gebhart/patrepeval huggingface dataset:
H&E image-based consensus molecular subtype classification of colorectal cancer using weak labeling. (2020)

e16097 Background: Using gene-expression, consensus molecular subtypes (CMS) divide colorectal cancers (CRC) into four categories with prognostic and therapy-predictive clinical utilities. These subtypes also manifest as different morphological phenotypes in whole-slide images (WSIs). Here, we implemented and trained a novel deep multiple instance learning (MIL) framework that requires only a single label per WSI to identify morphological biomarkers and accelerate CMS classification. Methods: Deep learning models can be trained by MIL frameworks to classify tissue in localized tiles from large ( &gt; 1 Gb) WSIs using only weakly supervised, slide-level classification labels. Here we demonstrate a novel framework that advances on instance-based MIL by using a multi-phase approach to training deep learning models. The framework allows us to train on WSIs that contain multiple CMS classes while further identifying previously undiscovered tissue features that have low or no correlation with any subtype. Identification of these uncorrelated features results in improved insights into the specific tissue features that are most associated with the four CMS classes and a more accurate classification of CMS status. Results: We trained and validated (n = 735 WSIs and 184 withheld WSIs, respectively) a ResNet34 convolutional neural network to classify 224x224 pixel tiles distributed across tumor, lymphocyte, and stroma tissue regions. The slide-level CMS classification probability was calculated by an aggregation of the tiles correlated with each one of the four subtypes. The receiver operating characteristic curves had the following one-vs-all AUCs: CMS1 = 0.854, CMS2 = 0.921, CMS3 = 0.850, and CMS4 = 0.866, resulting in an average AUC of 0.873. Initial tests to generalize to other data sets, such as TCGA, are promising and constitute one of the future directions of this work. Conclusions: The MIL framework robustly identified tissue features correlated with CMS groups, allowing for a more efficient classification of CRC samples. We also demonstrated that the morphological features indicative of different molecular subtypes can be identified from the deep neural network.
The Genomes On Line Database (GOLD) v.2: a monitor of genome projects worldwide (2005)

The Genomes On Line Database (GOLD) is a web resource for comprehensive access to information regarding complete and ongoing genome sequencing projects worldwide. The database currently incorporates information on over 1500 sequencing projects, of which 294 have been completed and the data deposited in the public databases. GOLD v.2 has been expanded to provide information related to organism properties such as phenotype, ecotype and disease. Furthermore, project relevance and availability information is now included. GOLD is available at http://www.genomesonline.org. It is also mirrored at the Institute of Molecular Biology and Biotechnology, Crete, Greece at http://gold.imbb.forth.gr/
Global Analysis of Genetic, Epigenetic and Transcriptional Polymorphisms in Arabidopsis thaliana Using Whole Genome Tiling Arrays (2008)

Whole genome tiling arrays provide a high resolution platform for profiling of genetic, epigenetic, and gene expression polymorphisms. In this study we surveyed natural genomic variation in cytosine methylation among Arabidopsis thaliana wild accessions Columbia (Col) and Vancouver (Van) by comparing hybridization intensity difference between genomic DNA digested with either methylation-sensitive (HpaII) or -insensitive (MspI) restriction enzyme. Single Feature Polymorphisms (SFPs) were assayed on a full set of 1,683,620 unique features of Arabidopsis Tiling Array 1.0F (Affymetrix), while constitutive and polymorphic CG methylation were assayed on a subset of 54,519 features, which contain a 5'CCGG3' restriction site. 138,552 SFPs (1% FDR) were identified across enzyme treatments, which preferentially accumulated in pericentromeric regions. Our study also demonstrates that at least 8% of all analyzed CCGG sites were constitutively methylated across the two strains, while about 10% of all analyzed CCGG sites were differentially methylated between the two strains. Within euchromatin arms, both constitutive and polymorphic CG methylation accumulated in central regions of genes but under-represented toward the 5' and 3' ends of the coding sequences. Nevertheless, polymorphic methylation occurred much more frequently in gene ends than constitutive methylation. Inheritance of methylation polymorphisms in reciprocal F1 hybrids was predominantly additive, with F1 plants generally showing levels of methylation intermediate between the parents. By comparing gene expression profiles, using matched tissue samples, we found that magnitude of methylation polymorphism immediately upstream or downstream of the gene was inversely correlated with the degree of expression variation for that gene. In contrast, methylation polymorphism within genic region showed weak positive correlation with expression variation. Our results demonstrated extensive genetic and epigenetic polymorphisms between Arabidopsis accessions and suggested a possible relationship between natural CG methylation variation and gene expression variation.
Carotid Glomectomy in Bronchial Asthma (1964)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Otolaryngology–Head & Neck Surgery HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Otolaryngology–Head & Neck Surgery journal
Ribozyme-targeting elucidates a direct role of pleiotrophin in tumor growth. (1994)

The growth and metastasis of solid tumors rely on the activities of polypeptide growth factors. However, numerous growth factors are expressed in tumors, and it is difficult to decipher which are essential for tumor progression. We found the secreted growth factor pleiotrophin (PTN) expressed at high levels in a number of human tumor cell lines as well as in tumor samples. To assess the role of PTN in tumor growth, we inactivated the PTN gene with PTN-targeted hammerhead ribozyme constructs. Cotransfection of PTN and of the ribozymes inhibited PTN-induced colony formation of PTN-responsive cells whereas a point mutant, catalytically inactive ribozyme was ineffective. Colony formation induced by transfections with a closely related growth factor (midkine) was not affected by the ribozymes. In human melanoma cells that express high levels of PTN mRNA, stable transfection with PTN-targeted ribozymes quenched production of PTN, inhibited colony formation of the cells, and prevented their tumor growth in mice. This demonstrates that expression of a growth factor can be a rate-limiting step for malignant progression and suggests that ribozymes could be used therapeutically to target tumor growth factors.
Cerebral Sinus Thrombosis in a Trauma Patient after Recombinant Activated Factor VII Infusion (2004)

SEVERAL investigators have reported the astonishing effect of recombinant activated factor VII (rFVIIa) in trauma patients with diffuse bleeding. Currently, rFVIIa is approved for the treatment of patients with hemophilia with inhibitors to factors VIII and IX. Conditions with increased thromboembolic risk, including trauma, extensive tissue damage, sepsis, arteriosclerosis, and disseminated intravascular coagulation, may be considered contraindications for the drug. Thrombotic complications in trauma patients are rarely observed. To our knowledge, this is the first report of a patient who experienced a cerebral sinus thrombosis in the posttraumatic period after rFVIIa administration.
Intermittent Hypoxia and the Practice of Anesthesia (2009)

Intermittent hypoxia, a powerful and unique stimulus, leads to physiologic changes that are distinct from those associated with either single or continuous hypoxic exposure. There is an accumulating body of evidence that the neurocognitive, inflammatory and cardiovascular symptoms that characterize the syndrome of obstructive sleep apnea are linked to the stimulus of intermittent hypoxia. In addition, altered sensitivities to opiates in children with obstructive sleep apnea have been linked to recurrent hypoxia during sleep. Therefore anesthesiologists should have an understanding of this important stimulus.
Levels of hepatitis C virus RNA and liver histology in chronic type C hepatitis. (1994)

The lowest levels of hepatitis C viremia are, in general, associated with minimal liver disease. Overall, histological severity of chronic hepatitis C infection best predicts HCV RNA levels.
The High Specificities of Phaseolus vulgaris Erythro- and Leukoagglutinating Lectins for Bisecting GlcNAc or β1–6-Linked Branch Structures, Respectively, Are Attributable to Loop B (2002)

Despite very similar tertiary structures based upon a common framework, legume lectins exhibit an amazing variety of sugar binding specificities. While most of these lectins recognize rather discrete sugar linkages, Phaseolus vulgaris erythroagglutinating and leukoagglutinating lectins (E(4)- and L(4)-PHA) are unique in recognizing larger structures. E(4)- and L(4)-PHA are known to recognize complex type N-glycans containing bisecting GlcNAc or a beta1,6-linked branch, respectively. However, the detailed mechanisms of molecular recognition are poorly understood. In order to dissect the contributions of different portions of each lectin, we carried out region-swapping mutagenesis between E(4)- and L(4)-PHA. We prepared six chimeric lectins by exchanging different combinations of loop B and the central portion of loop C, two of four loops thought to be important for the recognition of monosaccharides (Sharma, V., and Surolia, A. (1997) J. Mol. Biol. 267, 433-445). The chimeric lectins' sugar binding activities were evaluated quantitatively by surface plasmon resonance. These comparisons indicate that the high specificities of E(4)- and L(4)-PHA toward bisecting GlcNAc and beta1,6-linked branch structures are almost solely attributable to loop B. The contribution of the central portion of loop C to the recognition of those structural motifs was found to be negligible. Instead, it modulates affinity toward LacNAc residues present at the nonreducing terminus. Moreover, some of the chimeric lectins prepared in this study showed even higher specificities/affinities than native E(4)- and L(4)-PHA toward complex sugar chains containing either a bisecting GlcNAc residue or a beta1,6-linked branch.
Injectable scaffolds for tissue regeneration (2004)

Tissue engineering aims to develop functional substitutes for damaged or diseased tissues through complex constructs of living cells, bioactive molecules and three-dimensional porous scaffolds, which support cell attachment, proliferation and differentiation. Such constructs can be formed either by seeding cells within a pre-formed scaffold or through injection of a solidifiable precursor and cell mixture to the defective tissue. As cell and bioactive molecule carriers, injectable scaffolds are appealing, particularly from the clinical point of view, because they offer the possibility of homogeneously distributing cells and molecular signals throughout the scaffold and can be injected directly into cavities, even of irregular shape and size, in a minimally invasive manner. In this paper the challenges in designing an injectable scaffold from the viewpoint of materials chemistry and the solidification mechanisms of injectable precursors are discussed. The applications of injectable scaffolds in angiogenesis, bone repair and cartilage regeneration are described.
Clearance of a persistent paramyxovirus infection is mediated by cellular immune responses but not by serum-neutralizing antibody (1990)

Infection of the lungs of immunodeficient mice with the paramyxovirus simian virus 5 (SV5) was prolonged compared with the time course of infection in immunocompetent mice. Although there was a significant increase in both viral RNA and proteins, little infectious virus was produced. Adoptive transfer of immune lymphocytes (isolated from the spleens of mice previously infected with SV5) but not of nonimmune lymphocytes increased the speed of clearance of virus from the lungs of immunodeficient mice. In contrast, passive transfer of a pool of neutralizing monoclonal antibodies specific for the HN and F glycoproteins of SV5 did not have a significant effect on the speed of clearance of virus. Furthermore, no significant increase in the rate of virus clearance was observed upon adoptive transfer of purified immune B lymphocytes to SV5-infected immunodeficient mice despite production by the mice of high titers of neutralizing antibodies. Evidence is presented that CD8+ effector cells are primarily responsible for the clearance observed. The general significance of these results with respect to immune clearance of persistent virus infections is discussed.
Selective heat sensitivity of cancer cells. Biochemical and clinical studies (1967)

Biochemical and clinical studies have revealed a profound and selective toxic effect of elevated temperatures on tumor cells. Whereas the oxygen uptake of Novikoff hepatoma and Ehrlich ascites carcinoma cells was considerably less at 427deg;C than at 38°C, there was little difference in respiration at these two temperatures in normal and regenerating liver. The inhibition of the respiration of Novikoff hepatoma cells was irreversible after 90 min. There was no significant effect of temperature on anaerobic glycolysis. In 22 patients with cancers of the limbs the temperature in the tumors was raised to 41.5° to 43.5°C for several hours in 25 regional perfusions with prewarmed blood. Severe complications in some patients lead to six deaths and three immediate amputations. Intensive post-treatment care was required. Three patients failed to respond; four could not be evaluated and all others had regressions. Grossly the tumors disappeared totally in ten patients, of which three recurred. Histological evaluation of multiple biopsies demonstrated complete massive necrosis in eight cases, of which none recurred, although one died and three required amputations; of these, seven are alive and free of disease. In the cases with partial regression, the tumors all recurred and required amputation or other treatment. The most responsive tumor appeared to be melanoma. No conclusions about survivals can be drawn at present although four of seven patients with malignant melanomas treated only by heat perfusion are alive and well with functional limbs 28, 27, 11 and 7 months after treatment. Only one patient has died of metastases although two have been lost to follow-up.
The Diabetes Risk Score (2003)

The Diabetes Risk Score is a simple, fast, inexpensive, noninvasive, and reliable tool to identify individuals at high risk for type 2 diabetes.
Hyperphagia in cold-exposed rats is accompanied by decreased plasma leptin but unchanged hypothalamic NPY (1998)

Chronic cold exposure stimulates sympathetically driven thermogenesis in brown adipose tissue (BAT), resulting in fat mobilization, weight loss, and compensatory hyperphagia. Hypothalamic neuropeptide Y (NPY) neurons are implicated in stimulating food intake in starvation, but may also suppress sympathetic outflow to BAT. This study investigated whether the NPY neurons drive hyperphagia in rats that have lost weight through cold exposure. Rats exposed to 4 degrees C for 21 days weighed 14% less than controls maintained at 22 degrees C (P < 0.001). Food intake increased after 3 days and remained 10% higher thereafter (P < 0.001). Increase BAT activity was confirmed by 64, 96, and 335% increases in uncoupling protein-1 mRNA at 2, 8, and 21 days. Plasma leptin decreased during prolonged cold exposure. Cold-exposed rats showed no significant changes in NPY concentrations in any hypothalamic regions or in hypothalamic NPY mRNA at any time. We conclude that the NPY neurons are not activated during cold exposure. This is in contrast with starvation-induced hyperphagia, but is biologically appropriate since enhanced NPY release would inhibit thermogenesis causing potentially lethal hypothermia. Other neuronal pathways must therefore mediate hyperphagia in chronic cold exposure.
Transcription factor and liver-specific mRNA expression in facultative epithelial progenitor cells of liver and pancreas. (1995)

The pattern of mRNA expression for liver-specific proteins and liver-enriched transcription factors was studied in two models of facultative gut epithelial progenitor cells activation: D-galactosamine (GalN)-induced liver injury and dietary copper depletion leading to pancreatic acinar atrophy. After 5 weeks of copper deficiency (CuD), pancreatic acini of Fischer 344 rats underwent atrophy, associated with intense proliferation of small duct-like cells with oval-shaped nuclei. These cells resemble morphologically epithelial progenitor cells of the liver that proliferate after GalN administration. Activated pancreatic epithelial cells express mRNAs for liver-specific genes normally expressed in fetal liver, including alpha-fetoprotein, albumin, alpha-1 antitrypsin, glucose-6-phosphatase, and others, but not genes that are turned on after birth such as serine dehydratase, tyrosine aminotransferase, and multidrug resistance gene-1b. They express mRNAs for liver-enriched transcription factors including HNF-1 alpha, HNF-3 beta and gamma, HNF-4, and members of the CCAAT-enhancer binding protein (C/EBP) family. The only mRNA for a liver-enriched transcription factor not detected in the pancreas of CuD animals was HNF-3 alpha. Expression of HNF-3 alpha, beta, and gamma, and C/EBP-beta mRNA was highly activated in proliferating liver epithelial cells on days 2 and 3 after GalN injury. Increased expression of C/EBP-delta was observed first in the liver on day 1 after GalN administration and in the pancreas at 4 weeks after initiating CuD. We suggest that C/EBP-delta could be involved in the initial activation of epithelial progenitor cells and that HNF-3 alpha, beta, and gamma, and C/EBP-beta might participate in their maturation. We conclude further that pancreatic epithelial progenitor cells undertake differentiation through the hepatocyte lineage but cannot complete the differentiation program within the pancreatic milieu.
Structural and mechanical factors influencing infarct scar collagen organization (2000)

Although large collagen fibers in myocardial infarct scar are highly organized, little is known about mechanisms controlling this organization. The preexisting extracellular matrix may act as a scaffold along which fibroblasts migrate. Conversely, deformation within the ischemic area could guide fibroblasts so new collagen is oriented to counteract the stretch. To investigate these potential mechanisms, we infarcted three groups of pigs. Group 1 served as infarct controls. Group 2 had the endocardium slit longitudinally to alter local systolic deformation. Group 3 had a plug sectioned from ischemic tissue and rotated 90 degrees. The slit altered systolic deformation in the infarcted tissue, changing circumferential strain from expansion to compression and increasing radial strain and shears and the variability of collagen fiber angles but not the mean angle. In the plug pigs, when deformation, matrix orientation, and continuity are altered in the infarct area, the result is complete disarray in the organization of collagen within the infarct scar.
Mislocalization and Degradation of Human P23H-Rhodopsin-GFP in a Knockin Mouse Model of Retinitis Pigmentosa (2011)

P23H-hRho-GFP mice provide a valuable tool for evaluating the efficacy of potential therapies for ADRP that influence the levels or localization of P23H-rhodopsin.
A Pseudomonas aeruginosa quorum‐sensing molecule influences Candida albicans morphology (2004)

Candida albicans is an opportunistic pathogen that is commonly found as a member of the human microflora. The ability of C. albicans to alter its cellular morphology has been associated with its virulence; yeast cells are more prevalent in commensal interactions whereas filamentous cells appear important in opportunistic infections. C. albicans encounters a multitude of other microbial species in the host environment and it is likely that they impact the C. albicans transition between virulent and non-virulent states. Here, we report that C. albicans morphology is significantly affected by the presence of Pseudomonas aeruginosa, another opportunistic pathogen. In a screen using a C. albicans HWP1-lacZ strain to indicate regions of filamentous growth, we identified P. aeruginosa mutants incapable of inhibiting C. albicans filamentation. Through these studies, we found that 3-oxo-C12 homoserine lactone, a cell-cell signalling molecule produced by P. aeruginosa, was sufficient to inhibit C. albicans filamentation without affecting fungal growth rates. Both microscopic analysis and real-time reverse transcription polymerase chain reaction analysis of morphology-specific markers confirmed that filamentation was suppressed by 200 microM 3-oxo-C12 homoserine lactone. Structurally related compounds with a 12-carbon chain length, e.g. C12-acyl homoserine lactone and dodecanol also affected C. albicans filamentation at similar concentrations. In contrast, other acylated homoserine lactones of different chain lengths did not affect fungal morphology. The activity of 3OC12HSL is compared with that of farnesol, a C. albicans-produced molecule also with a C12-backbone. The effects that bacteria have on the morphology of C. albicans represents one of the ways by which bacteria can influence the behaviour of fungal cells.
New Integrative Method To Generate Bacillus subtilis Recombinant Strains Free of Selection Markers (2004)

The novel method described in this paper combines the use of blaI, which encodes a repressor involved in Bacillus licheniformis BlaP beta-lactamase regulation, an antibiotic resistance gene, and a B. subtilis strain (BS1541) that is conditionally auxotrophic for lysine. We constructed a BlaI cassette containing blaI and the spectinomycin resistance genes and two short direct repeat DNA sequences, one at each extremity of the cassette. The BS1541 strain was obtained by replacing the B. subtilis P(lysA) promoter with that of the P(blaP) beta-lactamase promoter. In the resulting strain, the cloning of the blaI repressor gene confers lysine auxotrophy to BS1541. After integration of the BlaI cassette into the chromosome of a conditionally lys-auxotrophic (BS1541) strain by homologous recombination and positive selection for spectinomycin resistance, the eviction of the BlaI cassette was achieved by single crossover between the two short direct repeat sequences. This strategy was successfully used to inactivate a single gene and to introduce a gene of interest in the Bacillus chromosome. In both cases the resulting strains are free of selection marker. This allows the use of the BlaI cassette to repeatedly further modify the Bacillus chromosome.