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Production and Characterization of Self-Assembled Virus-like Particles Comprising Capsid Proteins from Genotypes 3 and 4 Hepatitis E Virus (HEV) and Rabbit HEV Expressed in Escherichia coli 大肠杆菌中表达的由 3 型和 4 型戊型肝炎病毒(HEV)和兔 HEV 的囊膜蛋白组成的自组装病毒样颗粒的制备与表征
Pub Date : 2024-08-31 DOI: 10.3390/v16091400
Tominari Kobayashi, Masaharu Takahashi, Satoshi Ohta, Yu Hoshino, Kentaro Yamada, Suljid Jirintai, Putu Prathiwi Primadharsini, Shigeo Nagashima, Kazumoto Murata, Hiroaki Okamoto
The zoonotic transmission of hepatitis E virus (HEV) genotypes 3 (HEV-3) and 4 (HEV-4), and rabbit HEV (HEV-3ra) has been documented. Vaccination against HEV infection depends on the capsid (open reading frame 2, ORF2) protein, which is highly immunogenic and elicits effective virus-neutralizing antibodies. Escherichia coli (E. coli) is utilized as an effective system for producing HEV-like particles (VLPs). However, research on the production of ORF2 proteins from these HEV genotypes in E. coli to form VLPs has been modest. In this study, we constructed 21 recombinant plasmids expressing various N-terminally and C-terminally truncated HEV ORF2 proteins for HEV-3, HEV-3ra, and HEV-4 in E. coli. We successfully obtained nine HEV-3, two HEV-3ra, and ten HEV-4 ORF2 proteins, which were primarily localized in inclusion bodies. These proteins were solubilized in 4 M urea, filtered, and subjected to gel filtration. Results revealed that six HEV-3, one HEV-3ra, and two HEV-4 truncated proteins could assemble into VLPs. The purified VLPs displayed molecular weights ranging from 27.1 to 63.4 kDa and demonstrated high purity (74.7–95.3%), as assessed by bioanalyzer, with yields of 13.9–89.6 mg per 100 mL of TB medium. Immunoelectron microscopy confirmed the origin of these VLPs from HEV ORF2. Antigenicity testing indicated that these VLPs possess characteristic HEV antigenicity. Evaluation of immunogenicity in Balb/cAJcl mice revealed robust anti-HEV IgG responses, highlighting the potential of these VLPs as immunogens. These findings suggest that the generated HEV VLPs of different genotypes could serve as valuable tools for HEV research and vaccine development.
戊型肝炎病毒(HEV)基因型 3(HEV-3)和 4(HEV-4)以及兔 HEV(HEV-3ra)的人畜共患传播已有记录。针对 HEV 感染的疫苗接种依赖于荚膜(开放阅读框 2,ORF2)蛋白,该蛋白具有高度免疫原性,可激发有效的病毒中和抗体。大肠杆菌(E. coli)是生产 HEV 样颗粒(VLPs)的有效系统。然而,关于在大肠杆菌中生产这些 HEV 基因型的 ORF2 蛋白以形成 VLPs 的研究并不多。在本研究中,我们构建了 21 个重组质粒,在大肠杆菌中表达了 HEV-3、HEV-3ra 和 HEV-4 的各种 N 端和 C 端截短的 HEV ORF2 蛋白。我们成功获得了 9 个 HEV-3、2 个 HEV-3ra 和 10 个 HEV-4 ORF2 蛋白,它们主要定位于包涵体中。这些蛋白质在 4 M 尿素中溶解、过滤并进行凝胶过滤。结果显示,6 个 HEV-3、1 个 HEV-3ra 和 2 个 HEV-4 截短蛋白可以组装成 VLPs。纯化的 VLPs 分子量在 27.1 至 63.4 kDa 之间,经生物分析仪评估,纯度较高(74.7%-95.3%),每 100 mL 结核病培养基的产量为 13.9-89.6 mg。免疫电子显微镜证实这些 VLPs 来自 HEV ORF2。抗原性测试表明,这些 VLPs 具有典型的 HEV 抗原性。在 Balb/cAJcl 小鼠体内进行的免疫原性评估显示,这些 VLPs 具有很强的抗 HEV IgG 反应,突出了其作为免疫原的潜力。这些发现表明,生成的不同基因型的 HEV VLPs 可作为 HEV 研究和疫苗开发的宝贵工具。
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引用次数: 0
Outcomes of Corneal Transplantation for Herpetic Keratitis: A Narrative Review 角膜移植治疗疱疹性角膜炎的效果:叙述性综述
Pub Date : 2024-08-31 DOI: 10.3390/v16091403
Michele Nardella, Angeli Christy Yu, Massimo Busin, Roberta Rizzo, Giorgio Zauli
Herpes simplex virus (HSV) is one of the most common etiologic agents of corneal disease and a significant cause of corneal blindness worldwide. Although most cases can be successfully managed with medical therapy, HSV keratitis associated with visually significant stromal scarring often requires corneal transplantation for visual rehabilitation. While penetrating keratoplasty (PK) represented the traditional keratoplasty technique, the past few decades have seen a shift towards lamellar keratoplasty procedures, including deep anterior lamellar keratoplasty and mushroom keratoplasty. This paper describes the current surgical techniques and perioperative antiviral prophylaxis regimen for herpetic keratitis and reviews their postoperative clinical outcomes.
单纯疱疹病毒(HSV)是角膜疾病最常见的病原体之一,也是全球角膜失明的重要原因。虽然大多数病例可通过药物治疗成功控制,但伴有明显基质瘢痕的 HSV 角膜炎通常需要通过角膜移植来恢复视力。穿透性角膜移植术(PK)是传统的角膜移植技术,而在过去的几十年中,角膜移植术已转向板层角膜移植术,包括深前板层角膜移植术和蘑菇角膜移植术。本文介绍了目前治疗疱疹性角膜炎的手术技术和围手术期抗病毒预防方案,并回顾了其术后临床效果。
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引用次数: 0
Intra-Host Citrus Tristeza Virus Populations during Prolonged Infection Initiated by a Well-Defined Sequence Variant in Nicotiana benthamiana 在烟草中由定义明确的序列变异引发的长期感染期间宿主内柑橘赤霉病病毒的种群数量
Pub Date : 2024-08-30 DOI: 10.3390/v16091385
Tathiana Ferreira Sa Antunes, José C. Huguet-Tapia, Santiago F. Elena, Svetlana Y. Folimonova
Due to the error-prone nature of viral RNA-dependent RNA polymerases, the replication of RNA viruses results in a diversity of viral genomes harboring point mutations, deletions, insertions, and genome rearrangements. Citrus tristeza virus (CTV), a causal agent of diseases of economically important citrus species, shows intrinsic genetic stability. While the virus appears to have some mechanism that limits the accumulation of single-nucleotide variants, the production of defective viral genomes (DVGs) during virus infection has been reported for certain variants of CTV. The intra-host diversity generated during plant infection with variant T36 (CTV-T36) remains unclear. To address this, we analyzed the RNA species accumulated in the initially infected and systemic leaves of Nicotiana benthamiana plants inoculated with an infectious cDNA clone of CTV-T36, which warranted that infection was initiated by a known, well-defined sequence variant of the virus. CTV-T36 limited the accumulation of single-nucleotide mutants during infection. With that, four types of DVGs—deletions, insertions, and copy- and snap-backs—were found in all the samples, with deletions and insertions being the most common types. Hot-spots across the genome for DVG recombination and short direct sequence repeats suggest that sequence complementarity could mediate DVG formation. In conclusion, our study illustrates the formation of diverse DVGs during CTV-T36 infection. To the best of our knowledge, this is the first study that has analyzed the genetic variability and recombination of a well-defined sequence variant of CTV in an herbaceous host.
由于病毒 RNA 依赖性 RNA 聚合酶容易出错,RNA 病毒的复制导致病毒基因组的多样性,其中包含点突变、缺失、插入和基因组重排。柑橘三裂叶病毒(CTV)是柑橘类重要经济病害的病原体,具有内在的遗传稳定性。虽然该病毒似乎有某种机制限制单核苷酸变体的积累,但据报道,CTV 的某些变体在病毒感染过程中会产生有缺陷的病毒基因组(DVGs)。变体 T36(CTV-T36)在植物感染过程中产生的宿主内多样性仍不清楚。为了解决这个问题,我们分析了用 CTV-T36 的感染性 cDNA 克隆接种的烟草植物最初感染叶片和系统叶片中积累的 RNA 种类,这证明感染是由已知的、定义明确的病毒序列变体引发的。在感染过程中,CTV-T36 限制了单核苷酸突变体的积累。因此,在所有样本中都发现了四种类型的 DVG:缺失、插入、拷贝和快回,其中缺失和插入是最常见的类型。整个基因组中 DVG 重组和短直接序列重复的热点表明,序列互补性可能会介导 DVG 的形成。总之,我们的研究说明了在 CTV-T36 感染过程中形成了多种 DVG。据我们所知,这是第一项分析草本宿主中明确定义的 CTV 序列变体的遗传变异和重组的研究。
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引用次数: 0
Like a Rolling Stone? A Review on Spontaneous Clearance of Hepatitis C Virus Infection 像滚石一样?丙型肝炎病毒感染自发清除综述
Pub Date : 2024-08-30 DOI: 10.3390/v16091386
Piotr Rzymski, Michał Brzdęk, Krystyna Dobrowolska, Barbara Poniedziałek, Aleksandra Murawska-Ochab, Dorota Zarębska-Michaluk, Robert Flisiak
Elimination of hepatitis C virus (HCV) without the need for medical intervention, known as spontaneous clearance (SC), occurs at a significantly lower rate than in the case of hepatitis B virus infection and only in selected individuals, such as reportedly in Keith Richards, a guitarist of The Rolling Stones. The present paper provides an updated narrative review of the research devoted to the phenomenon in order to identify and discuss the demographic, lifestyle-related, clinical, viral genotype-related, and host genetic factors underpinning the SC occurrence. The body of evidence indicates that the likelihood of SC is decreased in older individuals, men, Black people, HIV-coinfected subjects, and intravenous drug and alcohol users. In turn, HBV coinfection and specific polymorphism of the genes encoding interferon lambda 3 (particularly at rs8099917) and interferon lambda 4 (particularly at rs12979860) and HLA genes increase the odds of SC. Numerous other host-specific genetic factors could be implicated in SC, but the evidence is limited only to certain ethnic groups and often does not account for confounding variables. SC of HCV infection is a complex process arising from a combination of various factors, though a genetic component may play a leading role in some cases. Understanding factors influencing the likelihood of this phenomenon justifies better surveillance of high-risk groups, decreasing health inequities in particular ethnic groups, and may guide the development of a prophylactic vaccine, which at present is not available, or novel therapeutic strategies. Further research is needed to elucidate the exact mechanisms underlying SC and to explore potential interventions that could enhance this natural antiviral response.
与乙型肝炎病毒感染相比,丙型肝炎病毒(HCV)在不需要医疗干预的情况下被清除(称为自发清除(SC))的比率要低得多,而且只发生在特定的人身上,例如据报道滚石乐队的吉他手基思-理查兹(Keith Richards)。本文对有关这一现象的研究进行了最新的叙述性综述,以确定并讨论导致自愈现象发生的人口统计学因素、生活方式相关因素、临床因素、病毒基因型相关因素和宿主遗传因素。大量证据表明,老年人、男性、黑人、HIV 共感染者以及静脉注射毒品和酗酒者发生 SC 的可能性较低。反过来,HBV 合并感染、编码λ干扰素 3(尤其是 rs8099917)和λ干扰素 4(尤其是 rs12979860)的基因以及 HLA 基因的特定多态性也会增加 SC 的发生几率。其他许多宿主特异性遗传因素也可能与 SC 有关,但这些证据仅限于某些种族群体,而且往往没有考虑混杂变量。HCV 感染的 SC 是一个复杂的过程,由多种因素共同作用产生,但遗传因素可能在某些病例中起主导作用。了解影响这一现象发生概率的因素有助于更好地监测高危人群,减少特定种族群体中的健康不平等现象,并可为开发预防性疫苗(目前尚无)或新型治疗策略提供指导。还需要进一步的研究来阐明 SC 的确切机制,并探索可增强这种自然抗病毒反应的潜在干预措施。
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引用次数: 0
Acute Chikungunya Virus Infection Triggers a Diverse Range of T Helper Lymphocyte Profiles 急性基孔肯雅病毒感染可诱发多种 T 辅助淋巴细胞特征
Pub Date : 2024-08-30 DOI: 10.3390/v16091387
Ramayana Morais de Medeiros Brito, Marília Farias de Melo, José Veríssimo Fernandes, Joanna Gardel Valverde, Paulo Marcos Matta Guedes, Josélio Maria Galvão de Araújo, Manuela Sales Lima Nascimento
Chikungunya virus (CHIKV) is an arbovirus causing acute febrile illness with severe joint pain, often leading to chronic arthralgia. This study investigated the adaptive immune responses during the early stages of symptomatic acute CHIKV infection, focusing on the transcription factors and cytokines linked to Th1, Th2, Th17, and Treg cells. Thirty-six individuals were enrolled: nine healthy controls and 27 CHIKV-positive patients confirmed by qRT-PCR. Blood samples were analyzed for the mRNA expression of transcription factors (Tbet, GATA3, FoxP3, STAT3, RORγt) and cytokines (IFN-γ, IL-4, IL-17, IL-22, TGF-β, IL-10). The results showed the significant upregulation of Tbet, GATA3, FoxP3, STAT3, and RORγt in CHIKV-positive patients, with RORγt displaying the highest increase. Correspondingly, cytokines IFN-γ, IL-4, IL-17, and IL-22 were upregulated, while TGF-β was downregulated. Principal component analysis (PCA) confirmed the distinct immune profiles between CHIKV-positive and healthy individuals. A correlation analysis indicated that higher Tbet expression correlated with a lower viral load, whereas FoxP3 and TGF-β were associated with higher viral loads. Our study sheds light on the intricate immune responses during acute CHIKV infection, characterized by a mixed Th1, Th2, Th17, and Treg response profile. These results emphasize the complex interplay between different adaptive immune responses and how they may contribute to the pathogenesis of Chikungunya fever.
基孔肯雅病毒(CHIKV)是一种虫媒病毒,可引起急性发热性疾病,并伴有严重的关节疼痛,通常会导致慢性关节痛。本研究调查了无症状急性基孔肯雅病毒感染早期的适应性免疫反应,重点是与 Th1、Th2、Th17 和 Treg 细胞相关的转录因子和细胞因子。研究人员共招募了 36 人:9 名健康对照组和 27 名经 qRT-PCR 确认为 CHIKV 阳性的患者。血液样本分析了转录因子(Tbet、GATA3、FoxP3、STAT3、RORγt)和细胞因子(IFN-γ、IL-4、IL-17、IL-22、TGF-β、IL-10)的 mRNA 表达。结果显示,在 CHIKV 阳性患者中,Tbet、GATA3、FoxP3、STAT3 和 RORγt 均明显上调,其中 RORγt 的上调幅度最大。相应地,细胞因子 IFN-γ、IL-4、IL-17 和 IL-22 上调,而 TGF-β 下调。主成分分析(PCA)证实,CHIKV 阳性者和健康人的免疫特征截然不同。相关分析表明,Tbet表达较高与病毒载量较低相关,而FoxP3和TGF-β则与病毒载量较高相关。我们的研究揭示了急性 CHIKV 感染期间错综复杂的免疫反应,其特点是 Th1、Th2、Th17 和 Treg 混合反应。这些结果强调了不同适应性免疫反应之间复杂的相互作用,以及它们可能如何促进基孔肯雅热的发病机制。
{"title":"Acute Chikungunya Virus Infection Triggers a Diverse Range of T Helper Lymphocyte Profiles","authors":"Ramayana Morais de Medeiros Brito, Marília Farias de Melo, José Veríssimo Fernandes, Joanna Gardel Valverde, Paulo Marcos Matta Guedes, Josélio Maria Galvão de Araújo, Manuela Sales Lima Nascimento","doi":"10.3390/v16091387","DOIUrl":"https://doi.org/10.3390/v16091387","url":null,"abstract":"Chikungunya virus (CHIKV) is an arbovirus causing acute febrile illness with severe joint pain, often leading to chronic arthralgia. This study investigated the adaptive immune responses during the early stages of symptomatic acute CHIKV infection, focusing on the transcription factors and cytokines linked to Th1, Th2, Th17, and Treg cells. Thirty-six individuals were enrolled: nine healthy controls and 27 CHIKV-positive patients confirmed by qRT-PCR. Blood samples were analyzed for the mRNA expression of transcription factors (Tbet, GATA3, FoxP3, STAT3, RORγt) and cytokines (IFN-γ, IL-4, IL-17, IL-22, TGF-β, IL-10). The results showed the significant upregulation of Tbet, GATA3, FoxP3, STAT3, and RORγt in CHIKV-positive patients, with RORγt displaying the highest increase. Correspondingly, cytokines IFN-γ, IL-4, IL-17, and IL-22 were upregulated, while TGF-β was downregulated. Principal component analysis (PCA) confirmed the distinct immune profiles between CHIKV-positive and healthy individuals. A correlation analysis indicated that higher Tbet expression correlated with a lower viral load, whereas FoxP3 and TGF-β were associated with higher viral loads. Our study sheds light on the intricate immune responses during acute CHIKV infection, characterized by a mixed Th1, Th2, Th17, and Treg response profile. These results emphasize the complex interplay between different adaptive immune responses and how they may contribute to the pathogenesis of Chikungunya fever.","PeriodicalId":501326,"journal":{"name":"Viruses","volume":"57 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142206996","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
The Dual Role of TRIM7 in Viral Infections TRIM7 在病毒感染中的双重作用
Pub Date : 2024-08-12 DOI: 10.3390/v16081285
Maria Gonzalez-Orozco, Carlos A. Rodriguez-Salazar, Maria I. Giraldo
The E3 ubiquitin ligase TRIM7 is known to have dual roles during viral infections. Like other TRIM proteins, TRIM7 can regulate the IFN pathway via the regulation of the cytosolic receptors RIG-I or MDA-5, which promote the production of type I interferons (IFN-I) and antiviral immune responses. Alternatively, under certain infectious conditions, TRIM7 can negatively regulate IFN-I signaling, resulting in increased virus replication. A growing body of evidence has also shown that TRIM7 can, in some cases, ubiquitinate viral proteins to promote viral replication and pathogenesis, while in other cases it can promote degradation of viral proteins through the proteasome, reducing virus infection. TRIM7 can also regulate the host inflammatory response and modulate the production of inflammatory cytokines, which can lead to detrimental inflammation. TRIM7 can also protect the host during infection by reducing cellular apoptosis. Here, we discuss the multiple functions of TRIM7 during viral infections and its potential as a therapeutic target.
已知E3泛素连接酶TRIM7在病毒感染过程中具有双重作用。与其他 TRIM 蛋白一样,TRIM7 可通过调节细胞膜受体 RIG-I 或 MDA-5 来调节 IFN 通路,从而促进 I 型干扰素(IFN-I)的产生和抗病毒免疫反应。另外,在某些感染条件下,TRIM7 还能负向调节 IFN-I 信号传导,导致病毒复制增加。越来越多的证据还表明,在某些情况下,TRIM7 可以泛素化病毒蛋白,促进病毒复制和致病,而在其他情况下,它可以通过蛋白酶体促进病毒蛋白降解,减少病毒感染。TRIM7 还能调节宿主的炎症反应,调节炎症细胞因子的产生,从而导致有害的炎症。TRIM7 还能在感染期间通过减少细胞凋亡来保护宿主。在此,我们将讨论 TRIM7 在病毒感染过程中的多种功能及其作为治疗靶点的潜力。
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引用次数: 0
A Comparative Evaluation of Three Diagnostic Assays for the Detection of Human Monkeypox 检测人类猴痘的三种诊断测定的比较评估
Pub Date : 2024-08-12 DOI: 10.3390/v16081286
Jing Qu, Xiaomin Zhang, Kun Liu, You Li, Ting Wang, Zhonggang Fang, Cheng Chen, Xiao Tan, Ying Lin, Qing Xu, Yan Yang, Wanqing Wang, Manyu Huang, Shiliang Guo, Ziqiu Chen, Wei Rao, Xiaolu Shi, Bo Peng
Accurate and early diagnosis of monkeypox virus (MPXV) is crucial for controlling epidemics and treating affected individuals promptly. This study aimed to assess the analytical and clinical performance of the MolecisionTM Monkeypox Virus qPCR Assay, Biorain Monkeypox Virus ddPCR Assay, and MAGLUMI® Monkeypox Virus Ag (chemiluminescence immunoassay, CLIA) Assay. Additionally, it aimed to compare the clinical application of antigen and nucleic acid assays to offer insights into using commercial monkeypox assay kits. Specimens from 117 clinical patients, serial diluted virus cell culture supernatant, and artificially created positive samples were tested to evaluate the performance of these assay kits for MPXV diagnostics. The Biorain Monkeypox Virus ddPCR Assay had a limit of detection (LoD) of 3.89 CCID50/mL, while the MolecisionTM Monkeypox Virus qPCR Assay had an LoD of 15.55 CCID50/mL. The MAGLUMI® Monkeypox Virus Ag (CLIA) Assay had an LoD of 0.500 pg/mL. The accuracy of the MolecisionTM Monkeypox Virus qPCR Assay was comparable to the Biorain Monkeypox Virus ddPCR Assay, and the MAGLUMI® Monkeypox Virus Ag (CLIA) Assay demonstrated high sensitivity. The specificity of all three MPXV diagnostic assays for clinical specimens with potential cross-reacting substances was 100%. In conclusion, this study provides valuable insights into the clinical application of monkeypox assays, supporting efforts to mitigate and control the spread of monkeypox.
猴痘病毒(MPXV)的早期准确诊断对于控制疫情和及时治疗患者至关重要。本研究旨在评估 MolecisionTM 猴痘病毒 qPCR 检测试剂盒、Biorain 猴痘病毒 ddPCR 检测试剂盒和 MAGLUMI® 猴痘病毒 Ag(化学发光免疫测定,CLIA)检测试剂盒的分析和临床性能。此外,该研究还旨在比较抗原和核酸检测法的临床应用,为使用商业猴痘检测试剂盒提供启示。对来自 117 名临床患者的标本、连续稀释的病毒细胞培养上清液和人工制造的阳性样本进行了测试,以评估这些用于 MPXV 诊断的检测试剂盒的性能。Biorain 猴痘病毒 ddPCR 检测试剂盒的检出限(LoD)为 3.89 CCID50/mL,而 MolecisionTM 猴痘病毒 qPCR 检测试剂盒的检出限(LoD)为 15.55 CCID50/mL。MAGLUMI® 猴痘病毒 Ag (CLIA) 检测试剂盒的 LoD 为 0.500 pg/mL。MolecisionTM 猴痘病毒 qPCR 检测试剂盒的准确度与 Biorain 猴痘病毒 ddPCR 检测试剂盒相当,而 MAGLUMI® 猴痘病毒 Ag (CLIA) 检测试剂盒则表现出较高的灵敏度。对于存在潜在交叉反应物质的临床样本,所有三种 MPXV 诊断测定的特异性均为 100%。总之,这项研究为猴痘检测方法的临床应用提供了宝贵的见解,有助于减轻和控制猴痘的传播。
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引用次数: 0
Outcomes of COVID-19 and Influenza in Cerebral Palsy Patients Hospitalized in the United States: Comparative Study of a Nationwide Database 美国住院脑瘫患者感染 COVID-19 和流感的结果:全国数据库比较研究
Pub Date : 2024-08-12 DOI: 10.3390/v16081284
Mohammed A. Quazi, Muhammad Hassan Shakir, Zohaa Faiz, Ibrahim Quraishi, Adeel Nasrullah, Hafiz Abdullah Ikram, Amir H Sohail, Sulaiman Sultan, Abu Baker Sheikh
Patients with cerebral palsy (CP) are particularly vulnerable to respiratory infections, yet comparative outcomes between COVID-19 and influenza in this population remain underexplored. Using the National Inpatient Sample from 2020–2021, we performed a retrospective analysis of hospital data for adults with CP diagnosed with either COVID-19 or influenza. The study aimed to compare the outcomes of these infections to provide insights into their impact on this vulnerable population. We assessed in-hospital mortality, complications, length of stay (LOS), hospitalization costs, and discharge dispositions. Multivariable logistic regression and propensity score matching were used to adjust for confounders, enhancing the analytical rigor of our study. The study cohort comprised 12,025 patients—10,560 with COVID-19 and 1465 with influenza. COVID-19 patients with CP had a higher in-hospital mortality rate (10.8% vs. 3.1%, p = 0.001), with an adjusted odds ratio of 3.2 (95% CI: 1.6–6.4). They also experienced an extended LOS by an average of 2.7 days. COVID-19 substantially increases the health burden for hospitalized CP patients compared to influenza, as evidenced by higher mortality rates, longer hospital stays, and increased costs. These findings highlight the urgent need for tailored strategies to effectively manage and reduce the impact of COVID-19 on this high-risk group.
脑性瘫痪(CP)患者特别容易受到呼吸道感染,但 COVID-19 和流感在这一人群中的比较结果仍未得到充分探讨。我们利用 2020-2021 年的全国住院患者样本,对确诊为 COVID-19 或流感的 CP 成人患者的住院数据进行了回顾性分析。该研究旨在比较这些感染的结果,以深入了解它们对这一弱势群体的影响。我们评估了院内死亡率、并发症、住院时间(LOS)、住院费用和出院处置。我们采用了多变量逻辑回归和倾向评分匹配来调整混杂因素,从而提高了研究分析的严谨性。研究队列包括 12025 名患者-10560 名 COVID-19 患者和 1465 名流感患者。COVID-19 CP 患者的院内死亡率较高(10.8% vs. 3.1%,p = 0.001),调整后的几率比为 3.2(95% CI:1.6-6.4)。他们的平均住院日也延长了 2.7 天。与流感相比,COVID-19 大大增加了住院 CP 患者的健康负担,表现为死亡率升高、住院时间延长和费用增加。这些研究结果突出表明,迫切需要制定有针对性的策略,以有效管理和减少 COVID-19 对这一高风险人群的影响。
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引用次数: 0
Forecasting Disease Burden with a Dynamic Transmission Model of Human Papillomavirus and Recurrent Respiratory Papillomatosis in the United States 利用美国人类乳头状瘤病毒和复发性呼吸道乳头状瘤病的动态传播模型预测疾病负担
Pub Date : 2024-08-11 DOI: 10.3390/v16081283
Cody Palmer, Edith Morais, Joseph Tota
Juvenile- and adult-onset recurrent respiratory papillomatosis (JORRP and AORRP) are rare but serious conditions that are caused by oral human papillomavirus (HPV) infections. The proliferation of wart-like growths throughout the respiratory tract can result in medical problems, including death. The current treatment scheme is surgery, though prevention of HPV infection through vaccination is available. A previously developed model for JORRP and AORRP was adapted to the United States using data on disease burden and HPV infection. The model was validated against post-vaccination reductions in disease and used to forecast the future burden of JORRP and AORRP, estimating the impact that HPV vaccination will have on these diseases. Between 2007 (the beginning of HPV vaccination in the US) and 2021, this model estimates that approximately 1393 lives, 22,867 Quality-Adjusted-Life-Years, and over USD 672 million in treatment costs have been saved by HPV vaccination. There is also a substantial reduction in JORRP and AORRP burden, with a 95% reduction in incidence by 2040. Moreover, between 2040 and 2121, the model predicts 3–11 total cases of HPV6/11-related JORRP in the US, and 36–267 total cases of HPV6/11-related AORRP. HPV vaccination in the United States has driven, and will continue to drive, substantial reductions in the public health and economic burden of HPV6/11-related JORRP and AORRP.
青少年和成人复发性呼吸道乳头状瘤病(JORRP 和 AORRP)是由口腔人类乳头状瘤病毒(HPV)感染引起的罕见但严重的疾病。疣状增生遍布整个呼吸道,可导致医疗问题,包括死亡。目前的治疗方案是手术,但可以通过接种疫苗来预防人乳头瘤病毒感染。利用疾病负担和人乳头瘤病毒感染的数据,对之前开发的 JORRP 和 AORRP 模型进行了调整,使其适用于美国。该模型根据接种疫苗后疾病的减少情况进行了验证,并用于预测 JORRP 和 AORRP 的未来负担,估计 HPV 疫苗接种对这些疾病的影响。据该模型估计,从 2007 年(美国开始接种 HPV 疫苗)到 2021 年,接种 HPV 疫苗可挽救约 1393 条生命、22867 个质量调整生命年以及超过 6.72 亿美元的治疗费用。此外,JORRP 和 AORRP 的负担也大幅降低,到 2040 年,发病率降低 95%。此外,根据模型预测,在 2040 年至 2121 年期间,美国与 HPV6/11 相关的 JORRP 总病例数为 3-11 例,与 HPV6/11 相关的 AORRP 总病例数为 36-267 例。美国的 HPV 疫苗接种已经并将继续推动大幅降低 HPV6/11 相关 JORRP 和 AORRP 的公共卫生和经济负担。
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引用次数: 0
A Bioinformatic Ecosystem for Bacteriophage Genomics: PhaMMSeqs, Phamerator, pdm_utils, PhagesDB, DEPhT, and PhamClust 噬菌体基因组学生物信息生态系统:PhaMMSeqs、Phamerator、pdm_utils、PhagesDB、DEPhT 和 PhamClust
Pub Date : 2024-08-10 DOI: 10.3390/v16081278
Christian H. Gauthier, Graham F. Hatfull
The last thirty years have seen a meteoric rise in the number of sequenced bacteriophage genomes, spurred on by both the rise and success of groups working to isolate and characterize phages, and the rapid and significant technological improvements and reduced costs associated with sequencing their genomes. Over the course of these decades, the tools used to glean evolutionary insights from these sequences have grown more complex and sophisticated, and we describe here the suite of computational and bioinformatic tools used extensively by the integrated research–education communities such as SEA-PHAGES and PHIRE, which are jointly responsible for 25% of all complete phage genomes in the RefSeq database. These tools are used to integrate and analyze phage genome data from different sources, for identification and precise extraction of prophages from bacterial genomes, computing “phamilies” of related genes, and displaying the complex nucleotide and amino acid level mosaicism of these genomes. While over 50,000 SEA-PHAGES students have primarily benefitted from these tools, they are freely available for the phage community at large.
在过去的三十年里,噬菌体基因组测序的数量急剧上升,这既得益于致力于分离和鉴定噬菌体的研究小组的崛起和成功,也得益于与噬菌体基因组测序相关的技术的飞速进步和成本的降低。在这几十年中,用于从这些序列中获取进化信息的工具变得越来越复杂和精密,我们在此介绍 SEA-PHAGES 和 PHIRE 等综合研究教育团体广泛使用的计算和生物信息学工具套件,它们共同负责 RefSeq 数据库中 25% 的完整噬菌体基因组。这些工具用于整合和分析不同来源的噬菌体基因组数据,从细菌基因组中识别和精确提取噬菌体,计算相关基因的 "噬菌体家族",并显示这些基因组复杂的核苷酸和氨基酸水平的镶嵌关系。SEA-PHAGES 的 50,000 多名学生主要受益于这些工具,而整个噬菌体社区也可以免费使用这些工具。
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Viruses
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