Distinct Types Research Articles

Interrogating “political masculinities”

This article interrogates the concept of “political masculinities” in terms of its usefulness as an analytical category. The article covers four major areas associated with the concept. First, some critical questions concerning the dichotomy between studying “men in politics” and “political masculinities” are offered. Second, concerns are raised regarding specific terms used in the current definition of political masculinities. Third, probing queries are presented on the conceptual utility of political masculinities as an analytical category. Finally, the article closes with a discussion of ex-US President Donald Trump, illustrating his distinct type of dominating masculinity and how this masculinity illuminates the substance and meaning of his “politics.”

Preliminary development and validation of the Indonesian Pediatric Epilepsy Questionnaire (INA-PEPSI) to determine epilepsy and distinguish focal and generalized epilepsy in infants and children with unprovoked seizure in low-resource settings.

To outline the preliminary development and validation of a questionnaire for diagnosing epilepsy and distinguishing focal and generalized epilepsy among infants and children in Indonesia, where electroencephalography and pediatric neurologists are generally not available. A 10-question questionnaire comprising of 43 items was developed through literature review and expert panel discussions. Then, the questionnaire was administered by pediatricians to 75 children aged 1 month to 18 years old presenting with >1 episode of unprovoked seizures at an interval of >24 h. Subsequently, the questionnaire was assessed for content validity with item-level and scale-level content validity indices and ratio, construct validity with item-total correlation tests, criterion validity with diagnostic parameter assessments, and inter-rater reliability using Cohen's kappa (κ) and internal consistency with Cronbach's alpha (α) coefficient. The questionnaire exhibited favorable internal validity and reliability in diagnosing epilepsy and distinguishing focal and generalized epilepsy, with excellent content (both indices and ratio at 1) and construct validity (rcount > rtable at p < 0.001), inter-rater reliability (κ = 0.86 and κ = 0.84), and internal consistency (α = 0.634 and α = 0.806). The questionnaire had a sensitivity and specificity of 96.4% (95%CI 89.1-99.5%) and 95.0% (79.5-99.6%) (area under the curve [AUC] 0.946 [0.900-0.992, p < 0.001]) in diagnosing epilepsy and 80.0% (57.4-95.7%) and 97.4% (89.7-99.2%) (AUC 0.889 [0.783-0.995, p < 0.001]) in distinguishing focal and generalized epilepsy, with a misdiagnosis rate of 4.0%. The questionnaire shows promising potential in diagnosing epilepsy and distinguishing focal and generalized epilepsy. Further external validation studies in larger and more diverse populations are required to confirm our findings. The diagnosis of epilepsy in children is challenging, particularly in resource-limited settings such as Indonesia, where advanced diagnostic tests and pediatric neurologists are scarce. The Indonesian Pediatric Epilepsy Questionnaire (INA-PEPSI) is designed to address these limitations by enabling healthcare professionals in Indonesia to diagnose epilepsy and classify its types without relying on advanced diagnostic tools. Although the questionnaire is still in the early stages of development and validation, this study demonstrates that the questionnaire exhibits good overall diagnostic performance in diagnosing epilepsy and distinguishing epilepsy types among Indonesian children.

A novel classification of senile dermatochalasis: insights from clinical and histological analysis.

Dermatochalasis is a common disorder of the elderly, often requiring upper blepharoplasty. Although it is mainly accepted as a process of aging, its clinical and histological findings vary among patients. The aim of this study was to classify types of dermatochalasis based on their clinical and histological findings. This retrospective study included patients with dermatochalasis who had undergone senile blepharoplasty at a single center. Clinical parameters such as margin-to-reflex distance 1 (MRD1), eyelid contour, visual field, and pre-existing medical conditions were assessed. Histological analysis was conducted of eyelid tissues stained with hematoxylin and eosin (H&E) and D2-40 to evaluate dermal edema, inflammation, lymphatic changes, and stromal depth. This study included 67 eyes of 35 patients. The mean age of the patients was 69.0 ± 8.3years, and the average MRD1 was 1.8 ± 1.3mm. In correlation analysis, two distinct types of dermatochalasis based on the histological findings were identified: lymphangiectasia-dominant and stromal edema-dominant types. The difference between nasal and temporal side MRD1(NT-MRD1) showed the area under the ROC curve of 0.718 of for distinguishing the two histological types of dermatochalasis was 0.718. Our novel classification of senile dermatochalasis based on morphological and histological analysis provides insights into the underlying pathology and may help to predict surgical outcomes and complications.

Multi-class plaque segmentation in Intravascular Ultrasound via inter-frame feature fusion and contrast feature extraction

Intravascular Ultrasound (IVUS) is an effective aid in diagnosing cardiovascular diseases, with plaque segmentation in IVUS images being a pivotal step in assessing vascular plaque risk. However, IVUS plaque segmentation encounters two major challenges: (1) the variability in plaque shapes makes it difficult to locate plaques accurately, and (2) distinguishing plaque types is challenging due to the similarity in visual features among different types. To tackle these challenges, we propose a novel framework for IVUS plaque segmentation. Our approach incorporates a segmentation network featuring a dual feature attention(DFA) module and a cross feature fusion(CFF) module. Additionally, we introduce contrastive learning to enhance plaque sensitivity and extract contrast features within our network. We evaluate our method using a private IVUS dataset, achieving the state-of-the-art performance with a Dice score of 84.79% and a 14.17 HD value. Our approach represents significant progress in the field of multi-class IVUS plaque segmentation, making it a more effective tool to assist doctors in diagnosing vascular plaques.

Crystallization Sequence of the Spodumene-Rich Alijó Pegmatite (Northern Portugal) and Related Metasomatism on Its Host Rock

The Barroso–Alvão region is an excellent setting for studying Li mineralization associated with granitic pegmatites and developing Li exploration techniques. Among the distinguished pegmatite types in this pegmatite field, the spodumene-bearing dyke from Alijó is a representative example of an Iberian Li–Cs–Ta (LCT) pegmatite currently under exploitation. In this work, we examine the internal evolution of the Alijó dyke and its external metasomatic effect on the surrounding metasediments, contributing to lithium exploration techniques. Electron microprobe analyses provided clues about the crystallization conditions and the degree of differentiation of the pegmatitic melt, whereas the external metasomatism induced by the spodumene-bearing pegmatite was studied through whole-rock geochemistry. The obtained results indicate that the primary crystallization of the studied dyke likely occurred at temperatures between 450–500 °C, with emplacement at shallow crustal levels of about 2–3 kbar. The high concentrations of trace elements such as Li, Cs, Rb, Be, Sn, Nb, Ta, Ge, U, and Tl in the pegmatitic melt suggests high availability of these elements, allowing their partitioning into an early exsolved fluid phase. The exsolution of this fluid phase, subtracting components such as F and B, from the pegmatitic melt would cause a significant undercooling of the melt. Moreover, the interaction of this expelled fluid with the country rock generated a metasomatic overprint in the surrounding metasedimentary host rocks. The metasomatic effect in Alijó is strongly influenced by the nature of the host metasediments, with a significantly higher grade of metasomatism observed in pelitic (mica-rich) samples compared to psammitic (mica-poor) samples collected at same distances from the dyke. The greisen developed close to the pegmatite contact reflects this metasomatic signature, characterized by the mobilization of at least B, F, Li, Rb, Cs, Sn, Be, Nb, Ta, and Tl. We cautiously suggest that whole rock Li concentrations greater than 300 ppm, combined with a minimum value of 1000 ppm for the sum of B, F, Li, Rb, Cs, and Sn in pelitic metasediments of Barroso–Alvão, may be indicative of a mineralized pegmatite in this region.

Soil Microbial Community Structure and Its Contribution to Carbon Cycling in the Yalu River Estuary Wetland

Wetland microbial communities play a vital role in ecosystem functioning, particularly in the intricate processes of carbon cycling. This study employed metagenomic sequencing to investigate the diversity, composition, structural differences, carbon cycling functional gene, and microbial species of soil microbial communities in five distinct soil types of the Yalu River estuary wetland, including shoal soil, bog soil, paddy soil, meadow soil, and brown forest soil. We further explored the influence of environmental factors on both the microbial community structure and carbon cycling functional genes. Our results revealed a bacterial-dominated soil microbial community, constituting about 97.6%. Archaea and fungi represented relatively minor fractions, at 1.9% and 0.4%, respectively. While no significant differences were observed in Chao1 indices between bacterial and fungal communities, the Shannon index revealed notable differences. Both Chao1 and Shannon indices exhibited significant variations within the archaeal communities. The dominant bacterial phyla were Proteobacteria, Actinobacteria, Acidobacteria, Bacteroidetes, and Nitrospirae. Thaumarchaeota, Crenarchaeota, and Euryarchaeota formed the major archaeal phyla, while Ascomycota, Mucoromycota, and Basidiomycota were the dominant fungal phyla. Non-metric multidimensional scaling (NMDS) analysis based on Bray-Curtis distance revealed notable differences in the bacterial, archaeal, and fungal community structures across the samples. Redundancy analysis (RDA) identified key environmental factors for the major phyla. Soil pH, soil organic carbon (SOC), electrical conductivity (EC), and total phosphorus (TP) were the main influencing factors for bacteria, while soil TP, EC, total sulfur (TS), and SOC were the primary drivers for archaeal phyla. Soil total nitrogen (TN) and EC were the main influencing factors for fungal phyla. Analysis of key carbon cycling pathway genes utilizing the Kyoto Encyclopedia of Genes and Genomes (KEGG) database and clustering heatmap revealed some variations in functional gene composition across different soil types. Mantel test indicated that pH, TN, and SOC were the primary environmental factors influencing microbial functional genes associated with soil carbon cycling. Stratified bar chart analysis further demonstrated that the major contributors to carbon cycling originated from corresponding dominatnt phyla and genera of Proteobacteria, Thaumarchaeota, Actinomycetota, Euryarchaeota, and Bacteroidota. The species and relative abundance of microorganisms associated with carbon cycling pathways varied among the samples. These findings provide a crucial reference for informing the conservation and sustainable management of wetland ecosystems in the Yalu River estuary.

MRI findings of closed hand injuries in adolescent goalkeepers: a case-based review.

Soccer-related injuries in youth goalkeepers are underrepresented in epidemiological studies, despite goalkeepers experiencing distinct types of upper limb injuries and training loads compared to outfield players. Digit injuries are particularly prevalent, with up to five times more upper extremity injuries reported in this position. Such injuries can lead to interphalangeal joint instability and an increased risk of reinjury. Mechanisms of injury include falls, axial loading of digits, and rotational force due to grasping activities. The proximal interphalangeal joint is the most frequently injured in sports, followed by the metacarpophalangeal joint of the thumb. Achieving precise diagnosis can be challenging due to the complex soft-tissue anatomy of the hand. Radiologists play a crucial role in accurate diagnosis through imaging studies, enabling timely treatment. This article focuses on closed traumatic finger and thumb injuries in adolescent goalkeepers, describing injury mechanisms and outlining relevant MRI features to facilitate proper clinical approaches for diagnosis based on imaging findings.

Fine-mapping causal tissues and genes at disease-associated loci.

Heritable diseases often manifest in a highly tissue-specific manner, with different disease loci mediated by genes in distinct tissues or cell types. We propose Tissue-Gene Fine-Mapping (TGFM), a fine-mapping method that infers the posterior probability (PIP) for each gene-tissue pair to mediate a disease locus by analyzing GWAS summary statistics (and in-sample LD) and leveraging eQTL data from diverse tissues to build cis-predicted expression models; TGFM also assigns PIPs to causal variants that are not mediated by gene expression in assayed genes and tissues. TGFM accounts for both co-regulation across genes and tissues and LD between SNPs (generalizing existing fine-mapping methods), and incorporates genome-wide estimates of each tissue's contribution to disease as tissue-level priors. TGFM was well-calibrated and moderately well-powered in simulations; unlike previous methods, TGFM was able to attain correct calibration by modeling uncertainty in cis-predicted expression models. We applied TGFM to 45 UK Biobank diseases/traits (average N = 316K) using eQTL data from 38 GTEx tissues. TGFM identified an average of 147 PIP > 0.5 causal genetic elements per disease/trait, of which 11% were gene-tissue pairs. Implicated gene-tissue pairs were concentrated in known disease-critical tissues, and causal genes were strongly enriched in disease-relevant gene sets. Causal gene-tissue pairs identified by TGFM recapitulated known biology (e.g., TPO-thyroid for Hypothyroidism), but also included biologically plausible novel findings (e.g., SLC20A2-artery aorta for Diastolic blood pressure). Further application of TGFM to single-cell eQTL data from 9 cell types in peripheral blood mononuclear cells (PBMC), analyzed jointly with GTEx tissues, identified 30 additional causal gene-PBMC cell type pairs at PIP > 0.5-primarily for autoimmune disease and blood cell traits, including the biologically plausible example of CD52 in classical monocyte cells for Monocyte count. In conclusion, TGFM is a robust and powerful method for fine-mapping causal tissues and genes at disease-associated loci.

Test Input Prioritization for 3D Point Clouds

3D point cloud applications have become increasingly prevalent in diverse domains, showcasing their efficacy in various software systems. However, testing such applications presents unique challenges due to the high-dimensional nature of 3D point cloud data and the vast number of possible test cases. Test input prioritization has emerged as a promising approach to enhance testing efficiency by prioritizing potentially misclassified test cases during the early stages of the testing process. Consequently, this enables the early labeling of critical inputs, leading to a reduction in the overall labeling cost. However, applying existing prioritization methods to 3D point cloud data is constrained by several factors: (1) inadequate consideration of crucial spatial information, and (2) susceptibility to noises inherent in 3D point cloud data. In this article, we propose PCPrior , the first test prioritization approach specifically designed for 3D point cloud test cases. The fundamental concept behind PCPrior is that test inputs closer to the decision boundary of the model are more likely to be predicted incorrectly. To capture the spatial relationship between a point cloud test and the decision boundary, we propose transforming each test (a point cloud) into a low-dimensional feature vector, toward indirectly revealing the underlying proximity between a test and the decision boundary. To achieve this, we carefully design a group of feature generation strategies, and for each test input, we generate four distinct types of features, namely spatial features, mutation features, prediction features, and uncertainty features. Through a concatenation of the four feature types, PCPrior assembles a final feature vector for each test. Subsequently, a ranking model is employed to estimate the probability of misclassification for each test based on its feature vector. Finally, PCPrior ranks all tests based on their misclassification probabilities. We conducted an extensive study based on 165 subjects to evaluate the performance of PCPrior, encompassing both natural and noisy datasets. The results demonstrate that PCPrior outperforms all of the compared test prioritization approaches, with an average improvement of 10.99% to 66.94% on natural datasets and 16.62% to 53% on noisy datasets.

LEXICAL DESYNONYMY IN B. VIAN’S NOVEL “FROTH ON THE DAYDREAM”

The article is dedicated to the studies of lexical desynonyms that are formed and transformed in the space of the operating time of the mental kineticism by means of cognitive polyoperations (psychomechanisms) during the first formal seizure by the thought of its movement in two stages: 1) phenomenological construction of the being and its structures and categories by the addresser as a result of which is formed the lexical primary structure having as basis “sublinguistic schemes”, typical models used to construct different simple and complex linguistic signs; 2) creation of simple secondary desynonymic linguistic signs from which the speaker chooses the co(n)textually (linguistically and/or situationally) pertinent structure. They are actualized in the form of ludic preferential options, according to the communicative intention to facilitate or to complicate the interpretation of the information to the receiver or to the author’s idiostyle, which are characterized by the asymmetry of semasiological and denotative meanings in the language and in the discourse at intrasign and intersigns levels. The goal of the article is to identify the processes of the formation and actualization of asymmetrical desynonymic signs, to identify the types of lexical desynonyms in B. Vian novel “Froth on the Daydream” and to justify their co(n)textual pertinence depending on the communicative intention and the idiostylistic features of the writer. In this research, we use the transformational method, which makes possible the identification of structural and semantic peculiarities of primary and secondary desynonymic constructions as asymmetrical signs in language and discourse, the method of systematization which helps to establish the typology of lexical desynonyms in the novel “Froth on the Daydream” by B. Vian and the linguo-stylistic and interpretative analyzes in order to reveal and characterize the idiostylistic features of the author and to justify the co(n)textual pertinence of the distinguished lexical desynonyms. In the process of analysis of the novel “Froth on the Daydream” by B. Vian, they revealed reduced, extended and quantitatively equacomponential desynonyms phonologically resembling or phonically identical to the primary structure, the derivative desynonyms, the preferential options with the surimpression and with a new semantic co(n)textual meaning in order to precise the author’s idea, to accentuate a qualifier of an object or a character, to transmit the supplementary information on аn exteriorized referent to the reader. All the distinguished types of lexical desynonyms perform the intra- and interphrasal stylistic‑expressive function reflecting the author’s individual vision of the objective reality. It is concluded that desynonymic lexical units represent biunambiguous emphatically accentuated linguo-discursive signs constructed and transformed in the space of the operating time of the causation of the linguo-discursive act which are not stabilized in use being substitutable in a particular co(n)text serving to enrich the intra- and interphrasal content by means of complementary co(n)textual semantic nuances facilitating or complicating the identification of desynonymized referents to the receiver.

Multiplexed Imaging Mass Cytometry Analysis Characterizes the Vascular Niche in Pancreatic Cancer.

Oncogenesis and progression of pancreatic ductal adenocarcinoma (PDAC) are driven by complex interactions between the neoplastic component and the tumor microenvironment, which includes immune, stromal, and parenchymal cells. In particular, most PDACs are characterized by a hypovascular and hypoxic environment that alters tumor cell behavior and limits the efficacy of chemotherapy and immunotherapy. Characterization of the spatial features of the vascular niche could advance our understanding of inter- and intratumoral heterogeneity in PDAC. In this study, we investigated the vascular microenvironment of PDAC by applying imaging mass cytometry using a 26-antibody panel on 35 regions of interest across 9 patients, capturing more than 140,000 single cells. The approach distinguished major cell types, including multiple populations of lymphoid and myeloid cells, endocrine cells, ductal cells, stromal cells, and endothelial cells. Evaluation of cellular neighborhoods identified 10 distinct spatial domains, including multiple immune and tumor-enriched environments as well as the vascular niche. Focused analysis revealed differential interactions between immune populations and the vasculature and identified distinct spatial domains wherein tumor cell proliferation occurs. Importantly, the vascular niche was closely associated with a population of CD44-expressing macrophages enriched for a proangiogenic gene signature. Taken together, this study provides insights into the spatial heterogeneity of PDAC and suggests a role for CD44-expressing macrophages in shaping the vascular niche. Significance: Imaging mass cytometry revealed that pancreatic ductal cancers are composed of 10 distinct cellular neighborhoods, including a vascular niche enriched for macrophages expressing high levels of CD44 and a proangiogenic gene signature.

Transient Interphase Microtubules Appear in Differentiating Sponge Cells.

Microtubules are an indispensable component of all eukaryotic cells due to their role in mitotic spindle formation, yet their organization and number can vary greatly in the interphase. The last common ancestor of all eukaryotes already had microtubules and microtubule motor proteins moving along them. Sponges are traditionally regarded as the oldest animal phylum. Their body does not have a clear differentiation into tissues, but it contains several distinguishable cell types. The choanocytes stand out among them and are responsible for creating a flow of water with their flagella and increasing the filtering and feeding efficiency of the sponge. Choanocyte flagella contain microtubules, but thus far, observing a developed system of cytoplasmic microtubules in non-flagellated interphase sponge cells has been mostly unsuccessful. In this work, we combine transcriptomic analysis, immunofluorescence, and electron microscopy with time-lapse recording to demonstrate that microtubules appear in the cytoplasm of sponge cells only when transdifferentiation processes are activated. We conclude that dynamic cytoplasmic microtubules in the cells of sponges are not a persistent but rather a transient structure, associated with cellular plasticity.

Identification of Key Genes in Angiogenesis of Breast and Prostate Cancers in the Context of Different Cell Types.

Angiogenesis involves the development of new blood vessels. Biochemical signals start this process in the body, which is followed by migration, growth, and differentiation of endothelial cells that line the inside wall of blood vessels. This process is vital for the growth of cancer cells and tumors. We started our analysis by composing a list of genes that have a validated impact in humans with respect to angiogenesis-related phenotypes. Here, we have investigated the expression patterns of angiogenesis-related genes in the context of previously published single-cell RNA-Seq data from prostate and breast cancer samples. Using a protein-protein interaction network, we showed how different modules of angiogenesis-related genes are overexpressed in different cell types. In our results, genes, such as ACKR1, AQP1, and EGR1, showed a strong cell type-dependent overexpression pattern in the two investigated cancer types, which can potentially be helpful in the diagnosis and follow-up of patients with prostate and breast cancer. Our work demonstrates how different biological processes in distinct cell types contribute to the angiogenesis process, which can provide clues regarding the potential application of targeted inhibition of the angiogenesis process.

Give them a fishing rod, if it is not urgent: The impact of help type on support for helpers' leadership.

Taking a follower's perspective on leadership and contributing to the new research stream on behaviors conducive to its emergence, we examined how distinct types of instrumental (task focused) helping-autonomy- versus dependency-helping-affected recipients' support for their helpers' leadership. Based on the literature on employees' needs for autonomy and mastery, combined with the empowering nature of autonomy-helping, we reasoned that autonomy- (vs. dependency-) helping typically signals greater benevolence toward recipients, enhancing their support for their helpers' leadership. Our findings were generalized across various samples (of U.S. and Israeli employees), manipulations, and research settings: simulations (Studies 1 and 2b), workplace role-play scenario (Study 2a), and recollections of helping events in the workplace (Study 3). We found that autonomy- (vs. dependency-) helping increased recipients' support for their helpers' leadership by heightening perceptions of helpers' benevolence-based (rather than ability-based) trustworthiness (Studies 1 and 3). We also showed time pressure to be a boundary condition under which the advantage of autonomy-helping disappeared (Studies 2a and 2b)-with dependency-helping then inducing comparable levels of perceived benevolence and thus similar support for the helper's potential leadership. Overall, we shed light on the development of informal leadership by uncovering how recipients interpret and respond to the two help types. Practically, this analysis opens the door to new ways for aspiring managers to enhance support for their leadership from potential followers, available even to those unlikely to be appointed to formal leadership positions. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Simulation approach to study kinetic heterogeneity of gadolinium catalytic system in the 1,4-cis-polyisoprene production

Abstract This article presents a novel simulation approach for solving the inverse problem of kinetic heterogeneity in polymerization processes, specifically focusing on the production of polyisoprene using a gadolinium chloride solvate-based catalytic system. The proposed method is based on the assumption that the distribution of active centers (ACs) can be described by model distributions. By utilizing primary physicochemical data, such as the polymerization rate and molecular weight distribution, the simulation approach automatically identifies the kinetic parameters, determining the Frenkel statistical parameter and solving the problem of kinetic heterogeneity. The experimental results revealed the presence of at least three distinct types of ACs, each contributing different proportions to the polymerization process. The simulation approach offers valuable insights into the complexities of catalytic systems and their role in polymerization, paving the way for optimizing reaction conditions and advancing industrial polymer synthesis processes. This study marks a significant step forward in understanding and controlling polymerization reactions, with potential implications for the development of innovative materials and industrial applications.

Clinicopathological and endoscopic features of Helicobacter pylori infection-negative gastric cancer in Japan: a retrospective study.

Helicobacter pylori infection-negative gastric cancer (HPNGC) has not been systematically investigated in consecutive patients. Hence, this study aimed to investigate the clinicopathological and endoscopic features of HPNGC. This single-center retrospective study selected participants from patients with gastric cancer who were treated at the Fukuoka University Chikushi Hospital between January 2013 and December 2021. Only patients diagnosed with HPNGC were enrolled, and their clinicopathological and endoscopic features were analyzed in detail. The prevalence of HPNGC in the present study was 2.6% (54/2112). The types of HPNGC observed in each gastric region were as follows: advanced gastric cancer was observed in the cardia; gastric adenocarcinoma of fundic-gland differentiation, gastric adenocarcinoma of foveolar-type presenting with whitish elevation and raspberry-like foveolar-type gastric adenocarcinoma, gastric adenocarcinoma arising in polyposis, and gastric adenocarcinoma with autoimmune gastritis were observed in the fundic gland region ranging from the gastric fornix to the gastric body; signet-ring cell carcinoma was observed in the gastric-pyloric transition region ranging from the lower gastric body to the gastric angle; and well-differentiated tubular adenocarcinoma with low-grade atypia was observed in the antrum. This study revealed that tumors from each gastric region exhibited distinct macroscopic and histological types in HPNGC.

Abstract 3911: A FGFR-p53 developmental signaling axis drives progression of salivary cancer

Abstract Mucoepidermoid carcinoma (MEC) is the most frequently occurring salivary gland (SG) malignancy. Treatments for high grade (HG) MEC are lacking due to a limited understanding of its diverse histological and clinical features. Consequently, patients with non-resectable HG MEC are often treated with adjuvant radiotherapy and suffer from increased rates of recurrence and metastasis with poor 5-year survival rates (30-50%) as compared to low grade (LG) MEC (76-95%). We previously demonstrated a role for IGF-1 signaling, an important mediator for SG development and branching morphogenesis, in MEC pathogenesis (Musicant et al, 2021). Here, we analyzed transcriptome profiles shared between fetal and adult normal parotid (PAR) tissues with MEC tumors to investigate programs involved in MEC progression. Using this information, we developed the first genetically engineered mouse model (GEMM) of advanced HG MEC via targeted oncogene expression in SG ductal cells. MEC samples from 21 PAR tumors (8 LG/13 HG), 8 age-matched normal, and 3 fetal PAR glands aged between 22-24 weeks of gestation (Saitou et al, 2020) were retrospectively collected from UCSF or UNC Surgical Pathology. RNAseq was performed on FFPE samples using Illumina HiSeq. Differential gene expression, gene set enrichment analyses (GSEA), and alternative splicing analyses were compared between fetal/normal/MEC according to tumor grade and CRTC1 (CREB-regulated transcription coactivator 1)/MAML2 (Mastermind-like 2) (C1/M2) status. Based on these analyses, we developed a GEMM combining C1/M2 expression with TP53 loss. GEMM tumors were subjected to RNAseq and reviewed by two independent pathologists for diagnostic confirmation of HG MEC.GSEA revealed significant overlap between MEC tumors and fetal SG for genes governing proliferation and developmental pathways associated with branching morphogenesis. Interestingly, upregulation of the negatively regulated p53 target FOXM1 along with a mutant-p53 gene signature (Troester et al, 2006) revealed that p53 dysregulation in HG tumors phenocopies that seen in fetal SG. Cre-inducible expression of C1/M2 alone was insufficient to induce MEC-like lesions when targeted to distinct salivary cell types (ductal Krt14-CreER, acinar Mist1-CreER, serous demilune Dcpp1-CreER). However, p53 alteration (Tp53KO) with ductal C1/M2 expression drove MEC formation with histological and molecular features of human HG-MEC. Notably, transcriptome profiles implicate an FGFR-p53 developmental signaling axis in MEC progression. Our autochthonous GEMM recapitulates advanced HG-MEC in vivo providing the field with a powerful platform for identifying pathways for developing targeted therapies. Taken together, the integrated bioinformatics and mouse modeling of this study provide a critical step toward elucidating salivary MEC progression and suggest a role for FGFR targeted therapies in the treatment of non-resectable HG MEC. Citation Format: Julia M. Billington, Adele M. Musicant, Jessica L. Cote, Jennifer Modliszewski, Yi-Hsuan Tsai, Luane J. Landuau, John Powers, Renee Betancourt, Radhika Sekhri, Ricardo J. Padilla, Juan C. Hernandez-Prera, David N. Hayes, Trevor G. Hackman, Omer Gokcumen, Sarah M. Knox, Jimena Guidice, Antonio L. Amelio. A FGFR-p53 developmental signaling axis drives progression of salivary cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3911.

Abstract 1151: Reconstruction of the spatial ecosystem of glioblastoma reveals relationships between tumor cell states and microenvironment

Abstract Glioblastoma multiforme (GBM) is the most aggressive form of primary brain tumor, with no curative treatment options. Multiple studies have characterized at single cell resolution the GBM as being composed of transcriptional cell states interconnected with components in the tumor immune microenvironment (TME). Our group proposed and validated the first single cell guided functional classification of GBM in four tumor-intrinsic cell states which informed clinical outcome and delivered therapeutic options. However, single cell technologies are unable to unravel the spatial relationships among the cell states of GBM and between GBM cell states and TME. Spatially resolved transcriptomic technologies are emerging as powerful tools to reconstruct the spatial architecture of a tissue. We performed spatial transcriptomics of multicellular regions of interest (ROI) in 6 primary IDH wild-type GBM and 2 recurrent GBM with both CosMx Spatial Molecular Imager, which analyzes 1,000 RNA probes and 64 proteins at single cell resolution, and GeoMx Digital Spatial Profiler which profiles the whole transcriptome (~18,000 genes) at ROI resolution. The development of computational tools aimed to integrate spatial proximity and CosMx derived single-cell transcriptomics revealed spatial segregation of the tumor cell clones and cellular states and highlighted recurrent patterns of cell states, distinct TME cell types associated with coherent histopathological features across multiple samples. The development of a spatial informed intercellular communication algorithm and the reconstruction of ligand-receptor-target networks will allow the discovery of tumor cell states-TME cross-talks and the biological signaling regulated by these interactions that are driving the heterogeneity of GBM and therefore potentially therapeutically targetable. Analysis of matched regions of interest profiled by GeoMx and spatial proteomics with CosMx further cross-validated the spatial ecosystem of glioblastoma as reconstructed at single-cell resolution. Our studies established a scalable approach to resolve the transcriptional heterogeneity of GBM and reconstruct the architecture of GBM cell states and tumor microenvironment. Citation Format: Bruno Adabbo, Simona Migliozzi, Luciano Garofano, Fulvio D'Angelo, Pedro Davila, Sakir H. Gultekin, Daniel Bilbao Cortes, Benjamin Currall, Sion L. Williams, Marc Sanson, Franck Bielle, Anna Luisa Di Stefano, Michele Ceccarelli, Anna Lasorella, Antonio Iavarone. Reconstruction of the spatial ecosystem of glioblastoma reveals relationships between tumor cell states and microenvironment [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 1151.

Diffusion-based Wasserstein generative adversarial network for blood cell image augmentation

White blood cells (WBC) are vital elements of the immune system, and their number and differential count are crucial for diagnosing blood-related disorders. While existing research has primarily focused on classifying easily distinguishable major WBC types, our study delves into a model encompassing up to 19 WBC classes, some of which exhibit irregular shapes and are challenging to differentiate manually. Convolutional Neural Networks (CNNs) have shown remarkable progress in accurately classifying these intricate WBC classes. However, the accuracy of these models depends mainly on the availability of enough appropriate datasets, which can be challenging to obtain for rare WBC classes. To address this, we introduce a generative model, the diffusion-based Wasserstein Generative Adversarial Network with Gradient Penalty (WGAN-GP). This model innovatively combines the Denoising Diffusion Probabilistic Model (DDPM) forward diffusion process with the WGAN-GP, leveraging DDPM’s noisy vectors as inputs for WGAN-GP’s generator. This fusion accelerates the generative process and significantly enhances the output’s fidelity, particularly for complex WBC images. Our model demonstrated its effectiveness on a dataset comprising 4,503 images across 19 WBC classes from Soonchunhyang University Bucheon Hospital, Korea, showing significant improvement in generating high-quality images for rare WBC classes and addressing data imbalance. We further combined pre-trained CNNs with Support Vector Machines (SVM) for classification, where our augmentation strategy led to the ResNet50-SVM model achieving an average accuracy of 95% in classifying the 19 WBC classes. This study not only addresses the data imbalance but also sets a new benchmark in WBC image analysis, demonstrating our model’s efficacy in generating high-quality data for rare classes.

Searching wide or staying close: the relative use of distinct organisational learning types in high and low novelty innovations

ABSTRACT Despite the acknowledged importance of organisational learning for new product development, there is a dearth of research into the relative use of distinct learning types as the innovation process unfolds. Our paper more fully engages with this issue, contrasting innovations of high versus low technological novelty. A qualitative study of innovation projects in the biopharmaceutical and medical device industries reveals that learning patterns vary in significant ways throughout the innovation process based on the underlying technological novelty of the offering. High novelty projects begin with an emphasis on vicarious learning from distant referents and shift to more internal experiential learning over time. Meanwhile, low novelty projects begin with experiential learning, pursue vicarious learning from proximate (industry peer) referents, and finish by returning to internal experience. We theorise a more general sequence of learning types throughout the innovation process based on our findings.