Dynamic Changes Research Articles

Development of Artificial Intelligence in Business Ethics and Regulatory Responsibilities in the Era of Artificial Intelligence

The purpose of this study is to analyze development of artificial intelligence in business ethics and regulatory responsibilities in the era of artificial intelligence. The research methods applied in this study are literature study, comparative regulatory analysis, regulatory analysis, and regulatory risk analysis. Through this research method, it is expected to provide a comprehensive picture of the regulatory framework, ethics, and responsibilities related to the development of artificial intelligence in a business context. The results of the study show that the implementation of a regulatory framework for the use of artificial intelligence in business faces a number of complex challenges, such as regulatory uncertainty, unclear regulatory obligations, data privacy and security, algorithmic bias, compliance with regulations and standards, ethical challenges in autonomous decisions, accountability in cases of failure, understanding by stakeholders, risks at the personal level, and changes in job and market dynamics. Keywords: Development, Artificial Intelligence, Business Ethics, Regulatory Responsibilities, Era of Artificial Intelligence

Single-cell RNA sequencing reveals the landscape of the cellular ecosystem of primary hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) cells, along with multiple nonmalignant stromal cells, such as fibroblasts, endothelial cells and immune cells, comprise an intricate cellular ecosystem, undergo dynamic phenotypic changes and present complicated cellular interactions, thus synergistically facilitating HCC initiation and progression and leading to treatment resistance. Clarifying the heterogeneity, cell plasticity and complexity of the cellular ecosystem of HCC will be highly beneficial for understanding HCC development and identifying novel therapeutic targets. Single-cell RNA sequencing (scRNA-seq) refers to profiling the transcriptome at single-cell resolution, and the development of scRNA-seq technology and analysis algorithms has greatly promoted the analysis of cell composition, cell subpopulation heterogeneity, development trajectory and cell-to-cell interactions in cell populations. In this review, we systematically summarized and discussed scRNA-seq in treatment-naive primary HCC and revealed the global cell composition of HCC; the widespread molecular heterogeneity of HCC cells; the molecular subtypes of fibroblasts; the cell composition, functional states and development trajectory of immune cells; and the frequent interactions between different cell types to systematically draw the landscape of the cellular ecosystem of primary HCC.

Isobaric crosslinking mass spectrometry technology for studying conformational and structural changes in proteins and complexes.

Dynamic conformational and structural changes in proteins and protein complexes play a central and ubiquitous role in the regulation of protein function, yet it is very challenging to study these changes, especially for large protein complexes, under physiological conditions. Here, we introduce a novel isobaric crosslinker, Qlinker, for studying conformational and structural changes in proteins and protein complexes using quantitative crosslinking mass spectrometry. Qlinkers are small and simple, amine-reactive molecules with an optimal extended distance of ~10 Å, which use MS2 reporter ions for relative quantification of Qlinker-modified peptides derived from different samples. We synthesized the 2-plex Q2linker and showed that the Q2linker can provide quantitative crosslinking data that pinpoints key conformational and structural changes in biosensors, binary and ternary complexes composed of the general transcription factors TBP, TFIIA, and TFIIB, and RNA polymerase II complexes.

Associations Between Plasma Levels of NLRP3 Protein, Interleukin-1 Beta and Features of Acute ST-Elevation Myocardial Infarction

Background. Phenotyping inflammation in ST-elevation myocardial infarction (STEMI) is a challenge for modern cardiology. NLRP3 inflammasome is a proven predictor of adverse outcomes in cardiovascular disease, but its specificity in stratifying inflammatory activity in patients with myocardial infarction (MI) has not been demonstrated. The aim of this paper is to describe the levels of NLRP3 protein and IL-1β concentrations and their changes in dynamics and associations with clinical, laboratory and instrumental characteristics of patients with STEMI. Methods. A total of 45 patients with STEMI were enrolled. Concentrations of NLRP3 and IL-1β were evaluated in arterial and venous EDTA blood from the infarct-related coronary and peripheral arteries and veins on days 1, 3 and 7 after MI. Results and Conclusions. The concentrations of markers were higher on the first day after MI with a maximum decrease on the third day. The levels of both markers in venous plasma correlated with those in arterial blood, allowing their routine determination in venous plasma on the first day after MI. IL-1β levels correlated directly with the wall motion index and inversely with left ventricular ejection fraction and stroke volume, which characterize the potential contribution to adverse myocardial remodeling. There were two multidirectional trends in changes in NLRP3 and IL-1β levels during hospitalization. Initially higher levels with a gradual decrease by day 7 were associated with a longer duration of myocardial ischemia and higher plasma troponin I levels. Further evaluation of the long-term outcomes of MI will allow identifying inflammatory factors that input to the development of secondary major adverse cardiac events and will provide a new step in the understanding of inflammatory phenotyping.

Changing the Formations of Unmanned Aerial Vehicles

The development of hierarchical structures of unmanned aerial vehicles (UAVs) increases the efficiency of unmanned aerial systems. The grouping of UAVs increases the region of recognition or force of assault. Achieving these requirements is possible through a UAV formation. The UAVs in the formation must be controlled and managed by a commander, but the commander cannot control individual UAVs. The UAVs within the formation have assigned specific individual tasks, so is possible to achieve the flight of the formation with minimum collisions between UAVs and maximized equipment utilization. This paper aims to present a method of formation control for multiple UAVs that allows dynamic changes in the constellations of UAVs. The article includes the results of tests and research conducted in real-world conditions involving a formation capable of adapting its configuration. The results are presented as an element of research for the autonomy swarm, which can be controlled by one pilot/operator. The control of a swarm consisting of many UAVs (several hundred) by one person is now a current problem. The article presents a fragment of research work on high-autonomy UAV swarms. Here is presented a field test that focuses on UAV constellation control.

Adult skull bone marrow is an expanding and resilient haematopoietic reservoir.

The bone marrow microenvironment is a critical regulator of haematopoietic stem cell self-renewal and fate1. Although it is appreciated that ageing, chronic inflammation and other insults compromise bone marrow function and thereby negatively affect haematopoiesis2, it is not known whether different bone compartments exhibit distinct microenvironmental properties and functional resilience. Here we use imaging, pharmacological approaches and mouse genetics to uncover specialized properties of bone marrow in adult and ageing skull. Specifically, we show that the skull bone marrow undergoes lifelong expansion involving vascular growth, which results in an increasing contribution to total haematopoietic output. Furthermore, skull is largely protected against major hallmarks of ageing, including upregulation of pro-inflammatory cytokines, adipogenesis and loss of vascular integrity. Conspicuous rapid and dynamic changes to the skull vasculature and bone marrow are induced by physiological alterations, namely pregnancy, but also pathological challenges, such as stroke and experimental chronic myeloid leukaemia. These responses are highly distinct from femur, the most extensively studied bone marrow compartment. We propose that skull harbours a protected and dynamically expanding bone marrow microenvironment, which is relevant for experimental studies and, potentially, for clinical treatments in humans.

Abstract A038: Investigating PD-L1 status in circulating tumor cells isolated from blood samples of lung cancer patients

Abstract Background: This research study aimed to assess the performance of a research use only (RUO) immunofluorescence (IF) assay targeting programmed death-ligand 1 (PD-L1) evolution in epithelial and/or mesenchymal circulating tumor cells (CTCs) isolated from blood using Parsortix® microfluidic technology. Upregulation of PD-L1 enables cancer cells to evade the host immune response. Assessment of PD-L1 status in the tumor, as determined by traditional tissue biopsy, can indicate if immunotherapy has the potential to be an effective treatment. However, PD-L1 expression in tumor biopsies may not reflect metastatic sites in their entirety and can become outdated during tumor evolution, as the process cannot be repeated due its invasive nature. Liquid biopsy offers a minimally invasive option for dynamic testing of PD-L1 in CTCs as patients undergo treatment. Methods: Analytical linearity, and specificity and sensitivity were assessed by spiking HCC1954 and Hs 578T cancer cell lines into the blood samples of 34 healthy volunteers. The assay was then evaluated in samples from 47 metastatic lung cancer patients, among which 32 had a known PD-L1 tissue status (19 positive, 13 negative). Up to six successive draws were taken for each patient, collected into Streck Cell-Free DNA blood collection tubes. ANGLE’s Parsortix® instruments were used to isolate spiked cancer cells or CTCs from blood samples based on their size and deformability. The CTC- enriched harvests were processed onto ANGLE’s CellKeepTM slides and IF stained with ANGLE’s Portrait® PD-L1 RUO assay for PD-L1 identification on CTCs. Slides were imaged on a BioView automated imaging system. Results: Analytical specificity of PD-L1 was 98% and analytical sensitivity was 81%. Analytical linearity (R2=0.91) was shown over a 0–500 cells range. In metastatic lung cancer patients, ≥1 CTC was identified in at least one draw for 91% of donors, with 55% of those donors exhibiting ≥1 PD-L1 positive CTC. A majority (81%) of donors exhibited a positive correlation between PD-L1 tissue status and CTC expression. However, the remaining 19% of donors exhibited discordance with a PD-L1 negative tissue status but PD-L1 positivity identified in ≥1 CTC. Of the PD-L1 positive CTCs identified, 98% expressed mesenchymal markers. Dynamic change was shown in all but one donor, with PD-L1 status of the CTCs changing over time. Conclusions: This study demonstrated the ability to determine PD-L1 status in CTCs from the blood of metastatic lung cancer patients and, subject to further study, the future potential to develop dynamic PD-L1 testing for advancement of more personalized cancer treatments. Patients with a PD-L1 negative tissue status exhibited PD-L1 positive CTCs, demonstrating the feasibility of a more repeatable and accurate assessment of PD-L1 status than can be achieved through a traditional tissue biopsy. Citation Format: Morgan Spode, Chloe Goodwin, Aarabhi Varatharajah, Aaron Cottingham, Elisha Duhig, Laura Kaja, David Greaves, Mariacristina Ciccioli, Anne-Sophie Pailhes-Jimenez. Investigating PD-L1 status in circulating tumor cells isolated from blood samples of lung cancer patients [abstract]. In: Proceedings of the AACR Special Conference: Liquid Biopsy: From Discovery to Clinical Implementation; 2024 Nov 13-16; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(21_Suppl):Abstract nr A038.

Abstract B023: Cell-free HPV-DNA dynamics during induction chemotherapy and response-stratified de-escalation in viral-mediated oropharyngeal cancer

Abstract Background: Cell-free HPV-DNA (cfHPV-DNA) in plasma represents a promising biomarker to grade treatment response and monitor for persistence/recurrence. We evaluated the dynamic changes of cfHPV-DNA during induction chemotherapy followed by response-stratified de-escalation in HPV associated (HPV+) oropharyngeal squamous cell cancer (OPSCC). Methods: A prospective biomarker clinical trial of response-stratified de-escalation therapy was conducted. Eligible patients had loco-regional HPV+ OPSCC and received induction chemotherapy with carboplatin and paclitaxel for three cycles followed by risk and response-stratified de-escalation with transoral robotic surgery (TORS), de-escalated radiation (RT) to 50Gy with or without cisplatin, or standard RT to 70Gy with cisplatin. Patients with deep response (>=50% tumor shrinkage per RECIST 1.1) qualified for de-escalated therapy. Cell-free HPV-DNA was measured using a CLIA-certified HPV-SEQ assay that utilizes NGS technology to detect and quantify HPV16 and HPV18 DNA in plasma at baseline, after each cycle of induction chemotherapy, during radiation, and post-treatment surveillance at 3, 6, 9, 12, 18, and 24 months following treatment. Results: Forty-six eligible patients were enrolled, with 464 cfHPV-DNA plasma samples analyzed (median 10 samples per patient). There were five recurrences (10.9%), all detected by HPV-SEQ. Baseline cfHPV-DNA was detected in 44/46 patients (96%). Patients with rapid early cfHPV-DNA clearance after one 3-week cycle of induction (>=95% clearance) predicted deep radiographic response following induction therapy (p=0.003). The detection of cfHPV-DNA at 3 months or later after treatment was associated with worse progression free survival (PFS), with 2-year PFS of 25% (95% CI 0.012-0.65) compared with patients without detectable cfHPV-DNA of 100% (95% CI 1.0-1.0); p<0.001). The longest lead-time from positive cfHPV-DNA to developing recurrent disease was 25 months. Conclusion: Rapid early clearance of cfHPV-DNA during induction has utility in predicting response to treatment. Detectable cfHPV-DNA following treatment is strongly associated with worse PFS. A subsequent trial using cfHPV-DNA to select patients for treatment de-escalation is ongoing. Clinicaltrials.gov ID: NCT04572100 Citation Format: Ari Rosenberg, Evgeny Izumchenko, John Cursio, Augustin Vannier, Aditya Juloori, Rohan Katipally, Rifat Hasina, Frederick Jones, Anna Starus, Elizabeth Blair, Daniel J. Haraf, Alexander T. Pearson, Everett E. Vokes, Nishant Agrawal. Cell-free HPV-DNA dynamics during induction chemotherapy and response-stratified de-escalation in viral-mediated oropharyngeal cancer [abstract]. In: Proceedings of the AACR Special Conference: Liquid Biopsy: From Discovery to Clinical Implementation; 2024 Nov 13-16; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(21_Suppl):Abstract nr B023.

Spatiotemporal Analysis of the Coupling Relationship Between Urban Infrastructure and Land Utilization in a Shrinking City: A Case Study of Hegang, Northeast China

Globally, urbanization is accelerating, with China witnessing a significant 40% rise in urbanization rate over the past 4 decades. However, the dynamic changes in the spatial coupling between infrastructure and utilization intensity during the early, middle, and late stages of urbanization are not clear. The trajectory of development and coupling within the urbanization process is crucial for understanding issues such as urban over-saturation and urban shrinkage. Using Hegang in Northeastern China as an example, we utilized high-resolution remote sensing data, examined the construction intensity of urban land use, analyzed the degree of coupling with utilization efficiency, and clarified the dynamic evolution of the binary relationship system between development and coupling. Results show that Hegang’s construction intensity has seen a continuous rise from 1992 to 2000, with a 200.06% increase over 28 years, while its coupling with utilization efficiency has experienced a significant drop in the 21st century, suggesting a persistent decline in the utilization of buildings and a notable urban shrinkage phenomenon. Considering development status and coupling degree, we delineate a characteristic urbanization state curve for Hegang, reflecting its progression through stages of “Underdeveloped, Highly coupled,” to “Underdeveloped, Weakly coupled”, and finally to “Highly developed, Weakly coupled”, offering insights into its urban development path. This research not only establishes a foundational data groundwork for future land-use planning in Hegang but also presents a replicable template for urbanization path analysis in other cities, contributing to a broader understanding of urban development dynamics.

Lactylation Modification as a Promoter of Bladder Cancer: Insights from Multi-Omics Analysis

Bladder cancer (BLAC) is a malignant tumor with high morbidity and mortality. The establishment of a prognostic model for BLAC is of great significance for clinical prognosis prediction and treatment guidance. Lactylation modification is a newly discovered post-transcriptional modification of proteins, which is closely related to the occurrence and development of tumors. Multiple omics data of BLAC were obtained from the GEO database and TCGA database. The Lasso algorithm was used to establish a prognostic model related to lactylation modification, and its predictive ability was tested with a validation cohort. Functional enrichment analysis, tumor microenvironment analysis, and treatment response evaluation were performed on the high- and low-risk groups. Single-cell and spatial transcriptome data were used to analyze the distribution characteristics of model genes and their changes during epithelial carcinogenesis. A prognostic model consisting of 12 genes was constructed. The survival rate of the high-risk group was significantly lower than that of the low-risk group. The multiple ROC curve showed that the prediction efficiency of the model was higher than that of the traditional clinical tumor grading. Functional enrichment analysis showed that glycolysis and hypoxia pathways were significantly upregulated in the high-risk group. The high-risk group was more sensitive to most first-line chemotherapy drugs, while the low-risk group had a better response to immunotherapy. Single-cell sequencing analysis revealed the dynamic changes of model genes during the transition of epithelial cells to squamous-differentiated cells. Spatial transcriptome analysis showed the spatial distribution characteristics of the model genes. The lactylation-related models have a satisfactory predictive ability and the potential to guide the clinical treatment of BLAC. This model has significant biological implications at the single-cell level as well as at the spatial level.

The Study of the State of Monoaminergic Systems in the Brain Structures of the Offsprings of Female BALB/C Mice at Different Stages of Formation of Autism Spectrum Disorders

The study of the status of norepinephrine-, dopamine- and serotonergic neurotransmitter systems of BALB/C mice brain structures on 15 and 64 days of postnatal development (PD) in the model of autistic disturbances induced by injection of of sodium valproate (SV, 400 mg/kg, s/c) to pregnant females was carried out using the HPLC/ED method. The level of both catechol- and indolamines in the brain structures of control group mice at the age of 15 days was significantly lower than in adult animals at the age of 64 days. Prenatal administration of SV caused a decrease in all parameters of monoaminergic neurotransmission in the striatum of offspring at the age of 15 days, but had no effect in other brain structures studied. Subsequently, the level of dopamine increased and by the 64th day of PD did not differ from the parameters of the control group. The parameters of the serotonergic system changed in a similar pattern, with the content of serotonin and the serotonin metabolite 5-OIAA in the striatum increasing gradually and reaching maximum values by the 64th day of PR. Our data allows to assume that the administration of SV to pregnant females affects the activity of the dopamine and serotonergic systems of the brain of the offspring, causing a decrease in their activity in the striatum by the 15th day of pregnancy, followed by restoration to control values by the 64th day, which we previously observed in male pups. Thus, the patterns of dynamic changes in the neurochemical profile do not differ between males and females.

DGTNet：dynamic graph attention transformer network for traffic flow forecasting

Abstract Graph-based traffic flow prediction plays a crucial role in urban traffic management and planning. In this paper, we propose a novel Dynamic Graph Attention Transformer Network (DGTnet), which is designed to address the issue of inadequately integrating of temporal and spatial dimensions in traditional models. DGTnet maintains temporal continuity while revealing the complex dynamic relationships between key nodes in the urban traffic system, capturing the periodic changes in the rhythm of city life. Specifically, this study adopts adaptive signal decomposition technology to decompose traffic data into multiple intrinsic mode functions (IMFs), effectively capturing the dynamic changes in traffic flow. This decomposition method is key to the implementation of DGTnet dynamic graph construction, enabling the analysis of traffic flow at different time scales, thereby providing a new perspective for traffic flow prediction research. In the traffic prediction module, we comprehensively consider node, edge, and graph structural information, adopting a multi-head self-attention mechanism to achieve direct cross-modeling in both temporal and spatial dimensions. Finally, we introduce a position-wise feed forward network layer to integrate different types of data and capture nonlinear relationships. The experimental results, based on the public transportation network data sets METR_LA, PEMS_BAY, PEMS03 and PEMS07, demonstrate that DGTNet exhibits notable enhancements in three evaluation indicators, namely the Mean Absolute Percentage Error (MAPE), the Root Mean Square Error (RMSE) and the Mean Absolute Error (MAE). The pertinent code has been made available for public access at https://github.com/chenjing0616/DGTNet.

Tracking dynamic deadlines in switched max-plus linear systems with uncontrollable workloads

AbstractModern safety-critical cyber-physical systems such as medical imaging equipment or autonomous vehicles need to respect strict deadlines on received data-processing workloads. These deadlines and workloads are dynamic and uncontrollable and the systems typically have only a limited discrete number of system configurations to respond to dynamic changes. The number and types of processors allocated to a data-processing task, their operating voltage and frequency, and the resolution and frequency of sensing (e.g., images) are examples of controllable configuration parameters. Guaranteeing dynamically changing deadlines under uncontrollable workloads with a limited discrete number of response options can be phrased as a multi-objective tracking problem for a switched max-plus linear system. This results in a combined scheduling and control problem. We propose an integrated state-feedback and model-predictive control solution that minimizes the number of deadline misses and the cost of implementation (e.g., energy consumption). We demonstrate the effectiveness of our approach through simulation.

Abstract B025: Monitoring response to immunotherapy in lung cancer using cell-free DNA fragmentomes

Abstract BACKGROUND: Immune checkpoint inhibition (ICI) continues to be a promising area of research with treatments continuing to show efficacy in late-stage cancers. The detection of disease progression for patients undergoing treatment with this modality remains challenging however given the lack of reliable biomarkers for which to monitor disease. Current methods including imaging can be challenging to evaluate as they do not always capture the timing and nature of clinical responses. Liquid biopsies may offer a solution by allowing for minimally invasive tumor monitoring during therapy. We previously reported on the DELFI Tumor Fraction (DELFI-TF) algorithm, as a tumor- and mutation-naive approach to monitoring using cell-free DNA (cfDNA) fragmentomes (Alipanahi et al., AACR 2023). In this study we examine the performance of DELFI-TF in a cohort of patients with metastatic NSCLC treated with ICI. METHODS: Longitudinal blood samples (n=323) were collected from NSCLC patients (n=109) which received ICI therapy. Whole genome sequencing at low coverage (∼4x) was performed following cfDNA extraction. DELFI-TF scores, predicted using fragmentome features, were used to monitor changes in circulating tumor DNA (ctDNA) levels and associated variations in disease burden. Predictions from DELFI-TF were compared to maximum observed mutation allele frequencies (maxMAF) from a targeted sequencing gene panel for the same samples. In order to determine the prognostic performance of DELFI-TF we evaluated ctDNA changes at baseline and within 3 to 9 weeks of ICI initiation. The presence of undetectable DELFI-TF, defined as below the observed limit of blank (LOB) within 3 to 9 weeks of ICI initiation, indicated a molecular response (mR). In contrast, the persistence of DELFI-TF within this interval signified molecular disease progression (mPD). RESULTS: We observed a strong correlation between DELFI-TF predictions and maxMAF (r=0.93, p<0.001). Further, changes in ctDNA predictions from baseline to the first post-treatment timepoint showed a high correlation between DELFI-TF and maxMAF (r=0.94, p<0.001). Patients with a higher disease burden prior to immunotherapy, as predicted by DELFI-TF and maxMAF, had shorter overall survival (OS) compared to patients with a lower disease burden (DELFI-TF: 11.4 v 33.0 months, p=0.006; maxMAF: 7.82 vs low 33.0 months, log-rank p=0.001). Among 79 patients evaluable for molecular response, 28 (35%) were classified as mPD and 51 (65%) were classified in the mR category. Patients with mR attained longer progression free survival (PFS;16.04 v 2.70 months, log-rank p<0.001) compared to those in the mPD group. Furthermore, assessment of landmark PFS at 6 months revealed a significant association between ctDNA molecular response and durable clinical benefit (DCB; p < 0.001, Fisher’s exact test). CONCLUSIONS: DELFI-TF is a low-cost, tumor and mutation naive approach that accurately monitors longitudinal dynamic changes in tumor burden and captures durable therapeutic responses in patients with metastatic NSCLC receiving immunotherapy. Citation Format: Lavanya Sivapalan, Bahar Alipanahi, Jamie E Medina, Bridget Tripp, Zachary L Skidmore, Paola Ghanem, Gavin Pereira, Nisha Rao, Kavya Velliangiri, Caitlin Schonewolf, Noushin Niknafs, Bryan Chesnick, Jennifer Tom, Stephen Cristiano, Peter Bach, Nicholas C Dracopoli, Robert B Scharpf, Victor Velculescu, Lorenzo Rinaldi, Valsamo Anagnostou. Monitoring response to immunotherapy in lung cancer using cell-free DNA fragmentomes [abstract]. In: Proceedings of the AACR Special Conference: Liquid Biopsy: From Discovery to Clinical Implementation; 2024 Nov 13-16; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(21_Suppl):Abstract nr B025.

Reduced graphene oxide loaded with tetrahedral framework nucleic acids for combating orthodontically induced root resorption.

Root resorption occurs outside the root or within the root canal. Regardless of its region, root resorption is irreversible and in severe cases, may even cause tooth loss. Clinically, the external surface root resorption is usually a side effect of orthodontic tooth movement. However, it is frustrating to note that there are almost no effective treatment strategies for orthodontically induced root resorption (OIRR) due to the complexity and ambiguity of etiology. In the current study, we successfully fabricated a delivery complex, reduced graphene oxide nanosheet loading with tetrahedral framework nucleic acids (tFNAs-rGO) through self-assembly. No significant cytotoxicity or organ-toxicity of the tFNAs-rGO complex was observed in cell counting kit-8 assay (CCK-8) and hematoxylin-eosin (HE) staining. Histological staining such as tartrate-resistant acid phosphatase (TRAP) staining and Micro-CT three-dimensional reconstruction were employed to explore the dynamic changes of root and peri-root tissues in OIRR mice. In vitro, we developed an induction microenvironment to testify the effects of the tFNAs-rGO delivery complex on periodontal ligament cells (PDLCs) and macrophages by quantitative RT-PCR, western blot, and immunofluorescence staining. The data showed the reduced the region of root resorption and downregulated osteoclastic activity in OIRR by the tFNAs-rGO complex treatment. Furthermore, our study demonstrated that the tFNAs-rGO delivery complex enhanced osteogenic differentiation of PDLCs and facilitated M2-phenotype polarization of macrophages to ameliorate OIRR. Collectively, the insight into the nanoscale dual-functional tFNAs-rGO delivery complex regulating the cell populations of PDLCs and macrophages in the root resorption remodeling proposes a promising therapeutic strategy for orthodontically induced root resorption.

Abstract PR005: Leveraging mass cytometry for phenotyping CTCs in SCLC liquid biopsies: Tracking therapy resistance at a personalized level

Abstract Liquid biopsies present a promising, minimally invasive procedure through which clinicians can assess and monitor disease status by interrogating circulating tumor cell (CTC) and immune cell phenotypes. In the case of Small-cell lung cancer (SCLC) – a type of lung cancer characterized by aggressive growth, dismal prognosis and limited treatment options - leveraging liquid biopsies and CTCs for evaluating disease status would be of great benefit, given that biopsies are scarce. Furthermore, SCLC CTC numbers are higher compared to other cancers, presenting a unique opportunity to utilize them for assessing SCLC therapy resistance and identifying new targetable markers. In this study, we leverage mass cytometry (i.e. CyTOF) to phenotype SCLC CTC phenotypes in longitudinal clinical specimens to assess therapy resistance at a personalized level. By using CyTOF - a multiplex cytometric approach that enables interrogation of 30-50 protein markers per single cell – we show that we are able to identify and analyze a significant number of CTCs and their heterogeneous expression profiles. To achieve this, we first optimized a CyTOF panel of ∼25-30 antibodies by using SCLC cell lines and blood specimens from healthy donors and SCLC patients. We show that by using this approach, we are able to identify and phenotype SCLC CTCs by using the combination of CD45 (negative expression) and CD56 positive expression with further validation achieved by TTF1 and SCLC subtype transcription factor expression (NEUROD1, POU2F3 and ASCL1). This approach avoids enriching for specific CTC epithelial phenotypes that express surface markers that fluctuate during epithelial- mesenchymal transition (EMT) (e.g. EpCAM, a common marker for isolating CTCs). For parallel immune profiling we assessed among others CD8/CD4 (T cells) and CD11b/HLA-DR (Myeloid-derived suppressor cells, MDSCs) expression. We then proceeded to interrogate CTC phenotypic differences in the naïve vs relapsed setting as well as dynamic changes in longitudinal blood specimens from SCLC patients by evaluating markers that describe immune suppression activity (PD-L1) and EMT status (E-Cadherin, Vimentin, MUC1, Twist and Slug). Importantly, we show that with our approach we can track in real time therapeutic targets that are currently being tested in clinical trials or have been recently FDA approved (e.g. pYAP and DLL3) and found that MUC1 and pYAP are significantly increased in CTCs detected in blood specimens of SCLC relapsed patients. Our immune profiling showed an increase of MDSC percentages and a decrease in the CD4/CD8 T cell ratio in the relapsed setting. Finally, when we used PHENOSTAMP, a previously developed reference EMT map for assessing EMT phenotypes in lung cancer clinical specimens, we observed an increase of EMT heterogeneity in CTCs in relapsed patients. Our study highlights the translational power of our approach in utilizing CyTOF for longitudinally tracking CTCs directly in SCLC patient liquid biopsies towards assessing therapy response and resistance at a personalized level. Citation Format: Loukia G Karacosta, Sayantan Bhattacharyya, Allison Stewart, Ashley Victorian, Ester F Lujan, Shafqat Ehsan, Subin Kim, Alberto Duarte, Runsheng Wang, Benedict Anchang, Jing Wang, Lauren Byers. Leveraging mass cytometry for phenotyping CTCs in SCLC liquid biopsies: Tracking therapy resistance at a personalized level [abstract]. In: Proceedings of the AACR Special Conference: Liquid Biopsy: From Discovery to Clinical Implementation; 2024 Nov 13-16; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(21_Suppl):Abstract nr PR005.

Traffic Awareness-Based Target Wake Time Scheduling in 802.11ax WLANs

In recent years, the rapid growth of mobile communication has led to the continuous expansion of network scale, and the energy consumption of wireless communication has also increased rapidly. Under the high-density networking conditions, frequent communication activities greatly increase the energy consumption. In order to reduce channel competition, optimize resource scheduling and reduce equipment power consumption, the target wake-up time (TWT) mechanism in IEEE 802.11ax system plays an important role through timely scheduling and transmission. To improve channel efficiency for multi-user (MU) transmission and tackle with complicated traffic conditions, this paper presents a traffic awareness-based TWT scheduling scheme (TAT). The traffic is predicted and classified using a spatio-temporal series model for traffic-based TWT parameter generation. Subsequently, the time–frequency scheduling table is developed to adaptively assign Resource Units (RUs) and time slices to active STAs. Simulation results show that TAT can guarantee the Quality of Service (QoS) under dynamic changes in power service and delay requirements while reducing power consumption, effectively meeting the energy-saving demands in the intelligent access scenarios for power terminals.

Life-history of invasive common carp, Cyprinus carpio, within a natural lake (Groenvlei), South Africa

Common carp, Cyprinus carpio, is a global invasive species illegally introduced into the Groenvlei system, South Africa, in the 1990s for recreational angling. To manage this population effectively, basic information is needed on its biology including growth and reproduction. This study examined the growth trends of C. carpio using otolith growth zone deposition rates which were validated using a chemical mark–recapture experiment (n = 16). From a total of 140 C. carpio, length-at-age was best described using the Von Bertalanffy growth model for males and females. The average lengths-at-50% maturity were estimated at 314 mm F L (males) and 262 mm F L (females). Compared with other South African C. carpio populations, the Groenvlei population is relatively fast growing and long lived, with the oldest female aged 20 years and the oldest male aged 18 years, likely facilitated by relatively favourable environmental conditions at Groenvlei. Data from this study provide a baseline at the commencement of C. carpio management interventions at Groenvlei and an opportunity to monitor changes in population dynamics facilitated by these efforts.

“There is a Mental Resistance”: Experiences of Involving Refugee Parents in a Youth Trauma Recovery Program from the Perspective of Participating Youth, Parents and Facilitators

AbstractScalable light-touch programs that align with the Trauma-Focused Cognitive Behavioral Therapy (TF-CBT) approach is becoming an established intervention model for refugee youth with symptoms of post-traumatic stress. Teaching Recovery Techniques (TRT) is one example and, as TF-CBT guidelines state, parent sessions are included as the model relies on parents to provide support and instigate the techniques. In addition to traumatic stress, refugee families are often subjected to acculturative, isolation and resettlement stress. This study sought to understand how refugee parental involvement in TRT functions in practice and how it is perceived by participating youth, parents, and facilitators in Sweden. Thirty semi-structured interviews (11 youth, 8 parents, and 11 TRT facilitators) were conducted by phone or videoconference, transcribed, and analyzed using Thematic Network Analysis. A global theme ‘Parental engagement in trauma recovery requires dedicated attention’ emerged. Three organizing themes sat within this global theme: (i) Shifting roles when adapting differently to a new context; (ii) Tendency to keep parents at a distance; and (iii) Parent sessions don’t just happen. Whilst the potential for refugee parent involvement was recognized, a number of factors preventing their participation were identified. Cultural adaptations within TRT facilitators’ training are recommended, including: raising awareness about contextual factors and changes in family dynamics with regard to trauma and migration; adopting culturally responsive ways to present parental involvement to youth and parents; adding positive parenting skills; addressing parental mental health and readiness; and preparing facilitators to redirect parents to adequate services, when needed.

Transforming agricultural land into agrotourism area: Environmental, economic and socio-cultural perspectives

This study investigates the impacts of converting agricultural land into agrotourism areas on environmental, socio-cultural, and economic perspectives within Batukliang District, Central Lombok Regency, Indonesia. With a case study approach, this qualitative descriptive research employed interviews with three target groups: local farmers, residents, and tourism actors. The findings revealed seven key points identified as influences affecting the socio-cultural aspects of land change, including community impact, cultural preservation, cultural identity loss, community dynamics change, local cultural commercialization, cultural heritage loss, and traditional livelihoods. The results also unveiled nine financial impacts, 8 of which were associated with economic implications such as economic challenges, risk management, brand building, costs and investments, market access, increased revenue, and income diversity, which contribute positively to local economic development. The study concluded that integrating community involvement empowerment strategies, income diversification, sustainable farming promotion, and land-use regulation is crucial for developing a successful sustainable agrotourism destination.