Single-dose replicating poxvirus vector-based RBD vaccine drives robust humoral and T cell immune response against SARS-CoV-2 infection

1. Download : Download high-res image (90KB)
2. Download : Download full-size image

     

Tumor-associated high endothelial venules mediate lymphocyte entry into tumors and predict response to PD-1 plus CTLA-4 combination immunotherapy

1. Download : Download high-res image (268KB)
2. Download : Download full-size image

     

Fungal mycobiome drives IL-33 secretion and type 2 immunity in pancreatic cancer

1. Download : Download high-res image (229KB)
2. Download : Download full-size image

     

Living with the financial consequences of cancer: A life course perspective

Abstract

Purpose

Financial hardship can be a major cause of distress among persons with cancer, resulting in chronic stress and impacting physical and emotional health. This paper provides an analysis of the lived experience of cancer patients’ financial hardship from diagnosis to post-treatment.     

RESIRT: A Phase 1 Study of Selective Internal Radiation Therapy Using Yttrium-90 Resin Microspheres in Patients With Primary Renal Cell Carcinoma

IntroductionSelective internal radiation therapy (SIRT) is a potential treatment of primary renal cell carcinoma (RCC) deemed unsuitable for conventional therapy. RESIRT is the first-in-human study to evaluate safety and feasibility of SIRT for primary RCC.Patients and MethodsPatients with RCC, unsuitable for, or who declined conventional therapy, were eligible. A single transfemoral micro-catheter administration of yttrium-90 (Y-90) resin microspheres (SIR-Spheres) was delivered super selectively via the renal artery to the tumour at intended radiation doses of 75, 100, 150, 200, 300 Gy and a final cohort with a procedural endpoint of “imminent stasis,” in a dose-escalation design. Post-SIRT follow-up was 12 months. Study endpoints included safety and toxicity 30-days and 12-months post-SIRT and tumour response (RECIST v1.1).ResultsIn total, 21 patients were enrolled, mean (SD) age was 75 (9.3) years, WHO performance status was 0 in 81%, 12 (57%) had stage 3 chronic kidney disease, and 7 (33%) had prior contralateral nephrectomy. Overall, 71% of patients completed 12 months of follow-up. Intended doses were delivered without any dose-limiting toxicity. Seventeen out of 21 (81%) patients experienced an adverse event (AE) from any cause within 30 days post-SIRT; all SIRT-related AEs were grade 1 to 2. Best overall tumour responses were partial response 1/21 (4.8%), stable disease 19/21 (90.5%) and progressive disease 1/21 (4.8%).ConclusionThis study demonstrated good tolerability of SIRT at all dose levels including “imminent stasis” in treating primary tumours in RCC patients otherwise unsuitable for conventional therapy. SIRT with Y-90 resin microspheres may be a feasible treatment option for RCC.     

Immunisation with the BCG and DTPw vaccines induces different programs of trained immunity in mice

In addition to providing pathogen-specific immunity, vaccines can also confer nonspecific effects (NSEs) on mortality and morbidity unrelated to the targeted disease. Immunisation with live vaccines, such as the BCG vaccine, has generally been associated with significantly reduced all-cause infant mortality. In contrast, some inactivated vaccines, such as the diphtheria, tetanus, whole-cell pertussis (DTPw) vaccine, have been controversially associated with increased all-cause mortality especially in female infants in high-mortality settings. The NSEs associated with BCG have been attributed, in part, to the induction of trained immunity, an epigenetic and metabolic reprograming of innate immune cells, increasing their responsiveness to subsequent microbial encounters. Whether non-live vaccines such as DTPw induce trained immunity is currently poorly understood. Here, we report that immunisation of mice with DTPw induced a unique program of trained immunity in comparison to BCG immunised mice. Altered monocyte and DC cytokine responses were evident in DTPw immunised mice even months after vaccination. Furthermore, splenic cDCs from DTPw immunised mice had altered chromatin accessibility at loci involved in immunity and metabolism, suggesting that these changes were epigenetically mediated. Interestingly, changing the order in which the BCG and DTPw vaccines were co-administered to mice altered subsequent trained immune responses. Given these differences in trained immunity, we also assessed whether administration of these vaccines altered susceptibility to sepsis in two different mouse models. Immunisation with either BCG or a DTPw-containing vaccine prior to the induction of sepsis did not significantly alter survival. Further studies are now needed to more fully investigate the potential consequences of DTPw induced trained immunity in different contexts and to assess whether other non-live vaccines also induce similar changes.     

血清胱抑素C和尿微量白蛋白联合检测在人类免疫缺陷病毒感染者肾功能损伤检测中的应用价值

目的评估血肌酐和尿常规的常规检测基础上联合血清胱抑素C和尿微量白蛋白检测在人类免疫缺陷病毒（HIV）感染者肾功能损伤检测中的应用价值。 方法以2019年2～5月于首都医科大学附属北京地坛医院感染一科住院的169例HIV感染者为研究对象，完善其尿常规、尿微量白蛋白、血肌酐、血清胱抑素C检测；分析尿蛋白及尿微量白蛋白的阳性检出率及其差异，血肌酐升高及血清胱抑素C升高的比例及其差异。计算应用替诺福韦酯（TDF）及合并丙型肝炎、高血压、糖尿病、肿瘤的肾功能损伤的相对危险度。 结果169例HIV感染者中尿常规示尿蛋白阳性者5例（3.0%），尿微量白蛋白升高者17例（10.1%），两者阳性检出率差异具有统计学意义（χ² = 5.9、P = 0.007）。血肌酐升高者10例（5.9%），血清胱抑素C升高者20例（11.8%），两者阳性检出率差异具有统计学意义（χ² = 3.0、P = 0.042）。在尿常规和血肌酐检测的基础上联合检测尿微量白蛋白和血清胱抑素C的总体阳性检出率为49例（30.0%）。CD4⁺ T淋巴细胞计数< 200个/μl与≥ 200个/μl组患者血清胱抑素C水平分别为0.94（0.83，1.05）mg/L、0.85（0.77，0.95）mg/L，差异具有统计学意义（Z =-3.02、P = 0.003）。应用TDF及合并丙型肝炎、高血压、糖尿病、肿瘤的肾功能损伤的相对危险度分别为1.1、1.5、1.9、2.2和1.4。 结论HIV感染者中，单纯以尿常规为依据评估有无蛋白尿，以血肌酐水平为依据评估肾小球滤过功能会低估肾功能损伤的患病率。在常规检测血肌酐和尿常规的基础上联合检测血清胱抑素C和尿微量白蛋白在提高HIV感染者肾功能损伤检出率方面具有重要的应用价值。低CD4⁺ T淋巴细胞计数、应用TDF及合并丙型肝炎、高血压、糖尿病、肿瘤均为肾功能损伤的危险因素。     

Acute toxicity of chlorpyrifos to the non-target organism Cnesterodon decemmaculatus

Chlorpyrifos is the most used insecticide in Argentina. Cnesterodon decemmaculatus is a widely distributed, endemic fish from Neotropical America. It attains high densities in the shallow water assemblages of Argentina and Brazil. The aim of this study was to assess the acute toxicity of chlorpyrifos to C. decemmaculatus. The mean 96-h LC₅₀ of three independent determinations was 105.3 (±?3.1) μg/L. Sublethal effects were observed. Swimming behavioral changes at each chlorpyrifos exposure concentration were reported. C. decemmaculatus represents a good model for ecotoxicological risk assessment.     

The effect of maternal antibodies on the cellular immune response after infant vaccination: A review

During the last few decades, maternal immunization as a strategy to protect young infants from infectious diseases has been increasingly recommended, yet some issues have emerged. Studies have shown that for several vaccines, such as live attenuated, toxoid and conjugated vaccines, high maternal antibody titers inhibit the infant’s humoral immune response after infant vaccination. However, it is not clear whether this decreased antibody titer has any clinical impact on the infant’s protection, as the cellular immune responses are often equally important in providing disease protection and may therefore compensate for diminished antibody levels. Reports describing the effect of maternal antibodies on the cellular immune response after infant vaccination are scarce, probably because such studies are expensive, labor intensive and utilize poorly standardized laboratory techniques. Therefore, this review aims to shed light on what is currently known about the cellular immune responses after infant vaccination in the presence of high (maternal) antibody titers both in animal and human studies. Overall, the findings suggest that maternally derived antibodies do not interfere with the cellular immune responses after infant vaccination. However, more research in humans is clearly needed, as most data originate from animal studies.