Open Profile Research Articles

ANALYSIS OF FLYASH AGGREGATE BEHAVIOR IN GEOPOLYMER CONCRETE BEAMS USING METHOD OF INITIAL FUNCTIONS (MATHEMATICAL PROGRAMMING)

The stipulated performance of flyash aggregates in geopolymer concrete beams (composite beam) has been explained using the Method of Initial Functions (MIF) via mathematical programming. This research has specifically focused on understanding its strength and durability characteristics. Geopolymer concrete is now being evaluated as a successful alternative in terms of sustainability in the construction sector and has used flyash, an industrial by-product, for several years as a major binder. The major theme adopted in the present research is concentrated on the mechanical and structural behavior of geopolymer concrete beams partially replaced by flyash aggregates for civil engineering applications. The present paper focuses on using the Method of Initial Functions to model and analyze beam behavior subjected to various loading conditions within a strong mathematical programming approach. In the current study, an explanatory analysis of the flexural strength, load-deflection characteristics, and crack opening profile is conducted without constructing a beam specimen by using MIF.

Sustainable and mechanical properties of Engineered Cementitious Composites with biochar: Integrating micro- and macro-mechanical insight

Engineered Cementitious Composites (ECC) are ductile, strain-hardening cementitious composites with a tightly controlled crack opening profile. A significant concern in the development and application of ECC is its high carbon emissions associated with high cement content consumption. As an emerging green additive, biochar can significantly cut down on the carbon emission of concrete products. However, research that integrates micro- and macro-mechanical insights with biochar incorporation is limited. In this study, micro-mechanical tools indicated that a certain amount of substitution biochar could enhance the tensile properties of ECC. The study assessed various properties including compressive strength, porosity, density, tensile performance, crack pattern, sustainability and cost of ECC with different biochar proportions. The findings showed that incorporating 10 %–20 % biochar effectively increased the tensile strain capacity and decreased the crack opening width in ECC materials. This improvement can be attributed to the introduction of finer biochar particles (≤75 μm) at the fiber/matrix interfacial transition zone, which alters the fiber-bridging force by reducing the chemical and frictional bond strength between the fiber and matrix, as revealed by micro-mechanical tests and microstructural inspection. Moreover, the utilization of biochar contributes to reducing the carbon emission of ECC, enhancing sustainability while maintaining a ∼10 % minimal reduction in compressive strength. Overall, this study introduces a novel approach for reusing low-carbon biomass waste in the production of building materials, offering potential advantages in micro- and macro-mechanical performance, cost-effectiveness, and environmental sustainability.

Single-cell transcriptomes and chromatin accessibility of endothelial cells unravel transcription factors associated with dysregulated angiogenesis in systemic sclerosis

ObjectivesVasculopathy emerges early in systemic sclerosis (SSc) and links to endothelial cell (EC) injury and angiogenesis. Understanding EC transcriptomes and epigenomes is crucial for unravelling the mechanisms involved.MethodsTranscriptomes and chromatin...

Analyzing factors influencing student engagement in an educative social media platform

ABSTRACT In the context of Social Media literacy, the success of educational interventions relies on designing motivational learning environments that seek students’ engagement. Despite existing achievements in social media education to include more appealing resources (e.g. gamification, authentic learning, interactive simulations), limited research has explored the factors that influence students’ engagement. This study aims to investigate the factors that influence engagement in an educational social media platform. Specifically, the factors that shape interest and enjoyment in Instareal, an educational tool that combines narrative scripts and collaborative learning flow patterns to educate teenagers about social media risks and challenges. To answer our research questions, we analyze the log data generated by high school students (N = 100) who tested a Social Media Literacy training with the support of Instareal. A factor analysis and a backward stepwise regression is performed over a dataset containing students’ traces of online activities and social interactions. The results show that factors such as the social participation of the students (comments, likes), curiosity (opening profiles, following others), and the quality of their answers influence interest and enjoyment within the platform. The results of this study offer new insights into measuring and enhancing student engagement when using educational social media environments.

Molecular characterization and gene expression of pattern recognition receptors in brown-marbled grouper (Epinephelus fuscoguttatus) fingerlings responding to vibriosis infection

The pathogen recognition system involves receptors and genes that play a crucial role in activating innate immune response in brown-marbled grouper (Epinephelus fuscoguttatus) as a control agent against various infections including vibriosis. Here, we report the molecular cloning of partial open reading frames, sequences characterization, and expression profiles of Pattern Recognition Receptors (PRRs) in brown-marbled grouper. The PRRs, namely pglyrp5, tlr5, ctlD, and ctlE in brown-marbled grouper, possess conserved domains and showed shared evolutionary relationships with other fishes, humans, mammals, birds, reptilians, amphibians, and insects. In infection experiments, up to 50% mortality was found in brown-marbled grouper fingerlings infected with Vibrio alginolyticus compared to 27% mortality infected Vibrio parahaemolyticus and 100% survival of control groups. It is also demonstrated that all four PRRs had higher expression in samples infected with V. alginolyticus compared to V. parahaemolyticus. This PRRs gene expression analysis revealed that all four PRRs expressed rapidly at 4-h post-inoculation even though the Vibrio count was only detected earliest at 12-h post-inoculation in samples. The highest expression recorded was from V. alginolyticus inoculated fish spleen with up to 73-fold change for pglyrp5 gene, followed by 14 to 38-fold expression for the same treatment in spleen, head kidney, and blood samples for other PRRs, namely tlr5, ctlD, and ctlE genes. Meanwhile less than a 10% increase in expression of all four genes was detected in spleen, head kidney, and blood samples inoculated with V. parahaemolyticus. These findings indicated that pglyrp5, tlr5, ctlD, and ctlE play important roles in the early immune response to vibriosis infected, brown-marbled grouper fingerlings.

Mesoscale Eddies Influence Coral Reef Environments in the Northwest Gulf of Mexico

AbstractCoral reefs globally are experiencing more frequent and severe warming events due to anthropogenic driven climate change. Subtropical reefs experience more seasonal variability than lower latitude reefs making them typically more resilient to climate change. With relatively stable coral cover in comparison to other global coral reefs, Flower Garden Banks National Marine Sanctuary (FGBNMS) in the Gulf of Mexico is a series of 17 reefs and banks located on the continental shelf‐edge containing a variety of shallow (0–30 m) and mesophotic (30–150 m) coral reef habitats. Here, we use satellite data products to associate open ocean Argo float profiles with eddy features over FGBNMS to study the shelf‐edge reef environment spanning nearly two decades (2003–2022). Satellite data show that FGBNMS is frequently influenced (∼15 days/month) by mesoscale eddies. The upper water column variability (0–25 m) is most influenced by the seasonal mixed layer despite eddy interaction. Subsurface seasonal ranges of temperature and salinity are enhanced or suppressed depending on the influence of eddies in relation to the mixed layer depth. Within the mesophotic zone (0–150 m), the largest range of thermal variability between anticyclonic and cyclonic eddies is between 50 and 150 m upwards of 5°C. However, these observed dynamics will likely change as a result of eddy variability associated with projected warming and Loop Current weakening, leading to increased thermal stress in the future.

#163 Multiome-seq and spatial transcriptomics of refractory PLA2RAb(+) membranous nephropathy reveals importance of immunomodulatory function of B cells

Abstract Background and Aims PLA2RAb-associated membranous nephropathy (MN) is a glomerulonephritis that may require immunosuppression to achieve proteinuria remission. However, the disease course is heterogeneous, and some patients exhibit refractory or relapsing nephrotic-range proteinuria. Additional biomarker studies are necessary to dissect the molecular profiles that reflect substantial differences in treatment response and clinical courses. Multiome-seq includes the investigation of gene expression profiles and ATAC-sequencing for open-chromatin regions, which may reveal pathophysiologic gene expression biomarkers and pathways. Method We performed multiome-sequencing of peripheral blood mononuclear cells (PBMCs) from 6 refractory or relapsing primary PLA2RAb-associated MN cases, 7 PLA2RAb-associated MN cases that reached complete remission, and disease controls including 6 minimal change disease and 6 diabetic kidney disease cases. We also collected PBMCs from 7 healthy controls. Cell type clustering, comparison of cell type proportions, and differential gene expression analysis were performed. Additionally, we conducted ATAC-sequencing analysis and identified open-chromatin profiles specific to the refractory or relapsing MN group. Lastly, we investigated the glomerular spatial transcriptome using GeoMx digital spatial profiling to determine whether transcriptomic profiles differ based on the disease courses of MN in the initial kidney tissue. Results We successfully identified diverse PBMCs in the multiome-seq data. In the DEG analysis, we identified a number of cell-type-specific DEGs in the refractory or relapsing MN cases. Of these, CD83 was the top gene that was lowly expressed in the B cells of refractory/relapsing MN compared to the remission cases. In the ATAC data, among the number of differentially expressed peaks, NFKB2 was the region that consistently showed a low open chromatin profile in the B cells of CD83. When comparing the cell subtype proportions, refractory or relapsing MN cases showed low regulatory T cells in the peripheral blood. Lastly, in the kidney tissue spatial transcriptomic profiling, there were no significant DEGs between the refractory/relapsing MN and MN with remission in the glomerulus. Conclusion The clinical course or risk of remission of PLA2RAb-associated MN was more likely a result of differences in systemic immunity rather than differences in the glomerular transcriptome at the initial diagnosis. Both CD83 and NFκB2 are well-known biomarkers of activated B cells that may have immunomodulatory roles leading to the enrichment of regulatory T cells. Such a deficient immunomodulatory status in refractory/relapsing PLA2RAb-associated MN may explain the disease course.

SEPARATED GEOTECHNICAL ENVIRONMENTS DURING THE RESEARCH OF THE TERRAIN AT THE LOCATION PLANNED FOR THE CONSTRUCTION OF THE SILOS IN KOZLUK NEAR ZVORNIK

<p>The construction of high-rise objects in solid rocks characterized by frequent changes in its vertical profile requires a more detailed study of lithological layers, tectonic characteristics and analysis of physical and mechanical parameters. Layers of different strength and characteristics in all elements make it possible to separate it by geological environments, in order to choose the most favorable one for the foundation of objects. As part of the construction of additional silos at the existing "Molaris" Mill complex in Kozluk near Zvornik, research was conducted at the central points of the future facilities and the immediate surroundings.</p> <p>Investigation works up to a depth of 12.0 m defined all the complexity of the terrain structure in a small area. Conducted research on rock samples from exploration works and from the open terrain profile showed differences in the physical and mechanical characteristics of softer rocks susceptible to solubility in water. Separated environments show that the foundation of objects cannot be done only in one environment, given the folds of the layers in a very small area.</p>

A defect opening profile reconstruction method based on multidirectional magnetic flux leakage detection

Magnetic flux leakage (MFL) is a popular technique for detecting defects. The opening profile reconstruction is one of the most popular concerns. The commonly used unidirectional magnetization-based methods easily lead to incomplete MFL information to reconstruct the opening profile. The superimposition of MFL signals from different directions would cause information cancellation, making it difficult for the existing data processing methods to reconstruct. To solve the issues, this study constructs a model-based method to inverse defect opening profiles. It builds the forward equations from one magnetic permeability to multidirectional MFL fields. Then the pseudo-inversion with Tikhonov regularization is applied as the inversion algorithm. The algorithm associates the forward equations and finds the solution that can fulfill them simultaneously. Such a method can combine multidirectional MFL information without cancellation. It reduces the ill-posed problems that exist in unidirectional inversion and makes the reconstructed profile complete and accurate. The comparison experiments have been carried out, and the results have proved the high accuracy of the proposed method.

Cardiac GR Mediates the Diurnal Rhythm in Ventricular Arrhythmia Susceptibility.

Ventricular arrhythmias (VAs) demonstrate a prominent day-night rhythm, commonly presenting in the morning. Transcriptional rhythms in cardiac ion channels accompany this phenomenon, but their role in the morning vulnerability to VAs and the underlying mechanisms are not understood. We investigated the recruitment of transcription factors that underpins transcriptional rhythms in ion channels and assessed whether this mechanism was pertinent to the heart's intrinsic diurnal susceptibility to VA. Assay for transposase-accessible chromatin with sequencing performed in mouse ventricular myocyte nuclei at the beginning of the animals' inactive (ZT0) and active (ZT12) periods revealed differentially accessible chromatin sites annotating to rhythmically transcribed ion channels and distinct transcription factor binding motifs in these regions. Notably, motif enrichment for the glucocorticoid receptor (GR; transcriptional effector of corticosteroid signaling) in open chromatin profiles at ZT12 was observed, in line with the well-recognized ZT12 peak in circulating corticosteroids. Molecular, electrophysiological, and in silico biophysically-detailed modeling approaches demonstrated GR-mediated transcriptional control of ion channels (including Scn5a underlying the cardiac Na+ current, Kcnh2 underlying the rapid delayed rectifier K+ current, and Gja1 responsible for electrical coupling) and their contribution to the day-night rhythm in the vulnerability to VA. Strikingly, both pharmacological block of GR and cardiomyocyte-specific genetic knockout of GR blunted or abolished ion channel expression rhythms and abolished the ZT12 susceptibility to pacing-induced VA in isolated hearts. Our study registers a day-night rhythm in chromatin accessibility that accompanies diurnal cycles in ventricular myocytes. Our approaches directly implicate the cardiac GR in the myocyte excitability rhythm and mechanistically link the ZT12 surge in glucocorticoids to intrinsic VA propensity at this time.

Abstract 334: Flexible and high-throughput microwell-based single-cell capture for multiomic ATAC-seq and RNA-seq profiling

Abstract The simultaneous profiling of chromatin accessibility and gene expression is an active area of interest for researchers studying how epigenetic changes regulate gene expression at the single-cell level. Here, we demonstrate the feasibility of single nuclei assay for transposase-accessible chromatin (snATAC) seq either with or without simultaneous gene expression profiling using the microwell-based BD Rhapsody™ HT Xpress System. Taking advantage of an eight-lane microwell cartridge, the BD Rhapsody™ HT Xpress System can support the snATAC seq assay with nuclei input ranging from 1,000 to 400,000 nuclei in a single experiment. To demonstrate the flexible throughput capabilities, 1,000 to 50,000 nuclei from cryopreserved peripheral blood mononuclear cells (PBMCs) were tagmented and loaded onto a single lane of the BD Rhapsody™ HT Xpress System. The snATAC assay libraries were prepared and sequenced, revealing multiple high-quality ATAC-seq metrics: high counts of unique ATAC fragments, high fraction of reads in peak regions (FRiP), and high transcriptional start site (TSS) enrichment score. The data were obtained consistently across the wide range of input nuclei with use of the gentle and robust nuclei loading capabilities of the BD Rhapsody™ HT Xpress System. Moreover, after capturing ATAC fragments, the BD Rhapsody™ Enhanced Cell Capture Beads are stable and can be stored at 4 °C for up to 3 months, allowing researchers the flexibility in sequencing subsets of nuclei or lanes for QC purposes before sequencing the entire library and returning to samples for complete sequencing. Furthermore, to demonstrate the consistency of both open chromatin profiling and mRNA gene expression as a combination (multiomic snATAC + snRNAseq), firstly, we compared snRNAseq data from a whole transcriptome assay (WTA) with snRNAseq from an ATAC+mRNA multiomic assay using the same sample. This strategy enabled us to show that there is negligible gene expression differences between snRNAseq from the BD whole transcriptome assay and snRNAseq from the multiomic scATAC and scRNA assay. Likewise, the snATACseq assay and snATACseq assay with simultaneous whole transcriptome profiling shows that chromatin accessibility profiling is equivalent with and without gene expression profiling. Enabling this new scATAC assay on the BD Rhapsody™ HT Xpress System can advance the study of epigenetic regulation of gene expression with a robust and flexible workflow. This will allow researchers to analyze both open chromatin and mRNA at varying nuclei inputs with single-cell resolution to understand the underlying molecular mechanisms in gene expression regulatory pathways. This assay can be readily extended to broader samples to gain greater understanding of disease states in immunology and immuno-oncology studies. For Research Use Only. Not for use in diagnostic or therapeutic procedures. © 2023 BD. All rights reserved. Citation Format: Rosary Nguyen, Hongduan Huang, Quyen Bao, Punya Narayan, Hye-Won Song, Elham Hatami, Zhiqi Zhang, Thomas McCarthy, Youngsook Kim, Ruifang Li, Chelsea Gordon, Larry Wang, Aruna Ayer. Flexible and high-throughput microwell-based single-cell capture for multiomic ATAC-seq and RNA-seq profiling [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 334.

Multi-omic analysis of longitudinal acute myeloid leukemia patient samples reveals potential prognostic markers linked to disease progression.

Relapse remains a determinant of treatment failure and contributes significantly to mortality in acute myeloid leukemia (AML) patients. Despite efforts to understand AML progression and relapse mechanisms, findings on acquired gene mutations in relapse vary, suggesting inherent genetic heterogeneity and emphasizing the role of epigenetic modifications. We conducted a multi-omic analysis using Omni-C, ATAC-seq, and RNA-seq on longitudinal samples from two adult AML patients at diagnosis and relapse. Herein, we characterized genetic and epigenetic changes in AML progression to elucidate the underlying mechanisms of relapse. Differential interaction analysis showed significant 3D chromatin landscape reorganization between relapse and diagnosis samples. Comparing global open chromatin profiles revealed that relapse samples had significantly fewer accessible chromatin regions than diagnosis samples. In addition, we discovered that relapse-related upregulation was achieved either by forming new active enhancer contacts or by losing interactions with poised enhancers/potential silencers. Altogether, our study highlights the impact of genetic and epigenetic changes on AML progression, underlining the importance of multi-omic approaches in understanding disease relapse mechanisms and guiding potential therapeutic interventions.

Exploring the role of student authors in the Journal of Librarianship and Information Science: Patterns, collaborations, and methodological insights

Assessing student participation in research and publication is essential, but this area has experienced limited exploration due to data constraints, despite the presence of open researcher profiles. Prior research noted modest student contributions but lacked in-depth analysis. Notably, in the Library and Information Science field, research on student-authored publications is scarce. This study analyzes data from student-authored papers in the Journal of Librarianship and Information Science from 1993 to 2022. Descriptive statistical analysis was employed, with various tables presenting yearly figures and data grouped by decades, along with charts to visualize changing trends over the years. The analysis reveals a significant increase in student engagement in research and publication, with student-authored papers constituting approximately 20% of all publications, highlighting their active participation in academic endeavors. Furthermore, this study underscores a marked shift toward collaborative research, with a substantial 88% of student authors engaging in internal or external collaborations for their publications. Additionally, nearly half of the student authors (48%) assumed the role of main authors, affirming their substantial contributions to research. Moreover, this study sheds light on the impact of research methodologies on student participation, with quantitative analysis emerging as the predominant approach for student-authored papers. Nevertheless, qualitative analysis may pose challenges for student-led research due to skill requirements. For future studies, broadening the scope of data collection to encompass a wider range of academic journals and analyzing the publication activities of graduate students from specific programs would be beneficial endeavors. In conclusion, this study enhances understanding of student authorship and its implications for academic publishing in the Library and Information Science field. It provides valuable insights into the evolving landscape of academic publishing and student involvement.

Integration of RNA-seq and ATAC-seq analyzes the effect of low dose neutron-γ radiation on gene expression of lymphocytes from oilfield logging workers

Objective: Although radiation workers are exposed to much lower doses of neutron-γ rays than those suffered in nuclear explosions and accidents, it does not mean that their health is not affected by radiation. Lower doses of radiation do not always cause morphological aberrations in chromosomes, so more sophisticated tests must be sought to specific alterations in the exposed cells. Our goal was to characterize the specific gene expression in lymphocytes from logging workers who were continuously exposed to low doses of neutron-γ radiation. We hypothesized that the combination of cell type-specific transcriptomes and open chromatin profiles would identify lymphocyte-specific gene alterations induced by long-term radiation with low-dose neutron-γ-rays and discover new regulatory pathways and transcriptional regulatory elements.Methods: Lymphocytes were extracted from workers who have been occupationally exposed to neutron-γ and workers unexposed to radiation in the same company. mRNA-seq and ATAC-seq (Assay for Transposase-Accessible Chromatin with high-throughput sequencing) were performed, followed integrative analysis to identify specific gene regulatory regions induced by neutron-γ radiation. A qPCR assay was then performed to verify the downregulation of RNA coding for ribosomal proteins and flow cytometry was used to detect ribosomal protein expression and cell cycle alterations.Results: We identified transcripts that were specifically induced by neutron-γ radiation and discovered differential open chromatin regions that correlated with these gene activation patterns. Notably, we observed a downward trend in the expression of both differentially expressed genes and open chromatin peaks. Our most significant finding was that the differential peak upregulated in ATAC-seq, while the differential gene was downregulated in the ribosome pathway. We confirmed that neutron-γ radiation leads to transcriptional inhibition by analyzing the most enriched promoters, examining RPS18 and RPS27A expression by qPCR, and analyzing protein-protein interactions of the differential genes. Ribosomal protein expression and cell cycle were also affected by neutron-γ as detected by flow cytometry.Conclusion: We have comprehensively analyzed the genetic landscape of human lymphocytes based on chromatin accessibility and transcript levels, enabling the identification of novel neutron-γ induced signature genes not previously known. By comparing fine-mapping of open chromatin and RNA reads, we have determined that neutron-γ specifically leads to downregulation of genes in the ribosome pathway, with pseudogenes potentially playing a crucial role.

ROCCO: a robust method for detection of open chromatin via convex optimization.

Analysis of open chromatin regions across multiple samples from two or more distinct conditions can determine altered gene regulatory patterns associated with biological phenotypes and complex traits. The ATAC-seq assay allows for tractable genome-wide open chromatin profiling of large numbers of samples. Stable, broadly applicable genomic annotations of open chromatin regions are not available. Thus, most studies first identify open regions using peak calling methods for each sample independently. These are then heuristically combined to obtain a consensus peak set. Reconciling sample-specific peak results post hoc from larger cohorts is particularly challenging, and informative spatial features specific to open chromatin signals are not leveraged effectively. We propose a novel method, ROCCO, that determines consensus open chromatin regions across multiple samples simultaneously. ROCCO employs robust summary statistics and solves a constrained optimization problem formulated to account for both enrichment and spatial dependence of open chromatin signal data. We show this formulation admits attractive theoretical and conceptual properties as well as superior empirical performance compared to current methodology. Source code, documentation, and usage demos for ROCCO are available on GitHub at: https://github.com/nolan-h-hamilton/ROCCO. ROCCO can also be installed as a stand-alone binary utility using pip/PyPI.

RESEARCH OF MARLY ROCKS ON THE TERRAIN FORECASTED FOR CONSTRUCTION OF SILOS OBJECTS

<p>Complexity of geological terrain built demands different level of research in order to obtain all necessary characteristics for the establishing of connections between the structure of the objects and the terrain. Frequent changes of rocks in vertical profile and their irregular settling related to creasing of the terrain during geological history makes choosing representative parameters harder. Layers of similar characteristics that are interconnected are separated into geological environments by taking medium values of the parameters within that environment.</p> <p>During the research, for the purpose of constructing of the silos objects, boreholes were drilled in the axis of each silos to a depth of 10.0 m. In a small area, there is a complex structure of the terrain, which, in addition to changes in the lithological composition, is also dictated by tectonic activity. Directly in the hinterland of the research conducted with boreholes, there is an open terrain profile with a height of about 6.0 m. By connecting the layers from the investigation works and the open profile on the terrain, a clearer picture of their position on the narrow part of the terrain was obtained.</p> <p>Frequent changes of layers of marly rocks and sandstones and their synclinal deposition demanded separation of certain geological environments with layers of the same characteristics. In addition to taking samples for laboratory tests, field tests of the solubility of marly rocks in the void at different temperatures were also conducted. In parallel with the samples from the investigation works, samples from the open terrain profile were examined. The results showed a shorter dissolution time of marly rocks from the open terrain profile compared to the same rocks taken from the core of the borehole.</p>

Genome-wide profiling of transcription factor activity in primary liver cancer using single-cell ATAC sequencing

Primary liver cancer (PLC) consists of two main histological subtypes; hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (iCCA). The role of transcription factors (TFs) in malignant hepatobiliary lineage commitment between HCC and iCCA remains underexplored. Here, we present genome-wide profiling of transcription regulatory elements of 16 PLC patients using single-cell assay for transposase accessible chromatin sequencing. Single-cell open chromatin profiles reflect the compositional diversity of liver cancer, identifying both malignant and microenvironment component cells. TF motif enrichment levels of 31 TFs strongly discriminate HCC from iCCA tumors. These TFs are members of the nuclear/retinoid receptor, POU, or ETS motif families. POU factors are associated with prognostic features in iCCA. Overall, nuclear receptors, ETS and POU TF motif families delineate transcription regulation between HCC and iCCA tumors, which may be relevant to development and selection of PLC subtype-specific therapeutics.

Application of the Ion Chamber Array in Magnetic Resonance Accelerator QA

The magnetic resonance accelerator (MR-Linac) is gradually widely used due to high-quality soft tissue contrast and real-time tracking. However, the special dosimetry characteristics and wide field sizes of MR-Linac increase the QA difficulty with conventional measurement method. The purpose of this study was to confirm an ion chamber array could be used for measuring the beam quality, the profiles, as well as the positioning accuracy of all MLC leaves efficiently, by comparing results with the conventional method. To propose a new QA approach for solving the common problem in data acquisition caused by the wide fields of MR-Linac. The research was based on a MR-Linac fixed with 1.5T MR and 7MeV energy photon beam. The conventional QA method adopted the MR water tank with a gantry angle of 0°and an SSD of 133.5 cm, both microdiamond and ionization chamber detector were used to acquire the dose profiles (PDD, inline, crossline and diagonal). Field sizes 1 × 1 cm2, 2 × 2 cm2, 3 × 3 cm2, 5 × 5 cm2, 10 × 10 cm2, 15 × 15 cm2, 22 × 22 cm2, 40 × 22 cm2,57 × 22 cm2 were measured with depth 13mm, 50mm, 100mm for vertical beam. As for the wide fields (larger than 15 × 15 cm2), two profiles of x axis (one from left to right, the other from right to left) needed to be gathered and then stitched into one final profile. A boot phantom with an ionization chamber detector was used for measuring beam quality. We defined the profiles measured by conventional method as the baseline. An ion chamber array was adopted to acquire TPR, PDD, profiles and MLC positioning, comparing to the conventional method. The center of ion chamber array was placed to the isocenter of MR-Linac, the array could move to the right and left offset positions through engaging the pin into correct hole of QA platform, such 'once positioning and twice movements' operation could finish within 3 minutes. The central detector of the ion chamber array was used for measuring beam quality. TPRs for different depths were acquired by stacking solid water on the ion chamber array. As for the profiles, we could get the final profile by 'once positioning and twice movements' efficiently. As for the positioning accuracy of MLC leaves, firstly the central leaf pair was put on y = 0 to measure 'open profile' under the open field. Then we moved the MLC leaves to different positions to get the n profile (n for different leaf positions). The ratio of n profile to open profile could show the positioning accuracy of MLC. We adopted 2D gamma (1mm / 2%) to compare the profiles between the ion chamber array and the conventional method, the results were within 98%. The beam quality consistency of ion chamber array comparing to the wedge tank was within 1% according to daily measurement. The ion chamber array could reflect the MLC positioning differences, the sensitivity was 0.5 mm. The ion chamber array showed a convenient QA method both for the dosimetry and for the MLC positioning accuracy which did reduce the overall measurement time, it was recommended for daily and monthly QA for MR-Linac.

Esfera pública digital e atores sociais que pautaram as discussões sobre vacinas no Instagram e Facebook no Brasil durante a pandemia de COVID-19 (2020-2021)

In this article, we aim to identify and categorize the voices that guided the debate on vaccines in the Brazilian digital public sphere in the first two years of the COVID-19 pandemic, a context in which vaccination gained relevance, as it consolidated itself as the main alternative to the control of the global health crisis. To this end, (i) a total of 3,878,408 valid posts related to the theme of vaccines made in Portuguese were collected by open profiles on Instagram and public pages on Facebook, between January 1, 2020, and December 31, 2021; (ii) the 500 social actors from each network who received the most comments on their posts were distributed into macro-categories, with the results pointing to a debate predominantly guided by lay voices, in which agents linked to journalistic activity, politics and public administration stood out. Celebrities and entertainment vehicles also stood out, helping to amplify the debate on vaccines. We highlight the fact that research institutions and scientific disseminators had little presence as mediators of the debate on the topic in the scope of our study.

Genome-wide open reading frame profiling identifies fibroblast growth factor signaling as a driver of PD-L1 expression in head and neck squamous cell carcinoma

Head and neck squamous cell carcinomas (HNSCC) are associated with significant treatment-related morbidity and poor disease-free and disease-specific survival, especially in the recurrent and metastatic (R/M HNSCC) setting. Inhibition of the programmed death-1/ligand-1 (PD-1/PD-L1) immune checkpoint is accepted as a first-line treatment strategy for R/M HNSCC and has expanded into the neoadjuvant, definitive, and adjuvant settings. To understand cellular signals modulating the PD-L1 in HNSCC, we profiled a HNSCC cell-line with a genome-wide open reading frame (ORF) library of 17,000 individual constructs (14,000 unique genes). We identified 335 ORFs enriched in PD-L1high cells and independently validated five of these ORFs (FGF6, IL17A, CD300C, KLR1C and NFKBIA) as drivers of PD-L1 upregulation. We showed that exogenous FGF ligand is sufficient to induce PD-L1 expression in multiple HNSCC cell lines and human immature dendritic cells. Accordingly, overexpression of FGFR1, FGFR3 or the FGFR3 S249C and D786N mutants common to HNSCC tumors also induced PD-L1 overexpression on tumor cells. Small molecule inhibition of FGF signaling abrogated PD-L1 upregulation in these models and also blocked “classical” IFNγ-regulated PD-L1 expression in a STAT1-independent manner. Finally, we found that FGF specifically upregulated a glycosylated form of PD-L1 in our study, and exogenous FGF led to concomitant upregulation of glycosyltransferases that may stabilize PD-L1 on the surface of HNSCC cells. Taken together, our study supports a potential role for FGF/FGFR pathway signaling as a mechanism driving immune escape and rationalizes further exploration of novel combination therapies to improve clinical responses to PD-1/PD-L1 axis inhibition in HNSCC.