SEARCH · Search PubMed
Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.
Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Colorectal cancer (CRC) remains a major health concern, with >150,000 new diagnoses and >50,000 deaths annually in the United States, underscoring an urgent need for improved screening, prognostication, disease management, and therapeutic approaches. The tumor microenvironment (TME)-comprising cancerous and immune cells interacting within the tumor's spatial architecture-plays a critical role in disease progression and treatment outcomes, reinforcing its importance as a prognostic marker for metastasis and recurrence risk. However, traditional methods for TME characterization, such as bulk transcriptomics and multiplex protein assays, lack sufficient spatial resolution. Although spatial transcriptomics (ST) allows for the high-resolution mapping of whole transcriptomes at near-cellular resolution, current ST technologies (eg, Visium and Xenium) are limited by high costs, low throughput, and issues with reproducibility, preventing their widespread application in large-scale molecular epidemiology studies. In this study, we refined and implemented virtual RNA inference (VRI) to derive ST-level molecular information directly from hematoxylin and eosin (H&E)-stained tissue images. Our VRI models were trained on the largest matched CRC ST data set to date, comprising 45 patients and >300,000 Visium spots from primary tumors. Using state-of-the-art deep learning models (UNI, ResNet-50, Vision Transformer, and Vision Mamba), we achieved a median Spearman's correlation coefficient of 0.546 between predicted and measured spot-level expression. As validation, VRI-derived gene signatures linked to specific tissue regions (tumor, interface, submucosa, stroma, serosa, muscularis, and inflammation) showed strong concordance with signatures generated via direct ST, and VRI performed accurately in estimating cell-type proportions spatially from H&E slides. In an expanded CRC cohort controlling for tumor invasiveness and clinical factors, we further identified VRI-derived gene signatures significantly associated with key prognostic outcomes, including metastasis status. Although certain tumor-related pathways are not fully captured by histology alone, our findings highlight the ability of VRI to infer a wide range of "histology-associated" biological pathways at near-cellular resolution without requiring ST profiling. Future efforts will extend this framework to expand TME phenotyping from standard H&E tissue images, with the potential to accelerate translational CRC research at scale.
Once a unit-based shared governance counselor model is established, the evolution from establishing the structure of shared governance toward the process of initiating goal-oriented activities begins. Nurturing staff participation, empowerment, and effective communication patterns are vital. The author shares strategies to address these issues and accelerate development of the transformational vision of shared governance.
The visual response to a flash given in the dark is known to saturate according to the Michaelis-Menten relationship. Nevertheless, the incremental response from increasing levels of mean luminance tends to follow a Weber-Fechner relationship well into the saturation range determined from the Michaelis-Menten results. This sensitivity transformation from Michaelis-Menten to Weber-Fechner is an important characteristic of light adaptation in the vertebrate retina. Recent studies concerning the role of calcium in photoreceptor adaptation have shown that the relaxation from peak to plateau in the response of isolated photoreceptors was absent under conditions in which adaptation was blocked. Comparing the pronounced relaxation from peak to plateau in turtle horizontal cells with the absence of such relaxation in the catfish response, we noted also that turtle incremental sensitivity shows a Weber-Fechner relationship while catfish incremental sensitivity more closely follows the local slope of the Michaelis-Menten relation. Based on these observations, we have obtained an expression to relate the relaxation from peak to plateau with the sensitivity transformation. We assume that adaptation shifts the half-maximum point of the Michaelis-Menten curve so that the light response relaxes to a plateau value equal to a specified fraction phi of the peak response. We show that this manipulation alone results in a transformation from Michaelis-Menten kinetics to Weber-Fechner sensitivity.
Explore the source record for details and available documents.
Plant diseases destroy 20-40% of global food production annually, posing a critical threat to food security for a projected population of 9.7 billion by 2050. Conventional diagnostic approaches relying on expert visual assessment are slow, costly, and unsuitable for modern agricultural scales. While deep convolutional neural networks demonstrated early promise, single-modality, image-centric systems consistently fail under real-world field conditions characterized by variable lighting, co-occurring infections, and cultivar diversity. This review synthesizes a decade of progress across four interconnected frontiers: the evolution of deep learning architectures for plant disease detection; the adaptation of foundation models including CLIP, SAM, and DINOv2 to agricultural contexts; the development of multimodal fusion frameworks integrating imagery, environmental, genomic, and hyperspectral data; and the transition from static disease diagnosis to descriptive comparison of reported metrics, which suggested that multimodal approaches frequently reported improved diagnostic performance relative to corresponding single-modality baselines, although direct cross-study comparison was limited by methodological heterogeneity. A systematic review following PRISMA guidelines identifies eligible comparative studies. Descriptive comparison of reported performance metrics across these studies indicated that multimodal approaches generally achieved higher accuracy and sensitivity than single-modality models, particularly for pre-symptomatic disease detection. Eight critical research gaps are identified, including the absence of a unified agricultural foundation model and limited climate-aware forecasting under non-stationary climate projections. A structured research agenda is proposed to accelerate translation from laboratory performance to globally equitable, field-deployable crop protection systems.
Mutation of the Drosophila melanogaster gene no-on-transient A (nonA) results in reduced visual acuity, behavior abnormalities, and an electrophysiological defect for which the mutant is named. We mapped the nonA gene genetically to a 20 kb interval within the 14C1,2 region of the X chromosome, isolated this chromosomal region, and used P element-mediated transformation to delimit the nonA gene to a 9 kb region. Analysis of cDNA clones indicates that this region encodes alternatively spliced transcripts encoding protein products of approximately 77 kd that differ only in their C-terminal 35 amino acids. Analysis of mutations generated in vitro in this transcription unit confirm that these transcripts are the products of the nonA gene.
The purpose of this study was to investigate the relationship between horizontal and vertical components of handwriting production when subjects were instructed to vary the size of these components separately or together. The effect of vision on these instructed size transformations also was examined. Eight female adults participated in the experiment. The basic task was to write the words 'poppy' and 'wood' cursively five times, the first time in their normal size and then with four size transformations. These transformations--one-fourth, one-half, double, and four-times their normal size--were made under three different sets of instructions (width only, height only, both) and in two visual conditions (normal, blindfolded), for a total of six sets of five repetitions. The individual slopes (changes in actual values across the transformation values) for width and height under instructions to change both parameters were almost identical to the width and height slopes under instructions to change only the single parameter, supporting the notion of the independence of the horizontal and vertical components. Further, an analysis of these individual slopes indicated that the size transformations were significantly greater (p less than 0.05) (and closer to the instructed values) with vision than without vision.
A number of ocular problems compromising vision occurred in a patient with chronic myeloid leukemia following blastic transformation. Hemorrhagic retinopathy developed with systemic relapse and resolved with control of systemic disease. Optic nerve involvement occurred with meningeal leukemia and was controlled with intrathecal cytosine arabinoside and methotrexate. Leukemic retinal infiltrates developed despite control of systemic and meningeal disease and were successfully treated with radiation therapy. Finally, bilateral vitreous hemorrhages occurred, severely impairing vision. Leukemic infiltration of the eye may occur with increasing frequency in CML as the survival following bastic transformation improves. Infiltration should be recognized and treated promptly if serious loss of vision is to be avoided. Central nervous system prophylaxis should be considered in patients achieving a complete response following therapy for transformation.
The visual representation of spatial patterns begins with a series of linear transformations: the stimulus is blurred by the optics, spatially sampled by the photoreceptor array, spatially pooled by the ganglion-cell receptive fields, and so forth. Models of human spatial-pattern vision commonly summarize the initial transformations by a single linear transformation that maps the stimulus into an array of sensor responses. Some components of the initial linear transformations (e.g., lens blurring, photoreceptor sampling) have been estimated empirically; others have not. A computable model must include some assumptions concerning the unknown components of the initial linear encoding. Even a modest sketch of the initial visual encoding requires the specification of a large number of sensors, making the calculations required for performance predictions quite large. We describe procedures for reducing the computational burden of current models of spatial vision that ensure that the simplifications are consistent with the predictions of the complete model. We also describe a method for using pattern-sensitivity measurements to estimate the initial linear transformation. The method is based on the assumption that detection performance is monotonic with the vector length of the sensor responses. We show how contrast-threshold data can be used to estimate the linear transformation needed to characterize threshold performance.
A paradox of sharp vision regardless of relatively large receptive fields of the retina is discussed. Transformation of images by the receptive fields or intersecting fields of vision of omma-tidia of the complex eye is described as an approximation of Bool functions by the implicant forms. Such an approximation results in the information compression. The compression coefficient is determined by the ratio between the implicants number and the number of points in the field of determination of the Bool function. The approximation errors strongly depend on the size of the receptive fields. With their increase the error abruptly decreases and only after passing the deep minimum it begins to slowly increase. The mechanism of information compression is a universal one and is similarly realized on the retina, facet and t.v. sets.
This paper presents a systematic analysis of the role of opponent type processing in colour vision and the relation between opponent type colour transformations and the initial three colour mechanisms. It is shown that efficient information transmission is achieved by a transformation of the initial three colour mechanisms into an achromatic and two opponent chromatic channels. The derivation of the transformation is dependent solely on criteria from information theory. Thus it provides a logical rationale reconciling opponent type processing as an optimal necessary step after the initial three colour mechanisms, unifying respectively the Hering and Young-Helmholtz approaches to colour vision. The effects of chromatic adaptation on the spectral response of the achromatic and two chromatic channels are discussed from the point of view of information theory. It is argued that adaptation serves as a dynamic readjustment of these responses, necessary to meet criteria of efficient colour information transmission. The results are confronted with empirical observations to test the principles of the theory and the relation to other theories is discussed. Within the same framework the issue of trichromacy is discussed. It is argued that a broad class of typical colour spectra can effectively be represented by three significant degrees of freedom that make up a trichromatic system.
The social, political, and economic forces operative in nineteenth-century Britain are briefly described. This permits tracing the birth of both the scientific study of individual differences and the field of eugenics to the infrastructure of society at that time. The distinction is made between the normative doctrine of individualism and the factual study of individual differences. It is argued that democratic--liberal--capitalistic--individualism, in part, conditioned the beginning of differential psychology and eugenics. In this process, Galton's liberal views concerning individual freedom and opportunity for full development became transformed into their dialectic--totalitarian--collectivism--a vision of an ideal state which did not come into being. It is paradoxically concluded that those same social forces which helped bring about the birth of differential psychology and the entailing eugenics ideology prevented the latter from being accepted and implemented.
An electrophysiological and anatomical study identified the sensory inputs to the "flank" of the mouse's superior colliculus, a large, ventrolateral extension of layer IV (stratum griseum intermediate) that has no overlying visual layers (II and III). Electrophysiological recordings with subsequent histological localization showed that the flank receives predominantly somatosensory projections from the perioral region but not visual input. In its caudal parts, the flank also has limb and trunk somatosensory inputs and auditory inputs. The perioral somatosensory projections to the flank are ordered somatotopically. The flank is considered part of the superior colliculus since the perioral inputs are adjacent to inputs from mystacial vibrissae in the more medial parts of the superior colliculus, hence forming a single continuous map. The finding that no visual responses occur above the flank (due to the absence of superficial layers) or within it is in accord with the concept of an intermodality "spatial register". Since flank neurons have somatosensory receptive fields in non-visible parts of the body and they lack visual responses, the flank may be involved more in tactile-dependent rather than in vision-dependent orienting behaviors. Thus, the superior colliculus may, in parallel, carry out sensorimotor transformations related to (1) shift of gaze and (2) tactile-dependent behaviors not involving vision.
Macromolecules carrying biological information often consist of independent modules containing recurring structural motifs. Detection of a specific structural motif within a protein (or DNA) aids in elucidating the role played by the protein (DNA element) and the mechanism of its operation. The number of crystallographically known structures at high resolution is increasing very rapidly. Yet, comparison of three-dimensional structures is a laborious time-consuming procedure that typically requires a manual phase. To date, there is no fast automated procedure for structural comparisons. We present an efficient O(n3) worst case time complexity algorithm for achieving such a goal (where n is the number of atoms in the examined structure). The method is truly three-dimensional, sequence-order-independent, and thus insensitive to gaps, insertions, or deletions. This algorithm is based on the geometric hashing paradigm, which was originally developed for object recognition problems in computer vision. It introduces an indexing approach based on transformation invariant representations and is especially geared toward efficient recognition of partial structures in rigid objects belonging to large data bases. This algorithm is suitable for quick scanning of structural data bases and will detect a recurring structural motif that is a priori unknown. The algorithm uses protein (or DNA) structures, atomic labels, and their three-dimensional coordinates. Additional information pertaining to the structure speeds the comparisons. The algorithm is straightforwardly parallelizable, and several versions of it for computer vision applications have been implemented on the massively parallel connection machine. A prototype version of the algorithm has been implemented and applied to the detection of substructures in proteins.
Many species of fish exhibit metamorphosis in which dramatic external transformations occur as a consequence of coordinated changes in gene expression within an organism. Because postembryonic development and change appears to be the rule rather than the exception in teleost fish species, we view metamorphosis as one of many developmental strategies in fish which have continued plasticity as a common theme. Metamorphic changes are manifested in the visual system by modification of photoreceptor peak sensitivity, rod photoreceptor cell addition, and retinal reorganization. These changes correspond to significant changes in the natural habitat of the animal and in its visual capabilities as demonstrated behaviorally. Thyroxine is the main metamorphic hormone as has also been found in amphibia. The sequence of metamorphic events occur in all teleosts, but they are compressed in time in direct developing animals suggesting that such animals might prove useful for understanding the evolution of metamorphosis in fish. It seems likely that rod photoreceptors may have evolved in conjunction with the change from larval to juvenile stage through metamorphosis in indirect developing fishes. During evolution, the contraction and/or loss of the larval stage has resulted in earlier appearance of rod photoreceptors during development although they always arise later than cone photoreceptors. This ontogenetic developmental sequence supports Walls's (1942) proposal that cones are phylogenetically older than rods and suggests that rods may have evolved several times.
Deans of the top-ranked schools of nursing in the United States were surveyed and asked to describe leadership behaviors. Mean scores indicated that values was reported as the most important transformative leadership theme followed by the themes of vision, people, motivation, and influence. The most important leadership attribute reported was a commitment to a higher code of ethical behavior. This study adds to the research literature on the nursing deanship and has important implications for the identification, selection, and training of exemplary leaders in nursing.