Downregulation of TRIB3 enhances the sensitivity of lung cancer cells to amino acid deprivation by suppressing AKT activation.

Tribbles pseudokinase 3 (TRIB3), a member of the mammalian Tribbles family, is implicated in multiple biological processes. This study aimed to investigate the biological functions of TRIB3 in lung cancer and its effect on amino acid-deprived lung cancer cells. TRIB3 mRNA expression was elevated in lung cancer tissues and cell lines compared to normal lung tissues and cells. TRIB3 knockdown markedly reduced the viability and proliferation of H1299 lung cancer cells. Deprivation of amino acids, particularly arginine, glutamine, lysine, or methionine, strongly increased TRIB3 expression via ATF4 activation in H1299 lung cancer cells. Knockdown of TRIB3 led to transcriptional downregulation of ATF4 and reduced AKT activation induced by amino acid deprivation, ultimately increasing the sensitivity of H1299 lung cancer cells to amino acid deprivation. Additionally, TRIB3 knockdown enhanced the sensitivity of H1299 cells to V-9302, a competitive antagonist of transmembrane glutamine flux. These results suggest that TRIB3 is a pro-survival regulator of cell viability in amino acid-deficient tumor microenvironments and a promising therapeutic target for lung cancer treatment.

Utility of Prostate Health Index Density for Biopsy Strategy in Biopsy-Naïve Patients With PI-RADS v2.1 Category 3 Lesions.

BACKGROUND: Category 3 lesions in PI-RADSv2.1 pose diagnostic challenges, complicating biopsy decisions. Recent biomarkers like prostate health index (PHI) have shown higher specificity in detecting clinically significant prostate cancer (csPCa) than prostate-specific antigen (PSA). Yet their integration with MRI remains understudied. PURPOSE: To evaluate the utility of PSA and PHI with its derivatives for detecting csPCa in biopsy-naïve patients with category 3 lesion on initial prostate MRI scan. STUDY TYPE: Retrospective. POPULATION: One hundred ninety-three biopsy-naïve patients who underwent MRI, PSA, and PHI testing, followed by both targeted and systematic biopsies. FIELD STRENGTH/SEQUENCE: Turbo spin-echo T2-weighted imaging, diffusion-weighted single-shot echo-planar imaging, and dynamic contrast-enhanced T1-weighted fast field echo sequence imaging in 3 T. ASSESSMENT: PHI density (PHID) and PSA density (PSAD) derived by dividing serum PHI and PSA with prostate volume (MRI based methodology suggested by PI-RADSv2.1). Risk-stratified models to evaluate the utility of markers in triaging patients for biopsy, including low-, intermediate-, and high-risk groups. STATISTICAL TESTS: Independent t-test, Mann-Whitney U test, Mantel-Haenszel test, generalized estimating equation, and receiver operating characteristic (ROC) curve analysis were used. Statistical significance defined as P < 0.05. RESULTS: CsPCa was found in 16.6% (32/193) of patients. PHID had the highest area under the ROC curve (AUROC) of 0.793, followed by PHI of 0.752, PSAD of 0.750, and PSA of 0.654. PHID with two cut-off points (0.88/mL and 1.82/mL) showed the highest potential biopsy avoidance of 47.7% (92/193) with 5% missing csPCa, and the lowest intermediate-risk group (borderline decision group) at 38.9% (75/193), compared to PSA and PHI. DATA CONCLUSION: PHID demonstrated better potential in triaging patients with category 3 lesions, possibly aiding more selective and confident biopsy decisions for csPCa detection, than traditional markers. EVIDENCE LEVEL: 4 TECHNICAL EFFICACY: Stage 5.

Discovery of a Novel Potent EGFR Inhibitor Against EGFR Activating Mutations and On-Target Resistance in NSCLC.

PURPOSE: Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKI) serve as the standard first-line therapy for EGFR-mutated non-small cell lung cancer (NSCLC). Despite the sustained clinical benefits achieved through optimal EGFR-TKI treatments, including the third-generation EGFR-TKI osimertinib, resistance inevitably develops. Currently, there are no targeted therapeutic options available postprogression on osimertinib. Here, we assessed the preclinical efficacy of BI-4732, a novel fourth-generation EGFR-TKI, using patient-derived preclinical models reflecting various clinical scenarios. EXPERIMENTAL DESIGN: The antitumor activity of BI-4732 was evaluated using Ba/F3 cells and patient-derived cell/organoid/xenograft models with diverse EGFR mutations. Intracranial antitumor activity of BI-4732 was evaluated in a brain-metastasis mouse model. RESULTS: We demonstrated the remarkable antitumor efficacy of BI-4732 as a single agent in various patient-derived models with EGFR_C797S-mediated osimertinib resistance. Moreover, BI-4732 exhibited activity comparable to osimertinib in inhibiting EGFR-activating (E19del and L858R) and T790M mutations. In a combination treatment strategy with osimertinib, BI-4732 exhibited a synergistic effect at significantly lower concentrations than those used in monotherapy. Importantly, BI-4732 displayed potent antitumor activity in an intracranial model, with low efflux at the blood-brain barrier. CONCLUSIONS: Our findings highlight the potential of BI-4732, a selective EGFR-TKI with high blood-brain barrier penetration, targeting a broad range of EGFR mutations, including C797S, warranting clinical development.

Computed tomography-based prediction model for identifying patients with high probability of non-muscle-invasive bladder cancer.

PURPOSE: To investigate computed tomography (CT)-based prediction model for identifying patients with high probability of non-muscle-invasive bladder cancer (NMIBC). METHODS: This retrospective study evaluated 147 consecutive patients who underwent contrast-enhanced CT and surgery for bladder cancer. Using corticomedullary-to-portal venous phase images, two independent readers analyzed bladder muscle invasion, tumor stalk, and tumor size, respectively. Three-point scale (i.e., from 0 to 2) was applied for assessing the suspicion degree of muscle invasion or tumor stalk. A multivariate prediction model using the CT parameters for achieving high positive predictive value (PPV) for NMIBC was investigated. The PPVs from raw data or 1000 bootstrap resampling and inter-reader agreement using Gwet's AC1 were analyzed, respectively. RESULTS: Proportion of patients with NMIBC was 81.0% (119/147). The CT criteria of the prediction model were as follows: (a) muscle invasion score < 2; (b) tumor stalk score > 0; and (c) tumor size < 3 cm. From the raw data, PPV of the model for NMIBC was 92.7% (51/55; 95% confidence interval [CI] 82.4-98.0) in reader 1 and 93.3% (42/45; 95% CI 81.7-98.6) in reader 2. From the bootstrap data, PPV was 92.8% (95% CI 85.2-98.3) in reader 1 and 93.4% (95% CI 84.9-99.9) in reader 2. The model's AC1 was 0.753 (95% CI 0.647-0.859). CONCLUSION: The current CT-derived prediction model demonstrated high PPV for identifying patients with NMIBC. Depending on CT findings, approximately 30% of patients with bladder cancer may have a low need for additional MRI for interpreting vesical imaging-reporting and data system.

Improved anticancer efficacy of methyl pyropheophorbide-a-incorporated solid lipid nanoparticles in photodynamic therapy.

Photodynamic therapy (PDT) is a promising anticancer treatment because it is patient-friendly and non-invasive. Methyl pyropheophorbide-a (MPPa), one of the chlorin class photosensitizers, is a drug with poor aqueous solubility. The purpose of this study was to synthesize MPPa and develop MPPa-loaded solid lipid nanoparticles (SLNs) with improved solubility and PDT efficacy. The synthesized MPPa was confirmed 1H nuclear magnetic resonance (1H-NMR) spectroscopy and UV-Vis spectroscopy. MPPa was encapsulated in SLN via a hot homogenization with sonication. Particle characterization was performed using particle size and zeta potential measurements. The pharmacological effect of MPPa was evaluated using the 1,3-diphenylisobenzofuran (DPBF) assay and anti-cancer effect against HeLa and A549 cell lines. The particle size and zeta potential ranged from 231.37 to 424.07 nm and - 17.37 to - 24.20 mV, respectively. MPPa showed sustained release from MPPa-loaded SLNs. All formulations improved the photostability of MPPa. The DPBF assay showed that SLNs enhanced the 1O2 generation from MPPa. In the photocytotoxicity analysis, MPPa-loaded SLNs demonstrated cytotoxicity upon photoirradiation but not in the dark. The PDT efficacy of MPPa improved following its entrapment in SLNs. This observation suggests that MPPa-loaded SLNs are suitable for the enhanced permeability and retention effect. Together, these results demonstrate that the developed MPPa-loaded SLNs are promising candidates for cancer treatment using PDT.

pH-Responsive Nano-transferosomes of Purpurin-18 Sodium Salt and Doxorubicin for Enhanced Anticancer Efficiency by Photodynamic and Chemo Combination Therapy.

Cancer is a devastating disease and a major human health concern. Various combination treatments have been developed to combat cancer. To obtain superior cancer therapy, the objective of this study was to synthesize purpurin-18 sodium salt (P18Na) and design P18Na- and doxorubicin hydrochloride (DOX)-loaded nano-transferosomes as a combination of photodynamic therapy (PDT) and chemotherapy for cancer. The characteristics of P18Na- and DOX-loaded nano-transferosomes were assessed, and the pharmacological efficacy of P18Na and DOX was determined using the HeLa and A549 cell lines. The nanodrug delivery system characteristics of the product were found to range from 98.38 to 217.50 nm and -23.63 to -41.10 mV, respectively. Further, the release of P18Na and DOX from nano-transferosomes exhibited a sustained pH-responsive behavior and burst in physiological and acidic environments, respectively. Accordingly, the nano-transferosomes effectively delivered P18Na and DOX into cancer cells, with less leakage in the body, and exhibited pH-responsive release in cancer cells. A photo-cytotoxicity study to HeLa and A549 cell lines revealed a size-dependent anti-cancer effect. These results suggest that the combined nano-transferosomes of P18Na and DOX are effective in the combination of PDT and chemotherapy for cancer.

New estimation method of limit pressures for thick curved pipes under internal pressure applicable to various bend angles.

In this study, a new estimation method of limit pressures (loads) is suggested for reliability design of curved pipes under high internal pressure and temperature. The curved pipes are used in boiler pipes in a supercritical thermal power plants. To find any design parameters and their dimensions in reliability design of curved pipes, various boilers in supercritical thermal power plants in operation were investigated. In order to analyse the effect of the design parameters on the limit pressure, the design of experiment (DOE) was applied to design a curved pipes with various combinations of design parameters, and then the FE limit load analyses were performed to obtain limit pressures. The thickness of the curved pipe has the greatest effect on the limit pressure among the design parameters. Although the bend angle is design parameter, the proposed estimation methods for easily calculating the limit load do not include the bend angle and then there have been difficulties in reliability design of curved pipes with any band angle. Therefore, to solve such difficulties, two estimation methods of limit pressure (load) including bend angle were suggested and the validity of the proposed estimation methods of limit load (plastic pressure) under internal pressure was objectively verified through statistical error analysis with the 60 FE analysis results which are different from the data used when the method was derived. The proposed estimation method applicable to various bend angles shows the best results in the evaluation of mean error, maximum error, and standard deviation of error, which are evaluation criteria. The proposed estimation method shows a very good result compared to existing methods, having the mean error of 0.89%, a maximum error of 2.50%, and a standard deviation of 0.70% for all data regardless of the bend angle.

CD8α+ dendritic cells potentiate antitumor and immune activities against murine ovarian cancers.

Dendritic cell (DC)-based immunotherapies have been shown to be a potential treatment option for various cancers; however, the exact strategies in ovarian cancer remain unknown. Here, we report the effectiveness of mouse CD8α+ DCs derived from bone marrow hematopoietic stem cells (BM-HSCs), equivalent to human CD141+ DCs, which have proven to be a highly superior subset. Mono-DCs from monocytes and stem-DCs from HSCs were characterized by CD11c+ CD80+ CD86+ and CD8α+ Clec9a+ expression, respectively. Despite a lower dose compared with Mono-DCs, mice treated with pulsed Stem-DCs showed a reduced amount of ascitic fluid and lower body weights compared with those of vehicle-treated mice. These mice treated with pulsed stem-DCs appeared to have fewer tumor implants, which were usually confined in the epithelium of tumor-invaded organs. All mice treated with DCs showed longer survival than the vehicle group, especially in the medium/high dose pulsed Stem-DC treatment groups. Moreover, the stem-DC-treated group demonstrated a low proportion of myeloid-derived suppressor cells and regulatory T cells, high interleukin-12 and interferon-γ levels, and accumulation of several tumor-infiltrating lymphocytes. Together, these results indicate that mouse CD8α+ DCs derived from BM-HSCs decrease tumor progression and enhance antitumor immune responses against murine ovarian cancer, suggesting that better DC vaccines can be used as an effective immunotherapy in EOC treatment. Further studies are necessary to develop potent DC vaccines using human CD141+ DCs.

Solid Lipid Nanoparticles of Curcumin Designed for Enhanced Bioavailability and Anticancer Efficiency.

Curcumin (Cur) has anticancer properties but exhibits poor aqueous solubility, permeability, and photostability. In this study, we aimed to develop a solid lipid nanoparticle (SLN) system to enhance Cur bioavailability. The characteristics of Cur-loaded SLNs prepared by sonication were evaluated using UV-vis and Fourier transform infrared spectroscopy. The mean particle size of the stearic acid-based, lauric acid-based, and palmitic acid-based SLNs was 14.70-149.30, 502.83, and 469.53 nm, respectively. The chemical interactions between Cur and lipids involved hydrogen bonding and van der Waals forces. The formulations with high van der Waals forces might produce a neat arrangement between Cur and lipids, leading to a decrease in particle size. The Cur formulations showed enhanced cytotoxicity in HeLa, A549, and CT-26 cells compared with pure Cur. Additionally, the anticancer effect is dependent on particle size and the type of cell line. Therefore, Cur-loaded SLNs have the potential for use in anticancer therapy.

Neurorobotic approaches to emulate human motor control with the integration of artificial synapse.

The advancement of electronic devices has enabled researchers to successfully emulate human synapses, thereby promoting the development of the research field of artificial synapse integrated soft robots. This paper proposes an artificial reciprocal inhibition system that can successfully emulate the human motor control mechanism through the integration of artificial synapses. The proposed system is composed of artificial synapses, load transistors, voltage/current amplifiers, and a soft actuator to demonstrate the muscle movement. The speed, range, and direction of the soft actuator movement can be precisely controlled via the preset input voltages with different amplitudes, numbers, and signs (positive or negative). The artificial reciprocal inhibition system can impart lifelike motion to soft robots and is a promising tool to enable the successful integration of soft robots or prostheses in a living body.

Ultrasonographic characteristics of Hürthle cell neoplasms: prediction of malignancy.

PURPOSE: This study investigated the ultrasound (US) features of malignancy in patients with Hürthle cell neoplasms (HCNs) of the thyroid gland. METHODS: The present study included 139 HCNs that had undergone surgical excision at a single institution from 1996 to 2020 and had preoperative US images. The sonographic characteristics of HCNs were correlated with their pathological results. The US findings associated with malignancy were explored using logistic regression analysis, and the diagnostic performance and cutoff were assessed using receiver operating characteristic analysis. RESULTS: The most common US findings of HCNs were a solid content (76.3%), oval to round shape (100%), hypoechogenicity (70.5%), a smooth margin (95.0%), the halo sign (90.6%), and no calcifications (93.5%). HCNs were commonly smaller in pathologic measurements than in US measurements (smaller, same, and greater than US measurements in 60.4%, 21.6%, and 18.0% of HCNs, respectively; P<0.001). On US, malignant nodules were significantly larger than benign nodules (3.4±1.6 cm vs. 2.2±1.2 cm, P<0.001). Multiple logistic regression showed that the US tumor size was an independent predictor of malignancy (P=0.001; odds ratio, 1.730 for a 1-cm increase [95% confidence interval, 1.258 to 2.375]). The best cutoff US tumor size for predicting malignancy was 3.35 cm (sensitivity, 53.1%; specificity, 87.9%). CONCLUSION: The US tumor size was found to be an independent predictor of malignancy in HCNs, and a US tumor size >3.35 cm might be used as a criterion to suggest malignancy. The size of HCNs often showed discrepancies between US and pathologic measurements.

Synthesis and Design of Purpurin-18-Loaded Solid Lipid Nanoparticles for Improved Anticancer Efficiency of Photodynamic Therapy.

Purpurin-18 (P18) is one of the essential photosensitizers used in photodynamic therapy (PDT), but its hydrophobicity causes easy coalescence and poor bioavailability. This study aimed to synthesize P18 and design P18-loaded solid lipid nanoparticles (SLNs) to improve its bioavailability. The characteristics of the synthesized P18 and SLNs were evaluated by particle characteristics and release studies. The effects of P18 were evaluated using the 1,3-diphenylisobenzofuran (DPBF) assay as a nonbiological assay and a phototoxicity assay against HeLa and A549 cell lines as a biological assay. The mean particle size and zeta potential of the SLNs were 164.70-762.53 nm and -16.77-25.54 mV, respectively. These results indicate that P18-loaded SLNs are suitable for an enhanced permeability and retention effect as a passive targeting anti-cancer strategy. The formulations exhibited a burst and sustained release based on their stability. The DPBF assay indicated that the PDT effect of P18 improved when it was entrapped in the SLNs. The photocytotoxicity assay indicated that P18-loaded SLNs possessed light cytotoxicity but no dark cytotoxicity. In addition, the PDT activity of the formulations was cell type- and size-dependent. These results suggest that the designed P18-loaded SLNs are a promising tool for anticancer treatment using PDT.

Commensurate Assembly of C60 on Black Phosphorus for Mixed-Dimensional van der Waals Transistors.

2D crystals can serve as templates for the realization of new van der Waals (vdW) heterostructures via controlled assembly of low-dimensional functional components. Among available 2D crystals, black phosphorus (BP) is unique due to its puckered atomic surface topography, which may lead to strong epitaxial phenomena through guided vdW assembly. Here, it is demonstrated that a BP template can induce highly oriented assembly of C60 molecular crystals. Transmission electron microscopy and theoretical analysis of the C60 /BP vdW heterostructure clearly confirm that the BP template results in oriented C60 assembly with higher-order commensurism. Lateral and vertical devices with C60 /BP junctions are fabricated via a lithography-free clean process, which allows one to investigate the ideal electrical properties of pristine C60 /BP junctions. Effective tuning of the C60 /BP junction barrier from 0.2 to 0.5 eV and maximum on-current density higher than 104  mA cm-2 are achieved with graphite/C60 /BP vertical vdW transistors. Due to the formation of high-quality C60 film and the semitransparent graphite top-electrode, the vertical transistors show high photoresponsivities up to ≈100 A W-1 as well as a fast response time under visible light illumination.

Biparametric Magnetic Resonance Imaging-Derived Nomogram to Detect Clinically Significant Prostate Cancer by Targeted Biopsy for Index Lesion.

BACKGROUND: Currently, it is necessary to investigate how to combine biparametric magnetic resonance imaging (bpMRI) with various clinical parameters for the detection of clinically significant prostate cancer (csPCa). PURPOSE: To develop a multivariate prebiopsy nomogram using clinical and bpMRI parameters for estimating the probability of csPCa. STUDY TYPE: Retrospective, single-center study. SUBJECTS: Two hundred and twenty-six patients who underwent targeted biopsy (TBx) for the MRI-suspected index lesion because of clinical suspicions of PCa. FIELD STRENGTH/SEQUENCE: A 3 T MRI including turbo spin-echo T2 -weighted and diffusion-weighted single-shot echo-planar imaging sequences. ASSESSMENT: Prebiopsy clinical and bpMRI parameters were patient age, biopsy history (biopsy-naïve or repeated biopsy status), prostate-specific antigen density (PSAD), Prostate Imaging-Reporting and Data System version 2.1 (PI-RADSv2.1), and apparent diffusion coefficient ratio (ADCR). ADCR was defined as mean ADC of the index lesion divided by mean ADC of the contralateral prostatic region. A multivariate prebiopsy nomogram for csPCa (i.e. Gleason sum ≥7) was developed. Area under the curve (AUC) of each parameter and prebiopsy nomogram was assessed. Five-fold cross-validation was performed for robust estimation of performance of the prebiopsy nomogram. STATISTICAL TESTS: Logistic regression, receiver-operating curve, and 5-fold cross-validation. P-value < 0.05 was considered statistically significant. RESULTS: Proportion of csPCa was 31.9% (72/226). The AUCs of age, biopsy-naïve status, PSAD, PI-RADSv2.1, ADCR, and prebiopsy nomogram were 0.657 (95% confidence interval [CI], 0.580-0.733), 0.593 (95% CI, 0.525-0.660), 0.762 (95% CI, 0.697-0.826), 0.824 (95% CI, 0.770-0.878), 0.829 (95% CI, 0.769-0.888), and 0.906 (95% CI, 0.863-0.948), respectively: AUC of nomogram was significantly different than that of individual parameter. In the 5-fold cross-validation, the mean AUC of the prebiopsy nomogram for csPCa was 0.888 (95% CI, 0.786-0.983). DATA CONCLUSIONS: This multivariate prebiopsy nomogram using clinical and bpMRI parameters may help estimate the probability of csPCa in patients undergoing TBx. ADCR seems to enhance the role of bpMRI in detecting csPCa. LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY: Stage 2.

Application of Immunoprofiling Using Multiplexed Immunofluorescence Staining Identifies the Prognosis of Patients with High-Grade Serous Ovarian Cancer.

Immunoprofiling has an established impact on the prognosis of several cancers; however, its role and definition in high-grade serous ovarian cancer (HGSOC) are mostly unknown. This study is to investigate immunoprofiling which could be a prognostic factor in HGSOC. We produced tumor microarrays of 187 patients diagnosed with HGSOC. We performed a multiplexed immunofluorescence staining using Opal Multiplex IHC kit and quantitative analysis with Vectra-Inform system. The expression intensities of programmed death-ligand 1 (PD-L1), CD4, CD8, CD20, FoxP3, and CK in whole tumor tissues were evaluated. The enrolled patients showed general characteristics, mostly FIGO stage III/IV and responsive to chemotherapy. Each immune marker showed diverse positive densities, and each tumor sample represented its immune characteristics as an inflamed tumor or noninflamed tumor. No marker was associated with survival as a single one. Interestingly, high ratios of CD8 to FoxP3 and CD8 to PD-L1 were related to the favorable overall survival (77 vs. 39 months, 84 vs. 47 months, respectively), and CD8 to PD-L1 ratio was also a significant prognostic factor (HR 0.621, 95% CI 0.420-0.917, p = 0.017) along with well-known clinical prognostic factors. Additionally, CD8 to PD-L1 ratio was found to be higher in the chemosensitive group (p = 0.034). In conclusion, the relative expression levels of CD8, FoxP3, and PD-L1 were significantly related to the clinical outcome of patients with HGSOC, which could be a kind of significant immunoprofiling of ovarian cancer patients to apply for treatment.

Completely foldable electronics based on homojunction polymer transistors and logics.

An increase in the demand for completely foldable electronics has motivated efforts for the development of conducting polymer electrodes having extraordinary mechanical stability. However, weak physical adhesion at intrinsic heterojunctions has been a challenge in foldable electronics. This paper reports the completely foldable polymer thin-film transistors (PTFTs) and logic gate arrays. Homojunction-based PTFTs were fabricated by selectively doping p-type diketopyrrolopyrrole-based semiconducting polymer films with FeCl3 to form source/drain electrodes. The doping process caused a gradual work function change with depth, which promoted charge injection to semiconducting regions and provided a low contact resistance. In addition, the interfacial adhesion in the PTFTs was improved by interfacial cross-linking between adjacent component layers. The electrical performance of the resulting PTFTs was maintained without noticeable degradation even after extreme folding, suggesting that the proposed fabrication strategy can further be applied to various semiconducting polymers for the realization of foldable electronics.

Prostate Imaging-Reporting and Data System: Comparison of the Diagnostic Performance between Version 2.0 and 2.1 for Prostatic Peripheral Zone.

OBJECTIVE: To compare the diagnostic performance between Prostate Imaging-Reporting and Data System version 2.0 (PI-RADSv2.0) and version 2.1 (PI-RADSv2.1) for clinically significant prostate cancer (csPCa) in the peripheral zone (PZ). MATERIALS AND METHODS: This retrospective study included 317 patients who underwent multiparametric magnetic resonance imaging and targeted biopsy for PZ lesions. Definition of csPCa was International Society of Urologic Pathology grade ≥ 2 cancer. Area under the curve (AUC), sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy for csPCa were analyzed by two readers. The cancer detection rate (CDR) for csPCa was investigated according to the PI-RADS categories. RESULTS: AUC of PI-RADSv2.1 (0.856 and 0.858 for reader 1 and 2 respectively) was higher than that of PI-RADSv2.0 (0.795 and 0.747 for reader 1 and 2 respectively) (both p < 0.001). Sensitivity, specificity, PPV, NPV, and accuracy for PI-RADSv2.0 vs. PI-RADSv2.1 were 93.2% vs. 88.3% (p = 0.023), 52.8% vs. 76.6% (p < 0.001), 48.7% vs. 64.5% (p < 0.001), 94.2% vs. 93.2% (p = 0.504), and 65.9% vs. 80.4% (p < 0.001) for reader 1, and 96.1% vs. 92.2% (p = 0.046), 34.1% vs. 72.4% (p < 0.001), 41.3% vs. 61.7% (p < 0.001), 94.8% vs. 95.1% (p = 0.869), and 54.3% vs. 78.9% (p < 0.001) for reader 2, respectively. CDRs of PI-RADS categories 1-2, 3, 4, and 5 for PI-RADSv2.0 vs. PI-RADSv2.1 were 5.9% vs. 5.9%, 5.8% vs. 12.5%, 39.8% vs. 56.2%, and 88.9% vs. 88.9% for reader 1; and 4.5% vs. 4.1%, 6.1% vs. 11.1%, 32.5% vs. 53.4%, and 85.0% vs. 86.8% for reader 2, respectively. CONCLUSION: Our data demonstrated improved AUC, specificity, PPV, accuracy, and CDRs of category 3 or 4 of PI-RADSv2.1, but decreased sensitivity, compared with PI-RADSv2.0, for csPCa in PZ.

Hysteresis Behavior of the Donor-Acceptor-Type Ambipolar Semiconductor for Non-Volatile Memory Applications.

Donor-acceptor-type organic semiconductor molecules are of great interest for potential organic field-effect transistor applications with ambipolar characteristics and non-volatile memory applications. Here, we synthesized an organic semiconductor, PDPPT-TT, and directly utilized it in both field-effect transistor and non-volatile memory applications. As-synthesized PDPPT-TT was simply spin-coated on a substrate for the device fabrications. The PDPPT-TT based field-effect transistor showed ambipolar electrical transfer characteristics. Furthermore, a gold nanoparticle-embedded dielectric layer was used as a charge trapping layer for the non-volatile memory device applications. The non-volatile memory device showed clear memory window formation as applied gate voltage increases, and electrical stability was evaluated by performing retention and cycling tests. In summary, we demonstrate that a donor-acceptor-type organic semiconductor molecule shows great potential for ambipolar field-effect transistors and non-volatile memory device applications as an important class of materials.

Double Negative Differential Resistance Device Based on Hafnium Disulfide/Pentacene Hybrid Structure.

Recently, combinations of 2D van der Waals (2D vdW) materials and organic materials have attracted attention because they facilitate the formation of various heterojunctions with excellent interface quality owing to the absence of dangling bonds on their surface. In this work, a double negative differential resistance (D-NDR) characteristic of a hybrid 2D vdW/organic tunneling device consisting of a hafnium disulfide/pentacene heterojunction and a 3D pentacene resistor is reported. This D-NDR phenomenon is achieved by precisely controlling an NDR peak voltage with the pentacene resistor and then integrating two distinct NDR devices in parallel. Then, the operation of a controllable-gain amplifier configured with the D-NDR device and an n-channel transistor is demonstrated using the Cadence Spectre simulation platform. The proposed D-NDR device technology based on a hybrid 2D vdW/organic heterostructure provides a scientific foundation for various circuit applications that require the NDR phenomenon.

Effectiveness of preoperative ultrasound-guided charcoal tattooing for localization of metastatic melanoma.

PURPOSE: Excision of metastatic lesions is an important treatment strategy in patients with malignant melanoma, both at the initial diagnosis and upon recurrence. Since nonpalpable lesions cannot be easily visualized in the surgical field, we evaluated the effectiveness of ultrasound (US)-guided tattooing using a charcoal suspension for the localization of nonpalpable metastatic lesions of malignant melanoma. METHODS: Between November 2009 and June 2019, we retrospectively reviewed 65 nonpalpable lesions in 29 patients with malignant melanoma who underwent preoperative US-guided tattooing using a charcoal suspension for histologically confirmed or suspected metastases. The characteristics of the tattooed lesions were analyzed. The effectiveness of the procedure was evaluated based on the detection rate in the surgical field and the presence or absence of residua on postoperative follow-up US. Procedure-related complications were also analyzed. RESULTS: Of 65 lesions, 33 (50.8%) were histologically confirmed as metastases before the tattooing procedure, while the other 32 were suspected of being metastases based on imaging studies. The mean lesion size was 9.8 mm (range, 1.3 to 24.4 mm). The final pathology revealed metastases in 59 lesions (90.8%), including lymph node (n=51), muscle (n=5), and in-transit (n=3) metastases. Sixty-one lesions (93.8%) were successfully detected intraoperatively and removed without residua on follow-up US. Four residual lesions were removed after repeated localization (n=2) or by intraoperative US (n=2). No relevant complications were noted. CONCLUSION: Preoperative US-guided tattooing localization can safely and effectively delineate nonpalpable metastatic melanoma lesions to aid in successful surgical excision.