HaN-Seg: The head and neck organ-at-risk CT and MR segmentation challenge.

BACKGROUND AND PURPOSE: To promote the development of auto-segmentation methods for head and neck (HaN) radiation treatment (RT) planning that exploit the information of computed tomography (CT) and magnetic resonance (MR) imaging modalities, we organized HaN-Seg: The Head and Neck Organ-at-Risk CT and MR Segmentation Challenge. MATERIALS AND METHODS: The challenge task was to automatically segment 30 organs-at-risk (OARs) of the HaN region in 14 withheld test cases given the availability of 42 publicly available training cases. Each case consisted of one contrast-enhanced CT and one T1-weighted MR image of the HaN region of the same patient, with up to 30 corresponding reference OAR delineation masks. The performance was evaluated in terms of the Dice similarity coefficient (DSC) and 95-percentile Hausdorff distance (HD95), and statistical ranking was applied for each metric by pairwise comparison of the submitted methods using the Wilcoxon signed-rank test. RESULTS: While 23 teams registered for the challenge, only seven submitted their methods for the final phase. The top-performing team achieved a DSC of 76.9 % and a HD95 of 3.5 mm. All participating teams utilized architectures based on U-Net, with the winning team leveraging rigid MR to CT registration combined with network entry-level concatenation of both modalities. CONCLUSION: This challenge simulated a real-world clinical scenario by providing non-registered MR and CT images with varying fields-of-view and voxel sizes. Remarkably, the top-performing teams achieved segmentation performance surpassing the inter-observer agreement on the same dataset. These results set a benchmark for future research on this publicly available dataset and on paired multi-modal image segmentation in general.

Tensile and Compressive Properties of Woven Fabric Carbon Fiber-Reinforced Polymer Laminates Containing Three-Dimensional Microvascular Channels.

Microvascular self-healing composite materials have significant potential for application and their mechanical properties need in-depth investigation. In this paper, the tensile and compressive properties of woven fabric carbon fiber-reinforced polymer (CFRP) laminates containing three-dimensional microvascular channels were investigated experimentally. Several detailed finite element (FE) models were established to simulate the mechanical behavior of the laminate and the effectiveness of different models was examined. The damage propagation process of the microvascular laminates and the influence of microvascular parameters were studied by the validated models. The results show that microvascular channels arranged along the thickness direction (z-direction) of the laminates are critical locations under the loads. The channels have minimal effect on the stiffness of the laminates but cause a certain reduction in strength, which varies approximately linearly with the z-direction channel diameter within its common design range of 0.1~1 mm. It is necessary to consider the resin-rich region formed around microvascular channels in the warp and weft fiber yarns of the woven fabric composite when establishing the FE model. The layers in the model should be assigned with equivalent unidirectional ply material in order to calculate the mechanical properties of laminates correctly.

DSFF-GAN: A novel stain transfer network for generating immunohistochemical image of endometrial cancer.

Immunohistochemistry (IHC) is a commonly used histological examination technique. Compared to Hematoxylin and Eosin (H&E) staining, it enables the examination of protein expression and localization in tissues, which is valuable for cancer treatment and prognosis assessment, such as the detection and diagnosis of endometrial cancer. However, IHC involves multiple staining steps, is time-consuming and expensive. One potential solution is to utilize deep learning networks to generate corresponding virtual IHC images from H&E images. However, the similarity of the IHC image generated by the existing methods needs to be further improved. In this work, we propose a novel dual-scale feature fusion (DSFF) generative adversarial network named DSFF-GAN, which comprises a cycle structure-color similarity loss, and DSFF block to constrain the model's training process and enhance its stain transfer capability. In addition, our method incorporates labeling information of positive cell regions as prior knowledge into the network to further improve the evaluation metrics. We train and test our model using endometrial cancer and publicly available breast cancer IHC datasets, and compare it with state-of-the-art methods. Compared to previous methods, our model demonstrates significant improvements in most evaluation metrics on both datasets. The research results show that our method further improves the quality of image generation and has potential value for the future clinical application of virtual IHC images.

Effect of Anisotropic Structural Depth on Orientation and Differentiation Behavior of Skeletal Muscle Cells.

Extensive research has been conducted to examine how substrate topological factors are involved in modulating the cell behavior. Among numerous topological factors, the vital influence of the touchable depth of substrates on cell behaviors has already been extensively characterized, but the response of cells to the topological structure at untouchable depth is still elusive. Herein, the influences of substrate depth on myoblast behaviors are systematically investigated using substrates with depths ranging from touchable depth (microgrooved) to untouchable depth (microbridges). The results show that an increase in microgroove depth is accompanied by an inhibited cell spreading, an enhanced elongation, and a more obvious orientation along microgrooves. Interestingly, myoblasts located on microbridges show a more pronounced elongation with increasing culture time but a position-dependent orientation. Myoblasts on the center and parallel boundary of microbridges orient along the bridges, while myoblasts on the vertical boundary align perpendicular to the microbridges. Moreover, the differentiation results of the myoblasts indicate that the differentiated myotubes can maintain this position-dependent orientation. The simulation of the stress field in cell monolayers suggests that the position-dependent orientation is caused by the comprehensive response of myoblasts to the substrate discontinuity and substrate depth. These findings provide valuable insights into the mechanism of cell depth sensing and could inform the design of tissue engineering scaffolds for skeletal muscle and biohybrid actuation.

Utilization of hepatitis B surface antigen-positive donors in liver transplantation for recipients with hepatocellular carcinoma: a retrospective and propensity score matching analysis.

Introduction: The use of extended criteria donor (ECD) grafts such as donor with infection of hepatitis B virus (HBV) is a potential solution for organ shortage. In this study, we aimed to evaluate the safety and long-term survival of utilization of hepatitis B surface antigen-positive (HBsAg+) donor livers in HCC patients using propensity score matching (PSM) analysis. Methods: Forty-eight donors with HBsAg-positive and 279 donors with HBsAg-negative were transplanted and enrolled in this study. PSM analysis were used to eliminate selection bias. Perioperative data and survival were collected and analyzed. Results: PSM generated 44 patient pairs. When comparing intra- and post-operative data, no significant difference was found between groups (P > 0.05). Patients with a HBsAg-positive donor had significantly worse progression-free survival (1-year: 65.9% vs. 90.9%; 3-year: 18.1% vs. 70.4%, P = 0.0060) and overall survival (1-year: 84.1% and 95.4%; 3-year: 27.2% vs. 79.5%, P = 0.0039). In multivariate analysis, donor HBsAg-positivity was an independent risk factor for survival and occurrence (P = 0.005 and 0.025, respectively). Conclusion: In conclusion, with adequate antiviral prophylaxis and treatment, utilization of HBsAg positive liver grafts did not increase the incidence of early-stage complications. However, patient with an HBsAg-positive graft had poorer progression-free survival and overall survival.

A randomized-controlled trial of ischemia-free liver transplantation for end-stage liver disease.

BACKGROUND & AIMS: Ischemia-reperfusion injury (IRI) has thus far been considered as an inevitable component of organ transplantation, compromising outcomes, and limiting organ availability. Ischemia-free organ transplantation is a novel approach designed to avoid IRI, with the potential to improve outcomes. METHODS: In this randomized-controlled clinical trial, recipients of livers from donors after brain death were randomly assigned to receive either an ischemia-free or a 'conventional' transplant. The primary endpoint was the incidence of early allograft dysfunction. Secondary endpoints included complications related to graft IRI. RESULTS: Out of 68 randomized patients, 65 underwent transplants and were included in the analysis. 32 patients received ischemia-free liver transplantation (IFLT), and 33 received conventional liver transplantation (CLT). Early allograft dysfunction occurred in two recipients (6%) randomized to IFLT and in eight (24%) randomized to CLT (difference -18%; 95% CI -35% to -1%; p = 0.044). Post-reperfusion syndrome occurred in three recipients (9%) randomized to IFLT and in 21 (64%) randomized to CLT (difference -54%; 95% CI -74% to -35%; p <0.001). Non-anastomotic biliary strictures diagnosed with protocol magnetic resonance cholangiopancreatography at 12 months were observed in two recipients (8%) randomized to IFLT and in nine (36%) randomized to CLT (difference, -28%; 95% CI -50% to -7%; p = 0.014). The comprehensive complication index at 1 year after transplantation was 30.48 (95% CI 23.25-37.71) in the IFLT group vs. 42.14 (95% CI 35.01-49.26) in the CLT group (difference -11.66; 95% CI -21.81 to -1.51; p = 0.025). CONCLUSIONS: Among patients with end-stage liver disease, IFLT significantly reduced complications related to IRI compared to a conventional approach. CLINICAL TRIAL REGISTRATION: chictr.org. ChiCTR1900021158. IMPACT AND IMPLICATIONS: Ischemia-reperfusion injury has thus far been considered as an inevitable event in organ transplantation, compromising outcomes and limiting organ availability. Ischemia-free liver transplantation is a novel approach of transplanting donor livers without interruption of blood supply. We showed that in patients with end-stage liver disease, ischemia-free liver transplantation, compared with a conventional approach, led to reduced complications related to ischemia-reperfusion injury in this randomized trial. This new approach is expected to change the current practice in organ transplantation, improving transplant outcomes, increasing organ utilization, while providing a clinical model to delineate the impact of organ injury on alloimmunity.

[Correlation between neutrophil/lymphocyte ratio combined with low-density lipoprotein cholesterol/high-density lipoprotein cholesterol ratio and severity of coronary artery disease in patients with acute coronary syndrome].

OBJECTIVE: To investigate the correlation between neutrophil/lymphocyte ratio (NLR) combined with low-density lipoprotein cholesterol/high-density lipoprotein cholesterol ratio (LDL-C/HDL-C) and severity of coronary lesions in patients with acute coronary syndrome (ACS). METHODS: Patients who were diagnosed with ACS due to chest pain and received emergency coronary angiography in the First Affiliated Hospital of University of Science and Technology of China and the Affiliated Hospital of Anhui Medical University from January 2017 to June 2020 were enrolled in the final analysis. The data of gender, age, body mass index (BMI), past history, emergency blood routine indicators [neutrophil (NEU), lymphocyte (LYM), monocyte (MON), eosinophil (EOS), basophil (BAS), red blood cell (RBC), mean corpuscular volume (MCV), blood red cell distribution width (RDW), mean platelet volume (MPV), platelet volume distribution width (PDW)], blood lipid index [triglyceride (TG), total cholesterol (TC), HDL-C, LDL-C, very low-density lipoprotein cholesterol (VLDL-C)], and coronary angiography were collected. The results of coronary angiography were evaluated by the Gensini score. According to the Gensini score, the patients were divided into the control group (Gensini score = 0, 55 cases) and the study group (Gensini score > 0, 889 cases), and then the patients in the study group were divided into the low-Gensini-score group (Gensini score < 66, 419 cases) and the high-Gensini-score group (Gensini score ≥ 66, 470 cases). The differences in the general baseline data of the four groups were compared, and the correlation between the statistically significant data and the Gensini score was linearly analyzed, and then the combined diagnostic factors (NLR combined with LDL-C/HDL-C ratio) were obtained by Logistic regression analysis. The receiver operator characteristic curve (ROC curve) was used to evaluate the predictive value of NLR combined with LDL-C/HDL-C ratio in predicting the severity of coronary artery lesions in patients with ACS. Finally, multivariate linear regression analysis was used to establish the predictive model between NLR combined with LDL-C/HDL-C ratio and Gensini score. RESULTS: A total of 944 patients were finally included. The differences in gender, age, BMI, hypertension, diabetes, smoking history, NEU, LYM, MON, EOS, RDW, TC, HDL-C, LDL-C, NLR, LDL-C/HDL-C ratio between the control group and the study group were statistically significant. The differences in BMI, hypertension, diabetes, smoking history, NEU, LYM, MON, EOS, TG, TC, HDL-C, LDL-C, NLR and LDL-C/HDL-C ratio between the low-Gensini-score group and the high-Gensini-score group were statistically significant. Linear regression analysis showed that compared with other indicators, the correlation between NLR, LDL-C/HDL-C ratio and Gensini score was stronger in the study group (r values were 0.634 and 0.663, respectively, both P < 0.05). Binary Logistic regression analysis of the indicators related to Gensini score showed that NEU, LYM, HDL-C and LDL-C were independent risk factors for coronary stenosis in patients with ACS [odds ratio (OR) were 0.189, 10.309, 13.993, 0.251, 95% confidence intervals (95%CI) were 0.114-0.313, 4.679-22.714, 3.402-57.559, 0.121-0.519, respectively, all P < 0.05]. ROC curve analysis showed that NLR combined with LDL-C/HDL-C ratio had higher predictive value in predicting the severity of coronary lesions in ACS patients [area under the ROC curve (AUC) was 0.952, 95%CI was 0.93-0.969], when the cutoff value was -3.152, the sensitivity was 98.20%, and the specificity was 81.60%. According to the results of multivariate linear regression analysis, the prediction model between NLR, LDL-C/HDL-C ratio and Gensini score was established, and the formula was Gensini score = -7.772+15.675×LDL-C/HDL-C ratio+8.288×NLR (R2 = 0.862). CONCLUSIONS: There is a significant correlation between emergency NLR combined with LDL-C/HDL-C ratio and Gensini score in patients with ACS at admission, which has a certain predictive value for the severity of coronary artery stenosis in patients with ACS, and can be used as a predictor for evaluating the severity of coronary artery disease.

A Mock Circulation Loop for In Vitro Hemodynamic Evaluation of Aorta: Application in Aortic Dissection.

PURPOSE: Aortic dissection (AD) is a catastrophic disease with complex hemodynamic conditions, however, understandings regarding its perfusion characteristics were not sufficient. In this study, a mock circulation loop (MCL) that integrated the Windkessel element and patient-specific silicone aortic phantoms was proposed to reproduce the aortic flow environment in vitro. MATERIALS AND METHODS: Patient-specific normal and dissected aortic phantoms with 12 branching vessels were established and embedded into this MCL. Velocities for aortic branches based on 20 healthy volunteers were regarded as the standardized data for flow division. By altering boundary conditions, the proposed MCL could mimic normal resting and left-sided heart failure (LHF) conditions. Flow rates and pressure status of the aortic branches could be quantified by separate sensors. RESULTS: In normal resting condition, the simulated heart rate and systemic flow rate were 60 bpm and 4.85 L/minute, respectively. For the LHF condition, the systolic and diastolic blood pressures were 75.94±0.77 mmHg and 57.65±0.35 mmHg, respectively. By tuning the vascular compliance and peripheral resistance, the flow distribution ratio (FDR) of each aortic branch was validated by the standardized data in the normal aortic phantom (mean difference 2.4%±1.70%). By comparing between the normal and dissected aortic models under resting condition, our results indicated that the AD model presented higher systolic (117.82±0.60 vs 108.75±2.26 mmHg) and diastolic (72.38±0.58 vs 70.46±2.33 mmHg) pressures, the time-average velocity in the true lumen (TL; 36.95 cm/s) was higher than that in the false lumen (FL; 22.95 cm/s), and the blood transport direction between the TL and FL varied in different re-entries. CONCLUSIONS: The proposed MCL could be applied as a research tool for in vitro hemodynamic analysis of the aorta diseases under various physical conditions.

Transplantation of Extended Criteria Donor Livers Following Continuous Normothermic Machine Perfusion Without Recooling.

BACKGROUND: Traditional liver transplant strategies with cold preservation usually result in ischemia-reperfusion injury (IRI) to the donor liver. Regular normothermic machine perfusion (NMP) donor livers suffer IRI twice. Here, we aimed to introduce a novel technique called continuous NMP without recooling to avoid a second IRI and its application in livers from extended criteria donors. METHODS: Seven donor livers transplanted following continuous NMP without recooling, 7 donor livers transplanted following standard NMP, and 14 livers under static cold storage (SCS) were included in this study. Perioperative outcomes were recorded and analyzed between groups. RESULTS: During the NMP without a recooling procedure, all livers cleared lactate quickly to normal levels in a median time of 100 min (interquartile range, 60-180) and remained stable until the end of perfusion. In the NMP without recooling and standard NMP groups, posttransplant peak aspartate aminotransferase and alanine aminotransferase levels were both significantly lower than those in the SCS group (P = 0.0015 and 0.016, respectively). The occurrence rate of early allograft dysfunction was significantly lower in the NMP without recooling group than in the SCS group (P = 0.022), whereas there was no difference in the NMP group with or without recooling (P = 0.462). CONCLUSIONS: Our pilot study revealed a novel technique designed to avoid secondary IRI. This novel technique is shown to have at least a comparable effect on the standard NMP, although more data are needed to show its superiority in the future.

Circulating Tumor Cell Is a Clinical Indicator of Pretransplant Radiofrequency Ablation for Patients with Hepatocellular Carcinoma.

INTRODUCTION: It is of great significance to confirm reliable indicators for the guidance of pretransplant radiofrequency ablation (RFA) for hepatocellular carcinoma (HCC). In this study, we aim to investigate whether circulating tumor cell (CTC) status is a clinical indicator for RFA before liver transplantation (LT) in HCC patients. METHOD: CTC analyses were measured in 79 HCC patients. Clinical outcomes including progression-free (PFS) and overall survival (OS) were compared and analyzed between patients with and without pretransplant RFA. RESULT: Forty-two patients were detected as CTC-positive and 18 patients received pretransplant RFA. Recurrence was correlated with CTC count (P=0.024), tumor number (P=0.035), liver cirrhosis (P=0.001), Milan criteria (P=0.003), and University of California San Francisco (UCSF) criteria (P=0.001). Kaplan-Meier analysis revealed that patients with CTC-positive had a lower PFS rate (P=0.0257). For CTC-positive patients, the PFS rate of the pretransplant RFA group was significantly higher than the non-pretransplant RFA group (100% vs. 46.7%, P=0.0236). For CTC-negative patients, both PFS rate and OS rate were similar and without significant differences. In multivariate analysis, pretransplant RFA was the independent factor for PFS (P=0.025). CONCLUSION: Pretransplant CTC status can guide the administration of pretransplant RFA in HCC patients which can improve PFS in CTC-positive HCC patients.

En bloc procurement of porcine abdominal multiple organ block for ex situ normothermic machine perfusion: a technique for avoiding initial cold preservation.

BACKGROUND: Normothermic machine perfusion (NMP) is a technique that maintains organs ex situ with normal metabolism, and organ function can be better preserved. The study of multiple-organ NMP is rarely reported. Multiple organ block (MOB) is a self-perfusing system for maintaining multiple organs ex situ, and porcine MOBs have been successfully preserved for 18 to 37 h. Due to the above context, we conceived to maintain abdominal multiple organ block (AMOB) ex situ utilizing NMP technology. METHODS: AMOBs were procured from Ba-Ma miniature pigs through en bloc procurement surgery. The process of cold preservation was eliminated between the procurement and machine perfusion, and a few minutes of warm ischemia emerged. Autologous whole blood was collected during procurement surgery as a perfusate component in the beginning. RESULTS: The median time of procurement surgery was approximately 220 min, and the median time of warm ischemia was 300 sec. Cases 1 and 2 suffered from repeated hypotension during the procurement surgery, and case 2 exhibited hemorrhage. After improved and optimized procurement processes, the vital signs of cases 3 to 5 remained stable during procurement. In the NMP phase, the flow increased slowly in cases 1 and 2 and did not remain stable even after continuous infusion of a high-dose vasodilator. The lactic acid level rapidly increased, and the levels of ALT and AST were obviously higher than those in cases 3 to 5. In contrast, the flow rate increased smoothly in cases 3 to 5. The lactic acid level remained stable during the first 10 h of perfusion. CONCLUSIONS: AMOB procurement from heart-beating pigs for NMP without initial cold preservation is technically feasible.

DTYMK Expression Predicts Prognosis and Chemotherapeutic Response and Correlates with Immune Infiltration in Hepatocellular Carcinoma.

INTRODUCTION: Hepatocellular carcinoma (HCC) is the most common malignant tumor of the liver. Identifying specific molecular markers that can predict HCC prognosis is extremely important. The protein deoxythymidylate kinase (DTYMK) has been reported to contribute to unfavorable prognosis in non-small cell lung cancer patients, but its role in the prediction of HCC patient prognosis has not been clarified. METHODS: Samples from the TCGA and GEO databases were consecutively enrolled for gene expression analysis, clinicopathology analysis, immune microenvironment analysis and chemotherapeutic response prediction. The results were validated using 86 samples from the First Affiliated Hospital of Sun Yat-sen University. Cox regression analysis was used to analyze the effect of DTYMK on progression-free survival (PFS) and overall survival (OS). Functional enrichment analysis was used to describe the marker pathways that were significantly related to DTYMK. TIMER (Tumor Immune Estimation Resource), TISIDB (Tumor and Immune System Interaction DataBase) and CIBERSORT (Cell type Identification By Estimating Relative Subsets Of RNA Transcripts) were used to explore the immune microenvironment. RESULTS: We found that DTYMK expression upregulation is associated with poor prognosis in HCC patients and tightly related to the pathways regulating the cell cycle and acid metabolism. Our findings revealed that hepatocellular carcinoma cell lines with high DTYMK expression were more sensitive to sorafenib and many other chemotherapeutic drugs. We also found an inhibiting effect of DTYMK on the immune microenvironment in the process of tumorigenesis. DISCUSSION: We found that DTYMK has potential as a new prognostic and chemotherapeutic response biomarker for HCC patients and correlates with the immune microenvironment in HCC. However, there are some deficiencies in our study. First, this is a retrospective study that may lead to selection bias. Second, the protein expression of DTYMK was investigated via immunohistochemical analysis. Finally, we did not explore the exact underlying molecular mechanisms of DTYMK in tumorigenesis in this study, which is needed to be clarified in future research.

Continuous Normothermic Machine Perfusion for Renovation of Extended Criteria Donor Livers Without Recooling in Liver Transplantation: A Pilot Experience.

Background: Ischemia injury affects the recovery of liver allograft function. We propose a novel technique aimed at avoiding a second ischemic injury: transplanting an extended criteria donor (ECD) liver directly under normothermic machine perfusion (NMP) without recooling. We studied two cases to evaluate the efficacy and safety of this technique. Methods: The perioperative characteristics and postoperative outcomes of two recipients of ECD livers were analyzed. Both transplantations were performed with continuous normothermic machine perfusion without recooling. Result: In case 1, the cause of donor death was anoxia, and the donor liver had hypernatremia before procurement. The recipient was diagnosed with decompensated cirrhosis. His model for end-stage liver disease (MELD) score was 38. In case 2, the donor liver was from a donor after cardiac death (DCD), and the donor had elevated aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels. The recipient was diagnosed with acute hepatic failure. His MELD score was 35. Both donor livers were maintained under NMP and then transplanted without recooling. The peak ALT and AST levels after surgery were 452 and 770 U/L in case 1 and 100 and 592 U/L in case 2. Neither early allograft dysfunction (EAD) nor primary graft non-function (PNF) was present in these two cases. Conclusion: In conclusion, our results demonstrate that continuous NMP without recooling is efficacious and safe for LT with extended criteria donor livers. Further investigations of this technique will be performed to confirm these promising results.

Application of ischaemia-free liver transplantation improves prognosis of patients with steatotic donor livers - a retrospective study.

The use of steatotic livers in liver transplantation (LT) is controversial. Ischaemia-free liver transplantation (IFLT) has obvious advantages for the recovery of allograft function. The aim of this study was to examine the effect of liver grafts with steatosis on outcome and the effect of IFLT with steatotic livers. 360 patients with LT were enrolled in this study. Perioperative characteristics and differences in outcome among different grades of steatotic groups, and between the IFLT and conventional LT (CLT) groups were analysed. Occurrence of early allograft dysfunction (EAD; 50%) and primary nonfunction (PNF; 20%) was significantly higher in the severe steatosis group (P < 0.001 and <0.001, respectively). Survival rate is significantly low in severe steatosis group (3-year: 60%, P = 0.0039). The IFLT group had a significantly lower occurrence of EAD than the CLT group (0% vs. 60%, P = 0.01). The level of postoperative peak AST, GGT and creatine were significantly lower in IFLT group (P = 0.009, 0.032 and 0.024, respectively). In multivariable analysis, IFLT and EAD were independent factors affecting postoperative survival. Severe steatotic livers lead to severe complications and poor outcomes in LT. IFLT has obvious advantages for reducing the rate of EAD in LT with steatotic livers.