nnSegNeXt: A 3D Convolutional Network for Brain Tissue Segmentation Based on Quality Evaluation.

Accurate and automated segmentation of brain tissue images can significantly streamline clinical diagnosis and analysis. Manual delineation needs improvement due to its laborious and repetitive nature, while automated techniques encounter challenges stemming from disparities in magnetic resonance imaging (MRI) acquisition equipment and accurate labeling. Existing software packages, such as FSL and FreeSurfer, do not fully replace ground truth segmentation, highlighting the need for an efficient segmentation tool. To better capture the essence of cerebral tissue, we introduce nnSegNeXt, an innovative segmentation architecture built upon the foundations of quality assessment. This pioneering framework effectively addresses the challenges posed by missing and inaccurate annotations. To enhance the model's discriminative capacity, we integrate a 3D convolutional attention mechanism instead of conventional convolutional blocks, enabling simultaneous encoding of contextual information through the incorporation of multiscale convolutional features. Our methodology was evaluated on four multi-site T1-weighted MRI datasets from diverse sources, magnetic field strengths, scanning parameters, temporal instances, and neuropsychiatric conditions. Empirical evaluations on the HCP, SALD, and IXI datasets reveal that nnSegNeXt surpasses the esteemed nnUNet, achieving Dice coefficients of 0.992, 0.987, and 0.989, respectively, and demonstrating superior generalizability across four distinct projects with Dice coefficients ranging from 0.967 to 0.983. Additionally, extensive ablation studies have been implemented to corroborate the effectiveness of the proposed model. These findings represent a notable advancement in brain tissue analysis, suggesting that nnSegNeXt holds the promise to significantly refine clinical workflows.

Enhancement of therapeutic potential of mesenchymal stem cell by IGF-1 delivery in PLGA microspheres for tissue regeneration.

The use of stem cell-based treatment systems is prevalent in regenerative medicine. To enhance the regenerative capabilities of stem cells, growth factors are typically incorporated into the treatment system. Nonetheless, traditional hydrogel-encapsulated or heparinized scaffolds that bind factors have limitations. In this study, we prepared a biomaterial strategy using uniform poly(lactic-co-glycolic) acid (PLGA) microspheres (uPLGA-Ms) fabricated by microfluidic to sustain delivery of insulin-like growth factor 1 (IGF-1), a critical protein for hMSCs biological functions. The uPLGA-Ms loaded IGF-1 were highly monodispersed through precise manipulation of the flow rate of the two-phase of the flow-focusing microchannle. The results showed that the uPLGA-Ms stabilize IGF-1 and provide a more efficient sustained delivery and cost-effective of growth factor. Gene expression analysis demonstrated the uPLGA delivery of IGF-1 results in a (enhanced) supported hMSCs expansion, survival, stemness, and secretion abilities comparable with the conventional soluble IGF-1 group. In summary, this material-based strategy to stabilize and sustain delivery of growth factor has broad potential to regeneration of various tissues and organs.

Effects of Flammulina velutipes mushroom residues on growth performance, apparent digestibility, serum biochemical indicators, rumen fermentation and microbial of Guizhou black goat.

Introduction: The primary objective of the current study was to evaluate the effects of Flammulina velutipes mushroom residue (FVMR) in a fermented total mixed ration (FTMR) diet on the fattening effect and rumen microorganisms in Guizhou black male goats. Methods: A total of 22 Guizhou black male goats were allocated into two groups using the Randomized Complete Block Design (RCBD) experimental design. The average initial weight was 22.41 ± 0.90 kg and with 11 goats in each group. The control group (group I) was fed the traditional fermentation total mixed ration (FTMR) diet without FVMR. Group II was fed the 30% FVMR in the FTMR diet. Results: The results showed that compared with group I, the addition of FVMR in the goat diet could reduce the feed cost and feed conversion ratio (FCR) of group II (p < 0.01). Notably, the apparent digestibility of crude protein (CP), acid detergent fiber (ADF), neutral detergent fiber (NDF), and dry matter (DM) were higher in group II (p < 0.01). The levels of growth hormone (GH), immunoglobulin A (IgA), and immunoglobulin M (IgM) in group II were higher than that of group I (p < 0.01), which the level of glutamic oxalacetic transaminase (ALT) and interleukin-6 (IL-6) was noticeably lower than that of group I (p < 0.01). 30% FVMR in FTMR diets had no effect on rumen fermentation parameters and microbial composition at the phylum level of Guizhou black male goats (p > 0.05). However, at the genus level, the relative abundance of bacteroidal_bs11_gut_group, Christensenellaceae_R-7_group and Desulfovibrio in group II was lower than in group I (p < 0.05), and the relative abundance of Lachnospiraceae_ND3007_group was higher than in group I (p < 0.01). Discussion: In conclusion, the results of the current study indicated that 30% FVMR in the FTMR diet improves rumen fermentation and rumen microbial composition in Guizhou black male goats, which improves growth performance, apparent digestibility, and immunity.

W-Net: A boundary-aware cascade network for robust and accurate optic disc segmentation.

Accurate optic disc (OD) segmentation has a great significance for computer-aided diagnosis of different types of eye diseases. Due to differences in image acquisition equipment and acquisition methods, the resolution, size, contrast, and clarity of images from different datasets show significant differences, resulting in poor generalization performance of deep learning networks. To solve this problem, this study proposes a multi-level segmentation network. The network includes data quality enhancement module (DQEM), coarse segmentation module (CSM), localization module (OLM), and fine segmentation stage module (FSM). In FSM, W-Net is proposed for the first time, and boundary loss is introduced in the loss function, which effectively improves the performance of OD segmentation. We generalized the model in the REFUGE test dataset, GAMMA dataset, Drishti-GS1 dataset, and IDRiD dataset, respectively. The results show that our method has the best OD segmentation performance in different datasets compared with state-of-the-art networks.

Efficacy of fecal microbiota transplantation in type 2 diabetes mellitus: a systematic review and meta-analysis.

OBJECTIVE: Type 2 diabetes mellitus (T2DM) is one of the common metabolic diseases worldwide, and studies have found significant differences in the composition and ratio of intestinal flora between patients with T2DM and normal glucose tolerance, and fecal microbiota transplantation (FMT) may modulate the composition of the intestinal microbiota thereby alleviating the hyperglycemic state. We conducted a meta-analysis and systematic review of existing randomized controlled trials (RCTs) to assess the efficacy of FMT in T2DM. METHODS: We conducted a computer search of PubMed, Embase, The Cochrane Library, and Web of Science to screen randomized controlled trials studies on FMT treatment for T2DM and extracted data from studies that met inclusion criteria. RevMan 5.4 software and Stata 11 software was used for meta-analysis. The indexes of Hemoglobin A1c (HbA1c), fasting plasma glucose (FPG), postprandial blood glucose (PBG), homeostasis model assessment of insulin resistance (HOMA-IR), triglycerides (TG), cholesterol (TC), low-density lipoprotein (LDL), high-density lipoprotein (HDL), body mass index (BMI), Aspartate Aminotransferase (AST), Alanine Transaminase (ALT), Systolic blood pressure (SBP) and Diastolic blood pressure (DBP) were mainly evaluated after FMT treatment of T2DM patients, and the changes of intestinal flora were evaluated. RESULTS: Four RCTs met the inclusion criteria and were included in the meta-analysis. Results of the meta-analysis showed that compared with the non-FMT group, FMT combined treatment could significantly reduce the PBG level in patients with type 2 diabetes (MD = -0.51, 95% CI: -1.42-0.40, P = 0.27). Compared with single FMT treatment, FMT combined treatment could reduce TG levels in patients with type 2 diabetes (MD = -0.60, 95% CI: -1.12~-0.07, P = 0.03). The levels of TG (MD = -0.26, 95% CI: -0.51~-0.02, P = 0.03), HOMA-IR (MD = -2.73, 95% CI: -4.71~0.75, P = 0.007) and HDL (MD = -0.06,95% CI: -0.10~-0.02, P = 0.003) were significantly decreased after treatment in the single FMT group. The level of TC (MD = -0.65, 95% CI: -1.00~-0.31, P = 0.0002) was significantly decreased after FMT combined treatment. Compared with before treatment, ALT (MD = -2.52, 95% CI: -3.86~-1.17, P = 0.0002) and DBP (MD = -2, 95% CI: -3.32~0.68, P = 0.003) levels decreased after treatment in the single FMT group and the FMT combined group. FPG (MD = -0.94, 95% CI: -1.86~-0.02, P = 0.04), TG (MD = -0.73, 95% CI: -1.42~-0.04, P = 0.04) and TC (MD = -0.94, 95% CI: -1.45~-0.43, P = 0.0003) were significantly decreased after combined drug and diet therapy. Secondly, FMT can promote the colonization and growth of donor-related flora in patients with type 2 diabetes. CONCLUSION: In patients with type 2 diabetes mellitus, FMT treatment can reduce the levels of PBG, TG, HOMA-IR, TC, ALT, and DBP, especially in the combined treatment regimen. In addition, FMT can reshape the intestinal flora and establish the balance of dominant flora.

Loxenatide attenuates ROS-mediated vascular endothelial progenitor cell damage and mitochondrial dysfunction via SIRT3/Foxo3 signaling pathway.

Diabetes mellitus (DM), becomes a main public health issue worldwide due to the rapid increase in DM patient numbers. The dysfunction of endothelial progenitor cells (EPCs) in DM patients plays a critical role in endothelial repair and the progression of DM-related vascular complications. Loxenatide is an a glucagon-like peptide 1 receptor agonist, which is used to control glycemic in type 2 diabetes patients. However, the role of Loxenatide in EPCs remains to be investigated. EPCs were isolated, characterized, and treated with Loxenatide, high-glucose, or 3-TYP. quantitative real-time polymerase chain reaction, flow cytometry, western blot, and cell counting kit-8 assay were employed to validate the expression of gene and protein expressions and cell viability, respectively. Application of Seahorse XFp to measure oxygen consumption and mitochondrial membrane potential (MMP) were measured by Seahorse XFp and MMP assay. Loxenatide attenuated high-glucose-induced reactive oxygen species (ROS) production and mitochondrial-dependent apoptosis of EPCs in a concentration-dependent manner. The EPC mitochondrial respiration dysfunction induced by high glucose was also repressed by the loxenatide treatment. The protection effect of Loxenatide on EPCs against high-glucose was applied by activating the sirtuin 3 (SIRT3)/Foxo3 signaling pathway. We demonstrated the regulatory role of Loxenatide in mitochondrial dysfunction and apoptosis of EPCs. We elucidated that Loxenatide protects EPC from high-glucose-induced apoptosis via ROS-mediated mitochondrial pathway through the SIRT3/Foxo3 signing pathway. This may provide a new therapeutical target for the treatment of DM-related vascular complications.

An empirical study on the reading response to picture books of children aged 5-6.

Picture book reading has drawn a great deal of attention, while the reading response to children's book has barely been noticed. This study therefore used the lag sequence analysis method to conduct an empirical study on the reading reaction of 60 5-6-year old children during collective picture book reading activities. Results indicated that the children had rich and diversified reading responses which mainly consisted of language description and emotional experience rather than careful observation of the picture books and in-depth understanding of the relationship between the pictures and text. In addition, the children's oral expression and vocabulary are important predictors of differences in the reading responses of children with different reading abilities. "Image observation to personal empirical reaction" is also the key behavioral sequence that distinguishes children with different reading abilities.

Synthesis and biological evaluation of thieno[3,2-c]pyrazol-3-amine derivatives as potent glycogen synthase kinase 3ß inhibitors for Alzheimer's disease.

Glycogen synthase kinase 3ß (GSK-3ß) is a potential target for anti-Alzheimer's disease (AD) drug development. In this study, a series of novel thieno[3,2-c]pyrazol-3-amine derivatives was synthesized and evaluated as potential GSK-3ß inhibitors by structure-based drug design. The thieno[3,2-c]pyrazol-3-amine derivative 54 with a 4-methylpyrazole moiety which interacted with Arg141 by π-cation interaction was identified as a potent GSK-3ß inhibitor with an IC50 of 3.4 nM and an acceptable kinase selectivity profile. In the rat primary cortical neurons, compound 54 showed neuroprotective effects on Aß-induced neurotoxicity. Western blot analysis indicated that 54 inhibited GSK-3ß by up-regulating the expression of phosphorylated GSK-3ß at Ser9 and down-regulating the expression of phosphorylated GSK-3ß at Tyr216. Meanwhile, 54 decreased tau phosphorylation at Ser396 in a dose-dependent way. In astrocytes and microglia cells, 54 inhibited the expression of inducible nitric oxide synthase (iNOS), indicating that 54 showed an anti-neuroinflammatory effect. In the AlCl3-induced zebrafish AD model, 54 significantly ameliorated the AlCl3-induced dyskinesia, demonstrating its anti-AD activity in vivo.

Oncogenic Wnt3a is a promising sensitive biomarker for monitoring hepatocarcinogenesis.

BACKGROUND: The effective treatment for hepatocellular carcinoma (HCC) depends on early diagnosis. Previously, the abnormal expression of Wnt3a as the key signaling molecule in the Wnt/ß-catenin pathway was found in HCC cells and could be released into the circulation. In this study, we used rat model of hepatocarcinogenesis to dynamically investigate the alteration of oncogenic Wnt3a and to explore its early monitor value for HCC. METHODS: Sprague-Dawley rats (SD) were fed with diet 2-fluorenylacetamide (2-FAA, 0.05%) for inducing hepatocarcinogenesis, and grouped based on liver morphological alteration by Hematoxylin & Eosin (H&E) staining; rats fed with normal chow were used as normal control (NC). Total RNA and protein were purified from rat livers. Differently expressed genes (DEGs) or Wnt3a mRNA, cellular distribution, and Wnt3a protein levels were analyzed by whole genome microarray with signal logarithm ratio (SLR log2cy5/cy3), immunohistochemistry, and enzyme-linked immunosorbent assay, respectively. RESULTS: Models of rat hepatocarcinogenesis were successfully established based on liver histopathological H&E staining. Rats were divided into the cell degeneration (rDeg), precancerosis (rPre-C) and HCC (rHCC) groups. Total numbers of the up- and down-regulated DEGs with SLR ≥ 8 were 55 and 48 in the rDeg group, 268 and 57 in the rPre-C group, and 312 and 201 in the rHCC group, respectively. Significantly altered genes were involved in cell proliferation, signal transduction, tumor metastasis, and apoptosis. Compared with the NC group, Wnt3a mRNA was increased by 4.6 folds (P < 0.001) in the rDeg group, 7.4 folds (P < 0.001) in the rPre-C group, and 10.4 folds (P < 0.001) in the rHCC group; the positive rates of liver Wnt3a were 66.7% (P = 0.001) in the rDeg group, 100% (P < 0.001) in the rPre-C group, and 100% (P < 0.001) in the rHCC group, respectively. Also, there were significant differences of liver Wnt3a (P < 0.001) or serum Wnt3a (P < 0.001) among different groups. CONCLUSIONS: Overexpression of Wnt3a was associated with rat hepatocarcinogenesis and it should be expected to be a promising monitoring biomarker for HCC occurrence at early stage.

Apatinib combined with camrelizumab in the treatment of recurrent/metastatic nasopharyngeal carcinoma: a prospective multicenter phase II study.

Background: Preclinical studies demonstrated that immune checkpoint inhibitors combined with antiangiogenic drugs have a synergistic anti-tumor effect. This present phase II trial aimed to evaluate the efficacy and safety of apatinib combined with camrelizumab in patients with recurrent/metastatic nasopharyngeal carcinoma (RM-NPC). Methods: Patients with RM-NPC were administered with apatinib at 250 mg orally once every day and with camrelizumab at 200 mg via intravenous infusion every 2 weeks until the disease progressed or toxicity became unacceptable. The objective response rate (ORR) was the primary endpoint, assessed using RECIST version 1.1. Progression-free survival (PFS), overall survival (OS), disease control rate (DCR) and safety were the key secondary endpoints. This study was registered with ClinicalTrials.gov, NCT04350190. Results: This study enrolled 26 patients with RM-NPC between January 14, 2021 and September 15, 2021. At data cutoff (March 31, 2023), the median duration of follow-up was 16 months (ranging from 1 to 26 months). The ORR was 38.5% (10/26), the disease control rate (DCR) was 61.5% (16/26), and the median PFS was 6 months (IQR 3.0-20.0). The median OS was 14 months (IQR 6.0-21.25). Treatment-related grade 3 or 4 adverse events occurred in seven (26.9%) patients, and comprised anemia (7.7%), stomatitis (3.8%), headache (3.8%), pneumonia (7.7%), and myocarditis (3.8%). There were no serious treatment-related adverse events or treatment-related deaths. Conclusion: In patients with RM-NPC, apatinib plus camrelizumab showed promising antitumor activity and manageable toxicities.

Effect of Mulberry Leaf TMR on Growth Performance, Meat Quality and Expression of Meat Quality Master Genes (ADSL, H-FABP) in Crossbred Black Goats.

This study was conducted to examine the effect of a mulberry leaf total mixed ration (TMR) diet on growth performance, apparent digestibility, meat quality and the expression of related meat-quality genes (ADSL, H-FABP) in crossbred black goats. Forty-four Guizhou crossbred black goats (Nubian black goat ♂ × Guizhou black goat ♀), weighing 33.43 ± 0.55 kg, were chosen. The goats were randomly divided into four groups, with 11 test replicates in each group. Group I was the control group and fed with the traditional feeding method of roughage and concentrate supplement without adding mulberry leaf. Group II was fed with a 40% mulberry leaf pellet TMR diet. Group III was fed with a freshly processed 40% mulberry leaf TMR diet. Group IV was fed with a 40% mulberry leaf fermented total mixed rations (FTMR) diet. The results showed that the average daily gain (ADG) of group II was significantly higher than that of group I and III (p < 0.05). The apparent digestibility of group II of ether extract (EE) and neutral detergent fiber (NDF) was significantly higher than that of group I (p < 0.05), and the apparent digestibility of dry matter (DM) and crude protein (CP) was significantly higher than that of group I (p < 0.01). Compared with group I, meat in group II had lower meat color lightness (L*) and yellowness (b*) values (p < 0.01) in the Longissimus thoracis et lumborum. The shear force of group II was significantly lower than that of group I (p < 0.05). The total fatty acids (TFA) of group II was significantly higher than that of groups I and III (p < 0.05), but the total saturated fatty acids (SFA) of group II was significantly lower that than of group I (p < 0.01). Subsequently, the Unsaturated fatty acids (USFA), Monounsaturated fatty acids (MUFA), and Polyunsaturated fatty acids (PUFA) of group II were significantly higher than those in group I (p < 0.01). The contents of total amino acids (TAA), total essential amino acids (EAA), total non-essential amino acids (NEAA) and total of major fresh-tasting amino acids (DAA) of groups II, III and IV were significantly higher than those of group I (p < 0.05), as well as the contents of IMP (p < 0.01). The expression of the H-FABP gene in the arm triceps of group II was significantly higher than that of groups I, III and IV (p < 0.05). The expression of the ADSL gene in the Longissimus thoracis et lumborum and biceps femoris of group II was significantly higher than that of group I (p < 0.05). Collectively, the results of the current study indicated that the mulberry leaf TMR diet improved the growth performance, apparent digestibility and expression of related meat-quality master genes (ADSL, H-FABP) in crossbred black goats, which promoted the deposition of intramuscular fat (IMF) and inosinic acid (IMP) and improved the composition of fatty acids and amino acids in the muscles.

Effects of targeted-edited oncogenic insulin-like growth factor-1 receptor with specific-sgRNA on biological behaviors of HepG2 cells.

BACKGROUND: Insulin-like growth factor-1 receptor (IGF-1R) is over-expressed in hepatocellular carcinoma (HCC). However, the relationship between IGF-1R activation and HCC progression remains unidentified. AIM: To investigate the effects of editing IGF-1R on the biological features of HCC cells. METHODS: Immunohistochemistry analyzed the expressions of IGF-1R and P-glyco protein (P-gp) in HCC tissues and their distal non-cancerous tissues (non-Ca). IGF-1R was edited with Crispr/Cas9 system, screened specific sgRNAs, and then transfected into HepG2 cells. CCK-8, scratch wound test detected cell proliferation, migration, invasion and transwell assays, respectively. Alterations of IGF-1R and P-gp were confirmed by Western blotting. Alterations of anti-cancer drug IC50 values were analyzed at the cell level. RESULTS: The positive rates of IGF-1R (93.6%, χ 2 = 63.947) or P-gp (88.2%, χ2 = 58.448) were significantly higher (P < 0.001) in the HCC group than those (36.6% in IGF-1R or 26.9% in P-gp) in the non-Ca group. They were positively correlated between high IGF-1R and P-gp expression, and they were associated with hepatitis B virus infection and vascular invasion of HCC. Abnormal expressions of circulating IGF-1R and P-gp were confirmed and associated with HCC progression. Biological feature alterations of HCC cells transfected with specific sgRNA showed IGF-1R expression down-regulation, cell proliferation inhibition, cell invasion or migration potential decreasing, and enhancing susceptibility of HepG2 cells to anti-cancer drugs. CONCLUSION: Edited oncogenic IGF-1R was useful to inhibit biological behaviors of HepG2 cells.

Clinical and radiomic features for predicting the treatment response of repetitive transcranial magnetic stimulation in major neurocognitive disorder: Results from a randomized controlled trial.

Image-guided repetitive transcranial magnetic stimulation (rTMS) has shown clinical effectiveness in senior adults with co-occurring depression and cognitive impairment, yet the imaging markers for predicting the treatment response are less investigated. In this clinical trial, we examined the efficacy and sustainability of 10 Hz rTMS for the treatment of depression and cognitive impairment in major neurocognitive disorder (NCD) patients and tested the predictive values of imaging-informed radiomic features in response to rTMS treatment. Fifty-five major NCD patients with depression were randomly assigned to receive a 3-week rTMS treatment of either active 10 Hz rTMS (n = 27) or sham rTMS (n = 28). Left dorsolateral prefrontal cortex (DLPFC) was the predefined treatment target. Based on individual structural magnetic resonance imaging scans, surface-based analysis was conducted to quantitatively measure the baseline radiomic features of left DLPFC. Severity of depression, global cognition and the serum brain-derived neurotrophic factor (BDNF) level were evaluated at baseline, 3-, 6- and 12-week follow-ups. Logistic regression analysis revealed that advanced age, higher baseline cognition and randomized group were associated with the remission of depression. Increased cortical thickness and gyrification in left DLPFC were the significant predictors of clinical remission and cognitive enhancement. A 3-week course of 10 Hz rTMS is an effective adjuvant treatment for rapid ameliorating depressive symptoms and enhancing cognitive function. Pre-treatment radiomic features of the stimulation target can predict the response to rTMS treatment in major NCD. Cortical thickness and folding of treatment target may serve as imaging markers to detect the responders. ChiCTR-IOR-16008191, registered on March 30, 2016.

Synthesis and biological evaluation of thieno[3,2-c]pyrazol-3-amine derivatives as potent glycogen synthase kinase 3ß inhibitors for Alzheimer's disease.

Glycogen synthase kinase 3ß (GSK-3ß) catalyses the hyperphosphorylation of tau protein in the Alzheimer's disease (AD) pathology. A series of novel thieno[3,2-c]pyrazol-3-amine derivatives were designed and synthesised and evaluated as potential GSK-3ß inhibitors by structure-guided drug rational design approach. The thieno[3,2-c]pyrazol-3-amine derivative 16b was identified as a potent GSK-3ß inhibitor with an IC50 of 3.1 nM in vitro and showed accepted kinase selectivity. In cell levels, 16b showed no toxicity on the viability of SH-SY5Y cells at the concentration up to 50 µM and targeted GSK-3ß with the increased phosphorylated GSK-3ß at Ser9. Western blot analysis indicated that 16b decreased the phosphorylated tau at Ser396 in a dose-dependent way. Moreover, 16b effectively increased expressions of ß-catenin as well as the GAP43, N-myc, and MAP-2, and promoted the differentiated neuronal neurite outgrowth. Therefore, the thieno[3,2-c]pyrazol-3-amine derivative 16b could serve as a promising GSK-3ß inhibitor for the treatment of AD.

Encouraging specific biomarkers-based therapeutic strategies for hepatocellular carcinoma.

The prevention, early discovery and effective treatment of patients with hepatocellular carcinoma (HCC) remain a global medical challenge. At present, HCC is still mainly treated by surgery, supplemented by vascular embolization, radio frequency, radiotherapy, chemotherapy and biotherapy. The application of multikinase inhibitor sorafenib, chimeric antigen receptor T cells, or PD-1/PD-L1 inhibitors can prolong the median survival of HCC patients. However, the treatment efficacy is still unsatisfactory due to HCC metastasis and postoperative recurrence. During the process of hepatocyte malignant transformation, HCC tissues can express and secrete many types of specific biomarkers, or oncogenic antigen molecules into blood, for example, alpha-fetoprotein, glypican-3, Wnt3a (one of the key signaling molecules in the Wnt/ß-catenin pathway), insulin-like growth factor (IGF)-II or IGF-I receptor, vascular endothelial growth factor, secretory clusterin and so on. In addition, combining immunotherapy with non-coding RNAs might improve anti-cancer efficacy. These biomarkers not only contribute to HCC diagnosis or prognosis, but may also become molecular targets for HCC therapy under developing or clinical trials. This article reviews the progress in emerging biomarkers in basic research or clinical trials for HCC immunotherapy.

Corrigendum: Comparison of Newtonian and Non-newtonian Fluid Models in Blood Flow Simulation in Patients With Intracranial Arterial Stenosis.

[This corrects the article DOI: 10.3389/fphys.2021.718540.].

Comparison of Newtonian and Non-newtonian Fluid Models in Blood Flow Simulation in Patients With Intracranial Arterial Stenosis.

BACKGROUND: Newtonian fluid model has been commonly applied in simulating cerebral blood flow in intracranial atherosclerotic stenosis (ICAS) cases using computational fluid dynamics (CFD) modeling, while blood is a shear-thinning non-Newtonian fluid. We aimed to investigate the differences of cerebral hemodynamic metrics quantified in CFD models built with Newtonian and non-Newtonian fluid assumptions, in patients with ICAS. METHODS: We built a virtual artery model with an eccentric 75% stenosis and performed static CFD simulation. We also constructed CFD models in three patients with ICAS of different severities in the luminal stenosis. We performed static simulations on these models with Newtonian and two non-Newtonian (Casson and Carreau-Yasuda) fluid models. We also performed transient simulations on another patient-specific model. We measured translesional pressure ratio (PR) and wall shear stress (WSS) values in all CFD models, to reflect the changes in pressure and WSS across a stenotic lesion. In all the simulations, we compared the PR and WSS values in CFD models derived with Newtonian, Casson, and Carreau-Yasuda fluid assumptions. RESULTS: In all the static and transient simulations, the Newtonian/non-Newtonian difference on PR value was negligible. As to WSS, in static models (virtual and patient-specific), the rheological difference was not obvious in areas with high WSS, but observable in low WSS areas. In the transient model, the rheological difference of WSS areas with low WSS was enhanced, especially during diastolic period. CONCLUSION: Newtonian fluid model could be applicable for PR calculation, but caution needs to be taken when using the Newtonian assumption in simulating WSS especially in severe ICAS cases.

A two-step process for energy-efficient conversion of food waste via supercritical water gasification: Process design, products analysis, and electricity evaluation.

The huge amount of food waste (FW), containing high organic matter content and moisture, is difficult to be well treated. Supercritical water gasification (SCWG) can efficiently convert FW to H2-rich syngas. However, it requires high energy input due to the high temperature and high pressure. This study provided an innovative "two-steps heating process" for the SCWG of FW, which firstly utilized hydrothermal (HT) pretreatment to shorter time of SCWG. The effects of different HT temperature (200 °C, 250 °C, 300 °C, 30 min) to SCWG temperature (480 °C, 30 min) and the different residence time (20 min HT - 40 min SCWG, 30 min HT - 30 min SCWG, and 40 min HT - 20 min SCWG) on total syngas yield, carbon conversion efficiency (CE), cold gas efficiency (CGE), and hydrogen conversion efficiency (HE) were studied. Moreover, the energy input by means of electricity consumption in each experiment was measured to determine the energy saving rate. The optimal condition (200 °C, 20 min HT - 40 min SCWG), obtaining the gas yield (17.22 mol/kg), CE (20.10%), CGE (22.13%), and HE (41.54%), was higher than the gas yield (16.53 mol/kg), CE (19.98%), CGE (20%), and HE (38.08%) of directly SCWG (60 min, 0 °C-480 °C). Moreover, the TOC of derived liquid and the pyrolysis characteristics of solid residues were analyzed. Additionally, it was also observed the HT pretreatment helped to reduce the electricity consumption. The highest energy saving rate was 15.58%.

Deep Learning Methodology for Differentiating Glioma Recurrence From Radiation Necrosis Using Multimodal Magnetic Resonance Imaging: Algorithm Development and Validation.

BACKGROUND: The radiological differential diagnosis between tumor recurrence and radiation-induced necrosis (ie, pseudoprogression) is of paramount importance in the management of glioma patients. OBJECTIVE: This research aims to develop a deep learning methodology for automated differentiation of tumor recurrence from radiation necrosis based on routine magnetic resonance imaging (MRI) scans. METHODS: In this retrospective study, 146 patients who underwent radiation therapy after glioma resection and presented with suspected recurrent lesions at the follow-up MRI examination were selected for analysis. Routine MRI scans were acquired from each patient, including T1, T2, and gadolinium-contrast-enhanced T1 sequences. Of those cases, 96 (65.8%) were confirmed as glioma recurrence on postsurgical pathological examination, while 50 (34.2%) were diagnosed as necrosis. A light-weighted deep neural network (DNN) (ie, efficient radionecrosis neural network [ERN-Net]) was proposed to learn radiological features of gliomas and necrosis from MRI scans. Sensitivity, specificity, accuracy, and area under the curve (AUC) were used to evaluate performance of the model in both image-wise and subject-wise classifications. Preoperative diagnostic performance of the model was also compared to that of the state-of-the-art DNN models and five experienced neurosurgeons. RESULTS: DNN models based on multimodal MRI outperformed single-modal models. ERN-Net achieved the highest AUC in both image-wise (0.915) and subject-wise (0.958) classification tasks. The evaluated DNN models achieved an average sensitivity of 0.947 (SD 0.033), specificity of 0.817 (SD 0.075), and accuracy of 0.903 (SD 0.026), which were significantly better than the tested neurosurgeons (P=.02 in sensitivity and P<.001 in specificity and accuracy). CONCLUSIONS: Deep learning offers a useful computational tool for the differential diagnosis between recurrent gliomas and necrosis. The proposed ERN-Net model, a simple and effective DNN model, achieved excellent performance on routine MRI scans and showed a high clinical applicability.

Application of 3D-Printed Orthopedic Cast for the Treatment of Forearm Fractures: Finite Element Analysis and Comparative Clinical Assessment.

OBJECTIVE: This pilot study is aimed at investigating the mechanical characteristics of a cast-wrapped fractured forearm and performing a clinical comparative study of our own developed 3D-printed orthopedic cast. METHODS: An integrated finite element (FE) model including a forearm and a 3D-printed cast wrapping the forearm was created. The distal radial ulna in this model was cut through to mimic the bone fracture. A 400 N force and 1 Nm rotation moment, which were much larger than the loading conditions encountered in daily life for a human being, were applied on the palm. We conducted a comparative clinical study by using statistical assessment. 60 patients with forearm fractures were selected and treated with manual reduction and external fixation cast. All patients were divided into three groups with equal members (20): (a) 3D-printed external cast group, (b) traditional plaster external fixation group, and (c) splint external fixation group. The clinical efficacy, wrist function, and patient satisfaction were scored and compared. RESULTS: In the condition of 400 N loading, the fracture displacements in anterior-posterior (AP), posterior-anterior (PA), medial to lateral (ML), and lateral to medial (LM) compression directions were 1.2648, 1.3253, 0.8503, and 0.8957 (mm), respectively, and the corresponding fracture stresses were 4.5986, 3.9129, and 5.0334, 7.9197 (MPa), respectively. In the inward (IR) and outward (OR) rotations, the fracture displacements were both 0.02628 (mm), and the corresponding fracture surface stresses were 0.1733 and 0.1723 (MPa), respectively. In the clinical efficacy, wrist function, and patient comfort evaluation, the total scores of group A were both higher than those in groups B and C (P < 0.05). CONCLUSION: A 3D-printed orthopedic cast was capable of exerting appropriate mechanical correction loads on specific areas to maintain optimal alignment of a fractured forearm and thus could achieve the favorable clinical efficacy and patient comfort.