Subpopulations of T Lymphocytes in the Peripheral Blood, Dermal Lesions and Lymph Nodes of Post Kala-azar Dermal Leishmaniasis Patients

Distribution of different subpopulations of T cells in the dermal lesions, lymph nodes and peripheral blood of post kala-azar dermal leishmaniasis (PKADL) patients was studied by using appropriate phenotypic markers for CD2⁺, CD4⁺ and CD8⁺ cells. Histopathological studies of skin lesions showed marginal to massive infiltration of mononuclear cells depending upon the duration of illness and type of lesions. Thus, while the hypopigmented patches were represented by small focal collections of lymphocytes with scanty parasites in the dermis, these were replaced at the nodular stage with massive granulomas consisting of lymphocytes, plasma cells and histiocytes with numerous amastigotes. The involvement of CD4⁺ and CD8⁺ cell types in these lesions also showed a gradual change from the appearance of a few cells of both the phenotypes in early hypopigmented type to massive accumulation of cells, primarily of CD8⁺ phenotype, in the granuloma of nodular type. However, the observed preponderance of CD8⁺ cells at the lesion site of chronic PKADL patients is in contrast to their peripheral blood CD4⁺/CD8⁺ cell ratio (1.9:1) which remained within the normal limits. Similar studies of lymph nodes from PKADL patients with lymphadenopathy revealed infiltration of the cortical areas by T cells which were more of CD8⁺ than CD4⁺ phenotypes. All these results document the involvement of CD8⁺ cells in leishmanoid lesions. Thus, it is likely that these cells, in association with appropriate subpopulations of CD4⁺ cells, play a profound role in the evolution of dermal pathology in PKADL.     

Semi-automatic tool for segmentation and volumetric analysis of medical images

Segmentation software is described, developed for medical image processing and run on Windows. The software applies basic image processing techniques through a graphical user interface. For particular applications, such as brain lesion segmentation, the software enables the combination of different segmentation techniques to improve its efficiency. The program is applied for magnetic resonance imaging, computed tomography and optical images of cryosections. The software can be utilised in numerous applications, including pre-processing for three-dimensional presentations, volumetric analysis and construction of volume conductor models.     

Epidermal Dendritic Cell Populations in the Flaky Skin Mutant Mouse

Flaky skin (gene symbol: fsn) is an autosomal recessive mouse mutation that causes pathologic changes in the skin yielding a papulosquamous disease resembling human psoriasis. Preliminary studies of epidermal sheets from foot pads of fsn/fsn mice stained for Ia⁺ Langerhans cells (LC) or Thy-1⁺ dendritic epidermal cells (Thy-1⁺ DEC) indicated a rise in LC numbers at the time of weaning, when the skin lesion becomes clinically evident. To further investigate this observation, epidermal sheets were obtained from the ear, dorsal skin, and foot pads from replicates of 6 female mice (both mutants and normal littermates) on weekly intervals from birth to 8 weeks of age. Dorsal skin epidermal thickness was quantitated by computer assisted image analysis and found to be significantly thickened from one week onward in the mutant mice. Using immunofluorescence microscopy, epidermal dendritic cell numbers were determined following staining with antibodies for the following markers: Ia, NLDC-145, and S-100 (for LC) or Thy 1.2 and asialc-GM1 (for Thy-1⁺ DEC). Use of all 5 markers to evaluate skin from 3 different locations yielded a subtle but significant increase in LC and Thy-1⁺ DEC in flaky skin mice. Of the three sites evaluated, the dorsal skin and ear epidermal sheets were most informative, which corresponded to the degree of pathological involvement. Mice doubly homozygous for fsn and for the severe combined immunodeficiency (scid) mutation developed the psoriasiform dermatitis. Bone marrow grafts from fsn/fsn homozygotes to homozygous scid/scid mice reproduce the skin lesion. These studies suggest that the psoriasiform dermatitis in the flaky skin mouse mutation is associated with abnormalities at the level of hematopoietic progenitor cells.     

结合通道权重更新与密集残差金字塔空间注意力的皮肤病变分割方法

皮肤病变分割是计算机辅助诊断黑色素瘤的关键步骤。为了精确提取出皮肤病变区域,本研究基于U-Net提出一种新的皮肤病变分割方法。该方法引入通道权重更新模块和密集残差金字塔空间注意力模块,分别从通道和空间上提取有效信息,突出病变特征,抑制无关特征,从而提升网络对病变区域的分割精度;此外,构造了一种加权边界损失函数,通过对病变轮廓进行强监督,减少病变边缘特征的丢失。实验表明在ISIC 2018和PH2皮肤镜图像数据集中,该方法的Dice系数分别达到了91.3%、92.2%,相比U-Net提升了5.0%、4.3%。     

Automatic Pectoral Muscle Region Segmentation in Mammograms Using Genetic Algorithm and Morphological Selection

In computer-aided diagnosis systems for breast mammography, the pectoral muscle region can easily cause a high false positive rate and misdiagnosis due to its similar texture and low contrast with breast parenchyma. Pectoral muscle region segmentation is a crucial pre-processing step to identify lesions, and accurate segmentation in poor-contrast mammograms is still a challenging task. In order to tackle this problem, a novel method is proposed to automatically segment pectoral muscle region in this paper. The proposed method combines genetic algorithm and morphological selection algorithm, incorporating four steps: pre-processing, genetic algorithm, morphological selection, and polynomial curve fitting. For the evaluation results on different databases, the proposed method achieves average FP rate and FN rate of 2.03 and 6.90% (mini MIAS), 1.60 and 4.03% (DDSM), and 2.42 and 13.61% (INBreast), respectively. The results can be comparable performance in various metrics over the state-of-the-art methods.     

小鼠背部皮肤的在体阻抗谱实验研究

皮肤中角质层与其他层面阻抗的巨大差异,使得将皮肤作为一个整体的阻抗特性研究较难开展。研究在体条件下无创或微创地检测与分析包含角质层的小鼠背部皮肤的阻抗特性。使用Agilent 4294A阻抗分析仪,测量麻醉状态下的15只C57BL/6小鼠背部皮肤的电阻抗频谱,使用表面电极和银针电极,分别对应皮肤和活性皮肤层阻抗数据。在整个实验频率范围(40～10⁷ Hz)内,随频率升高,皮肤阻抗幅值呈现-20dB/dec下降;活性皮肤层在40~10³ Hz之间幅值呈现-10 dB/dec下降,而在10³~10⁷ Hz之间呈现-3dB/dec下降。皮肤相位随频率上升呈现V型曲线,而活性皮肤层相位呈现Π型曲线。低频时,皮肤阻抗完全由角质层阻抗组成,活性皮肤层的贡献可以忽略不计;当频率为10⁵ Hz时,活性皮肤层阻抗占皮肤的10%多,而在10⁷ Hz以上时,活性皮肤层阻抗占整个皮肤的80%以上。皮肤阻抗与活性皮肤层阻抗在10³ Hz以下具有显著性差异(P<0.05),在10⁴ Hz以上无显著性差异。结果表明,表面电极与银针电极相结合的对比分析方法能够在微创前提下有效分析角质层在皮肤阻抗中的作用。     

Collagen fibril organization in the pregnant endometrium of decorin-deficient mice

In the pregnant mouse endometrium, collagen fibrillogenesis is characterized by the presence of very thick collagen fibrils which are topographically located exclusively within the decidualized stroma. This dynamic biological process is in part regulated by the small leucine-rich proteoglycans decorin and biglycan. In the present study we utilized wild-type (Dcn^+/+) and decorin-deficient (Dcn^−/−) time-pregnant mice to investigate the evolution of non-decidualized and decidualized collagen matrix in the uterine wall of these animals. Ultrastructural and morphometric analyses revealed that the organization of collagen fibrils in the pregnant endometrium of both non-decidualized and decidualized stroma showed a great variability of shape and size, regardless of the genotype. However, the decidualized endometrium from Dcn^−/− mice contained fibrils with larger diameter and more irregular contours as compared to the wild-type littermates. In the Dcn^−/− animals, the proportion of thin (10–50 nm) fibrils was also higher as compared to Dcn^+/+ animals. On day 7 of pregnancy, biglycan was similarly localized in the decidualized endometrium in both genotypes. Lumican immunostaining was intense both in decidualized and non-decidualized stroma from Dcn^−/− animals. The present results support previous findings suggesting that decorin participates in uterine collagen fibrillogenesis. In addition, we suggest that the absence of decorin disturbs the process of lateral assembly of thin fibrils, resulting in very thick collagen fibrils with irregular profiles. Our data further suggest that decorin, biglycan and lumican might play an interactive role in collagen fibrillogenesis in the mouse endometrium, a process modulated according to the stage of pregnancy.     

Fully automated gradient based breast boundary detection for digitized X-ray mammograms

Accurate segmentation of the breast from digital mammograms is an important pre-processing step for computerized breast cancer detection. In this study, we propose a fully automated segmentation method. Noise on the acquired mammogram is reduced by median filtering; multidirectional scanning is then applied to the resultant image using a moving window 15×1 in size. The border pixels are detected using the intensity value and maximum gradient value of the window. The breast boundary is identified from the detected pixels filtered using an averaging filter. The segmentation accuracy on a dataset of 84 mammograms from the MIAS database is 99%.     

Bioluminescent imaging of Ca2+ activity reveals spatiotemporal dynamics in glial networks of dark-adapted mouse retina

Glial Ca²⁺ excitability plays a key role in reciprocal neuron–glia communication. In the retina, neuron–glia signalling is expected to be maximal in the dark, but the glial Ca²⁺ signal characteristics under such conditions have not been evaluated. To address this question, we used bioluminescence imaging to monitor spontaneous Ca²⁺ changes under dark conditions selectively in Müller cells, the principal retinal glial cells. By combining this imaging approach with network analysis, we demonstrate that activity in Müller cells is organized in networks of coactive cells, involving 2–16 cells located distantly and/or in clusters. We also report that spontaneous activity of small networks (2–6 Müller cells) repeat over time, sometimes in the same sequential order, revealing specific temporal dynamics. In addition, we show that networks of coactive glial cells are inhibited by TTX, indicating that ganglion and/or amacrine neuronal cells probably regulate Müller cell network properties. These results represent the first demonstration that spontaneous activity in adult Müller cells is patterned into correlated networks that display repeated sequences of coactivations over time. Furthermore, our bioluminescence technique provides a novel tool to study the dynamic characteristics of glial Ca²⁺ events in the retina under dark conditions, which should greatly facilitate future investigations of retinal dark-adaptive processes.     

A new scenario for the evolutionary origin of hair, feather, and avian scales

In zoology it is well known that birds are characterized by the presence of feathers, and mammals by hairs. Another common point of view is that avian scales are directly related to reptilian scales. As a skin embryologist, I have been fascinated by the problem of regionalization of skin appendages in amniotes throughout my scientific life. Here I have collected the arguments that result from classical experimental embryology, from the modern molecular biology era, and from the recent discovery of new fossils. These arguments shape my view that avian ectoderm is primarily programmed toward forming feathers, and mammalian ectoderm toward forming hairs. The other ectoderm derivatives – scales in birds, glands in mammals, or cornea in both classes – can become feathers or hairs through metaplastic process, and appear to have a negative regulatory mechanism over this basic program. How this program is altered remains, in most part, to be determined. However, it is clear that the regulation of the Wnt/beta‐catenin pathway is a critical hub. The level of beta‐catenin is crucial for feather and hair formation, as its down‐regulation appears to be linked with the formation of avian scales in chick, and cutaneous glands in mice. Furthermore, its inhibition leads to the formation of nude skin and is required for that of corneal epithelium. Here I propose a new theory, to be further considered and tested when we have new information from genomic studies. With this theory, I suggest that the alpha‐keratinized hairs from living synapsids may have evolved from the hypothetical glandular integument of the first amniotes, which may have presented similarities with common day terrestrial amphibians. Concerning feathers, they may have evolved independently of squamate scales, each originating from the hypothetical roughened beta‐keratinized integument of the first sauropsids. The avian overlapping scales, which cover the feet in some bird species, may have developed later in evolution, being secondarily derived from feathers.     

基于U型稠密特征融合的皮肤病灶分割

皮肤病灶图像分割可作为医学相关类疾病辅助诊断的重要依据。针对皮肤病灶区域结构复杂和尺度信息参差错落的特点,提出一种基于U型稠密特征融合的皮肤病灶分割方法。编码器利用稠密网络结构和空洞空间金字塔池化充分提取特征与融合,由稠密空间注意力模块与深度可分离卷积解码深层特征,防止病灶区域周围噪声干扰,同时引入融合压缩注意力模块进一步提高分割性能,通过二值交叉熵与Jaccard系数结合的损失函数优化。在ISBI 2016皮肤病灶数据集进行仿真评估,Jaccard相似度和Dice系数分别达到86.87%和92.98%,有助于提高皮肤病灶诊断效率。     

基于多尺度编码-解码网络的皮肤病变图像分割

针对皮肤病变图像分割在医疗诊断中的作用,提出一种基于多尺度编码-解码网络的皮肤病变图像分割算法。该算法继承了SegNet网络结构的训练速度快、训练模型存储小等特点,采用多尺度输入的方式增强了网络对皮肤病变图像的充分学习。此外,在编码网络中的pool2层输出一个二进制双线性插值的中间预测特征图到解码层的最后一层卷积块进行级联输入提高最终的分割精度。实验结果表明,采用多尺度编码-解码网络对皮肤病变图像分割具有极好的效果,在其他医学图像分割方面也能进行广泛应用。     

Automated breast tumor detection and segmentation with a novel computational framework of whole ultrasound images

Due to the low contrast and ambiguous boundaries of the tumors in breast ultrasound (BUS) images, it is still a challenging task to automatically segment the breast tumors from the ultrasound. In this paper, we proposed a novel computational framework that can detect and segment breast lesions fully automatic in the whole ultrasound images. This framework includes several key components: pre-processing, contour initialization, and tumor segmentation. In the pre-processing step, we applied non-local low-rank (NLLR) filter to reduce the speckle noise. In contour initialization step, we cascaded a two-step Otsu-based adaptive thresholding (OBAT) algorithm with morphologic operations to effectively locate the tumor regions and initialize the tumor contours. Finally, given the initial tumor contours, the improved Chan-Vese model based on the ratio of exponentially weighted averages (CV-ROEWA) method was utilized. This pipeline was tested on a set of 61 breast ultrasound (BUS) images with diagnosed tumors. The experimental results in clinical ultrasound images prove the high accuracy and robustness of the proposed framework, indicating its potential applications in clinical practice.

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Graphical abstract ?

     

Slow removal of Na+ channel inactivation underlies the temporal filtering property in the teleost thalamic neurons

It has been previously shown that the 'large cell' in the corpus glomerulosum (CG) of a teleost brain has a low-pass temporal filtering property. It fires a single spike only in response to temporally sparse synaptic inputs and thus extracts temporal aspects of afferent activities. To explore the ionic mechanisms underlying this property, we quantitatively studied voltage-gated Na⁺ channels of the large cell in the CG slice preparation of the marine filefish by means of whole-cell patch clamp recordings in the voltage-clamp mode. Recorded Na⁺ current was well described using the Hodgkin-Huxley ' m³h ' model. It was revealed that the Na⁺ channels have a novel feature: remarkably slow recovery from inactivation. In other words, the time constant for the ' h ' gate was extremely large (∼100 ms at −80 to −50 mV). In order to test whether the analysed Na⁺ current serves as a mechanism for filtering, the behaviour of the membrane model incorporating the Na⁺ channel was simulated using a computer program called NEURON. In response to current injections, the membrane model displayed low-pass filtering and firing properties similar to those reported in real cells. The present results suggest that slow removal of Na⁺ channel inactivation serves as a crucial mechanism for the low-pass temporal filtering property of the large cell. The simulation study also suggested that velocity and/or amplitude of a spike propagating though an axon expressing Na⁺ channels of this type could potentially be modulated depending on the preceding activities of the cells.     

Quantitative spectroscopic diffuse optical tomography of the breast guided by imperfect a priori structural information

Spectroscopic diffuse optical tomography (DOT) can directly image the concentrations of physiologically significant chromophores in the body. This information may be of importance in characterizing breast tumours and distinguishing them from benign structures. This paper studies the accuracy with which lesions can be characterized given a physiologically realistic situation in which the background architecture of the breast is heterogeneous yet highly structured. Specifically, in simulation studies, we assume that the breast is segmented into distinct glandular and adipose regions. Imaging with a high-resolution imaging modality, such as magnetic resonance imaging, in conjunction with a segmentation by a clinical expert, allows the glandular/adipose boundary to be determined. We then apply a two-step approach in which the background chromophore concentrations of each region are estimated in a nonlinear fashion, and a more localized lesion is subsequently estimated using a linear perturbational approach. In addition, we examine the consequences which errors in the breast segmentation have on estimating both the background and inhomogeneity chromophore concentrations.     

一种提高直肠癌诊断精度的基于U型网络和残差块的电子计算机断层扫描图像分割算法EI北大核心CSCD

作为确定病灶与诊断的重要基础,医学图像分割已成为生物医学领域中极其重要的热门研究领域之一,其中基于全卷积神经网络和U型网络(U-net)等神经网络的医学图像分割算法得到越来越多研究人员的重视。目前,医学图像分割算法应用于直肠癌诊断的研究报道较少,且已有的研究对直肠癌的分割结果精度不高。本文提出了一种结合图像裁剪和预处理方法的编码—解码卷积网络模型。该模型在U型网络的基础上,借鉴残差网络思想,用残差块代替传统的卷积块,有效避免了梯度消失的问题。此外,本文还采用了图像增广的方法提高了所提模型的泛化能力,并在"泰迪杯"数据挖掘挑战赛所提供的数据集进行测试。测试结果表明,本文提出的基于残差块的改进U型网络模型结合图像裁剪预处理,可以大大提高直肠癌的分割精度,得到的戴斯系数在验证集上达到0.97。     

高频超声对正常正中神经显像及其临床意义

目的 通过高频超声探查上肢正中神经全程并熟练掌握正中神经的超声探查手法,选取超声易于辨识的解剖位点测量正中神经的横截面积（CSA）并探讨其与周围组织的关系,提供正常参考值范围并为临床诊断外周神经疾病提供依据。 方法 对240例健康志愿者沿正中神经走行进行高频超声探查,依次测量5个位点 ［腕管（腕横纹处）、前臂中点、正中神经穿出旋前圆肌处、肱骨髁上处及肱骨中点处］的CSA,每个位点重复测量３次取其均值,并进行CSA与身高、体重的相关性分析。 结果 高频超声显示,正常人正中神经横截面呈筛网状低回声图像,在不同部位分别显示为圆形、椭圆形或三角形,纵截面上成束状平行排列的低回声被断续的条带状高回声分割。探查得出,正中神经在上述5个位点的CSA均值以及双侧上肢之间同一位点处正中神经的CSA差异无统计学意义。 结论 正中神经在高频超声下全程可探及,显示率为100％;在不同部位的正常值及超声声像图略有差异,差异有统计学意义;正中神经的CSA在上臂段最粗,腕管处次之,前臂段最细。     

结合贝叶斯最优分类器的GACV模型对医学彩色细胞图像进行分割

目的:本文对GACV模型进行改进,并用改进的模型对医学彩色细胞图像进行分割。方法:本文在GACV模型基础上加入了贝叶斯最优分类器,得到了结合贝叶斯最优分类器的GACV模型,并用该模型对医学彩色细胞图像进行分割。结果:应用本文提出的模型分割3组不同特点的医学彩色细胞图像,分割结果显示,该模型能正确将细胞从不同噪声环境中分割出来。结论:结合贝叶斯最优分类器的GACV模型对弱边界,噪声以及复杂背景有很强的鲁棒性可以有效、准确的分割医学彩色细胞图像。     

Refined Residual Deep Convolutional Network for Skin Lesion Classification

Skin cancer is the most common type of cancer that affects humans and is usually diagnosed by initial clinical screening, which is followed by dermoscopic analysis. Automated classification of skin lesions is still a challenging task because of the high visual similarity between melanoma and benign lesions. This paper proposes a new residual deep convolutional neural network (RDCNN) for skin lesions diagnosis. The proposed neural network is trained and tested using six well-known skin cancer datasets, PH2, DermIS and Quest, MED-NODE, ISIC2016, ISIC2017, and ISIC2018. Three different experiments are carried out to measure the performance of the proposed RDCNN. In the first experiment, the proposed RDCNN is trained and tested using the original dataset images without any pre-processing or segmentation. In the second experiment, the proposed RDCNN is tested using segmented images. Finally, the utilized trained model in the second experiment is saved and reused in the third experiment as a pre-trained model. Then, it is trained again using a different dataset. The proposed RDCNN shows significant high performance and outperforms the existing deep convolutional networks.

     

The interleukin-5 messenger RNA expression in a patient with idiopathic hypereosinophilic syndrome

Interleukin-5 has a specific role in various eosinophilic activities. It is the predominant cytokine produces by activated T-lymphocytes isolated from patients with idiopathic hypereosinophilic syndrome. We studied a young patient suffering from idiopathic hypereosinophilic syndrome who presented with Horner's syndrome, peripheral neuropathy and skin ulcers. The IL-5 gene expression by CD4⁺ T-lymphocytes and the peripheral eosinophil count were raised. The skin ulcers continued to deteriorate despite a swift reduction of the IL-5 gene expression and peripheral eosinophil count following systemic corticosteroid treatment. We suggest that peripheral eosinophilia may not be responsible for the damage in skin lesions and more aggressive treatment may be required.