GateView: A Multi-Omics Platform for Gene Feature Analysis of Virus Receptors within Human Normal Tissues and Tumors.

Viruses are obligate intracellular parasites that rely on cell surface receptor molecules to complete the first step of invading host cells. The experimental method for virus receptor screening is time-consuming, and receptor molecules have been identified for less than half of known viruses. This study collected known human viruses and their receptor molecules. Through bioinformatics analysis, common characteristics of virus receptor molecules (including sequence, expression, mutation, etc.) were obtained to study why these membrane proteins are more likely to become virus receptors. An in-depth analysis of the cataloged virus receptors revealed several noteworthy findings. Compared to other membrane proteins, human virus receptors generally exhibited higher expression levels and lower sequence conservation. These receptors were found in multiple tissues, with certain tissues and cell types displaying significantly higher expression levels. While most receptor molecules showed noticeable age-related variations in expression across different tissues, only a limited number of them exhibited gender-related differences in specific tissues. Interestingly, in contrast to normal tissues, virus receptors showed significant dysregulation in various types of tumors, particularly those associated with dsRNA and retrovirus receptors. Finally, GateView, a multi-omics platform, was established to analyze the gene features of virus receptors in human normal tissues and tumors. Serving as a valuable resource, it enables the exploration of common patterns among virus receptors and the investigation of virus tropism across different tissues, population preferences, virus pathogenicity, and oncolytic virus mechanisms.

Predicting tall-cell subtype of papillary thyroid carcinomas independently with preoperative multimodal ultrasound.

OBJECTIVES: This study aimed to explore the differences between tall-cell subtype of papillary thyroid carcinoma (TCPTC) and classical papillary thyroid carcinoma (cPTC) using multimodal ultrasound, and identify independent risk factors for TCPTC to compensate the deficiency of preoperative cytological and molecular diagnosis on PTC subtypes. METHODS: Forty-six TCPTC patients and 92 cPTC patients were included. Each patient received grey-scale ultrasound, colour Dopplor flow imaging (CDFI) and shear-wave elastography (SWE) preoperatively. Clinicopathologic information, grey-scale ultrasound features, CDFI features and SWE features of 98 lesions were compared using univariate analysis to find out predictors of TCPTC, based on which, a predictive model was built to differentiate TCPTC from cPTC and validated with 40 patients. RESULTS: Univariate and multivariate analyses identified that extra-thyroidal extension (odds ratio [OR], 15.12; 95% CI, 2.26-115.44), aspect ratio (≥0.91) (OR, 29.34; 95% CI, 1.29-26.23), and maximum diameter ≥14.6 mm (OR, 20.79; 95% CI, 3.87-111.47) were the independent risk factors for TCPTC. Logistic regression equation: P = 1/1+ExpΣ[-5.099 + 3.004 × (if size ≥14.6 mm) + 2.957 × (if aspect ratio ≥ 0.91) + 2.819 × (if extra-thyroidal extension). The prediction model had a good discrimination performance for TCPTC: the area under the receiver-operator-characteristic curve, sensitivity, and specificity were 0.928, 0.848, and 0.954 in cohort 1, and the corresponding values in cohort 2 were 0.943, 0.923, and 0.926, respectively. CONCLUSION: Ultrasound has the potential for differential diagnosis of TCPTC from cPTC. A prediction model based on ultrasound characteristics (extra-thyroidal extension, aspect ratio ≥0.91, and maximum diameter ≥14.6 mm) was useful in predicting TCPTC. ADVANCES IN KNOWLEDGE: Multimodal ultrasound prediction of TCPTC was a supplement to preoperative cytological diagnosis and molecular diagnosis of PTC subtypes.

[Cloning and functional analysis of 3ß-hydroxysteroid dehydrogenase gene involved in biosynthesis of digitoxin].

Digitoxin, an important secondary metabolite of Digitalis purpurea, is a commonly used cardiotonic in clinical practice. 3ß-Hydroxysteroid dehydrogenase(3ßHSD) is a key enzyme involved in the biosynthesis of digitoxin. It belongs to the short-chain dehydrogenase/reductase(SDR) family, playing a role in the biosynthesis of cardiac glycosides by oxidizing and isomerizing the precursor sterol. In this study, two 3ßHSD genes were cloned from D. purpurea. The results showed that the open reading frame(ORF) of Dp3ßHSD1 was 780 bp, encoding 259 amino acid residues. The ORF of Dp3ßHSD2 was 774 bp and encoded 257 residues. Dp3ßHSD1/2 had the cofactor binding site TGxxxA/GxG and the catalytic site YxxxK. In vitro experiments confirmed that Dp3ßHSD1/2 catalyzed the generation of progesterone from pregnenolone, and Dp3ßHSD1 had stronger catalytic capacity than Dp3ßHSD2. The expression level of Dp3ßHSD1 was much higher than that of Dp3ßHSD2 in leaves, and digitoxin was only accumulated in leaves. The results implied that Dp3ßHSD1 played a role in the dehydrogenation of pregnenolone to produce progesterone in the biosynthesis of digitoxin. This study provides a reference for further exploring the biosynthetic pathway of cardiac glycosides in D. purpurea.

Deciphering the role and mechanism of nano zero-valent iron on medium chain fatty acids production from CO2 via chain elongation in microbial electrosynthesis.

The integrated system of microbial electrosynthesis (MES) coupled with chain elongation has been considered a promising platform for carboxylic acids production. However, this biotechnology is still in its infancy, and many limitations are needed to be transcended, such as low electron transfer efficiency between cathode and microbes. In this study, nano zero-valent iron (NZVI) was employed to improve carboxylic acid production in the integrated system, and the promotion mechanisms were revealed. Results suggested that the highest production concentrations of acetate, butyrate, and caproate were observed at 7.5 g/L optimized NZVI dosage, increasing the total yield and coulomb efficiency by 23.7 % and 40.3 % compared to the control. Mechanism studies indicated that the hydrogen and electron released by the anaerobic corrosion of NZVI could be used as additional reducing equivalents, thereby enhancing the electron transfer performance. Besides, NZVI was also proven to facilitate the formation of electroactive biofilms according to the results of biofilm characterization and total DNA. In functional microbes' respect, the moderate NZVI enriched the chain elongator in biofilm, like Clostridium_sensu-stricto_12, and upregulated the activities of key enzymes of homoacetogenesis and chain elongation metabolic pathways, like carbon-monoxide dehydrogenase and hydroxyacyl-CoA dehydratase. This study provided the evidence and revealed how NZVI assisted carboxylic acid production from CO2 via chain elongation in MES.

Predicting malignancy in thyroid nodules based on conventional ultrasound and elastography: the value of predictive models in a multi-center study.

BACKGROUND: This study aimed to establish predictive models based on features of Conventional Ultrasound (CUS) and elastography in a multi-center study to determine appropriate preoperative diagnosis of malignancy in thyroid nodules with different risk stratification based on 2017 Thyroid Imaging Reporting and Data System by the American College of Radiology (ACR TI-RADS) guidelines. METHODS: Five hundred forty-eight thyroid nodules from three centers pathologically confirmed by the cytology or histology were retrospectively enrolled in the study, which were examined by CUS and elastography before fine needle aspiration (FNA) and surgery. Characteristics of CUS of thyroid nodules were reviewed according to 2017 ACR TI-RADS. Binary logistic regression analysis was used to develop the prediction models based on the different risk stratification of CUS features and elastography which were statistically significant. Values of predictive models were evaluated regarding the discrimination and calibration. RESULTS: Binary logistic regression showed that patients' age, taller-than-wider, lobulated or irregular boundary, extra-thyroid extension, microcalcification and the elastic parameter of Virtual touch tissue imaging quantification (VTIQ) max were independent predictors for thyroid malignancy (p < 0.05) in the ACR model and showed the area under the curve (AUC) in training (0.912) and validation cohort (internal and external: 0.877 vs 0.935). Predictive models showed predictors in ACR TR4 and TR5 for malignancy and diagnostic performance of AUC in training, internal and external validation cohort respectively: the VTIQ max (p < 0.001) with AUC of 0.809 vs 0.842 vs 0.705 and the age, taller than wide, VTIQ max variables with AUC of 0.859 vs 0.830 vs 0.906 in validation cohort. All predictive models have better calibration capabilities (p > 0.05). CONCLUSIONS: Predictive models combined CUS and elastography features would aid clinicians to make appropriate preoperative diagnosis of thyroid nodules among different risk stratification. The elastography parameter of VTIQ max has the priority in distinguishing thyroid malignancy with moderately suspicious (ACR TR4).

[Functional characterization and enzymatic properties of flavonoid glycosyltransferase gene CtUGT49 in Carthamus tinctorius].

Carthami Flos, as a traditional blood-activating and stasis-resolving drug, possesses anti-tumor, anti-inflammatory, and immunomodulatory pharmacological activities. Flavonoid glycosides are the main bioactive components in Carthamus tinctorius. Glycosyltransferase deserves to be studied in depth as a downstream modification enzyme in the biosynthesis of active glycoside compounds. This study reported a flavonoid glycosyltransferase CtUGT49 from C. tinctorius based on the transcriptome data, followed by bioinformatic analysis and the investigation of enzymatic properties. The open reading frame(ORF) of the gene was 1 416 bp, encoding 471 amino acid residues with the molecular weight of about 52 kDa. Phylogenetic analysis showed that CtUGT49 belonged to the UGT73 family. According to in vitro enzymatic results, CtUGT49 could catalyze naringenin chalcone to the prunin and choerospondin, and catalyze phloretin to phlorizin and trilobatin, exhibiting good substrate versatility. After the recombinant protein CtUGT49 was obtained by hetero-logous expression and purification, the enzymatic properties of CtUGT49 catalyzing the formation of prunin from naringenin chalcone were investigated. The results showed that the optimal pH value for CtUGT49 catalysis was 7.0, the optimal temperature was 37 ℃, and the highest substrate conversion rate was achieved after 8 h of reaction. The results of enzymatic kinetic parameters showed that the K_m value was 209.90 µmol·L~(-1) and k_(cat) was 48.36 s~(-1) calculated with the method of Michaelis-Menten plot. The discovery of the novel glycosyltransferase CtUGT49 is important for enriching the library of glycosylation tool enzymes and provides a basis for analyzing the glycosylation process of flavonoid glycosides in C. tinctorius.

Identification of a cytochrome P450 from Tripterygium hypoglaucum (Levl.) Hutch that catalyzes polpunonic acid formation in celastrol biosynthesis.

Tripterygium hypoglaucum (Levl.) Hutch, a traditional Chinese medicinal herb with a long history of use, is widely distributed in China. One of its main active components, celastrol, has great potential to be developed into anti-cancer and anti-obesity drugs. Although it exhibits strong pharmacological activities, there is a lack of sustainable sources of celastrol and its derivatives, making it crucial to develop novel sources of these drugs through synthetic biology. The key step in the biosynthesis of celastrol is considered to be the cyclization of 2,3-oxidosqualene into friedelin under the catalysis of 2,3-oxidosqualene cyclases. Friedelin was speculated to be oxidized into celastrol by cytochrome P450 oxidases (CYP450s). Here, we reported a cytochrome P450 ThCYP712K1 from Tripterygium hypoglaucum (Levl.) Hutch that catalyzed the oxidation of friedelin into polpuonic acid when heterologously expressed in yeast. Through substrate supplementation and in vitro enzyme analysis, ThCYP712K1 was further proven to catalyze the oxidation of friedelin at the C-29 position to produce polpunonic acid, which is considered a vital step in the biosynthesis of celastrol, and will lay a foundation for further analysis of its biosynthetic pathway.

Contrast-enhanced ultrasound in the assessment of Crohn's disease activity: comparison with computed tomography enterography.

BACKGROUND AND OBJECTIVE: Continuous assessment of disease activity remains a huge challenge during the follow-ups of patients with Crohn's disease (CD). In this paper, we aimed to evaluate the performance of contrast-enhanced ultrasound (CEUS) by comparing with computed tomography enterography (CTE) in the assessment of disease activity in CD. MATERIALS AND METHODS: Fifty-two patients diagnosed with CD were included in this study, using the CEUS and CTE as imaging methods for comparison. The selected parameters included the location and thickness of the thickest part of the intestinal wall, mesenteric fat proliferation, mesenteric vessels change, enhancement pattern and the presence of complications. Patients were clinically assessed using the Crohn's disease activity index (CDAI), C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR). Simple endoscopic score for Crohn's disease (SES-CD) was regarded as the reference standard. RESULTS: The location of the thickest part of the intestinal wall (κ = 0.653), bowel wall thickness (ICC = 0.795), mesenteric vessels change (κ = 0.692) and complications (κ = 0.796) displayed substantial agreement (0.61-0.80) between CEUS and CTE, while the detection of mesenteric fat proliferation (κ = 0.395) and enhancement pattern (κ = 0.288) showed fair consistency (0.21-0.40) for comparison. In CEUS, bowel wall thickness, mesenteric fat proliferation, enhancement pattern and mesenteric vessels change were statistically significant in assessing CD activity, while bowel wall thickness, mesenteric fat proliferation and mesenteric vessels change in CTE. Bowel wall thickness showed the best diagnostic performance in the assessment of CD activity at CEUS and CTE. CONCLUSION: CEUS provides a radiation-free and effective way to assess the CD activity in comparison with CTE, which also avoids frequent colonoscopy examinations, improves tolerance of patients, and reduces the cost of medical care, thereby serving as a useful tool for CD follow-up.

Ultrasound-based computer-aided diagnosis for cytologically indeterminate thyroid nodules with different radiologists.

PURPOSE: To evaluate a computer-aided diagnosis (CAD) technique in predicting malignancy for cytologically indeterminate thyroid nodules (TNs) as compared with different experienced radiologists. METHOD: 436 patients with 436 cytologically indeterminate TNs on fine-needle aspiration cytology (FNAC) were included and all were confirmed by surgical pathology. They were retrospectively analyzed with respect to ultrasound (US) characteristics using a commercially available CAD system (AmCAD-UT; AmCad BioMed, Taiwan, China) and reviewed by one junior and one senior radiologists.The CAD system and different experienced radiologists stratified the risk of malignancy using ACR TI-RADS category. The diagnostic performance by different experienced radiologists independently and after consulting the CAD (different experienced radiologists + CAD) and by the CAD alone were compared. RESULTS: The different experienced radiologists showed significantly higher specificities than the CAD system alone. The combination of radiologist and CAD system showed improved diagnostic performance with an AUC (Area under the curve) of 0.740 in the senior radiologist and 0.677 in the junior radiologist, as compared with CAD (AUC: 0.585) alone (all P < 0.05). The combination of senior radiologist and CAD system had the highest diagnostic performance (AUC: 0.740) and specificity (68.9%) compared to the others (all P < 0.05). CONCLUSION: The CAD system may play the potential role as a decision-making assistant alongside radiologists for differential diagnosis of TNs with indeterminate cytology.

Facile Preparation of Hydrophobic PLA/PBE Micro-Nanofiber Fabrics via the Melt-Blown Process for High-Efficacy Oil/Water Separation.

Polylactic acid (PLA) micro-nanofiber fabrics with a large specific surface area and excellent biodegradability are commonly used in oil/water separation; however, challenges remain due to their poor mechanical properties. Herein, a thermoplastic polylactic acid/propylene-based elastomer (PLA/PBE) polymer was prepared by blending PLA with PBE. Then, PLA/PBE micro-nanofiber fabrics were successfully prepared using a melt-blown process. The results show that the PLA/PBE micro-nanofiber fabric has a three-dimensional porous structure, improving the thermal stability and fluidity of the PLA/PBE blended polymers. The PLA/PBE micro-nanofiber fabric demonstrated a significantly reduced average fiber diameter and an enhanced breaking strength. Moreover, the water contact angle of the prepared samples is 134°, which suggests a hydrophobic capacity. The oil absorption rate of the fabric can reach 10.34, demonstrating excellent oil/water separation performance. The successful preparation of PLA/PBE micro-nanofiber fabrics using our new method paves the way for the large-scale production of promising candidates for high-efficacy oil/water separation applications.

Metabolic Engineering of Saccharomyces cerevisiae for High-Level Friedelin via Genetic Manipulation.

Friedelin, the most rearranged pentacyclic triterpene, also exhibits remarkable pharmacological and anti-insect activities. In particular, celastrol with friedelin as the skeleton, which is derived from the medicinal plant Tripterygium wilfordii, is a promising drug due to its anticancer and antiobesity activities. Although a previous study achieved friedelin production using engineered Saccharomyces cerevisiae, strains capable of producing high-level friedelin have not been stably engineered. In this study, a combined strategy was employed with integration of endogenous pathway genes into the genome and knockout of inhibiting genes by CRISPR/Cas9 technology, which successfully engineered multiple strains. After introducing an efficient TwOSC1T502E, all strains with genetic integration (tHMG1, ERG1, ERG20, ERG9, POS5, or UPC2.1) showed a 3.0∼6.8-fold increase in friedelin production compared with strain BY4741. Through further double knockout of inhibiting genes, only strains GD1 and GD3 produced higher yields. Moreover, strains GQ1 and GQ3 with quadruple mutants (bts1; rox1; ypl062w; yjl064w) displayed similar increases. Finally, the dominant strain GQ1 with TwOSC1T502E was cultured in an optimized medium in shake flasks, and the final yield of friedelin reached 63.91 ± 2.45 mg/L, which was approximately 65-fold higher than that of the wild-type strain BY4741 and 229% higher than that in ordinary SD-His-Ura medium. It was the highest titer for friedelin production to date. Our work provides a good example for triterpenoid production in microbial cell factories and lays a solid foundation for the mining, pathway analysis, and efficient production of valuable triterpenoids with friedelin as the skeleton.

Predicting malignancy in thyroid nodules with benign cytology results: The role of Conventional Ultrasound, Shear Wave Elastography and BRAF V600E.

BACKGROUND: Ultrasound-guided fine-needle aspiration (US-FNA) is the most accurate method for preoperative diagnosis of thyroid nodules, but how to deal with false negative results? OBJECTIVE: This study aimed to find preoperative diagnosis methods including Conventional Ultrasound (CUS), Shear Wave Elastography (SWE) and BRAF V600E testing to differentiate false negative nodules. METHODS: Forty-nine nodules in 49 patients with benign FNA results and pathological diagnoses were included. CUS and SWE features were evaluated. BRAF V600E analysis was performed after FNA. Diagnostic performances of three methods were analyzed in predicting malignancy in benign FNA results. RESULTS: Twenty-seven of 49 nodules were malignant, and 22 nodules were benign. Hypoechogenicity, taller-than-wider, irregular boundary, microcalcification, SWE max, SWE mean and BRAF V600E mutation were risk factors for malignancy. All 7 malignant nodules with BRAF V600E mutations and 18 of 20 malignant nodules without BRAF V600E mutations have two or more suspicious CUS features. Six of 7 malignant nodules with BRAF V600E mutations and 16 of 20 malignant nodules without BRAF V600E mutations had SWE mean value greater than the cut-off value. CONCLUSIONS: CUS, SWE and BRAF V600E were diagnostic tools for malignancy in FNA benign nodules. Further clinical decisions should be considered for nodules with two or more suspicious CUS features and SWE parameters greater than cut-off values whether BRAF V600E is mutational or not.

Mitochondria-Targeted Nanocarriers Promote Highly Efficient Cancer Therapy: A Review.

Mitochondria are the primary organelles which can produce adenosine triphosphate (ATP). They play vital roles in maintaining normal functions. They also regulated apoptotic pathways of cancer cells. Given that, designing therapeutic agents that precisely target mitochondria is of great importance for cancer treatment. Nanocarriers can combine the mitochondria with other therapeutic modalities in cancer treatment, thus showing great potential to cancer therapy in the past few years. Herein, we summarized lipophilic cation- and peptide-based nanosystems for mitochondria targeting. This review described how mitochondria-targeted nanocarriers promoted highly efficient cancer treatment in photodynamic therapy (PDT), chemotherapy, combined immunotherapy, and sonodynamic therapy (SDT). We further discussed mitochondria-targeted nanocarriers' major challenges and future prospects in clinical cancer treatment.

Preparation of Anti-Aristolochic Acid I Monoclonal Antibody and Development of Chemiluminescent Immunoassay and Carbon Dot-Based Fluoroimmunoassay for Sensitive Detection of Aristolochic Acid I.

Aristolochic acid (AA) toxicity has been shown in humans regarding carcinogenesis, nephrotoxicity, and mutagenicity. Monitoring the AA content in drug homologous and healthy foods is necessary for the health of humans. In this study, a monoclonal antibody (mAb) with high sensitivity for aristolochic acid I (AA-I) was prepared. Based on the obtained mAb, a chemiluminescent immunoassay (CLEIA) against AA-I was developed, which showed the 50% decrease in the RLUmax (IC50) value of 1.8 ng/mL and the limit of detection (LOD) of 0.4 ng/mL. Carbon dots with red emission at 620 nm, namely rCDs, were synthesized and employed in conventional indirect competitive enzyme-linked immunosorbent assay (icELISA) to improve the assay sensitivity of a fluoroimmunoassay (FIA). Oxidized 3,3'',5,5''-tetramethylbenzidine dihydrochloride (oxTMB) can quench the emission of the rCDs through the inner-filter effect; therefore, the fluorescence intensity of rCDs can be regulated by the concentration of mAb. As a result, the assay sensitivity of FIA was improved by five-fold compared to CLEIA. A good relationship between the results of the proposed assays and the standard ultra-high performance liquid chromatography-triple quadrupole mass spectrometer (UPLC-QQQ-MS/MS) of real samples indicated good accuracy and practicability of CLEIA and FIA.

A Comparative Analysis of Two Machine Learning-Based Diagnostic Patterns with Thyroid Imaging Reporting and Data System for Thyroid Nodules: Diagnostic Performance and Unnecessary Biopsy Rate.

Background: The risk stratification system of the American College of Radiology Thyroid Imaging Reporting and Data System (ACR TI-RADS) for thyroid nodules is affected by low diagnostic specificity. Machine learning (ML) methods can optimize the diagnostic performance in medical image analysis. However, it is unknown which ML-based diagnostic pattern is more effective in improving diagnostic performance for thyroid nodules and reducing nodule biopsies. Therefore, we compared ML-assisted visual approaches and radiomics approaches with ACR TI-RADS in diagnostic performance and unnecessary fine-needle aspiration biopsy (FNAB) rate for thyroid nodules. Methods: This retrospective study evaluated a data set of ultrasound (US) and shear wave elastography (SWE) images in patients with biopsy-proven thyroid nodules (≥1 cm) from the Shanghai Tenth People's Hospital (743 nodules in 720 patients from September 2017 to January 2019) and an independent test data set from the Ma'anshan People's Hospital (106 nodules in 102 patients from February 2019 to April 2019). Six US features and five SWE parameters from the radiologists' interpretation were used for building the ML-assisted visual approaches. The radiomics features extracted from the US and SWE images were used with ML methods for developing the radiomics approaches. The diagnostic performance for differentiating thyroid nodules and the unnecessary FNAB rate of the ML-assisted visual approaches and the radiomics approaches were compared with ACR TI-RADS. Results: The ML-assisted US visual approach had the best diagnostic performance than the US radiomics approach and ACR TI-RADS (area under the curve [AUC]: 0.900 vs. 0.789 vs. 0.689 for the validation data set, 0.917 vs. 0.770 vs. 0.681 for the test data set). After adding SWE, the ML-assisted visual approach had a better diagnostic performance than US alone (AUC: 0.951 vs. 0.900 for the validation data set, 0.953 vs. 0.917 for the test data set). When applying the ML-assisted US+SWE visual approach, the unnecessary FNAB rate decreased from 30.0% to 4.5% in the validation data set and from 37.7% to 4.7% in the test data set in comparison to ACR TI-RADS. Conclusions: The ML-assisted dual modalities visual approach can assist radiologists to diagnose thyroid nodules more effectively and considerably reduce the unnecessary FNAB rate in the clinical management of thyroid nodules.

Improving the diagnosis of AUS/FLUS thyroid nodules using an algorithm with combination of BRAFV600E mutation analysis and ultrasound pattern-based risk stratification.

PURPOSE: To propose a diagnostic algorithm for improving the diagnosis of atypia of undetermined significance or follicular lesion of undetermined significance (AUS/FLUS) thyroid nodules. METHODS: This study retrospectively enrolled 77 consecutive patients with 81 AUS/FLUS nodules who underwent preoperative BRAFV600E mutation analysis. A new diagnostic algorithm was proposed that BRAFV600E mutation analysis for the Fine-needle aspiration cytology specimen was firstly carried out, in which positive BRAFV600E mutation indicated malignancy and classification of the nodules with negative BRAFV600E mutation was further performed based on ultrasound pattern-based risk stratification of American Thyroid Association Guidelines. The diagnostic performance of the new diagnostic algorithm was evaluated. RESULTS: The sensitivity, specificity, positive predictive value, negative predictive value, accuracy, and area under the receiver operating characteristic curve (AUROC) of new diagnostic algorithm were 94.6%, 84.0%, 91.4%, 86.9%, 90.1%, and 0.893, respectively. The proposed diagnostic algorithm significantly increased the diagnostic performances (AUROC: 0.893 vs. 0.837 and 0.795), sensitivity (94.6% vs. 71.4% and 75.0%), and accuracy (90.1% vs. 79.0% and 77.8%) compared with BRAFV600E mutation analysis alone and ultrasound pattern-based risk stratification alone (all P < 0.05). CONCLUSION: The proposed diagnostic algorithm is helpful for improving the diagnosis of AUS/FLUS nodules, which might be as a routine approach.

Multimodal Ultrasound Imaging in Breast Imaging-Reporting and Data System 4 Breast Lesions: A Prediction Model for Malignancy.

The purpose of this study was to develop, validate and test a prediction model for discriminating malignant from benign breast lesions using conventional ultrasound (US), US elastography of strain elastography and contrast-enhanced ultrasound (CEUS). The study included 454 patients with breast imaging-reporting and data system (BI-RADS) category 4 breast lesions identified on histologic examinations. Firstly, 228 breast lesions (cohort 1) were analyzed by logistic regression analysis to identify the risk factors, and a breast malignancy prediction model was created. Secondly, the prediction model was validated in cohort 2 (84 patients) and tested in cohort 3 (142 patients) by using analysis of the area under the receiver operating characteristic curve (AUC). Univariate regression indicated that age ≥40 y, taller than wide shape on US, early hyperenhancement on CEUS and enlargement of enhancement area on CEUS were independent risk factors for breast malignancy (all p < 0.05). The logistic regression equation was established as follows: p = 1/1+Exp∑[-5.066 + 3.125 x (if age ≥40 y) + 1.943 x (if taller than wide shape) + 1.479 x (if early hyperenhancement) + 4.167 x (if enlargement of enhancement area). The prediction model showed good discrimination performance with an AUC of 0.967 in cohort 1, 0.948 in cohort 2 and 0.920 in cohort 3. By using the prediction model to selectively downgrade category 4a lesions, the re-rated BI-RADS yield an AUC of 0.880 (95% confidence interval [CI], 0.794-0.965) in cohort 2 and 0.870 (95% CI, 0.801-0.939) in cohort 3. The specificity increased from 0.0% (0/35) to 80.0% (28/35) without loss of sensitivity (from 100.0% to 95.9%, p = 0.153) in cohort 2. Similarly, the specificity increased from 0.0% (0/58) to 77.6% (45/58) without loss of sensitivity (from 100.0% to 96.4%, p = 0.081) in cohort 3. Multimodal US showed good diagnostic performance in predicting breast malignancy of BI-RADS category 4 lesions. Although the loss of sensitivity was existing, the addition of multimodal US to US BI-RADS could improve the specificity in BI-RADS category 4 lesions, which reduced unnecessary biopsies.

Ultrasound validation of predictive model for central cervical lymph node metastasis in papillary thyroid cancer on BRAF.

Aim: To compare the value of predictive power of the models for central cervical lymph node metastasis (CLNM) in papillary thyroid carcinomas (PTCs). Patients & methods: 220 PTCs were prospectively enrolled into the study with pathological examination. We established a new risk model with univariate and multivariate analyses and receiver-operating characteristic curves were plotted. Z-test was performed to compare the area under two curves and validated the predictive model for central CLNM in PTCs. The comparison of previous and new predictive model was analyzed. Results: Microcalcification, capsule contact or involvement, internal flow and BRAFV600E mutation were four independent risk factors for PTCs with central CLNMs. The area under the curves for the new and the previous model were 0.948 and 0.934 (p = 0.572), respectively. Conclusion: Two predictive models showed strong consistency in predicting central CLNM in PTCs. The predictive model may be helpful in selecting appropriate treatment method in PTCs.

Diagnostic Performance Evaluation of Practice Guidelines, Elastography and Their Combined Results for Thyroid Nodules: A Multicenter Study.

The purpose of this multicenter study was to compare the differential diagnostic value of the 2015 American Thyroid Association (ATA) and 2017 American College of Radiology (ACR) practice guidelines and elastography in thyroid nodules. This study also investigated whether the diagnostic value of practice guidelines can be improved, and the unnecessary biopsy rate decreased in combination with elastography. A total of 498 thyroid nodules were evaluated using the ATA and the ACR guidelines. Strain elastography, acoustic radiation force impulse imaging and point-shear wave elastography were used to assess the nodules. The suspicious levels were downgraded or upgraded after combination and unnecessary biopsy rates were calculated, respectively. The diagnostic performance of the practice guidelines was better than that of elastography. The ACR guidelines had a lower unnecessary biopsy rate and similar diagnostic performance compared with the ATA guidelines. The unnecessary biopsy rates significantly decreased when the ACR guidelines were combined with elastography, but the rates did not decrease when the ATA guidelines were combined with elastography.

Conventional ultrasound characteristics, TI-RADS category and shear wave speed measurement between follicular adenoma and follicular thyroid carcinoma.

The purpose of the study was to explore the differences of conventional ultrasound characteristics, thyroid imaging reporting and data system (TI-RADS) category and shear wave speed (SWS) measurement between follicular adenoma (FA) and follicular thyroid carcinoma (FTC). Twenty-eight FTCs and 67 FAs proven by surgery were retrospectively included for analysis. Conventional ultrasound and point-shear wave elastography (p-SWE) were performed in all of the included patients. The ultrasound features, American Thyroid Association (ATA) TI-RADS category and American College of Radiology (ACR) TI-RADS category, SWS measurement were compared between the two groups. Receiver operating characteristic (ROC) curve was performed and area under ROC curve (AUC) was obtained for significant features. There were no statistical differences in mean age (46.9±15.7years vs. 48.6±13.6years, P = 0.639), gender (9 males, 32.1% vs. 18 males, 29.0%, P = 0.766) and mean diameter (28.3±16.2 mm vs. 33.8±11.9 mm, P = 0.077) between FTCs and FAs. Hypoechogenicity, lobulated or irregular margin, macrocalcification were more common in FTCs than FAs (all P < 0.05). Mean SWS of FTCs (2.29±0.64 m/s) was slightly higher than that of FAs (1.94±0.68 m/s) (P = 0.023). The AUCs were 0.655, 0.744, and 0.744 with the cut-off SWS≥1.89 m/s, ACR TI-RADS category 4 and intermediate suspicion of ATA TI-RADS category. The sensitivity and AUC were 82.1% and 0.812 with combined ultrasound features of hypoechogenicity, lobulated or irregular margin and macrocalcification. In Conclusion, SWS measurement and TI-RADS categories were useful for the identification of FTCs from FAs.