the evidence in diagnosing HCC and evaluating treatment response after locoregional treatment using CT/MRI LI-RADS. The results are compared with other HCC diagnosis guidelines, and future directions are described.

Percentages of Hepatocellular Carcinoma in LI-RADS Categories with CT and MRI: A Systematic Review and Meta-Analysis.

Background The Liver Imaging Reporting and Data System (LI-RADS) CT and MRI algorithm applies equally to CT, MRI with extracellular contrast agents (ECA-MRI), and MRI with gadoxetate (Gx-MRI). Purpose To estimate pooled percentages of hepatocellular carcinoma (HCC) and overall malignancy for each LI-RADS category with CT and MRI. Materials and Methods MEDLINE and EMBASE databases were searched for research articles (January 2014-April 2021) reporting the percentages of observations in each LI-RADS category with use of versions 2014, 2017, or 2018. Study design, population characteristics, imaging modality, reference standard, and numbers of HCC and non-HCC malignancies in each category were recorded. A random-effects model evaluated the pooled percentage of HCC and overall malignancy for each category. Results There were 49 studies with 9620 patients and a total 11 562 observations, comprising 7921 HCCs, 1132 non-HCC malignancies, and 2509 benign entities. No HCC or non-HCC malignancies were reported with any modality in the LR-1 category. The pooled percentages of HCC for CT, ECA-MRI, and Gx-MRI, respectively, were 10%, 6%, and 1% for LR-2 (P = .16); 48%, 31%, and 38% for LR-3 (P = .42); 76%, 64%, and 77% for LR-4 (P = .62); 96%, 95%, and 96% for LR-5 (P = .76); 88%, 76%, and 78% for LR-5V or LR-TIV (tumor in vein) (P = .42); and 20%, 30%, and 35% for LR-M (P = .32). Most LR-M (93%-100%) and LR-5V or LR-TIV (99%-100%) observations were malignant, regardless of modality. Conclusion There was no difference in percentages of hepatocellular carcinoma and overall malignancy between CT, MRI with extracellular contrast agents, and MRI with gadoxetate for any Liver Imaging Reporting and Data System categories. © RSNA, 2023 Supplemental material is available for this article See also the editorial by Ronot in this issue.

Diagnostic performance of CT versus MRI Liver Imaging Reporting and Data System category 5 for hepatocellular carcinoma: a systematic review and meta-analysis of comparative studies.

OBJECTIVE: To compare the performance of Liver Imaging Reporting and Data System category 5 (LR-5) for diagnosing HCC between CT and MRI using comparative studies. METHODS: The MEDLINE and EMBASE databases were searched from inception to April 21, 2021, to identify studies that directly compare the diagnostic performance of LR-5 for HCC between CT and MRI. A bivariate random-effects model was fitted to calculate the pooled per-observation sensitivity and specificity of LR-5 of each modality, and compare the pooled estimates of paired data. Subgroup analysis was performed according to the MRI contrast agent. RESULTS: Seven studies with 1145 observations (725 HCCs) were included in the final analysis. The pooled per-observation sensitivity of LR-5 for diagnosing HCC was higher using MRI (61%; 95% confidence interval [CI], 43-76%; I2 = 95%) than CT (48%; 95% CI, 31-65%; I2 = 97%) (p < 0.001). The pooled per-observation specificities of LR-5 did not show statistically significant difference between CT (96%; 95% CI, 92-98%; I2 = 0%) and MRI (93%; 95% CI, 88-96%; I2 = 16%) (p = 0.054). In the subgroup analysis, extracellular contrast agent-enhanced MRI showed significantly higher pooled per-observation sensitivity than gadoxetic acid-enhanced MRI for diagnosing HCC (73% [95% CI, 55-85%] vs. 55% [95% CI, 39-70%]; p = 0.007), without a significant difference in specificity (93% [95% CI, 80-98%] vs. 94% [95% CI, 87-97%]; p = 0.884). CONCLUSIONS: The LR-5 of MRI showed significantly higher pooled per-observation sensitivity than CT for diagnosing HCC. The pooled per-observation specificities of LR-5 were comparable between the two modalities. KEY POINTS: • The pooled sensitivity of LR-5 using MRI was higher than that using CT (61% versus 48%), but the pooled specificities of LR-5 were not significantly different between CT and MRI (96% versus 93%). • Subgroup analysis according to the MRI contrast media showed a significantly higher pooled per-observation sensitivity using ECA-enhanced MRI than with EOB-enhanced MRI (73% versus 55%), and comparable specificities (93% versus 94%). • Although LI-RADS provides a common diagnostic algorithm for CT or MRI, the per-observation performance of LR-5 can be affected by the imaging modality as well as the MRI contrast agent.

LIPID transfer proteins regulate store-operated calcium entry via control of plasma membrane phosphoinositides.

The ER-resident proteins STIM1 together with the plasma membrane (PM)-localized Orai1 channels constitute the molecular components of the store-operated Ca2+ entry (SOCE) pathway. Prepositioning of STIM1 to the peripheral ER close to the PM ensures its efficient interaction with Orai1 upon a decrease in the ER luminal Ca2+ concentration. The C-terminal polybasic domain of STIM1 has been identified as mediating the interaction with PM phosphoinositides and hence positions the molecule to ER-PM contact sites. Here we show that STIM1 requires PM phosphatidylinositol 4-phosphate (PI4P) for efficient PM interaction. Accordingly, oxysterol binding protein related proteins (ORPs) that work at ER-PM junctions and consume PI4P gradients exert important control over the Ca2+ entry process. These studies reveal an important connection between non-vesicular lipid transport at ER-PM contact sites and regulation of ER Ca2+store refilling.

Metabolic routing maintains the unique fatty acid composition of phosphoinositides.

Phosphoinositide lipids (PPIn) are enriched in stearic- and arachidonic acids (38:4) but how this enrichment is established and maintained during phospholipase C (PLC) activation is unknown. Here we show that the metabolic fate of newly synthesized phosphatidic acid (PA), the lipid precursor of phosphatidylinositol (PI), is influenced by the fatty acyl-CoA used with preferential routing of the arachidonoyl-enriched species toward PI synthesis. Furthermore, during agonist stimulation the unsaturated forms of PI(4,5P)2 are replenished significantly faster than the more saturated ones, suggesting a favored recycling of the unsaturated forms of the PLC-generated hydrolytic products. Cytidine diphosphate diacylglycerol synthase 2 (CDS2) but not CDS1 was found to contribute to increased PI resynthesis during PLC activation. Lastly, while the lipid transfer protein, Nir2 is found to contribute to rapid PPIn resynthesis during PLC activation, the faster re-synthesis of the 38:4 species does not depend on Nir2. Therefore, the fatty acid side-chain composition of the lipid precursors used for PI synthesis is an important determinant of their metabolic fates, which also contributes to the maintenance of the unique fatty acid profile of PPIn lipids.

Utility of Diffusion-Weighted MRI for Detection of Locally Recurrent Pancreatic Cancer After Surgical Resection.

BACKGROUND. Overlapping imaging findings between local tumor recurrence and postsurgical fibrosis represent a major clinical challenge after pancreatic ductal adeno-carcinoma (PDAC) resection. OBJECTIVE. The purpose of this study was to compare the diagnostic performance of MRI with and without DWI for differentiating locally recurrent tumor and postsurgical fibrosis after PDAC resection. METHODS. This retrospective study included 66 patients (35 men, 31 women; mean age, 60.5 years) who underwent PDAC resection between January 2009 and March 2016, postoperative surveillance CT showing a soft-tissue lesion at the operative site or at the site of peripancreatic vessels, and subsequent MRI with DWI for further evaluation. CT at least 6 months after MRI served as the reference standard, with increase in size of the soft tissue by 5 mm or more differentiating locally recurrent tumor (n = 26) and postsurgical fibrosis (n = 40). Two observers in consensus evaluated MRI characteristics of the soft-tissue lesions. Two additional observers independently reviewed MRI examinations in two separate sessions (conventional MRI alone vs MRI with DWI), recording likelihood of recurrent tumor using a 1-5 scale. ROC analysis was performed, considering scores of 4 or 5 as positive. RESULTS. Subjective diffusion restriction was more common in locally recurrent tumor than postsurgical fibrosis (88.5% vs 25.0%, p = .01). Median ADC was lower for locally recurrent tumor than postsurgical fibrosis (1.3 vs 1.7 × 10-3 mm2/s, p < .001). For both observers, MRI with DWI in comparison with conventional MRI alone showed higher AUC for diagnosis of locally recurrent tumor (observer 1: 0.805 vs 0.707, p = .048; observer 2: 0.898 vs 0.637, p < .001) and higher sensitivity (observer 1: 88.5% vs 61.5%, p = .008; observer 2: 84.6% vs 42.3%, p = .001) but no difference in specificity (observer 1: 72.5% vs 80.0%, p = .08; observer 2, 95.0% vs 85.0%, p = .10). Interobserver agreement was moderate for conventional MRI (κ = 0.41) and good for conventional MRI with DWI (κ = 0.62). CONCLUSION. The addition of DWI to conventional MRI improves the differentiation of locally recurrent tumor and postsurgical fibrosis after PDAC resection, primarily because of improved sensitivity for recurrence. CLINICAL IMPACT. The findings indicate a potential role for MRI with DWI in surveillance protocols after PDAC resection.

Second-line Sonazoid-enhanced ultrasonography for Liver Imaging Reporting and Data System category 3 and 4 on gadoxetate-enhanced magnetic resonance imaging.

PURPOSE: This study investigated the utility of second-line contrast-enhanced ultrasonography (CEUS) using Sonazoid in Liver Imaging Reporting and Data System category 3 (LR-3) and 4 (LR-4) observations on gadoxetate-enhanced magnetic resonance imaging (MRI). METHODS: This retrospective study included LR-3 or LR-4 observations on gadoxetate-enhanced MRI subsequently evaluated with CEUS from 2013 to 2017. The presence of MRI features, CEUSarterial phase hyperenhancement (CEUS-APHE), and Kupffer phase defect (KPD) was evaluated. Multivariable logistic regression analysis was performed to identify significant imaging features associated with the diagnosis of hepatocellular carcinoma (HCC). The optimal diagnostic criteria were investigated using the McNemar test. RESULTS: In total, 104 patients with 104 observations (63 HCCs) were included. The presence of both CEUS-APHE and KPD on CEUS enabled the additional detection of 42.3% (11/26) of LR-3 HCCs and 78.4% (29/37) of LR-4 HCCs. Transitional phase (TP) hypointensity (adjusted odds ratio [OR], 10.59; P<0.001), restricted diffusion (adjusted OR, 7.55; P=0.004), and KPD (adjusted OR, 7.16; P=0.003) were significant imaging features for HCC diagnosis. The presence of at least two significant imaging features was optimal for HCC diagnosis (sensitivity, specificity, and accuracy: 88.9%, 78.1%, and 84.6%, respectively), with significantly higher sensitivity than the presence of both CEUS-APHE and KPD (sensitivity, specificity, and accuracy: 63.5% [P=0.001], 92.7% [P=0.077], and 75.0% [P=0.089], respectively). CONCLUSION: The combined interpretation of gadoxetate-enhanced MRI and second-line CEUS using Sonazoid, focusing on TP hypointensity, restricted diffusion, and KPD, may be optimal for further characterizing LR-3 and LR-4 observations.

An integrative model of new product evaluation: A systematic investigation of perceived novelty and product evaluation in the movie industry.

The literature on perceived novelty and product evaluation has diverged into two disparate streams of research. The first stream builds on theories of curiosity and argues that the perceived novelty of a new product benefits product evaluation because it induces curiosity and provides evaluators (e.g., customers) with positive experiences in learning new features of the product and in resolving their curiosity. In contrast, the second stream adopts theories of expectation violations and argues that perceived novelty decreases product evaluation because it violates evaluators' expectations of a new product and requires burdensome efforts to make sense of the product. The main goal of our research is to resolve this theoretical inconsistency by offering an integrative model of new product evaluation that proposes an inverted U-shaped curvilinear relationship between perceived novelty and product evaluation. Based on this model, we further examine whether a producer's reputation plays an ironic moderating role in this curvilinear relationship. Utilizing content analysis and big data approaches with a large sample of 49,835 reviews of 147 movies in the movie industry, we found that an evaluator's perception of the novelty of a new movie benefited product evaluation but only when that perceived novelty was moderate; at higher levels of perceived novelty, the product evaluation decreased. In addition, we compared the curves of high vs. low reputation producers and found that perceived novelty penalized product evaluation of new movies created by high reputation producers.

Incorporation of Ancillary MRI Features Into the LI-RADS Treatment Response Algorithm: Impact on Diagnostic Performance After Locoregional Treatment of Hepatocellular Carcinoma.

BACKGROUND. The LI-RADS treatment response algorithm may lack sufficient sensitivity for viable tumor after locoregional treatment (LRT) for hepatocellular carcinoma (HCC). OBJECTIVE. The purpose of our study was to evaluate the impact of incorporation of ancillary MRI features on the diagnostic performance of the LI-RADS treatment response algorithm after LRT for HCC. METHODS. This retrospective study included 141 patients (114 men, 27 women; median age, 56 years) who underwent gadoxetic acid-enhanced MRI after LRT for HCC between October 2005 and January 2020 and subsequent liver surgery. Two readers assessed lesions for LI-RADS features of viability for ancillary MRI features (transitional phase [TP] hypointensity, hepatobiliary phase [HBP] hypointensity, DWI hyperintensity or low ADC, and mild-to-moderate T2 hyperintensity). Interobserver agreement was assessed before reaching consensus. Significant ancillary features were identified using random forest analysis. The impact of incorporation of significant ancillary features on diagnostic performance for incomplete pathologic necrosis (IPN; pathologically viable tumor > 0 mm) was assessed using McNemar tests. RESULTS. Complete pathologic necrosis (CPN) was observed in 88 of 181 (48.6%) lesions. Interreader agreement was almost perfect for LI-RADS features of viability (κ = 0.92-0.97) and was substantial to almost perfect for ancillary features (κ = 0.73-0.94). Random forest analysis identified TP hypointensity (present in 8.0%, 25.0%, and 75.3% of lesions with CPN, viable tumor < 10 mm, and viable tumor ≥ 10 mm, respectively) and HBP hypointensity (9.2%, 25.0%, and 74.0%, respectively) as significant ancillary features. For detecting IPN, LR-TR (treatment response) Viable or LR-TR Equivocal had higher sensitivity than LR-TR Viable (71.0% vs 57.0%, respectively; p = .001) but had lower specificity (86.4% vs 94.3%, p = .02). However, LR-TR Viable or LR-TR Equivocal and TP hypointensity showed higher sensitivity than LR-TR Viable (64.5% vs 57.0%, p = .02) without a significantly different specificity (90.9% vs 94.3%, p = .25). LR-TR Viable or LR-TR Equivocal and HBP hypointensity also showed higher sensitivity than LR-TR Viable (65.6% vs 57.0%, p = .01) without a significantly different specificity (90.8% vs 94.3%, p = .25). CONCLUSION. TP hypointensity and HBP hypointensity increase the sensitivity of LI-RADS treatment response algorithm for viable tumor without lowering specificity. CLINICAL IMPACT. The two identified ancillary features may improve tumor viability assessment and planning of additional therapies after LRT for HCC.