One-shot neuroanatomy segmentation through online data augmentation and confidence aware pseudo label.

Recently, deep learning-based brain segmentation methods have achieved great success. However, most approaches focus on supervised segmentation, which requires many high-quality labeled images. In this paper, we pay attention to one-shot segmentation, aiming to learn from one labeled image and a few unlabeled images. We propose an end-to-end unified network that joints deformation modeling and segmentation tasks. Our network consists of a shared encoder, a deformation modeling head, and a segmentation head. In the training phase, the atlas and unlabeled images are input to the encoder to get multi-scale features. The features are then fed to the multi-scale deformation modeling module to estimate the atlas-to-image deformation field. The deformation modeling module implements the estimation at the feature level in a coarse-to-fine manner. Then, we employ the field to generate the augmented image pair through online data augmentation. We do not apply any appearance transformations cause the shared encoder could capture appearance variations. Finally, we adopt supervised segmentation loss for the augmented image. Considering that the unlabeled images still contain rich information, we introduce confidence aware pseudo label for them to further boost the segmentation performance. We validate our network on three benchmark datasets. Experimental results demonstrate that our network significantly outperforms other deep single-atlas-based and traditional multi-atlas-based segmentation methods. Notably, the second dataset is collected from multi-center, and our network still achieves promising segmentation performance on both the seen and unseen test sets, revealing its robustness. The source code will be available at https://github.com/zhangliutong/brainseg.

Secretion of IFN-γ by specific T cells in HCMV infection.

One major risk for recipients undergoing allogeneic hematopoietic stem cell transplants (allo-HSCTs) is infection with the human cytomegalovirus (HCMV). For HCMV treatment, it is especially crucial to be able to differentiate between recipients who are at high risk of reactivation and those who are not. In this study, HCMV-DNA was collected from 60 HLA-A*02 allo-HSCT recipients before and after transplantation. After transplantation, the release of interferon (IFN)-γ by T cells specific to HCMV was assessed using the enzyme-linked immunospot assay (ELISPOT). The results show that the median viral load (VL) was significantly higher in the HCMV persistent-infection group compared to the non-persistent-infection group (p = 0.002), and that the late-infection rate was considerably higher in the high-VL group compared to the low-VL group (p = 0.014). The uninfected group had a considerably higher median IFN-γ spot-forming cell (SFC) count than the persistent-infection group (p = 0.001), and IFN-γ SFC counts correlated negatively and linearly with VLs (r = -0.397, p = 0.002). The immune-response groups showed significantly difference in median VL (p = 0.018), and the high immune response group had a reduced late-infection rate than the no/low immune response groups (p = 0.049). Our study showed that allo-HSCT recipients with a high VL at an early transplantation stage were at high risk for late HCMV infection. Further HCMV reactivation can be prevented by HCMV-specific T cells secreting enough IFN-γ.

Quantile difference estimation with censoring indicators missing at random.

In this paper, we define estimators of distribution functions when the data are right-censored and the censoring indicators are missing at random, and establish their strong representations and asymptotic normality. Besides, based on empirical likelihood method, we define maximum empirical likelihood estimators and smoothed log-empirical likelihood ratios of two-sample quantile difference in the presence and absence of auxiliary information, respectively, and prove their asymptotic distributions. Simulation study and real data analysis are conducted to investigate the finite sample behavior of the proposed methods.

Prospects of Cytomegalovirus-Specific T-Cell Receptors in Clinical Diagnosis and Therapy.

Human cytomegalovirus (HCMV) is responsible for widespread infections worldwide. In immunocompetent individuals it is typically latent, while infection or reactivation in immunocompromised individuals can result in severe clinical symptoms or even death. Although there has been significant progress in the treatment and diagnosis of HCMV infection in recent years, numerous shortcomings and developmental limitations persist. There is an urgent need to develop innovative, safe, and effective treatments, as well as to explore early and timely diagnostic strategies for HCMV infection. Cell-mediated immune responses are the primary factor controlling HCMV infection and replication, but the protective role of humoral immune responses remains controversial. T-cells, key effector cells of the cellular immune system, are critical for clearing and preventing HCMV infection. The T-cell receptor (TCR) lies at the heart of T-cell immune responses, and its diversity enables the immune system to differentiate between self and non-self. Given the significant influence of cellular immunity on human health and the indispensable role of the TCR in T-cell immune responses, we posit that the impact of TCR on the development of novel diagnostic and prognostic methods, as well as on patient monitoring and management of clinical HCMV infection, will be far-reaching and profound. High-throughput and single-cell sequencing technologies have facilitated unprecedented quantitative detection of TCR diversity. With these current sequencing technologies, researchers have already obtained a vast number of TCR sequences. It is plausible that in the near future studies on TCR repertoires will be instrumental in assessing vaccine efficacy, immunotherapeutic strategies, and the early diagnosis of HCMV infection.

Autonomous Robotic Ultrasound Vascular Imaging System With Decoupled Control Strategy for External-Vision-Free Environments.

OBJECTIVE: Ultrasound (US) probes scan over the surface of the human body to acquire US images in clinical vascular US diagnosis. However, due to the deformation and specificity of different human surfaces, the relationship between the scan trajectory of the skin and the internal tissues is not fully correlated, which poses a challenge for autonomous robotic US imaging in a dynamic and external-vision-free environment. Here, we propose a decoupled control strategy for autonomous robotic vascular US imaging in an environment without external vision. METHODS: The proposed system is divided into outer-loop posture control and inner-loop orientation control, which are separately determined by a deep learning (DL) agent and a reinforcement learning (RL) agent. First, we use a weakly supervised US vessel segmentation network to estimate the probe orientation. In the outer loop control, we use a force-guided reinforcement learning agent to maintain a specific angle between the US probe and the skin in the dynamic imaging processes. Finally, the orientation and the posture are integrated to complete the imaging process. RESULTS: Evaluation experiments on several volunteers showed that our RUS could autonomously perform vascular imaging in arms with different stiffness, curvature, and size without additional system adjustments. Furthermore, our system achieved reproducible imaging and reconstruction of dynamic targets without relying on vision-based surface information. CONCLUSION AND SIGNIFICANCE: Our system and control strategy provides a novel framework for the application of US robots in complex and external-vision-free environments.

Reactivation of occult hepatitis B virus infection in a renal transplant recipient.

We report a case of hepatitis B virus (HBV) reactivation in a renal transplant recipient. Reactivation manifested as an occult infection with detectable HBV-DNA and negativity for hepatitis B surface antigen (HBsAg). The anti-HBs antibody titre was above the protective threshold and continued to rise, to 951.36 mIU/ml, after HBV reactivation. Sequencing revealed multiple vaccine- and diagnostic-escape mutations in the major hydrophilic region of HBsAg. This case demonstrates both reactivation of an HBV escape mutant in a vaccinated patient and host immunity after virus mutation.

Spatiotemporal reconstruction method of carotid artery ultrasound from freehand sonography.

PURPOSE: 4D reconstruction based on radiation-free ultrasound can provide valuable information about the anatomy. Current 4D US technologies are either faced with limited field-of-view (FoV), technical complications, or cumbersome setups. This paper proposes a spatiotemporal US reconstruction framework to enhance its ability to provide dynamic structure information. METHODS: We propose a spatiotemporal US reconstruction framework based on freehand sonography. First, a collecting strategy is presented to acquire 2D US images in multiple spatial and temporal positions. A morphology-based phase extraction method after pose correction is presented to decouple the compounding image variations. For temporal alignment and reconstruction, a robust kernel regression model is established to reconstruct images in arbitrary phases. Finally, the spatiotemporal reconstruction is demonstrated in the form of 4D movies by integrating the US images according to the tracked poses and estimated phases. RESULTS: Quantitative and qualitative experiments were conducted on the carotid US to validate the feasibility of the proposed pipeline. The mean phase localization and heart rate estimation errors were 0.07 ± 0.04 s and 0.83 ± 3.35 bpm, respectively, compared with cardiac gating signals. The assessment of reconstruction quality showed a low RMSE (<0.06) between consecutive images. Quantitative comparisons of anatomy reconstruction from the generated US volumes and MRI showed an average surface distance of 0.39 ± 0.09 mm on the common carotid artery and 0.53 ± 0.05 mm with a landmark localization error of 0.60 ± 0.18 mm on carotid bifurcation. CONCLUSION: A novel spatiotemporal US reconstruction framework based on freehand sonography is proposed that preserves the utility nature of conventional freehand US. Evaluations on in vivo datasets indicated that our framework could achieve acceptable reconstruction performance and show potential application value in the US examination of dynamic anatomy.

Augmented reality navigation with ultrasound-assisted point cloud registration for percutaneous ablation of liver tumors.

PURPOSE: We present a novel augmented reality (AR) surgical navigation method with ultrasound-assisted point cloud registration for percutaneous ablation of liver tumors. A preliminary study is carried out to verify its feasibility. METHODS: Two three-dimensional (3D) point clouds of the liver surface are derived from the preoperative images and intraoperative tracked US images, respectively. To compensate for the soft tissue deformation, the point cloud registration between the preoperative images and the liver is performed using the non-rigid iterative closest point (ICP) algorithm. A 3D AR device based on integral videography technology is designed to accurately display naked-eye 3D images for surgical navigation. Based on the above registration, naked-eye 3D images of the liver surface, planning path, entry points, and tumor can be overlaid in situ through our 3D AR device. Finally, the AR-guided targeting accuracy is evaluated through entry point positioning. RESULTS: Experiments on both the liver phantom and in vitro pork liver were conducted. Several entry points on the liver surface were used to evaluate the targeting accuracy. The preliminary validation on the liver phantom showed average entry-point errors (EPEs) of 2.34 ± 0.45 mm, 2.25 ± 0.72 mm, 2.71 ± 0.82 mm, and 2.50 ± 1.11 mm at distinct US point cloud coverage rates of 100%, 75%, 50%, and 25%, respectively. The average EPEs of the deformed pork liver were 4.49 ± 1.88 mm and 5.02 ± 2.03 mm at the coverage rates of 100% and 75%, and the average covered-entry-point errors (CEPEs) were 4.96 ± 2.05 mm and 2.97 ± 1.37 mm at 50% and 25%, respectively. CONCLUSION: Experimental outcomes demonstrate that the proposed AR navigation method based on US-assisted point cloud registration has achieved an acceptable targeting accuracy on the liver surface even in the case of liver deformation.

An accurate 3D augmented reality navigation system with enhanced autostereoscopic display for oral and maxillofacial surgery.

BACKGROUND: Oral and maxillofacial surgery demands high precision navigation to achieve optimal surgical outcomes. Augmented reality (AR) has been a promising solution for intuitive and accurate guidance, whereas existing systems have room for improvement. METHODS: We propose a high quality and accurate in situ AR navigation system. Enhanced image quality is achieved by deploying eye tracking in lenticular-based autostereoscopic display. Viewpoint tracking and optical tracking are integrated to assure accurate in situ images. RESULTS: The proposed system can provide in situ AR images in real-time, with a viewing angle of 59.5° × 49.1°, 3D image resolution of 0.35 × 0.21 mm, and image accuracy of 0.99 ± 0.70 mm. A maxillary drilling experiment obtains average position error of 1.12 ± 0.30 mm and localization time of 8.7 ± 3.9 s, significantly better than conventional 2D navigation system. CONCLUSIONS: The proposed system can display high-quality AR images and therefore reduce positioning error and operating time.

ELISPOT assay of interferon-γ secretion for evaluating human cytomegalovirus reactivation risk in allo-HSCT recipients.

Human cytomegalovirus (HCMV) is a common cause of significant morbidity and mortality in transplant recipients after allogeneic hematopoietic stem cell transplantation (allo-HSCT). We evaluated interferon-γ (IFN-γ) secretion by HCMV NLV-specific CD8+ T cells in HCMV-reactivated allo-HSCT recipients using an enzyme-linked immunospot (ELISPOT) assay at 3 months post-transplantation. Blood samples from 47 recipients were tested for HCMV DNAemia, HCMV pp65 antigenemia, and anti-HCMV immunoglobulins (IgG/IgM) over 3 months post-transplantation. Of the 47 transplant recipients, 26 were HLA-A*02 positive and 21 were HLA-A*02 negative. The results were essentially consistent between the 47 transplant recipients and the HLA-A*02-positive recipients. HCMV DNAemia was not linearly correlated with IFN-γ spot-forming cells (SFCs) counts; IFN-γ SFCs counts did not differ significantly between the HCMV DNAemia-positive and -negative groups, whereas the HCMV-DNA virus loads were inversely correlated with the IFN-γ SFCs counts. HCMV pp65 antigenemia was not linearly correlated with IFN-γ SFCs counts; IFN-γ SFCs counts in the HCMV pp65 antigenemia-positive and -negative groups were similar. More IFN-γ SFCs counts were detected in transplant recipients with high anti-HCMV-IgG antibody titers than in those with low anti-HCMV-IgG titers pre-transplantation in the 47 recipients. Anti-HCMV-IgG antibody titers were positively linearly correlated with IFN-γ SFCs counts in HLA-A*02-positive recipients. The HCMV infection indicators used to monitor HCMV reactivation had different values in transplant recipients. The use of the IFN-γ SFCs counts measured by ELISPOT to evaluate the risk of HCMV reactivation needs further study.

Seroprevalence of AIH-related autoantibodies in patients with acute hepatitis E viral infection: a prospective case-control study in China.

The seroprevalenc of autoimmune hepatitis (AIH)-related antibodies in patients, particularly Asians, with acute hepatitis E (AHE) is unclear. In this study, we investigated whether acute hepatitis E virus (HEV) infection is associated with the seroprevalence of AIH-related autoantibodies and assessed their impact on the disease characteristics. AIH-related autoantibodies were detected by indirect immunofluorescence in 198 AHE patients and 50 type 1 AIH patients. The positivity rates of against nuclear antigen (ANA) and smooth muscles antibody (SMA) in AHE patients were 37.4% and 22.7%, and the total positivity rate was 50%. Compared to those in AIH patients, the positivity rates of ANA-H and SMA-AA were significantly lower (35.1% vs. 82.1% and 4.4% vs. 88.4%). Female gender and the ALT level, but not immunosuppressive or antiviral drugs, were independently predictive of the presence of AIH-related autoantibodies in AHE patients. Fifty-two patients positive for AIH-related autoantibodies were followed up for 12 months. During this period, 33 of them became negative and 19 remained positive, albeit with significantly decreased titres. In conclusions, the seroprevalence of AIH-related autoantibodies in AHE patients was elevated, particularly in females, but their subspecificities and titres differed from those of type 1 AIH. Acute HEV infection may be related to AIH.Abbreviations: AIH: autoimmune hepatitis; AHE: acute hepatitis E; ANA: against nuclear antigen; SMA: smooth muscles antibody; ANA-H: ANA with homogeneous pattern; SMA-AA: SMA with anti-actin pattern; Anti-LKM1: anti- liver-kidney microsomes-1 antibody; ANCA: anti-neutrophil cytoplasmic antibody; AMA: anti-mitochondrial antibody; Anti-SLA: anti-soluble liver antigen; Anti-LC1: anti-liver cytoplasmic type 1 antibody; pANCA: perinuclear antineutrophil cytoplasmic antibody.

Risk Factors Analysis for Human Cytomegalovirus Viremia in Donor+/Recipient+ Hematopoietic Stem Cell Transplantation.

OBJECTIVE: To assess the rate of, and risk factors for, human cytomegalovirus viremia (HCMV) in donor+/recipient+ (HCMV serostatus matched) hematopoietic stem-cell transplantation (HSCT) recipients. METHODS: HCMV DNA from 144 donor+/recipient+ HSCT recipients was examined by quantitative polymerase chain reaction (qPCR). RESULTS: The cumulative incidence of HCMV viremia was 69.4% (100/144) during the 48 weeks after HSCT. In a multivariate analysis, acute graft-versus-host disease (aGVHD) was discovered to be a risk factor for the occurrence of HCMV viremia (P = .006). The cumulative incidence of HCMV viremia and increasing DNA loads were significantly associated with aGVHD occurrence (P = .001 for each). The occurrence of late-term HCMV viremia was associated with aGVHD (P = .001) and a higher DNA load during the first 12 weeks after HSCT (P = .04). CONCLUSIONS: aGVHD is a risk factor for HCMV viremia. Recipients with aGVHD who have a high HCMV DNA load should be strictly monitored to prevent HCMV activation.

Relationship between T-cell receptor beta chain sequences and human cytomegalovirus infection in allogeneic hematopoietic stem cell transplant recipients.

In the present study, clonal amplifications of T-cell receptor ß variable (TCR BV) linked to human cytomegalovirus (HCMV) infection were detected in recipients of allogeneic hematopoietic stem cell transplants (HSCT), and certain relationships between them were identified. Furthermore, the relationship between TCR BV sequences and HCMV infections was investigated. The results indicated that the 3 recipients of HSCT had monoclonal expansion of specific TCR BV clones following HSCT. Among these recipients, 2 suffered from pp65 and immediate early (IE) antigenemia. These patients demonstrated preferential expansion of TCR BV9 (QVRGGTDTQ) and TCR BV11 (VATDFQ). The remaining recipient did not express TCR BV9 and TCR BV11, nor did this individual have pp65 and IE antigenemia. These results suggest that expression of TCR BV9 and TCR BV11 may be associated with HCMV antigenemia, and may be involved in the immune response. The amino acid sequences 'QVRGGTDTQ' and 'VATDFQ' may be involved in HCMV reactivation in patients who have undergone HSCT. Assessment of the TCR BV families may provide valuable insight into HCMV pathogenesis and may aid in the diagnosis and therapy for HSCT recipients infected with HCMV.

Herpesvirus infections in hematopoietic stem cell transplant recipients seropositive for human cytomegalovirus before transplantation.

BACKGROUND: Viral infections are a major cause of morbidity and mortality after hematopoietic stem cell transplantation (HSCT). The effect of herpesvirus infections in human cytomegalovirus (HCMV)-seropositive (IgG-positive/IgM-negative) HSCT recipients remains poorly understood. The risk factors associated with Epstein-Barr virus (EBV), HCMV, and human herpes virus type 6 (HHV-6) infections after HSCT, both alone and in combination, were investigated in this study. METHODS: Peripheral blood specimens were collected from 44 HSCT recipients and examined for viral DNA using quantitative fluorescence PCR assays. Risk factors for EBV, HCMV, and HHV-6 infections were analyzed by binary logistic regression, and relationships between these viruses were analyzed using the Chi-square test. RESULTS: EBV, HCMV, and HHV-6 were detected in 50%, 45.45%, and 25% of HCMV-seropositive (IgG-positive/IgM-negative) HSCT recipients, respectively. Male sex (p=0.007) and conditioning regimens including anti-thymocyte globulin (ATG) (p=0.034) were strongly associated with an increased risk of EBV infection. Graft-versus-host disease (GVHD) prophylaxis with corticosteroids was a risk factor for both EBV (p=0.013) and HCMV (p=0.040) infections, while EBV infection (p=0.029) was found to be an independent risk factor for HHV-6 infection. Pre-existing HHV-6 infection was associated with lower rates of HCMV infection (p=0.002); similarly, pre-existing HCMV infection was protective against HHV-6 infection (p=0.036). CONCLUSIONS: HCMV-seropositive (IgG-positive/IgM-negative) HSCT recipients exhibited a high rate of herpesvirus infections, particularly EBV. ATG and male sex were strongly associated with an increased risk of EBV infection. GVHD prophylaxis with prednisone was found to affect both EBV and HCMV infections. Prior infection with EBV was shown to promote HHV-6 infection. Taken together, these data highlight the need for active monitoring of herpesvirus infections in patients undergoing HSCT.

[T cell receptor ß-chain CDR3 spectratyping and cytomegalovirus activation in allogeneic hematopoietic stem cell transplant recipients].

Objective: To explore the association between T-cell receptor beta variable (TCR BV) complementarity determining region 3 (CDR3) spectratyping and CMV activation in the recipients of allogeneic hematopoietic stem cell transplantation (HSCT). Methods: Fluorescence quantitative PCR melting curve analysis was used to sequence 24 TCR BV families in 7 HSCT recipients and 3 healthy controls. CMV-pp65 antigenemia was measured by immunohistochemical staining. Plasma IgM specific for CMV was identified using ELISA. Relationship between TCR BV families and CMV activation was statistically analyzed.Results: Twenty-four TCR BV families were expressed in 3 healthy controls, while TCR BV CDR3 sequencing results in 7 recipients turned out to be BV9, BV11, BV17, BV20 and so on. Amino acid sequence features were as follows:TCR BV9 contained "QVRGGTDTQ", TCR BV11 contained "VATDEQ" and "LGDEQ", TCR BV17 contained "IGQGNTEA", and TCR BV20 contained "VGLAANEQ". Five recipients suffered from pp65 antigenemia in 3 month after transplantation, and pp65-positive cells ranged from 2 to 15 per 5×104 white blood cells. Three recipients were CMV-IgM positive. No significant differences were found in TCR BV families between pp65-positive recipients and pp65-negative recipients (all P>0.05). But there was statistically significant difference in frequency of TCR BV11 between CMV-IgM negative recipients and CMV-IgM positive recipients (P<0.05).Conclusion: T cell immune response was characterized by special TCR BV CDR3 spectratyping in HSCT recipients, and TCR BV11 expression may be associated with CMV activation.

Preliminary exploration of HLA-A 1101-restricted human cytomegalovirus glycoprotein B-specific CD8⁺ T cells in allogeneic stem-cell transplant recipients.

T-cell responses directed against human cytomegalovirus (HCMV) glycoprotein B (gB) contribute to protective immunity against HCMV infection in both animal models and humans. However, the gB-specific human CD8(+) T cell responses remain poorly understood. gB antigen-specific CD8(+) T cells were stained with seven major histocompatibility complex (MHC)-peptide pentamers in 16 human leukocyte antigen (HLA)-A 1101-positive, HCMV-seropositive patients following hematopoietic stem cell transplantation (HSCT). Of these seven pentamers, the most frequent CD8(+) T-cell responses were directed against the gB332-340 peptide. These gB332-340-specific CD8(+) T cells were strongly associated with the presence of plasma HCMV immunoglobulin M in all HSCT recipients and exhibited a probable causal relationship with the level of pp65 antigenemia. Together, these data suggest a role for gB332-340-specific CD8(+) T cells in HCMV reactivation after HSCT. Furthermore, the pentamer assay may be valuable in detecting antigen-specific CD8(+) T cells.

Evaluation of human cytomegalovirus-specific CD8+ T-cells in allogeneic haematopoietic stem cell transplant recipients using pentamer and interferon-γ-enzyme-linked immunospot assays.

BACKGROUND: Reactivation of latent human cytomegalovirus (HCMV) is a frequent complication following allogeneic haematopoietic stem cell transplantation (HSCT). Evaluation of the quantity and function of HCMV-specific CD8+ T-cell responses after HSCT may play a crucial role in the prevention of HCMV reactivation. OBJECTIVES: To investigate the mechanism of HCMV-specific T-cell immune responses after HSCT in HCMV-specific CD8+ T cells. STUDY DESIGN: HCMV-specific CD8+ T cells were quantified using human leucocyte antigen (HLA) pentamer staining and functionally analysed by interferon-γ-enzyme-linked immunospot (IFN-γ-ELISPOT) assay with a pp65495-503 peptide in recipients four years after HSCT. RESULTS: The absolute number of pp65495-503-specific CD8+ T cells did not differ significantly (p>0.05) between samples with antigenaemia and those without antigenaemia given a mean of 54.5/µl and 40.5/µl, respectively, in 21 HLA-A* 0201 patients after HSCT. The level of pp65495-503-specific CD8+ T cells>20/µl of peripheral blood was maintained 90 days after transplantation. There was a significant difference in the spot count of IFN-γ-secreting T cells between samples with antigenaemia (mean, 507/2.5×10(5)PBMCs) and those without antigenaemia (mean, 216/2.5×10(5)PBMCs; p<0.05). CONCLUSION: pp65495-503-specific CD8+ T cells may not be sufficient to control HCMV reactivation in recipients after HSCT. However, the combination of pentamer and IFN-γ-ELISPOT assays may be valuable for evaluating HCMV-specific CD8+ T cells. Further studies on HCMV-specific T-cell immune responses continue to be performed for the prevention of persistent HCMV reactivation.