Spatial Analysis Research Articles

Correction to: Estimation of industry-level productivity with cross-sectional dependence by using spatial analysis

Correction to: Estimation of industry-level productivity with cross-sectional dependence by using spatial analysis

Cutaneous T cell lymphoma atlas reveals malignant TH2 cells supported by a B cell-rich tumor microenvironment

AbstractCutaneous T cell lymphoma (CTCL) is a potentially fatal clonal malignancy of T cells primarily affecting the skin. The most common form of CTCL, mycosis fungoides, can be difficult to diagnose, resulting in treatment delay. We performed single-cell and spatial transcriptomics analysis of skin from patients with mycosis fungoides-type CTCL and an integrated comparative analysis with human skin cell atlas datasets from healthy and inflamed skin. We revealed the co-optation of T helper 2 (TH2) cell-immune gene programs by malignant CTCL cells and modeling of the tumor microenvironment to support their survival. We identified MHC-II+ fibroblasts and dendritic cells that can maintain TH2 cell-like tumor cells. CTCL tumor cells are spatially associated with B cells, forming tertiary lymphoid structure-like aggregates. Finally, we validated the enrichment of B cells in CTCL and its association with disease progression across three independent patient cohorts. Our findings provide diagnostic aids, potential biomarkers for disease staging and therapeutic strategies for CTCL.

Comparative and Spatial Transcriptome Analysis of Rhododendron decorum Franch. During the Flowering Period and Revelation of the Plant Defense Mechanism

Background: Rhododendron is a globally distributed and extensive genus, comprising over 1000 species. In the southwestern mountains of China, there exists a remarkable diversity of Rhododendron, with Yunnan Province alone harboring more than 600 species. R. decorum Franch. has long been utilized by local communities for its medicinal and edible properties. However, the transcriptional regulation function, medicinal properties, and edibility characteristics of R. decorum Franch. currently lack a solid theoretical basis. Methods: Total RNA was extracted from leaves, corollas and androecium/gynoecium of R. decorum Franch. in Heqing county, followed by the construction of cDNA libraries and the de novo assembly of transcriptomes. Results: A total of 63,050 unigenes were extracted from the flowers and leaf organs of R. decorum Franch. Among these unigenes, 43,517 were predicted to be coding sequences, with 32,690 being effectively annotated. Differential gene expression enrichment was observed among different organs within their respective transcriptomes; notably floral organs exhibited significant defense against plant diseases along with signal transduction functions. Furthermore, during the flower harvesting period, all floral organs exhibited gene enrichment pathways associated with carbohydrate metabolism. Additionally, the stamen and pistil displayed flavonoid metabolism pathways, suggesting their potential applications as functional food or medicine. Conclusions: Our results shed light on plant–pathogen defense mechanisms and the molecular bias of flavonoids biosynthesis on flower organs during the flowering period, which might help to understand the consumption of R. decorum Franch. corollas by the Bai nationality of Heqing county.

Hypercube Pooling for Visual Semantic Embedding

Visual Semantic Embedding ( VSE ) is a primary model for cross-modal retrieval, wherein the global feature aggregator is a crucial component of the VSE model. In recent research, the General Pooling Operator ( GPO ) aggregator, which weighs the features reconstructed from the local feature set to aggregate, facilitates the related models to achieve good retrieval performance. However, the reason for the effectiveness remains to be explored. To enhance the rationality of aggregator designs, we analyze the reason from the perspective of feature space. Indeed, for each data, the local feature set forms a hypercube containing abundant data information, and the feature learned by GPO measures the hypercube, thereby representing the data. The geometric structure of the hypercube implies that the set containing all points within the hypercube is a convex set, so the feature learned by weighted aggregation is an interior point of the hypercube. However, using the interior point to measure the hypercube leads to some problems in feature representation and model optimization, as well as the reduction of retrieval efficiency caused by weight computation. For example, the related pair’s features may be far, while the unrelated ones may be close. To measure the hypercube more clearly and alleviate the problems mentioned above, we propose Hypercube Pooling ( HCP ) aggregator. Specifically, HCP concatenates the Max and Min Pooling features as the global features. This aggregation method has multiple advantages, e.g., the learned global feature represents all hyperplanes of the hypercube that contain critical information and hypercube geometric structure. Moreover, HCP adds normalization-before-concatenation and reduces the usual setting of margin in the loss function by half to avoid gradient loss caused by the difference in the feature value and dimensionality doubling. The experimental results on the Flickr30K and MSCOCO datasets show that the HCP model has excellent performance with high efficiency, confirming the correctness of the spatial analysis and the effectiveness of the HCP aggregator.

Exploring Park and Ride: A Spatial Analysis of Transit Catchment in Outer Melbourne

Public transportation is essential for improving urban mobility, enhancing travel quality, reducing reliance on private vehicles, and alleviating traffic congestion. However, inadequate public transportation in outer Melbourne is a significant issue limiting urban development. While existing research primarily focuses on walking distance to define service catchments, commuters in transit-disadvantaged or outlying urban areas often drive to transit, noted as the park-and-ride mode. This research uniquely examines drive-distance catchments for park-and-ride transit accessibility in outer Melbourne, using spatial SQL and GIS techniques to provide a detailed, multi-dimensional analysis of population coverage, parking capacity, and accessibility gaps. This approach fills a gap in the existing literature by offering adaptable insights and approaches to other outer urban areas with transit disadvantages. The findings underscore the necessity for targeted enhancements in public transportation in outer Melbourne: Most of the outer residents concentrate near the train stations, though significant spatial gaps exist; The general accessibility status of residential mesh blocks is found; Parking capacity varies with high tension found at certain stations. This study contributes insights to create more equitable and sustainable transportation systems by providing a detailed spatial analysis of current transit coverage and identifying critical gaps.

Abstract C035: Spatially limited stroma-mediated resistance potentiates targeted therapy resistance through an integration of multiple juxtacrine and paracrine mechanisms

Abstract Despite the ability to induce strong clinical responses, therapies that target mutational drivers of oncogenic signaling are not curative in advanced cancers, as a subset of cancer cells is capable of surviving therapy and evolving resistance. While therapy resistance is commonly viewed as a cell-intrinsic phenomenon, multiple factors produced by tumors can also confer strong therapy resistance. In contrast to the detailed elucidation of molecular mediators of cell-intrinsic and stroma-mediated (SM) resistance, the relative importance of cell-intrinsic and SM resistance to in vivo therapeutic responses remains poorly defined. To address this gap of knowledge, we used a well-characterized experimental model of ALK+ lung cancer H3122 cell line that exemplifies a duality observed across common models of targetable cancers. Under standard stroma-free in vitro cultures, H3122 cells can survive under therapeutically relevant concentrations of ALK inhibitors (ALKi), eventually acquiring cell-intrinsic therapy resistance. At the same time, co-culture with stromal fibroblasts drastically reduces the sensitivity of H3122 cells to ALKi, indicating the relevance of SM resistance. To understand the impact of SM resistance on in vivo responses, we sought to identify the mechanism(s) responsible for the therapy-protective effects of stromal fibroblasts, subsequently interrogating the impact of the disruption of this mechanism on in vivo therapeutic responses. Our in vitro studies with a large panel of primary stromal fibroblast isolates identified the HGF-cMET axis as the major mechanism responsible for ALKi desensitization. Surprisingly, xenograft validation studies demonstrated a weak effect of HGF-cMET modulation. Histological analyses of tumor tissues revealed that this relative weakness is attributable to a strong, spatially limited HGF-independent component of SM resistance. Mechanistic follow-up demonstrated that the HGF-independent component of SM resistance integrates the effect of multiple well-known juxtacrine and paracrine-acting mechanisms. Whereas the multifactorial nature of stroma-mediated resistance prevented a clear assessment of its relative contribution to in vivo therapy responses, our spatial analyses indicate that SM resistance dominates the ability of tumors to avoid therapeutic elimination. Surprisingly, we found that SM resistance was also a substantial contributor to tumor relapse, indicating that in vivo therapy resistance can integrate both cell-intrinsic and cell-extrinsic effects. This duality of therapy resistance and the multifactorial underpinning of both cell-intrinsic and stroma-mediated resistance present a challenge to therapeutic strategies focused on identifying and targeting specific resistance mechanisms. Our studies suggest that this limitation can be overcome by shifting the therapeutic focus towards shared orthogonal therapeutic sensitivities of tumor cells within residual disease. Citation Format: Bina Desai, Tatiana Miti, Sandhya Prabhakaran, Daria Miroshnychenko, Menkara Henry, Viktoriya Marusyk, Chandler Gatenbee, Marilyn Bui, Jacob Scott, Philipp M. Altrock, Eric Haura, Alexander R.A. Anderson, David Basanta, Andriy Marusyk. Spatially limited stroma-mediated resistance potentiates targeted therapy resistance through an integration of multiple juxtacrine and paracrine mechanisms [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Tumor-body Interactions: The Roles of Micro- and Macroenvironment in Cancer; 2024 Nov 17-20; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2024;84(22_Suppl):Abstract nr C035.

Accurate, Fast, and Non-Destructive Net Charge Measurement of Levitated Nanoresonators Based on Maxwell Speed Distribution Law

Nanoscale resonant devices based on optical tweezers are widely used in the field of precision sensing. In the process of driving the nanoresonator based on the Coulomb force, the real-time, precise regulation of the charge carried by the charged resonator is essential for continuous manipulation. However, the accuracy of the existing charge measurement methods for levitated particles is low, and these methods cannot meet the needs of precision sensing. In this study, a novel net charge measurement protocol for levitated particles based on spatial speed statistics is proposed. High-precision mass measurement based on Maxwell’s rate distribution law is the basis for improving the accuracy of charge measurement, and accurate measurement of net charge can be achieved by periodic electric field driving. The error of net charge measurement is less than 7.3% when the pressure is above 0.1 mbar, while it can be less than 0.76% at 10 mbar. This proposed method features real-time, high-precision, non-destructive, and in situ measurement of the net charge of particles in the medium vacuum, which provides new solutions for practical problems in the fields of high-precision sensing and nano-metrology based on levitated photodynamics.

Abstract B044: Spatial transcriptomics reveals a distinct B cell signature in the dormant prostate cancer bone microenvironment

Abstract Background & Objective: Prostate cancer (PCa) cells frequently disseminate to bone where they can remain dormant for extended periods. The precise cellular and molecular mechanisms responsible remain largely unknown. The advent of spatial transcriptomics provides a unique opportunity to study key bone microenvironment-dormant PCa cell interactions in situ. Here, we developed a novel immunocompetent in vivo model of PCa dormancy in bone and employed the technology to address this major gap in knowledge. Methods: We established an in vitro protocol to induce dormancy in multiple PCa cell lines, including the C57BL/6 murine PCa cell line, RM1. Isogenic active and dormant PCA cells underwent bulk RNA Seq. We used an intra- iliac artery (IIA) approach to allow niche-specific seeding of dormant PCa within the bone. Spatial transcriptomics (10X Visium) was performed on tissue sections and R packages (Seurat & CellChat) were used for data analysis. Results: We validated in vitro PCa dormancy via cell cycle analysis, membrane dye retention and ERK/p38 ratio. RNASeq analysis of dormant PCa cells (vs. active) revealed upregulation of immunomodulatory genes such as, GDF15, BDNF, A2M, VGF, NLRP1, and CD55. C57BL/6 immunocompetent mice were inoculated with active or dormant RM1 cells via IIA. Majority of active RM1 mice reached endpoint within 15 days. In contrast, mice bearing dormant RM1 (D-RM1) had extended survival and were removed from study after 30 days. Histological analysis revealed solitary D-RM1 (panCK+/Ki67-/CC3-) on endosteal surfaces compared to macrometastases (high Ki67+) in the active RM1 group. Using IIA PBS injected tumor naïve bones as a control, we applied spatial transcriptomics (10X Visium) to interrogate the microenvironment surrounding active and dormant RM1 PCa cells. Bioinformatic analyses demonstrated higher expression of B cell markers (CD19, CD79a, CD79b, Ighm, and Pax5) and enhanced B cell activation/antigen phagocytosis signature in the D- RM1 group compared to other groups. We validated the presence of CD19 B-cells in proximity to the D-RM1 cells in subsequent tissue sections. In contrast, B cells were located less frequently and to the periphery of active RM1 metastases. Inference analysis using CellChat also identified a significant and distinct signaling pattern between CD55 and CD97 in the B cell enriched clusters in D-RM1 group. CD55/CD97 interaction is a noted mediator of B cell homing. These data suggest a potential role for distinct populations of B cells during the establishment of PCa dormancy in bone. Conclusion: Spatial transcriptomic analysis of the dormant PCa bone microenvironment reveals an enrichment of CD19+ B cells with a distinct signaling pattern. Given their known roles in immune tolerance we posit that infiltrating B cells may play a role in protecting and sustaining newly disseminated dormant PCa cells from immune mediated elimination. Citation Format: Mostafa M. Nasr, Ryan T. Bishop, Haley du Bois, Tao Li, Jeremy S. Frieling, Conor C. Lynch. Spatial transcriptomics reveals a distinct B cell signature in the dormant prostate cancer bone microenvironment [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Tumor-body Interactions: The Roles of Micro- and Macroenvironment in Cancer; 2024 Nov 17-20; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2024;84(22_Suppl):Abstract nr B044.

Abstract B038: Establishing a screening platform to identify key signaling molecules regulating cold tumor formation through immune evasion and exclusion

Abstract Many trial data have shown that cancer immunotherapy can successfully induce long lasting anti-cancer immune responses and increased the survival rate of cancer patients. One of the key challenges facing cancer immunotherapy is the low response rate of cancer patients to immunotherapy, suggesting that these cancer patients may have acquired resistance toward immunotherapy before treatments. Therefore, there is an unmet need for identifying the underlying mechanisms that promote resistance. One important hypothesis is that immune-excluded tumors (so called cold tumors) that lack of functional T cells have been often found in cancer patients who cannot respond well to cancer immunotherapy. To address this, we have successfully established a preclinical model for cold lung tumors, conducted RNA-seq, performed hallmark gene set enrichment analysis (GSEA) on cold tumor cells sorted in vivo, and identified several candidates associated with epithelial-mesenchymal transition, Wnt signaling, type I and II interferon (IFN) signaling, and p53 signaling. We hypothesize that their roles may either promote or inhibit the formation of cold tumors. One of the molecular candidates we identified, a molecule designated as IRC001, represents a crucial proof of concept for our experimental tumor model. We have unveiled a novel role for IRC001 in enhancing anti-tumor immunity, leading to the transformation of cold tumors into hot tumors and facilitating swift tumor regression through pathways reliant on T cells and type I IFN signaling. Our mechanistic studies have shown that IRC001 can trigger type I IFN signaling by engaging STING/TBK-1/IRF3-dependent pathways. To delve deeper into the spatial and molecular distinctions in mouse tumors (± IRC001), we initiated a preliminary study utilizing 10x Genomics/Visium to examine the spatial variations between these tumor types. Significantly, our spatial transcriptomic analysis revealed consistent immune-excluded and immune-enriched characteristics compared to traditional RNA sequencing methods. We conducted an analysis of TCGA datasets (The Cancer Genome Atlas) and observed that elevated IRC001 expression is associated with improved prognosis in SKCM (Skin Cutaneous Melanoma). Furthermore, our bioinformatics analysis revealed that melanoma patients exhibiting heightened IRC001 expression displayed positive responses to immune checkpoint blockade therapies. Therefore, we believe that our experimental tumor model can provide vital insights into the cold tumor microenvironment, shaping future therapeutic strategies, and pinpointing molecular candidates that can assist in selecting patients for successful immunotherapy. Citation Format: Yi-Ting Liao, Li-Mei Chen, Wen-Jye Lin. Establishing a screening platform to identify key signaling molecules regulating cold tumor formation through immune evasion and exclusion [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Tumor-body Interactions: The Roles of Micro- and Macroenvironment in Cancer; 2024 Nov 17-20; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2024;84(22_Suppl):Abstract nr B038.

Estimating ambient population density using physical features from GIS and machine learning: a study based on Japanese neighborhood

ABSTRACT This research aimed to develop an alternative method for estimating ambient population density at the neighborhood scale by utilizing a simple and universally available dataset. Physical environment data from GIS & OSM databases, basic statistics, and population density data from Mobile Spatial Statistics were combined to train tree-based Machine Learning models. The experiment resulted in an XGBoost model using 16 features capable of estimating ambient population density across three classes of outcome with 75.9% accuracy. The trained models were analyzed and visualized using SHAP and Partial Dependence Plot techniques to reveal feature importance and their threshold values. The study concludes that physical features can be effectively used as predictors of ambient population density and highlights areas for further investigation.

Abstract B008: Therapy-protective peristromal niches mediate positive ecological interaction between therapy-sensitive and therapy-resistant cells, altering the evolutionary dynamics of acquired targeted therapy resistance in lung cancers

Abstract Pharmacological inhibitors of oncogenic signaling, such as drugs that target ALK kinase (ALKi) in ALK+ lung cancers, can induce strong and durable clinical responses. However, targeted therapies are not curative in advanced cancers and even strong responders eventually develop resistance. While therapy resistance is typically attributed to cell-intrinsic (epi)mutational characteristics of tumor cells, it can also result from interactions of tumor cells with the tumor microenvironment (TME). In contrast to the detailed elucidation of the molecular mediators of therapy resistance, our knowledge of the evolutionary dynamics underlying the resistance emergence, including the impact of TME, remains poorly defined. A key open question in understanding the evolutionary dynamics of therapy resistance is whether relapse results from an expansion of pre-existing therapy-resistant subpopulations or from a bona fide gradual evolutionary process. To elucidate this question, we integrated experimental mouse studies with mathematical modeling, interrogating therapeutic responses of therapy-naïve experimental xenograft ALK+ tumors, spiked-in with differentially labeled resistant cells. We found that ALKi treatment induced a rapid expansion of resistant cells, which drastically reduced the magnitude and duration of remissions. Surprisingly, our in silico analyses pointed to the existence of a strong positive ecological interaction between therapy-resistant and therapy-sensitive competitors. Using a combination of spatial analyses, experimental studies, and mathematical modeling, we found that this interaction was mediated by peristromal niches that protected therapy-sensitive tumor cells. Specifically, by limiting tumor regression, the therapy- induced expansion of resistant cells limited the loss of protective peristromal niches, while the subsequent resumption of tumor growth created new peristromal niches capable of supporting the survival and proliferation of therapy-sensitive cells. While this niche-mediated interaction had only a marginal impact on the transition from remission to relapse, enhanced survival of therapy-sensitive cells potentiated their ability to adapt to ALKi, leading to a higher diversity of resistance phenotypes. In summary, our study has revealed a new type of indirect, niche-mediated ecological interaction between therapy-resistant and therapy-sensitive cells. The rapid expansion of rare pre-existent resistant cells and fast transition to relapse challenge a common assumption of the pre-existence of therapy resistance. Finally, our results highlight the essentiality of TME considerations in understanding the evolutionary dynamic underlying the development of therapy resistance. Citation Format: Mark Robertson-Tessi, Bina Desai, Tatiana Miti, Pragya Kumar, Sagnik Yarlagadda, Rishi Shah, Robert Vander Velde, Daria Miroshnychenko, David Basanta, Alexander Anderson, Andriy Marusyk. Therapy-protective peristromal niches mediate positive ecological interaction between therapy-sensitive and therapy-resistant cells, altering the evolutionary dynamics of acquired targeted therapy resistance in lung cancers [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Tumor-body Interactions: The Roles of Micro- and Macroenvironment in Cancer; 2024 Nov 17-20; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2024;84(22_Suppl):Abstract nr B008.

Abstract C039: The impact of antiangiogenic therapy on blood vessels and CD8 infiltration in renal cancer metastases is space, time, site, dose, and drug dependent

Abstract Clear cell renal cell carcinoma (ccRCC) is the most prevalent renal neoplasm, with bone as a major site for distant spread in 35% to 40% of the patients. These metastases are typically osteolytic, resistant to treatments, hence result in a variety of skeletal-related complications strongly contributing to mortality. A key feature of ccRCC is the loss of function of the von Hippel–Lindau (VHL) protein leading to extensive angiogenesis. Consequently, different anti-angiogenic tyrosine kinase inhibitors (TKIs) are used as the first or subsequent line of treatment for these patients as single agents or in combination with immune checkpoint inhibitors. However, limited data about their efficacy in bone metastasis is available, and their impact on the immune infiltrate, including effector CD8 cells, is unclear. We hypothesized that TKIs, by inhibiting angiogenesis, significantly reprogram the microenvironment and limit immune infiltration in space, time, dose, and drug dependent fashion. To test these hypotheses, we developed an immunocompetent mouse model of bone metastasis by orthotopical intratibial implantation of luciferase-GFP-positive mouse RENCA-VHL- cell line. Interestingly, intratibial injections gave rise to metastases in lungs, creating a unique opportunity to study two metastatic sites. Three different TKIs currently used in patients were tested and compared to control: axitinib (A), cabozantinib (C), and lenvantinib (L). Outcomes were monitored by macroscopic bioluminescence detection in vivo, 3D multiparametric spatial analysis of bones and lungs, in vivo, and ex vivo. Compared to control-treated mice, high doses of A, C, and L significantly reduced tumor progression in both tumor sites. Even though these TKIs are clinically considered equal, significant differences in their efficacy were noted. Spatial analysis of tumor cells and blood vessels showed a significant decrease in blood vessels formation in both an organ- and TKI-specific pattern over time. Additionally, the reduction of neo angiogenesis in treated tumors directly limited the infiltration of CD8 cells, which localized at the interface with tumor free bone/lung tissue. Interestingly, TKI dose reduction significantly improved CD8 infiltration, while controlling tumor size. TKI withdrawal, instead, led to rapid progression of tumor in both sites and significantly shortened mice survival. In conclusion, we established bone and lung metastatic models of ccRCC and characterized and compared the effects of three antiangiogenic TKIs on angiogenesis and CD8 infiltration. TKIs reduced tumor growth and progression, because of blood vessel formation inhibition. Furthermore, TKI treatment reduced the infiltration of effector T cells in tumors in a dose-dependent manner, an outcome that can have a major impact when TKIs are combined with immunotherapy, a preferential therapeutic regimen for ccRCC patients. Overall, we believe our studies provide important insights and efficacy predictions for innovative therapeutic applications in ccRCC bone metastatic patients. Citation Format: Stefan Maksimovic, Nina Costanza Boscolo, Ludovica La Posta, Matthew T. Campbell, Eleonora Dondossola. The impact of antiangiogenic therapy on blood vessels and CD8 infiltration in renal cancer metastases is space, time, site, dose, and drug dependent [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Tumor-body Interactions: The Roles of Micro- and Macroenvironment in Cancer; 2024 Nov 17-20; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2024;84(22_Suppl):Abstract nr C039.

Advanced single-cell and spatial analysis with high-multiplex characterization of circulating tumor cells and tumor tissue in prostate cancer: Unveiling resistance mechanisms with the CoDuCo in situ assay.

Metastatic prostate cancer is a highly heterogeneous and dynamic disease and practicable tools for patient stratification and resistance monitoring are urgently needed. Liquid biopsy analysis of circulating tumor cells (CTCs) and circulating tumor DNA are promising, however, comprehensive testing is essential due to diverse mechanisms of resistance. Previously, we demonstrated the utility of mRNA-based in situ padlock probe hybridization for characterizing CTCs. We have developed a novel combinatorial dual-color (CoDuCo) assay for in situ mRNA detection, with enhanced multiplexing capacity, enabling the simultaneous analysis of up to 15 distinct markers. This approach was applied to CTCs, corresponding tumor tissue, cancer cell lines, and peripheral blood mononuclear cells for single-cell and spatial gene expression analysis. Using supervised machine learning, we trained a random forest classifier to identify CTCs. Image analysis and visualization of results was performed using open-source Python libraries, CellProfiler, and TissUUmaps. Our study presents data from multiple prostate cancer patients, demonstrating the CoDuCo assay's ability to visualize diverse resistance mechanisms, such as neuroendocrine differentiation markers (SYP, CHGA, NCAM1) and AR-V7 expression. In addition, druggable targets and predictive markers (PSMA, DLL3, SLFN11) were detected in CTCs and formalin-fixed, paraffin-embedded tissue. The machine learning-based CTC classification achieved high performance, with a recall of 0.76 and a specificity of 0.99. The combination of high multiplex capacity and microscopy-based single-cell analysis is a unique and powerful feature of the CoDuCo in situ assay. This synergy enables the simultaneous identification and characterization of CTCs with epithelial, epithelial-mesenchymal, and neuroendocrine phenotypes, the detection of CTC clusters, the visualization of CTC heterogeneity, as well as the spatial investigation of tumor tissue. This assay holds significant potential as a tool for monitoring dynamic molecular changes associated with drug response and resistance in prostate cancer.

The High-Resolution Archaeology of Shared Courtyards at Old Dongola (14th–16th Century a.d., Sudan): an Intensive Approach to Domestic Open Spaces

ABSTRACT Identifying the dynamics of domestic open spaces remains a challenging task. This research applies an adjusted theoretical framework of activity areas to characterize domestic open spaces in the 14th–16th century a.d. in Old Dongola, Sudan. Activity areas were defined as sedimentations of residues of recurring cycles of changing actions rather than stable components of space. To identify domestic space, this research utilizes high-resolution methods: analyses of multiple chemical elements, spatial distribution of objects, and botanical remains of courtyard occupational surfaces, combined with spatial statistics using local Moran’s I autocorrelation. The relationships between the remains of human and non-human actions are discussed in terms of the material affordances affecting their deposition within the archaeological layers. Application of these methods allowed for the identification of areas of domestic tasks related to high concentrations of elements, as well as clusters of tools located on their edges. Botanical data corroborated often vague identifications of activities based on geochemistry.

Exploring the Path of Balanced Development: The Decoupling Evaluation of Agricultural Production Efficiency and Land Carrying Capacity

ABSTRACTHigh‐quality development in agriculture is crucial for maintaining the harmonious balance between human society and the natural environment, and promoting this development model is one of the key measures to alleviate land degradation issues. This study, grounded in the PRED theory (Population, Resources, Environment, and Development theory) framework, establishes an evaluation system for high‐quality agricultural development by selecting 128 cities within the Yangtze River Economic Belt as its samples. It quantifies land carrying capacity, utilizes the Stochastic Frontier Analysis (SFA) model to assess agricultural production efficiency, and applies the Tapio decoupling model to analyze the interplay between these two factors. The results reveal that the land resource carrying index has risen from 1.245 to 1.70, indicating an escalating tension between population and food resources. Furthermore, agricultural production efficiency has seen a 16.56% increase, reflecting positive advancements in agricultural production across the region. Spatial distribution analysis shows that the standard deviation ellipse is concentrated in the mid and lower reaches, centered in Changde, Hunan, and expanding westward, with a broader coverage area and perimeter. Additionally, the decoupling relationship between land carrying capacity and agricultural production efficiency primarily manifests in three forms: strong negative decoupling, weak decoupling, and expansive negative decoupling. This research offers significant insights for effectively mitigating the strain between population growth and resource‐environmental carrying capacity.

Spatial and Temporal Analysis of Severe Dust Storm in Iraq in May 2022

Dust storms are a common ecological occurrence in many world‘s countries, mainly in dry and semi-dry parts. Dust storms tremendously influence human health, the environment, the climate, and numerous social aspects. In this paper, spatial and temporal analysis, metrological triggers, and trajectory, dust exporting areas of a severe dust storm that occurred in Iraq on May 16, 2022, were investigated. The dust storm's backward trajectory was determined using HYSPLIT model, which is then compared with MODIS and Meteosat satellite images. The weather is then analyzed using the NCEP/NCAR Reanalysis model, and the approximate area of these sources was determined using Landsat 8 satellite image classification method. The results revealed that the HYSPLIT model trajectory of the dust storm agreed with MODIS and Meteosat satellite visuals. The primary dust storm sources and their areas are identified. The first source is from the shared border region between Syria (Rif-Dimasshq) and Jordan (north of Al-Ruwaished), with an area of about 775 km2. The second is from the northwestern regions of Iraq, specifically north of Anbar and south of Nineveh, with an area of about 905 km2.

Leveraging GIS for sustainable tourism development: A comprehensive spatial approach

Abstract. This paper explores the application of Geographic Information Systems (GIS) as a pivotal tool in the spatial analysis and sustainable development of tourism. By mapping tourism resources, analyzing visitor flows, and planning for accessibility and infrastructure, GIS enables a nuanced understanding and management of tourism's spatial dynamics. We delve into the innovative use of GIS for personalized itinerary planning, augmented reality experiences, safety, risk management, environmental impact assessments, resource management, conservation, stakeholder engagement, and community planning. Through a series of methodical processes, GIS facilitates the visualization of natural and cultural attractions, optimizes visitor experiences, and ensures the sustainability of tourism development. The integration of spatial data with advanced analytical tools supports the creation of dynamic, inclusive, and environmentally responsible tourism strategies. This paper highlights the critical role of GIS in shaping future tourism practices, underlining the importance of spatial analysis in fostering a balanced approach to tourism that benefits local communities, preserves cultural heritage, and minimizes ecological footprints.

Radiocarbon chronology and settlement patterns in the Bronze Age of the Qaidam Basin, Northwestern China.

Prehistoric settlement patterns on the Tibetan Plateau, particularly in the Qaidam Basin, have drawn significant scholarly interest. Yet, limited data have hindered a comprehensive understanding the Bronze Age chronology and landscape exploitation in this region. This paper presents 24 newly obtained radiocarbon dates from eight archaeological sites within the Qaidam Basin on the Tibetan Plateau. Integrated with existing 14C data and spatial analysis, these findings reveal an overall continuous occupation of the basin from ca. 3600-2500 calBP, with a gradual shift from expansive lowland settlements to smaller, ephemeral high-altitude structures, identified around 3350 calBP. This change is consistent with demonstrated periods of climate degradation which likely drove strategic adaptations in landscape management and subsistence methods. Overall, this research not only establishes a more robust chronology for the Qaidam Basin's Bronze Age, but also advances the discussion on human-environment interactions in high-altitude areas during late prehistory.

Mapping and assessing the future provision of lake ecosystem services in Lithuania

Lakes supply multiple ecosystem services (ES), key to supporting socio-ecologic systems and human well-being. In the context of future land use and climate changes, it is imperative to anticipate potential impacts on lake ES supply. Hence, studies that deal with future lake ES, such as mapping, are lacking. In this work, we mapped and assessed the future supply of three ES: (1) maintenance of nursery conditions (nursery ES), (2) maintenance of chemical conditions of freshwaters (nutrient regulation ES), and (3) direct and indirect cultural outputs (recreation ES) in Lithuania. Four future scenarios were utilised, integrating land use and climate changes: A0 - business as usual; A1-urbanisation; A2: land abandonment and afforestation; and A3 - agricultural intensification. The projected year was 2050, following the intermediate Representative Concentration Pathway (RCP 4.5). The future scenarios were simulated using the open-source software Dinamica EGO based on a 6-step modelling framework. Statistical differences among the scenarios and ES were analysed by applying a Kruskal-Wallis ANOVA test. Spatial analysis was done by performing a Moran's I and Getis-Ord (Gi∗) hotspot analysis. The results showed significant differences in nursery and nutrient regulation ES. The highest supply in nursery ES was observed for the A0 scenario. For nutrient regulation ES, the lowest ES supply was identified for the A1 scenario and for recreation ES, the highest was found in the A2 scenario. The eastern and northeastern regions of Lithuania showed a high ES supply. Hot spots were only identified in the eastern region. These regions are associated with a high area covered by forests and protected areas. The central region shows a low ES supply, identified as a cold spot where the agricultural landscape dominates. The results of the PCA analysis revealed an association between nursery and recreation ES. Nutrient regulation was not associated with the other two ES. Mapping and assessing the impact of future scenarios is vital to anticipating the potential dynamics of lake ES, especially in the context of climate change. This information is essential in the context of environmental management, helping decision-makers to ensure a sustainable ES supply and contributing to human wellbeing.

Determining the Optimal Fire Station Locations in Baghdad Al-Rusafa Using GIS Models and Data

The study of sitology has a long historical background and has recently attracted the attention of many researchers. One of its most important branches is the location of fire stations, which are of great importance in major cities. One of the most important features of an appropriate location is increasing coverage and reducing access time. In this research, geographic information systems were used to choose the most appropriate sites on the Al-Rasafa side in the city of Baghdad/Iraq to facilitate access to the scene of the accident as soon as possible from the fire stations and through the use of the geographical database of the city of Baghdad. GIS analysis was used to build the mathematical model that was adopted based on a number of criteria, including land use, distance to commercial malls, government and educational institutions, hospitals, and distance from existing fire stations. A weight was given to each of these criteria using the Overlay Weighted tool from spatial analysis in geographic information systems to determine the most appropriate areas. Then the road network was added to the criteria used, and then the selection was made on the areas close to the main roads, so the search results were to determine the best sites in Al-Karrada, Al-Sadr City, and Al-Adhamiya.