BACKGROUND & AIMS: :The key component in the so-called EPRI effective dose equivalent (EDE) methodology is an algorithm that utilizes two dosimeters (instead of multiple dosimeters) to predict the EDE for external photon exposures. The exposure scenarios that were previously studied in deriving the algorithm include parallel photon beams and point sources 33 cm from the body surface. The motivation for this study was the need to investigate source locations within 33 cm from the body so the method is more widely applicable. The ORNL stylized mathematical human phantoms and the MCNP code were used to calculate organ doses in this study. This paper presents the EDE data for point gamma sources at 0.3, 1.0, and 1.5 MeV, respectively, which are located at 10 cm from the surface of the body. The results and analyses show that the locations ranging from the overhead to the foot have resulted in conservative ratios except for two general regions near the front upper thigh and directly overhead. If all locations considered in this study were averaged for each photon energy, the overall ratio is on the conservative side. These data suggest that the EPRI EDE methodology is still valid for sources located 10 cm from the body, although the chance for resulting in a non-conservative estimate of the EDE has increased in comparison with the sources located at 30 cm from the body. Finally, this paper provides recommendations on how to apply the EPRI EDE methodology.

背景与目标： ：所谓的EPRI有效剂量当量（EDE）方法中的关键组件是一种算法，该算法利用两个剂量计（而不是多个剂量计）来预测外部光子暴露的EDE。先前在推导算法时曾研究过的曝光场景包括平行光子束和距体表33 cm的点光源。这项研究的动机是需要调查距人体33厘米以内的放射源位置，因此该方法更广泛地适用。在本研究中，使用了ORNL程式化的数学人体模型和MCNP代码来计算器官剂量。本文介绍了分别位于距人体表面10 cm处的0.3 MeV，1.0 MeV和1.5 MeV的点伽马源的EDE数据。结果和分析表明，从头顶到脚的位置范围导致了保守的比率，除了大腿前上方和直接头顶附近的两个一般区域。如果在本研究中考虑的所有位置均针对每种光子能量求平均值，则总体比率处于保守的一面。这些数据表明，EPRI EDE方法对于距离人体10厘米处的放射源仍然有效，尽管与位于人体30厘米处的放射源相比，导致EDE非保守估计的机会有所增加。最后，本文提供了有关如何应用EPRI EDE方法的建议。

BACKGROUND & AIMS: OBJECTIVE:Functional near-infrared spectroscopy (fNIRS) is a non-invasive optical technique for bedside evaluation of cerebral metabolism that has clinical potential for monitoring the efficacy of pharmacological treatment. In this pilot study, we investigated the cognitive effects of methylphenidate (MP) on prefrontal function using fNIRS in healthy subjects. METHODS:Thirteen right-handed healthy subjects underwent working memory tasks (0-back and 2-back) after a single oral dose of MP (20 mg) or placebo administered in a double-blind crossover design on two different days separated by 1-3 days. We measured changes in oxyhemoglobin (oxy-Hb) and deoxyhemoglobin (deoxy-Hb) concentrations during the tasks in bilateral prefrontal regions after MP or placebo administration using two-channel fNIRS. RESULTS:There were significantly more correct responses and fewer missed responses during the 2-back task performance after MP treatment as compared with placebo. Baseline-corrected oxy-Hb was significantly decreased after MP treatment compared with the placebo in the 2-back task in the right frontal region but was not different in the 0-back task. Baseline-corrected deoxy-Hb and total-Hb concentrations were not significant between MP and placebo conditions in either of the cognitive tasks. CONCLUSIONS:These data are consistent with previous positron emission tomography findings of MP-mediated reduction in lateral prefrontal activity accompanied by improved cognitive performance.

背景与目标： 目的：功能性近红外光谱法（fNIRS）是一种非侵入性光学技术，可在床头评估脑部新陈代谢，具有监测药理学疗效的临床潜力。在这项初步研究中，我们调查了健康受试者中使用fNIRS的哌醋甲酯（MP）对前额叶功能的认知作用。
方法：13名右撇子健康受试者在双盲交叉设计中，在两天内分别以双盲交叉设计给予单次口服MP（20 mg）或安慰剂，进行了工作记忆任务（0背和2背）。 3天。我们在使用双通道fNIRS进行MP或安慰剂给药后，测量了双侧前额叶区域任务期间氧合血红蛋白（oxy-Hb）和脱氧血红蛋白（deoxy-Hb）浓度的变化。
结果：与安慰剂相比，MP治疗后的2背任务执行过程中，正确的反应明显多，漏掉的反应少。与安慰剂相比，MP处理后基线校正的oxy-Hb在右额叶区域的2后卫任务中较安慰剂显着降低，但在0后卫任务中无差异。在任一认知任务中，MP和安慰剂条件之间经基线校正的脱氧血红蛋白和总血红蛋白浓度均不显着。
结论：这些数据与以前的正电子发射断层扫描所发现的MP介导的侧前额叶活动减少以及认知能力改善相一致。

BACKGROUND & AIMS: :This study sought to investigate the relationship between going outdoor daily and prefrontal cortex activation during execution of the VFT using near-infrared spectroscopy (NIRS) in community-dwelling older adults. Blood oxygenation changes in left and right prefrontal cortices were measured in twenty older adults (mean age 76.1 ± 6.7 years) by NIRS during VFT performance. In this task, participants were required to pronounce as many nouns as possible beginning with the letters "Shi," "I," and "Re." Changes in oxygenated hemoglobin (oxy-Hb) levels during the VFT were compared between two groups defined by the frequency of going outdoors: daily or non-daily within a week. Participants in both groups exhibited significantly increased oxy-Hb levels in the left and right prefrontal cortices during the VFT compared to a resting baseline condition. After controlling for age and gender, there were significant group-by-condition interactions on oxy-Hb levels with less activation during the execution of the VFT over both cortices in the non-daily group (left: F=4.76, p=0.04; right: F=6.32, p=0.02). These findings indicate that going outdoors daily is associated with increased activation in the prefrontal cortices during VFT performance in community-dwelling older adults.

背景与目标： ：这项研究旨在调查居住在社区的老年人中，每天进行户外运动与使用近红外光谱（NIRS）进行VFT期间前额叶皮层激活之间的关系。在VFT表现期间，通过NIRS对20名老年人（平均年龄76.1±6.7岁）测量了左前额叶皮层和右前额叶皮层中的血液氧合变化。在此任务中，要求参与者以字母“ Shi”，“ I”和“ Re”开头的尽可能多的名词发音。在VFT期间，比较了两组由户外活动频率定义的两组之间的氧化血红蛋白（oxy-Hb）水平的变化：每天或一周内的非每天一次。与静止的基线状态相比，两组的参与者在VFT期间左，右前额叶皮层的氧合血红蛋白水平均显着升高。在控制了年龄和性别之后，非每日组的两个皮层在执行VFT时，氧合血红蛋白水平存在显着的组间条件交互作用，而激活较少（左：F = 4.76，p = 0.04；右：F = 6.32，p = 0.02）。这些发现表明，在社区居住的老年人中，每天进行户外运动与在VFT表现中前额叶皮层的激活增加有关。

BACKGROUND & AIMS: :The structures of d(GCAATTGC)2 and its complex with berenil in solution were analyzed by two-dimensional 1H NMR spectroscopy. Intra- and internucleotide nuclear Overhauser effect (NOE) connectivities demonstrate that the octanucleotide duplex is primarily in the B conformation. Binding with berenil stabilizes the duplex with respect to thermal denaturation by about 10 degrees C, based on the appearance of the imino proton signals. The berenil-d(GCAATTGC)2 system is in fast exchange on the NMR time scale. The two-dimensional NMR data reveal that berenil binds in the minor groove of d(GCAATTGC)2. The aromatic drug protons are placed within 5 A of the H2 proton of both adenines, the H1', H5', and H5" of both thymidines, and the H4', H5', and H5" of the internal guanosine. The amidine protons on berenil are also close to the H2 proton of both adenines. The duplex retains an overall B conformation in the complex with berenil. At 18 degrees C, NOE contacts at longer mixing times indicate the presence of end-to-end association both in the duplex alone and also in its complex with berenil. These intermolecular contacts either vanished or diminished substantially at 45 degrees C. Two molecular models are proposed for the berenil-(GCAATTGC)2 complex; one has hydrogen bonds between the berenil amidine protons and the carbonyl oxygen, O2, of the external thymines, and the other has hydrogen bonds between the drug amidine protons and the purine nitrogen, N3, of the internal adenines. Quantitative analysis of the NOE data favors the second model.

背景与目标： ：用二维1H NMR光谱分析了d（GCAATTGC）2的结构及其与苯磺酸的络合物。核苷酸内和核苷酸间核豪沃效应（NOE）的连通性表明，八核苷酸双链体主要位于B构象中。基于亚氨基质子信号的出现，与苯磺酸酯的结合相对于热变性使双链体稳定约10℃。 berenil-d（GCAATTGC）2系统在NMR时标上可以快速交换。二维NMR数据表明，苯胺醇结合在d（GCAATTGC）2的小沟中。芳香族药物质子位于两个腺嘌呤的H2质子，两个胸苷的H1'，H5'和H5”以及内部鸟苷的H4'，H5'和H5”的5 A之内。苯甲腈上的质子也接近两个腺嘌呤的H2质子。该双链体在与贝内尔的复合物中保留了整体的B构象。在18摄氏度时，NOE在较长混合时间下的接触表明在双链体中及其与苯甲腈的复合物中不仅存在端对端缔合。这些分子间的接触在45摄氏度时基本消失或减弱。对于berenil-（GCAATTGC）2配合物，提出了两种分子模型。一个在苯胺基am质子与外部胸腺嘧啶的羰基氧O2之间具有氢键，另一个在药物am质子与内部腺嘌呤的嘌呤氮N3之间具有氢键。 NOE数据的定量分析有利于第二种模型。

BACKGROUND & AIMS: :We evaluated the differences in strength of the associations of prevalent cardiovascular disease and lower extremity arterial atherosclerosis to common carotid intima-media thickness, assessed by near wall measurements only, by far wall measurements only, and by the average of near and far wall measurements. The study was based on data from 1500 participants of the Rotterdam Study, a single-center-population-based prospective follow-up study among 7983 subjects, aged 55 years or over. Comparison of the strength of the associations of near wall intima-media thickness and of combined near and far wall intima-media thickness to cardiovascular disease and lower extremity arterial atherosclerosis revealed significantly stronger associations compared to associations observed for far wall intima-media thickness, in particular for stroke and lower extremity arterial disease. We conclude that near wall common carotid intima-media thickness measurement provides at least as good an indicator of atherosclerosis elsewhere and of cardiovascular risk as the far wall intima-media thickness measurement.

背景与目标： ：我们评估了常见心血管疾病和下肢动脉粥样硬化与颈总动脉内膜中层厚度之间的关联强度差异，仅通过近壁测量，仅远壁测量以及近壁和远壁测量的平均值来评估。该研究基于来自鹿特丹研究的1500名参与者的数据，鹿特丹研究是一项基于单中心人群的前瞻性随访研究，涉及对象为7983名年龄在55岁以上的受试者。比较近壁内膜-中层厚度和近，远壁内膜-中层厚度联合对心血管疾病和下肢动脉粥样硬化的强度，发现与远壁内膜-中层厚度相关的关联明显更强。特别适用于中风和下肢动脉疾病。我们得出的结论是，近壁普通颈动脉内膜中层厚度测量至少可以提供与远壁内膜中层厚度测量一样好的动脉粥样硬化和心血管风险的指标。

BACKGROUND & AIMS: :This research firstly investigated the inhibitory effect of isoquercitrin (ISQ) on Ovalbumin (OVA) glycation. The mechanism was elucidated through the interaction between OVA and ISQ, and changes in glycation sites and degree of each site as deduced by spectroscopy, spectrometry and molecular docking. ISQ significantly inhibited OVA glycation by attenuating the conformational change induced by glycation. It quenched the fluorescence of Trp via static mechanism, and exposed Trp residues to a more hydrophobic surroundings. Formation of OVA-ISQ complex was a endothermic processing driven by hydrophobic interactions, van der Waals forces and hydrogen bonds. LC-Orbitrap-MS/MS revealed that ISQ altered the location of glycation and alleviated the glycation degree of most sites. Molecular docking results indicated that ISQ inserted into the hydrophobic pocket of OVA with six hydrogen bonds and one π-π stacking formed between ISQ and the amino acid residues of OVA, leading to the altered glycation activity of some sites.

背景与目标： ：本研究首先研究了异槲皮苷（ISQ）对卵清蛋白（OVA）糖基化的抑制作用。通过OVA和ISQ之间的相互作用以及通过光谱学，光谱学和分子对接推导的糖基化位点和每个位点的程度的变化阐明了该机理。 ISQ通过减弱糖基化诱导的构象变化来显着抑制OVA糖基化。它通过静态机制淬灭了Trp的荧光，并使Trp残基暴露于疏水性更高的环境中。 OVA-ISQ复合物的形成是由疏水相互作用，范德华力和氢键驱动的吸热过程。 LC-Orbitrap-MS / MS表明，ISQ改变了糖基化的位置并减轻了大多数位点的糖基化程度。分子对接结果表明，ISQ以六个氢键插入到OVA的疏水口袋中，在ISQ与OVA的氨基酸残基之间形成一个π-π堆积，从而导致某些位点的糖基化活性发生了改变。

BACKGROUND & AIMS: :A decoupling structure using an additional LC resonant configuration for NMR transmit coils is analysed and the probe sensitivity of the receive coil with the decoupled transmit coil is calculated using simple circuit models. An adjustment-free technique for the decoupling circuit under different loading conditions is proposed using the calculated results and demonstrated by experiments. The proposed method can simplify the probe operation.

背景与目标： ：分析了使用附加LC谐振配置的NMR发送线圈的去耦结构，并使用简单的电路模型计算了具有去耦发送线圈的接收线圈的探头灵敏度。利用计算结果，提出了一种在不同负载条件下去耦电路的免调整技术，并通过实验进行了验证。所提出的方法可以简化探测操作。

BACKGROUND & AIMS: :We are reporting a case of pyrethroid poisoning with atypical presentation in a 21-month-old toddler who was transferred to us from a peripheral center. Signs and symptoms at presentation were predominantly of cardiopulmonary dysfunction contrary to more common presenting features of gastrointestinal and neurological impairment. The reason for this seems to be the aspiration pneumonitis as a consequence of vomiting induced by parents at home, rather than the toxin itself even though a rather rapid progression of lung injury does not rule out the possibility. He had developed decreased level of consciousness and increased work of breathing after ingestion, which had progressed to Acute Respiratory Distress Syndrome, septic shock, and multi organ failure. He even had a brief cardiac arrest with Return of Spontaneous Circulation after 5 min of cardiopulmonary resuscitation, immediately after arrival at our unit, which seemed more likely to be a consequence of inappropriate management during transfer of the child. In addition to antibiotics and vasopressors, he required high frequency oscillatory ventilation and prone positioning initially, and lung-protective conventional ventilation later. His cardiopulmonary status improved gradually and he was successfully extubated after 12 days. Other organ systems also showed complete recovery. Even though Magnetic Resonance Imaging of brain done a few days after cardiac arrest showed features suggestive of hypoxic-ischemic encephalopathy he showed complete neurological recovery. He was thriving well at three-month follow-up with no neurological deficits, good exercise tolerance, and normal renal and liver function. Atypical presentation of pyrethroid poisoning is associated with significant morbidities and there seems to no reliable parameters in children to identify the risk of the same. Considering that there is no specific antidote, prompt, and aggressive supportive therapy is necessary for a favorable outcome. This case highlights several important aspects in the care of the pediatric patient after ingestion of insecticides. First, attempt to induce emesis, especially outside of a healthcare facility is not only ineffective but also highly dangerous, and should not be done. Second, unstable patients require inter and intrahospital transfer by experienced and trained personnel; and lastly, management for these complex and atypical cases should be done as early as possible in a center which is equipped to provide high level of circulatory and ventilatory support while prioritizing neuro-protective measures, and neurologic recovery and rehabilitation.

背景与目标： ：我们正在报告一例21岁大的婴儿中从典型的外围中心转移给我们的拟除虫菊酯中毒事件。表现时的体征和症状主要是心肺功能障碍，与胃肠道和神经功能障碍的更常见表现特征相反。造成这种情况的原因似乎是由父母在家中引起的呕吐引起的吸入性肺炎，而不是毒素本身，即使肺损伤的迅速发展并不排除了这种可能性。摄入后，他的意识水平下降，呼吸工作增加，已发展为急性呼吸窘迫综合症，败血性休克和多器官衰竭。他在到达我们单位后立即进行了5分钟的心肺复苏，甚至在短暂的心脏骤停后恢复了自发性循环，这似乎更可能是由于孩子转移过程中处理不当造成的。除了抗生素和血管升压药外，他还需要高频振荡通气和俯卧位，之后需要常规的肺保护通气。他的心肺状态逐渐好转，并在12天后成功拔管。其他器官系统也显示出完全恢复。即使心脏骤停后几天进行的脑磁共振成像显示出提示缺氧缺血性脑病的特征，他仍显示出完全的神经功能恢复。在三个月的随访中，他表现良好，没有神经功能缺损，良好的运动耐受性以及正常的肾和肝功能。拟除虫菊酯中毒的非典型表现与高发病率相关，儿童中似乎没有可靠的参数可确定其危险性。考虑到没有特定的解毒剂，迅速而积极的支持疗法对于取得良好的结果是必要的。该病例突出显示了在摄入杀虫剂后对小儿患者进行护理的几个重要方面。首先，尝试引起呕吐，尤其是在医疗机构外部进行呕吐，不仅效果不佳，而且非常危险，因此不应该这样做。其次，不稳定的患者需要经验丰富且训练有素的人员进行医院内部和医院之间的转移；最后，应对这些复杂和非典型病例的治疗应尽早在中心进行，该中心应提供高水平的循环和通气支持，同时优先考虑神经保护措施以及神经系统的恢复和康复。

BACKGROUND & AIMS: :Precision spectroscopy of atomic systems1 is an invaluable tool for the study of fundamental interactions and symmetries2. Recently, highly charged ions have been proposed to enable sensitive tests of physics beyond the standard model2-5 and the realization of high-accuracy atomic clocks3,5, owing to their high sensitivity to fundamental physics and insensitivity to external perturbations, which result from the high binding energies of their outer electrons. However, the implementation of these ideas has been hindered by the low spectroscopic accuracies (of the order of parts per million) achieved so far6-8. Here we cool trapped, highly charged argon ions to the lowest temperature reported so far, and study them using coherent laser spectroscopy, achieving an increase in precision of eight orders of magnitude. We use quantum logic spectroscopy9,10 to probe the forbidden optical transition in 40Ar13+ at a wavelength of 441 nanometres and measure its excited-state lifetime and g-factor. Our work unlocks the potential of highly charged ions as ubiquitous atomic systems for use in quantum information processing, as frequency standards and in highly sensitive tests of fundamental physics, such as searches for dark-matter candidates11 or violations of fundamental symmetries2.

背景与目标： ：原子系统的精密光谱学1是研究基本相互作用和对称性2的宝贵工具。最近，由于高电离的离子对基本物理的高敏感性和对外部扰动的不敏感性，已提出了高电荷的离子以实现超出标准模型2-5的物理敏感性测试和实现高精度原子钟3,5。它们的外电子具有很高的结合能。但是，到目前为止，这些思想的实现受到了低光谱精度（百万分之几）的阻碍[6-8]。在这里，我们将捕获的高电荷氩离子冷却到迄今为止报告的最低温度，并使用相干激光光谱法对其进行研究，从而将精度提高了八个数量级。我们使用量子逻辑光谱法9,10来探测40Ar13在441纳米波长处的禁止光学跃迁，并测量其激发态寿命和g因子。我们的工作释放了高电荷离子作为量子信息处理，频率标准和基础物理的高度敏感测试（如搜索暗物质候选物11或违反基本对称性2）中无处不在的原子系统的潜力。

BACKGROUND & AIMS: :We developed a pH dependent amino heptamethine cyanine based theranostic probe (I2-IR783-Mpip) that can be activated by near infrared light. I2-IR783-Mpip, in acidic condition, exhibited an intense, broad NIR absorption band (820-950 nm) with high singlet oxygen generation upon exposure to NIR light (~850 nm). Theoretical calculations showed that the protonation of the probe in an acidic environment decreased the molecular orbital energy gaps and increased the intramolecular charge transfer efficiency. I2-IR783-Mpip exhibited good photodynamic efficiency towards liver hepatocellular carcinoma cells under physiological and slightly acidic conditions while normal human embryonic kidney cells remained alive under the same conditions. Detection of intracellular reactive oxygen species (ROS) in cells treated with I2-IR783-Mpip after NIR light exposure confirmed PDT efficiency of the probe in acidic environment. Moreover, I2-IR783-Mpip also demonstrated efficient phototoxicity under deep-seated tumour cell system. We believed this is the first PDT agent that possesses intrinsic tumour binding and selectively eradicate tumour in acidic environment under 850 nm NIR lamp.

背景与目标： ：我们开发了一种基于pH的氨基七甲胺花菁基治疗药物探针（I2-IR783-Mpip），该探针可被近红外光激活。 I2-IR783-Mpip在酸性条件下表现出强烈的宽广的NIR吸收带（820-950-nm），并且在暴露于NIR光（〜850 nm）时会产生大量单线态氧。理论计算表明，在酸性环境中探针的质子化作用减小了分子轨道的能隙，并提高了分子内电荷转移效率。 I2-IR783-Mpip在生理和微酸性条件下对肝肝癌细胞表现出良好的光动力学效率，而正常的人胚胎肾细胞在相同条件下仍然存活。在NIR曝光后，用I2-IR783-Mpip处理的细胞中细胞内活性氧（ROS）的检测证实了该探针在酸性环境中的PDT效率。此外，I2-IR783-Mpip在深层肿瘤细胞系统下也表现出有效的光毒性。我们相信这是第一种具有内在的肿瘤结合能力并能够在850nm nm近红外灯下在酸性环境中根除肿瘤的PDT药物。

BACKGROUND & AIMS: BACKGROUND:Oleaginous fungi can accumulate lipids by utilizing a wide range of waste substrates. They are an important source for the industrial production of omega-6 polyunsaturated fatty acids (gamma-linolenic and arachidonic acid) and have been suggested as an alternative route for biodiesel production. Initial research steps for various applications include the screening of fungi in order to find efficient fungal producers with desired fatty acid composition. Traditional cultivation methods (shake flask) and lipid analysis (extraction-gas chromatography) are not applicable for large-scale screening due to their low throughput and time-consuming analysis. Here we present a microcultivation system combined with high-throughput Fourier transform infrared (FTIR) spectroscopy for efficient screening of oleaginous fungi. RESULTS:The microcultivation system enables highly reproducible fungal fermentations throughout 12 days of cultivation. Reproducibility was validated by FTIR and HPLC data. Analysis of FTIR spectral ester carbonyl peaks of fungal biomass offered a reliable high-throughput at-line method to monitor lipid accumulation. Partial least square regression between gas chromatography fatty acid data and corresponding FTIR spectral data was used to set up calibration models for the prediction of saturated fatty acids, monounsaturated fatty acids, polyunsaturated fatty acids, unsaturation index, total lipid content and main individual fatty acids. High coefficients of determination (R2 = 0.86-0.96) and satisfactory residual predictive deviation of cross-validation (RPDCV = 2.6-5.1) values demonstrated the goodness of these models. CONCLUSIONS:We have demonstrated in this study, that the presented microcultivation system combined with rapid, high-throughput FTIR spectroscopy is a suitable screening platform for oleaginous fungi. Sample preparation for FTIR measurements can be automated to further increase throughput of the system.

背景与目标： 背景：油脂性真菌可以利用多种废物底物来积累脂质。它们是工业生产omega-6多不饱和脂肪酸（γ-亚麻酸和花生四烯酸）的重要来源，并已被建议作为生物柴油生产的替代途径。用于各种应用的初始研究步骤包括筛选真菌，以便找到具有所需脂肪酸组成的有效真菌生产者。传统的培养方法（摇瓶）和脂质分析（萃取气相色谱法）由于通量低且分析费时，因此不适用于大规模筛选。在这里，我们介绍了结合高通量傅立叶变换红外（FTIR）光谱的微培养系统，以有效筛选油性真菌。
结果：微培养系统能够在整个培养的12天中实现高度可重复的真菌发酵。通过FTIR和HPLC数据验证了可重复性。真菌生物质的FTIR光谱酯羰基峰分析提供了一种可靠的高通量在线方法来监测脂质积累。气相色谱脂肪酸数据和相应的FTIR光谱数据之间的偏最小二乘回归用于建立校准模型，用于预测饱和脂肪酸，单不饱和脂肪酸，多不饱和脂肪酸，不饱和指数，总脂质含量和主要单个脂肪酸。较高的测定系数（R2 = 0.86-0.96）和令人满意的交叉验证残差预测偏差（RPDCV = 2.6-5.1）证明了这些模型的优越性。
结论：我们在这项研究中证明，所提出的微培养系统与快速，高通量FTIR光谱相结合是一种适合油性真菌的筛选平台。 FTIR测量的样品制备可以自动化，以进一步提高系统的通量。

BACKGROUND & AIMS: :Genome-wide association studies for non-syndromic orofacial clefting (OFC) have identified single nucleotide polymorphisms (SNPs) at loci where the presumed risk-relevant gene is expressed in oral periderm. The functional subsets of such SNPs are difficult to predict because the sequence underpinnings of periderm enhancers are unknown. We applied ATAC-seq to models of human palate periderm, including zebrafish periderm, mouse embryonic palate epithelia, and a human oral epithelium cell line, and to complementary mesenchymal cell types. We identified sets of enhancers specific to the epithelial cells and trained gapped-kmer support-vector-machine classifiers on these sets. We used the classifiers to predict the effects of 14 OFC-associated SNPs at 12q13 near KRT18. All the classifiers picked the same SNP as having the strongest effect, but the significance was highest with the classifier trained on zebrafish periderm. Reporter and deletion analyses support this SNP as lying within a periderm enhancer regulating KRT18/KRT8 expression.

背景与目标： ：针对非综合征性口面部裂口（OFC）的全基因组关联研究已经确定了基因位点的单核苷酸多态性（SNP），该基因位点的风险相关基因在口腔周皮中表达。这种SNPs的功能子集很难预测，因为皮损增强子的序列基础是未知的。我们将ATAC-seq应用于人pa上皮模型，包括斑马鱼皮per，小鼠胚胎上皮上皮细胞和人口腔上皮细胞系，以及互补的间充质细胞类型。我们确定了特定于上皮细胞的增强子集，并在这些集合上训练了空缺-kmer支持向量机分类器。我们使用分类器来预测KRT18附近12q13处14个与OFC相关的SNP的影响。所有分类器都选择了效果最强的相同SNP，但在对斑马鱼皮毛进行训练的分类器中，意义最高。记者和删除分析支持此SNP，因为它位于调节KRT18 / KRT8表达的皮层增强剂中。

BACKGROUND & AIMS: :Techniques enabling in situ monitoring of drug solubilization and changes in the solid-state of the drug during the digestion of milk and milk-based formulations are valuable for predicting the effectiveness of such formulations in improving the oral bioavailability of poorly water-soluble drugs. We have recently reported the use of low-frequency Raman scattering spectroscopy (region of analysis <200 cm-1) as an analytical approach to probe solubilization of drugs during digestion in milk using ferroquine (SSR97193) as the model compound. This study investigates the wider utilization of this technique to probe the solubilization behavior of other poorly water-soluble drugs (halofantrine, lumefantrine, and clofazimine) in not only milk but also infant formula in the absence or presence of bile salts during in vitro digestion. Multivariate analysis was used to interpret changes to the spectra related to the drug as a function of digestion time, through tracking changes in the principal component (PC) values characteristic to the drug signals. Characteristic low-frequency Raman bands for all of the drugs were evident after dispersing the solid drugs in suspension form in milk and infant formula. The drugs were generally solubilized during the digestion of the formulations as observed previously for ferroquine and correlated with behavior determined using small-angle X-ray scattering (SAXS). A greater extent of drug solubilization was also generally observed in the infant formula compared to milk. However, in the case of the drug clofazimine, the correlation between low-frequency Raman scattering and SAXS was not clear, which may arise due to background interference from clofazimine being an intense red dye, which highlights a potential limitation of this new approach. Overall, the in situ monitoring of drug solubilization in milk and milk-based formulations during digestion can be achieved using low-frequency Raman scattering spectroscopy, and the information obtained from studying this spectral region can provide better insights into drug solubilization compared to the mid-frequency Raman region.

背景与目标： ：在牛奶和乳基制剂消化过程中，能够原位监测药物溶解度和药物固态变化的技术对于预测此类制剂在改善水溶性差的药物的口服生物利用度方面的有效性非常有价值。最近，我们报道了使用低频拉曼散射光谱法（分析区域<200 cm-1）作为分析方法，使用铁喹（SSR97193）作为模型化合物，在牛奶消化过程中探查药物的增溶作用。这项研究调查了这项技术的广泛应用，以探究在体外消化过程中不存在或存在胆汁盐的情况下，牛奶中以及婴儿配方食品中其他水溶性差的药物（氟安定，鲁美汀和氯氟嗪明）的增溶行为。通过追踪药物信号特征的主成分（PC）值的变化，使用多变量分析将与药物有关的光谱变化解释为消化时间的函数。将固体药物以悬浮形式分散在牛奶和婴儿配方食品中后，所有药物的特征性低频拉曼谱带都很明显。如先前对于铁喹所观察到的，通常在制剂的消化过程中药物被溶解并且与使用小角X射线散射（SAXS）确定的行为相关。与牛奶相比，通常在婴儿配方食品中也观察到更大程度的药物增溶作用。但是，在使用氯氟齐明药物的情况下，低频拉曼散射与SAXS之间的相关性尚不清楚，这可能是由于氯氟齐明是强红色染料引起的背景干扰所致，这突显了这种新方法的潜在局限性。总体而言，使用低频拉曼散射光谱仪可以在消化过程中对牛奶和基于牛奶的配方中的药物溶解度进行原位监测，与中段相比，通过研究该光谱区域获得的信息可以提供对药物溶解度的更深入了解。频率拉曼地区。

BACKGROUND & AIMS: OBJECTIVE:Cognitive deficits are prominent in schizophrenia. Patients have an average score one standard deviation below normal on a broad spectrum of cognitive tests. It has been repeatedly noted, however, that 20%-25% of patients differ from this general pattern and score close to normal on neuropsychological testing. This study used brain morphometry to 1) identify brain abnormalities associated with more severe cognitive deficits and 2) help determine whether cognitively relatively intact patients perform better because they have less severe illness or because they have a different illness. METHOD:Patients were assigned to a neuropsychologically near normal (N=21) subgroup if they scored within 0.5 standard deviation of healthy comparison subjects (N=30) on four tests of attention and verbal and nonverbal working memory, and to a neuropsychologically impaired (N=54) group if they scored at least 1.0 standard deviation below that of comparison subjects. Subgroup assignments were confirmed with the California Verbal Learning Test and degraded-stimulus Continuous Performance Test. Volumes of ventricular compartments, hippocampus, amygdala, thalamus, cerebellum, and regional cortical gray and white matter were dependent variables. Differences among groups were evaluated by using linear mixed-model multivariate analyses with gender, age, and height as covariates. RESULTS:Both neuropsychologically near normal and neuropsychologically impaired patients had markedly smaller gray matter and larger third ventricle volumes than healthy comparison subjects. Only neuropsychologically impaired patients, however, had significantly smaller white matter and larger lateral ventricle volumes than healthy comparison subjects. CONCLUSIONS:Although both neuropsychologically impaired and neuropsychologically near normal patients have marked neuropathology in their gray matter, the relative absence of white matter pathology in the neuropsychologically near normal group suggests the possibility of differences in the disease process.

背景与目标： 目的：在精神分裂症中认知功能障碍较为突出。在广泛的认知测试中，患者的平均得分比正常人低1个标准差。但是，已经反复指出，有20％-25％的患者不同于这种一般模式，并且在神经心理学测试中得分接近正常。这项研究使用了脑形态计量学，以：1）识别与更严重的认知缺陷相关的脑部异常； 2）帮助确定相对完好的认知患者是否因病情较轻或疾病不同而表现更好。
方法：如果患者在四项注意力和言语及非言语工作记忆测试中得分均在健康比较对象（N = 30）的0.5个标准差之内，则被划分为接近神经心理学（N = 21）的亚组，并被划分为神经心理障碍（ N = 54）组，如果他们的得分至少比比较对象的得分低1.0个标准差。亚组的分配通过加利福尼亚语言学习测试和降级刺激持续表现测试得到确认。心室区，海马区，杏仁核，丘脑，小脑以及局部皮质灰色和白色物质的体积是因变量。组之间的差异通过使用性别，年龄和身高作为协变量的线性混合模型多元分析进行评估。
结果：与健康的比较对象相比，神经心理学上接近正常和神经心理学上受损的患者均具有显着较小的灰质和较大的第三脑室容积。但是，只有神经心理学障碍的患者比健康对照者的白质明显减少，侧脑室容积更大。
结论：尽管神经心理学上受损和神经心理学上接近正常的患者在其灰质方面都有明显的神经病理学，但神经心理学上接近正常组的白质病理相对不存在，提示在疾病过程中存在差异的可能性。

BACKGROUND & AIMS: :Cancer communication near the end of life has a growing evidence base, and requires clinicians to draw on a distinct set of communication skills. Patients with advanced and incurable cancers are dealing with the emotional impact of a life-limiting illness, treatment decisions that are complex and frequently involve consideration of clinical trials, and the challenges of sustaining hope while also having realistic goals. In this review, the authors sought to provide a guide to important evidence about communication for patients with advanced cancer regarding communication at diagnosis, discussing prognosis, decision making about palliative anticancer therapy and phase 1 trials, advance care planning, transitions in focus from anticancer to palliative care, and preparing patients and families for dying and death.

背景与目标： ：生命快要结束时的癌症交流有越来越多的证据基础，并要求临床医生利用一套独特的交流技巧。患有晚期和无法治愈的癌症的患者正在应对限寿疾病的情感影响，复杂且经常涉及临床试验考虑的治疗决策以及维持希望并同时实现现实目标的挑战。在这篇综述中，作者试图为晚期癌症患者的诊断，沟通，预测预后，姑息抗癌治疗的决策和1期临床试验，预先护理计划，重点从抗癌向治疗的沟通等方面的重要证据提供指南。姑息治疗，为患者和家属的死亡和死亡做准备。