组学时代下机器学习方法在临床决策支持中的应用

随着组学技术的不断发展,对于不同层次和类型的生物数据的获取方法日益成熟。在疾病诊治过程中会产生大量数据,通过机器学习等人工智能方法解析复杂、多维、多尺度的疾病大数据,构建临床决策支持工具,辅助医生寻找快速且有效的疾病诊疗方案是非常必要的。在此过程中,机器学习等人工智能方法的选择显得尤为重要。基于此,本文首先从类型和算法角度对临床决策支持领域中常用的机器学习等方法进行简要综述,分别介绍了支持向量机、逻辑回归、聚类算法、Bagging、随机森林和深度学习,对机器学习等方法在临床决策支持中的应用做了相应总结和分类,并对它们的优势和不足分别进行讨论和阐述,为临床决策支持中机器学习等人工智能方法的选择提供有效参考。     

Naturally prion resistant mammals: A utopia?

Each known abnormal prion protein (PrP^Sc) is considered to have a specific range and therefore the ability to infect some species and not others. Consequently, some species have been assumed to be prion disease resistant as no successful natural or experimental challenge infections have been reported. This assumption suggested that, independent of the virulence of the PrP^Sc strain, normal prion protein (PrP^C) from these ‘resistant’ species could not be induced to misfold. Numerous in vitro and in vivo studies trying to corroborate the unique properties of PrP^Sc have been undertaken. The results presented in the article “Rabbits are not resistant to prion infection” demonstrated that normal rabbit PrP^C, which was considered to be resistant to prion disease, can be misfolded to PrP^Sc and subsequently used to infect and transmit a standard prion disease to leporids. Using the concept of species resistance to prion disease, we will discuss the mistake of attributing species specific prion disease resistance based purely on the absence of natural cases and incomplete in vivo challenges. The BSE epidemic was partially due to an underestimation of species barriers. To repeat this error would be unacceptable, especially if present knowledge and techniques can show a theoretical risk. Now that the myth of prion disease resistance has been refuted it is time to re-evaluate, using the new powerful tools available in modern prion laboratories, whether any other species could be at risk.     

Developing new hospital-at-home models based on Comprehensive Geriatric Assessment: Implementation recommendations by the Working Group on Hospital-at-Home and Community Geriatrics of the Catalan Society of Geriatrics and Gerontology

Last decade, the Government of Catalonia have urged an integrated care strategy for planning the care model to older populations living with frailty, multimorbidity and advanced illnesses. Based on international evidence that was reviewed by a group of experts from the Catalan Society of Gerontology and Geriatrics, we summarised some recommendation to adapt hospital-at-home care to older populations in our system. We defined Comprehensive Geriatric Assessment (CGA) hospital-at-home (HaH) as a specialised home hospitalisation service formed by interdisciplinary teams, characterised by using the clinical methodology of CGA, and by adapting geriatric units’ protocols for the provision of person-centred care at home. Main benefits of CGA-HaH in these populations are: response to heath crises according to individualised care plans based on the situational diagnosis carried out by Primary Care teams; provision of a comprehensive health and social approach tailored to the complexity of cases and situations; and adaptation of multipurpose hospitalisation, by working on different person-centred care, aspects, such as caregivers support on care provision, focusing on function or home adaptation.     

自身免疫性大疱病合并侵袭性肺曲霉病:3例报告

目的通过典型病例回顾探讨自身免疫性大疱病糖皮质激素治疗过程中合并肺曲霉病的诊断和治疗情况。方法报告3例自身免疫性大疱病合并侵袭性肺曲霉病病例。3例病例均行痰镜检、培养、抗原检测、胸部CT或者坏死组织病理检查。分离病原菌经形态学和分子生物学鉴定为烟曲霉、黄曲霉和刺孢裸胞壳。结果 3例病例证实为侵袭性肺曲霉病。进行以伏立康唑为主的综合治疗后均治愈。结论自身免疫性大疱病糖皮质激素治疗过程中应警惕肺曲霉病的发生。多种实验室检查可以帮助早期诊断,提高疗效。     

Acetylation changes tau interactome to degrade tau in Alzheimer’s disease animal and organoid models

Alzheimer's disease (AD) is an age‐related neurodegenerative disease. The most common pathological hallmarks are amyloid plaques and neurofibrillary tangles in the brain. In the brains of patients with AD, pathological tau is abnormally accumulated causing neuronal loss, synaptic dysfunction, and cognitive decline. We found a histone deacetylase 6 (HDAC6) inhibitor, CKD‐504, changed the tau interactome dramatically to degrade pathological tau not only in AD animal model (ADLP^APT) brains containing both amyloid plaques and neurofibrillary tangles but also in AD patient‐derived brain organoids. Acetylated tau recruited chaperone proteins such as Hsp40, Hsp70, and Hsp110, and this complex bound to novel tau E3 ligases including UBE2O and RNF14. This complex degraded pathological tau through proteasomal pathway. We also identified the responsible acetylation sites on tau. These dramatic tau‐interactome changes may result in tau degradation, leading to the recovery of synaptic pathology and cognitive decline in the ADLP^APT mice.     

复合型菌剂对雏鸡体内溶血素的影响

利用由鸡粪肠球菌、鸡非致病性大肠埃希菌、芽胞杆菌、酵母菌和乳酸菌组成的复合型菌剂灌喂雏鸡后,再用绵羊红细胞腹腔注射免疫4d,使雏鸡体内产生溶血素（IgM）。通过测定其血清中溶血素的效价,发现灌服不同菌量的雏鸡所产生的溶血素效价比没有灌服的对照组所产生的溶血素效价高出22％～32％。     

Virus diseases of farmed shrimp in the Western Hemisphere (the Americas): a review

Penaeid shrimp aquaculture is an important industry in the Americas, and the industry is based almost entirely on the culture of the Pacific White Shrimp, Litopenaeus vannamei. Western Hemisphere shrimp farmers in 14 countries in 2004 produced more than 200,000 metric tons of shrimp, generated more than $2 billion in revenue, and employed more than 500,000 people. Disease has had a major impact on shrimp aquaculture in the Americas since it became a significant commercial entity in the 1970s. Diseases due to viruses, rickettsial-like bacteria, true bacteria, protozoa, and fungi have emerged as major diseases of farmed shrimp in the region. Many of the bacterial, fungal and protozoan caused diseases are managed using improved culture practices, routine sanitation, and the use of chemotherapeutics. However, the virus diseases have been far more problematic to manage and they have been responsible for the most costly epizootics. Examples include the Taura syndrome pandemic that began in 1991-1992 when the disease emerged in Ecuador, and the subsequent White Spot Disease pandemic that followed its introduction to Central America from Asia in 1999. Because of their socioeconomic significance to shrimp farming, seven of the nine crustacean diseases listed by the World Animal Organization (OIE) are virus diseases of shrimp. Of the seven virus diseases of penaeid shrimp, five are native to the Americas or have become enzootic following their introduction. The shrimp virus diseases in the Americas are increasingly being managed by exclusion using a combination of biosecurity and the practice of culturing domesticated specific pathogen-free (SPF) stocks or specific pathogen-resistant (SPR) stocks. Despite the significant challenges posed by disease, the shrimp farming industry of the Americas has responded to the challenges posed by disease and it has developed methods to manage its diseases and mature into a sustainable industry.     

Pharmacological and genetic evaluation of proposed roles of mitogen-activated protein kinase/extracellular signal-regulated kinase kinase (MEK), extracellular signal-regulated kinase (ERK), and p90(RSK) in the control of mTORC1 protein signaling by phorbol esters

The mammalian target of rapamycin complex 1 (mTORC1) links the control of mRNA translation, cell growth, and metabolism to diverse stimuli. Inappropriate activation of mTORC1 can lead to cancer. Phorbol esters are naturally occurring products that act as potent tumor promoters. They activate isoforms of protein kinase C (PKCs) and stimulate the oncogenic MEK/ERK signaling cascade. They also activate mTORC1 signaling. Previous work indicated that mTORC1 activation by the phorbol ester PMA (phorbol 12-myristate 13-acetate) depends upon PKCs and may involve MEK. However, the precise mechanism(s) through which they activate mTORC1 remains unclear. Recent studies have implicated both the ERKs and the ERK-activated 90-kDa ribosomal S6 kinases (p90(RSK)) in activating mTORC1 signaling via phosphorylation of TSC2 (a regulator of mTORC1) and/or the mTORC1 component raptor. However, the relative importance of each of these kinases and phosphorylation events for the activation of mTORC1 signaling is unknown. The recent availability of MEK (PD184352) and p90(RSK) (BI-D1870) inhibitors of improved specificity allowed us to address the roles of these protein kinases in controlling mTORC1 in a variety of human and rodent cell types. In parallel, we used specific shRNAs against p90(RSK1) and p90(RSK2) to further test their roles in regulating mTORC1 signaling. Our data indicate that p90(RSKs) are dispensable for the activation of mTORC1 signaling by phorbol esters in all cell types tested. Our data also reveal striking diversity in the requirements for MEK/ERK in the control of mTORC1 between different cell types, pointing to additional signaling connections between phorbol esters and mTORC1, which do not involve MEK/ERK. This study provides important information for the design of efficient strategies to combat the hyperactivation of mTORC1 signaling by oncogenic pathways.     

特定人群超重及肥胖与相关疾病患病分析

目的:分析特定人群超重患病率,以及超重与高血压、糖尿病、血脂异常、脂肪肝等相关疾病的关系,为及早预防慢性非传染性疾病奠定基础。方法:对平房地区采取长效避孕措施的603名户籍农村已婚育龄妇女进行健康体检,按体重指数(BMI)分为正常组、超重组和肥胖组,比较各组间高血压、高血糖、高血脂、脂肪肝等相关疾病检出率的差异。结果:特定人群超重发病率及超重相关疾病检出率的差异均具有统计学意义(P<0.01)。结论:平房地区特定人群超重及肥胖发病率未明显高于国内平均水平及全市水平。但超重及肥胖与高血压、糖尿病、血脂异常、脂肪肝等疾病存在较大相关关系,为了进一步降低心脑血管高危因素和死亡率,需采取早期、有效的措施控制超重和肥胖倾向。     

Mitochondrial acyl carrier proteins in <Emphasis Type="Italic">Arabidopsis thaliana</Emphasis> are predominantly soluble matrix proteins and none can be confirmed as subunits of respiratory Complex I

Arabidopsis mitochondria are predicted to contain three acyl carrier proteins (ACPs). These small proteins are involved in fatty acid and lipoic acid synthesis in other organisms and have been previously reported to be subunits of respiratory Complex I in mitochondria in mammals, fungi and plants. Recently, the mammalian mitochondrial ACP (mtACP) has been shown to be largely a soluble matrix protein but also to be minimally associated with Complex I (Cronan et al. 2005), consistent with its involvement in synthesis of lipoic acid for TCA cycle decarboxylating dehydrogenases in the matrix but contrary to earlier claims it was primarily a Complex I subunit. We have investigated the localization of the ACPs in Arabidopsis mitochondria. Evidence is presented that mtACP1 and mtACP2 dominate the ACP composition in Arabidopsis mitochondria, and both are present in the mitochondrial matrix rather than in the membrane. No significant amounts of mtACPs were detected in Complex I isolated by blue native gel electrophoresis, rather mtACPs were detected at low molecular mass in the soluble fraction, showing that in A. thaliana mtACPs are predominately free soluble matrix proteins.