一种基于近似熵特征分类的冠心病诊断方法

对104例冠心病人心电Holter信号进行心率变异性的分析,计算RR间期序列的近似熵指标的24h分段变化趋势图,并于健康对照组作比较,验证了近似熵这个心率变异性非线性参数的意义.通过LDA(线性鉴别分析)的模式识别方法对病人及健康人的24h变化趋势图进行模式识别和分类,平均正确分类率达99.03%.分类的结果表明,冠心病患者与健康人相比在白天,尤其在早上6点到中午12点间,近似熵指标的降低更明显,利用此时间段作分类正确率更高.     

A novel interface consisting of homologous immunoglobulin superfamily members with multiple functions

Immunoglobulin superfamily (IgSF) members account for a large proportion of cell adhesion molecules that perform important immunological functions, including recognizing a variety of counterpart molecules on the cell surface or extracellular matrix. The findings that CD155/poliovirus receptor (PVR) and CD112/nectin-2 are the ligands for CD226/platelet and T-cell activation antigen 1 (PTA1)/DNAX accessory molecular-1 (DNAM-1), CD96/tactile and Washington University cell adhesion molecule (WUCAM) and that CD226 is physically and functionally associated with lymphocyte function-associated antigen-1 (LFA-1) on natural killer (NK) and activated T cells have largely expanded our knowledge about the functions of CD226, CD96, WUCAM and LFA-1 and their respective ligands, CD155, CD112, intercellular adhesion molecule (ICAM)-1 and junctional adhesion molecule (JAM)-1. The interactions of these receptors and their ligands are involved in many key functions of immune cells including naive T cells, cytotoxic T cells, NK cells, NK T cells, monocytes, dendritic cells, mast cells and platelets/megakaryocytes.     

A model for single and multiple knowledge based networks

The inherent black-box nature of neural networks is an important drawback with respect to the problem of explanation of neural network responses. Although several articles have tackled the problem of rule extraction from a single neural network, just a few papers have investigated rule extraction from several combined neural networks. In this article we describe how to translate symbolic rules into the Discretized Interpretable Multi-Layer Perceptron (DIMLP) and how to extract rules from one or several combined neural networks. Our approach consists of characterizing discriminant hyperplane frontiers. Unordered rules are extracted in polynomial time with respect to the size of the problem and the size of the network. Moreover, the degree of matching between extracted rules and neural network responses is 100% on training examples. We applied single DIMLP networks to 17 data sets related to medical diagnosis and medical prognosis problems. Results based on 10-fold cross-validation showed that the DIMLP model was on average as accurate as standard multi-layer perceptrons (MLP). Furthermore, DIMLP networks were significantly more accurate than CN2 on eight problems, whereas only on one problem CN2 was better than DIMLP. Finally, a non-Hodgkin lymphoma diagnosis problem based on classification of electrophoresis gels was defined. It turned out that ensembles of DIMLP networks were significantly more accurate than CN2 (96.1% +/- 1.4 versus 82.7% +/- 4.0). Finally, symbolic rules revealed the presence of five important spots for the discrimination of the class of Lymphocyte Leukemia/Chronic Lymphoid Leukemia (Lc/LLc), and the class of Centrocytic Lymphoma (Cc).     

Vogt-Koyanagi-Harada syndrome in two patients with immunoglobulin A nephropathy

We describe herein 2 patients who developed Vogt-Koyanagi-Harada syndrome in the course of renal biopsy-proven immunoglobulin A (IgA) nephropathy. A 61-year-old man with an 11-year history of IgA nephropathy and a 16-year history of thyroiditis, and a 56-year-old man with a 5-year history of IgA nephropathy developed Vogt-Koyanagi-Harada syndrome. At the time of the eye disease presentation, IgA nephropathy was stable without corticosteroids in both patients. Vogt-Koyanagi-Harada syndrome was successfully treated with intravenous administration of prednisolone tapered from 200 mg daily. Vogt-Koyanagi-Harada syndrome is associated with IgA nephropathy, suggesting a similar autoimmune mechanism for both diseases.     

基于改进SOLO＿v2的糖尿病黄斑水肿分割模型

糖尿病黄斑水肿（DME）是导致糖尿病患者视力损害的常见原因。光学相干断层扫描技术（OCT）有助于增强对糖尿病视网膜病变的早期检测和预防。目前,OCT图像中的DME区域存在大量散斑噪声及小目标区域,现有的实例分割方法存在漏分割等问题。针对上述问题,本文利用特征金字塔转换器（FPT）改进SOLO＿v2模型,提出了一种新的DME分割模型（SOLO-OCT）,包括：（1）利用基于双域滤波去噪算法去除图像上存在的大量散斑噪声,提高输入图像质量;（2）引入FPT,提高模型对小目标的识别能力和学习能力;（3）改进非极大值抑制（NMS）算法,缓解对小目标区域的漏分割问题。将SOLO-OCT模型与其他实例分割模型（包括Mask R-CNN、SOLO和SOLO＿v2）进行了比较,以评估其对DME区域的分割性能。与Mask R-CNN、SOLO和SOLO＿v2模型相比,SOLO-OCT模型对DME区域的分割精度（mAP）提高了3.1%,对小目标DME区域的分割精度（APs）提高了2.2%,而单幅图像的处理时间（Fps）只增加了0.009 9 s。本文提出的DME分割模型（SOLO-OCT）可用于大规模糖尿病...     

A novel diagnostic platform based on multiplex ligase detection-PCR and microarray for simultaneous detection of swine viruses

Simultaneous detection and identification of multiple pathogens is required in many diagnostic fields. In this study a novel method based on a multiplex ligase detection (LD)-polymerase chain reaction (PCR) and microarray (MLPM) is described to detect simultaneously several swine viruses involved in reproductive and/or respiratory problems. The multiplex diagnostic system was validated using standard plasmids, and clinical samples. Using this strategy as few as 10 copies of target plasmids were detected successfully. Each probe pair yielded specific positive signal only in its target site. In addition, when six target plasmids were present simultaneously sufficient robust signals were generated in their corresponding sites of six plasmid templates and no obvious signals were detected in non-target sites. Compared to real-time PCR, the MLPM showed specificities and sensitivities of 95.7-100% and 100% for 47 clinical samples tested, respectively. The results demonstrate that this novel assay is a specific, sensitive, and multiplex diagnostic method for detection of multiple pathogens and can also be adapted easily for diagnostic purposes.     

The epipharynx-kidney axis triggers glomerular vasculitis in immunoglobulin A nephropathy

Macroscopic hematuria concomitant with acute pharyngitis is a characteristic feature of immunoglobulin A nephropathy (IgAN). Although the underlying mechanism of worsening hematuria has not been fully elucidated, activation of the innate immune system of nasopharynx-associated lymphoid tissue is thought to play an important role. The epipharynx is an immunologically activated site even under normal conditions, and enhanced activation of innate immunity is likely to occur in response to airborne infection. As latent but significant epipharyngitis presents in most IgAN patients, it is plausible that acute pharyngitis due to airway infection may contribute as a trigger of the epipharyngeal innate immune system, which is already upregulated in the chronically inflamed environment. The aim of this review was to discuss the mechanism of epipharynx-kidney axis involvement in glomerular vasculitis responsible for the worsening of hematuria in IgAN.

     

Expression of human T cell immunoglobulin domain and mucin-3 on kidney tissue from immunoglobulin A nephropathy patients

The aim of this study was to evaluate the expression of human T cell immunoglobulin domain and mucin-3 (Tim-3) in renal tissue from patients with immunoglobulin A nephropathy (IgAN) and without IgAN and to evaluate the difference in Tim-3 expression between them. A total of 71 patients with IgAN as IgA group and 13 patients without IgAN as control group were enrolled in the present study. Patients in IgAN accepted percutaneous renal biopsy. We examined the expression of Tim-3 in renal tissue and the serological parameters in serum from all enrolled cases. The expression of Tim-3 and serological parameters were compared between the different groups. Positive staining of Tim-3 protein was seen in 94.3 % patients with IgAN (67 out of 71), but only 15.4 % (2 out of 13) in the cases without IgAN were positive staining of Tim-3. There were significant differences between two groups in almost all serological markers, which reflect IgAN activity. There was a nearly positive correlation between pathological manifestations and expression degree of Tim-3. High immuno-reactivity of Tim-3 was found to be significantly correlated with serological grade (p < 0.001) in IgA group, but there was no such phenomenon in control group. The results showed that there was the expression of Tim-3 in renal tissue from the patients with IgAN, but rarely expression in cases without IgAN. Expression of Tim-3 was associated with the diseases’ activity.     

Fibrillary glomerulonephritis mimicking membranous nephropathy – A diagnostic pitfall

Kidney biopsies in 2 females with nephrotic syndrome were suggestive of membranous nephropathy at routine light microscopy and immunohistochemistry. Electron microscopy on re-embedded paraffin tissue, however, revealed that the light microscopic pattern was due to a fibrillary glomerulonephritis with a dominant membranous manifestation.     

Field evaluation of a novel differential diagnostic reagent for detection of Mycobacterium bovis in cattle

In the search for improved tools with which to control bovine tuberculosis, the development of enhanced immunodiagnostic reagents is a high priority. Such reagents are required to improve the performance of tuberculin-based reagents and allow the discrimination of vaccinated cattle from those infected with Mycobacterium bovis. In this study, we identified the immunodominant, frequently recognized peptides from Rv3873, Rv3879c, Rv0288, and Rv3019c, which, together with peptides comprising the current lead diagnostic antigens, ESAT-6 and CFP-10, were formulated into a peptide cocktail. In a test of naturally infected cattle, this cocktail was significantly better than tuberculin was for identifying skin test-negative animals with confirmed bovine tuberculosis. In addition, the specificity of this cocktail was not compromised by Mycobacterium bovis BCG vaccination. In summary, our results prioritize this peptide-based, fully synthetic reagent for assessment in larger trials.     

Hybricomb. A novel diagnostic tool for DNA probing

A technique is described in which unlabeled DNA probes are immobilized on the plastic surface of a 12-tooth comb and used to capture homologs by a hybridization procedure. In the examples described, cellular DNA from cervical biopsies is chemically labeled using the Chemi-probe system. The sample containing labeled DNA is then hybridized with the immobilized unlabeled probe (reverse hybridization). By means of this technique, human papillomavirus sequences can be detected with a sensitivity comparable to that of radioactive probe procedures. DNA hybrids are visualized as colored spots on each tooth by moving the comb through the reagent solutions of the prefilled developing plate. The whole procedure requires less than 50 minutes hands-on time, and the results are obtained in a few hours. Application of the technique to the detection and typing of mycoplasma DNA is also reported.     

A novel fluorescent sensitive assay for detection of differential T cell mediated lysis of multiple adherent target cells

There are few studies that have investigated T cell mediated lysis of adherent cells. We have developed a novel, rapid and sensitive fluorescent dye-swap assay that allows efficient detection of adherent target cell lysis. The assay allows simultaneous use of multiple differentially sensitised targets and facilitates concomitant surface or intracellular effector cell phenotypic analysis.     

High-dose intravenous immunoglobulin pulse therapy in patients with progressive immunoglobulin A nephropathy: a long-term follow-up

In progressive immunoglobulin A nephropathy (IgAN), intravenous immunoglobulin (IVIg) treatment has been used to delay disease progression, but the long-term efficacy is largely unknown. We report the clinical outcomes after IVIg therapy in six male patients with progressive IgAN [median glomerular filtration rate (GFR) 31 ml/min per 1.73 m(2)] followed for a median observation period of 8 years. In this single-arm, non-randomized study, IVIg was given monthly at a dose of 2 g/kg body weight for 6 months. The course of renal function was assessed by linear regression analysis of GFR and proteinuria, and was compared to eight patients with IgAN (median GFR 29 ml/min per 1.73 m(2)) without IVIg as a contemporaneous control group. IgAN disease progression was delayed after IVIg therapy on average for 3 years. The mean loss of renal function decreased from -1.05 ml/min per month to -0.15 ml/min per month (P = 0.024) and proteinuria decreased from 2.4 g/l to 1.0 g/l (P = 0.015). The primary end-point (GFR < 10 ml/min or relapse) occurred 5.2 years (median; range 0.4-8.8) after the first IVIg pulse, and after 1.3 years (median; range 0.8-2.4) in the control group (P = 0.043). In Kaplan-Meier analysis, the median renal survival time with IVIg was prolonged by 3.5 years (IVIg 4.7 years versus control 1.2 years; P = 0.006). IVIg pulse therapy may be considered as a treatment option to reduce the loss of renal function and improve proteinuria in patients with progressive IgAN.     

Shot sequencing based on biological equivalent dose considerations for multiple isocenter Gamma Knife radiosurgery

Rapid delivery of multiple shots or isocenters is one of the hallmarks of Gamma Knife radiosurgery. In this study, we investigated whether the temporal order of shots delivered with Gamma Knife Perfexion would significantly influence the biological equivalent dose for complex multi-isocenter treatments. Twenty single-target cases were selected for analysis. For each case, 3D dose matrices of individual shots were extracted and single-fraction equivalent uniform dose (sEUD) values were determined for all possible shot delivery sequences, corresponding to different patterns of temporal dose delivery within the target. We found significant variations in the sEUD values among these sequences exceeding 15% for certain cases. However, the sequences for the actual treatment delivery were found to agree (<3%) and to correlate (R2 = 0.98) excellently with the sequences yielding the maximum sEUD values for all studied cases. This result is applicable for both fast and slow growing tumors with α/β values of 2 to 20 according to the linear-quadratic model. In conclusion, despite large potential variations in different shot sequences for multi-isocenter Gamma Knife treatments, current clinical delivery sequences exhibited consistent biological target dosing that approached that maximally achievable for all studied cases.     

A murine model of phosphate nephropathy

We established a murine model of phosphate nephropathy with secondary hyperparathyroidism. db/db mice, which develop obesity and type 2 diabetes mellitus, were uninephrectomized at the age of 6 weeks and were fed either standard chow or a phosphorus-rich diet during the next 8 weeks. Thereafter, renal cryosections showed abundant tubular casts with a strong histochemical von Kossa reaction in all db/db mice on the phosphorus-rich diet but none in the controls. X-ray diffraction and Raman spectroscopy proved that these tubular casts consist mostly of hydroxyapatite Ca₅(PO₄)₃(OH). These intraluminal precipitations were located in distal tubuli and collecting ducts and were associated with degenerative tubular changes and peritubular infiltration of T cells and macrophages. In line, kidneys of db/db mice on the phosphorus-rich diet displayed significantly increased mRNA expression of the T_H1 cytokines interferon γ, IL-6, and tumor necrosis factor α. In addition, mice developed signs of secondary hyperparathyroidism as shown by elevated serum phosphate, decreased serum calcium, and increased parathyroid hormone, osteopontin, and fibroblast growth factor 23 levels. db/db mice on the phosphorus-rich diet also presented with significantly lower body weight, lower homeostasis model assessment of insulin resistance index, and hypertrophic cardiomyopathy. Thus, we provide a murine model of phosphate nephropathy and secondary hyperparathyroidism, which can be used for future pharmacologic and pathophysiologic studies to analyze the effect of hyperphosphatemia on renal, metabolic, and cardiovascular phenotypes.Inorganic phosphorus is essential for multiple biological functions, such as intracellular signal transduction, the production and function of cell membranes, and energy exchange. Although more than 80% of total body phosphorus is stored in bone and teeth, phosphorus is also found in the intracellular compartment and in serum (primarily in the form of anions such as H₂PO₄⁻ and HPO₄²⁻, which are commonly referred to as phosphate). In the steady state, serum phosphate levels are maintained within the physiological range by regulation of dietary absorption, bone formation, bone resorption, and by renal excretion. In the presence of a normal kidney function, renal excretion of excess phosphate is primarily responsible for maintaining phosphate balance. This regulation relies on the inhibition of the tubular sodium phosphate cotransporters and on increased levels of fibroblast growth factor 23 (FGF23) and parathyroid hormone.^1–4Hyperphosphatemia occurs whenever the amount of phosphate in the extracellular space exceeds the renal capacity for excretion. Hyperphosphatemia is, thus, a nearly universal complication of advanced renal failure. Large observational studies have also shown a graded association between levels of serum phosphate and all-cause mortality in patients with chronic renal failure. The positive phosphate balance seems to cause an accelerated progression of vascular calcification.^5–8An acute phosphate load that overwhelms renal capacity for excretion can be derived from endogenous and exogenous sources. Large amounts of endogenous phosphates are released from intracellular stores in tumor lysis syndrome, rhabdomyolysis, and lactic acidosis. Acute hyperphosphatemia can also result from ingestion of excessive amounts of phosphate-containing laxatives and enemas administered for colonoscopy preparation.⁹ Both endogenous and exogenous phosphate loads can lead to phosphate nephropathy.^10–15 Acute phosphate nephropathy is a clinical pathologic entity characterized by acute and subsequent chronic renal failure due to tubular precipitation of calcium phosphate deposits forming crystals of hydroxyapatite.¹⁶ It often followed exposure to oral sodium phosphate bowel purgatives, which were withdrawn from the market in December 2008 after a respective warning from the US Food and Drug Administration. Inadequate hydration and chronic kidney disease are established risk factors for acute phosphate nephropathy.¹⁶ Most of our present information on phosphate nephropathy derives from case series and retrospective epidemiologic analyses.^{11,14,17–19} Moreover, there is no specific therapy for established phosphate nephropathy.To study hyperphosphatemia and its renal, metabolic, and cardiovascular complications in more detail, we established and present herein a new animal model for phosphate nephropathy with established secondary hyperparathyroidism.     

A 3D point-kernel multiple scatter model for parallel-beam SPECT based on a gamma-ray buildup factor

A three-dimensional (3D) point-kernel multiple scatter model for point spread function (PSF) determination in parallel-beam single-photon emission computed tomography (SPECT), based on a dose gamma-ray buildup factor, is proposed. This model embraces nonuniform attenuation in a voxelized object of imaging (patient body) and multiple scattering that is treated as in the point-kernel integration gamma-ray shielding problems. First-order Compton scattering is done by means of the Klein-Nishina formula, but the multiple scattering is accounted for by making use of a dose buildup factor. An asset of the present model is the possibility of generating a complete two-dimensional (2D) PSF that can be used for 3D SPECT reconstruction by means of iterative algorithms. The proposed model is convenient in those situations where more exact techniques are not economical. For the proposed model's testing purpose calculations (for the point source in a nonuniform scattering object for parallel beam collimator geometry), the multiple-order scatter PSF generated by means of the proposed model matched well with those using Monte Carlo (MC) simulations. Discrepancies are observed only at the exponential tails mostly due to the high statistic uncertainty of MC simulations in this area, but not because of the inappropriateness of the model.     

Purification of horse immunoglobulin isotypes based on differential elution properties of isotypes from protein A and protein G columns

Elution properties of horse immunoglobulin isotypes from protein A and protein G columns were examined. IgGa and IgGb isotypes were bound to protein A and protein G columns and were eluted by adjusting the pH of the elution buffer from 8.0 to 2.0. IgGc bound to protein G column but not to protein A column while IgG(T) bound to both columns. IgM and IgA apparently appeared not to bind to either column. New methods for purification of serum isotypes were developed using protein A and protein G columns as well as formerly established methods. Using these methods, it was possible to obtain purified isotypes for establishment of immunological assays for practical clinical use.     

Evaluation of growth parameters inParamecium caudatum test model for standardization of biological screening

We standardizedParamecium caudatum test model on the basis of identification of a quasichemical model representing the processes of population growth in the presence of nickel(II) sulfate, a toxic substance. The density of paramecium population depends on the time of exposure at different concentrations of nickel(II) sulfate. Ecotoxicological equation for population development was used to analyze the experimental data and to determine the standard kinetic parameters of population development in the presence of a toxic substance. An algorithm is developed for evaluation of quality of paramecium culture. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 127, No. 6, pp. 717–720, June, 1999