Prevalence and prognosis of molecularly defined familial hypercholesterolemia in patients with acute coronary syndrome

BackgroundFamilial hypercholesterolemia (FH) can elevate serum low-density lipoprotein cholesterol (LDL-C) levels, which can promote the progression of acute coronary syndrome (ACS). However, the effect of FH on the prognosis of ACS remains unclear.MethodsIn this prospective cohort study, 223 patients with ACS having LDL-C ≥ 135.3 mg/dL (3.5 mmol/L) were enrolled and screened for FH using a multiple-gene FH panel. The diagnosis of FH was defined according to the ACMG/AMP criteria as carrying pathogenic or likely pathogenic variants. The clinical features of FH and the relationship of FH to the average 16.6-month risk of cardiovascular events (CVEs) were assessed.ResultsThe prevalence of molecularly defined FH in enrolled patients was 26.9%, and coronary artery lesions were more severe in patients with FH than in those without (Gensini score 66.0 vs. 28.0, respectively; P < 0.001). After lipid lowering, patients with FH still had significantly higher LDL-C levels at their last visit (73.5 ± 25.9 mg/dL vs. 84.7 ± 37.1 mg/dL; P = 0.013) compared with those without. FH increased the incidence of CVEs in patients with ACS [hazard ratio (HR): 3.058; 95% confidence interval (CI): 1.585–5.900; log-rank P < 0.001].ConclusionFH is associated with an increased risk of CVEs in ACS and is an independent risk factor for ACS. This study highlights the importance of genetic testing of FH-related gene mutations in patients with ACS

The Transcription Factor TCF1 Preserves the Effector Function of Exhausted CD8 T Cells During Chronic Viral Infection

The long-term persistence of viral antigens drives virus-specific CD8 T cell exhaustion during chronic viral infection. Yet exhausted, CD8 T cells are still endowed with certain levels of effector function, by which they can keep viral replication in check in chronic infection. However, the regulatory factors involved in regulating the effector function of exhausted CD8 T cell are largely unknown. Using mouse model of chronic LCMV infection, we found that the deletion of transcription factor TCF-1 in LCMV-specific exhausted CD8 T cells led to the profound reduction in cytokine production and degranulation. Conversely, ectopic expression of TCF-1 or using agonist to activate TCF-1 activities promotes the effector function of exhausted CD8 T cells. Mechanistically, TCF-1 fuels the functionalities of exhausted CD8 T cells by promoting the expression of an array of key effector function-associated transcription regulators, including Foxo1, Zeb2, Id3, and Eomes. These results collectively indicate that targeting TCF-1 mediated transcriptional pathway may represent a promising immunotherapy strategy against chronic viral infections by reinvigorating the effector function of exhausted virus-specific CD8 T cells

A Network-Aware Virtual Machine Allocation in Cloud Datacenter

Part 2: Session 2: Cloud Resource ManagementInternational audienceIn a cloud computing environment, virtual machine allocation is an important task for providing infrastructure services. Generally, the datacenters, on which a cloud computing platform runs, are distributed over a wide area network. Therefore, communication cost should be taken into consideration when allocating VMs across servers of multiple datacenters. A network-aware VM allocation algorithm for cloud is developed. It tries to minimize the communication cost and latency between servers, with the number of VMs, VM configurations and communication bandwidths are satisfied to users. Specifically, a two-dimensional knapsack algorithm is applied to solve this problem. The algorithm is evaluated and compared with other ones through experiments, which shows satisfying results

The complete mitochondrial genome of Xylotrechus namanganensis (Coleoptera: Cerambycidae)

The complete mitochondrial genome of Xylotrechus namanganensis was sequenced. The genome size was 15,565 bp, which consists of 13 protein-encoding genes, 22 tRNA-encoding genes, 2 rRNA-encoding genes and 1D-loop control region. The base composition of mitogenome was biased toward A + T content, of which was 73.21%. The phylogenetic tree based on complete mitogenome sequences revealed that T. namanganensis had a closer relationship with X. grayii

Low-Illumination Image Enhancement in the Space Environment Based on the DC-WGAN Algorithm

Owing to insufficient illumination of the space station, the image information collected by the intelligent robot will be degraded, and it will not be able to accurately identify the tools required for the robot’s on-orbit maintenance. This situation increases the difficulty of the robot’s maintenance in a low-illumination environment. We proposes a novel enhancement method for images under low-illumination, namely, a deep learning algorithm based on the combination of deep convolutional and Wasserstein generative adversarial networks (DC-WGAN) in CIELAB color space. The original low-illuminance image is converted from the RGB space to the CIELAB color space which is relatively close to human vision, to accurately estimate the illumination image, and effectively reduce the effect of uneven illumination. DC-WGAN is applied to enhance the brightness component by increasing the width of the generation network to obtain more image features. Subsequently, the LAB is converted into RGB space to obtain the final enhanced image. The feasibility of the algorithm is verified by experiments on low-illuminance image under general, special, and actual conditions and comparing the experimental results with four commonly used algorithms. This study lays a technical foundation for robot target recognition and on-orbit maintenance in a space environment

Hyperprogression to camrelizumab in a patient with esophageal squamous cell carcinoma harboring EGFR kinase domain duplication

Background Previous studies have reported that the amplification of some genes, such as Murine Double Minute 2 or 4 and Epidermal Growth Factor Receptor (EGFR), may be related to hyperprogressive disease (HPD). Exploring somatic gene alterations might be an effective method to predict HPD. Herein we characterize the somatic alterations in a patient with esophageal squamous cell carcinoma (ESCC) who developed HPD to investigate the potential origins of HPD.Case presentation A man in his mid-40s was diagnosed with ESCC. After the failure of first-line treatment with cisplatin and docetaxel, the patient participated in a phase III randomized, open, multicenter clinical trial (CTR20170307) and subsequently received camrelizumab. After 4 weeks of immunotherapy, the tumor size increased by 79% compared with baseline imaging; the progressive pace was 2.5-fold higher than preimmunotherapy, and a new liver metastasis appeared. A rare EGFR exon 2–28 duplication was discovered in both preimmunotherapy and postimmunotherapy tumor tissues.Conclusion This is the first report on a patient with ESCC harboring rare EGFR kinase domain duplication in exons 2–28 and developing HPD in the process of camrelizumab treatment. This case suggested that EGFR kinase domain duplication might be associated with HPD. Administration of immune checkpoint inhibitor monotherapy in this subgroup of patients harboring EGFR kinase domain duplication should be performed with caution. These results need to be further confirmed in a larger cohort of patients

Intra-Articular Injection of Human Synovial Membrane-Derived Mesenchymal Stem Cells in Murine Collagen-Induced Arthritis: Assessment of Immunomodulatory Capacity In Vivo

The aim of this study was to evaluate the efficacy of human synovial membrane-derived MSCs (SM-MSCs) in murine collagen-induced arthritis (CIA). Male mice (age 7–9 weeks) were injected intra-articularly with SM-MSCs obtained from patients with osteoarthritis, on days 28, 32, and 38 after bovine type II collagen immunization. The efficacy of SM-MSCs in CIA was evaluated clinically and histologically. Cytokine profile analyses were performed by real-time polymerase chain reaction and multiplex analyses. Splenic helper T (Th) cell and regulatory B cell subsets were analyzed by flow cytometry. Intra-articular SM-MSC injection ameliorated the clinical and histological severity of arthritis. Decrease in tumor necrosis factor-α, interferon-γ, and interleukin- (IL-) 17A and increase in IL-10 production were observed after SM-MSC treatment. Flow cytometry showed that Th1 and Th17 cells decreased, whereas Th2, regulatory T (Treg), and PD-1+CXCR5+FoxP3+ follicular Treg cells increased in the spleens of SM-MSC-treated mice. Regulatory B cell analysis showed that CD21hiCD23hi transitional 2 cells, CD23lowCD21hi marginal zone cells, and CD19+CD5+CD1d+IL-10+ regulatory B cells increased following SM-MSC treatment. Our results demonstrated that SM-MSCs injected in inflamed joints in CIA had a therapeutic effect and could prevent arthritis development and suppress immune responses via immunoregulatory cell expansion