BACKGROUND & AIMS: :Former long-term mining and smelting of pollymetallic ores in the Middle Spiš area caused a serious contamination problem of the environment with heavy metals and metalloids, especially mercury (Hg). Several studies have reported concentration of Hg in the area but this paper provides first detailed characterization of Hg contamination of different environmental components in agricultural, forest, grassland and urban ecosystems. The ecosystems are in different distances from emission sources - former mercury and copper smelting plants in NE Slovakia. Total Hg content was studied in soil/substrate samples (n = 234) and characteristic biological samples (Athyrium filix-femina (L.) Roth, Macrolepiota procera (Scop.) Singer, Boletus edulis Bull., Cyanoboletus pulverulentus (Opat.) Gelardi, Vizzini & Simonini, Triticum aestivum (L.), Poa pratensis (L.)) (n = 234) collected in the above-mentioned ecosystems. The level of contamination and environmental risks were assessed by contamination factor (Cf), index of geoaccumulation (Igeo) and potential environmental risk index (PER). To determine the level of transition of Hg from abiotic to biotic environment, bioconcentration factor (BCF) was used. To determine a health risk resulting from regular and long-term consumption of the locally available species, the results of the Hg content were compared with the Provisional Tolerable Weekly Intake (PTWI) for Hg defined by World Health Organization. The results suggest that almost 63% of the area belong to the very high risk category and 80% of the sampling sites shown very high contamination factor. Geoaccumulation index showed that almost 30% of the area is very strongly contaminated and only 8% is not contaminated with Hg. Spearman's correlation relationship confirmed that the values of PER, BCF, Cf and Igeo decreased with an increasing distance from the pollution source. The percentage of contribution to PTWI ranged between 5.76-69.0% for adults and 11.5-138% for children. Mushroom M. procera showed the highest %PTWI among the tested biological samples. Studied ecotoxicological parameters showed high level of health risk for population living in the area. Consumption of the crops grown in the area and mainly edible wild mushrooms might negatively affect the health of the consumers in the long-term.

背景与目标： ：斯皮什中部地区过去长期开采和冶炼金属金属矿石，严重污染了环境中的重金属和准金属，特别是汞（Hg）。几项研究报告了该地区汞的浓度，但是本文首先详细介绍了农业，森林，草原和城市生态系统中不同环境成分的汞污染特征。生态系统与排放源的距离不同-斯洛伐克东北部以前的汞和铜冶炼厂。在土壤/底物样品（n = 234）和特征性生物样品（Athyrium filix-femina（L.）Roth，Macrolepiota procera（Scop。）歌手，Boletus edulis Bull。，Cyanoboletus pulverulentus（Opat。）Gelardi中研究了总汞含量，维齐尼和西蒙尼尼，普通小麦（L.），波阿普拉（L.））（n = 234）收集在上述生态系统中。通过污染因子（Cf），地质累积指数（Igeo）和潜在环境风险指数（PER）评估污染水平和环境风险。为了确定汞从非生物环境向生物环境的过渡水平，使用了生物浓缩因子（BCF）。为了确定长期和长期食用当地可用物种而引起的健康风险，将汞含量的结果与世界卫生组织确定的汞的暂定每周耐受摄入量（PTWI）进行了比较。结果表明，几乎63％的区域属于极高风险类别，而80％的采样点显示极高的污染因子。地质累积指数表明，该地区近30％的区域受到非常严重的污染，只有8％的区域未被Hg污染。 Spearman的相关关系证实，PER，BCF，Cf和Igeo的值随着距污染源距离的增加而降低。成人对PTWI的贡献百分比在5.76-69.0％之间，儿童为11.5-138％。在所测试的生物样品中，蘑菇proc。procera显示出最高的％PTWI。研究的生态毒理学参数显示出该地区居民的健康风险较高。从长远来看，该地区种植的农作物和主要是食用野生蘑菇的消费可能会对消费者的健康产生负面影响。

BACKGROUND & AIMS: :In the present study, we investigated the effects of repeated morphine pre-treatment on impairment of spatial memory acquisition induced by intra dorsal hippocampus (intra-CA1) administration of the non-selective cannabinoid CB1/CB2 receptor agonist, WIN55,212-2 in adult male rats. 2-day version of Morris water maze task has been used for the assessment of spatial memory. On the training day, rats were trained by a single training session of eight trials and 24 h later a probe trial test consist of 60s free swim period without a platform and the visible test was administered. Animals received pre-treatment subcutaneous (s.c.) injections of morphine, once daily for three days followed by five days drug-free treatment before training trials. The results indicated that bilateral pre-training intra-CA1 infusions of WIN55,212-2 (0.25 and 0.5 μg/rat) impaired acquisition of spatial memory on the training and test day. The amnesic effect of WIN55, 212-2 (0.5 μg/rat) was prevented in rats previously injected with morphine (20 mg/kg/day × 3 days, s.c.). Improvement in spatial memory acquisition in morphine-pretreated rats was inhibited by once daily administration of naloxone (1 and 2 mg/kg, s.c.) 15 min prior to injection of morphine for three days. The results suggest that sub-chronic morphine treatment may produced sensitization to cannabinoids, which in turn reversed the impairment of spatial memory acquisition induced by WIN55,212-2 and mu- opioid receptors may play an important role in this effect.

背景与目标： ：在本研究中，我们研究了重复吗啡预处理对非选择性大麻素CB1 / CB2受体激动剂WIN55,212-2背侧海马内（intra-CA1）给药引起的空间记忆获得障碍的影响在成年雄性大鼠中。莫里斯水迷宫任务的2天版本已用于评估空间记忆。在训练当天，通过八次试验的单次训练对大鼠进行了训练，并且在24小时后，探针试验测试包括无平台的60秒钟自由游泳期，并进行了可见测试。在训练试验前，动物每天接受一次皮下（s.c.）皮下注射吗啡治疗，连续三天，然后进行五天的无毒治疗。结果表明，WIN55,212-2的双边训练前CA1输注（0.25和0.5μg/大鼠）在训练和测试当天损害了空间记忆的获取。在事先注射吗啡（20 mg / kg /天×3天，s.c.）的大鼠中，WIN55，212-2（0.5μg/只）的记忆消除得到了预防。在吗啡注射前三天，每天一次给予纳洛酮（1和2 mg / kg，皮下注射），抑制吗啡预处理的大鼠的空间记忆获得性的改善受到抑制，时间为15分钟。结果表明，亚慢性吗啡治疗可能对大麻素产生致敏作用，从而逆转了由WIN55,212-2引起的空间记忆获得障碍，而多阿片受体可能在这种作用中起重要作用。

BACKGROUND & AIMS: :Mitochondrial swelling is a hallmark of mitochondrial dysfunction, and is an indicator of the opening of the mitochondrial permeability transition pore. We introduce here a novel quantitative in situ single-cell assay of mitochondrial swelling based on standard wide-field or confocal fluorescence microscopy. This morphometric technique quantifies the relative diameter of mitochondria labeled by targeted fluorescent proteins. Fluorescence micrographs are spatial bandpass filtered transmitting either high or low spatial frequencies. Mitochondrial swelling is measured by the fluorescence intensity ratio of the high- to low-frequency filtered copy of the same image. We have termed this fraction the "thinness ratio". The filters are designed by numeric optimization for sensitivity. We characterized the thinness ratio technique by modeling microscopic image formation and by experimentation in cultured cortical neurons and astrocytes. The frequency domain image processing endows robustness and subresolution sensitivity to the thinness ratio technique, overcoming the limitations of shape measurement approaches. The thinness ratio proved to be highly sensitive to mitochondrial swelling, but insensitive to fission or fusion of mitochondria. We found that in situ astrocytic mitochondria swell upon short-term uncoupling or inhibition of oxidative phosphorylation, whereas such responses are absent in cultured cortical neurons.

背景与目标： ：线粒体肿胀是线粒体功能障碍的标志，并且是线粒体通透性过渡孔开放的指示。我们在此介绍一种基于标准的宽视野或共聚焦荧光显微镜的线粒体肿胀的新型定量原位单细胞测定方法。这种形态计量技术可量化靶向荧光蛋白标记的线粒体的相对直径。荧光显微照片是经过空间带通滤波的，可以传输高空间频率或低空间频率。线粒体肿胀是通过同一图像的高频至低频过滤副本的荧光强度比来衡量的。我们称此分数为“薄度比”。滤波器是通过数值优化设计的，以提高灵敏度。我们通过对显微图像形成进行建模并在培养的皮层神经元和星形胶质细胞中进行实验来表征稀薄率技术。频域图像处理赋予了稀薄率技术以鲁棒性和子分辨率灵敏度，克服了形状测量方法的局限性。薄度比证明对线粒体肿胀高度敏感，但对线粒体的裂变或融合不敏感。我们发现，在短期解偶联或抑制氧化磷酸化后，原位星形胶质细胞线粒体膨胀，而在培养的皮层神经元中则没有这种反应。

BACKGROUND & AIMS: :Regression methods for the analysis of paired measurements produced by two fallible assay methods are described and their advantages and pitfalls discussed. The difficulties for the analysis, as in any errors-in-variables problem lies in the lack of identifiability of the model and the need to introduce questionable and often naïve assumptions in order to gain identifiability. Although not a panacea, the use of instrumental variables and associated instrumental variable (IV) regression methods in this area of application has great potential to improve the situation. Large samples are frequently needed and two-phase sampling methods are introduced to improve the efficiency of the IV estimators.

背景与目标： ：描述了用于分析由两种易失分析方法产生的配对测量值的回归方法，并讨论了它们的优点和陷阱。像任何变量误差问题一样，分析的困难在于缺乏模型的可识别性，并且需要引入可疑且通常为幼稚的假设以获取可识别性。尽管不是万能药，但在此应用领域中使用工具变量和相关的工具变量（IV）回归方法具有改善这种情况的巨大潜力。经常需要大样本，并且引入了两阶段采样方法以提高IV估计器的效率。

BACKGROUND & AIMS: :Intravenous injections into nude mice of 5 mg/kg methotrexate (MTX) linked to the antibody to human high molecular weight-melanoma associated antigen (HMW-MAA), monoclonal antibody (mAb) 225.28, an IgG2a, on days 1, 4, 7, 10 and 14, starting 24 h after subcutaneous inoculation of 2 x 10(6) cultured human M21 melanoma cells inhibited mean tumor volume by 90% on day 14 and by 65% on day 50 after the beginning of the treatment. Injections of equimolar amounts of free MTX and MTX linked to normal mouse IgG or to an isotype-matched myeloma protein did not inhibit tumor growth significantly. MTX linked to mAb 225.28 did not inhibit the xenograft of a subline of human melanoma cell line M21 without detectable expression of HMW-MAA. In a clonogenic assay, the MTX-225.28 conjugate was three times more potent in inhibiting the growth of M21 melanoma cells than free MTX, but did not inhibit the growth of kidney carcinoma cells Caki-1, which do not express high-Mr MAA. In contrast, MTX linked to the mAb DAL K29, reacting with kidney carcinoma cells Caki-1, inhibited their growth but did not affect that of melanoma cells. M21 melanoma cells isolated from the residual tumor of a mouse treated with the MTX-225.28 conjugate did not differ in their reactivity with mAb 225.28 and in their sensitivity to MTX when compared with M21 cells from an untreated mouse.

背景与目标： ：在第1天，第4天，静脉注射5 mg / kg甲氨蝶呤（MTX）与人高分子量黑素瘤相关抗原（HMW-MAA）抗体，单克隆抗体（mAb）225.28和IgG2a抗体相连。在皮下接种2 x 10（6）培养的人M21黑色素瘤细胞后24小时开始，如图7、10和14所示，治疗开始后第14天的平均肿瘤体积抑制了90％，第50天的平均肿瘤抑制了65％。注射等摩尔量的游离MTX和与正常小鼠IgG或同型匹配的骨髓瘤蛋白连接的MTX不会显着抑制肿瘤的生长。没有检测到HMW-MAA表达，与mAb 225.28连接的MTX不会抑制人黑素瘤细胞系M21亚系的异种移植。在克隆形成试验中，MTX-225.28缀合物在抑制M21黑色素瘤细胞生长方面比游离MTX强三倍，但不抑制不表达高Mr MAA的肾癌细胞Caki-1的生长。相反，与单克隆抗体DAL K29连接的MTX与肾癌细胞Caki-1反应，抑制了它们的生长，但不影响黑色素瘤细胞的生长。与未经处理的小鼠的M21细胞相比，从用MTX-225.28偶联物治疗的小鼠的残留肿瘤中分离出的M21黑色素瘤细胞与mAb 225.28的反应性和对MTX的敏感性没有差异。

BACKGROUND & AIMS: :Globba lancangensis is a typical myrmecochorous perennial herb found in southwest China. In 2002 and 2003, seed dispersal by ants was examined. Twelve ant species were recorded and found to move seeds 0.01-3.35 m. This removal promoted seed dispersal. In 2003, ant exclusion was made in 4 of 8 study plots for 1 year to practically detect the effects of ant dispersal. As a result, nearest neighbor analyses indicated that although ant dispersal could not significantly change the mean nearest neighbor distance, it obviously reduced the clustering degree of seedlings. Spatial genetic structure (SGS) of mature plants in 2003 and sequent seedlings in 2004 were investigated with intersimple sequence repeats. The whole correlagram of all individuals from 2003 showed significant positive autocorrelations between genetic and geographical distances within 4 m, suggesting a patchy structure at such short distances in the studied population. This pattern is likely associated with limited seed dispersal. The comparative analysis of fine-scale correlograms (<4 m) for ant-excluded treatment indicated lacking ants as the primary dispersers could have a similar pattern to ant dispersal presence, which is likely due to the restriction of ant dispersal distance. In conclusion, ant-mediated dispersal contributes to reduce seedling clustering degree and plays a minor role in developing and maintaining the local SGS in G. lancangensis.

背景与目标： 兰科（Globba lancangensis）是在中国西南部发现的一种典型的多年生食虫性多年生草本植物。在2002年和2003年，研究了蚂蚁对种子的传播。记录了十二种蚂蚁物种，发现它们移动种子0.01至3.35 m。这种去除促进了种子的分散。 2003年，在8个研究小区中的4个进行了1年的蚂蚁排除，以实际检测蚂蚁扩散的影响。结果，最近邻分析表明，尽管蚂蚁散布不能显着改变平均最近邻距离，但明显降低了幼苗的聚集度。利用简单的序列重复进行了2003年成熟植物和2004年随后幼苗的空间遗传结构研究。从2003年开始，所有个体的整体相关图谱都显示4m以内的遗传距离与地理距离之间存在显着的正自相关，这表明在如此短的距离内，研究人群中的斑片结构。这种模式可能与种子散播受限有关。排除蚂蚁的处理的细尺度相关图（<4 m）的比较分析表明缺少蚂蚁，因为主要分散剂可能具有与蚂蚁分散存在相似的模式，这很可能是由于蚂蚁分散距离的限制所致。总之，蚂蚁介导的散布有助于降低幼苗的聚集程度，并且在澜沧G的局部SGS的发育和维持中起着较小的作用。

BACKGROUND & AIMS: PURPOSE:A pattern electroretinogram (PERG) in which stimuli displaying the frequency-doubling (FD) illusion are presented simultaneously to multiple parts of the visual field was evaluated for its ability to diagnose glaucoma. This multiregion FD PERG is referred to in the current study as the MFP. METHODS:The nine stimulus regions were temporally modulated at incommensurate frequencies typically producing an FD percept. Two other spatial scales of the stimuli were also investigated. The sensitivity and specificity of MFP were examined using linear and quadratic discriminant methods. RESULTS:Even with the simpler linear discriminant classification, sensitivities and specificities of 100% were obtained in eyes with moderate to severe glaucoma. Of eyes with glaucoma strongly suspected, 67% were classified as being glaucomatous. Stimulus patterns having differing spatial scales produced different PERG visual field dependencies. CONCLUSIONS:The differing results for the 16-fold change in spatial scale may reflect the accessing of different mechanisms. The MFP method appears to have significant value for the diagnosis of glaucoma.

背景与目标： 目的：评估其中显示倍频（FD）幻觉的刺激同时出现在视野的多个部分的模式视网膜电图（PERG）的诊断青光眼的能力。在当前研究中，此多区域FD PERG被称为MFP。
方法：九个刺激区域在不适当的频率下进行时间调制，通常会产生FD感知。还研究了刺激的其他两个空间尺度。使用线性和二次判别方法检查了MFP的敏感性和特异性。
结果：即使采用简单的线性判别分类，中度至重度青光眼的敏感性和特异性仍达到100％。在强烈怀疑患有青光眼的眼睛中，有67％被归类为青光眼。具有不同空间比例的刺激模式会产生不同的PERG视野依赖性。
结论：空间尺度16倍变化的不同结果可能反映了不同机制的进入。 MFP方法似乎对青光眼的诊断具有重要价值。

BACKGROUND & AIMS: STUDY DESIGN:Cross-sectional. OBJECTIVE:To investigate predictors of increased frontal plane knee projection angle (FPKPA) in athletes. BACKGROUND:The underlying mechanisms that lead to increased FPKPA are likely multifactorial and depend on how the musculoskeletal system adapts to the possible interactions between its distal and proximal segments. Bivariate and linear analyses traditionally employed to analyze the occurrence of increased FPKPA are not sufficiently robust to capture complex relationships among predictors. The investigation of nonlinear interactions among biomechanical factors is necessary to further our understanding of the interdependence of lower-limb segments and resultant dynamic knee alignment. METHODS:The FPKPA was assessed in 101 athletes during a single-leg squat and in 72 athletes at the moment of landing from a jump. The investigated predictors were sex, hip abductor isometric torque, passive range of motion (ROM) of hip internal rotation (IR), and shank-forefoot alignment. Classification and regression trees were used to investigate nonlinear interactions among predictors and their influence on the occurrence of increased FPKPA. RESULTS:During single-leg squatting, the occurrence of high FPKPA was predicted by the interaction between hip abductor isometric torque and passive hip IR ROM. At the moment of landing, the shank-forefoot alignment, abductor isometric torque, and passive hip IR ROM were predictors of high FPKPA. In addition, the classification and regression trees established cutoff points that could be used in clinical practice to identify athletes who are at potential risk for excessive FPKPA. CONCLUSION:The models captured nonlinear interactions between hip abductor isometric torque, passive hip IR ROM, and shank-forefoot alignment.

背景与目标： 研究设计：横断面。
目的：探讨运动员额叶膝关节前凸角（FPKPA）增加的预测因素。
背景：导致FPKPA增加的潜在机制可能是多因素的，取决于肌肉骨骼系统如何适应其远端和近端节段之间的可能相互作用。传统上用于分析FPKPA增加的发生的双变量和线性分析不够稳健，无法捕获预测变量之间的复杂关系。对生物力学因素之间的非线性相互作用的研究对于进一步了解下肢节段之间的相互依赖性以及由此产生的动态膝关节对准是必要的。
方法：单腿深蹲时对101名运动员进行了FPKPA评估，跳跃着陆时对72名运动员进行了FPKPA评估。研究的预测指标包括性别，髋关节外展肌等距扭矩，髋关节内部旋转（IR）的被动运动范围（ROM）和小腿前掌对准。使用分类树和回归树来研究预测变量之间的非线性相互作用及其对增加的FPKPA发生的影响。
结果：在单腿下蹲期间，通过髋外展肌等长扭矩与被动髋关节IR ROM的相互作用预测了高FPKPA的发生。在着陆时，小腿前掌对准，外展肌等距扭矩和被动髋关节IR ROM是高FPKPA的预测指标。此外，分类树和回归树确定了临界点，可在临床实践中使用该临界点来识别可能存在过量FPKPA潜在风险的运动员。
结论：该模型捕获了髋关节外展肌等长扭矩，被动髋关节IR ROM和小腿前掌对准之间的非线性相互作用。

BACKGROUND & AIMS: BACKGROUND:Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a complex disease, whose exact cause remains unclear. A wide range of risk factors has been proposed that helps understanding potential disease pathogenesis. However, there is little consistency for many risk factor associations, thus we undertook an exploratory study of risk factors using data from the UK ME/CFS Biobank participants. We report on risk factor associations in ME/CFS compared with multiple sclerosis participants and healthy controls. METHODS:This was a cross-sectional study of 269 people with ME/CFS, including 214 with mild/moderate and 55 with severe symptoms, 74 people with multiple sclerosis (MS), and 134 healthy controls, who were recruited from primary and secondary health services. Data were collected from participants using a standardised written questionnaire. Data analyses consisted of univariate and multivariable regression analysis (by levels of proximity to disease onset). RESULTS:A history of frequent colds (OR = 8.26, P <= 0.001) and infections (OR = 25.5, P = 0.015) before onset were the strongest factors associated with a higher risk of ME/CFS compared to healthy controls. Being single (OR = 4.41, P <= 0.001), having lower income (OR = 3.71, P <= 0.001), and a family history of anxiety is associated with a higher risk of ME/CFS compared to healthy controls only (OR = 3.77, P < 0.001). History of frequent colds (OR = 6.31, P < 0.001) and infections before disease onset (OR = 5.12, P = 0.005), being single (OR = 3.66, P = 0.003) and having lower income (OR = 3.48, P = 0.001), are associated with a higher risk of ME/CFS than MS. Severe ME/CFS cases were associated with lower age of ME/CFS onset (OR = 0.63, P = 0.022) and a family history of neurological illness (OR = 6.1, P = 0.001). CONCLUSIONS:Notable differences in risk profiles were found between ME/CFS and healthy controls, ME/CFS and MS, and mild-moderate and severe ME/CFS. However, we found some commensurate overlap in risk associations between all cohorts. The most notable difference between ME/CFS and MS in our study is a history of recent infection prior to disease onset. Even recognising that our results are limited by the choice of factors we selected to investigate, our findings are consistent with the increasing body of evidence that has been published about the potential role of infections in the pathogenesis of ME/CFS, including common colds/flu.

背景与目标： 背景：肌痛性脑脊髓炎/慢性疲劳综合症（ME / CFS）是一种复杂的疾病，其确切病因尚不清楚。已经提出了广泛的风险因素，有助于理解潜在的疾病发病机理。但是，许多危险因素关联的一致性很少，因此我们使用来自英国ME / CFS生物银行参与者的数据对危险因素进行了探索性研究。我们报告与多发性硬化症参与者和健康对照相比，ME / CFS中的危险因素关联。
方法：这是一项横断面研究，从原发性和继发性患者中招募了269名ME / CFS患者，包括214名轻度/中度患者和55名严重症状患者，74名多发性硬化症（MS）患者和134名健康对照者健康服务。使用标准化的书面调查表从参与者收集数据。数据分析包括单变量和多变量回归分析（根据疾病发病程度的接近程度）。
结果：与健康对照相比，发作前有频繁感冒（OR = 8.26，P <= 0.001）和感染（OR = 25.5，P = 0.015）的病史是与ME / CFS风险较高相关的最强因素。单身（OR = single4.41，P <= 0.001），收入较低（OR = income3.71，P <= 0.001），且有焦虑症的家族史与仅健康对照者相比具有较高的ME / CFS风险（OR = 3.77，P <0.001）。经常感冒（OR = 6.31，P <0.001）和疾病发作前感染的病史（OR = 5.12，P = 0.005），单身（OR = 3.66，P = 0.003）并且收入较低（OR = 3.48，P = 0.001），与MS相比，ME / CFS的风险更高。严重的ME / CFS病例与ME / CFS发病年龄较低（OR = 0.63，P = 0.022）和神经系统疾病家族史（OR = 6.1，P = 0.001）有关。
结论：ME / CFS与健康对照组，ME / CFS和MS以及轻度-中度和重度ME / CFS之间存在明显的风险差异。但是，我们发现所有队列之间的风险关联存在相应的重叠。在我们的研究中，ME / CFS和MS之间最显着的差异是疾病发作之前最近的感染史。即使认识到我们的结果受到我们选择调查的因素的选择的限制，我们的发现也与越来越多的证据相一致，该证据已发表，有关感染在ME / CFS发病机理中的潜在作用，包括普通感冒/流感。

BACKGROUND & AIMS: BACKGROUND:The purpose of this study was to explore the association of five factors personality traits, as predictor variables, with the anxiety and depression as joint dependent variables in an Iranian adult population. SUBJECTS AND METHODS:A total of 3175 subjects living in Isfahan participated in this cross-sectional population-based study (SEPAHAN) and completed self-administered questionnaires about demographic, life style, gastrointestinal disorders, personality traits, social support, and psychological problems. Data was analyzed using bivariate multiple binary logistic regression in R Free statistical software. RESULTS:The results indicated high scores of neuroticisms increase the risk of anxiety and depression after adjustment for the potential confounders in total sample (OR (95% CI): 1.22 (1.19-1.24) and 1.19 (1.17-1.21), respectively) as well as in both male and female. In contrast, joint inverse associations were found between anxiety and depression with high extraversion (OR (95% CI): 0.90 (0.88-0.92) and 0.91 (0.89-0.92), respectively), agreeableness (0.93 (0.91-0.96) and 0.94 (0.92-0.96) respectively) and conscientiousness scores (0.95 (0.93-0.97) and 0.95 (0.94-0.97) respectively) as well as in both male and female. Furthermore, higher scores of openness had significant inverse association with depression in male. CONCLUSION:The present study indicated that higher scores of neuroticism, however lower extraversion, conscientiousness and agreeableness scores are risk factors for both anxiety and depression in Iranian adult population. It is suggested to perform family studies or twin and genetic association studies with considering combinations of personality traits (personality styles), and also measuring personality traits at the facet level.

背景与目标： 背景：本研究的目的是探讨伊朗成年人口中五项因素的人格特质（作为预测变量）与焦虑和抑郁作为联合因变量之间的关系。
受试者与方法：总共3175名居住在伊斯法罕的受试者参加了这项基于人群的横断面研究（SEPAHAN），并完成了有关人口统计学，生活方式，胃肠道疾病，人格特质，社会支持和心理问题的自我管理问卷。在R Free统计软件中使用双变量多元二元logistic回归分析数据。
结果：结果表明，对总样本中潜在的混杂因素进行调整后，高分的神经质增加了焦虑和抑郁的风险（OR（95％CI）：1.22（1.19-1.24）和1.19（1.17-1.21））以及男性和女性。相比之下，焦虑和抑郁之间的关节逆向关联具有高外向性（OR（95％CI）：0.90（0.88-0.92）和0.91（0.89-0.92）），顺应性（0.93（0.91-0.96）和0.94） （分别为0.92-0.96）和尽责分数（分别为0.95（0.93-0.97）和0.95（0.94-0.97））以及男性和女性。此外，较高的开放度得分与男性抑郁症呈显着的负相关。
结论：本研究表明，神经质评分较高，但外向性，尽责性和可取性评分较低是伊朗成年人口焦虑和抑郁的危险因素。建议进行家庭研究或双胞胎和遗传关联研究，同时考虑人格特质（人格风格）的组合，并在层面上测量人格特质。

BACKGROUND & AIMS: In the scope of a multi-center-study 35 resection specimens from patients with locally advanced non-small cell lung cancer after neoadjuvant chemotherapy and radiation were processed histologically and graded according to the following regression grading systemcomplete tumor regression. In 15 patients with grade II a to III tumor regression roughly concentric foci of various size with a sequence of central tumor necrosis, narrow foam cell rim, vascular granulation tissue and peripheral scar formation were demonstrated as characteristic feature of response to neoadjuvant therapy. In patients with grade IIb to III tumor regression ("responders") median survival time of 27.9 months was significantly longer than in patients with grade I to II a tumor regression ("non-responders") with a median survival time of 12.7 months.

背景与目标： 在一项多中心研究的范围内，对35位来自新辅助化疗和放疗后局部晚期非小细胞肺癌患者的切除标本进行了组织学处理，并根据以下回归分级系统对肿瘤进行了完全回归。在15例IIa至III级肿瘤消退的患者中，各种大小的同心灶与一系列中央肿瘤坏死，狭窄的泡沫细胞边缘，血管肉芽组织和周围疤痕形成被证明是对新辅助治疗反应的特征。在具有IIb至III级肿瘤消退（“应答者”）的患者中，平均存活时间为27.9个月，明显比具有I至II级肿瘤消退（“非应答者”）的患者中位存活时间为12.7个月。

BACKGROUND & AIMS: :In early phase clinical trial, finding maximum-tolerated dose (MTD) is a very important goal. Many researches show that finding a correct MTD can improve drug efficacy and safety significantly. Usually, dose-finding trials start from very low doses, so in many cases, more than 50% patients or cohorts do not have dose-limiting toxicity (DLT), but DLT may occur suddenly and increase fast along with just two or three doses. Although some fantastic models were built to find MTD, little consideration was given to those '0 DLTs' and the 'jump' of DLTs. In this paper, we developed a Bayesian zero-inflated binomial regression for dose-finding study, which analyses dose-finding data from two aspects: 1) observation of only zeros, 2) number of DLTs based on binomial distribution, so it can help us analyse if the cohorts without DLT have potential possibility to have DLT and fit the 'jump' of DLTs.

背景与目标： ：在早期临床试验中，找到最大耐受剂量（MTD）是非常重要的目标。许多研究表明，找到正确的MTD可以显着提高药物疗效和安全性。通常，剂量寻找试验从非常低的剂量开始，因此在许多情况下，超过50％的患者或队列没有剂量限制性毒性（DLT），但是DLT可能突然发生并且仅以两或三剂就可以快速增加。尽管构建了一些出色的模型来查找MTD，但很少考虑那些“ 0 DLT”和DLT的“跳跃”。在本文中，我们开发了用于剂量查找研究的贝叶斯零膨胀二项式回归，它从两个方面分析了剂量查找数据：1）仅观察零，2）基于二项式分布的DLT数量，因此可以提供帮助我们分析了没有DLT的人群是否有可能拥有DLT并适应DLT的“跳跃”。

BACKGROUND & AIMS: BACKGROUND:Road traffic injuries (RTIs) have been one of the most critical public health problems in Thailand for decades. The objective of this study was to examine to what extent provincial economy was associated with RTIs, road traffic deaths and case fatality rate in Thailand. METHODS:A secondary data analysis on time-series data was applied. The unit of analysis was a panel of 77 provinces during 2012-2016. Data were obtained from relevant public authorities, including the Ministry of Public Health. Descriptive statistics and econometric models, using negative binomial (NB) regression, negative binomial regression with random-effects (RE) model, and spatial Durbin model (SDM) were employed. The main predictor variable was gross domestic product (GDP) per capita and the outcome variables were incidence proportion of RTIs, traffic deaths and case fatality rate. The analysis was adjusted for key covariates. RESULTS:The incidence proportion of RTIs rose from 449.0 to 524.9 cases per 100,000 population from 2012 till 2016, whereas the incidence of traffic fatalities fluctuated between 29.7 and 33.2 deaths per 100,000 population. Case fatality rate steadily stood at 0.06-0.07 deaths per victim. RTIs and traffic deaths appeared to be positively correlated with provincial economy in the NB regression and the RE model. In the SDM, a log-Baht increase in GDP per capita (equivalent to a growth of GDP per capita by about 2.7 times) enlarged the incidence proportion of injuries and deaths by about a quarter (23.8-30.7%) with statistical significance. No statistical significance was found in case fatality rate by the SDM. The SDM also presented the best model fitness relative to other models. CONCLUSION:The incidence proportion of traffic injuries and deaths appeared to rise alongside provincial prosperity. This means that RTIs-preventive measures should be more intensified in economically well-off areas. Furthermore, entrepreneurs and business sectors that gain economic benefit in a particular province should share responsibility in RTIs prevention in the area where their businesses are running. Further studies that explore others determinants of road safety, such as patterns of vehicles used, attitudes and knowledge of motorists, investment in safety measures, and compliance with traffic laws, are recommended.

背景与目标： 背景：道路交通伤害（RTI）一直是泰国几十年来最严重的公共卫生问题之一。这项研究的目的是研究泰国的省级经济在多大程度上与RTI，道路交通事故死亡和病死率相关。
方法：对时间序列数据进行二次数据分析。分析单位是2012-2016年期间由77个省组成的小组。数据来自包括公共卫生部在内的相关公共部门。采用负二项式（NB）回归，带随机效应的负二项式回归（RE）模型和空间Durbin模型（SDM）进行描述性统计和计量经济学模型。主要的预测变量是人均国内生产总值（GDP），结果变量是RTI发生率，交通死亡和病死率。针对关键协变量对分析进行了调整。
结果：从2012年到2016年，RTIs的发病率从449.0例增加到524.9例/每100,000人口，而交通死亡的发生率在每100,000例死亡的29.7至33.2例之间波动。病死率稳步上升为每位受害者死亡0.06-0.07。在NB回归和RE模型中，RTIs和交通事故死亡与省级经济似乎呈正相关。在SDM中，人均GDP的对数铢增长（相当于人均GDP增长约2.7倍）使受伤和死亡的发生率增加了约四分之一（23.8-30.7％），具有统计意义。 SDM的病死率未发现统计学意义。 SDM还提供了相对于其他模型的最佳模型适用性。
结论：交通伤害和死亡的发生比例随着省的繁荣而上升。这意味着在经济上较富裕的地区应进一步加强预防RTIs的措施。此外，在特定省份中获得经济利益的企业家和商业部门应在其经营所在的地区共同承担预防RTI的责任。建议进行进一步研究，以探索其他影响道路安全的因素，例如所用车辆的模式，驾车者的态度和知识，对安全措施的投资以及是否遵守交通法规。

BACKGROUND & AIMS: :Metastatic melanoma is one of the most immunogenic malignancies due to its high rate of mutations and neoantigen formation. Response to BRAF inhibitors (BRAFi) may be determined by intratumoral immune activation within melanoma metastases. To evaluate whether CD8+ T cell infiltration and distribution within melanoma metastases can predict clinical response to BRAFi, we developed a methodology to integrate immunohistochemistry with automated image analysis of CD8+ T cell position. CD8+ distribution patterns were correlated with gene expression data to identify and quantify "hot" areas within a tumor. Furthermore, the relative activation of CD8+cells, based on transcriptomic analysis, and their relationship to other CD8+ T cells and non-CD8+ cells within the tumor suggested a less crowded distribution of cells around activated CD8+ T cells. Furthermore, the relative activation of these CD8+ T cells was associated with improved clinical outcomes and decreased tumor cell proliferation. This study demonstrates the potential of digital pathomics to incorporate immune cell spatial distribution within metastases and RNAseq analysis to predict clinical response to BRAF inhibition in metastatic melanoma.

背景与目标： ：转移性黑素瘤由于其高突变率和新抗原形成而成为最具免疫原性的恶性肿瘤之一。对BRAF抑制剂（BRAFi）的反应可以通过黑色素瘤转移瘤内的肿瘤内免疫激活来确定。为了评估黑色素瘤转移中CD8 T细胞的浸润和分布是否可以预测对BRAFi的临床反应，我们开发了一种方法，将免疫组织化学与CD8 T细胞位置的自动图像分析相结合。 CD8分布模式与基因表达数据相关联，以鉴定和量化肿瘤内的“热”区域。此外，基于转录组学分析，CD8细胞的相对活化及其与肿瘤内其他CD8 T细胞和非CD8细胞的关系表明，活化的CD8 T细胞周围的细胞分布较少。此外，这些CD8 T细胞的相对活化与改善的临床结果和减少的肿瘤细胞增殖有关。这项研究证明了数字病理学在转移中结合免疫细胞空间分布和RNAseq分析来预测转移性黑色素瘤对BRAF抑制的临床反应的潜力。