Receptor-like cytoplasmic kinases PBL34/35/36 are required for CLE peptide-mediated signaling to maintain shoot apical meristem and root apical meristem homeostasis in Arabidopsis.

Shoot apical meristem (SAM) and root apical meristem (RAM) homeostasis is tightly regulated by CLAVATA3 (CLV3)/EMBRYO SURROUNDING REGION-related (CLE) peptide signaling. However, the intracellular signaling components after CLV3 is perceived by the CLV1-CLV3-INSENSITIVE KINASE (CIK) receptor complex and CLE25/26/45 are sensed by the BARELY ANY MERISTEM (BAM)-CIK receptor complex are unknown. Here, we report that PBS1-LIKE34/35/36 (PBL34/35/36), a clade of receptor-like cytoplasmic kinases, are required for both CLV3-mediated signaling in the SAM and CLE25/26/45-mediated signaling in the RAM. Physiological assays showed that the SAM and RAM of pbl34 pbl35 pbl36 were resistant to CLV3 and CLE25/26/45 treatment, respectively. Genetic analyses indicated that pbl34 pbl35 pbl36 greatly enhanced the SAM defects of clv2 and rpk2 but not clv1, and did not show additive effects with bam3 and cik2 in the RAM. Further biochemical assays revealed that PBL34/35/36 interacted with CLV1, BAM1/3, and CIKs, and were phosphorylated by CLV1 and BAM1. All these results suggest that PBL34/35/36 act downstream of CLV1 and BAM1/3 to mediate the CLV3 and CLE25/26/45 signals in maintaining SAM and RAM homeostasis, respectively. Our findings shed light on how CLE signals are transmitted intracellularly after being perceived by cell surface receptor complexes.

Multiparametric US for Identifying Metabolic Dysfunction-associated Steatohepatitis: A Prospective Multicenter Study.

Background Noninvasive evaluation of metabolic dysfunction-associated fatty liver disease (MAFLD) with multiparametric US is essential, but multicenter studies are lacking. Purpose To evaluate the ability of multiparametric US with attenuation imaging (ATI) and two-dimensional (2D) shear-wave elastography (SWE) for predicting metabolic dysfunction-associated steatohepatitis (MASH) in participants with MAFLD, regardless of hepatitis B virus infection status. Materials and Methods This prospective cross-sectional multicenter study of consecutive adults with MAFLD who underwent multiparametric US with ATI and 2D SWE, as well as liver biopsy, from September 2020 to June 2022 was conducted in 12 tertiary hospitals in China. Multivariable logistic regression was performed to assess risk factors associated with MASH. Area under the receiver operating characteristic curve (AUC) analysis was used to evaluate diagnostic performance in predicting MASH in training and validation groups (6:4 ratio of participants), and for a post hoc subgroup analysis of hepatitis B virus infection and diabetes. Results A total of 424 participants (median age, 47 years; IQR, 34-59 years; 244 male) were evaluated, including 332 participants (78%) with MASH and 92 (22%) without. Attenuation coefficient (AC) (odds ratio [OR], 3.32 [95% CI: 1.94, 5.71]; P < .001), alanine aminotransferase (ALT) level (OR, 4.42 [95% CI: 1.78, 10.94]; P = .001), and international normalized ratio (INR) (OR, 0.59 [95% CI: 0.37, 0.95]; P = .03) were independently associated with MASH. A combined model (AC, ALT, and INR) had AUCs of 0.85 (95% CI: 0.79, 0.91) and 0.77 (95% CI: 0.69, 0.85) for predicting MASH in the training and validation groups, respectively. AUC values for the subgroups with and without diabetes were 0.83 (95% CI: 0.72, 0.94) and 0.81 (95% CI: 0.75, 0.87) and for the subgroups with and without hepatitis B were 0.82 (95% CI: 0.74, 0.90) and 0.79 (95% CI: 0.71, 0.87), respectively. Conclusion A model combining AC, ALT level, and INR showed good discrimination ability for predicting MASH in participants with MAFLD. Clinical trial registration no. NCT04551716 © RSNA, 2024 Supplemental material is available for this article. See also the editorial by Reuter in this issue.

Prognostic Value of the Gustave Roussy Immune Score in Lung Cancer: A Meta-Analysis.

PURPOSE: To clarify the prognostic role of the Gustave Roussy immune (GRIm) score in lung cancer. METHODS: The PubMed, Embase, Web of Science, and China National Knowledge Infrastructure databases were searched up to March 30, 2024. The primary outcomes included overall survival (OS) and progression-free survival (PFS). Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated to evaluate the associations between the GRIm score and survival, and subgroup analyses were performed based on pathological type (non-small cell lung cancer vs. small cell lung cancer), tumor stage (advanced vs. limited stage) and treatment approach (immune checkpoint inhibitor vs. surgery vs. chemotherapy). RESULTS: Eight studies with 1,333 participants were included. The pooled results showed that a higher GRIm score predicted worse OS (HR = 1.96, 95% CI: 1.54-2.49, P < 0.001) and PFS (HR = 1.64, 95% CI: 1.22-2.21, P = 0.001). Subgroup analyses for OS and PFS showed similar results. However, subgroup analyses for PFS indicated that the association between the GRIm score and PFS was nonsignificant among patients with small cell lung cancer (P = 0.114) and among patients treated with chemotherapy (P = 0.276). CONCLUSION: The GRIm score might serve as a novel prognostic factor for lung cancer. Additional studies are still needed to verify these findings.

3D-CEUS/MRI-CEUS fusion imaging vs 2D-CEUS after locoregional therapies for hepatocellular carcinoma: a multicenter prospective study of therapeutic response evaluation.

OBJECTIVES: To compare the diagnostic accuracy of 3D contrast-enhanced ultrasound (CEUS)/MRI-CEUS fusion imaging with 2D-CEUS in assessing the response of hepatocellular carcinoma (HCC) to locoregional therapies in a multicenter prospective study. MATERIALS AND METHODS: A consecutive series of patients with HCC scheduled for locoregional treatment were enrolled between April 2021 and March 2023. Patients were randomly divided into 3D-CEUS/MRI-CEUS fusion imaging group (3D/fusion group) or 2D-CEUS group (2D group). CEUS was performed 1 week before and 4-6 weeks after locoregional treatment. Contrast-enhanced MRI (CE-MRI) 4-6 weeks after treatment was set as the reference standard. CEUS images were evaluated for the presence or absence of viable tumors. Diagnostic performance criteria, including sensitivity, specificity, accuracy, and area under the curve (AUC), were determined for each modality. RESULTS: A total of 140 patients were included, 70 patients in the 2D group (mean age, 60.2 ± 10.4 years) and 70 patients in the 3D/fusion group (mean age, 59.8 ± 10.6 years). The sensitivity of the 3D/fusion group was 100.0% (95% CI: 75.9, 100.0), higher than that of the 2D group (55.6%, 95% CI: 22.7, 84.7; p = 0.019). The specificity of the 3D/fusion group was 96.3% (95% CI: 86.2, 99.4), which was comparable to that of the 2D group (98.4%, 95% CI: 90.0, 99.9; p = 0.915). The AUC of the 3D/fusion group was 0.98 (95% CI: 0.95, 1.00), higher than that of the 2D group (0.77, 95% CI: 0.56, 0.98; p = 0.020). CONCLUSION: 3D-CEUS/MRI-CEUS fusion imaging exhibits superior diagnostic accuracy in evaluating the treatment response to locoregional therapies for HCC. CLINICAL RELEVANCE STATEMENT: 3D-CEUS/MRI-CEUS fusion imaging can be applied for post-treatment assessment of residual tumors in HCC undergoing locoregional treatment, offering potential benefits in terms of accurate diagnosis and clinical management. KEY POINTS: Evaluating for HCC recurrence following locoregional therapy is important. 3D-CEUS/MRI-CEUS fusion imaging achieved a higher sensitivity than 2D-CEUS in assessing residual tumors after locoregional therapies. 3D-CEUS/MRI-CEUS fusion imaging can help clinicians intervene early in residual HCC lesions after locoregional treatment.

Impact of deep muscle invasion on nodal status and survival in patients with pT2 esophageal squamous cancer.

BACKGROUND: Whether T2 esophageal squamous cell carcinoma should be subclassified remains controversial. We aimed to investigate the impact of the depth of muscularis propria invasion on nodal status and survival outcomes. METHODS: We identified patients with pT2 esophageal squamous cell carcinoma who underwent primary surgery from January 2009 to June 2017. Clinical data were extracted from prospectively maintained databases. Tumor muscularis propria invasion was stratified into superficial or deep. Binary logistic regression was used to determine risk factors for lymph node metastases. The impact of the depth of muscularis propria invasion on survival was investigated using Kaplan‒Meier analysis and a Cox proportional hazard regression model. RESULTS: A total of 750 patients from three institutes were investigated. The depth of muscularis propria invasion (odds ratio [OR]: 3.95, 95% confidence interval [CI]: 2.46-6.35; p < 0.001) was correlated with lymph node metastases using logistic regression. T substage (hazard ratio [HR]: 1.37, 95% CI: 1.05-1.79; p < 0.001) and N status (HR: 1.51, 95% CI: 1.05-2.17; p < 0.001) were independent risk factors in multivariate Cox regression analysis. The deep muscle invasion was associated with worse overall survival (HR: 1.52, 95% CI: 1.19-1.94; p = 0.001) than superficial, specifically in T2N0 patients (HR: 1.38, 95% CI: 1.08-1.94; p = 0.035). CONCLUSIONS: We found that deep muscle invasion was associated with significantly worse outcomes and recommended the substaging of pT2 esophageal squamous cell carcinoma in routine pathological examination.

Mapping of lymph node metastasis from esophageal squamous cell carcinoma after neoadjuvant treatment: a prospective analysis from a high-volume institution in China.

The study aimed to describe the prevalence of lymph node metastases per lymph node station for esophageal squamous cell carcinoma (ESCC) after neoadjuvant treatment. Clinicopathological variables of ESCC patients were retrieved from the prospective database of the Surgical Esophageal Cancer Patient Registry in West China Hospital, Sichuan University. A two-field lymphadenectomy was routinely performed, and an extensive three-field lymphadenectomy was performed if cervical lymph node metastasis was suspected. According to AJCC/UICC 8, lymph node stations were investigated separately. The number of patients with metastatic lymph nodes divided by those who underwent lymph node dissection at that station was used to define the percentage of patients with lymph node metastases. Data are also separately analyzed according to the pathological response of the primary tumor, neoadjuvant treatment regimens, pretreatment tumor length, and tumor location. Between January 2019 and March 2023, 623 patients who underwent neoadjuvant therapy followed by transthoracic esophagectomy were enrolled. Lymph node metastases were found in 212 patients (34.0%) and most frequently seen in lymph nodes along the right recurrent nerve (10.1%, 58/575), paracardial station (11.4%, 67/587), and lymph nodes along the left gastric artery (10.9%, 65/597). For patients with pretreatment tumor length of >4 cm and non-pathological complete response of the primary tumor, the metastatic rate of the right lower cervical paratracheal lymph nodes is 10.9% (10/92) and 10.6% (11/104), respectively. For patients with an upper thoracic tumor, metastatic lymph nodes were most frequently seen along the right recurrent nerve (14.2%, 8/56). For patients with a middle thoracic tumor, metastatic lymph nodes were most commonly seen in the right lower cervical paratracheal lymph nodes (10.3%, 8/78), paracardial lymph nodes (10.2%, 29/285), and lymph nodes along the left gastric artery (10.4%, 30/289). For patients with a lower thoracic tumor, metastatic lymph nodes were most frequently seen in the paracardial station (14.2%, 35/247) and lymph nodes along the left gastric artery (13.1%, 33/252). The study precisely determined the distribution of lymph node metastases in ESCC after neoadjuvant treatment, which may help to optimize the extent of lymphadenectomy in the surgical management of ESCC patients after neoadjuvant therapy.

Evaluation of Safety, Efficacy, and Compliance of Intralymphatic Immunotherapy for Allergic Rhinoconjunctivitis: A Systematic Review and Meta-Analysis.

INTRODUCTION: Intralymphatic immunotherapy (ILIT) is an emerging type of allergen immunotherapy with fewer injections and shorter course for allergic rhinoconjunctivitis (ARC). The efficacy and safety have not been confirmed by informative and powerful evidence yet. METHODS: A systematic review and meta-analysis were conducted through electronic searching with PubMed, Web of Science, Embase, Scopus, and China National Knowledge Infrastructure (CNKI). The safety (incidence of adverse events [AEs]), compliance (percent of patients completing treatment), and clinical efficacy of ILIT were evaluated. Clinical efficacy could be assessed by improvement of subjective symptom and rescue medication use or the nasal tolerance to specific allergen. This study is registered with PROSPERO (CRD42022353562). RESULTS: 12 randomized controlled trials (RCTs) comparing ILIT with placebo and 3 trials (2 RCTs and one case-control study) comparing ILIT and SCIT were included in this review. Totally, 582 patients diagnosed as AR or ARC were enrolled. Almost all the AEs were mild-to-moderate reactions except 2 patients developed anaphylactic reactions at the intralymphatic injection dose 5,000 SQ-U in one study. ILIT got higher incidence of local AEs than placebo, but their incidence of systemic AEs was similar. ILIT was safer than SCIT (p < 0.05). Almost all the patients could complete ILIT treatment, and the most common reason for discontinuation of ILIT was AEs. The compliance of patients receiving ILIT seemed higher than patients receiving SCIT. ILIT could significantly ameliorate subjective allergic symptoms, especially for seasonal ARC, and increase nasal tolerance, similar to SCIT. CONCLUSION: ILIT was a safe and effective treatment for ARC and could achieve comparable clinical improvement with SCIT with shorter duration and higher compliance. Moreover, ILIT was safer than SCIT.

Application of ultrasound shear wave elastography in pre-operative and quantitative prediction of clinically relevant post-operative pancreatic fistula after pancreatectomy: a prospective study for the investigation of risk evaluation model.

OBJECTIVES: The aim of this study was to modify recognized clinically relevant post-operative pancreatic fistula (CR-POPF) risk evaluation models with quantitative ultrasound shear wave elastography (SWE) values and identified clinical parameters to improve the objectivity and reliability of the prediction. METHODS: Two prospective, successive cohorts were initially designed for the establishment of CR-POPF risk evaluation model and the internal validation. Patients who scheduled to receive pancreatectomy were enrolled. Virtual touch tissue imaging and quantification (VTIQ)-SWE was used to quantify pancreatic stiffness. CR-POPF was diagnosed according to 2016 International Study Group of Pancreatic Fistula standard. Recognized peri-operative risk factors of CR-POPF were analyzed, and the independent variables selected from multivariate logistic regression were used to build the prediction model. RESULTS: Finally, the CR-POPF risk evaluation model was built in a group of 143 patients (cohort 1). CR-POPF occurred in 52/143 (36%) patients. Constructed from SWE values and other identified clinical parameters, the model achieved an area under the receiver operating characteristic curve of 0.866, with sensitivity, specificity, and likelihood ratio of 71.2%, 80.2%, and 3.597 in predicting CR-POPF. Decision curve of modified model revealed a better clinical benefit compared to the previous clinical prediction models. The models were then examined via internal validation in a separate collection of 72 patients (cohort 2). CONCLUSIONS: Risk evaluation model based on SWE and clinical parameters is a potential non-invasive way to pre-operatively, objectively predict CR-POPF after pancreatectomy. CLINICAL RELEVANCE STATEMENT: Our modified model based on ultrasound shear wave elastography may provide an easy access in pre-operative and quantitative evaluating the risk of CR-POPF following pancreatectomy and improve the objectivity and reliability of the prediction compared to previous clinical models. KEY POINTS: • Modified prediction model based on ultrasound shear wave elastography (SWE) provides an easy access for clinicians to pre-operatively, objectively evaluate the risk of clinically relevant post-operative pancreatic fistula (CR-POPF) following pancreatectomy. • Prospective study with validation showed that the modified model provides better diagnostic efficacy and clinical benefits compared to previous clinical models in predicting CR-POPF. • Peri-operative management of CR-POPF high-risk patients becomes more possible.

Changes in vaginal microbiome after focused ultrasound treatment of high-risk human papillomavirus infection-related low-grade cervical lesions.

BACKGROUND: In this study, the changes of vaginal microbiome after focused ultrasound (FU) treatment were evaluated to explore the possible mechanism of FU in the treatment of high-risk human papillomavirus (HR-HPV) infection. METHODS: This study was nested in the FU arm of a prospective cohort study. A total of 37 patients diagnosed with HR-HPV infection-related cervical low-grade squamous intraepithelial lesion (LSIL) who met the inclusion criteria were enrolled in this study from October 2020 to November 2021, and these patients were treated with FU. We used 16S ribosomal RNA (16S rRNA) gene amplicon sequencing to profile the vaginal microbiota composition of patients before and 3 months after FU treatment. RESULTS: After FU treatment, HR-HPV was cleared in 24 patients, with a clearance rate of 75.0% (24/32). Lactobacillus iners was the predominant species among all samples. No significant difference was found in alpha-diversity index before and 3 months after FU treatment (P > 0.05), but the rarefaction curves showed that the vaginal microbial diversity before FU treatment was higher than that after FU treatment. Linear discriminant analysis (LDA) effect size (LEfSe) showed that Bifidobacterium contributed the most to the difference between the two groups at the genus level, and the abundance after FU treatment was significantly higher than that before treatment (P = 0.000). CONCLUSIONS: The decrease of vaginal microbial diversity may be related to the clearance of HR-HPV infection, and FU treatment contributed to the decrease of vaginal microbial diversity. Increased Bifidobacterium abundance in the vaginal microbiome may be associated with clearance of HR-HPV infection, and FU treatment may contribute to the increase in Bifidobacterium abundance. TRIAL REGISTRATION NUMBER:  This study was registered in the Chinese Clinical Trial Registry on 23/11/2020 (ChiCTR2000040162).

Efficacy and pregnancy outcomes of focused ultrasound for cervical high-grade squamous intraepithelial lesions.

OBJECTIVE: To investigate the efficacy and adverse effects of focused ultrasound (FU) in the treatment of high-grade squamous intraepithelial lesions (HSIL) and follow up on pregnancy outcomes in patients. METHODS: This retrospective study recruited 57 patients aged 20-40 years with cervical HSIL combined with HR-HPV infection who received FU treatment between September 2019 and April 2022. Clinical data of the patients were obtained from hospital records. HSIL cure rate and cumulative HR-HPV clearance rate were assessed after treatment. Patients were followed up on fertility and pregnancy outcomes after treatment by telephone interviews until April 1, 2023. RESULTS: During a 6-month follow-up, the HSIL cure rate was 73.7%, and a statistical difference between CIN2 and CIN3 (75.6% vs. 66.7%, p = 0.713) was not present. HSIL -recurrence was not observed during the follow-up period, and the median follow-up duration was 12 months. The cumulative HR-HPV clearance rates at the 6- and 12-month follow-ups were 56.1% and 75.4%, respectively. The median clearance time of HR-HPV was 6 (95% confidence interval, 5.46-6.54) months. The clearance rate was higher in HPV16/18 than in non-HPV16/18 (86.7% vs. 62.9%, p = 0.038). After treatment, the successful pregnancy rate in patients with fertility intentions and spontaneous abortion rate were 73.9% and 5.9%, respectively. Preterm birth, preterm premature rupture of membranes, or low-birth-weight infants were not observed. CONCLUSION: FU treatment can regress HSIL and accelerate HR-HPV clearance in young women of childbearing age with cervical HSIL associated with HR-HPV infection, and has no significant adverse effects on pregnancy outcomes.

Electric field promotes dermal fibroblast transdifferentiation through activation of RhoA/ROCK1 pathway.

With the increased incidence of age-related and lifestyle-related diseases, chronic wounds are sweeping the world, where recent studies reveal that dysfunction of fibroblast plays an indispensable role. Endogenous electric field (EF) generated by skin wound disrupting an epithelial layer has been used as an alternative clinical treatment in chronic wound by modulating cellular behaviours, including fibroblasts transdifferentiation. Although many molecules and signaling pathways have been reported associated with fibroblasts transdifferentiation, studies investigating how the electric field affects the cellular pathways have been limited. For this purpose, a model of electric field treatment in vitro was established, where cells were randomly divided into control and electrified groups. The changes of protein expression and distribution were detected under different conditions, along with Zeiss imaging system observing the response of cells. Results showed that fibroblast transdifferentiation was accompanied by increased expression of a-SMA and extracellular matrix (COL-1 and COL-3) under the EF. Simultaneously, fibroblast transdifferentiation was also consistent with changes of cell arrangement and enhanced motility. Furthermore, we found that electric field activated RhoA signaling pathways activity. Y-27632, a RhoA inhibitor, which was used to treat fibroblasts, resulted in reduced transdifferentiation. The connection between electric field and RhoA signaling pathways is likely to be significant in modulating fibroblast transdifferentiation in acute injury and tissue remodeling, which provides an innovative idea for the molecular mechanism of EF in promoting chronic wound healing.

Differential diagnosis of gallbladder neoplastic polyps and cholesterol polyps with radiomics of dual modal ultrasound: a pilot study.

PURPOSE: To verify whether radiomics techniques based on dual-modality ultrasound consisting of B-mode and superb microvascular imaging (SMI) can improve the accuracy of the differentiation between gallbladder neoplastic polyps and cholesterol polyps. METHODS: A total of 100 patients with 100 pathologically proven gallbladder polypoid lesions were enrolled in this retrospective study. Radiomics features on B-mode ultrasound and SMI of each lesion were extracted. Support vector machine was used to classify adenomas and cholesterol polyps of gallbladder for B-mode, SMI and dual-modality ultrasound, respectively, and the classification results were compared among the three groups. RESULTS: Six, eight and nine features were extracted for each lesion at B-mode ultrasound, SMI and dual-modality ultrasound, respectively. In dual-modality ultrasound model, the area under the receiver operating characteristic curve (AUC), classification accuracy, sensitivity, specificity, and Youden's index were 0.850 ± 0.090, 0.828 ± 0.097, 0.892 ± 0.144, 0.803 ± 0.149 and 0.695 ± 0.157, respectively. The AUC and Youden's index of the dual-modality model were higher than those of the B-mode model (p < 0.05). The AUC, accuracy, specificity and Youden's index of the dual-modality model were higher than those of the SMI model (p < 0.05). CONCLUSIONS: Radiomics analysis of the dual-modality ultrasound composed of B-mode and SMI can improve the accuracy of classification between gallbladder neoplastic polyps and cholesterol polyps.

The Preliminary Application of Simultaneous Display of Contrast-Enhanced Ultrasound and Micro-Flow Imaging Technology in the Diagnosis of Hepatic Tumors.

OBJECTIVES: To evaluate the value of simultaneous display of contrast-enhanced ultrasound and micro-flow imaging technology (CEUS-MFI) in intra-tumoral vessel detection and hepatic tumor diagnosis. METHODS: A total of 82 patients with 82 focal liver lesions were enrolled in this study. Each patient received ultrasound exams including color Doppler flow imaging (CDFI), micro-flow imaging (MFI), contrast-enhanced ultrasound (CEUS), and CEUS-MFI with a Philips EPIQ7 ultrasound imaging system. The intra-tumoral vessels detected by CDFI, MFI, and CEUS-MFI were compared, respectively. The accuracy and confidence of using CEUS and CEUS-MFI in diagnosing hepatic tumors were also compared. RESULTS: CEUS-MFI was capable of detecting more hepatic intra-tumoral vessels than MFI (P = .000) and CDFI (P = .000). Compared with CEUS, CEUS-MFI improved the diagnostic accuracy of hepatic lesions (P = .009). Particularly, among the correctly diagnosed hepatic lesions, the number of cases where radiologists diagnosed with great confidence was increased from 88.4% (61/69) with CEUS only to 92.4% (73/79) with CEUS-MFI (P = .041). CONCLUSIONS: CEUS-MFI is sensitive in detecting hepatic intra-tumoral vessels and can improve the accuracy and confidence of radiologists in diagnosing hepatic lesions.

A Comparative Study of Ultrasound Attenuation Imaging, Controlled Attenuation Parameters, and Magnetic Resonance Spectroscopy for the Detection of Hepatic Steatosis.

OBJECTIVES: To investigate the methodology and clinical application of ultrasound attenuation imaging (ATI) and comparative analyze the diagnostic performance of ATI and controlled attenuation parameters (CAP) for detecting and grading hepatic steatosis. METHODS: A total of 159 patients with NAFLD were prospectively enrolled. CAP and ATI examinations were performed within a week before proton magnetic resonance spectroscopy (1 H-MRS). Ten liver attenuation coefficient (AC) measurements by ATI were obtained in each patient. The interclass correlation coefficients (ICCs) of the intraobserver consistencies and the ICCs between the median of the first two through the first nine measurements and all 10 measurements were calculated. The correlations between 1 H-MRS, CAP, biological data, and ATI were evaluated. The significant factors associated with ATI and the diagnostic performance of ATI and CAP for detecting hepatic steatosis was evaluated. RESULTS: The median value of AC for detecting hepatic steatosis was 0.831 dB/cm/MHz. For the intraobserver consistency of ATI, the ICC was 0.931. Compared with 10 measurements, a minimum of four ATI measurements was required. The correlation of AC with hepatic fat fraction (HFF) was significantly higher than that of CAP (0.603 vs 0.326, P = .0015). The HFF and triglyceride (TG) were the significant factors for the ATI. The area under the receiver operating characteristics (ROC) curves of ATI and CAP were 0.939 and 0.788 for detecting ≥10% hepatic steatosis; 0.751 and 0.572 for detecting >33% hepatic steatosis. The cutoff values of ATI and CAP were 0.697 dB/cm/MHz and 310 dB/m for detecting ≥10% hepatic steatosis; 0.793 dB/cm/MHz and 328 dB/m for detecting >33% hepatic steatosis. The sensitivity of ATI and CAP were 85.92% and 52.11% for detecting ≥10% hepatic steatosis; 87.50% and 82.14% for detecting >33% hepatic steatosis. The specificity of ATI and CAP were 94.12% and 100% for detecting ≥10% hepatic steatosis; 54.37% and 43.69% for detecting >33% hepatic steatosis. CONCLUSIONS: ATI technology showed excellent intraobserver consistency and the optimal minimum number of ATI measurements was 4. ATI is a promising noninvasive, quantitative and convenient tool for assessing hepatic steatosis.

Optimization of O/W Emulsion Solvent Evaporation Method for Itraconazole Sustained Release Microspheres.

Itraconazole, a commonly used antifungal drug in the clinic approved by U.S. Food and Drug Administration (FDA), has been gradually found to have anti-tumor, angiogenesis inhibition and other pharmacological activities. However, its poor water solubility and potential toxicity limited its clinical application. In order to improve the water solubility and reduce the side effects caused by the high concentration of itraconazole, a novel preparation method of itraconazole sustained release microspheres was established in this study. Firstly, five kinds of polylactic acid-glycolic acid (PLGA) microspheres loaded with itraconazole were prepared by oil/water (O/W) emulsion solvent evaporation and then characterized by infrared spectroscopy. Then the particle size and morphology of the microspheres were observed by scanning electron microscope (SEM) and transmission electron microscope (TEM). After that, the particle size distribution, drug loading rate, entrapment efficiency, and drug release experiments were evaluated. Our results showed the microspheres prepared in this study had uniform particle size distribution and good integrity. Further study found that the average drug loading of the five kinds of microspheres prepared with PLGA 7505, PLGA 7510, PLGA 7520, PLGA 5020 and PLGA 0020 were 16.88, 17.72, 16.72, 16.57, and 16.64%, respectively, and the encapsulation rate all reached about 100%. More surprisingly, the release experimental results showed that the microspheres prepared with PLGA 7520 did not show sudden release, showing good sustained release performance and high drug release rate. To sum up, this study optimized the preparation method of sustained-release microspheres without sudden release, which provides a new solution for the delivery of itraconazole in the clinic.

Ultrasound Elastography for Characterization of Focal Liver Lesions.

Focal liver lesions (FLL) are typically detected by conventional ultrasound or other imaging modalities. After the detection of FLL, further characterization is essential, and this can be done by contrast-enhanced imaging techniques, e.g., contrast-enhanced ultrasound (CEUS) and magnetic resonance imaging (MRI) or by means of biopsy with histological evaluation. Elastographic techniques are nowadays integrated into high-end ultrasound systems and their value for the detection of severe liver fibrosis and cirrhosis has been shown in studies and meta-analyses. The use of an ultrasound elastographic technique for the differentiation of malignant and benign liver tumors is less well-established. This review summarizes the current data on utility and performance of ultrasound elastography for the characterization of FLL.

New Rosane Diterpenoids and Their Analogs from Euphorbia ebracteolata Hayata.

Phytochemical investigation of the roots of Euphorbia ebracteolata Hayata resulted in the isolation of three new rosane diterpenoids, euphebracteolatins C-E (1-3), along with fourteen known analogs (4-17). Their structures were determined on the basis of extensive spectroscopic analysis including HR-ESI-MS, 1D and 2D NMR. Euphebracteolatin C (1) contains a C-1/C-10 double bond and a keto group at C-7, and euphebracteolatins D and E (2-3) possess an aromatic ring-A in their skeleton. The plausible biogenetic pathways of all the isolates were also proposed. Furthermore, compounds 1 and 9 showed selective cytotoxicity against HepG2 cells with IC50 values of 14.29 and 12.33 µM, respectively, and 2-3 displayed moderate cytotoxicity against three human cancer lines, with IC50 values ranging from 23.69 to 39.25 µM.

Three-dimensional assessment of facial asymmetry in class III subjects, part 2: evaluating asymmetry index and asymmetry scores.

OBJECTIVES: To evaluate the outcomes of corrective surgical treatment for craniofacial asymmetry using four different methods with the aim of developing the best technique for craniofacial asymmetry assessment. MATERIALS AND METHODS: CBCT images of twenty-one class III subjects with surgically corrected craniofacial asymmetry and twenty-one matched controls were analyzed. Twenty-seven hard tissue landmarks were used to quantify asymmetry using the following methodologies: the asymmetry index (AI), asymmetry scores based on the clinically derived midline (CM), Procrustes analysis (PA), and modified Procrustes analysis (MPA). RESULTS: Modified Procrustes analysis successfully identified pre-operative asymmetry and revealed severe asymmetry at the mandibular regions compared to controls, which was comparable to the asymmetry index and clinically derived midline methods, while Procrustes analysis masked the asymmetric characteristics. Likewise, when comparing the post-surgical outcomes, modified Procrustes analysis not only efficiently determined the changes evidencing decrease in facial asymmetry but also revealed significant residual asymmetry in the mandible, which was congruent with the asymmetry index and clinically derived midline methods but contradictory to the results shown by Procrustes analysis. CONCLUSIONS: In terms of quantifying cranio-facial asymmetry, modified Procrustes analysis has evidenced to produce promising results that were comparable to the asymmetry index and the clinically derived midline, making it a more viable option for craniofacial asymmetry assessment. CLINICAL RELEVANCE: Modified Procrustes analysis is proficient in evaluating cranio-facial asymmetry with more valid clinical representation and has potential applications in assessing asymmetry in a wide spectrum of patients, including syndromic patients.

Ultrasound fusion imaging for improving diagnostic and therapeutic strategies of focal liver lesions: A preliminary study.

PURPOSE: To assess the effect of ultrasound (US) fusion imaging on the clinical diagnostic and therapeutic strategies of focal liver lesions, which are difficult to detect or diagnose by conventional US. METHODS: From November 2019 to June 2022, 71 patients with invisible or undiagnosed focal liver lesions who underwent fusion imaging combining US with CT or MR were included in this retrospective study. The reasons for US fusion imaging were as follows: (1) lesions that were undetectable or inconspicuous on B-mode US; (2) post-ablation lesions that could not be assessed accurately by B-mode US; (3) to evaluate whether the lesions detected by B-mode US that were consistent with those presented on MRI/CT images. RESULTS: Of the 71 cases, 43 cases were single lesions, and 28 cases were multiple lesions. Among the 46 cases which were invisible on conventional US, the display rate of lesions using US-CT/MRI fusion imaging was 30.8%, and that combined with CEUS was 76.9%. US-guided biopsy was performed in 30 patients after the detection and localization determined by fusion imaging, with a positive rate of 73.3%. Six patients with recurrence after ablation therapy were all detected and located accurately after fusion imaging, and 4 of them successfully underwent ablation therapy again. CONCLUSION: Fusion imaging contributes to the understanding of the anatomical relationship between lesion location and blood vessels. Additionally, fusion imaging can improve the diagnostic confidence, be helpful to guide interventional operations, and hence be conducive to clinical therapeutic strategies.

Deep Learning for Genomics: From Early Neural Nets to Modern Large Language Models.

The data explosion driven by advancements in genomic research, such as high-throughput sequencing techniques, is constantly challenging conventional methods used in genomics. In parallel with the urgent demand for robust algorithms, deep learning has succeeded in various fields such as vision, speech, and text processing. Yet genomics entails unique challenges to deep learning, since we expect a superhuman intelligence that explores beyond our knowledge to interpret the genome from deep learning. A powerful deep learning model should rely on the insightful utilization of task-specific knowledge. In this paper, we briefly discuss the strengths of different deep learning models from a genomic perspective so as to fit each particular task with proper deep learning-based architecture, and we remark on practical considerations of developing deep learning architectures for genomics. We also provide a concise review of deep learning applications in various aspects of genomic research and point out current challenges and potential research directions for future genomics applications. We believe the collaborative use of ever-growing diverse data and the fast iteration of deep learning models will continue to contribute to the future of genomics.