Focus: A Multifaceted Battle Against Cancer: Extracting Knowledge from Chemical Imaging Data Using Computational Algorithms for Digital Cancer Diagnosis

Fourier transform infrared (FTIR) spectroscopic imaging is an emerging microscopy modality for clinical histopathologic diagnoses as well as for biomedical research. Spectral data recorded in this modality are indicative of the underlying, spatially resolved biochemical composition but need computerized algorithms to digitally recognize and transform this information to a diagnostic tool to identify cancer or other physiologic conditions. Statistical pattern recognition forms the backbone of these recognition protocols and can be used for highly accurate results. Aided by biochemical correlations with normal and diseased states and the power of modern computer-aided pattern recognition, this approach is capable of combating many standing questions of traditional histology-based diagnosis models. For example, a simple diagnostic test can be developed to determine cell types in tissue. As a more advanced application, IR spectral data can be integrated with patient information to predict risk of cancer, providing a potential road to precision medicine and personalized care in cancer treatment. The IR imaging approach can be implemented to complement conventional diagnoses, as the samples remain unperturbed and are not destroyed. Despite high potential and utility of this approach, clinical implementation has not yet been achieved due to practical hurdles like speed of data acquisition and lack of optimized computational procedures for extracting clinically actionable information rapidly. The latter problem has been addressed by developing highly efficient ways to process IR imaging data but remains one that has considerable scope for progress. Here, we summarize the major issues and provide practical considerations in implementing a modified Bayesian classification protocol for digital molecular pathology. We hope to familiarize readers with analysis methods in IR imaging data and enable researchers to develop methods that can lead to the use of this promising technique for digital diagnosis of cancer.     

High frequency residues: A new set of signals for detectability studies of an X-ray imaging system

A new set of signals for studying detectability of an X-ray imaging system is presented. The results obtained with these signals are intended to complement the NEQ results.The signals are generated from line spread profiles by progressively removing their lower frequency components and the resulting high frequency residues (HFRs) form the set of signals to be used in detectability studies. Detectability indexes for these HFRs are obtained using a non-prewhitening (NPW) observer and a series of edge images are used to obtain the HFRs, the covariance matrices required by the NPW model and the MTF and NPS used in NEQ calculations. The template used in the model is obtained by simulating the processes of blurring and sampling of the edge images. Comparison between detectability indexes for the HFRs and NEQ are carried out for different acquisition techniques using different beam qualities and doses.The relative sensitivity shown by detectability indexes using HFRs is higher than that of NEQ, especially at lower doses. Also, the different observers produce different results at high doses: while the ideal Bayesian observer used by NEQ distinguishes between beam qualities, the NPW used with the HFRs produces no differences between them.Delta functions used in HFR are the opposite of complex exponential functions in terms of their support in the spatial and frequency domains. Since NEQ can be interpreted as detectability of these complex exponential functions, detectability of HFRs is presented as a natural complement to NEQ in the performance assessment of an imaging system.     

The biometry of gills of 0-group European flounder

The gill surface area of 0-group, post-metamorphic Pleuronectes flesus L. was examined using digital image analysis software and expressed in relation to body mass according to the equation log Y=loga+c logW ( a =239·02; c =0·723). The components that constitute gill area, total filament length, interlamellar space and unilateral lamellar area were measured. The measurement of the length of every filament on all eight arches showed that commonly used methods of calculation can lead to an under-estimation of up to 24% of total filament length. Direct measurements of unilateral lamellar area with digital image analysis showed that previously reported gill area data for the same species was over-estimated by as much as 58%. In addition, in this species the neglect of gill pouch asymmetry after metamorphosis, can bring about a 14% over-estimation of total gill area.     

Evaluation of microwave hyperthermia applicators.

Hyperthermia has been used in conjunction with radiation and chemotherapy for cancer treatment. When using electromagnetic heating, applicators are critical components in contact with or in proximity to patients and can be the determining factor for effective and safe treatment. Tissue absorption of electromagnetic energy is determined by many factors. Three cases are shown to illustrate the complexity of microwave heating: 1) The BSD MA-151 applicator has good center heating on a muscle-only phantom as shown in the operation manual. When fat slabs of 0.25, 0.5, 1, and 2 cm thick were added, two hot spots near the periphery of the applicator were evident on all fat surfaces, exposed at 631 MHz. At 915 MHz, the heating was elongated on the surface of the models with 0.25- and 2-cm fat, and two hot spots were observed on the 0.5- and 1-cm fat surfaces. 2) Heating patterns of the Clini-Therm applicators on a muscle-only phantom, as indicated in the operations guide, are elliptical with their major axes perpendicular to the electric field. However, when a bolus is used, the elliptical pattern is parallel to the E field. 3) Heating patterns in cylindrical structures were studied with inhomogeneous models of limbs. Arm and thigh models consisting of fat, bone, and muscle material were heated with Clini-Therm L, M, and MS applicators at 915 MHz. In addition to the geometric effect, the results indicated that placing the applicators with E field parallel to the long axis of cylindrical structures can minimize required power, produce less heating of fats and reduce stray radiation. In conclusion, to apply penetrating microwave or other RF fields for tissue heating, one must simulate the clinical exposure conditions as closely as possible to obtain useful heating patterns.     

Effects of platelet-derived growth factor and fibroblast growth factor on free intracellular calcium and mitogenesis

Although increased free intracellular calcium (Cai) may be one of the main regulators of cell growth and differentiation, studies in cell populations have implied that not all growth factors produce Cai increases. In order to examine in more detail whether Cai increases were related to mitogenesis, we used digital image analysis of intracellular Fura-2 fluorescence to measure Cai in individual BALB/c 3T3 cells stimulated with either platelet-derived growth factor (PDGF) or fibroblast growth factor (FGF). We found that PDGF induced larger and more prolonged Cai increases than FGF did, but that both growth factors induced an initial rapid increase in Cai (less than 2 min) followed by a later sustained increase (greater than 20 min). Only the prolonged Cai increase required extracellular calcium. Following PDGF treatment (1-8 units/ml), the percentage of cells with a large peak Cai increase (greater than twofold) correlated with the percentage of cells made competent (subsequent growth in 1% platelet-poor-plasma). In contrast, purified bovine basic FGF (200-800 pg/ml) and recombinant human acidic FGF (10-300 ng/ml) produced peak Cai increases that were not directly correlated with mitogenesis. In addition, concentrations of intracellular Quin 2 that inhibited Cai transients also inhibited PDGF stimulation but not FGF stimulation of mitogenesis. Thus, Cai increases are necessary for mitogenesis in BALB/c 3T3 cells stimulated by PDGF, but not that stimulated by FGF.     

Cineanthropometric Study in Spanish Judoists

Anthropometric characteristics of proportionality, body composition and somatotype have been determined in a group of 72 Spanish judoists. The sample includes the junior male and female National Team, and seniors competitors in the last Olimpic Games held in 1992, and participants in the National Championship of 1993. The methodology has been used according to Weiner and Lourie(1981)and MOGAP procedures described by Borms et al. (1979). The obtained results show a similar proportionality profile and mesoendomorphic mean somatotype in both male and female series. However, were found significant differences between sexes as well as depending of weight categories.     

Carbamylcholine-induced morphological changes and spatial dynamics of [Ca2+]c in Harderian glands of guinea pigs: calcium-dependent lipid secretion and contraction of myoepithelial cells

To determine whether lipid-secreting cells have cytosolic Ca²⁺ concentration ([Ca²⁺]_c)-related secretory mechanisms, morphological changes and intracellular calcium dynamics of Harderian glands of guinea pigs stimulated by secretagogs were studied by electron microspy and Fura-2/AM digital image analysis. Control glandular cells contained large lipid vacuoles that were bordered by multi-layered membranes. Rough-surfaced endoplasmic reticulum, mitochondria, and smooth-surfaced endoplasmic reticulum may be involved in lipid vacuole formation. Myoepithelial cells surrounded alveoli. After carbamylcholine (CCh, 10^–6, 10^–5, and 10^–3 M) stimulation, lipid materials within the membranous structures were frequently discharged by an exocytotic mechanism. Conspicuous deformation of glandular cells caused by vigorous contraction of myoepithelial cells was observed in isolated alveoli after 10^–6M CCh stimulation, whereas the deformaties of glandular tissues perfused via vessels were small even after 10^–3M CCh stimulation. Connective tissue between glandular alveoli inhibited unbridled myoepithelial-cell contraction. Fura-2/AM digital imaging analysis revealed that CCh stimulation caused an increase in [Ca²⁺]_c in isolated alveoli. The morphological reactions and changes in [Ca²⁺]_c were prevented by atropine. When extracellular calcium ions were absent, enhanced extrusion of lipid vacuoles, myoepithelial-cell contraction, and a rise in [Ca²⁺]_c after CCh stimulation were not observed. Nicotine and catecholamines had no effect on the secretion or on the dynamics of [Ca²⁺]_c. It can be concluded that acetylcholine elicits exocytosis in glandular cells and contraction of the myoepithelial cells of Harderian glands, accompanied by an increase in [Ca²⁺]_c. The dynamics of [Ca²⁺]_c of the gland alveoli are mostly dependent on extracellular Ca²⁺.     

Three research priorities for just and sustainable urban systems: Now is the time to refocus

Now is the time to refocus efforts in urban research and design. A changing climate and extreme weather events are presenting unique challenges to urban systems around the world. These challenges illuminate the social barriers that accompany disruptive events such as resource inequities and injustices. In this perspective, we provide three research priorities for just and sustainable urban systems that help to address these matters. The three research priorities are: (1) social equity and justice, (2) circularity, and (3) digital twins. Conceptual context and future research directions are provided for each. For social equity and justice, the future directions are mandatory equity analysis and inclusionary practices, understanding and reconciling historical injustices, and intentional integration with diverse community stakeholders. For circularity applications, they are better metrics for integration, more robust evaluation frameworks, and dynamic modeling at multiple spatial and temporal scales. Future directions for digital twins include developing principles to reduce complexity, integrating model and system components, and reducing barriers to data access. These research priorities are core to meeting several of the United Nations Sustainable Development Goals (i.e., 1—No Poverty, 8—Decent Work and Economic Growth, 10—Reduced Inequalities, and 11—Sustainable Cities and Communities). Useful social and technical matters are discussed throughout, where we highlight the importance of prioritizing localized research efforts, provide guidance for community-engaged research and co-development practices, and explain how these priorities interact to align with the evolving field of industrial ecology.     

仿脑组织体模研究进展

仿脑组织体模是指可以有效模拟人脑组织形状、性质的等效材料组织或数字模型,可以在实验中代表人脑组织的某些生理特性从而达到特定的研究目标,根据其物理形态,通常可分为固体、液体、数字体模3类。仿脑组织体模具有安全经济,配置简单并且可重复使用的优势,被广泛应用于脑部疾病诊断、系统安全性评估等研究。本文就仿脑组织体模的分类、物理特性和脑科学研究应用3方面进行论述,在阐述当前仿脑组织体模与真实脑组织存在一定性质差异的同时也说明其在替代真实脑组织实验上有良好的应用前景。