Endometrial Glandular Dysplasia (EmGD): morphologically and biologically distinctive putative precursor lesions of Type II endometrial cancers

In this article, the authors briefly review the historical evolution of the various putative precursor lesions for Type II endometrial cancers, with an emphasis on the newly defined "Endometrial Glandular Dysplasia (EmGD)". The evidentiary basis for delineating serous EmGD as the most probable precursor lesions to endometrial serous carcinoma is reviewed in detail. An argument is advanced for the discontinuation of the term serous "endometrial intraepithelial carcinoma (EIC)" as a descriptor for a supposedly intraepithelial, precancerous lesion. Preliminary evidence is also presented that suggests that there is a morphologically recognizable "clear cell EmGD" that probably represents a precancerous lesion to endometrial clear cell carcinomas

Age dependent association of endometrial polyps with increased risk of cancer involvement

BACKGROUND: Endometrial polyps (EMPs) are commonly encountered in routine surgical pathology practice, but opinions differ on whether they are intrinsically a marker for concurrent or subsequent malignancy. The objectives of the present study are 1) to investigate the age-group in which EMP are most commonly encountered 2) to document the age-group in which EMP are most commonly associated with malignancies 3) To investigate whether the age of diagnosis of the various carcinoma subtypes in EMPs is congruent with published data on similar malignancies arising in non-polypoid endometrium and 4) To investigate whether the histologic subtype distribution of malignancies associated with EMPs are similar or different from the distribution of malignancies arising from non-polypoid endometrium based on published data. PATIENTS AND METHODS: All cases of EMPs were retrieved from the files of Yale-New Haven Hospital for the period 1986–1995. The patients were divided into 5 age groups: Each group was further subclassified based on an association (or lack thereof) of EMPs with endometrial carcinoma. Chi-square test was used to compare the proportion of malignancy associated EMPs between the age groups. RESULTS: We identified 513 EMPs, of which 209 (41%) were from biopsy specimens and 304 (59%) from hysterectomy specimens. Sixty six (13%) of all EMPs were malignant. The 66 malignant EMPs included 58 endometrioid, 6 serous, 1 carcinosarcoma, and 1 clear cell carcinoma. In age group >35, only 1(2.5%) of 40 EMPs was associated with endometrial malignancy. In contrast, 37(32%) of 115 EMPs were associated with malignancy in the age group > 65. The frequency of malignant EMPs increased with age and reached statistical significance in the age group >65 (p < 0.001). The most common histologic type of malignancy was endometrioid adenocarcinoma. CONCLUSIONS: EMPs show statistically significant age dependent association with malignant tumor involvement. Careful search for malignancy, particularly in women with multiple risk factors is advised in daily practice. Additional studies are needed to address the histological features and immunohistochemical profiles in the context of association between endometrioid and high-grade endometrial carcinoma and endometrial polyps

Ovarian serous carcinoma: recent concepts on its origin and carcinogenesis

Recent morphologic and molecular genetic studies have led to a paradigm shift in our conceptualization of the carcinogenesis and histogenesis of pelvic (non-uterine) serous carcinomas. It appears that both low-grade and high-grade pelvic serous carcinomas that have traditionally been classified as ovarian in origin, actually originate, at least in a significant subset, from the distal fallopian tube. Clonal expansions of the tubal secretory cell probably give rise to serous carcinomas, and the degree of ciliated conversion is a function of the degree to which the genetic hits deregulate normal differentiation. In this article, the authors review the evidentiary basis for aforementioned paradigm shift, as well as its potential clinical implications

Prompt-Specific Poisoning Attacks on Text-to-Image Generative Models

Data poisoning attacks manipulate training data to introduce unexpected behaviors into machine learning models at training time. For text-to-image generative models with massive training datasets, current understanding of poisoning attacks suggests that a successful attack would require injecting millions of poison samples into their training pipeline. In this paper, we show that poisoning attacks can be successful on generative models. We observe that training data per concept can be quite limited in these models, making them vulnerable to prompt-specific poisoning attacks, which target a model's ability to respond to individual prompts. We introduce Nightshade, an optimized prompt-specific poisoning attack where poison samples look visually identical to benign images with matching text prompts. Nightshade poison samples are also optimized for potency and can corrupt an Stable Diffusion SDXL prompt in <100 poison samples. Nightshade poison effects "bleed through" to related concepts, and multiple attacks can composed together in a single prompt. Surprisingly, we show that a moderate number of Nightshade attacks can destabilize general features in a text-to-image generative model, effectively disabling its ability to generate meaningful images. Finally, we propose the use of Nightshade` and similar tools as a last defense for content creators against web scrapers that ignore opt-out/do-not-crawl directives, and discuss possible implications for model trainers and content creators

Cascaded Detail-Preserving Networks for Super-Resolution of Document Images

The accuracy of OCR is usually affected by the quality of the input document image and different kinds of marred document images hamper the OCR results. Among these scenarios, the low-resolution image is a common and challenging case. In this paper, we propose the cascaded networks for document image super-resolution. Our model is composed by the Detail-Preserving Networks with small magnification. The loss function with perceptual terms is designed to simultaneously preserve the original patterns and enhance the edge of the characters. These networks are trained with the same architecture and different parameters and then assembled into a pipeline model with a larger magnification. The low-resolution images can upscale gradually by passing through each Detail-Preserving Network until the final high-resolution images. Through extensive experiments on two scanning document image datasets, we demonstrate that the proposed approach outperforms recent state-of-the-art image super-resolution methods, and combining it with standard OCR system lead to signification improvements on the recognition results

Magnetically Controllable Polymer Nanotubes from a Cyclized Crosslinker for Site-Specific Delivery of Doxorubicin

Externally controlled site specific drug delivery could potentially provide a means of reducing drug related side effects whilst maintaining, or perhaps increasing therapeutic efficiency. The aim of this work was to develop a nanoscale drug carrier, which could be loaded with an anti-cancer drug and be directed by an external magnetic field. Using a single, commercially available monomer and a simple one-pot reaction process, a polymer was synthesized and crosslinked within the pores of an anodized aluminum oxide template. These polymer nanotubes (PNT) could be functionalized with iron oxide nanoparticles for magnetic manipulation, without affecting the large internal pore, or inherent low toxicity. Using an external magnetic field the nanotubes could be regionally concentrated, leaving areas devoid of nanotubes. Lastly, doxorubicin could be loaded to the PNTs, causing increased toxicity towards neuroblastoma cells, rendering a platform technology now ready for adaptation with different nanoparticles, degradable pre-polymers and various therapeutics

Characteristics and Evolutionary Analysis of Photosynthetic Gene Clusters on Extrachromosomal Replicons: from Streamlined Plasmids to Chromids.

Aerobic anoxygenic photoheterotrophic bacteria (AAPB) represent a bacteriochlorophyll a -containing functional group. Substantial evidence indicates that highly conserved photosynthetic gene clusters (PGCs) of AAPB can be transferred between species, genera, and even phyla. Furthermore, analysis of recently discovered PGCs carried by extrachromosomal replicons (exPGCs) suggests that extrachromosomal replicons (ECRs) play an important role in the transfer of PGCs. In this study, 13 Roseobacter clade genomes from seven genera that harbored exPGCs were used to analyze the characteristics and evolution of PGCs. The identification of plasmid-like and chromid-like ECRs among PGC-containing ECRs revealed two different functions: the spread of PGCs among strains and the maintenance of PGCs within genomes. Phylogenetic analyses indicated two independent origins of exPGCs, corresponding to PufC-containing and PufX-containing puf operons. Furthermore, the two different types of operons were observed within different strains of the same Tateyamaria and Jannaschia genera. The PufC-containing and PufX-containing operons were also differentially carried by chromosomes and ECRs in the strains, respectively, which provided clear evidence for ECR-mediated PGC transfer. Multiple recombination events of exPGCs were also observed, wherein the majority of exPGCs were inserted by replication modules at the same genomic positions. However, the exPGCs of the Jannaschia strains comprised superoperons without evidence of insertion and therefore likely represent an initial evolutionary stage where the PGC was translocated from chromosomes to ECRs without further combinations. Finally, a scenario of PGC gain and loss is proposed that specifically focuses on ECR-mediated exPGC transfer to explain the evolution and patchy distribution of AAPB within the Roseobacter clade. IMPORTANCE The evolution of photosynthesis was a significant event during the diversification of biological life. Aerobic anoxygenic photoheterotrophic bacteria (AAPB) share physiological characteristics with chemoheterotrophs and represent an important group associated with bacteriochlorophyll-dependent phototrophy in the environment. Here, characterization and evolutionary analyses were conducted for 13 bacterial strains that contained photosynthetic gene clusters (PGCs) carried by extrachromosomal replicons (ECRs) to shed light on the evolution of chlorophototrophy in bacteria. This report advances our understanding of the importance of ECRs in the transfer of PGCs within marine photoheterotrophic bacteria

IMP3 signatures of fallopian tube: a risk for pelvic serous cancers

BACKGROUND:Recent advances suggest fallopian tube as the main cellular source for women's pelvic serous carcinoma (PSC). In addition to TP53 mutations, many other genetic changes are involved in pelvic serous carcinogenesis. IMP3 is an oncofetal protein which has recently been observed to be overexpressed in benign-looking tubal epithelia. Such findings prompted us to examine the relationship between IMP3 over-expression, patient age and the likelihood of development of PSC.METHODS:Fallopian tubes from three groups (low-risk, high-risk, and PSC) of patients with matched ages were studied. Age was recorded in 10years intervals ranging from age 20 to older than 80. The number of IMP3 signatures (defined by 10 or more tubal secretory cells stained positively and continuously in benign appearing tubal mucosa) from both tubal fimbria and ampulla segments was measured. The data was analyzed by standard contingency table and Poisson distribution methods after age adjustment. IMP3 overexpression was also examined in serous tubal intraepithelial carcinoma and PSC.RESULTS:The positive IMP3-stained cells are mainly tubal secretory cells. The absolute number of tubal IMP3 signatures increased significantly within each age group. Age remained a significant risk factor for serous neoplasia after age adjustment. IMP3 signatures were more frequent in the patients of both high-risk and PSC groups. The presence of IMP3 signatures in tubal mucosa was significantly associated with tubal or pelvic serous carcinogenesis (p<0.001).CONCLUSIONS:The findings suggest that tubal secretory cells with IMP3 signatures showing growth advantage could potentially serve as a latent precancer biomarker for tubal or pelvic serous carcinomas in women.This item is part of the UA Faculty Publications collection. For more information this item or other items in the UA Campus Repository, contact the University of Arizona Libraries at [email protected]