BACKGROUND & AIMS: :Transparent exopolymer particles (TEP) are a class of marine gel particles and important links between surface ocean biology and atmospheric processes. Derived from marine microorganisms, these particles can facilitate the biological pumping of carbon dioxide to the deep sea, or act as cloud condensation and ice nucleation particles in the atmosphere. Yet, environmental controls on TEP abundance in the ocean are poorly known. Here, we investigated some of these controls during the first multiyear time-series on TEP abundance for the Fram Strait, the Atlantic gateway to the Central Arctic Ocean. Data collected at the Long-Term Ecological Research observatory HAUSGARTEN during 2009 to 2014 indicate a strong biological control with highest abundance co-occurring with the prymnesiophyte Phaeocystis pouchetii. Higher occurrence of P. pouchetii in the Arctic Ocean has previously been related to northward advection of warmer Atlantic waters, which is expected to increase in the future. Our study highlights the role of plankton key species in driving climate relevant processes; thus, changes in plankton distribution need to be accounted for when estimating the ocean's biogeochemical response to global change.

背景与目标： ：透明的外聚合物颗粒（TEP）是一类海洋凝胶颗粒，是海洋表面生物学与大气过程之间的重要纽带。这些微粒源自海洋微生物，可促进二氧化碳向深海的生物泵送，或在大气中充当云凝结和冰核形核的微粒。然而，对海洋中TEP丰度的环境控制知之甚少。在这里，我们调查了Fram海峡（通往中北冰洋的大西洋门户）的TEP丰度的第一个多年期序列中的一些控制措施。长期生态研究天文台HAUSGARTEN在2009年至2014年期间收集的数据表明，与褐藻类植物Phaeocystis pouchetii共同出现的生物控制力最高。在北冰洋，Pouchetii的高发以前与大西洋较温暖的水域向北平流有关，预计将来还会增加。我们的研究强调了浮游生物关键物种在驱动气候相关过程中的作用；因此，在估算海洋对全球变化的生物地球化学反应时，必须考虑浮游生物分布的变化。

BACKGROUND & AIMS: :Fungi produce a variety of secondary metabolites (SMs), low-molecular weight compounds associated with many potentially useful biologic activities. The examples of biotechnologically relevant fungal metabolites include penicillin, a β-lactam antibiotic, and lovastatin, a cholesterol-lowering drug. The discovery of pharmaceutical lead compounds within the microbial metabolic pools relies on the selection and biochemical characterization of promising strains. Not all SMs are produced under standard cultivation conditions, hence the uncovering of chemical potential of investigated strains often requires the use of induction strategies to awake the associated biosynthetic genes. Triggering the secondary metabolic pathways can be achieved through the variation of cultivation conditions and growth media composition. The alternative strategy is to use genetic engineering to activate the respective genomic segments, e.g. by the manipulation of regulators or chromatin-modifying enzymes. Recently, whole-genome sequencing of several fungi isolated from the Chernobyl accident area was reported by Singh et al. (Genome Announc 2017; 5:e01602-16). These strains were selected for exposure to microgravity at the International Space Station. Biochemical characterization of fungi cultivated under extreme conditions is likely to provide valuable insights into the adaptation mechanism associated with metabolism and, possibly, a catalog of novel molecules of potential pharmaceutical importance.

背景与目标： ：真菌产生多种次级代谢产物（SMs），低分子量化合物，与许多潜在有用的生物活性有关。与生物技术相关的真菌代谢物的例子包括青霉素（一种β-内酰胺抗生素）和洛伐他汀（一种降低胆固醇的药物）。在微生物代谢池中发现药物先导化合物依赖于有前途的菌株的选择和生化特性。并非所有SM都是在标准培养条件下生产的，因此要揭示被调查菌株的化学潜能，通常需要使用诱导策略来唤醒相关的生物合成基因。触发次级代谢途径可以通过改变培养条件和生长培养基组成来实现。另一种策略是使用基因工程来激活各自的基因组片段，例如通过调节剂或染色质修饰酶的操作。最近，Singh等报道了从切尔诺贝利事故地区分离出的几种真菌的全基因组测序。 （Genome Announc 2017; 5：e01602-16）。这些菌株被选择在国际空间站暴露于微重力中。在极端条件下培养的真菌的生化特性可能会提供与代谢相关的适应机制的有价值的见解，并可能提供具有潜在药物重要性的新型分子的目录。

BACKGROUND & AIMS: :Brucella species are pathogenic agents that cause brucellosis, a debilitating zoonotic disease that affects a large variety of domesticated animals and humans. Brucella melitensis and Brucella abortus are considered major health threats because of their highly infectious nature and worldwide occurrence. The availability of the annotated genomes for these two species has allowed a comparative proteomics study of laboratory grown B. melitensis 16M and B. abortus 2308 by two-dimensional (2-D) gel electrophoresis and peptide mass fingerprinting. Computer-assisted analysis of the different 2-D gel images of strains 16M and 2308 revealed significant quantitative and qualitative differences in their protein expression patterns. Proteins involved in membrane transport, particularly the high affinity amino acids binding proteins, and those involved in Sec-dependent secretion systems related to type IV and type V secretion systems, were differentially expressed. Differential expression of these proteins may be responsible for conferring specific host preference in the two strains 2308 and 16M.

背景与目标： 布鲁氏菌属是引起布鲁氏菌病的病原体，布鲁氏菌病是一种使人畜共患的令人衰弱的人畜共患疾病，影响多种驯养的动物和人类。布鲁氏菌和流产布鲁氏菌被认为是主要的健康威胁，因为它们具有高度的传染性和在世界范围内广泛存在。这两个物种的注释基因组的可获得性允许通过二维（2-D）凝胶电泳和肽质量指纹图谱对实验室生长的B. melitensis 16M和B.abortus 2308进行蛋白质组学比较研究。对菌株16M和2308的不同2-D凝胶图像的计算机辅助分析显示，它们的蛋白质表达模式存在明显的定量和定性差异。差异表达了膜运输中涉及的蛋白质，特别是高亲和力氨基酸结合蛋白，以及涉及与IV型和V型分泌系统有关的Sec依赖性分泌系统的蛋白质。这些蛋白质的差异表达可能是在两个菌株2308和16M中赋予特定宿主偏好的原因。

BACKGROUND & AIMS: :In ectotherms, lower temperatures in high-latitude environments would theoretically reduce the annual growth rates of individuals. If slower growth and resultant smaller body size reduce fitness, individuals in higher latitudes may evolve compensatory responses. Two alternative models of such latitudinal compensation are possible: Model I: thermal reaction norms for growth rates of high-latitude individuals may be horizontally shifted to a lower range of temperatures, or Model II: reaction norms may be vertically shifted so that high-latitude individuals can grow faster across all temperatures. Model I is expected when annual growth rates in the wild are only a function of environmental temperatures, whereas Model II is expected when individuals in higher latitudes can only grow during a shorter period of a year. A variety of mixed strategies of these two models are also possible, and the magnitude of horizontal versus vertical variation in reaction norms among latitudinal populations will be indicative of the importance of "temperature" versus "seasonality" in the evolution of latitudinal compensation. However, the form of latitudinal compensation may be affected by possible genetic constraints due to the genetic architecture of reaction norms. In this study, we examine the inter- and intrapopulation variations in thermal reaction norms for growth rate of the medaka fish Oryzias latipes. Common-environment experiments revealed that average reaction norms differed primarily in elevation among latitudinal populations in a manner consistent with Model II (adaptation to "seasonality"), suggesting that natural selection in high latitudes prefers individuals that grow faster even within a shorter growing season to individuals that have longer growing seasons by growing at lower temperatures. However, intrapopulation variation in reaction norms was also vertical: some full-sibling families grew faster than others across all temperatures examined. This tendency in intrapopulation genetic variation for thermal reaction norms may have restricted the evolution of latitudinal compensation, irrespective of the underlying selection pressure.

背景与目标： ：在等温线中，高纬度环境中的低温理论上会降低个人的年增长率。如果较慢的生长和由此产生的较小的体型降低了适应性，则高纬度地区的人们可能会出现代偿性反应。这种纬度补偿的两个替代模型是可能的：模型I：高纬度个体生长速率的热反应规范可以水平移动到较低的温度范围，或者模型II：反应规范可以垂直移动以使高纬度个人可以在所有温度下更快地成长。当野外的年增长率仅是环境温度的函数时，可以预期为模型I，而当纬度较高的人只能在较短的一年内增长时，则可以预测为模型II。这两种模型的多种混合策略也是可能的，并且在纬度种群之间反应规范的水平相对于垂直变化的大小将指示“温度”相对于“季节性”在纬度补偿演变中的重要性。但是，由于反应规范的遗传结构，纬度补偿的形式可能会受到可能的遗传约束的影响。在这项研究中，我们研究了aka对印度med鱼Oryzias latipes生长速度的热反应规范中的种群间和种群内变化。共同环境实验表明，平均反应规范主要在纬度种群之间以与II型一致（适应“季节性”）的方式不同，这表明高纬度地区的自然选择更倾向于即使在较短的生长季节中生长速度更快的个体，也不符合模型II的要求。生长在较低温度下的生长季节较长的个体。但是，种群内反应规范的变化也是垂直的：在所有考察的温度范围内，一些全兄弟家庭的生长速度快于其他家庭。无论潜在的选择压力如何，热反应范围内种群遗传变异的这种趋势都可能限制了纬度补偿的演变。

BACKGROUND & AIMS: :We compared serotype distributions of Streptococcus pneumoniae isolates from patients aged <5 and o5 years with invasive pneumococcal disease in New South Wales, Australia, and antibiotic susceptibilities of isolates from the <5 years age group only, before (2002–2004) and after(2005–2009) introduction of the 7-valent pneumococcal conjugate vaccine (PCV7). Overall, there were significant decreases in the mean annual number of referred isolates (770 vs. 515) and the proportion belonging to PCV7 serotypes (74% vs. 38%), but non-PCV7 serotypes, particularly 19A, increased (5% vs. 18%). All changes were more marked in the <5 years age group.Susceptibility testing of isolates from the <5 years age group showed variation in resistance between serotypes, but significant overall increases in penicillin non-susceptibility (23% vs. 31%),ceftriaxone resistance (2% vs. 12%) and multidrug resistance (4% vs. 7%) rates ; erythromycin resistance fell (32% vs. 25%). Continued surveillance is needed to monitor changes following the introduction of 13-valent PCV in 2012.

背景与目标： ：我们比较了澳大利亚新南威尔士州<5和o5岁患有侵袭性肺炎球菌疾病的患者的肺炎链球菌分离株的血清型分布和仅<5岁年龄组的分离株的抗生素敏感性（2002-2004年之前和之后） （2005-2009）引入了7价肺炎球菌结合疫苗（PCV7）。总体而言，转介的分离株的年均数量显着减少（770比515）和属于PCV7血清型的比例（74％比38％），但非PCV7血清型，特别是19A血清型增加（5％vs。 18％）。在<5岁年龄组中所有变化均更为明显。<5岁年龄组的分离株的药敏试验显示，血清型之间的耐药性存在差异，但青霉素的非药敏性总体显着增加（23％vs. 31％），头孢曲松耐药率（2％vs. 12％）和多药耐药性（4％vs. 7％）比率；红霉素耐药性下降（32％对25％）。在2012年推出13价PCV之后，需要持续进行监测以监测变化。

BACKGROUND & AIMS: :During the production of clinical-grade retroviral vector supernatant, we noted significant differences in the lactate production and glucose consumption of various producer cell lines submitted to the National Gene Vector Laboratory (NGVL). Since differences in growth characteristics could be important in determining the optimal culture conditions for maximizing titer, we studied the growth characteristics of three commonly used packaging cell lines: PA317, PG13 and GP+envAM12. A transformed phenotype, assessed by the ability to form colonies in semisolid media, was evident in all three packaging cell lines tested. In confluent cultures, the rates of glucose consumption and lactate production (per cell per hour) were similar for the three lines tested, but the growth rate and culture density varied. PA317 and PG13 continued to expand after reaching confluence, resulting in higher cell densities and subsequent rapid depletion of glucose within the 24-hr observation period. When the cell lines were evaluated for titer optimization, the slower growing packaging cell line GP+envAM12 generally provided the highest titer after 8 hr of culture in confluent roller bottles, while most vectors introduced into PA317 and PG13 cells yielded optimal titers after 24 hr of culture. We also found that the improved titers obtained by culturing cells at 32 degrees C previously reported for PA317 cells do not apply to other packaging cell lines. In particular, PG13 rapidly lost titer when grown at the lower temperature. Our findings suggest that optimization of titer requires careful consideration of the culture conditions, which should be individualized for the vector producer cell line.

背景与目标： 在临床级逆转录病毒载体上清液的生产过程中，我们注意到提交给国家基因载体实验室（NGVL）的各种生产细胞系的乳酸生产和葡萄糖消耗存在显着差异。由于生长特性的差异对于确定最大滴度的最佳培养条件可能很重要，因此我们研究了三种常用包装细胞系的生长特性：PA317，PG13和GP envAM12。通过在半固体培养基中形成菌落的能力评估的转化表型在所有测试的三种包装细胞系中均很明显。在融合培养物中，三个试验品系的葡萄糖消耗速率和乳酸产生速率（每细胞每小时）相似，但是生长速率和培养密度不同。达到汇合后，PA317和PG13继续扩增，导致更高的细胞密度，随后在24小时观察期内葡萄糖迅速耗竭。当评估细胞系的滴度优化时，生长缓慢的包装细胞系GP envAM12在融合滚瓶中培养8小时后通常提供最高滴度，而导入PA317和PG13细胞的大多数载体在培养24小时后产生最佳滴度。我们还发现先前报道的PA317细胞通过在32摄氏度下培养细胞获得的改进的滴度不适用于其他包装细胞系。特别是，PG13在较低温度下生长时会迅速失去效价。我们的发现表明效价的优化需要仔细考虑培养条件，应针对载体生产细胞株进行个性化。

BACKGROUND & AIMS: :Complete nucleotide sequence of the tissue culture-adapted ATCC-Wa strain of human rotavirus NSP4 was determined. Sequence analysis detected two alternate forms of the gene with a nucleotide difference at position 331 (A or G) in the coding sequence (NSP4-A or NSP4-G) leading to a change from neutral glutamine97 in NSP4-A to a positively charged arginine97 in NSP4-G originating from the same ATCC-Wa preparation. In addition to this, both forms of ATCC-Wa NSP4 revealed three mutations at nucleotide positions 88 (T to C), 142 (C to T) and 572 (G to A), when compared to the previously reported NSP4 sequence from virulent Wa strain. The former two mutations were in the coding sequence and resulted in a leucine16 to serine16 and a proline34 to leucine34 change, while the third mutation was in the 3' non-coding region of the gene. The two amino acid changes may contribute to the 'tissue culture-adaptation' of ATCC-Wa strain. The ATCC-Wa NSP4 sequence was found to differ from the previously reported NSP4 sequence of attenuated Wa strain by lacking a mutation at 133 (T to C), though the mutations at 88 and 142 were present in both strains. Furthermore, comparison of deduced amino acid sequence of NSP4 from human, bovine, porcine and simian rotavirus strains identified a seven-residue (positions 135-141) inter-species variable domain in its C-terminal region.

背景与目标： ：测定了适应于组织培养的人轮状病毒NSP4的ATCC-Wa株的核苷酸序列。序列分析检测到两种替代形式的基因，其核苷酸序列在编码序列（NSP4-A或NSP4-G）的331位（A或G）处存在核苷酸差异，导致从NSP4-A中的中性谷氨酰胺97变为带正电荷的精氨酸97来自相同ATCC-Wa制备物的NSP4-G中的B.除此之外，与先前报道的来自强毒Wa的NSP4序列相比，两种形式的ATCC-Wa NSP4都在核苷酸位置88（T到C），142（C到T）和572（G到A）处显示了三个突变。拉紧。前两个突变位于编码序列中，导致亮氨酸16变为丝氨酸16，脯氨酸34变为亮氨酸34的变化，而第三个突变位于基因的3'非编码区域。这两个氨基酸变化可能有助于ATCC-Wa菌株的“组织培养适应性”。发现ATCC-Wa NSP4序列与先前报道的减毒Wa菌株的NSP4序列有所不同，因为它在133（T至C）处没有突变，尽管这两个菌株中都存在88和142处的突变。此外，从人，牛，猪和猿猴轮状病毒株推导的NSP4推导的氨基酸序列的比较鉴定出在其C末端区域中的七个残基（位置135-141）种间可变结构域。

BACKGROUND & AIMS: :Metabolic responses to food influence risk of cardiometabolic disease, but large-scale high-resolution studies are lacking. We recruited n = 1,002 twins and unrelated healthy adults in the United Kingdom to the PREDICT 1 study and assessed postprandial metabolic responses in a clinical setting and at home. We observed large inter-individual variability (as measured by the population coefficient of variation (s.d./mean, %)) in postprandial responses of blood triglyceride (103%), glucose (68%) and insulin (59%) following identical meals. Person-specific factors, such as gut microbiome, had a greater influence (7.1% of variance) than did meal macronutrients (3.6%) for postprandial lipemia, but not for postprandial glycemia (6.0% and 15.4%, respectively); genetic variants had a modest impact on predictions (9.5% for glucose, 0.8% for triglyceride, 0.2% for C-peptide). Findings were independently validated in a US cohort (n = 100 people). We developed a machine-learning model that predicted both triglyceride (r = 0.47) and glycemic (r = 0.77) responses to food intake. These findings may be informative for developing personalized diet strategies. The ClinicalTrials.gov registration identifier is NCT03479866.

背景与目标： 食物代谢反应影响心脏代谢疾病的风险，但缺乏大规模的高分辨率研究。我们在英国招募了n = 1002的双胞胎和无关的健康成年人参加PREDICT 1研究，并在临床和在家中评估了餐后代谢反应。我们观察到在同一餐后血液中甘油三酸酯（103％），葡萄糖（68％）和胰岛素（59％）的餐后反应中存在较大的个体间差异（通过群体变异系数（标准偏差/平均值，％）衡量）。餐后脂肪血症的人特异性因素（如肠道微生物组）的影响（膳食中的大量营养素（3.6％））比餐后营养素（3.6％）的影响更大，而餐后血糖的影响则不大（分别为6.0％和15.4％）；遗传变异对预测的影响不大（葡萄糖为9.5％，甘油三酸酯为0.8％，C肽为0.2％）。研究结果在美国队列中独立验证（n = 100人）。我们开发了一种机器学习模型，该模型可以预测甘油三酸酯（r = 0.47）和血糖（r = 0.77）对食物摄入的反应。这些发现可能有助于制定个性化的饮食策略。 ClinicalTrials.gov的注册标识符为NCT03479866。

BACKGROUND & AIMS: Background:Research focused on extreme environments is often associated with difficulties in obtaining fresh plant material. Herbaria may provide great support as they house large collections of specimens from different parts of the world. Accordingly, there is also a growing interest in methods using herbarium specimens in molecular studies. Much of the literature on herbarium DNA is aimed to improve extraction and PCR amplification and is focused mostly on vascular plants. Here, I provide a brief study of DNA extraction efficiency from moss herbarium specimens, emphasizing the importance of herbaria as an invaluable source of material from hard-to-access geographical areas, such as the Antarctic region. Methods:The presented study is based on herbarium collections of 25 moss species collected in the austral polar regions between 1979 and 2013. The majority of samples were obtained using the DNeasy Plant Mini Kit (Qiagen, Hilden, Germany). The remaining, smaller part was extracted using an adapted CTAB-based approach. The performance of DNA extraction methods in terms of PCR amplification success was measured by testing several DNA fragments of various size. Furthermore, in order to estimate of DNA fragmentation level, an automated on-chip electrophoresis system was used. Results:Results reveal that DNA purity and the length of the target genetic region are the fundamental agents which drive the successful PCR reaction. Conversely, the DNA yield and specimen age seem to be less relevant. With this study, I present also an optimized CTAB-based approach which may effectively suppress inhibitors in the herbarium DNA. This method can be considered a cheaper alternative to column-based technology, particularly useful for dealing with a large number of samples. Results of this study confirmed previous reports and contribute to filling the existing gap in molecular analyses which involve the use of herbarium collections of mosses.

背景与目标： 背景：针对极端环境的研究通常与获取新鲜植物材料有关。草本植物可能会提供很大的支持，因为它们会收集来自世界各地的大量标本。因此，在分子研究中使用植物标本室标本的方法也越来越引起人们的兴趣。关于植物标本室DNA的许多文献旨在改善提取和PCR扩增，并且主要集中在维管植物上。在这里，我对从苔藓植物标本室标本中提取DNA的效率进行了简要研究，强调了草as作为难以接近的地理区域（如南极地区）的宝贵材料来源的重要性。
方法：本研究基于1979年至2013年在南极地区收集的25种苔藓植物标本室的收集。大部分样品是使用DNeasy Plant Mini Kit（Qiagen，Hilden，德国）获得的。使用基于CTAB的方法提取剩余的较小部分。通过测试几种大小不同的DNA片段，可以测量DNA提取方法在PCR扩增成功率方面的性能。此外，为了估计DNA片段化水平，使用了自动芯片上电泳系统。
结果：结果表明，DNA纯度和靶基因区域的长度是驱动成功PCR反应的基本因素。相反，DNA产量和标本年龄似乎不太相关。通过这项研究，我还提出了一种基于CTAB的优化方法，该方法可以有效抑制植物标本室DNA中的抑制剂。可以认为该方法是基于列的技术的更便宜的替代方法，对处理大量样品特别有用。这项研究的结果证实了以前的报道，并有助于填补分子分析中现有的空白，其中涉及使用植物标本室收集的苔藓。

BACKGROUND & AIMS: IMPORTANCE:The terms "personalized oncology" and "precision oncology" have increased in usage and have generated considerable traction in terms of public attention and research funding. To our knowledge, no prior study has as thoroughly documented the use of the "precision oncology" terminology over the last decade. OBJECTIVE:To determine how the use of the terms "personalized oncology" and "precision oncology" have changed over time. DESIGN:A retrospective literature analysis using two databases (PubMed and Scopus) over 10 years was performed. Manuscripts using either term "personalized oncology" or "precision oncology" were collected. Manuscripts published in 2011, 2013, 2015, 2017 and through 30 June 2019 were pulled for text analysis. Common reasons for exclusion were if the search term appeared in the institution name only, the search term appeared only in keyword or publication title, or the search term was used to justify the relevance or application of research with no clear definition. SETTING:Manuscripts published and catalogued in PubMed or Scopus. RESULTS:In our study, we analysed 399 unique manuscripts published over the last decade. Over time, the terminology has shifted from "personalized oncology" to "precision oncology". Targeted therapy, molecular biomarker-guided tumour profiling and next generation sequencing (ie, "omics-guided tumor profiling") are the three most common definitions of the term. While these definitions are somewhat overlapping in concept, over the decade we observed an increase in the number of distinct interpretations of "precision oncology", ranging from structural biology to clinical practice. CONCLUSIONS AND RELEVANCE:We have observed that the phrase "precision oncology" is shifting, overlapping and expanding in definition. This all-encompassing approach to defining "precision oncology" ironically renders the term imprecise. Our analysis highlights the inherent challenges in defining novel movements in medicine.

背景与目标： 重要信息：“个性化肿瘤学”和“精密肿瘤学”这两个术语的使用有所增加，并且在公众关注和研究经费方面已经产生了可观的吸引力。据我们所知，在过去的十年中，没有任何先前的研究能充分记录“精确肿瘤学”术语的使用。
目的：确定术语“个性化肿瘤学”和“精密肿瘤学”的使用随着时间的变化如何。
设计：使用两个数据库（PubMed和Scopus）进行了10年的回顾性文献分析。收集使用术语“个性化肿瘤学”或“精密肿瘤学”的手稿。分别提取2011年，2013年，2015年，2017年和2019年6月30日之前出版的手稿进行文本分析。排除的常见原因是：搜索词仅出现在机构名称中，搜索词仅出现在关键字或出版物标题中，或者使用搜索词来说明研究的相关性或应用性，而没有明确的定义。
设置：在PubMed或Scopus中出版和分类的手稿。
结果：在我们的研究中，我们分析了过去十年出版的399种独特手稿。随着时间的流逝，术语已从“个性化肿瘤学”转变为“精密肿瘤学”。靶向治疗，分子生物标志物指导的肿瘤分析和下一代测序（即“组学指导的肿瘤分析”）是该术语的三个最常见定义。尽管这些定义在概念上有些重叠，但是在过去的十年中，我们观察到从结构生物学到临床实践，对“精确肿瘤学”的不同解释的数量有所增加。
结论与相关性：我们已经观察到“精确肿瘤学”一词在定义上正在转移，重叠和扩展。具有讽刺意味的是，这种定义“精确肿瘤学”的方法使术语“不精确”成为现实。我们的分析突显了定义医学中新颖运动的内在挑战。

BACKGROUND & AIMS: OBJECTIVE:To evaluate the clinical characteristics and laboratory test results in pregnant women with coronavirus disease 2019 (COVID-19). METHODS:A retrospective study to review and compare clinical data including electronic medical records and laboratory tests from pregnant and nonpregnant patients admitted the Central Hospital of Wuhan, China from December 8, 2019 to April 1, 2020. RESULTS:A total of 72 women (30 pregnant and 42 nonpregnant) with COVID-19 were included. No patients developed severe pneumonia during the study. Compared with the nonpregnant group, pregnant patients were admitted to hospital earlier (0.25 vs 11.00 days; P<0.001), presented milder symptoms, had a higher rate of asymptomatic infection (26.7% vs 0%), and shorter length of hospital stay (14.5 vs 17.0 days; P<0.01). Laboratory test results showed that levels of inflammation markers such as white blood cell count, neutrophil count and percentage, C-reactive protein, procalcitonin, and D-dimer were significantly higher in pregnant women, whereas mean lymphocyte percentage was significantly lower compared with nonpregnant women. CONCLUSION:In some respects, the clinical characteristics and laboratory test results of COVID-19 in pregnant patients seems to be distinctive from their nonpregnant counterparts. Appropriate advice and positive treatment might be critical to the prognosis when dealing with these pregnant patients. Pregnant patients with COVID-19 had their own positive clinical characteristics and special laboratory test results. Responsive medical advice and active treatment for those patients are critical to recovery.

背景与目标： 目的：评估2019年冠状病毒病孕妇的临床特征和实验室检查结果（COVID-19）。
方法：一项回顾性研究，旨在回顾和比较2019年12月8日至2020年4月1日收治于中国武汉市中心医院的孕妇和非孕妇的临床数据，包括电子病历和实验室检查结果。
结果：总共包括72例COVID-19的妇女（30例孕妇和42例未妊娠）。在研究期间，没有患者出现严重的肺炎。与未怀孕组相比，怀孕患者较早入院（0.25 vs 11.00天; P <0.001），症状较轻，无症状感染率较高（26.7％vs 0％），住院时间较短（ 14.5天与17.0天； P <0.01）。实验室测试结果显示，孕妇的炎症标志物（如白细胞计数，中性粒细胞计数和百分比，C反应蛋白，降钙素和D-二聚体）的水平显着较高，而平均淋巴细胞百分比与未怀孕的女性相比明显较低。 。
结论：在某些方面，COVID-19在孕妇中的临床特征和实验室检查结果似乎与非孕妇有区别。当与这些怀孕的患者打交道时，适当的建议和积极的治疗可能对预后至关重要。孕妇的COVID-19患者具有自己的阳性临床特征和特殊的实验室检查结果。对这些患者的响应性医疗建议和积极治疗对于康复至关重要。

BACKGROUND & AIMS: :Glioblastoma (GBM) is the most common malignancy of the central nervous system, and most patients with GBM die of the disease despite standard treatment. By clarifying the molecular abnormalities that drive the malignant phenotype of GBM, various drugs that specifically target tumor cells and the tumor microenvironment have been developed. These drugs, including drugs targeting growth factor receptors and their downstream signaling pathways, angiogenesis, aberrant metabolism, epigenetic deregulation, and aberrant immune microenvironments, have been investigated in preclinical or clinical trials. However, these drugs that significantly inhibited the growth of GBM in the preclinical stage have not produced survival benefits in patients with GBM. One reason for their failure is the lack of a definite driver gene to select patients most likely to benefit. Another reason is the inadequate pharmacokinetic properties of the drugs owing of the blood-brain barrier. In the present review, we discuss progress in the development of target therapeutic strategies. Furthermore, we discuss the development of nanomaterials that act as local drug delivery systems to penetrate the blood-brain barrier for managing GBM.

背景与目标： ：胶质母细胞瘤（GBM）是中枢神经系统最常见的恶性肿瘤，尽管接受了标准治疗，大多数GBM患者仍死于该病。通过阐明驱动GBM恶性表型的分子异常，已开发出了多种专门针对肿瘤细胞和肿瘤微环境的药物。已经在临床前或临床试验中研究了这些药物，包括靶向生长因子受体及其下游信号传导途径，血管生成，异常代谢，表观遗传失调和异常免疫微环境的药物。但是，这些在临床前阶段显着抑制GBM生长的药物尚未对GBM患者产生生存益处。他们失败的原因之一是缺乏确定的驱动基因来选择最有可能受益的患者。另一个原因是由于血脑屏障的缘故，药物的药代动力学特性不足。在目前的审查中，我们讨论目标治疗策略的发展进展。此外，我们讨论了用作局部药物传递系统的纳米材料的开发，以穿透血脑屏障来管理GBM。

BACKGROUND & AIMS: :Biotin prototrophy is a rare, incompletely understood, and industrially relevant characteristic of Saccharomyces cerevisiae strains. The genome of the haploid laboratory strain CEN.PK113-7D contains a full complement of biotin biosynthesis genes, but its growth in biotin-free synthetic medium is extremely slow (specific growth rate [μ] ≈ 0.01 h-1). Four independent evolution experiments in repeated batch cultures and accelerostats yielded strains whose growth rates (μ ≤ 0.36 h-1) in biotin-free and biotin-supplemented media were similar. Whole-genome resequencing of these evolved strains revealed up to 40-fold amplification of BIO1, which encodes pimeloyl-coenzyme A (CoA) synthetase. The additional copies of BIO1 were found on different chromosomes, and its amplification coincided with substantial chromosomal rearrangements. A key role of this gene amplification was confirmed by overexpression of BIO1 in strain CEN.PK113-7D, which enabled growth in biotin-free medium (μ = 0.15 h-1). Mutations in the membrane transporter genes TPO1 and/or PDR12 were found in several of the evolved strains. Deletion of TPO1 and PDR12 in a BIO1-overexpressing strain increased its specific growth rate to 0.25 h-1 The effects of null mutations in these genes, which have not been previously associated with biotin metabolism, were nonadditive. This study demonstrates that S. cerevisiae strains that carry the basic genetic information for biotin synthesis can be evolved for full biotin prototrophy and identifies new targets for engineering biotin prototrophy into laboratory and industrial strains of this yeast.IMPORTANCE Although biotin (vitamin H) plays essential roles in all organisms, not all organisms can synthesize this vitamin. Many strains of baker's yeast, an important microorganism in industrial biotechnology, contain at least some of the genes required for biotin synthesis. However, most of these strains cannot synthesize biotin at all or do so at rates that are insufficient to sustain fast growth and product formation. Consequently, this expensive vitamin is routinely added to baker's yeast cultures. In this study, laboratory evolution in biotin-free growth medium yielded new strains that grew as fast in the absence of biotin as in its presence. By analyzing the DNA sequences of evolved biotin-independent strains, mutations were identified that contributed to this ability. This work demonstrates full biotin independence of an industrially relevant yeast and identifies mutations whose introduction into other yeast strains may reduce or eliminate their biotin requirements.

背景与目标： ：生物素原养是酿酒酵母菌株的一种罕见，尚未完全理解并且在工业上具有相关性的特征。单倍体实验室菌株CEN.PK113-7D的基因组包含完整的生物素生物合成基因，但在不含生物素的合成培养基中的生长极为缓慢（比生长率[μ]≈0.01 h-1）。在重复的分批培养和加速器中进行的四个独立进化实验得出的菌株在无生物素和补充生物素的培养基中的生长速率（μ≤0.36 h-1）相似。这些进化菌株的全基因组重测序揭示了BIO1的40倍扩增，该BIO1编码庚二酰辅酶A（CoA）合成酶。在不同的染色体上发现了BIO1的其他副本，其扩增与大量的染色体重排相符。 BIO1在菌株CEN.PK113-7D中的过表达证实了该基因扩增的关键作用，该菌株能够在不含生物素的培养基中生长（μ= 0.15 h-1）。在一些进化的菌株中发现了膜转运蛋白基因TPO1和/或PDR12的突变。在过表达BIO1的菌株中TPO1和PDR12的缺失将其比生长速率提高到0.25 h-1。这些基因中无效突变的作用是非可累加的，这些突变以前未与生物素代谢相关。这项研究表明，具有生物素合成基本遗传信息的酿酒酵母菌株可以进化为完整的生物素原营养素，并确定将生物素原营养素工程化到该酵母的实验室和工业菌株中的新靶标。尽管生物素（维生素H）起着至关重要的作用。在所有生物体中发挥作用，并非所有生物体都能合成这种维生素。面包酵母的许多菌株是工业生物技术中的重要微生物，至少含有一些生物素合成所需的基因。然而，这些菌株中的大多数不能完全合成生物素，或者不能以足以维持快速生长和产物形成的速率合成生物素。因此，通常将这种昂贵的维生素添加到面包师的酵母培养物中。在这项研究中，实验室在无生物素生长培养基中的进化产生了新菌株，该菌株在不存在生物素的情况下的生长速度与在存在生物素的情况下一样快。通过分析进化的不依赖生物素的菌株的DNA序列，鉴定出有助于此能力的突变。这项工作证明了与工业相关的酵母具有完全的生物素独立性，并鉴定了突变，将其引入其他酵母菌株可以降低或消除其对生物素的需求。

BACKGROUND & AIMS: :Taste aversion learning (TAL) can be induced by associating a flavor intake with the immediate or delayed (30 min) intragastric administration of a noxious substance, e.g., hypertonic NaCl. The objective of this study was to analyze the induction of c-Fos immunoreactivity in the intermediate nucleus of the solitary nucleus (iNST) after acquisition of a contiguous or delayed TAL, offering the flavor for voluntary consumption in both cases. The behavioral results obtained indicate that, although the learning was established under both experimental conditions, an increase in c-Fos induction was only produced in the group that learned by means of a non-delayed TAL. Immunohistochemical analyses revealed the participation of different brain structures in these two TAL modalities. Thus, the nucleus of the solitary tract may be involved in the TAL procedure in which voluntary flavor intake and intragastric administration of the noxious visceral stimulus are contiguous but not in delayed TAL, which would depend on other anatomical circuits that do not include the iNST.

背景与目标： ：通过将风味物质的摄入与有害物质（例如高渗氯化钠）的立即或延迟（30分钟）胃内给药相关联，可以诱发厌味学习（TAL）。这项研究的目的是分析获得连续或延迟的TAL后在单核中间核（iNST）中诱导c-Fos免疫反应性，为这两种情况提供自愿食用的风味。所获得的行为结果表明，尽管在两个实验条件下均建立了学习，但是仅在通过非延迟TAL学习的组中才产生了c-Fos诱导的增加。免疫组织化学分析揭示了这两种TAL模式中不同大脑结构的参与。因此，孤立道的核可能参与TAL程序，其中有害的内脏刺激的自愿性风味摄入和胃内给药是连续的，但TAL延迟不参与，这取决于不包括iNST的其他解剖回路。

BACKGROUND & AIMS: BACKGROUND:Cohen's κ coefficient is often used as an index to measure the agreement of inter-rater determinations. However, κ varies greatly depending on the marginal distribution of the target population and overestimates the probability of agreement occurring by chance. To overcome these limitations, an alternative and more stable agreement coefficient was proposed, referred to as Gwet's AC1. When it is desired to combine results from multiple agreement studies, such as in a meta-analysis, or to perform stratified analysis with subject covariates that affect agreement, it is of interest to compare several agreement coefficients and present a common agreement index. A homogeneity test of κ was developed; however, there are no reports on homogeneity tests for AC1 or on an estimator of common AC1. In this article, a homogeneity score test for AC1 is therefore derived, in the case of two raters with binary outcomes from K independent strata and its performance is investigated. An estimation of the common AC1 between strata and its confidence intervals is also discussed. METHODS:Two homogeneity tests are provided: a score test and a goodness-of-fit test. In this study, the confidence intervals are derived by asymptotic, Fisher's Z transformation and profile variance methods. Monte Carlo simulation studies were conducted to examine the validity of the proposed methods. An example using clinical data is also provided. RESULTS:Type I error rates of the proposed score test were close to the nominal level when conducting simulations with small and moderate sample sizes. The confidence intervals based on Fisher's Z transformation and the profile variance method provided coverage levels close to nominal over a wide range of parameter combination. CONCLUSIONS:The method proposed in this study is considered to be useful for summarizing evaluations of consistency performed in multiple or stratified inter-rater agreement studies, for meta-analysis of reports from multiple groups and for stratified analysis.

背景与目标： 背景：科恩（Cohen）的κ系数通常用作衡量评估者之间确定性一致性的指标。但是，κ取决于目标人群的边际分布而有很大差异，并且高估了偶然发生共识的可能性。为了克服这些限制，提出了另一种更稳定的协议系数，称为Gwet's AC1。当需要合并多个协议研究的结果（例如在荟萃分析中）或对影响协议的主题协变量进行分层分析时，比较几个协议系数并给出一个共同的协议索引是很有意义的。开展了κ均匀性测试；但是，没有关于AC1的同质性测试或常见AC1的估计量的报告。因此，在两个评级者具有来自K个独立层的二元结果的情况下，本文得出了AC1的同质性得分测试，并对其性能进行了研究。还讨论了对地层及其置信区间之间的公共AC1的估计。
方法：提供两种同质性测试：得分测试和拟合优度测试。在这项研究中，置信区间是通过渐近，Fisher's Z变换和轮廓方差方法得出的。进行了蒙特卡洛模拟研究，以检验所提出方法的有效性。还提供了使用临床数据的示例。
结果：在进行中小样本规模的仿真时，建议的分数测试的I类错误率接近标称水平。基于Fisher的Z变换和轮廓方差方法的置信区间在广泛的参数组合范围内提供了接近标称的覆盖范围。
结论：本研究中提出的方法被认为有助于总结在多个或分层的评分者间协议研究中进行的一致性评估，对来自多个组的报告进行荟萃分析以及进行分层分析。