Pattern Of Invasion Research Articles

NFS-22. INVESTIGATING MALIGNANT TRANSFORMATION IN NF1 PEDIATRIC GLIOMAS USING AN IPSCS-DERIVED CEREBRAL ORGANOID MODEL

Abstract BACKGROUND Neurofibromatosis Type 1 (NF1) is an autosomal dominant tumor predisposition syndrome affecting 1 in 3000 children around the world. Although NF1 inactivation is recognized as the cause of low-grade glioma (LGG) development, little is known about subsequent genetic alterations that lead to malignant transformation. One of the limitations in understanding the molecular events underlying the malignant transformation of NF1 gliomas is the lack of appropriate NF1 preclinical models for its comprehensive profiling. OBJECTIVE Brain organoids have emerged as powerful in vitro models for studying the interaction between tumor cells and the tumor microenvironment. In this study, we present a novel cerebral organoid model, developed to investigate the molecular events leading to malignant transformation in NF1 pediatric gliomas. METHODS Induced pluripotent stem cells (iPSCs)-derived cerebral organoids were generated using NF1wt and NF1mut iPSCs, the latter reprogrammed from patients with plexiform neurofibromas (Carlos III Health Institute, Spain). Immunofluorescence analysis was performed at four different developmental stages to confirm their correct cytoarchitectural development and differentiation into heterogeneous cell populations. Furthermore, four mCherry-labelled isogenic glioma cells lines, RES 186 wild type, NF1-/-, CDKN2a-/-,NF1-/-/CDKN2a-/- were co-cultured with the developed cerebral organoids and their migration potential and invasiveness were compared using two-photon microscopy. RESULTS/DISCUSSION NF1mut cerebral organoids display ventricular-like zone at early stages of development (d15-d30), characterized by luminal Sox2+ neural stem cells surrounded by Tuj1+ immature neuron. These organized structures disappear at later stages, while progenitor cells start to differentiate into fully mature neurons and glial cells (d45-d60). Additionally, after 10 days of co-culture, all four RES186 isogenic cell lines infiltrated the organoid structure with different invasion patterns. The established organoid model will provide a platform for evaluating the impact of sequential mutational events on LGG transformation, taking into consideration the role exerted by the tumor microenvironment in supporting tumor cell invasion and migration.

Comparison of PD-L1, VISTA, LAG-3, and GAL-3 Expressions and Their Relationships to Mismatch Repair Protein and p53 Expression in 529 Cases of Endometrial Carcinoma.

The aim of this study is to evaluate the expressions of programmed death-ligand 1 (PD-L1), V-domain Ig suppressor of T-cell activation (VISTA), lymphocyte activation gene-3 (LAG-3), and galectin-3 (GAL-3), in mismatch repair-deficient (MMRd)/MMR-proficient and abnormal p53 expressing endometrial carcinomas and their relationship with clinical-histopathological features. Patients who underwent surgery for endometrial carcinoma between January 2008 and December 2018 were included in the study. Immunohistochemical analysis of MLH1, PMS2, MSH2, MSH6, p53, PD-L1, VISTA, LAG-3, and GAL-3 was performed on the tissue samples of microarray. A total of 529 patients were included. MMRd and p53-mutant tumors accounted for 31.5% and 11.5% of cases, respectively. PD-L1 and LAG-3 expressions in the MMRd and p53-mutant groups were higher than in the MMR-proficient group (P < 0.001). GAL-3 expression in the MMR-proficient group was statistically higher than in the MMRd and p53-mutant groups (P < 0.001). Mean age, grade, International Federation of Gynecology and Obstetrics stage, lymphovascular invasion, and lymph node metastasis were significantly higher in the p53-mutant group (P < 0.001). In the group with PD-L1 expression, nonendometrioid histologic type, tumor grade, and lymphovascular invasion were significantly higher (P < 0.001). Tumor grade, lymphovascular invasion, lymph node metastasis, and microcystic, elongated and fragmented pattern of invasion were significantly higher in the group with high VISTA expression (P < 0.05). Tumor grade was significantly higher in the group with LAG-3 expression (P < 0.001). Immunohistochemically determined subgroups and PD-L1, VISTA, LAG-3, and GAL-3 expression levels may be useful indicators of molecular features, and clinical outcomes also may have important implications for the development of targeted therapies in endometrial carcinoma.

Tumor-stroma contact ratio - a novel predictive factor for tumor response to chemoradiotherapy in locally advanced oropharyngeal cancer

The growth pattern of oropharyngeal squamous cell carcinomas (OPSCC) varies from compact tumor cell aggregates to diffusely infiltrating tumor cell-clusters. The influence of the growth pattern on local tumor control and survival has been studied mainly for surgically treated oral cavity carcinomas on a visual basis. In this study, we used multiplex immunofluorescence staining (mIF) to examine the antigens pan-cytokeratin, p16INK4a, Ki67, CD271, PD-L1, and CD8 in pretherapeutic biopsies from 86 OPSCC. We introduce Tumor-stroma contact ratio (TSC), a novel parameter, to quantify the relationship between tumor cells in contact with the stromal surface and the total number of epithelial tumor cells. mIF tumor cores were analyzed at the single-cell level, and tumor-stromal contact area was quantified using the R package "Spatstat". TSC was correlated with the visually assessed invasion pattern by two independent investigators. Furthermore, TSC was analyzed in relation to clinical parameters and patient survival data to evaluate its potential prognostic significance.Higher TSC correlated with poor response to (chemo-)radiotherapy (r = 0.3, p < 0.01), and shorter overall (OS) and progression-free (PFS) survival (median OS: 13 vs 136 months, p < 0.0001; median PFS: 5 vs 85 months, p < 0.0001). Visual categorization of growth pattern according to established criteria of tumor aggressiveness showed interobserver variability increasing with more nuanced categories (2 categories: k = 0.7, 95 %-CI: 0.55 - 0.85; 4 categories k = 0.48, 95 %-CI: 0.35 - 0.61).In conclusion, TSC is an objective and reproducible computer-based parameter to quantify tumor-stroma contact area. We demonstrate its relevance for the response of oropharyngeal carcinomas to primary (chemo-)radiotherapy.

Enhancing prognostic insights: myometrial invasion patterns in endometrial carcinoma, with emphasis on MELF pattern-a comprehensive review and meta-analysis.

The microcystic, elongated, and fragmented (MELF) pattern, characterized by myxoid and inflamed stroma, is readily identifiable as a form of myometrial infiltration. This meta-analysis endeavors to assess the prognostic significance of MELF infiltration patterns in patients diagnosed with endometrial cancer. A comprehensive literature search, spanning until 11 October 2023, across PubMed, Embase, Cochrane, and Web of Science databases, identified 23 relevant studies involving 5199 patients. Data analysis was performed using Stata 16.0. Analysis indicates that MELF infiltration predicts a higher risk of lymph node metastasis in endometrial cancer patients [hazard ratios (HR) = 5.05; 95% confidence interval (CI), 3.62-7.05; P < 0.05]. Notably, this association remains consistent across various patient demographics, analytical approaches, study designs, and treatment modalities. However, MELF infiltration does not significantly correlate with recurrence (HR = 1.05; 95% CI, 0.73-1.52; P > 0.05), overall survival (HR = 1.24; 95% CI, 0.91-1.68; P > 0.05), or disease-free survival (HR = 1.40; 95% CI, 0.85-2.28; P > 0.05). While MELF infiltration heightens the risk of lymph node metastasis in endometrial cancer, its impact on recurrence, overall survival, and disease-free survival remains statistically insignificant.

A New Phase Diagram for Fluid Invasion Patterns as a Function of Pore‐Scale Heterogeneity, Surface Roughness, and Wettability

AbstractUnderstanding how different flow patterns emerge at various macro‐ and pore scale heterogeneity, pore wettability and surface roughness is remains a long standing scientific challenge. Such understanding allows to predict the amount of trapped fluid left behind, of crucial importance to applications ranging from microfluidics and fuel cells to subsurface storage of carbon and hydrogen. We examine the interplay of wettability and pore‐scale heterogeneity including both pore angularity and roughness, by a combination of micro‐CT imaging of 3D grain packs with direct visualization of 2D micromodels. The micromodels are designed to retain the key morphological and topological properties derived from the micro‐CT images. Different manufacturing techniques allow us to control pore surface roughness. We study the competition between flow through the pore centers and flow along rough pore walls and corners in media of increasing complexity in the capillary flow regime. The resulting flow patterns and their trapping efficiency are in excellent agreement with previous μ‐CT results. We observe different phase transitions between the following flow regimes (phases): (a) Frontal/compact advance, (b) wetting and drainage Invasion percolation, and (c) Ordinary percolation. We present a heterogeneity‐wettability‐roughness phase diagram that predicts these regimes.

Emotion Dynamics among Late Adolescents and Emerging Adults: The Role of Maternal Privacy Invasion Perceptions.

Prior research suggests that youth experience immediate emotional distress following privacy invasion, but it is unclear whether and how persistent privacy invasion over longer periods destabilizes the intrapersonal emotional regulatory functions that privacy serves. This study investigated whether late adolescents and emerging adults who reported different patterns of maternal privacy invasion over a full academic year showed differences in emotion regulation, as reflected by the frequency and lability of negative and positive emotional experiences. Participants were first-year university students (n = 349; 60.2% female) in Hong Kong, aged 17 to 24 (MT1 = 18.20, SDT1 = 1.10). They self-reported maternal privacy invasion perceptions and negative and positive emotions 16 times, at bi-weekly intervals. Latent class growth analyses divided participants into a Higher Invasion Perceptions group (24.9%), a Moderate Invasion Perceptions group (46.4%), and a Lower Invasion Perceptions group (28.7%). A one-way MANCOVA examined potential differences in negative and positive emotion dynamics across groups, indexed by frequency (means) and instability (mean square of successive differences and probability of acute change). In line with predictions, both the Higher Invasion and Moderate Invasion groups reported higher negative emotion frequency and instability, compared to the Lower Invasion group. However, groups showed no significant differences regarding positive emotion frequency and instability. The findings indicate that perceptions of maternal privacy invasion predict youth's negative emotion regulation processes over their first collegiate year. Prolonged, higher levels of maternal privacy invasion may disrupt the intrapersonal regulatory functions that privacy serves over time.

Control of invasive conifers in temperate Andean forests promotes native vegetation restoration, but requires continuous management

Non-native conifers have been planted widely because of their growth potential and wood quality. However, many of them have become invasive in the introduced ranges. In Chile, the initial introduction of non-native conifers helped the recovery of degraded land, but today some pine species present a high invasion risk when they are not properly managed, leading to detrimental impacts on natural ecosystems and biodiversity. Such is the case of Douglas fir (Pseudotsuga menziesii), a species listed as invasive in south-central Chile, as well as in many other countries, when it establishes beyond the original plantation range. The main goal of this research was to characterize the invasion pattern of P. menziesii within a recently-declared protected area nearby the Conguillío National Park in the Andes Cordillera. We aimed at determining the key factors that promote the invasion of P. menziesii outside the original plantations. We established five 1,000 m2 sampling transects (i.e., 100×10 m), considering two invasion conditions: (i) within the native forest and (ii) far into open scrub areas, both adjacent to P. menziesii plantations. We measured forest structure, soil nutrients, the floristic composition and pine regeneration before and after controlling the invasion within each study conditions. We found that P. menziesii density and soil nutrient availability in the soil decreased with the distance from the plantation. In addition, an increase in native species cover was found after removing pines, but also noted the ability of P. menziesii to readily re-invade the native forest after removal. These results indicate the need for continuous control of P. menziesii, especially inside the native forest at the early stages of invasion. We discuss the need for better plantation management to prevent its spread into natural areas and protect native forests from non-native conifers invasion.

Impact of temperature and season on ant foraging activity of two invasive species in a Mediterranean urban area

Abstract Invasive species often have harmful effects on human activities and biodiversity. The Tapinoma nigerrimum complex includes three species that exhibit invasive traits and the ability to form supercolonies, including Tapinoma magnum and Tapinoma darioi. While these species are native to the Mediterranean basin, they have recently been reported as invasive in more northern regions of Europe. However, T. magnum and T. darioi show different invasion patterns in Europe, suggesting differences in thermal preferences between these species. We aimed to determine whether there was any difference in activity pattern depending on temperature or season between the two Tapinoma species and between Tapinoma and co‐occurring native Mediterranean ants. We measured ambient temperature and ant foraging activity around the nest entrances of T. darioi and T. magnum in urbanised sites around Montpellier, southern France, over almost 1 year. We did not detect differences in activity between the two species according to temperature, but T. magnum was more active than T. darioi in winter. Compared to the co‐occurring native species, the two Tapinoma species were more active at low temperatures and earlier in the year. These results suggest that the difference in invasion success between T. magnum and T. darioi may not be explained by temperature preference. The difference in activity between native Mediterranean species and invasive Tapinoma suggests a coexistence through niche partitioning. In addition, our results suggest that control measures against invasive Tapinoma species would be more effective if applied at the end of winter.

Histology of Bronchiolar Tumor Spread Through Air Spaces.

The clinical significance of lung tumor spread through air spaces (STAS) has been extensively studied, and is recognized as a unique pattern of invasion. Previous studies of STAS have focused primarily on STAS in alveolar spaces, whereas STAS in the bronchiolar spaces (bronchiolar STAS) has been described in only a few case reports only. Here, we examined 306 cases of primary lung adenocarcinoma and found that bronchiolar STAS was present in 18%. Bronchiolar STAS was associated with an inferior prognosis, more advanced stage, and higher histologic grade. No significant difference in clinicopathological factors or prognosis was observed between cases with bronchiolar STAS and those with alveolar STAS alone. Notably, bronchiolar STAS often occurred simultaneously with alveolar STAS and endobronchial spread of adenocarcinoma, particularly when bronchiolar STAS was present outside the main tumor. We also identified cases where bronchiolar STAS and endobronchial spread of adenocarcinoma occurred simultaneously in the same bronchi or bronchioles located outside the main tumor, as well as cases with bronchiolar STAS adjacent to intrapulmonary metastatic nodules. Our results highlight the significant role of bronchiolar STAS in the aerogenous spread of adenocarcinoma cells. Bronchiolar STAS can be regarded as a histologic variant of alveolar STAS. This study also supports the idea that STAS is not a tissue processing artifact, but a true biological process with clinical implications, offering histologic evidence of aerogenous spread in lung adenocarcinoma.

Abstract B025: Luminal-to-basal phenotypic plasticity promotes invasive phenotypes in a live-imaging assay using patient-derived bladder tumor organoids

Abstract Lineage plasticity in cancer is characterized by changes in cell state that are often associated with tumor progression and treatment resistance. While nearly all non-muscle invasive bladder cancer (NMIBC) tumors have a luminal epithelial phenotype, many muscle invasive bladder cancers (MIBC) display a basal identity. NMIBC to MIBC progression may therefore be related to a phenotypic switch from luminal-to-basal subtypes, which in turn may be associated with poorer clinical outcomes. However, current understanding of the molecular processes linking cell plasticity and tumor invasion is limited, due in part to a lack of physiologically relevant in vitro models and assays. To address these questions, we are utilizing a living biobank of 82 patient-derived bladder tumor organoid lines that our group has established. These organoids represent a 3-dimensional, heterogeneous model system for studying bladder cancer, as they can be genetically manipulated and recapitulate the molecular and histopathological features of the parental tumor. Notably, in previous work, we described luminal-to-basal phenotypic plasticity in a subset of organoid lines derived from luminal tumors, which display a shift to basal/squamous identity in culture that is reversible by orthotopic xenografting. In current studies, we are investigating cell migration and invasiveness using a live-imaging assay that we have developed to examine bladder tumor organoid outgrowth in vitro. Importantly, this assay allows longitudinal visualization as well as quantitation of invasiveness over a four-day time span. Analysis of over 25 organoid lines with plastic, stable luminal, and stable basal properties has revealed a broad spectrum of organoid outgrowth phenotypes that do not correlate with cell proliferation or clinical parameters. Instead, the degree of outgrowth correlates precisely with luminal-to-basal phenotypic plasticity, as assessed by transcriptome analyses, immunofluorescence microscopy, and in vivo xenografting. Organoid lines with minimal outgrowth have stable luminal phenotypes, whereas lines that produce their own extracellular matrix to create a leading edge of migrating cells have plastic phenotypes. Furthermore, movies of the invading organoids reveal distinct cell migratory patterns, as several organoid lines display collective migration that generates an invasive front at the leading edge. This collective migration phenotype is distinct from phenotypic plasticity, is at least partially independent from organoid outgrowth, and is undergoing further analysis. Thus, our organoid outgrowth assay identifies two different parameters of invasive potential, one of which correlates with phenotypic plasticity. Our findings characterize bladder tumor invasion patterns for the first time and suggest that lineage plasticity in NMIBC represents a key mechanism that promotes tumor invasion in MIBC. Citation Format: Clementine Le Coz, John R. Christin, Talal Syed, Zejian Wang, Caroline J. Laplaca, Andrew T. Lenis, Michael M. Shen. Luminal-to-basal phenotypic plasticity promotes invasive phenotypes in a live-imaging assay using patient-derived bladder tumor organoids [abstract]. In: Proceedings of the AACR Special Conference on Bladder Cancer: Transforming the Field; 2024 May 17-20; Charlotte, NC. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(10_Suppl):Abstract nr B025.

Reproducibility of Assessment of Lepidic (Noninvasive) Patterns in Lung Adenocarcinoma With Cytokeratin Immunostain Compared With Hematoxylin and Eosin and the Proposed New International Association for the Study of Lung Cancer (IASLC) Algorithm

IntroductionLepidic growth is considered noninvasive in lung nonmucinous adenocarcinoma, whereas other patterns are invasive. Considerable interobserver variability in assessing “invasion” has been reported. We assessed the utility of cytokeratin 7 (CK7) stain and recently proposed International Association for the Study of Lung Cancer criteria to improve assessment of noninvasion in lung adenocarcinoma. MethodsFour pathologists (two staff, two trainees) assessed 158 hematoxylin and eosin (HE)- and CK7-stained slides of 108 pT1N0-2 nonmucinous lung adenocarcinoma cases. Scoring took place in four rounds. First, sections were independently scored for percentage of noninvasive or probable noninvasive and invasive or probable invasive patterns. Second, after a consensus scoring algorithm for CK7 was formulated, the slides were rescored. Subsequent third-round scoring was conducted only on HE slides using the 2023 International Association for the Study of Lung Cancer proposed criteria, and fourth-round scoring on both HE and CK7 slides simultaneously. Intraclass correlation coefficient (ICC) was calculated for each round. Recurrence-free survival was assessed using Cox proportional hazards regression methods. ResultsIn the first two rounds, interobserver concordance was consistently higher with CK7 (ICC range = 0.44–0.6) than HE (range = 0.24–0.49) scores. The IASLC proposed algorithm improved ICC of HE scores to 0.60 (95% confidence interval: 0.52–0.67), and round 4 HE and CK7 combined improved ICC to 0.75 (95% confidence interval: 0.70–0.80). Continuous measures of averaged noninvasive and probable noninvasive scores on HE were associated with improved recurrence-free survival (hazard ratio: 0.83–0.86). ConclusionsCK7 staining consistently increased interobserver concordance in assessment of invasive versus noninvasive patterns than HE. Combining CK7 with the 2023 IASLC criteria for morphologic features of invasion may further improve the interobservers’ concordance for the recognition of lepidic growth in nonmucinous lung adenocarcinoma.

Exploring the Dynamic Invasion Pattern of the Black-Headed Fall Webworm in China: Susceptibility to Topography, Vegetation, and Human Activities.

The fall webworm (FWW), H. cunea (Drury) (Lepidoptera: Erebidae: Arctiidae), is an extremely high-risk globally invasive pest. Understanding the invasion dynamics of invasive pests and identifying the critical factors that promote their spread is essential for devising practical and efficient strategies for their control and management. The invasion dynamics of the FWW and its influencing factors were analyzed using standard deviation ellipse and spatial autocorrelation methods. The analysis was based on statistical data on the occurrence of the FWW in China. The dissemination pattern of the FWW between 1979 and 2022 followed a sequence of "invasion-occurrence-transmission-outbreak", spreading progressively from coastal to inland regions. Furthermore, areas with high nighttime light values, abundant ports, and non-forested areas with low vegetation cover at altitudes below 500 m were more likely to be inhabited by the black-headed FWW. The dynamic invasion pattern and the driving factors associated with the fall webworm (FWW) provide critical insights for future FWW management strategies. These strategies serve not only to regulate the dissemination of insects and diminish migratory tendencies but also to guarantee the implementation of efficient early detection systems and prompt response measures.

A comprehensive overview of metaplastic breast cancer: Features and treatments.

Metaplastic breast cancer is a rare, aggressive, and chemotherapy-resistant subtype of breast cancers, accounting for less than 1% of invasive breast cancers, characterized by adenocarcinoma with spindle cells, squamous epithelium, and/or mesenchymal tissue differentiation. The majority of metaplastic breast cancers exhibit the characteristics of triple-negative breast cancer and have unfavorable prognoses with a lower survival rate. This subtype often displays gene alterations in the PI3K/AKT pathway, Wnt/β-catenin pathway, and cell cycle dysregulation and demonstrates epithelial-mesenchymal transition, immune response changes, TP53 mutation, EGFR amplification, and so on. Currently, the optimal treatment of metaplastic breast cancer remains uncertain. This article provides a comprehensive review on the clinical features, molecular characteristics, invasion and metastasis patterns, and prognosis of metaplastic breast cancer, as well as recent advancements in treatment strategies.

Outcomes of patients in nasopharyngeal adenoid cystic carcinoma in the IMRT era: a single-center experience

ObjectiveNasopharyngeal adenoid cystic carcinoma (NACC) is a rare malignancy with special biological features. Controversies exist regarding the treatment approach and prognostic factors in the IMRT era. This study aimed to evaluate the long-term outcomes and management approaches in NACC.MethodsFifty patients with NACC at our institution between 2010 and 2020 were reviewed. Sixteen patients received primary radiotherapy (RT), and 34 patients underwent primary surgery.ResultsBetween January 2010 and October 2020, a total of 50 patients with pathologically proven NACC were included in our analysis. The median follow-up time was 58.5 months (range: 6.0–151.0 months). The 5-year overall survival rate (OS) and progression-free survival rate (PFS) were 83.9% and 67.5%, respectively. The 5-year OS rates of patients whose primary treatment was surgery and RT were 90.0% and 67.3%, respectively (log-rank P = 0.028). The 5-year PFS rates of patients whose primary treatment was surgery or RT were 80.8% and 40.7%, respectively (log-rank P = 0.024). Multivariate analyses showed that nerve invasion and the pattern of primary treatment were independent factors associated with PFS.ConclusionsDue to the relative insensitivity to radiation, primary surgery seemed to provide a better chance of disease control and improved survival in NACC. Meanwhile, postoperative radiotherapy should be performed for advanced stage or residual tumours. Cranial nerve invasion and treatment pattern might be important factors affecting the prognosis of patients with NACC.

Metastasis of small cell lung cancer to bilateral extraocular muscles: a case report

BackgroundOrbital metastasis is a possible complication of small cell lung cancer and a pattern of bilateral invasion of the extraocular muscles has rarely been reported in literature.Case presentationA 46-year-old white male with a past medical history of smoking and stage IV small cell lung carcinoma presented with loss of vision and pain in the left eye. Examination revealed bilateral proptosis and left afferent pupillary defect, and visual acuity was hand motion on the left eye and 4/10 on the right eye. An orbital computed tomography scan showed a compression of the left optic nerve between the extraocular muscles at the apex, and a lateral canthotomy was performed for a new-onset compressive optic neuropathy, with residual visual improvement. There was also significant enlargement of the extraocular muscles in the right orbit. The patient was maintained in palliative treatment with both chemotherapy and local medical and surgical (amniotic membrane cover for exposure keratopathy) ophthalmological treatments until he eventually died 5 months after.ConclusionBilateral metastasis to the extraocular muscles is a very rare manifestation of small cell lung cancer and the palliative treatment in these cases is challenging.

Abstract PO3-15-09: LobSig4 is a superior and readily implementable ILC-focussed prognostic biomarker set

Abstract Invasive Lobular Carcinoma (ILC) is the most common special histological subtype of breast cancer. ILC typically present as Oestrogen and Progesterone Receptor positive cancers, without over-expression of HER2 and are defined by their invasive pattern of growth. Despite clinical and biological differences, including diverse sites of metastasis, ILC are managed in the same way as the more commonly diagnosed, Invasive Carcinomas of no special type. Previously, we derived the LobSig lobular specific gene signature in an attempt to prognosticate within an otherwise homogeneous tumour category. We showed that this set of genes could stratify Grade 2 and Nottingham Prognostic Index moderate tumours into high and low risk groups. Herein, we use a nanoString nCounter custom codeset and immunohistochemistry to validate the LobSig signature. Using a CoxBoost analysis we further refined the geneset to 14 genes of interest which we examined using Immunohistochemistry on a large panel of ILC with clinical follow up data. Four targets showed a significant association with breast cancer specific survival, with high levels correlating with the poorest outcomes. Considering the expression data for these 4 candidates together, we performed a Cox Proportional Hazard Regression resulting in a combined prognostic power of (P=0.00034, HR=8.07 (CI 2.58-25.30)), which has superior prognostic power over variables including tumor size and patient age. ‘LobSig4’ represents a readily implementable and informative biomarker set for prognostication in Invasive Lobular Carcinoma. Citation Format: Lauren Kalinowski, Jamie Kutasovic, Sriganesh Srihari, Yufan Feng, Samir Lal, Kaltin Ferguson, Haarika Chittoory, Anna Sokolova, Malcolm Lim, Priyakshi Kalita De Croft, Sunil Lakhani, Peter Simpson, Amy McCart Reed. LobSig4 is a superior and readily implementable ILC-focussed prognostic biomarker set [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-15-09.

Honey bee (Apis mellifera) nurse bee visitation of worker and drone larvae increases Varroa destructor mite cell invasion.

The life cycle of Varroa destructor, the ectoparasitic mite of honey bees (Apis mellifera), includes a dispersal phase, in which mites attach to adult bees for transport and feeding, and a reproductive phase, in which mites invade worker and drone brood cells just prior to pupation to reproduce while their bee hosts complete development. In this study, we wanted to determine whether increased nurse bee visitations of adjacent drone and worker brood cells would increase the likelihood of Varroa mites invading those cells. We also explored whether temporarily restricting the nurses' access to sections of worker brood for 2 or 4h would subsequently cause higher nurse visitations, and thus, higher Varroa cell invasions. Temporarily precluding larvae from being fed by nurses subsequently led to higher Varroa infestation of those sections in some colonies, but this pattern was not consistent across colonies. Therefore, removing highly infested sections of capped worker brood could be further explored as a potential mechanical/cultural method for mite control. Our results provide more information on how nurse visitations affect the patterns of larval cell invasion by Varroa. Given that the mite's successful reproduction depends on the nurses' ability to visit and feed developing brood, more studies are needed to understand the patterns of Varroa mite invasion of drone and worker cells to better combat this pervasive honey bee parasite.

Insight into evolution of invasive patterns on fingering phenomenon during immiscible two-phase flow through pore structure

Understanding fingering, as a challenge to stable displacement during the immiscible flow, has become a crucial phenomenon for geological carbon sequestration, enhanced oil recovery, and groundwater protection. Typically governed by gravity, viscous and capillary forces, these factors lead invasive fluids to occupy pore space irregularly and incompletely. Previous studies have demonstrated capillary numbers, describing the viscous and capillary forces, to quantificationally induce evolution of invasion patterns. While the evolution mechanisms of invasive patterns have not been deeply elucidated under the constant capillary number and three variable parameters including velocity, viscosity, and interfacial tension. Our research employs two horizontal visualization systems and a two-phase laminar flow simulation to investigate the tendency of invasive pattern transition by various parameters at the pore scale. We showed that increasing invasive viscosity or reducing interfacial tension in a homogeneous pore space significantly enhanced sweep efficiency, under constant capillary number. Additionally, in the fingering crossover pattern, the region near the inlet was prone to capillary fingering with multi-directional invasion, while the viscous fingering with unidirectional invasion was more susceptible occurred in the region near the outlet. Furthermore, increasing invasive viscosity or decreasing invasive velocity and interfacial tension promoted the extension of viscous fingering from the outlet to the inlet, presenting that the subsequent invasive fluid flows toward the outlet. In the case of invasive trunk along a unidirectional path, the invasive flow increased exponentially closer to the outlet, resulting in a significant decrease in the width of the invasive interface. Our work holds promising applications for optimizing invasive patterns in heterogeneous porous media.

Characterization and identification of gas invasion patterns in magnesium lithium phyllosilicate suspensions

Characterization and identification of gas invasion patterns in magnesium lithium phyllosilicate suspensions

A Study of Histological and Clinical Parameters and Their Correlation With Lymph Node Metastasis and Two-Year Survival in 50 Cases of Oral Squamous Cell Carcinoma.

Oral squamous cell carcinoma (OSCC)is one of the most prevalent malignant neoplasms in South Asia and a major public health problem in India. The purpose of the study was to identify correlations among various clinicopathological parameters of OSCC in a tertiary care center in the Eastern Uttar Pradesh population of North India.The study is imperative due to the scarcity of available data from this region. A retrospective observational study was conducted on the cases received in the Department of Pathology over the period of January 2021 to December 2021. The study analyzed cases of OSCC, focusing on various factors such as age, gender, habits, tumor site, tumor size, differentiation, tumor-stroma ratio, tumor-infiltrating lymphocytes, tumor budding, worst pattern of invasion, depth of invasion, perineural invasion, lymphovascular invasion, underlying bone and overlying skin involvement, regional lymph node metastasis, and overall two-year survival. The mean age of the patients was 47.80 ± 12.48 years, and the male-to-female ratio was 15.6:1. Buccal mucosa was the most frequently affected site followed by the tongue. Fifty-six percent of cases reported with a history of tobacco abuse. Thirty-six percent of the patients had regional lymph node metastasis and exhibited a strong association with younger age, substance abuse, higher tumor size, tongue as a site, moderate-to-poor tumor differentiation, low tumor-infiltrating lymphocytes, and higher perineural and lymphovascular invasion. Moreover, at the end of the two-year survival analysis, 34% of patients succumbed to the disease. Overall survival was observed to be significantly better with <2 cm maximum tumor size, well-differentiated tumor morphology, higher tumor-infiltrating lymphocytes, and no nodal metastasis. The study highlights the intricate correlations of various histopathological factors in OSCC, shedding light on their potential implications for prognosis.