Risk-based cost-benefit analysis of alternative vaccines against COVID-19 in Brazil: Coronavac vs. Astrazeneca vs. Pfizer

We propose a probabilistic model to quantify the cost-benefit of mass Vaccination Scenarios (VSs) against COVID-19. Through this approach, we conduct a six-month simulation, from August 31st, 2021 to March 3rd, 2022, of nine VSs, i.e., the three primary vaccine brands in Brazil (CoronaVac, AstraZeneca and Pfizer), each with three different vaccination rates (2nd doses per week). Since each vaccine has different individual-level effectiveness, we measure the population-level benefit as the probability of reaching herd immunity (HI). We quantify and categorize the cost-benefit of VSs through risk graphs that show: (i) monetary cost vs. probability of reaching HI; and (ii) number of new deaths vs. probability of reaching HI. Results show that AstraZeneca has the best cost-benefit when prioritizing acquisition costs, while Pfizer is the most cost-beneficial when prioritizing the number of deaths. This work provides helpful information that can aid public health authorities in Brazil to better plan VSs. Furthermore, our approach is not restricted to Brazil, the COVID-19 pandemic, or the mentioned vaccine brands. Indeed, the method is flexible so that this study can be a valuable reference for future cost-benefit analyses in other countries and pandemics, especially in the early stages of vaccination, when data is scarce and uncertainty is high.     

Vaccine effectiveness against onward transmission of SARS-CoV2-infection by variant of concern and time since vaccination,Belgian contact tracing, 2021

BackgroundDuring the first half of 2021, we observed high vaccine effectiveness (VE) against SARS-CoV2-infection. The replacement of the alpha-‘variant of concern’ (VOC) by the delta-VOC and uncertainty about the time course of immunity called for a re-assessment.MethodsWe estimated VE against transmission of infection (VET) from Belgian contact tracing data for high-risk exposure contacts between 26/01/2021 and 14/12/2021 by susceptibility (VEs) and infectiousness of breakthrough cases (VEi) for a complete schedule of Ad26.COV2.S, ChAdOx1, BNT162b2, mRNA-1273 as well as infection-acquired and hybrid immunity. We used a multilevel Bayesian model and adjusted for personal characteristics (age, sex, household), background exposure, calendar week, VOC and time since immunity conferring-event.FindingsVET-estimates were higher for mRNA-vaccines, over 90%, compared to viral vector vaccines: 66% and 80% for Ad26COV2.S and ChAdOx1 respectively (Alpha, 0–50 days after vaccination). Delta was associated with a 40% increase in odds of transmission and a decrease of VEs (72–64%) and especially of VEi (71–46% for BNT162b2). Infection-acquired and hybrid immunity were less affected by Delta. Waning further reduced VET-estimates: from 81% to 63% for BNT162b2 (Delta, 150–200 days after vaccination). We observed lower initial VEi in the age group 65–84 years (32% vs 46% in the age group 45–64 years for BNT162b2) and faster waning. Hybrid immunity waned slower than vaccine-induced immunity.InterpretationVEi and VEs-estimates, while remaining significant, were reduced by Delta and waned over time. We observed faster waning in the oldest age group. We should seek to improve vaccine-induced protection in older persons and those vaccinated with viral-vector vaccines.     

医学影像纹理分析在软组织肿瘤中的研究进展

近年来凭借大数据及深度学习使得以纹理分析(Texture Analysis)为代表的影像组学迅猛发展。随着纹理分析方法及影像新技术的不断研发应用,近年来纹理分析被越来越多的应用于临床研究,为疾病、尤其是肿瘤的诊断、分级与疗效预测评估提供有价值的医学影像依据。本文总结了纹理分析的常用方法、流程,并对软组织肿瘤的研究现况进行调查,作一综述。     

刺果甘草全基因组Survey及叶绿体基因组特征分析＊

目的 基于基因组Survey分析对刺果甘草Glycyrrhiza pallidiflora Maxim.基因组大小和杂合率进行估计，并通过叶绿体基因组序列特征对其在甘草属Glycyrrhiza L.中的系统发育位置进行研究。方法 使用二代测序技术对刺果甘草进行测序，采用K-mer方法对测序reads进行分析，估算刺果甘草基因组大小和杂合率，使用生物信息学方法进行叶绿体基因组组装、注释和系统发育分析。结果 Survey分析结果显示其基因组大小约为577.82 Mb，杂合度约为0.31%，重复序列比例约为53.72%。叶绿体基因组长度为127，267 bp，不具有典型的四分体结构，总GC含量为34.32%，包含110个基因，其中76个蛋白质编码基因，30个tRNA基因和4个rRNA基因。系统发育分析表明，刺果甘草与圆果甘草G. squamulosa Franch.亲缘较接近。结论 刺果甘草存在低杂合和重复序列较多的特点，为了更好地对全基因组进行序列拼接和组装，可尝试采用三代测序结合二代测序的分析策略进行基因组组装；刺果甘草叶绿体全基因组比对和系统发育分析，为后续开展甘草属遗传多样性研究和分子鉴定标记筛选提供了重要依据。     

基于Oncomine数据库分析分泌性磷蛋白1在肝细胞癌中的表达及临床意义

目的分析分泌性磷蛋白1(SPP1)在肝细胞癌中的表达,探索其对肝癌患者预后的影响。方法基于Oncomine数据库,对肝细胞癌中的SPP1差异表达情况进行分析,探讨其意义;利用Kaplan Meier-Plotter在线分析工具,对患者生存情况进行分析;基于String数据库在线构建蛋白互作网络。结果在筛选到的4项研究中,肝癌组SPP1基因的表达分别为4.92±0.24,0.35±0.30,-0.92±0.29和5.12±0.50,与相应正常组表达量1.96±0.28,-1.23±0.06,-2.93±0.13和1.89±0.31相比较均显著增高,差异均有统计学意义(均P <0.001);SPP1高表达组患者诊断后总体中位生存期为37.8个月,较SPP1低表达组(84.4个月)明显降低,差异有统计学意义(P <0.001);在男性(41.0个月vs 84.7个月)、亚洲人群(7.2个月vs 56.2个月)、GradeⅢ级(5.7个月vs23.7个月)或未感染肝炎病毒患者(25.2个月vs 70.5个月)亚组中的总体生存期均显著下降(错误发现率<5%,P <0.001)。透明质酸受体、整合素β1、基质金属蛋白酶7、金属蛋白酶组织抑制因子1、白细胞介素6和纤维连接蛋白1等是显著的节点基因。结论 SPP1与肝细胞癌进展显著相关,高SPP1表达与HCC患者的不良存活密切相关。     

Four cases of sodium nitrite suicidal ingestion: A new trend and a relevant Forensic Pathology and Toxicology challenge

Sodium nitrite (NaNO₂) is an inorganic compound commonly used as a food additive, antifreeze admixture, and fertilizer. Its toxicity mechanism is mainly represented by the oxidation of ferrous iron to ferric iron of one of the four heme structures in haemoglobin with the onset of methaemoglobin. The mechanism of death by sodium nitrite toxicity is severe hypoxia. We present four cases of suicidal sodium nitrite ingestion that closely occurred within a two months-period. Self-poisoning with sodium nitrite actually represents an increasing trend in nitrates’ related deaths. In order to reach a precise diagnosis of NaNO₂ intoxication, a complete toxicological analysis should be carried out including not only MetHb blood levels but also nitrites and nitrites in standard or alternative matrices as a routine procedure. Autopsy should be carefully performed to detect common indicators of hypoxia or more rarely evident typical by themselves-non specific signs of sodium nitrite toxicity. Suicidal manner of death should be carefully considered when circumstantial data support that ingestion of large amounts of NaNO₂ occurred as a consequence of a self-injurious behaviour. Relevant informations include victim’s previous Internet or book researches about paths to follow to commit suicide with sodium nitrate, employment and past medical history, with strong regard to psychiatric diseases as well as eventual taking psycotropic drugs.Finally, an accurate integration of autoptic and toxicological results with circumstantial data is necessary to make correct diagnosis of death due to acute respiratory failure secondary to suicidal sodium nitrite ingestion.     

黄花蒿Dof基因家族鉴定及在GA-UV处理下对青蒿素生物合成的影响＊

目的 Dof（DNA binding with one finger）家族是高等植物中特有的一类转录因子家族，参与植物中光、激素、非生物胁迫等多种胁迫响应调控。本研究基于全基因组数据对黄花蒿Dof（AaDof）转录因子家族进行鉴定及表达模式分析，探究Dof家族基因在青蒿素合成调控中的作用。方法 经PFAM数据库鉴定获得AaDof序列，通过生物信息学软件分析其理化性质、亚细胞定位、基因结构、蛋白保守结构以及启动子序列结合元件等，并基于赤霉素（Gibberellic acid， GA）、紫外线B（UV-B）及二者协同胁迫下黄花蒿转录组数据对其表达模式进行分析。结果 本研究从全基因组水平共鉴定出51个AaDof基因，均含有保守的C₂-C₂单锌指结构，依据系统发育分析分为8个亚族，同一亚族内基因结构与蛋白保守结构域相对保守。亚细胞定位预测显示12个AaDof蛋白定位在细胞外，其余均定位在细胞核。启动子元件分析发现AaDof家族基因启动子区富含光、激素等多种响应元件。对AaDof在GA、UV-B和GA+UV-B处理下的表达模式分析发现，AaDof基因对GA胁迫处理响应较弱，仅有少量基因敏感，其表达主要受到UV-B胁迫影响。C1及C2.1亚族大部分基因在UV-B胁迫下上调表达，而A亚族大部分基因在UV-B胁迫下下调表达。qRT-PCR验证表明AaDof1、AaDof17和AaDof44在GA和UV-B处理下表达量显著上调，推测其可能通过参与GA和UV-B调控网络，正向调控青蒿素生物合成。结论 本研究系统鉴定了黄花蒿AaDof家族基因并筛选了3个可能正向调控青蒿素生物合成的候选AaDof基因，为黄花蒿Dof家族基因功能研究及其在青蒿素生物合成中的调控机制解析奠定基础。     

Cost-effectiveness frameworks for comparing genome and exome sequencing versus conventional diagnostic pathways: A scoping review and recommended methods

PurposeMethodological challenges have limited economic evaluations of genome sequencing (GS) and exome sequencing (ES). Our objective was to develop conceptual frameworks for model-based cost-effectiveness analyses (CEAs) of diagnostic GS/ES.MethodsWe conducted a scoping review of economic analyses to develop and iterate with experts a set of conceptual CEA frameworks for GS/ES for prenatal testing, early diagnosis in pediatrics, diagnosis of delayed-onset disorders in pediatrics, genetic testing in cancer, screening of newborns, and general population screening.ResultsReflecting on 57 studies meeting inclusion criteria, we recommend the following considerations for each clinical scenario. For prenatal testing, performing comparative analyses of costs of ES strategies and postpartum care, as well as genetic diagnoses and pregnancy outcomes. For early diagnosis in pediatrics, modeling quality-adjusted life years (QALYs) and costs over ≥20 years for rapid turnaround GS/ES. For hereditary cancer syndrome testing, modeling cumulative costs and QALYs for the individual tested and first/second/third-degree relatives. For tumor profiling, not restricting to treatment uptake or response and including QALYs and costs of downstream outcomes. For screening, modeling lifetime costs and QALYs and considering consequences of low penetrance and GS/ES reanalysis.ConclusionOur frameworks can guide the design of model-based CEAs and ultimately foster robust evidence for the economic value of GS/ES.     

Effect of orbital wall resection areas in the treatment of patients with endocrine orbitopathy

In patients treated by orbital wall decompression for endocrine orbitopathy (EO) there is limited evidence on the effect of orbital wall resections. Thus, the aim of this study was to evaluate the effect of one, two, and three-wall resections on orbital parameters to determine if any such correlations exist. Preoperative and postoperative data from all patients at a tertiary care centre who underwent decompression surgery from 2010 - 2020 were digitally analysed. The effect of the number and area of resected walls on orbital area, orbital volume, and Hertel value, and the effect of lateral rim advancement (LARA) were determined. A total of 131 orbital areas showed an increase from a mean (SD) preoperative area of 42.0 (4.6) cm² to 47.3 (6.1) cm² postoperatively (p<0.001). In total, the mean (SD) area of osseous wall removed in all patients was 6.2 (1.7) cm² at the lateral orbit (n = 129), 6.7 (2.3) cm² at the orbital floor (n = 123), and 5.8 (1.8) cm² at the medial orbital wall (n =30). The mean (SD) orbital volume increased by 6.0 (3.0) cm³ after decompression. There was also a significant reduction in exophthalmos of 7.3 (3.2) mm (from 25.2 (3.9) to 17.9 (3.5), p<0.001). LARA was performed in 50 patients. Changes in volume and area, and reduction in exophthalmos were not significantly different with or without LARA. The postoperative effects of orbital wall resection are predictable and exhibit a relation with six units of change. Two-wall resection is the most common intervention.