Macrophage hitchhiking for systematic suppression in postablative multifocal HCC.

BACKGROUND AND AIMS: HCC, particularly the multifocal HCC, features aggressive invasion and dismal prognosis. Locoregional treatments were often refractory to eliminate tumor tissue, resulting in residual tumor cells persisting and subsequent progression. Owing to problematic delivery to the tumor tissue, systemic therapies, such as lenvatinib (LEN) therapy, show limited clinical benefit in preventing residual tumor progression. Therefore, more advanced strategies for postablative multifocal HCC are urgently needed. APPROACH AND RESULTS: Motivated by the chemotaxis in tumor penetration of macrophages, we report a strategy named microinvasive ablation-guided macrophage hitchhiking for the targeted therapy toward HCC. In this study, the strategy leverages the natural inflammatory gradient induced by ablation to guide LEN-loaded macrophages toward tumor targeting, which increased by ~10-fold the delivery efficiency of LEN in postablative HCC in vivo. Microinvasive ablation-guided macrophage hitchhiking has demonstrated significant antitumor activity in various HCC models, including the hydrodynamic tail vein injection multifocal HCC mouse model and the orthotopic xenograft HCC rabbit model, systematically inhibiting residual tumor progression after ablation and prolonging the median survival of tumor-bearing mice. The potential antitumor mechanism was explored using techniques such as flow cytometry, ELISA, and immunohistochemistry. We found that the strategy significantly suppressed tumor cell proliferation and neovascularization, and such enhanced delivery of LEN stimulated systemic immune responses and induced durable immune memory. CONCLUSIONS: The macrophage hitchhiking strategy demonstrates exceptional therapeutic efficacy and biosafety across various species, offering promising prospects for clinical translation in controlling residual tumor progression and improving outcomes following HCC ablation.

Strong, Lightweight, and Shape-Memory Bamboo-Derived All-Cellulose Aerogels for Versatile Scaffolds of Sustainable Multifunctional Materials.

Strong, lightweight, and shape-memory cellulose aerogels have great potential in multifunctional applications. However, achieving the integration of these features into a cellulose aerogel without harsh chemical modifications and the addition of mechanical enhancers remains challenging. In this study, a strong, lightweight, and water-stimulated shape-memory all-cellulose aerogel (ACA) is created using a combination strategy of partial dissolution and unidirectional freezing from bamboo. Benefiting from the firm architecture of cellulose microfibers bridging cellulose nanofibers /regenerated cellulose aggregated layers and the bonding of different cellulose crystal components (cellulose Iß and cellulose II), the ACA, with low density (60.74 mg cm-3 ), possesses high compressive modulus (radial section: 1.2 MPa, axial section: 0.96 MPa). Additionally, when stimulated with water, the ACA exhibits excellent shape-memory features, including highly reversible compression-resilience and instantaneous fold-expansion behaviors. As a versatile scaffold, ACA can be integrated with hydroxyapatite, carboxyl carbon nanotubes, and LiCl, respectively, via a simple impregnation method to yield functionalized cellulose composites for applications in thermal insulation, electromagnetic interference shielding, and piezoresistive sensors. This study provides inspiration and a reliable strategy for the elaborately structural design of functional cellulose aerogels endows application prospects in various multifunction opportunities.

Glymphatic Imaging in Pediatrics.

The glymphatic system, which facilitates cerebrospinal fluid (CSF) flow through the brain parenchyma, is important for brain development and waste clearance. Advances in imaging techniques, particularly magnetic resonance imaging, have make it possible to evaluate glymphatic structures and functions in vivo. Recently, several studies have focused on the development and alterations of the glymphatic system in pediatric disorders. This review discusses the development of the glymphatic system, advances of imaging techniques and their applications in pediatric disorders. First, the results of the reviewed studies indicate that the development of the glymphatic system is a long-lasting process that continues into adulthood. Second, there is a need for improved glymphatic imaging techniques that are non-invasive and fast to improve suitability for pediatric applications, as some of existing methods use contrast injection and are susceptible to motion artifacts from long scanning times. Several novel techniques are potentially feasible for pediatric patients and may be used in the future. Third, the glymphatic dysfunction is associated with a large number of pediatric disorders, although only a few have recently been investigated. In conclusion, research on the pediatric glymphatic system remains an emerging field. The preliminary applications of glymphatic imaging techniques have provided unique insight into the pathological mechanism of pediatric diseases, but mainly limited in visualization of enlarged perivascular spaces and morphological measurements on CSF volumes. More in-depth studies on glymphatic functions are required to improve our understanding of the mechanisms underlying brain development and pediatric diseases. LEVEL OF EVIDENCE: 5 TECHNICAL EFFICACY: Stage 3.

Auditory Effects of Acoustic Noise From 3-T Brain MRI in Neonates With Hearing Protection.

BACKGROUND: Neonates with immature auditory function (eg, weak/absent middle ear muscle reflex) could conceivably be vulnerable to noise-induced hearing loss; however, it is unclear if neonates show evidence of hearing loss following MRI acoustic noise exposure. PURPOSE: To explore the auditory effects of MRI acoustic noise in neonates. STUDY TYPE: Prospective. SUBJECTS: Two independent cohorts of neonates (N = 19 and N = 18; mean gestational-age, 38.75 ± 2.18 and 39.01 ± 1.83 weeks). FIELD STRENGTH/SEQUENCE: T1-weighted three-dimensional gradient-echo sequence, T2-weighted fast spin-echo sequence, single-shot echo-planar imaging-based diffusion-tensor imaging, single-shot echo-planar imaging-based diffusion-kurtosis imaging and T2-weighted fluid-attenuated inversion recovery sequence at 3.0 T. ASSESSMENT: All neonates wore ear protection during scan protocols lasted ~40 minutes. Equivalent sound pressure levels (SPLs) were measured for both cohorts. In cohort1, left- and right-ear auditory brainstem response (ABR) was measured before (baseline) and after (follow-up) MRI, included assessment of ABR threshold, wave I, III and V latencies and interpeak interval to determine the functional status of auditory nerve and brainstem. In cohort2, baseline and follow-up left- and right-ear distortion product otoacoustic emission (DPOAE) amplitudes were assessed at 1.2 to 7.0 kHz to determine cochlear function. STATISTICAL TEST: Wilcoxon signed-rank or paired t-tests with Bonferroni's correction were used to compare the differences between baseline and follow-up ABR and DPOAE measures. RESULTS: Equivalent SPLs ranged from 103.5 to 113.6 dBA. No significant differences between baseline and follow-up were detected in left- or right-ear ABR measures (P > 0.999, Bonferroni corrected) in cohort1, or in DPOAE levels at 1.2 to 7.0 kHz in cohort2 (all P > 0.999 Bonferroni corrected except for left-ear levels at 3.5 and 7.0 kHz with corrected P = 0.138 and P = 0.533). DATA CONCLUSION: A single 40-minute 3-T MRI with equivalent SPLs of 103.5-113.6 dBA did not result in significant transient disruption of auditory function, as measured by ABR and DPOAE, in neonates with adequate hearing protection. EVIDENCE LEVEL: 2. TECHNICAL EFFICACY: Stage 5.

Secukinumab in patients with moderate-to-severe hidradenitis suppurativa based on prior biologic exposure: an efficacy and safety analysis from the SUNSHINE and SUNRISE phase III trials.

BACKGROUND: Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease associated with a substantial disease burden. Secukinumab has previously been reported to have sustained efficacy with a favourable safety profile in patients with moderate-to-severe HS. It is unknown whether prior biologic exposure affects the efficacy and safety of secukinumab. OBJECTIVES: To investigate the efficacy and safety of secukinumab in patients with moderate-to-severe HS based on prior exposure to -biologics. METHODS: This was an analysis of the SUNSHINE and SUNRISE phase III trials of secukinumab in patients with moderate-to-severe HS. Patients were randomized at baseline to receive secukinumab every 2 (SECQ2W) or 4 weeks (SECQ4W), or placebo for 16 weeks. After week 16, patients on the SECQ2W and SECQ4W schedules remained on the same treatment regimen, while patients randomized to placebo were switched to either SECQ2W or SECQ4W up to week 52. Assessments based on prior exposure to biologics included Hidradenitis Suppurativa Clinical Response (HiSCR), abscess and inflammatory nodule (AN) count, flare rates, HS-related pain [numerical rating scale 30 (NRS30)], 55% reduction in the International Hidradenitis Suppurativa Severity Score System (IHS4-55), Dermatology Life Quality Index, EuroQol-5D and safety. RESULTS: Overall, 1084 patients were randomized in the SUNSHINE and SUNRISE trials and included in this analysis; 255 (23.5%) were biologic-experienced [SECQ2W (n = 80); SECQ4W (n = 81); placebo (n = 94)] and 829 (76.5%) were biologic-naïve [SECQ2W (n = 281); SECQ4W (n = 279); placebo (n = 269)]. At week 16, responses were more efficacious for secukinumab than for placebo with regard to HiSCR in patients who were biologic-experienced {SECQ2W 37.0% [odds ratio (OR) 1.60, 95% confidence interval (CI) 0.83-3.08]; SECQ4W 38.8% [OR 1.67, 95% CI 0.86-3.22]; placebo 27.3%} and biologic-naïve [SECQ2W 45.6% (OR 1.64, 95% CI 1.15-2.33); SECQ4W 45.4% (OR 1.61, 95% CI 1.13-2.29); placebo 34.2%]. Similar results were observed for AN count, NRS30 and IHS4-55. The higher response seen at week 16 with secukinumab was sustained, with a trend toward improvement over time, through to week 52 in both subgroups. Additional efficacy was observed for quality-of-life assessments, and no differences in safety between subgroups were observed. CONCLUSIONS: Regardless of prior biologic exposure, secukinumab was efficacious in improving the signs and symptoms of HS. This finding positions secukinumab as the first option in patients who are biologic-naïve, as well as in patients who have previously been treated with other biologic therapy, based on individual patient needs.

Hidradenitis suppurativa (HS) is a chronic skin disease that causes painful boils. HS is common and affects about 0.4% of the world's population. Treating the condition is difficult, but drugs called 'biologics' can help to improve the symptoms. For example, secukinumab is a biologic drug that has been shown to be effective and well-tolerated for the treatment of HS. In this analysis, we investigated whether previous treatment with biologics could affect the effectiveness and tolerability of secukinumab. This analysis included data from two identical clinical trials (called SUNSHINE and SUNRISE) that recruited adult patients with HS who had moderate-to-severe disease. In these trials, patients took secukinumab 300 mg every 2 weeks or every 4 weeks for 1 year, or a placebo for 4 months and then switched to secukinumab until 1 year. At regular intervals, the effectiveness and tolerability of secukinumab were examined and the results were compared between patients who had previously used another biologic and patients who had never used a biologic before. After 16 weeks, patients who took secukinumab had better results than the patients who took a placebo, independent of previous biologic use. Secukinumab was still effective and had improved results over 1 year of treatment in both subgroups. Regardless of whether patients had previously been taking another biologic, secukinumab was just as tolerable as placebo and there were no new safety risks. Our analysis shows that secukinumab is effective and tolerable, regardless of whether patients have previously used another biologic drug.

Assessment of the glymphatic function in children with attention-deficit/hyperactivity disorder.

OBJECTIVES: Whether the alternation of the glymphatic system exists in neurodevelopmental disease still remains unclear. In this study, we investigated structural and functional changes in the glymphatic system in the treatment-naïve attention-deficit/hyperactivity disorder (ADHD) children by quantitatively measuring the Virchow-Robin spaces (VRS) volume and diffusion tensor image-analysis along the perivascular space (DTI-ALPS). METHODS: Forty-seven pediatric ADHD patients and 52 age- and gender-matched typically developing (TD) children were recruited in this prospective study. The VRS volume was calculated using a semi-automated approach in axial T2-weighted images. Diffusivities along the x-, y-, and z-axes in the projection, association, and subcortical neural fiber areas were measured. The ALPS index, a ratio that accentuated water diffusion along the perivascular space, was calculated. The Mann-Whitney U test was used to compare the quantitative parameters; Pearson's correlation was used to analyze the correlation with clinical symptoms. RESULTS: The cerebral VRS volume (mean, 15.514 mL vs. 11.702 mL) and the VRS volume ratio in the ADHD group were larger than those in the TD group (all p < 0.001). The diffusivity along the x-axis in association fiber area and ALPS index were significantly smaller in the ADHD group vs. TD group (mean, 1.40 vs.1.59, p < 0.05 after false discovery rate adjustment). Besides, the ALPS index was related to inattention symptoms of ADHD (r = - 0.323, p < 0.05). CONCLUSIONS: Our study suggests that the glymphatic system alternation may participate in the pathogenesis of ADHD, which may be a new research direction for exploring the mechanisms of psycho-behavioral developmental disorders. Moreover, the VRS volume and ALPS index could be used as the metrics for diagnosing ADHD. CLINICAL RELEVANCE STATEMENT: Considering the potential relevance of the glymphatic system for exploring the mechanisms of attention deficit/hyperactivity, the Virchow-Robin spaces volume and the analysis along the perivascular space index could be used as additional metrics for diagnosing the disorder. KEY POINTS: • Increased Virchow-Robin space volume and decreased analysis along the perivascular space index were found in the treatment-naïve attention-deficit/hyperactivity disorder children. • The results of this study indicate that the glymphatic system alternation may have a valuable role in the pathogenesis of attention-deficit/hyperactivity disorder. • The analysis along the perivascular space index is correlated with inattention symptoms of attention-deficit/hyperactivity disorder children.

Impaired glymphatic system revealed by DTI-ALPS in cerebral palsy due to periventricular leukomalacia: relation with brain lesion burden and hand dysfunction.

PURPOSE: Preterm children with cerebral palsy (CP) often have varying hand dysfunction, while the specific brain injury with periventricular leukomalacia (PVL) cannot quite explain its mechanism. We aimed to investigate glymphatic activity using diffusion tensor image analysis along the perivascular space (DTI-ALPS) method and evaluate its association with brain lesion burden and hand dysfunction in children with CP secondary to PVL. METHODS: We retrospectively enrolled 18 children with bilateral spastic CP due to PVL and 29 age- and sex-matched typically developing controls. The Manual Ability Classification System (MACS) was used to assess severity of hand dysfunction in CP. A mediation model was performed to explore the relationship among the DTI-ALPS index, brain lesion burden, and the MACS level in children with CP. RESULTS: There were significant differences in the DTI-ALPS index between children with CP and their typically developing peers. The DTI-ALPS index of the children with CP was lower than that of the controls (1.448 vs. 1.625, P = 0.003). The mediation analysis showed that the DTI-ALPS index fully mediated the relationship between brain lesion burden and the MACS level (c' = 0.061, P = 0.665), explaining 80% of the effect. CONCLUSION: This study provides new insights into the neural basis of hand dysfunction in children with CP, demonstrating an important role of glymphatic impairment in such patients. These results suggest that PVL might affect hand function in children with CP by disrupting glymphatic drainage.

Effectiveness of Low-frequency Pulse Electrical Stimulation Combined with Dexamethasone in Treating Facial Nerve Paralysis and Its Impact on Facial Nerve Function and Electromyography.

Objective: This study aimed to evaluate the efficacy of adjunct low-frequency pulse electrical stimulation alongside dexamethasone in the treatment of facial nerve paralysis and its subsequent effects on facial nerve function and electromyographic parameters. With the aim of addressing a knowledge gap in the field, this research provides valuable insights into the potential benefits of combining these treatments and their impact on clinical outcomes, facial nerve functionality, and electromyographic dynamics. Methods: A cohort of 66 patients with facial nerve paralysis treated at our institution between April 2018 and November 2021 were randomly assigned to either an observation (n=33) or an experimental group (n=33). The observation group received standard pharmacotherapy, including Western medications and Daqinjiao decoction, along with dexamethasone. The experimental group was administered low-frequency pulse electrical stimulation in addition to the observation group's regimen. Outcomes assessed were clinical efficacy, facial nerve paralysis scoring, facial nerve functional scoring and indices, electromyographic latency, amplitude ratios between affected and unaffected sides, as well as any adverse events. Results: The experimental group demonstrated a significant improvement over the observation group in clinical treatment outcomes, facial nerve paralysis scores, and facial nerve function scores (P < .05 for all). Furthermore, electromyographic analysis revealed shorter latency periods and greater amplitude ratios in the experimental group's facial muscles post-treatment (P < .05). No significant difference was observed in the incidence of adverse reactions between the two groups (P > .05). Conclusion: The integration of low-frequency pulse electrical stimulation with dexamethasone therapy significantly ameliorates the severity of facial nerve paralysis, enhances facial nerve function, and improves electromyographic signals in facial muscles without increasing adverse effects. These findings support the clinical value and safety of this combined treatment approach for facial nerve paralysis, suggesting its suitability for broader clinical application. These results suggest that this combined treatment approach holds promise for broader clinical application, potentially providing a more effective and safer therapeutic option for patients with facial nerve paralysis. Implementing this approach in clinical practice may lead to improved treatment outcomes, better functional recovery, and enhanced quality of life for affected individuals.

Pseudoaneurysm of the mitral-aortic intervalvular fibrosa in children diagnosed by echocardiography: Two case reports.

Pseudoaneurysm of the mitral-aortic intervalvular fibrosa is rare, particularly in children, and is potentially fatal. This article presents two cases of pediatric mitral-aortic intervalvular fibrosa pseudoaneurysm: one secondary to infective endocarditis and the other confirmed to be congenital in nature. The characteristic echocardiographic manifestations of mitral-aortic intervalvular fibrosa pseudoaneurysm demonstrated in this study will enhance diagnostic efficacy and guide early clinical intervention.

A CT-based deep learning radiomics nomogram outperforms the existing prognostic models for outcome prediction in clear cell renal cell carcinoma: a multicenter study.

OBJECTIVES: To develop and validate a CT-based deep learning radiomics nomogram (DLRN) for outcome prediction in clear cell renal cell carcinoma (ccRCC), and its performance was compared with the Stage, Size, Grade, and Necrosis (SSIGN) score, the University of California, Los Angeles, Integrated Staging System (UISS), the Memorial Sloan-Kettering Cancer Center (MSKCC), and the International Metastatic Renal Cell Database Consortium (IMDC). METHODS: A multicenter of 799 localized (training/ test cohort, 558/241) and 45 metastatic ccRCC patients were studied. A DLRN was developed for predicting recurrence-free survival (RFS) in localized ccRCC patients, and another DLRN was developed for predicting overall survival (OS) in metastatic ccRCC patients. The performance of the two DLRNs was compared with that of the SSIGN, UISS, MSKCC, and IMDC. Model performance was assessed with Kaplan-Meier curves, time-dependent area under the curve (time-AUC), Harrell's concordance index (C-index), and decision curve analysis (DCA). RESULTS: In the test cohort, the DLRN achieved higher time-AUCs (0.921, 0.911, and 0.900 for 1, 3, and 5 years, respectively), C-index (0.883), and net benefit than SSIGN and UISS in predicting RFS for localized ccRCC patients. The DLRN provided higher time-AUCs (0.594, 0.649, and 0.754 for 1, 3, and 5 years, respectively) than MSKCC and IMDC in predicting OS for metastatic ccRCC patients. CONCLUSIONS: The DLRN can accurately predict outcomes and outperformed the existing prognostic models in ccRCC patients. CLINICAL RELEVANCE STATEMENT: This deep learning radiomics nomogram may facilitate individualized treatment, surveillance, and adjuvant trial design for patients with clear cell renal cell carcinoma. KEY POINTS: • SSIGN, UISS, MSKCC, and IMDC may be insufficient for outcome prediction in ccRCC patients. • Radiomics and deep learning allow for the characterization of tumor heterogeneity. • The CT-based deep learning radiomics nomogram outperforms the existing prognostic models in ccRCC outcome prediction.

Convolutional neural network for detecting rib fractures on chest radiographs: a feasibility study.

BACKGROUND: Chest radiography is the standard investigation for identifying rib fractures. The application of artificial intelligence (AI) for detecting rib fractures on chest radiographs is limited by image quality control and multilesion screening. To our knowledge, few studies have developed and verified the performance of an AI model for detecting rib fractures by using multi-center radiographs. And existing studies using chest radiographs for multiple rib fracture detection have used more complex and slower detection algorithms, so we aimed to create a multiple rib fracture detection model by using a convolutional neural network (CNN), based on multi-center and quality-normalised chest radiographs. METHODS: A total of 1080 radiographs with rib fractures were obtained and randomly divided into the training set (918 radiographs, 85%) and the testing set (162 radiographs, 15%). An object detection CNN, You Only Look Once v3 (YOLOv3), was adopted to build the detection model. Receiver operating characteristic (ROC) and free-response ROC (FROC) were used to evaluate the model's performance. A joint testing group of 162 radiographs with rib fractures and 233 radiographs without rib fractures was used as the internal testing set. Furthermore, an additional 201 radiographs, 121 with rib fractures and 80 without rib fractures, were independently validated to compare the CNN model performance with the diagnostic efficiency of radiologists. RESULTS: The sensitivity of the model in the training and testing sets was 92.0% and 91.1%, respectively, and the precision was 68.0% and 81.6%, respectively. FROC in the testing set showed that the sensitivity for whole-lesion detection reached 91.3% when the false-positive of each case was 0.56. In the joint testing group, the case-level accuracy, sensitivity, specificity, and area under the curve were 85.1%, 93.2%, 79.4%, and 0.92, respectively. At the fracture level and the case level in the independent validation set, the accuracy and sensitivity of the CNN model were always higher or close to radiologists' readings. CONCLUSIONS: The CNN model, based on YOLOv3, was sensitive for detecting rib fractures on chest radiographs and showed great potential in the preliminary screening of rib fractures, which indicated that CNN can help reduce missed diagnoses and relieve radiologists' workload. In this study, we developed and verified the performance of a novel CNN model for rib fracture detection by using radiography.

Mapping white matter maturational processes and degrees on neonates by diffusion kurtosis imaging with multiparametric analysis.

White matter maturation has been characterized by diffusion tensor (DT) metrics. However, maturational processes and degrees are not fully investigated due to limitations of univariate approaches and limited specificity/sensitivity. Diffusion kurtosis imaging (DKI) provides kurtosis tensor (KT) and white matter tract integrity (WMTI) metrics, besides DT metrics. Therefore, we tried to investigate performances of DKI with the multiparametric analysis in characterizing white matter maturation. Developmental changes in metrics were investigated by using tract-based spatial statistics and the region of interest analysis on 50 neonates with postmenstrual age (PMA) from 37.43 to 43.57 weeks. Changes in metrics were combined into various patterns to reveal different maturational processes. Mahalanobis distance based on DT metrics (DM,DT ) and that combing DT and KT metrics (DM,DT-KT ) were computed, separately. Performances of DM,DT-KT and DM,DT were compared in revealing correlations with PMA and the neurobehavioral score. Compared with DT metrics, WMTI metrics demonstrated additional changing patterns. Furthermore, variations of DM,DT-KT across regions were in agreement with the maturational sequence. Additionally, DM,DT-KT demonstrated stronger negative correlations with PMA and the neurobehavioral score in more regions than DM,DT . Results suggest that DKI with the multiparametric analysis benefits the understanding of white matter maturational processes and degrees on neonates.

The radiomics-based tumor heterogeneity adds incremental value to the existing prognostic models for predicting outcome in localized clear cell renal cell carcinoma: a multicenter study.

PURPOSE: Tumor heterogeneity, which is associated with poor outcomes, has not been exhibited in the University of California, Los Angeles, Integrated Staging System (UISS), and the Stage, Size, Grade and Necrosis (SSIGN) scores. Radiomics allows an in-depth characterization of heterogeneity across the tumor, but its incremental value to the existing prognostic models for clear cell renal cell carcinoma (ccRCC) outcome is unknown. The purpose of this study was to evaluate the association between the radiomics-based tumor heterogeneity and postoperative risk of recurrence in localized ccRCC, and to assess its incremental value to UISS and SSIGN. METHODS: A multicenter 866 ccRCC patients derived from 12 Chinese hospitals were studied. The endpoint was recurrence-free survival (RFS). A CT-based radiomics signature (RS) was developed and assessed in the whole cohort and in the subgroups stratified by UISS and SSIGN. Two combined nomograms, the R-UISS (combining RS and UISS) and R-SSIGN (combining RS and SSIGN), were developed. The incremental value of RS to UISS and SSIGN in RFS prediction was evaluated. R statistical software was used for statistics. RESULTS: Patients with low radiomics scores were 4.44 times more likely to experience recurrence than those with high radiomics scores (P<0.001). Stratified analysis suggested the association is significant among low- and intermediate-risk patients identified by UISS and SSIGN. The R-UISS and R-SSIGN showed better predictive capability than UISS and SSIGN did with higher C-indices (R-UISS vs. UISS, 0.74 vs. 0.64; R-SSIGN vs. SSIGN, 0.78 vs. 0.76) and higher clinical net benefit. CONCLUSIONS: The radiomics-based tumor heterogeneity can predict outcome and add incremental value to the existing prognostic models in localized ccRCC patients. Incorporating radiomics-based tumor heterogeneity in ccRCC prognostic models may provide the opportunity to better surveillance and adjuvant clinical trial design.

A Crack Size Quantification Method Using High-Resolution Lamb Waves.

Traditional tone burst excitation cannot attain a high output resolution, due to the time duration. The received signal is much longer than that of excitation during the propagation, which can increase the difficulty of signal processing, and reduce the resolution. Therefore, it is of significant interest to develop a general methodology for crack quantification through the optimal design of the excitation waveform and signal-processing methods. This paper presents a new crack size quantification method based on high-resolution Lamb waves. The linear chirp (L-Chirp) signal and Golay complementary code (GCC) signal are used as Lamb wave excitation signals. After dispersion removal, these excitation waveforms, based on pulse compression, can effectively improve the inspection resolution in plate-like structures. A series of simulations of both healthy plates and plates with different crack sizes are performed by Abaqus CAE, using different excitation waveforms. The first wave package of the S0 mode after pulse compression is chosen to extract the damage features. A multivariate regression model is proposed to correlate the damage features to the crack size. The effectiveness of the proposed crack size quantification method is verified by a comparison with tone burst excitation, and the accuracy of the crack size quantification method is verified by validation experiments.

Impacts of skull stripping on construction of three-dimensional T1-weighted imaging-based brain structural network in full-term neonates.

BACKGROUND: Skull stripping remains a challenge for neonatal brain MR image analysis. However, little is known about the accuracy of how skull stripping affects the neonatal brain tissue segmentation and subsequent network construction. This paper therefore aimed to clarify this issue by comparing two automatic (FMRIB Software Library's Brain Extraction Tool, BET; Infant Brain Extraction and Analysis Toolbox, iBEAT) and a semiautomatic (iBEAT with manual correction) processes in constructing 3D T1-weighted imaging (T1WI)-based brain structural network. METHODS: Twenty-two full-term neonates (gestational age, 37-42 weeks; boys/girls, 13/9) without abnormalities on MRI who underwent brain 3D T1WI were retrospectively recruited. Two automatic (BET and iBEAT) and a semiautomatic preprocessing (iBEAT with manual correction) workflows were separately used to perform the skull stripping. Brain tissue segmentation and volume calculation were performed by a Johns Hopkins atlas-based method. Sixty-four gray matter regions were selected as nodes; volume covariance network and its properties (clustering coefficient, Cp; characteristic path length, Lp; local efficiency, Elocal; global efficiency, Eglobal) were calculated by GRETNA. Analysis of variance (ANOVA) was used to compare the differences in the calculated volume between three workflows. RESULTS: There were significant differences in volumes of 50 brain regions between the three workflows (P < 0.05). Three neonatal brain structural networks presented small-world topology. The semiautomatic workflow showed remarkably decreased Cp, increased Lp, decreased Elocal, and decreased Eglobal, in contrast to the two automatic ones. CONCLUSIONS: Imperfect skull stripping indeed affected the accuracy of brain structural network in full-term neonates.

Inter-site harmonization based on dual generative adversarial networks for diffusion tensor imaging: application to neonatal white matter development.

BACKGROUND: Site-specific variations are challenges for pooling analyses in multi-center studies. This work aims to propose an inter-site harmonization method based on dual generative adversarial networks (GANs) for diffusion tensor imaging (DTI) derived metrics on neonatal brains. RESULTS: DTI-derived metrics (fractional anisotropy, FA; mean diffusivity, MD) are obtained on age-matched neonates without magnetic resonance imaging (MRI) abnormalities: 42 neonates from site 1 and 42 neonates from site 2. Significant inter-site differences of FA can be observed. The proposed harmonization approach and three conventional methods (the global-wise scaling, the voxel-wise scaling, and the ComBat) are performed on DTI-derived metrics from two sites. During the tract-based spatial statistics, inter-site differences can be removed by the proposed dual GANs method, the voxel-wise scaling, and the ComBat. Among these methods, the proposed method holds the lowest median values in absolute errors and root mean square errors. During the pooling analysis of two sites, Pearson correlation coefficients between FA and the postmenstrual age after harmonization are larger than those before harmonization. The effect sizes (Cohen's d between males and females) are also maintained by the harmonization procedure. CONCLUSIONS: The proposed dual GANs-based harmonization method is effective to harmonize neonatal DTI-derived metrics from different sites. Results in this study further suggest that the GANs-based harmonization is a feasible pre-processing method for pooling analyses in multi-center studies.

The Genome Analysis of Methylobacterium populi YC-XJ1 with Diverse Xenobiotics Biodegrading Capacity and Degradation Characteristics of Related Hydrolase.

Methylobacterium populi YC-XJ1 isolated from desert soil exhibited a diverse degrading ability towards aromatic oxyphenoxypropionic acid esters (AOPPs) herbicide, phthalate esters (PAEs), organophosphorus flame retardants (OPFRs), chlorpyrifos and phoxim. The genome of YC-XJ1 was sequenced and analyzed systematically. YC-XJ1 contained a large number of exogenous compounds degradation pathways and hydrolase resources. The quizalofop-p-ethyl (QPE) degrading gene qpeh2 and diethyl phthalate (DEP) degrading gene deph1 were cloned and expressed. The characteristics of corresponding hydrolases were investigated. The specific activity of recombinant QPEH2 was 0.1 ± 0.02 U mg-1 for QPE with kcat/Km values of 1.8 ± 0.016 (mM-1·s-1). The specific activity of recombinant DEPH1 was 0.1 ± 0.02 U mg-1 for DEP with kcat/Km values of 0.8 ± 0.02 (mM-1·s-1). This work systematically illuminated the metabolic versatility of strain YC-XJ1 via the combination of genomics analysis and laboratory experiments. These results suggested that strain YC-XJ1 with diverse xenobiotics biodegrading capacity was a promising candidate for the bioremediation of polluted sites.

Biodegradation of Bisphenol A by Sphingobium sp. YC-JY1 and the Essential Role of Cytochrome P450 Monooxygenase.

Bisphenol A (BPA) is a widespread pollutant threatening the ecosystem and human health. An effective BPA degrader YC-JY1 was isolated and identified as Sphingobium sp. The optimal temperature and pH for the degradation of BPA by strain YC-JY1 were 30 °C and 6.5, respectively. The biodegradation pathway was proposed based on the identification of the metabolites. The addition of cytochrome P450 (CYP) inhibitor 1-aminobenzotriazole significantly decreased the degradation of BPA by Sphingobium sp. YC-JY1. Escherichia coli BL21 (DE3) cells harboring pET28a-bisdAB achieved the ability to degrade BPA. The bisdB gene knockout strain YC-JY1ΔbisdB was unable to degrade BPA indicating that P450bisdB was an essential initiator of BPA metabolism in strain YC-JY1. For BPA polluted soil remediation, strain YC-JY1 considerably stimulated biodegradation of BPA associated with the soil microbial community. These results point out that strain YC-JY1 is a promising microbe for BPA removal and possesses great application potential.

Associations of gestational age and birth anthropometric indicators with brain white matter maturation in full-term neonates.

Newborn assessments, including gestational age (GA) and anthropometric measurements (birth weight, crown-heel length, head circumference) are routinely performed in pediatric settings, being used as important indicators in assessing neonatal development. Close associations of these birth indicators with later cognitive abilities were also reported. However, specific associations of these indicators with white matter (WM) development during the neonatal period remain unclear, as well as the extent to which they influence WM maturation. To address this issue, 51 full-term neonates (GA range, 37-42 weeks) with no abnormalities on MRI were retrospectively recruited. Specific correlations between birth indicators and WM maturation, quantified by diffusion tensor imaging (DTI)-metrics (fractional anisotropy, mean diffusivity, axial diffusivity, radial diffusivity), were identified by using DTI tract-based spatial statistics and automated fiber-tract quantification. Our findings suggest that (a) higher GA, birth weight, and crown-heel length may indicate greater WM maturation in full-term neonates, while head circumference presented weak correlation with WM maturation during early newborn period; (b) among the four indicators examined, GA was the one most associated with WM maturation. We believe that this study advances our knowledge of specific correlations between birth indicators and neonatal brain development and provides a valuable reference for future neonatal studies.

Proper timing for the evaluation of neonatal brain white matter development: a diffusion tensor imaging study.

OBJECTIVE: We aimed to determine the timing for assessing birth status of the developing brain (i.e. brain maturity at birth) by exploring the postnatal age-related changes in neonatal brain white matter (WM). METHODS: The institutional review board approved this study and all informed parental consents were obtained. 133 neonates (gestational age, 30-42 weeks) without abnormalities on MRI were studied with regard to WM development by diffusion tensor imaging-derived fractional anisotropy (FA). Tract-based spatial statistics (TBSS), locally-weighted scatterplot smoothing (LOESS) and piecewise linear-fitting were used to investigate the relationship between FA and postnatal age. FA along corticospinal tract (CST), optic radiation (OR), auditory radiation (AR) and thalamus-primary somatosensory cortex (thal-PSC) were extracted by automated fibre-tract quantification; their differences and associations with neonatal neurobehavioural scores at various postnatal age ranges were analysed by Wilcoxon's rank-sum test and Pearson's correlation. RESULTS: Using TBSS, postnatal age (days 1-28) positively correlated with FA in multiple WMs, including CST, OR, AR and thal-PSC (p<0.05). On the other hand, when narrowing the postnatal age window to days 1-14, no significant correlation was found, suggesting a biphasic WM development. LOESS and piecewise linear-fitting indicated that FA increased mildly before day 14 and its growth accelerated thereafter. Both FA and correlations with neurobehavioural scores in postnatal age range 2 (days 15-28) were significantly higher than in range 1 (days 1-14) (FA comparison: p<0.05; maximal correlation-coefficient: 0.693 vs. 0.169). CONCLUSION: Brain WM development during the neonatal stage includes two phases, i.e. a close-to-birth period within the first 14 days and a following accelerated maturation period. Therefore, evaluations of birth status should preferably be performed during the first period. KEY POINTS: • Brain white matter development within the first two postnatal weeks resembles a close-to-birth maturation. • Brain white matter development in the audio-visual, sensorimotor regions accelerates after two postnatal weeks. • Postnatal age-related effects should be considered in comparing preterm and term neonates.