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PubMed2025

Artificial intelligence-powered spatial analysis of tumor microenvironment in patients with non-small cell lung cancer with acquired resistance to EGFR tyrosine kinase inhibitor.

PURPOSE: This study evaluated the dynamic changes in the tumor microenvironment (TME) in patients with non-small cell lung cancer (NSCLC) and acquired resistance to epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) using an artificial intelligence (AI)-powered spatial TME analyzer. We then assessed the predictive efficacy of immune-checkpoint inhibitors (ICIs)-based treatment. EXPERIMENTAL DESIGN: An AI-powered whole-slide image analyzer was used to segment cancer areas (CAs) and cancer stroma and to identify tumor-infiltrating lymphocytes (TILs), tertiary lymphoid structures, fibroblasts, and endothelial cells (ECs) in the tumor tissue. We analyzed 143 NSCLC samples after resistance to EGFR-TKIs from two cohorts: (1) 89 patients treated with ICI monotherapy and (2) 54 patients from the ATTLAS phase III trial comparing atezolizumab plus bevacizumab, paclitaxel, and carboplatin (ABCP) versus pemetrexed plus carboplatin. RESULTS: Post-TKI samples showed reduced TILs in the CA (p=0.045) and increased ECs in the CA (p=0.005) compared with pre-TKI samples. These changes differed according to EGFR mutation subtype. Higher TILs in CA were associated with a better overall response rate (ORR) and progression-free survival (PFS). Similarly, higher EC levels in CA correlated with improved ORR and PFS. In the ATTLAS cohort, these factors were associated with clinical benefits from ABCP, with a significant association with TILs and a marginal association with ECs. CONCLUSION: Our findings suggest that EGFR-TKIs affect the immune landscape of patients with EGFR-mutated NSCLC. Higher TILs or ECs in the CA were significantly associated with a favorable response to subsequent ICI-based treatment. TRIAL REGISTRATION NUMBER: NCT03991403.

Aged↗
PubMed1984

Spatial analysis of evoked potentials in man--a review.

Steps in brain information processing are reflected on the scalp as changes of the electric potential which is evoked by the stimulus. However, for a given recording point on the scalp, there is no absolute amplitude or phase information of the electric brain potential. This means that the shape of an evoked potential waveform which is recorded from a given scalp location crucially depends on the location of the chosen reference. Only unbiased results of evoked potential data evaluation can be hoped to elucidate or map successfully into information processing models established by other methods, e.g. behavior measurements. Conventional recordings vs a common reference contain only one of many possible sets of waveshapes. In order to avoid ambiguities or bias of results, the entire evoked potential data set firstly must be analysed over space, and reference-independent parameters must be extracted. For each time point, the spatial distribution of the potentials is viewed as field map. The parameter extraction in a direct approach at each time point includes, e.g. locations of field peaks and troughs, voltage and gradient between them, and global electrical field power; or, parameters via the first or second spatial derivative of the electric field. In the second step, changes of these reference-independent field measurements are analysed over time. At component latency which is defined by maximal, global field power or by voltage range, mapped field distributions can be compared using maximal/minimal field value locations or complete maps. Significantly different field configurations establish the activity of non-identical neural generators. Classification of the field configurations (examination of orbits of field extrema over time) leads to the segmentation of series of field maps (multichannel EP data) into short epochs of stationary spatial configurations (i.e. spatially characterized components) with equal consideration of all recording points, and without the amplitude criterion. The application of these principles to the following problems is discussed: comparison of evoked potentials between different analysis times, in particular pre-stimulus and post-stimulus electric brain states; zero baseline for measurement; reference electrode; identification of evoked components in time and space. Illustrations of these problems include functional differences of input-analysing sub-systems, and the topography of cognition- and speech-related electric brain activity.

Brain↗
PubMed1992

Spatial analysis of transcriptional activation in fetal rat jejunal and ileal gut epithelium.

In the week before birth (days 15-21 of the 22-day gestation period), the fetal rat small intestinal epithelium undergoes rapid proliferation and differentiation. The developing gut changes from a mesenchymal tube lined by endoderm to a complex absorptive surface composed of differentiated epithelium overlying nascent villi. To begin to characterize the molecular events that take place in nascent intestinal epithelial cells as cytodifferentiation proceeds from jejunum to ileum, we examined spatial, temporal, and cellular patterns of transcriptional activation of the rat liver fatty acid-binding protein (L-FABP) and apolipoprotein (apo) AIV genes. In situ hybridization analyses revealed that transcription of both genes is activated in the jejunum between fetal days 17 and 18, yet their expression is not initiated in the ileum until 1-2 days later. Transcriptional activation proceeds in a "wavelike" fashion along the horizontal length of the gut and coincides with villus morphogenesis. As nascent villi emerge, heterogeneous cellular accumulation of L-FABP mRNA occurs in both fetal jejunal and ileal epithelium, but persists only in the ileum. In contrast, cellular expression of apo AIV mRNA in nascent epithelium is predominantly homogeneous in both regions of the gut. These results indicate that transcriptional activation in the fetal gut epithelium is a complex, dynamic process that is spatially regulated along the horizontal axis of the intestine. Initiation of transcription in enterocytes is closely linked to villus morphogenesis and histological cytodifferentiation.

Animals↗
PubMed1988

Temporal and spatial analysis of cartilage proteoglycan core protein gene expression during limb development by in situ hybridization.

As limb mesenchymal cells differentiate into chondrocytes they initiate the synthesis of a cartilage-specific sulfated proteoglycan, cartilage-characteristic type II collagen, and other cartilage-specific proteins. In the present study, in situ hybridization with a 32P-labeled cloned cDNA probe complementary to mRNA encoding the core protein of cartilage proteoglycan has been used to visualize and localize the accumulation of cartilage proteoglycan core protein mRNA sequences during development of the chick limb bud in vivo. When the probe was hybridized to sections through 7-day (stage 32) limbs, an intense hybridization signal was observed over the well-differentiated cartilage rudiments of the limb, while no signal above background was observed over nonchondrogenic tissues including muscle, loose connective tissue, and epidermis. At early stages of limb development, an accumulation of silver grains representing hybridizable core protein mRNA first became detectable in the proximal central core of the limb where the prechondrogenic condensation of mesenchymal cells that characterizes the onset of cartilage differentiation was occurring. In fact, the pattern of silver grain accumulation closely followed the pattern of mesenchymal cell condensation, and no hybridizable core protein mRNA sequences were detectable in the limb bud prior to condensation. Cartilage-characteristic type II collagen mRNA was colocalized with core protein mRNA in the condensing central core of the limb suggesting that the genes for these two major constituents of cartilage matrix are coordinately regulated at the onset of chondrogenesis. Furthermore, the appearance of hybridizable core protein mRNA was closely followed by the appearance of the protein for which it codes as detected by immunohistochemical staining with monospecific antibody. These observations support the hypothesis that at the initial stages of limb chondrogenesis core protein gene expression is controlled primarily at the transcriptional level.

Aggrecans↗
PubMed1988

Journey patterns of the elderly and disabled in the Cotswolds: a spatial analysis.

The decline of services and transport provision in the North Cotswolds has led to a progressive deterioration in the welfare of the elderly and disabled. This study, based on interviews with 498 individuals in eight typical parishes, relates the travel behaviour of these groups to health status, personal circumstances, the grade and location of services, and mode of transport. The repercussions of the 1985 Transport Act for the car-less and severely disabled are then examined. Given the increased loadings on domiciliary support systems, the case is argued for coordinated initiatives in alternative transport provision which relate, sensitively, to the needs of the different groups among the elderly and disabled.

Activities of Daily Living↗
PubMed1985

A spatial analysis of the blood-brain barrier damage in experimental allergic encephalomyelitis.

Experimental allergic encephalomyelitis was induced in young male Lewis rats. Following the development of neurological signs, the local distribution of perivascular inflammatory cellular infiltrates and the local blood-to-tissue transfer constants (K1) of alpha-aminoisobutyric acid (AIB) were determined, and these results were compared. Perivascular infiltrative lesions were generally found near areas of the CNS that normally lack an effective blood-brain barrier (BBB) such as the choroid plexus and the entry zones of the cranial and spinal nerve roots. This distribution pattern indicates that the entry of the causative agent into CNS tissue may be by way of the permeable microvessels of these structures. In tissue around inflamed veins, the mean transfer constant was slightly but significantly increased (2.8 +/- 1.5 microliter g-1 min-1) compared with uninvolved regions (0.9 +/- 0.2 microliter g-1 min-1) and similar areas in control animals (0.9 +/- 0.3 microliter g-1 min-1). Analysis of the autoradiographic method of determining transfer constants suggested that the AIB influx rate in the lesion areas may actually be manyfold larger than measured, that BBB permeability may be greatly increased at such sites, and that the areas of lymphocytic infiltration and increased K values may be virtually identical.

Aminoisobutyric Acids↗
PubMedDate not supplied

[Spatial analysis of tonal superthreshold signals in dolphins].

Hearing characteristics under the conditions of spacial indetermination of overthreshold tonic signal were studied on dolphins Tursiops truncatus by the method of motordigestive conditional reflexes. High efficiency of spacial analysis on the frequencies 5, 20, 80, 100 kHz was shown. The criterium of relative loss of information in the channel was used for evaluating integral index of efficiency of dolphin spacial hearing.

Animals↗