Baseline neutrophil-lymphocyte ratio and platelet-lymphocyte ratio appear predictive of immune treatment related toxicity in hepatocellular carcinoma

BACKGROUND A well-recognized class effect of immune checkpoint inhibitors(ICI)is immune-related adverse events(IrAEs)ranging from low grade toxicities to life-threatening end organ damage requiring permanent discontinuation of ICI.Deaths are reported in<5%of patients treated with ICI.There are,however,no reliable markers to predict the onset and severity of IrAEs.We tested the association between neutrophil-lymphocyte ratio(NLR)and platelet-lymphocyte ratio(PLR)at baseline with development of clinically significant IrAEs(grade≥2)in hepatocellular carcinoma(HCC)patients treated with ICI.AIM To test the association between NLR and PLR at baseline with development of clinically significant IrAEs(grade≥2)in HCC patients treated with ICI.METHODS Data was extracted from an international database from a consortium of 11 tertiary-care referral centers.NLR=absolute neutrophil count/absolute lymphocyte count(ALC)and PLR=platelet count/ALC.Cutoff of 5 was used for NLR and 300 for PLR based on literature.We also tested the association between RESULTS Data was collected from 361 patients treated between 2016-2020 across the United States(67%),Asia(14%)and Europe(19%).Most patients received Nivolumab(n=255,71%).One hundred sixty-seven(46%)patients developed at least one IrAE,highest grade 1 in 80(48%),grade≥2 in 87(52%)patients.In a univariable regression model PLR>300 was significantly associated with a lower incidence of grade≥2 IrAEs(OR=0.40;P=0.044).Similarly,a trend was observed between NLR>5 and lower incidence of grade≥2 IrAEs(OR=0.58;P=0.097).Multivariate analyses confirmed PLR>300 as an independent predictive marker of grade≥2 IrAEs(OR=0.26;P=0.011),in addition to treatment with programmed cell death ligand 1(PD-1)/cytotoxic T lymphocyte-associated protein-4(OR=2.57;P=0.037)and PD-1/tyrosine kinase inhibitor(OR=3.39;P=0.01)combinations.Antibiotic use was not associated with IrAE incidence(OR=1.02;P=0.954).Patients treated with steroids had a>2-fold higher incidence of grade≥2 IrAEs(OR=2.74;P<0.001),although 74%were prescribed steroids for the treatment of IrAEs.CONCLUSION Given that high baseline NLR and PLR are associated with a decreased incidence of IrAEs,lower baseline NLR and PLR may be predictive biomarkers for the appearance of IrAEs in HCC treated with ICI.This finding is in keeping with several studies in solid tumors that have shown that baseline NLR and PLR appear predictive of IrAEs.

Chemically modified carbon-based electrodes for the determination of paracetamol in drugs and biological samples

Paracetamol is a non-steroidal, anti-inflammatory drug widely used in pharmaceutical applications for its sturdy, antipyretic and analgesic action. However, an overdose of paracetamol can cause fulminant hepatic necrosis and other toxic effects. Thus, the development of advantageous analytical tools to detect and determine paracetamol is required. Due to simplicity, higher sensitivity and selectivity as well as costefficiency, electrochemical sensors were fully investigated in last decades. This review describes the advancements made in the development of electrochemical sensors for the paracetamol detection and quantification in pharmaceutical and biological samples. The progress made in electrochemical sensors for the selective detection of paracetamol in the last 10 years was examined, with a special focus on highly innovative features introduced by nanotechnology. As the literature is rather extensive, we tried to simplify this work by summarizing and grouping electrochemical sensors according to the by which manner their substrates were chemically modified and the analytical performances obtained.

Examining heterogeneity of stromal cells in tumor microenvironment based on pan-cancer single-cell RNA sequencing data

Tumor tissues contain both tumor and non-tumor cells,which include infiltrated immune cells and stromal cells,collectively called the tumor microenvironment(TME).Single-cell RNA sequencing(sc RNAseq)enables the examination of heterogeneity of tumor cells and TME.In this review,we examined sc RNAseq datasets for multiple cancer types and evaluated the heterogeneity of major cell type composition in different cancer types.We further showed that endothelial cells and fibroblasts/myofibroblasts in different cancer types can be classified into common subtypes,and the subtype composition is clearly associated with cancer characteristic and therapy response.

Assessing the Influence of Climate Extremes on Ecosystems and Human Health in Southwestern Amazon Supported by the PULSE-Brazil Platform

The complexity of multi-dimensional climate, environmental and human health information complicates bringing together scientists, civil society, and decision makers to provide adequate mitigation and adaptation options for the consequences of global environmental change. To provide an effective pathway to conciliate (integrate) these datasets, we present PULSE-Brazil as the Platform for Understanding Long-term Sustainability of Ecosystems and human health. The overarching aim of this paper is to focus on two study cases in the Brazilian state of Acre, 1) analyzing recent socio-environmental disasters such as the impacts of droughts and consequent increases in fire detections on the incidence of respiratory diseases, and 2) evaluating the impacts of temperature increases in combination with rainfall seasonality upon the incidence of Dengue fever. Based on data available in PULSE-Brazil platform, we also aim to provide insights on the consequences of future climate variability on ecosystems and human health. Finally, we provide a discussion on the collaborative process between scientists and policymakers that defined the PULSE-Brazil platform specifications and datasets and propose a conceptual pathway for promoting the interaction between science and policy during the process of producing a tool that allows the understating of climate-relate processes. Our results clearly demonstrated that ecosystems are under increased fire risk in the future that will, in turn, affect the health of human populations. Moreover, humans are also exposed to critical Dengue fever outbreaks with the projected increase in minimum temperatures. Therefore, minimizing the impacts of these potentially ascending socio-environmental problems is the first step for adapting to a changing climate in the Amazon region. We expect that PULSE-Brazil will serve not only as a technical tool for supporting governance, management, mitigation and long-term adaptation plans for climate impacts and natural disasters, but also will take advantage of its graphical capabilities to be an instructive vehicle that facilitates information flow for societal governance.

飞行时间图像传感器的建模和运动误差分析

在动态场景中,飞行时间图像传感器的高频多相操作会产生运动模糊,使运动区域内产生错误的三维原始数据,同时增加了电路设计难度。为了减小运动模糊的影响,本文对动态场景下飞行时间图像传感器进行建模。所建模型可以通过简单的参数设置快速完成传感器的参数设定,以仿真动态场景中各条件下的三维图像,从而分析运动误差。本文基于该成像模型,在不同的运动速度和帧频下分析了运动误差对成像质量的影响,探究了动态场景中两种曝光方式之间的成像质量差异,获得了具有高成像质量和低电路设计难度的最优成像指标。采用德州仪器(TI)公司的飞行时间相机对成像模型进行了评估,结果表明,在静态和动态场景中,模型仿真数据与相机实测数据匹配良好。

Biomarkers for therapy selection in metastatic urothelial cancer

The treatment of metastatic urothelial cancer(mUC)has been transformed by recent progress in clinical trials and drug development.There are now three therapeutic classes with proven benefits in mUC:chemotherapy,immunotherapy,and targeted therapy.The optimal sequence and combination of these classes remain to be defined.Biomarker development is essential to guide treatment selection at each therapeutic juncture.Two biomarkers,programmed death-ligand 1 expression and fibroblast growth factor receptor alterations,have been incorporated into the mUC treatment paradigm thus far.This review discusses predictive biomarkers in development and their potential to influence mUC treatment selection moving forward.

优雅灰调

内敛、沉稳的灰色,表面上看似呆板、单调,但实际上它比黑色丰富,比白色深沉,少了些许凌厉与强烈,给人的视觉感受不至于过分冰冷或者强烈。表现力十足的灰色似东方水墨间的行云流水,有低吟浅唱般的含蓄,静水流深般的婉转,优雅从容的气度,让一切喧嚣归于平静。天性低调的灰色就像一位不露声色的女子,没有哗众取宠的举止,却在深深浅浅的变化调子中折射出不同的个性,并富有宽阔的搭配空间,无论是与亮色搭配,或是与柔和的过渡色彩融合,灰色仍旧能保持颜色的亮丽属性,在温和淡雅中突显一丝高贵,并且获得最大的感官享受。