BACKGROUND & AIMS: This paper reports on the application of an artificial neural network to the clinical analysis of ophthalmological data. In particular a 2-dimensional Kohonen self-organising feature map (SOM) is used to analyse visual field data from glaucoma patients. Importantly, the paper addresses the problem of how the SOM can be utilised to accommodate the noise within the data. This is a particularly important problem within longitudinal assessment, where detecting significant change is the crux of the problem in clinical diagnosis. Data from 737 glaucomatous visual field records (Humphrey Visual Field Analyzer, program 24-2) are used to train a SOM with 25 nodes organised on a square grid. The SOM clusters the data organising the output map such that fields with early and advanced loss are at extreme positions, with a continuum of change in place and extent of loss represented by the intervening nodes. For each SOM node 100 variants, generated by a computer simulation modelling the variability that might be expected in a glaucomatous eye, are also classified by the network to establish the extent of noise upon classification. Field change is then measured with respect to classification of a subsequent field, outside the area defined by the original field and its variants. The significant contribution of this paper is that the spatial analysis of the field data, which is provided by the SOM, has been augmented with noise analysis enhancing the visual representation of longitudinal data and enabling quantification of significant class change.

背景与目标： 本文报告了人工神经网络在眼科数据临床分析中的应用。特别是二维Kohonen自组织特征图 (SOM) 用于分析青光眼患者的视野数据。重要的是，本文解决了如何利用SOM来容纳数据中的噪声的问题。在纵向评估中，这是一个特别重要的问题，在纵向评估中，检测出明显的变化是临床诊断问题的关键。来自737青光眼视野记录 (Humphrey视野分析仪，程序24-2) 的数据用于训练具有25个节点的SOM在方形网格上。SOM对组织输出图的数据进行聚类，以使具有早期和高级损失的字段处于极端位置，并且由中间节点表示连续的变化和损失程度。对于每个SOM节点100变体，由对青光眼眼中可能预期的可变性建模的计算机模拟生成，也由网络分类以建立分类时的噪声程度。然后，针对原始字段及其变体定义的区域之外的后续字段的分类来测量字段变化。本文的重要贡献在于，由SOM提供的现场数据的空间分析已通过噪声分析得到了增强，从而增强了纵向数据的视觉表示并能够量化重大的类别变化。

BACKGROUND & AIMS: :This study reports extensive characterization of the silicone gel (3-4680, Dow Corning, Midland, MI), for potential use as an artificial dural sealant in long-term electrophysiological experiments in neurophysiology. Dural sealants are important to preserve the integrity of the intracranial space after a craniotomy and in prolonging the lifetime and functionality of implanted brain probes. In this study, we report results of our tests on a commercially available silicone gel with unique properties that make it an ideal dural substitute. The substitute is transparent, elastic, easy to apply, and has re-sealing capabilities, which makes it desirable for applications where multiple penetrations by the brain probe is desirable over an extended period of time. Cytotoxicity tests (for up to 10 days) with fibroblasts and in vivo tests (for 12 weeks) show that the gel is non-toxic and does not produce any significant neuronal degeneration when applied to the rodent cortex even after 12 weeks. In vivo humidity testing showed no sign of CSF leakage for up to 6 weeks. The gel also allows silicon microprobes to penetrate with forces less than 0.5 mN, and a 200-microm diameter stainless steel microprobe with a blunt tip to penetrate with a force less than 2.5 mN. The force dependency on the velocity of penetration and thickness of the gel was also quantified and empirically modeled. The above results demonstrate that the silicone gel (3-4680) can be a viable dural substitute in long-term electrophysiology of the brain.

背景与目标： : 这项研究报告了有机硅凝胶 (3-4680，Dow Corning，Midland，MI) 的广泛表征，可在神经生理学的长期电生理实验中用作人工硬脑膜密封剂。硬脑膜密封剂对于保持开颅手术后颅内空间的完整性以及延长植入的脑探针的寿命和功能至关重要。在这项研究中，我们报告了我们对具有独特性能的市售有机硅凝胶的测试结果，使其成为理想的硬脑膜替代品。该替代品是透明的，弹性的，易于应用，并且具有重新密封能力，这使得它适合在较长的时间内需要通过大脑探针进行多次穿透的应用。用成纤维细胞进行的细胞毒性测试 (长达10天) 和体内测试 (12周) 表明，即使在12周后将凝胶应用于啮齿动物皮层，该凝胶无毒且不会产生任何明显的神经元变性。体内湿度测试显示长达6周没有CSF泄漏的迹象。凝胶还允许硅微探针以小于0.5 mN的力穿透，并且具有钝尖端的200微米直径的不锈钢微探针以小于2.5 mN的力穿透。还对渗透速度和凝胶厚度的力依赖性进行了量化和经验建模。上述结果表明，硅酮凝胶 (3-4680) 在大脑的长期电生理中可以是可行的硬脑膜替代物。

BACKGROUND & AIMS: :In this study, oxygen and nitrate regulation of transcription and subsequent protein expression of the unique narK1K2GHJI respiratory operon of Pseudomonas aeruginosa were investigated. Under the control of PLAC, P. aeruginosa was able to transcribe nar and subsequently express methyl viologen-linked nitrate reductase activity under aerobic conditions without nitrate. Modulation of PLAC through the LacI repressor enabled us to assess both transcriptional and posttranslational regulation by oxygen during physiological whole-cell nitrate reduction.

背景与目标： : 在这项研究中，研究了铜绿假单胞菌独特的narK1K2GHJI呼吸操纵子的氧和硝酸盐对转录的调节以及随后的蛋白表达。在PLAC的控制下，铜绿假单胞菌能够转录nar，随后在有氧条件下无硝酸盐的情况下表达甲基紫精连接的硝酸还原酶活性。通过LacI阻遏物对PLAC的调节使我们能够评估生理全细胞硝酸盐还原过程中氧气的转录和翻译后调节。

BACKGROUND & AIMS: :Lubrication mechanisms and contact mechanics have been analysed in a new generation of 'cushion form' bearings for artificial hip joints, which comprise low elastic modulus layers on the articulating surfaces. Comparisons have been made with 'hard' bearings used in existing prostheses and also with the natural hip joint. Lubricating film thicknesses are enhanced by larger contact areas and lower contact pressures. For a fixed contact area, simultaneous changes in layer thickness and radial clearance have been shown to have a small effect on elastohydrodynamic film thickness. Hard bearings designed with the same contact area as the cushion bearings produced a similar film thickness, but lubricant film thickness is not optimized in current designs. The main advantage of using a cushion bearing with low elastic modulus layers was found to be associated with microelastohydrodynamic lubrication. Careful selection of the elastic modulus is important in order to ensure that this lubrication regime was effective. Low elastic modulus layers may also produce local deformations, which enhance squeeze film action. The elastic modulus of the material should not be lower than necessary to produce effective microelastohydrodynamic lubrication, as a further reduction in modulus only increases the strain distribution in the material. A lubricant film thickness of 0.3 microns has been predicted for a cushion hip prosthesis with a femoral head diameter of 32 mm and radius of contact zone of 16 mm, using a 2 mm thick layer with an elastic modulus of 20 MPa.

背景与目标： : 润滑机制和接触力学已在新一代的 “缓冲形式” 轴承中进行了分析，该轴承用于人造髋关节，在铰接表面上包括低弹性模量层。已与现有假体中使用的 “硬” 轴承以及自然髋关节进行了比较。通过较大的接触面积和较低的接触压力来增强润滑膜的厚度。对于固定接触面积，层厚度和径向间隙的同时变化已显示出对弹性流体动力膜厚度的影响很小。与缓冲轴承具有相同接触面积的硬轴承产生了相似的膜厚度，但是在当前设计中润滑剂膜厚度并未得到优化。发现使用具有低弹性模量层的缓冲轴承的主要优点与微弹性流体动力润滑有关。为了确保这种润滑方式有效，仔细选择弹性模量很重要。低弹性模量层还可能产生局部变形，从而增强了挤压膜的作用。材料的弹性模量不应低于产生有效的微弹性流体动力润滑所必需的，因为模量的进一步降低只会增加材料中的应变分布。对于具有32毫米的股骨头直径和16毫米的接触区半径的缓冲髋关节假体，使用弹性模量为20 mpa的2毫米厚层，已经预测了0.3微米的润滑剂膜厚度。

BACKGROUND & AIMS: AIM:To compare the long-term local control of hepatocellular carcinoma (HCC) and risk of peritoneal seeding via percutaneous radiofrequency ablation (RFA) using artificial ascites with those of RFA without artificial ascites. MATERIALS AND METHODS:The Institutional Review Board approved this retrospective study. From April 2005 to February 2008, 160 patients (121 men, 39 women; age range 36-79 years) with a single subcapsular HCC (mean size 2.19 cm) were treated with ultrasonography-guided percutaneous RFA as a first-line therapy. Forty-four patients were treated with RFA using artificial ascites, whereas the other 116 patients were treated without artificial ascites. The cumulative local tumour progression (LTP) and peritoneal seeding were compared in both groups using follow-up computed tomography (CT). Cumulative LTP rates were analysed using the Kaplan-Meier method and the log-rank test. Risk of peritoneal seeding was investigated by means of multivariate analysis. RESULTS:The overall median follow-up period was 52.5 months (range 13-76 months). The 1, 2, 4, and 6 year cumulative LTP rates were 17.1, 27.6, 35.2, and 35.2%, respectively, in the group with artificial ascites, and 8, 15.2, 26.6, and 34.4% in the group without artificial ascites, without significant difference (p = 0.332). The rates of peritoneal seeding were 6.8% (3/44) in the group with artificial ascites and 2.6% (3/116) in the group without artificial ascites, a non-significant difference (p = 0.347). The biopsy prior to RFA was the independent risk factor of peritoneal seeding regardless of the use of artificial ascites. CONCLUSION:Long-term local tumour control and risk of peritoneal seeding were comparable for RFA with or without artificial ascites when used as a first-line therapy for subcapsular HCC.

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BACKGROUND & AIMS: :The World Health Organization and other institutions are considering Artificial Intelligence (AI) as a technology that can potentially address some health system gaps, especially the reduction of global health inequalities in low- and middle-income countries (LMICs). However, because most AI-based health applications are developed and implemented in high-income countries, their use in LMICs contexts is recent and there is a lack of robust local evaluations to guide decision-making in low-resource settings. After discussing the potential benefits as well as the risks and challenges raised by AI-based health care, we propose five building blocks to guide the development and implementation of more responsible, sustainable, and inclusive AI health care technologies in LMICs.

背景与目标： : 世界卫生组织和其他机构正在考虑将人工智能 (AI) 视为一种技术，可以潜在地解决某些卫生系统差距，特别是减少中低收入国家 (lmic) 的全球卫生不平等现象。然而，由于大多数基于人工智能的卫生应用程序是在高收入国家开发和实施的，它们在lmic背景下的使用是最近的，并且缺乏强有力的本地评估来指导低资源环境下的决策。在讨论了基于人工智能的医疗保健带来的潜在好处以及风险和挑战之后，我们提出了五个构建模块，以指导lmic中更具责任感，可持续性和包容性的人工智能医疗技术的开发和实施。

BACKGROUND & AIMS: :Artificial sweeteners such as saccharin, aspartame, acesulfame-K, and cyclamate produce at high concentrations an unpleasant after-taste that is generally attributed to bitter and metallic taste sensations. To identify receptors involved with the complex perception of the above compounds, preference tests were performed in wild-type mice and mice lacking the TRPV1 channel or the T1R3 receptor, the latter being necessary for the perception of sweet taste. The sweeteners, including cyclamate, displayed a biphasic response profile, with the T1R3 mediated component implicated in preference. At high concentrations imparting off-taste, omission of TRPV1 reduced aversion. In a heterologous expression system the Y511A point mutation in the vanilloid pocket of TRPV1 did not affect saccharin and aspartame responses but abolished cyclamate and acesulfame-K activities. The results rationalize artificial sweetener tastes and off-tastes by showing that at low concentrations, these molecules stimulate the gustatory system through the hedonically positive T1R3 pathway, and at higher concentrations, their aversion is partly mediated by TRPV1.

背景与目标： : 人造甜味剂，例如糖精，阿斯巴甜，安赛蜜和甜蜜素在高浓度下会产生令人不快的后味，通常归因于苦味和金属味。为了鉴定与上述化合物的复杂感知有关的受体，在野生型小鼠和缺乏TRPV1通道或T1R3受体的小鼠中进行了偏好测试，后者是感知甜味所必需的。甜味剂 (包括甜蜜素) 表现出双相反应，优先考虑T1R3介导的成分。在高浓度赋予异味时，省略TRPV1会减少厌恶。在异源表达系统中，TRPV1的香草样口袋中的Y511A点突变不影响糖精和阿斯巴甜反应，但消除了甜蜜素和乙酰磺胺酸钾活性。结果通过显示在低浓度下，这些分子通过享乐阳性的T1R3途径刺激味觉系统，从而合理化了人造甜味剂的味道和味道，而在较高浓度下，它们的厌恶部分由trpv1介导。

BACKGROUND & AIMS: :This paper is based on a panel discussion held at the Artificial Intelligence in Medicine Europe (AIME) conference in Amsterdam, The Netherlands, in July 2007. It had been more than 15 years since Edward Shortliffe gave a talk at AIME in which he characterized artificial intelligence (AI) in medicine as being in its "adolescence" (Shortliffe EH. The adolescence of AI in medicine: will the field come of age in the '90s? Artificial Intelligence in Medicine 1993;5:93-106). In this article, the discussants reflect on medical AI research during the subsequent years and characterize the maturity and influence that has been achieved to date. Participants focus on their personal areas of expertise, ranging from clinical decision-making, reasoning under uncertainty, and knowledge representation to systems integration, translational bioinformatics, and cognitive issues in both the modeling of expertise and the creation of acceptable systems.

背景与目标： : 本文基于在2007年7月荷兰阿姆斯特丹举行的欧洲医学人工智能 (AIME) 会议上举行的小组讨论。自爱德华·肖特利夫 (Edward Shortliffe) 在AIME发表演讲以来，已经有15年多了，他在演讲中将医学中的人工智能 (AI) 描述为处于 “青春期” (Shortliffe EH。医学中的人工智能的青春期: 该领域会在90年代成熟吗？人工智能在医学1993;5:93-106)。在本文中，讨论者反思了随后几年的医学AI研究，并描述了迄今为止已达到的成熟度和影响力。参与者专注于他们的个人专业领域，从临床决策，不确定性下的推理和知识表示到系统集成，转化生物信息学以及在专业知识建模和可接受系统创建中的认知问题。

BACKGROUND & AIMS: :The patch-clamp technique was used to examine the plasma membranes of sensitive yeast spheroplasts exposed to partially purified killer toxin preparations. Asolectin liposomes in which the toxin was incorporated were also examined. Excised inside-out patches from these preparations often revealed at 118 pS conductance appearing in pairs. The current through this conductance flickered rapidly among three states: dwelling mostly at the unit-open state, less frequently at the two-unit-open state, and more rarely at the closed state. Membrane voltages from -80 to 80 mV had little influence on the opening probability. The current reversed near the equilibrium potential of K+ in asymmetric KCl solutions and also reversed near O mV at symmetric NaCl vs. KCl solutions. The two levels of the conductance were likely due to the toxin protein, as treatment of spheroplasts or liposomes with extracellular protein preparations from isogenic yeasts deleted for the toxin gene gave no such conductance levels. These results show that in vivo the killer-toxin fraction can form a cation channel that seldom closes regardless of membrane voltage. We suggest that this channel causes the death of sensitive yeast cells.

背景与目标： : 膜片钳技术用于检查暴露于部分纯化的杀伤毒素制剂的敏感酵母原生质膜。还检查了掺入毒素的分子脂质体。从这些制剂中切除的由内而外的斑块通常显示成对出现的118 pS电导。通过此电导的电流在三种状态下迅速闪烁: 主要停留在单元打开状态，在两个单元打开状态下频率较低，而在关闭状态下则很少。从-80到80 mV的膜电压对打开概率几乎没有影响。在不对称的KCl溶液中，电流在K的平衡电位附近反转，在对称的NaCl与KCl溶液中，电流在O mV附近反转。两个水平的电导可能是由于毒素蛋白引起的，因为用从毒素基因中删除的等基因酵母的细胞外蛋白制剂处理原生质体或脂质体没有这种电导水平。这些结果表明，在体内，杀伤毒素部分可以形成阳离子通道，无论膜电压如何，该通道很少闭合。我们建议该通道会导致敏感的酵母细胞死亡。

BACKGROUND & AIMS: :To facilitate more accurate spore proteomic analysis, the current study focuses on inducing homogeneous sporulation by overexpressing kinA and assesses the effect of synchronized sporulation initiation on spore resistance, structures, the germination behavior at single-spore level and the proteome. The results indicate that, in our set up, the sporulation by overexpressing kinA can generate a spore yield of 70% within 8 h. The procedure increases spore wet heat resistance and thickness of the spore coat and cortex layers, whilst delaying the time to spore phase-darkening and burst after addition of germinant. The proteome analysis reveals that the upregulated proteins in the kinA induced spores, compared to spores without kinA induction, as well as the 'wildtype' spores, are mostly involved in spore formation. The downregulated proteins mostly belong to the categories of coping with stress, carbon and nitrogen metabolism, as well as the regulation of sporulation. Thus, while kinA overexpression enhances synchronicity in sporulation initiation, it also has profound effects on the central equilibrium of spore formation and spore germination, through modulation of the spore molecular composition and stress resistance physiology.

背景与目标： : 为了促进更准确的孢子蛋白质组学分析，当前的研究重点是通过过度表达kinA诱导均质孢子形成，并评估同步孢子形成对孢子抗性，结构，单孢子水平的发芽行为和蛋白质组的影响。结果表明，在我们的设置中，过表达基纳的孢子形成可以在8小时内产生70% 的孢子产量。该程序增加了孢子的耐湿热性以及孢子被膜和皮质层的厚度，同时延迟了添加生发期后孢子相变暗和破裂的时间。蛋白质组分析表明，与没有基纳诱导的孢子以及 “野生型” 孢子相比，基纳诱导的孢子中上调的蛋白质主要参与孢子的形成。下调的蛋白质主要属于应对应激，碳和氮代谢以及孢子形成的调节。因此，尽管kinA过表达增强了孢子形成的同步性，但通过调节孢子分子组成和抗逆性生理，它也对孢子形成和孢子萌发的中心平衡产生了深远的影响。

BACKGROUND & AIMS: :The objective was to compare the endometrial thickness (ET) in a frozen embryo transfer (FET) cycle between transdermal and vaginal estrogen. Our secondary objectives were to compare the patient satisfaction and the pregnancy outcomes. Prospective monocentric cohort study between 01/2017 and 12/2017 at a single institution. Choice of administration was left to the patient. 119 cycles had transdermal estrogen (T-group) and 199 had vaginal estrogen (V-group). The ET at 10 ± 1 days of treatment was significantly higher in the T-group compared to the V-group (9.9 vs 9.3 mm, p = 0.03). In the T-group, the mean duration of treatment was shorter (13.6 vs 15.5 days, p < 0.001). The rate of cycle cancelation was comparable between the two groups (12.6% vs 8.5%, p = 0.24). Serum estradiol levels were significantly lower (268 vs 1332 pg/ml, p < 0.001), and serum LH levels were significantly higher (12.1 ± 16.5 vs 5 ± 7.5 mIU/ml, p < 0.001) in the T-group. Patient satisfaction was higher in the T-group (p = 0.04) and 85.7% (36/42) of women who had received both treatments preferred the transdermal over the vaginal route. Live birth rates were comparable between the two groups (18% vs 19%, p = 0.1). Transdermal estrogen in artificial FET cycles was associated with higher ET, shorter treatment duration and better tolerance.

背景与目标： : 目的是比较经皮和阴道雌激素在冷冻胚胎移植 (FET) 周期中的子宫内膜厚度 (ET)。我们的次要目标是比较患者的满意度和妊娠结局。单一机构01/2017和12/2017之间的前瞻性单中心队列研究。给药的选择留给患者。119周期有透皮雌激素 (T组)，199有阴道雌激素 (V组)。T组治疗10  ±   1天的ET显著高于V组 (9.9 vs 9.3  mm，p   =   0.03)。在T组中，平均治疗时间较短 (13.6天vs 15.5天，p  <  0.001)。两组的周期取消率相当 (12.6% vs 8.5%，p   =   0.24)。T组血清雌二醇水平显著降低 (268 vs 1332  pg/ml，p  <  0.001)，血清LH水平显著升高 (12.1   ±   16.5 vs 5   ±   7.5 mIU/ml，p  <  0.001)。T组患者满意度较高 (p   =   0.04)，接受过两种治疗的女性中有85.7% (36/42) 更喜欢透皮而不是阴道途径。两组的活产率相当 (18% vs 19%，p   =   0.1)。人工FET周期中的经皮雌激素与更高的ET，更短的治疗持续时间和更好的耐受性相关。

BACKGROUND & AIMS: :We analysed the genome-wide regulatory properties of an artificial transcription activator in which the DNA-binding domain of the yeast transcription factor, Pdr1, was fused to the activation domain of Gal4 (Pdr1*GAD). This Pdr1*GAD chimera was put under the control of the inducible GAL1 promoter. DNA microarray analyses showed that all the target genes upregulated by the well-studied native gain-of-function Pdr1-3 mutant were similarly activated by the chimerical factor Pdr1*GAD upon galactose induction. Additionally, this kinetic approach led us not only to confirm previously published targets, but also to define a hierarchy among members of the Pdr1 regulon. Our observations prove, for the first time at the complete genome level, that the DNA-binding domain of Pdr1 is sufficient to guide its specificity. We propose that this approach could be useful for the study of new transcription factors identified in silico from sequenced organisms. Complete data are available at www.biologie.ens.fr/yeast-publi.html.

背景与目标： : 我们分析了人工转录激活因子的全基因组调控特性，其中酵母转录因子Pdr1的DNA结合结构域与Gal4 (Pdr1 * GAD) 的激活结构域融合。将该Pdr1 * GAD嵌合体置于诱导型GAL1启动子的控制下。DNA微阵列分析表明，经过充分研究的天然功能获得Pdr1-3突变体上调的所有靶基因在半乳糖诱导后被嵌合因子Pdr1 * GAD类似地激活。此外，这种动力学方法不仅使我们确认了先前发布的目标，而且还定义了Pdr1正则子成员之间的层次结构。我们的观察首次在完整基因组水平上证明，Pdr1的DNA结合域足以指导其特异性。我们建议这种方法可用于研究从测序生物在计算机中鉴定的新转录因子。完整的数据可在www.biologie.ens.fr/yeast-publi.html获得。

BACKGROUND & AIMS: :Recent studies have shown that balance performance assessment based on artificial intelligence (AI) is feasible. However, balance control is very complex and requires different subsystems to participate, which have not been evaluated individually yet. Furthermore, these studies only classified individual's balance performance across limited grades. Therefore, in this study we attempted to implement AI to precisely evaluate different types of balance control subsystems (BCSes). First, a total of 224 commonly used and newly developed features were extracted from the center of pressure (CoP) data for each participant, respectively. Then, regressors were employed in order to map these features to the evaluation scores given by physical therapists, which include the total score in Mini-Balance-Evaluation-Systems-Tests (Mini-BESTest) and its sub-scores on BCSes, namely anticipatory postural adjustments (APA), reactive postural control (RPC), sensory orientation (SO), and dynamic gait (DG). Their scoring ranges should be 0-28, 0-6, 0-6, 0-6, and 0-10, respectively. The results show that their minimum mean absolute errors from AI estimation reach up to 2.658, 0.827, 0.970, 0.642, and 0.98, respectively. In sum, our study is a preliminary study for assessing BCSes based on AI, which shows its possibility to be used in the clinics in the future.

背景与目标： : 最近的研究表明，基于人工智能 (AI) 的平衡绩效评估是可行的。但是，平衡控制非常复杂，需要不同的子系统参与，尚未对其进行单独评估。此外，这些研究仅对个人在有限等级中的平衡表现进行了分类。因此，在这项研究中，我们尝试实现AI来精确评估不同类型的平衡控制子系统 (BCSes)。首先，分别从每个参与者的压力中心 (CoP) 数据中提取了总共224个常用和新开发的特征。然后，使用回归变量将这些特征映射到物理治疗师给出的评估分数，其中包括迷你平衡评估系统测试 (Mini-BESTest) 中的总分及其在BCSes上的子分数，即预期姿势调整 (APA)，反应姿势控制 (RPC)，感觉方向 (SO) 和动态步态 (DG)。他们的得分范围应分别为0-28、0-6和0-10。结果表明，来自AI估计的最小平均绝对误差分别达到2.658、0.827、0.970、0.642和0.98。总而言之，我们的研究是基于AI评估BCSes的初步研究，表明其将来有可能在诊所中使用。