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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. [ABSTRACT FROM AUTHOR]

Objectives: To investigate the imaging features of pancreatic ductal adenocarcinoma (PDAC) with histological large duct pattern. Methods: Our study included 37 patients (mean age, 66.5 years; 22 women) with surgically proven PDAC with histological large duct pattern, whose imaging features were classified into four types: Type I, solid mass; Type II, predominantly cystic mass with intracystic solid components; Type III, predominantly solid mass with intratumoral cysts; and Type IV, solid mass with peritumoral retention cysts or pseudocysts. Two radiologists independently analyzed both CT and MRI images for the morphological type, presence of abrupt main pancreatic duct (MPD) cutoff, adjacent vascular invasion, diffusion restriction, and reached consensus. Results: On CT, 26 patients (70.3%) had Type I tumors, five (13.5%) had Type II, three (8.1%) had Type III, and three (8.1%) had Type IV. Among the 26 patients with Type I tumors on CT, 16 had tumors with multiple intratumoral cysts within the solid mass on MRI and were subsequently classified as Type III. Accordingly, 10 patients (27.0%) were classified as Type I, five (13.5%) as Type II, 19 (51.7%) as Type III, and three (8.1%) as Type IV on MRI. Of the 37 patients, 27 (73.0%) had an abrupt MPD cutoff, 15 (40.5%) had adjacent vascular invasion, and 25 (67.6%) had diffusion restriction on MRI. Conclusions: Predominantly solid pancreatic masses with small intratumoral cysts visualized on MRI may be a characteristic imaging finding of PDAC with histological large duct pattern, and differentiate it from conventional PDAC or other cystic pancreatic tumors. Clinical relevance statement: Radiologists should be familiar with the various imaging features of PDAC with histological large duct pattern and should be aware that it may mimic other solid or cystic tumors of the pancreas. Key Points: Imaging features of pancreatic ductal adenocarcinoma with histological large duct pattern can be classified into four types. This pathology more frequently appears as a predominantly solid mass with intratumoral cysts on MRI than on CT. Adding MRI to CT may help identify pancreatic ductal adenocarcinoma with histological large duct pattern. [ABSTRACT FROM AUTHOR]

Cancer therapies have evolved from traditional chemotherapy to more precise molecular-targeted immunotherapies, which have been associated with improved side effects and outcomes. These modern strategies rely on cancer-specific biomarkers that differentiate malignant from normal cells. The B7 family of immune checkpoint molecules is crucial for cancer immune evasion and a prime therapeutic target. B7-H6, a recently identified member of the B7 family, has emerged as a promising therapeutic target. Unlike other B7 proteins, B7-H6 is not expressed in healthy tissues but is upregulated in several cancers. It binds to NKp30, activating natural killer (NK) cells and triggering immune responses against cancer cells. This review explores the expression of B7-H6 in different cancers, the factors that regulate its expression, and its intrinsic and extrinsic pathways. Additionally, we discuss potential anticancer therapies targeting B7-H6, highlighting its significance in advancing precision medicine. Understanding the role of B7-H6 in cancer immunity may inform the development of appropriate therapies that exploit its cancer-specific expression. [ABSTRACT FROM AUTHOR]

Background & Aims: Accumulating evidence suggests that certain imaging features of hepatocellular carcinoma (HCC) may have prognostic implications. This study aimed to intraindividually compare MRIs with extracellular contrast agent (ECA‐MRI) and hepatobiliary agent (HBA‐MRI) for prognostic imaging features of HCC and to compare the prediction of microvascular invasion (MVI) and early recurrence between the two MRIs. Methods: The present study included 102 prospectively enrolled at‐risk patients (median age, 61.0 years; 83 men) with surgically resected single HCC with both preoperative ECA‐MRI and HBA‐MRI between July 2019 and June 2023. The McNemar test was used to compare each prognostic imaging feature between the two MRIs. Significant imaging features associated with MVI were identified by multivariable logistic regression analysis, and early recurrence rates (<2 years) were compared between the two MRIs. Results: The frequencies of prognostic imaging features were not significantly different between the two MRIs (p =.07 to >.99). Non‐smooth tumour margin (ECA‐MRI, odds ratio [OR] = 5.30; HBA‐MRI, OR = 7.07) and peritumoral arterial phase hyperenhancement (ECA‐MRI, OR = 4.26; HBA‐MRI, OR = 4.43) were independent factors significantly associated with MVI on both MRIs. Two‐trait predictor of venous invasion (presence of internal arteries and absence of hypoattenuating halo) on ECA‐MRI (OR = 11.24) and peritumoral HBP hypointensity on HBA‐MRI (OR = 20.42) were other predictors of MVI. Early recurrence rates of any two or more significant imaging features (49.8% on ECA‐MRI vs 51.3% on HBA‐MRI, p =.75) were not significantly different between the two MRIs. Conclusion: Prognostic imaging features of HCC may be comparable between ECA‐MRI and HBA‐MRI. [ABSTRACT FROM AUTHOR]

This article studies the effects of higher bank capital requirements. Using new firm-lender matched credit data from South Korea, we document that Basel III coincided with a 25% decline in credit from regulated banks, and an increase of similar magnitude from non-bank (shadow) lenders. We use our data to estimate the effect of capital requirements on bank credit, and the spillover effect of the reform on non-bank lending. We then build a general equilibrium model with heterogeneous banks and firms that replicates these micro estimates. We find that Basel III can account for most of the observed decrease in regulated bank lending and about three quarters of the increase in shadow lending. The latter is driven exclusively by general equilibrium effects of the reform. [ABSTRACT FROM AUTHOR]

Objectives: To predict tumor recurrence in patients who underwent surgical resection of ampullary adenocarcinoma using preoperative magnetic resonance (MR) imaging findings combined with clinical findings. Methods: In this multicenter study, a total of 113 patients (mean age, 62.9 ± 9.8 years; 58 men and 55 women) with ampullary adenocarcinoma who underwent preoperative MR imaging and surgery with margin-negative resection between 2006 and 2017 were retrospectively included. The MR imaging findings were evaluated by two radiologists. Preoperative clinical findings were obtained. Cox proportional regression analyses were used to identify the independent prognostic factors for recurrence-free survival (RFS). A nomogram was created based on the multivariable analysis and was internally validated. Results: Multivariable analysis revealed that presence of infiltrative tumor margin (hazard ratio [HR]: 2.18, p = 0.019), adjacent organ invasion (HR: 3.31, p = 0.006), adjacent vessel invasion (HR: 5.42, p = 0.041), peripancreatic lymph node enlargement (HR: 2.1, p = 0.019), and jaundice (HR: 1.93, p = 0.043) were significantly associated with worse RFS of ampullary adenocarcinoma after surgical resection. These MR imaging and clinical findings were used to construct a nomogram. On internal validation, the calibration plots showed excellent agreement between the predicted probabilities and the actual rates of tumor recurrence, with Harrell's c-index of 0.746. Conclusions: Combination of preoperative MR imaging and clinical findings can be useful for predicting tumor recurrence after surgical resection of ampullary adenocarcinoma. Identifying these features before surgery may aid in better treatment planning and management of these patients. Clinical relevance statement: A predictive nomogram using preoperative MR imaging and clinical findings can be useful in estimating the recurrence-free survival after surgical resection of ampullary adenocarcinoma. Key Points: • Presently, tumor size on imaging is the only non-invasive factor that correlates with recurrence-free survival from ampullary adenocarcinoma; other factors are obtained postoperatively. • Infiltrative tumor margin, adjacent organ invasion, adjacent vessel invasion, peripancreatic lymph node enlargement on MRI, and jaundice are significant predictors for recurrence. • A nomogram incorporating significant MR imaging and clinical findings showed good performance in predicting recurrence-free survival, which can help in treatment planning. [ABSTRACT FROM AUTHOR]

A critical bottleneck toward all-solid-state batteries lies in how the solid(electrode)-solid(electrolyte) interface is fabricated and maintained over repeated cycles. Conventional composite cathodes, with crystallographically distinct electrode/electrolyte interfaces of random particles, create complexities with varying (electro)chemical compatibilities. To address this, we employ an epitaxial model system where the crystal orientations of cathode and solid electrolyte are precisely controlled, and probe the interfaces in real-time during co-sintering by in situ electron microscopy. The interfacial reaction is highly dependent on crystal orientation/alignment, especially the availability of open ion channels. Interfaces bearing open ion paths of NCM are more susceptible to interdiffusion, but stabilize with the early formed passivation layer. Conversely, interfaces with closed ion pathway exhibit stability at intermediate temperatures, but deteriorate rapidly at high temperature due to oxygen evolution, increasing interfacial resistance. The elucidation of these distinct interfacial behaviors emphasizes the need for decoupling collective interfacial properties to enable rational design in solid-state batteries. A bottleneck in solid-state batteries is the solid electrode-electrolyte interface being maintained over repeated cycles. Here, the authors use an epitaxial model system to probe and control the interface in real time. [ABSTRACT FROM AUTHOR]

Background: The impact of excluding intrahepatic segmental vessels from regions of interest (ROIs) on liver stiffness measurement (LSM) via magnetic resonance elastography (MRE) remains uncertain. Purpose: To determine the effect of excluding intrahepatic segmental vessels from ROIs on LSM obtained from MRE. Material and Methods: This retrospective analysis included 95 participants who underwent successful two-dimensional gradient recalled-echo MRE before hepatic tumor resection (n = 49) or living liver donation (n = 46). The conventional LSM was determined by manually drawing ROIs on the elastogram within the 95% confidence region, staying 1 cm within the liver capsule and excluding large hilar vessels, the gallbladder, hepatic lesions, and artifacts. In addition, the modified LSM was determined by excluding intrahepatic segmental vessels. LSMs obtained by the two methods were compared with paired sample signed-rank test. Diagnostic performance for advanced fibrosis was calculated and compared using McNemar's test and Delong's test. The stage of hepatic fibrosis was assessed using surgical specimens by the METAVIR system. Results: The modified LSM was larger than the conventional LSM (2.4 kPa vs. 2.2 kPa in reader 1; 2.7 kPa vs. 2.4 kPa in reader 2; P < 0.001). The modified LSM showed superior sensitivity (0.841 vs. 0.659 in reader 1; 0.864 vs. 0.705 in reader 2; P < 0.05) and area under the curve (0.901 vs. 0.820 in reader 1; 0.912 vs. 0.843 in reader 2; P < 0.05) for detecting advanced fibrosis (≥F3) than conventional LSM. Conclusion: The exclusion of intrahepatic segmental vessels from ROIs in MRE affected the LSM and enhanced diagnostic performance for advanced fibrosis. [ABSTRACT FROM AUTHOR]

Purpose: International expert panels proposed new nomenclatures, metabolic dysfunction-associated fatty liver disease (MAFLD) in 2020 and metabolic dysfunction-associated steatotic liver disease (MASLD) in 2023, along with revised diagnostic criteria to replace non-alcoholic fatty liver disease (NAFLD). We aimed to investigate the differences in NAFLD, MAFLD, and MASLD prevalence with changing nomenclature in a health check-up using magnetic resonance imaging-derived proton density fat fraction (MRI-PDFF) to assess hepatic steatosis. We also examined the prevalence of the sub-classifications of steatotic liver disease (SLD) and the differences in characteristics among the sub-categories. Methods: We included 844 participants who underwent liver MRI-PDFF at our health check-up clinic between January 2020 and November 2022. Hepatic steatosis was defined as MRI-PDFF ≥ 5%. Participants were categorized according to NAFLD, MAFLD, MASLD, and sub-classifications of SLD. Results: The prevalence rates of NAFLD, MAFLD, and MASLD were 25.9%, 29.5%, and 25.2%, respectively. 30.5% of the participants was categorized as SLD. The prevalence rates of the SLD sub-categories were 25.2% for MASLD, 3.7% for MASLD and alcohol-associated liver disease (MetALD), 0.1% for alcohol-associated liver disease, 1.3% for specific etiology SLD, and 0.1% for cryptogenic SLD. Compared with patients in the MASLD group, those in the MetALD group were younger, predominantly male, and exhibited higher levels of serum aspartate aminotransferase, gamma-glutamyl transpeptidase, and triglycerides. Conclusion: The prevalences of NAFLD and MASLD assessed using MRI-PDFF were similar, with MASLD accounting for 97.3% of the patients with NAFLD. The separate MetALD sub-category may have clinical characteristics that differ from those of MASLD. [ABSTRACT FROM AUTHOR]

BACKGROUND: Circulating tumor DNA (ctDNA) is a promising non-invasive marker for detection, diagnosis, treatment selection, and prognosis of hepatocellular carcinoma (HCC). OBJECTIVE: This study aimed to examine the utility of ctDNA as a prognostic and predictive tool in HCC patients treated with nivolumab. METHODS: We analyzed pre-treatment ctDNA from 44 HCC patients using comprehensive genomic testing on a commercially available platform. We utilized log rank test and univariate Cox models to correlate overall survival (OS) and progression-free survival (PFS) with ctDNA expressions. RESULTS: Of 44 patients, 77.3% were men with median age of 67 years. All but 3 patients had at least one alteration identified, and TP53 was the most commonly altered gene (52.3%). Median OS was 17.5 months (95% CI: 12.7, NA). Mutations involving PIK3CA, BRCA1, and CCND1 amplification were associated with shorter OS (P 0.0001, 0.0001 and 0.01, respectively). Median PFS time was 4.01 months (95% CI: 3.06, 9.33). Mutations involving KIT and PIK3CA were associated with shorter PFS (P 0.0001 and 0.0004, respectively), while mutation involving CTNNB1 were associated with longer PFS (p = 0.04). CONCLUSIONS: ctDNA profiling may provide a benefit for prediction of survival and progression of HCC patients treated with nivolumab. Future studies are needed for confirmation. [ABSTRACT FROM AUTHOR]

Introduction: With locally advanced pancreatic cancer (LAPC), uncontrolled local tumor growth frequently leads to mortality. Advancements in radiotherapy (RT) techniques have enabled conformal delivery of escalated‐dose RT (EDR), which may have potential local control and overall survival (OS) benefits based on retrospective and early prospective studies. With evidence for EDR emerging, we characterized the adoption of EDR across the United States and its associated outcomes. Methods: We searched the National Cancer Database for nonsurgically managed LAPC patients diagnosed between 2004 and 2019. Pancreas‐directed RT with biologically effective doses (BED10) ≥39 and ≤70 Gy was labeled conventional‐dose RT (CDR), and BED10 >70 and ≤132 Gy was labeled EDR. We identified associations of EDR and OS using logistic and Cox regressions, respectively. Results: Among the definitive therapy subset (n = 54,115) of the entire study cohort (n = 91,493), the most common treatments were chemotherapy alone (69%), chemotherapy and radiation (29%), and RT alone (2%). For the radiation therapy subset (n = 16,978), use of pancreas‐directed RT remained between 13% and 17% over the study period (ptrend > 0.999). Using multivariable logistic regression, treatment at an academic/research facility (adjusted odds ratio [aOR] 1.46, p < 0.001) and treatment between 2016 and 2019 (aOR 2.54, p < 0.001) were associated with greater receipt of EDR, whereas use of chemotherapy (aOR 0.60, p < 0.001) was associated with less receipt. Median OS estimates for EDR and CDR were 14.5 months and 13.0 months (p < 0.0001), respectively. For radiation therapy subset patients with available survival data (n = 13,579), multivariable Cox regression correlated EDR (adjusted hazard ratio 0.85, 95% confidence interval 0.80–0.91; p < 0.001) with longer OS versus CDR. Discussion and Conclusions: Utilization of EDR has increased since 2016, but overall utilization of RT for LAPC has remained at less than one in five patients for almost two decades. These real‐world results additionally provide an estimate of effect size of EDR for future prospective trials. [ABSTRACT FROM AUTHOR]

Background Accurate prognostic stratification of hepatocellular carcinoma (HCC) is vital for clinical trial enrollment and treatment allocation. Multiple scoring systems have been created to predict patient survival, but no standardized scoring systems account for radiologic tumor features. We sought to create a generalizable scoring system for HCC which incorporates standardized radiologic tumor features and more accurately predicts overall survival (OS) than established systems. Methods Clinicopathologic parameters were collected from a prospectively collected cohort of patients with HCC treated at a single institution. Imaging studies were evaluated for tumor characteristics. Patients were randomly divided into a training set for identification of covariates that impacted OS and a validation set. Cox models were used to determine the association of various factors with OS and a scoring system was created. Results We identified 383 patients with HCC with imaging and survival outcomes, n  = 255 in the training set and 128 in the validation cohort. Factors associated with OS on multivariate analysis included: tumor margin appearance on CT or MRI (hazard ratio [HR] 1.37, 95% CI, 1.01-1.88) with infiltrative margins portending worse outcomes than encapsulated margins, massive tumor morphology (HR 1.64, 95% CI, 1.06-2.54); >2 lesions (HR 2.06, 95% CI, 1.46-2.88), Child-Turcotte-Pugh class C (HR 3.7, 95% CI, 2.23-6.16), and portal vein thrombus (HR 2.41, 95% CI, 1.71-3.39). A new scoring system was developed and more predictive of OS than other well-established systems. Conclusions Incorporation of standardized imaging characteristics to established clinical and lab predictors of outcome resulted in an improved predictive scoring system for patients with HCC. [ABSTRACT FROM AUTHOR]

PURPOSE: Isocitrate dehydrogenase (IDH) 1 / 2 genomic alterations (GA) occur in 20% of intrahepatic cholangiocarcinoma (iCCA); however, the immunogenomic landscape of IDH1-/2- mutated iCCA is largely unknown. METHODS: Comprehensive genomic profiling (CGP) was performed on 3,067 cases of advanced iCCA. Tumor mutational burden (TMB), PD-L1 expression (Dako 22C3), microsatellite instability (MSI), and genomic loss of heterozygosity (gLOH) as a surrogate marker for homologous recombination deficiency were examined. RNA sequencing of 73 patient samples was analyzed for differences in stromal/immune cell infiltration, immune marker expression, and T-cell inflammation. Tissue microarray arrays were subjected to multiplex immunohistochemistry and colocalization analysis in 100 surgical samples. Retrospective clinical data were collected for 501 patients with cholangiocarcinoma to examine median overall survival (mOS) in IDH1/2 + versus IDH wt. RESULTS: Of 3,067 iCCA cases subjected to CGP, 426 (14%) were IDH1 + and 125 (4%) were IDH2+. IDH1 GA included R132C (69%) and R132L/G/S/H/F (16%/7%/4%/3%/<1%). IDH2 GA occurred at R172 (94.4%) and R140 (6.6%). No significant difference was seen in median gLOH between IDH1 + versus IDH wt iCCA (P =.37), although patterns of comutations differed. MSI-High (P =.009), TMB ≥10 mut/Mb (P <.0001), and PD-L1 positivity were lower in IDH1/2+ versus IDHwt iCCA. Resting natural killer cell population, CD70, and programmed cell death 1 expression were significantly higher in non– IDH 1-mutated cases, whereas V-set domain containing T-cell activation inhibitor 1 (B7-H4) expression was significantly higher in IDH1 +. No significant difference in mOS was observed between IDH1/2 + versus IDH wt patients. CONCLUSION: Significant differences in GA and immune biomarkers are noted between IDH1 / 2 + and IDH wt iCCA. IDH1-/2 -mutated tumors appear immunologically cold without gLOH. These immunogenomic data provide insight for precision targeting of iCCA with IDH alterations. Comprehensive genomic profiling and immune biomarker analysis in IDH1-/2-altered cholangiocarcinoma. [ABSTRACT FROM AUTHOR]

This qualitative study explored the experiences of nursing students whose clinical practice in mental health nursing had been substituted with virtual simulation programs due to the COVID-19 pandemic. The participants were ten nursing students who had undergone a virtual simulation program-centered practice, replacing the traditional clinical practice in mental health nursing and previous clinical practice in mental health nursing. The data were collected through in-depth individual interviews from January to February 2021. Following Braun and Clarke's method, the thematic analysis identified five themes and ten sub-themes. The five themes included the following: (1) lack of vibrancy in the actual clinical setting, (2) limited direct and indirect practical experience, (3) performing diverse roles in a virtual setting, (4) learner-directed practicum, and (5) sense of relief due to a safe virtual practicum environment. The participants recognized the limitations of the practice, particularly regarding communication with patients with mental disorders in the virtual simulation program. However, their perception of nursing underwent a positive change through the indirect clinical practice experience. Accordingly, it is necessary to develop a platform for the mental health nursing practicum that can easily interact with clients and to establish a hybrid practice that combines the clinical practice and virtual simulation practice. [ABSTRACT FROM AUTHOR]

Introduction: In this study, we explored the potential of plasma growth hormone (GH) as a prognostic biomarker in patients with advanced HCC treated with durvalumab plus tremelimumab (D+T). Methods: In this study, we included 16 patients with advanced HCC who received D+T at MD Anderson Cancer Center between 2022 and 2023 and had plasma GH measurements recorded before treatment. Plasma GH levels were measured from prospectively collected blood samples and were correlated with progression-free survival (PFS) and overall survival (OS). The cutoff for normal GH levels in women and men was defined as =3.7 µg/L and =0.9 µg/L, respectively. The Kaplan-Meier method was employed to compute the median OS and PFS, while the Log rank test was applied to compare the survival outcomes between the GH-high and GH-low groups. Results: Sixteen patients were included in this analysis, two female and fourteen male, with a median age of 65.5 years. At the time of the analysis, the 6-month OS rate was 100% among GH-low patients (6 patients) and 30% among GH-high patients (10 patients). OS was significantly longer in GH-low patients (not evaluable) compared to GH-high patients (3.94 months) (p = 0.030). PFS was also significantly longer in GH-low patients (not evaluable) compared to the GH-high patients (1.87 months) (p = 0.036). Conclusion: Plasma GH is a prognostic biomarker in patients with advanced HCC treated with D+T. Given the relatively small patient cohort size, this finding should be further validated in larger randomized clinical trials in advanced HCC patients. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

O2-type lithium-rich layered oxides, known for mitigating irreversible transition metal migration and voltage decay, provide suitable framework for exploring the inherent properties of oxygen redox. Here, we present a series of O2-type lithium-rich layered oxides exhibiting minimal structural disordering and stable voltage retention even with high anionic redox participation based on the nominal composition. Notably, we observe a distinct asymmetric lattice breathing phenomenon within the layered framework driven by excessive oxygen redox, which includes substantial particle-level mechanical stress and the microcracks formation during cycling. This chemo-mechanical degradation can be effectively mitigated by balancing the anionic and cationic redox capabilities, securing both high discharge voltage (~ 3.43 V vs. Li/Li+) and capacity (~ 200 mAh g−1) over extended cycles. The observed correlation between the oxygen redox capability and the structural evolution of the layered framework suggests the distinct intrinsic capacity fading mechanism that differs from the previously proposed voltage fading mode. O2-type Li-rich layered cathodes suppress voltage decay and aid in oxygen redox research. Here, the authors report trilateral relationship among anionic redox utilization, bulk chemo-mechanical degradation, and electrochemical fading, which can be mitigated by balancing the redox center capabilities. [ABSTRACT FROM AUTHOR]

Efforts to treat cancer using chimeric antigen receptor (CAR)-T therapy have made astonishing progress and clinical trials against hematopoietic malignancies have demonstrated their use. However, there are still disadvantages which need to be addressed: high costs, and side effects such as Graft-versus-Host Disease (GvHD) and Cytokine Release Syndrome (CRS). Therefore, recent efforts have been made to harness the properties of certain immune cells to treat cancer—not just T cells, but also natural killer (NK) cells, macrophages (Mφ), dendritic cells (DC), etc. In this paper, we will introduce immune cell-based cellular therapies that use various immune cells and describe their characteristics and their clinical situation. The development of immune cell-based cancer therapy fully utilizing the unique advantages of each and every immune cell is expected to enhance the survival of tumor patients owing to their high efficiency and fewer side effects. [ABSTRACT FROM AUTHOR]

Background: Hepatocellular carcinoma (HCC) can be diagnosed without pathologic confirmation in high‐risk patients. Therefore, it is necessary to compare current imaging criteria for noninvasive‐diagnosis of HCC. Purpose: To systematically compare performance of 2018 European Association for the Study of the Liver (EASL) criteria and Liver Imaging Reporting and Data System (LI‐RADS) for noninvasive‐diagnosis of HCC. Study Type: Systematic review and meta‐analysis. Subjects: Eight studies with 2232 observations, including 1617 HCCs. Field Strength/Sequence: 1.5 T, 3.0 T/T2‐weighted, unenhanced T1‐weighted in‐/opposed‐phases, multiphase T1‐weighted imaging. Assessment: Following the Preferred Reporting Items for Systematic Reviews and Meta‐Analyses (PRISMA) guidelines, two reviewers independently reviewed and extracted data, including patient characteristics, index test, reference standard and outcomes, from studies intraindividually comparing the sensitivities and specificities of 2018 EASL‐criteria and LR‐5 of LI‐RADS for HCC. Risk of bias and concerns regarding applicability were evaluated using QUADAS‐2 tool. Subgroup analysis was performed based on observation size (≥20 mm, 10–19 mm). Statistical Tests: Bivariate random‐effects model to calculate pooled per‐observation sensitivity and specificity of both imaging criteria, and pooled estimates of intraindividual paired data were compared considering the correlation. Forest and linked‐receiver‐operating‐characteristic plots were drawn, and study heterogeneity was assessed using Q‐test and Higgins‐index. Publication bias was evaluated by Egger's test. A P‐value <0.05 was considered statistically significant, except for heterogeneity (P < 0.10). Results: The sensitivity for HCC did not differ significantly between the imaging‐based diagnosis using EASL‐criteria (61%; 95% CI, 50%–73%) and LR‐5 (64%; 95% CI, 53%–76%; P = 0.165). The specificities were also not significantly different between EASL‐criteria (92%; 95% CI, 89%–94%) and LR‐5 (94%; 95% CI, 91%–96%; P = 0.257). In subgroup analysis, no statistically significant differences were identified in the pooled performances between the two criteria for observations ≥20 mm (sensitivity P = 0.065; specificity P = 0.343) or 10–19 mm (sensitivity P > 0.999; specificity P = 0.851). There was no publication bias for EASL (P = 0.396) and LI‐RADS (P = 0.526). Data Conclusion: In the present meta‐analysis of paired comparisons, the pooled sensitivities and specificities were not significantly different between 2018 EASL‐criteria and LR‐5 of LI‐RADS for noninvasive‐diagnosis of HCC. Evidence Level: 3. Technical Efficacy: Stage 2. [ABSTRACT FROM AUTHOR]

Analytical methods based on the mass balance approach were developed for the purity evaluation of tetracycline hydrochloride, a representative salt compound used in pure veterinary drug analysis. The purity assignment method was used to quantify individual classes of impurities via independent analytical techniques. The mass fraction of the free base or salt form contained in a high-purity organic compound with a hydrochloride salt can be determined. The chloride content by ion chromatography-conductivity detector (IC-CD) and general classes of impurities, including structurally related impurities by liquid chromatography–ultraviolet (LC-UV) detector, water by Karl Fischer (KF) coulometric titration, residual solvents by headspace sampler gas chromatography/mass spectrometry (HS-GC/MS), and non-volatiles by thermogravimetric analyzer (TGA), were considered to calculate the purity of the mass fraction. The chloride content of the salt compound can be considered the main impurity in the mass fraction of the free base in the salt compound. A purity assay using quantitative nuclear magnetic resonance (q-NMR) as a direct determination method was performed to confirm the results of the mass balance method. The assigned purities of the tetracycline free form and its salt form in mass fraction were (898.80 ± 1.60) mg/g and (972.65 ± 1.58) mg/g, respectively, which are traceable to the international system of units (SI). Thus, the procedure for evaluating the purity of the free base and salt forms in the salt compound is newly demonstrated in this study. [ABSTRACT FROM AUTHOR]

Background: Low socioeconomic status (SES) patients with early-stage hepatocellular carcinoma (HCC) receive procedural treatments less often and have shorter survival. Little is known about the extent to which these survival disparities result from treatment-related disparities versus other causal pathways. We aimed to estimate the proportion of SES-based survival disparities that are mediated by treatment- and facility-related factors among patients with stage I–II HCC. Methods: We analyzed patients aged 18–75 years diagnosed with stage I–II HCC in 2008–2016 using the National Cancer Database. Inverse odds weighting mediation analysis was used to calculate the proportion mediated by three mediators: procedure type, facility volume, and facility procedural interventions offered. Intersectional analyses were performed to determine whether treatment disparities played a larger role in survival disparities among Black and Hispanic patients. Results: Among 46,003 patients, 15.0% had low SES, 71.6% had middle SES, and 13.4% had high SES. Five-year overall survival was 46.9%, 39.9%, and 35.7% among high, middle, and low SES patients, respectively. Procedure type mediated 45.9% (95% confidence interval [CI] 31.1–60.7%) and 36.7% (95% CI 25.7–47.7%) of overall survival disparities for low and middle SES patients, respectively, which was more than was mediated by the two facility-level mediators. Procedure type mediated a larger proportion of survival disparities among low–middle SES Black (46.6–48.2%) and Hispanic patients (92.9–93.7%) than in White patients (29.5–29.7%). Conclusions: SES-based disparities in use of procedural interventions mediate a large proportion of survival disparities, particularly among Black and Hispanic patients. Initiatives aimed at attenuating these treatment disparities should be pursued. [ABSTRACT FROM AUTHOR]

Introduction: Circulating inflammatory cytokines play critical roles in tumor-associated inflammation and immune responses. Recent data have suggested that several interleukins (ILs) mediate carcinogenesis in hepatocellular carcinoma (HCC). However, the predictive and prognostic value of circulating ILs is yet to be validated. Our study aimed to evaluate the association of the serum ILs with overall survival (OS) and clinicopathologic features in a large cohort of HCC patients. Methods: We prospectively collected data and serum samples from 767 HCC patients treated at the University of Texas MD Anderson Cancer Center between 2001 and 2014, with a median follow-up of 67.4 months (95% confidence interval [CI]: 52.5, 83.3). Biomarker association with OS was evaluated by the log-rank method. Results: The median OS in this cohort was 14.2 months (95% CI: 12, 16.1 months). Clinicopathologic features were more advanced, and OS was significantly inferior in patients with high circulating levels of IL1-R1, IL-6, IL-8, IL-10, IL-15, IL-16, and IL-18. Conclusion: Our study shows that several serum IL levels are valid prognostic biomarker candidates and potential targets for therapy in HCC. [ABSTRACT FROM AUTHOR]

Implicit large-eddy simulations of Mach 2.05 turbulent boundary layer interactions with oblique impinging shock-waves were carried out for shock generator angles of 8° and 9°. Both the streamwise extent of the separated region and the intensity of the velocity fluctuations are augmented when the strength of the impinging oblique shock-wave is increased from 8° to 9°. Temporal Fourier transforms of the spanwise-averaged wall-pressure coefficient indicate low-frequency unsteadiness at separation and mid-frequency content downstream of reattachment. The wall-pressure fluctuations were analyzed with the proper orthogonal decomposition. The modal analysis reveals pronounced 3D low-frequency wall-pressure fluctuations for the stronger interaction. Overall, the present findings provide advanced perspectives on low-frequency wall-pressure fluctuations in turbulent shock-wave boundary layer interactions that may lead to spanwise non-uniformity of the separation and shedding with possible implications for the design of structural panels on high-speed vehicles. [ABSTRACT FROM AUTHOR]

Simple Summary: Hepatocellular carcinoma (HCC) is the most common type of liver cancer, accounting for approximately 85–90% of all cases of liver cancer worldwide. The gut microbiome can serve as a potential non-invasive biomarker for early HCC detection and may also impact the effectiveness of immunotherapy in cancer treatment. This review examines the gut microbiome's role as a predictive and diagnostic marker for HCC and explores its potential as a novel therapeutic approach, particularly in the context of immunotherapy. The microbiome is pivotal in maintaining health and influencing disease by modulating essential inflammatory and immune responses. Hepatocellular carcinoma (HCC), ranking as the third most common cause of cancer-related fatalities globally, is influenced by the gut microbiome through bidirectional interactions between the gut and liver, as evidenced in both mouse models and human studies. Consequently, biomarkers based on gut microbiota represent promising non-invasive tools for the early detection of HCC. There is a growing body of evidence suggesting that the composition of the gut microbiota may play a role in the efficacy of immunotherapy in different types of cancer; thus, it could be used as a predictive biomarker. In this review, we will dissect the gut microbiome's role as a potential predictive and diagnostic marker in HCC and evaluate the latest progress in leveraging the gut microbiome as a novel therapeutic avenue for HCC patients, with a special emphasis on immunotherapy. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the impact of salvage locoregional therapy (salvage-LT) on survival of hepatocellular carcinoma (HCC) patients presenting with intrahepatic tumor progression following radiotherapy. Methods: This single-institution retrospective analysis included consecutive HCC patients having intrahepatic tumor progression following radiotherapy during 2015–2019. Overall survival (OS) was calculated from the date of intrahepatic tumor progression after initial radiotherapy by using the Kaplan–Meier method. Log-rank tests and Cox regression models were used for univariable and multivariable analyses. An inverse probability weighting was used to estimate treatment effect of salvage-LT considering confounding factors. Results: A total of 123 patients (mean age ± SD, 70 years ± 10; 97 men) were evaluated. Among those, 35 patients underwent 59 sessions of salvage-LT, including transarterial embolization/chemoembolization (n = 33), ablation (n = 11), selective internal radiotherapy (n = 7), and external beam radiotherapy (n = 8). At a median follow-up of 15.1 months (range, 3.4–54.5 months), the median OS was 23.3 months in patients who received salvage-LT and 6.6 months who did not. At multivariate analysis, ECOG performance status, Child–Pugh class, albumin-bilirubin grade, extrahepatic disease, and lack of salvage-LT were independent predictors of worse OS. After inverse probability weighting, salvage-LT was associated with a survival benefit of 8.9 months (95% CI: 1.1, 16.7 months; p = 0.03). Conclusions: Salvage locoregional therapy is associated with increased survival in HCC patients suffering from intrahepatic tumor progression following initial radiotherapy. [ABSTRACT FROM AUTHOR]

Background Despite the clinical benefit of immune checkpoint inhibitors (ICIs), patients with a viral hepatitis have been excluded from clinical trials because of safety concerns. The purpose of this study was to determine the incidence rate of adverse events (AEs) in patients with viral hepatitis who received ICIs for cancer treatment. Materials and Methods We conducted a retrospective study in patients with cancer and concurrent hepatitis B or C, who had undergone treatment with ICI at MD Anderson Cancer Center from January 1, 2010 to December 31, 2019. Results Of the 1076 patients screened, we identified 33 with concurrent hepatitis. All 10 patients with HBV underwent concomitant antiviral therapy during ICI treatment. Sixteen of the 23 patients with HCV received it before the initiation of ICI. The median follow-up time was 33 months (95% CI, 23-45) and the median duration of ICI therapy was 3 months (IQR, 1.9-6.6). Of the 33 patients, 12 (39%) experienced irAEs (immune-related adverse events) of any grade, with 2 (6%) having grade 3 or higher. None of the patients developed hepatitis toxicities. Conclusion ICIs may be a therapeutic option with an acceptable safety profile in patients with cancer and advanced liver disease. [ABSTRACT FROM AUTHOR]

A certified reference material (CRM), KRISS CRM 108–02-006, was developed for the accurate analysis of low levels of acrylamide in infant formula matrices. The CRM is an infant formula fortified with acrylamide at a similar level as that stipulated by the European Union regulation for baby food. Commercially available infant formulas were processed by freeze-drying, and the subsequent homogenization of the fortified material to produce 961 bottles of the CRM in one batch. The CRM bottles containing approximately 15 g of the material in each unit were stored in a storage room at − 70 ℃. High-purity acrylamide was used as the primary reference material, and its purity was assessed using an in-house mass-balance method to obtain results metrologically traceable to the International System of Units. The acrylamide content of the infant formula CRM was evaluated using isotope dilution–liquid chromatography/mass spectrometry as a reference method, which was established by our research group. An acrylamide content of 55.7 ± 2.1 μg/kg was assigned as the certified value of the CRM with the expanded uncertainty at a 95% confidence level. The homogeneity study showed good uniformity of the acrylamide content among units, providing a relative standard deviation of 1.2% of the mean value. A stability study was also performed by monitoring the CRM under different temperature conditions and periods. The stability results indicated that the acrylamide content in the CRM under the storage conditions of − 70 ℃ remained stable for up to 10 months. [ABSTRACT FROM AUTHOR]

Introduction: Tumor-related liver failure (TRLF) is the most common cause of death in patients with intrahepatic cholangiocarcinoma (ICC). Though we previously showed that liver radiotherapy (L-RT) for locally advanced ICC is associated with less frequent TRLF and longer overall survival (OS), the role of L-RT for patients with extrahepatic metastatic disease (M1) remains undefined. We sought to compare outcomes for M1 ICC patients treated with and without L-RT. Methods: We reviewed ICC patients that found to have M1 disease at initial diagnosis at a single institution between 2010 and 2021 who received L-RT, matching them with an institutional cohort by propensity score and a National Cancer Database (NCDB) cohort by frequency technique. The median biologically effective dose was 97.5 Gy (interquartile range 80.5–97.9 Gy) for L-RT. Patients treated with other local therapies or supportive care alone were excluded. We analyzed survival with Cox proportional hazard modeling. Results: We identified 61 patients who received L-RT and 220 who received chemotherapy alone. At median follow-up of 11 months after diagnosis, median OS was 9 months (95% confidence interval [CI] 8–11) and 21 months (CI: 17–26) for patients receiving chemotherapy alone and L-RT, respectively. TRLF was the cause of death more often in the patients who received chemotherapy alone compared to those who received L-RT (82% vs. 47%; p = 0.001). On multivariable propensity score-matched analysis, associations with lower risk of death included duration of upfront chemotherapy (hazard ratio [HR] 0.82; p = 0.005) and receipt of L-RT (HR: 0.40; p = 0.002). The median OS from diagnosis for NCDB chemotherapy alone cohort was shorter than that of the institutional L-RT cohort (9 vs. 22 months; p < 0.001). Conclusion: For M1 ICC, L-RT associated with a lower rate of death due to TRLF and longer OS versus those treated with chemotherapy alone. Prospective studies of L-RT in this setting are warranted. [ABSTRACT FROM AUTHOR]

Glycine max Merr. (GM) is a functional food that provides many beneficial phytochemicals. However, scientific evidence of its antidepressive and sedative activities is scarce. The present study was designed to investigate the antidepressive and calmative effects of GM and its biologically active compound, genistein (GE), using electroencephalography (EEG) analysis in an electric foot shock (EFS)-stressed rat. The underlying neural mechanisms of their beneficial effects were determined by assessing corticotropin-releasing factor (CRF), serotonin (5-HT), and c-Fos immunoreactivity in the brain using immunohistochemical methods. In addition, the 5-HT2C receptor binding assay was performed because it is considered a major target of antidepressants and sleep aids. In the binding assay, GM displayed binding affinity to the 5-HT2C receptor (IC50 value of 14.25 ± 11.02 µg/mL). GE exhibited concentration-dependent binding affinity, resulting in the binding of GE to the 5-HT2C receptor (IC50, 77.28 ± 26.57 mg/mL). Administration of GM (400 mg/kg) increased non-rapid eye movement (NREM) sleep time. Administration of GE (30 mg/kg) decreased wake time and increased rapid eye movement (REM) and NREM sleep in EPS-stressed rats. In addition, treatment with GM and GE significantly decreased c-Fos and CRF expression in the paraventricular nucleus (PVN) and increased 5-HT levels in the dorsal raphe in the brain. Overall, these results suggest that GM and GE have antidepressant-like effects and are effective in sleep maintenance. These results will benefit researchers in developing alternatives to decrease depression and prevent sleep disorders. [ABSTRACT FROM AUTHOR]

Homotopy multiplications on H-spaces and homotopy comultiplications on co-H-spaces play an important role in topology for many reasons. They are the duals with each other in the sense of Eckmann and Hilton, and have many kinds of examples to construct a binary operation of homotopy classes on loop multiplications and suspension comultiplications to give the group structure on the set of homotopy classes. In the current work, we investigate every possibility of homotopy comultiplications and focus on the study of associative and commutative comultiplications on the wedge product of (a sufficiently large number of) spheres as a generalization of the papers [5, 6, 19]. In particular, we observe some patterns on the types of associative and commutative comultiplications on the wedge product of spheres. [ABSTRACT FROM AUTHOR]

Background Limited data from small series have suggested that brain metastases from biliary tract cancers (BrM-BTC) affect ≤2% of patients with BTC. We sought to review our experience with patients with BrM-BTC and to identify associations of tumor-related molecular alterations with outcomes. Materials and Methods A retrospective review of patients with BTC seen at a tertiary referral center from 2005 to 2021 was performed; patients with BrM-BTC were identified, and clinical and molecular data were collected. Results Twenty-one of 823 patients with BTC (2.6%) developed BrM. For patients with BrM-BTC, median follow-up time was 27.9 months after primary BTC diagnosis and 3.1 months after BrM diagnosis. Median time from primary diagnosis to diagnosis of BrM was 14.4 [range, 1.1-66.0] months. Median overall survival (OS) from primary diagnosis was 31.5 [2.9-99.8] months and median OS from BrM diagnosis was 4.2 [0.2-33.8] months. Patients who underwent BrM-directed therapy trended toward longer OS following BrM diagnosis than patients receiving supportive care only (median 6.5 vs 0.8 months, P =.060). The BrM-BTC cohort was enriched for BRAF (30%), PIK3CA (25%), and GNAS (20%) mutations. patients with BrM-BTC with BRAF mutations trended toward longer OS following BrM diagnosis (median 13.1 vs 4.2 months, P =. 131). Conclusion This is the largest series of patients with BrM-BTC to date and provides molecular characterization of this rare subgroup of patients with BTC. Patients with BrM-BTC may be more likely to have BRAF mutations. With advances in targeted therapy for patients with BTC with actionable mutations, continued examination of shifting patterns of failure, with emphasis on BrM, is warranted. [ABSTRACT FROM AUTHOR]

Highlights: The Li-mediated artificial synapses with a vertical two-terminal configuration capable of various synaptic behaviors, including bio-plausible synaptic plasticity, were successfully demonstrated for the first time and thoroughly explored Synaptic characteristics based on the progressive dearth of Li in LixCo2 films are precisely controlled over the weight control spike, achieving extraordinary weight control functionality. In artificial neural network simulation, LixCoO2-based neuromorphic system showed excellent accuracy comparable to the theoretical maximum due to the low nonlinearity and programming error, suggesting feasibility of hardware neural network implementation. Recently, artificial synapses involving an electrochemical reaction of Li-ion have been attributed to have remarkable synaptic properties. Three-terminal synaptic transistors utilizing Li-ion intercalation exhibits reliable synaptic characteristics by exploiting the advantage of non-distributed weight updates owing to stable ion migrations. However, the three-terminal configurations with large and complex structures impede the crossbar array implementation required for hardware neuromorphic systems. Meanwhile, achieving adequate synaptic performances through effective Li-ion intercalation in vertical two-terminal synaptic devices for array integration remains challenging. Here, two-terminal Au/LixCoO2/Pt artificial synapses are proposed with the potential for practical implementation of hardware neural networks. The Au/LixCoO2/Pt devices demonstrated extraordinary neuromorphic behaviors based on a progressive dearth of Li in LixCoO2 films. The intercalation and deintercalation of Li-ion inside the films are precisely controlled over the weight control spike, resulting in improved weight control functionality. Various types of synaptic plasticity were imitated and assessed in terms of key factors such as nonlinearity, symmetricity, and dynamic range. Notably, the LixCoO2-based neuromorphic system outperformed three-terminal synaptic transistors in simulations of convolutional neural networks and multilayer perceptrons due to the high linearity and low programming error. These impressive performances suggest the vertical two-terminal Au/LixCoO2/Pt artificial synapses as promising candidates for hardware neural networks [ABSTRACT FROM AUTHOR]

Background: The Liver Imaging Reporting and Data System (LI‐RADS) is a comprehensive system for standardizing the terminology and interpretation of liver imaging. The association between the LI‐RADS category and tumor recurrence in patients with intrahepatic cholangiocarcinomas (iCCAs) has not yet been evaluated in a multicenter study. Purpose: To retrospectively investigate the preoperative clinical and imaging features associated with recurrence‐free survival (RFS) after curative resection of iCCAs and to identify the role of the LI‐RADS category in at‐risk patients. Study Type: Retrospective, multicenter. Subjects: A total of 113 patients (mean age: 61.1 years; 74 men, 39 women) who underwent preoperative contrast‐enhanced MRI and curative surgical resection for a single treatment‐naive iCCA between 2008 and 2021. Filed Strength/Sequence: A 3 T dual gradient‐echo T1WI with in‐ and opposed‐phase, turbo spin‐echo T2WI, diffusion‐weighted echo‐planar images, and three‐dimensional gradient‐echo T1WI before and after administration of contrast agent. Assessment: MR imaging features were evaluated and assigned for each lesion using LI‐RADS version 2018. RFS was calculated from the date of surgery to tumor recurrence or the last imaging date without evidence of recurrence. Factors affecting RFS were evaluated using clinical and imaging features. Statistical Tests: Cox proportional hazards model, Kaplan–Meier method, and log‐rank test. A P‐value of <0.05 was considered statistically significant. Results: A total of 93 (82.3%) were categorized as LR‐M and 20 (17.7%) were categorized as LR‐4 or 5. In the multivariable analysis, LR‐M category (hazard ratio [HR], 8.035; 95% confidence interval [CI], 1.096–58.931) and a tumor size >3 cm on MRI (HR, 2.690; 95% CI, 1.319–5.487) were independent factors for poor RFS. The 5‐year RFS rate was significantly higher in patients with iCCA categorized as LR‐4 or 5 than in those categorized as LR‐M (94.4% vs. 51.9%, respectively). Data Conclusion: Patients with iCCA categorized as LR‐4 or 5 may have a better RFS than those categorized as LR‐M. Evidence Level: 3 Technical Efficacy: Stage 2 [ABSTRACT FROM AUTHOR]

Multivitamin tablet certified reference material (CRM, 108-10-019) was developed for the analysis of seven water-soluble vitamins, including thiamine, riboflavin, nicotinamide, pantothenic acid, pyridoxine, biotin, and folic acid. The CRM was prepared in powder form by grinding multivitamin tablets and then mixing, sieving, and bottling the powder. For the certification of each water-soluble vitamin, the isotope dilution mass spectrometry based on the liquid chromatography was applied. The methods for each analyte were validated by confirming the repeatability and reproducibility and by comparing with other CRMs. The property values and uncertainties for the vitamins were determined with 10 units from sample stored at − 20 °C. The homogeneity of each certified component was also examined in the range of 0.48–2.2%. All certified values for the seven water-soluble vitamins were stable for 3 or 6 years after the initial certification under storage conditions at − 20 °C. For fat-soluble vitamins, including retinol, α-tocopherol, cholecalciferol, and phylloquinone, two expert laboratories participated in analyses based on official methods, and the mean values of the reported results were assigned as reference values. The multivitamin tablet CRM (108-10-019) will be useful for validating analytical methods and for ensuring the quality of results for vitamin analysis in multivitamin tablets or similar products. [ABSTRACT FROM AUTHOR]

Acquired resistance to systemic treatments is inevitable in most cancers, but the genetic basis for this in many cancer types has remained elusive due to constraints in obtaining tissue specimens longitudinally. In the management of gastrointestinal cancers, molecular profiling is conventionally performed at a single time point, although serial evaluations may yield biological insights that inform treatment decisions. We characterize genetic changes in serial liquid biopsies which provide real-time snapshots of tumor genetics and heterogeneity in refractory non-colorectal gastrointestinal cancers, and determine the clinical utility of repeat circulating tumor DNA (ctDNA) testing. In a national cohort of 449 patients with pancreatic, biliary, esophagogastric, and hepatocellular cancers, resistance to conventional therapies is broadly associated with tumor evolution. Emergent ctDNA alterations only detectable at progression occurs in 63% of patients and are frequently associated with treatment actionability. Tumor mutation burden is dynamic in cancers undergoing treatment, but is not associated with time to progression. Objective tumor responses in a case series of patients receiving treatment matched to emergent alterations show that repeat liquid biopsies may have clinical benefit by expanding treatment options in advanced gastrointestinal cancers. Acquired resistance can be associated with genetic changes, however, clinical molecular profiling is usually only considered at the time of diagnosis. Here, the authors use serial ctDNA profiling of 449 gastrointestinal cancers to demonstrate widespread tumour evolution associated with treatment resistance and its potential implications for treatment. [ABSTRACT FROM AUTHOR]

Objectives: To construct a predictive nomogram for differentiating malignant from benign ampullary strictures using contrast-enhanced computed tomography (CT) findings combined with clinical findings. Methods: In this retrospective study, 152 patients with ampullary stricture (98 benign and 54 malignant) who underwent contrast-enhanced CT were included. Various imaging findings of the ampulla, bile duct, main pancreatic duct, and periampullary area were evaluated and clinical findings including the presence of jaundice, carbohydrate antigen 19-9 level, and history of cholecystectomy were collected. Among them, statistically significant findings were identified using univariable and multivariable logistic regression analyses. A nomogram was constructed to differentiate benign and malignant ampullary strictures and was internally validated. Results: Multivariable analysis revealed that jaundice (odds ratio [OR]: 17.33, p < 0.001), presence of an ampullary mass (OR: 24.40, p < 0.001), non-similar enhancement of the ampulla to the duodenum (OR: 31.96, p = 0.003), and proportional dilatation of the bile duct (OR: 7.98, p = 0.001) were independent significant factors for predicting the malignant ampullary stricture, and were used to construct a nomogram. Among them, non-similar enhancement of the ampulla to the duodenum showed the highest OR and predictor point on the nomogram. The calibration plots showed excellent agreement between the predicted probabilities and the actual rates of malignant ampullary strictures, on internal validation. Conclusions: Combination of clinical and imaging findings could aid in predicting malignant ampullary strictures using significant findings of jaundice, presence of ampullary mass, non-similar enhancement of the ampulla to the duodenum, and proportional dilatation of the bile duct. Key Points: • The presence of jaundice, ampullary mass, non-similar enhancement of the ampulla, and proportional bile duct dilatation were significant findings for predicting malignant ampullary strictures. • Non-similar enhancement of the ampulla to the duodenum was a significant feature with the highest odds ratio for differentiating benign and malignant ampullary strictures. • The nomogram constructed using contrast-enhanced computed tomography imaging and clinical findings could aid in predicting malignant ampullary strictures. [ABSTRACT FROM AUTHOR]

Background: Hepatic steatosis (HS) can be comprehensively assessed by visually comparing the hepatic and vessel attenuation on unenhanced computed tomography (CT). We aimed to evaluate the reliability and reproducibility of a CT-based visual grading system (VGS) for comprehensive assessment of HS. Methods: In this retrospective study, a four-point VGS based on the visual comparison of liver and hepatic vessels was validated by six reviewers with diverse clinical experience using the unenhanced CT images of 717 potential liver donors. The diagnostic performance of VGS and quantitative indices (difference and ratio of the hepatic and splenic attenuation) to diagnose HS were evaluated using multi-reader multi-case receiver operating characteristics (ROC) analysis (reference: pathology). The interobserver agreement was assessed using Fleiss κ statistics. Results: Using the VGS, all six reviewers showed areas under the ROC curves (AUROCs) higher than 0.9 for diagnosing total steatosis (TS) ≥ 30%, macrovesicular steatosis (MaS) ≥ 30%, and MaS ≥ 10%. No difference was noted between the AUROCs of the VGS and quantitative indices (p ≥ 0.1). The reviewers showed substantial agreement (Fleiss κ, 0.61). Most discrepancies occurred between the two lowest grades of VGS (81.5%; 233/283), in which most subjects (97.0%; 226/233) had a MaS < 10%. The average-reader sensitivity and specificity of the VGS were 0.80 and 0.94 to detect TS ≥ 30% and 0.93 and 0.81 to detect MaS ≥ 10%. Conclusion: VGS was reliable and reproducible in assessing HS. It may be useful as a non-invasive and simple tool for comprehensive HS assessment. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background Previous studies report increasing cholangiocarcinoma (CCA) incidence up to 2015. This contemporary retrospective analysis of CCA incidence and mortality in the US from 2001-2017 assessed whether CCA incidence continued to increase beyond 2015. Patients and Methods Patients (≥18 years) with CCA were identified in the National Cancer Institute Surveillance, Epidemiology, and End Results 18 cancer registry (International Classification of Disease for Oncology [ICD-O]-3 codes: intrahepatic [iCCA], C221; extrahepatic [eCCA], C240, C241, C249). Cancer of unknown primary (CUP) cases were identified (ICD-O-3 : C809; 8140/2, 8140/3, 8141/3, 8143/3, 8147/3) because of potential misclassification as iCCA. Results Forty-thousand-and-thirty CCA cases (iCCA, n=13,174; eCCA, n=26,821; iCCA and eCCA, n=35) and 32,980 CUP cases were analyzed. From 2001-2017, CCA, iCCA, and eCCA incidence (per 100 000 person-years) increased 43.8% (3.08 to 4.43), 148.8% (0.80 to 1.99), and 7.5% (2.28 to 2.45), respectively. In contrast, CUP incidence decreased 54.4% (4.65 to 2.12). CCA incidence increased with age, with greatest increase among younger patients (18-44 years, 81.0%). Median overall survival from diagnosis was 8, 6, 9, and 2 months for CCA, iCCA, eCCA, and CUP. From 2001-2016, annual mortality rate declined for iCCA (57.1% to 41.2%) and generally remained stable for eCCA (40.9% to 37.0%) and for CUP (64.3% to 68.6%). Conclusions CCA incidence continued to increase from 2001-2017, with greater increase in iCCA versus eCCA, whereas CUP incidence decreased. The divergent CUP versus iCCA incidence trends, with overall greater absolute change in iCCA incidence, provide evidence for a true increase in iCCA incidence that may not be wholly attributable to CUP reclassification. [ABSTRACT FROM AUTHOR]

Interleukin-7 (IL-7) is a multipotent cytokine that maintains the homeostasis of the immune system. IL-7 plays a vital role in T-cell development, proliferation, and differentiation, as well as in B cell maturation through the activation of the IL-7 receptor (IL-7R). IL-7 is closely associated with tumor development and has been used in cancer clinical research and therapy. In this review, we first summarize the roles of IL-7 and IL-7Rα and their downstream signaling pathways in immunity and cancer. Furthermore, we summarize and discuss the recent advances in the use of IL-7 and IL-7Rα as cancer immunotherapy tools and highlight their potential for therapeutic applications. This review will help in the development of cancer immunotherapy regimens based on IL-7 and IL-7Rα, and will also advance their exploitation as more effective and safe immunotherapy tools. [ABSTRACT FROM AUTHOR]

Background Previous studies report increasing cholangiocarcinoma (CCA) incidence up to 2015. This contemporary retrospective analysis of CCA incidence and mortality in the US from 2001-2017 assessed whether CCA incidence continued to increase beyond 2015. Patients and Methods Patients (≥18 years) with CCA were identified in the National Cancer Institute Surveillance, Epidemiology, and End Results 18 cancer registry (International Classification of Disease for Oncology [ICD-O]-3 codes: intrahepatic [iCCA], C221; extrahepatic [eCCA], C240, C241, C249). Cancer of unknown primary (CUP) cases were identified (ICD-O-3 : C809; 8140/2, 8140/3, 8141/3, 8143/3, 8147/3) because of potential misclassification as iCCA. Results Forty-thousand-and-thirty CCA cases (iCCA, n=13,174; eCCA, n=26,821; iCCA and eCCA, n=35) and 32,980 CUP cases were analyzed. From 2001-2017, CCA, iCCA, and eCCA incidence (per 100 000 person-years) increased 43.8% (3.08 to 4.43), 148.8% (0.80 to 1.99), and 7.5% (2.28 to 2.45), respectively. In contrast, CUP incidence decreased 54.4% (4.65 to 2.12). CCA incidence increased with age, with greatest increase among younger patients (18-44 years, 81.0%). Median overall survival from diagnosis was 8, 6, 9, and 2 months for CCA, iCCA, eCCA, and CUP. From 2001-2016, annual mortality rate declined for iCCA (57.1% to 41.2%) and generally remained stable for eCCA (40.9% to 37.0%) and for CUP (64.3% to 68.6%). Conclusions CCA incidence continued to increase from 2001-2017, with greater increase in iCCA versus eCCA, whereas CUP incidence decreased. The divergent CUP versus iCCA incidence trends, with overall greater absolute change in iCCA incidence, provide evidence for a true increase in iCCA incidence that may not be wholly attributable to CUP reclassification. [ABSTRACT FROM AUTHOR]

The all-solid-state battery (ASSB) has become one of the most promising next-generation battery systems, since the aspect of safety has emerged as a crucial criterion for new large-scale applications such as in electric vehicles. Despite the recent remarkable progress in the performance enhancement, the real-world implementation of the ASSB still requires full comprehension/evaluation of its properties and performance under various practical operational conditions. Unlike batteries employed in conventional electronic devices, those in electric vehicles—the major application that the ASSB is expected to be employed—would be exposed to wide temperature variations (−20 to ∼70 °C) at various states of charges due to their outdoor storage and irregular discharge/rest/charge conditions depending on vehicle drivers' usage patterns. Herein, we investigate the reliability of a Li6PS5Cl-based ASSB system in practically harsh but plausible storage conditions and reveal that it is vulnerable to elevated-temperature storage as low as 70 °C, which, in contrast to the common belief, causes significant degradation of the electrolyte and consequently irreversible buildup of the cell resistance. It is unraveled that this storage condition induces the decomposition of Li6PS5Cl in contact with the cathode material, involving the SOx gas evolution particularly at charged states, which creates a detrimental porous cathode/electrolyte interface, thereby leading to the large interfacial resistance. Our findings indicate that the stability of the solid electrolyte, which has been believed to be failsafe, needs to be carefully revisited at various practical operational conditions for actual applications in ASSBs. [ABSTRACT FROM AUTHOR]