Activation Analysis Research Articles

Essential and toxic elements determination in Ampelodesma mauritanicum plant based on gamma-ray spectrometry

Due to the scarcity of data on both basic and toxic chemical elements in medicinal and fodder plants in Algeria, this study focused on evaluating the content of these elements in the Ampelodesma mauritanicum plant grown in the Ghardaia region of Southern Algeria. This plant is commonly used by Bedouins in traditional medicine and as fodder, and has applications in construction, decontamination, and water purification. Based on gamma-ray spectrometry for neutron activation analysis, the study identified and categorized a total of 25 mineral and trace elements into essential, non-essential, and potentially toxic groups. Essential elements exhibited varying concentrations, with potassium being the most abundant, followed by sodium, calcium, iron, zinc, chromium, cobalt, and selenium. The study also assessed potentially toxic elements, all found below the estimated permissible limits established by FAO/WHO. Quality control was ensured through the analysis of certified reference materials. The findings provide valuable insights into the elemental composition of Ampelodesma mauritanicum, offering significant implications for medicinal and nutritional applications while ensuring analytical accuracy and reliability.

Petrographic and geochemical analyses of pottery from Wadi Tanuf, Oman: Approaching pottery production in south‐eastern Arabia during the second and first millennia BCE

AbstractThis study describes the petrographic and geochemical characteristics of pottery collected from Mugharat al‐Kahf and WTN02 in Wadi Tanuf, north‐central Oman, to clarify interregional similarities and differences in pottery production techniques and examine the existence of interregional trade in pottery with respect to changes in mobile communities. Potsherds from these sites were characterised using thin‐section petrography and instrumental neutron activation analysis. Results revealed that several clay fabrics and tempers were used during the Wadi Suq period (2000–1600 BCE). A region‐wide similarity exists in pottery‐making techniques in terms of the tempering of specific minerals (Oman ophiolite) used in the Early Iron Age (1300–300 BCE). Geochemical results indicate differences in clay sources between the Wadi Suq period and the Early Iron Age in Wadi Tanuf and the unlikelihood of the interregional trade of domestic pottery.

Correlation between nutrients, rare earth elements and heavy metals in O. Sativa rice plant organs by instrumentation neutron activation analysis and proton induced x-ray emission techniques

The accumulation of halogens and metals from roots to stems, leaves and grains of Oryza sativa rice plant collected in Northern Senegal (St Louis region) at the same stages of growth but at different salinity soil levels was investigated by measuring their elemental concentration by invasive instrumental techniques of neutron activation analysis and proton induced x-ray emission. The normalized elemental concentration of Na, Cl, K, (Cs, Rb, Sr, Sb, Ba Ca, Sc, Ti, V, Cr, Mn, Fe, Co, Cu, Zn, As, Se, Br, Rb, Sb was correlated with one of rare earth elements, La, Ce, Sm, Yb, Nd, Eu, Tb, Tm, and Lu) and the one of the heavy metals Hf, Ta and Th and to assess their subsequent distribution within the Oryza sativa rice plant in a particular salinity environment. The exploration of the experimental data was performed by applying machine learning techniques with Python to find their elemental correlations. This study shows that the accumulation of iron is highly correlated with the amount of rare earth elements and heavy metals investigated. We observe an inverse correlation between Fe and Cl concentrations in the roots and stems of the Oryza sativa rice plant, in which higher levels of Fe in the roots relative to stems correspond to lower levels of Cl. We also remark that there is no accumulation of rare earth elements in the root tissues of the different Oryza sativa rice plants studied. Whereas, in the stem, leaf, and grain organs there is a strong correlation between metal contents and rare earth elements.

Capture enhanced neutron irradiation for the treatment of the Alzheimer Disease: Micro-nanodosimetric characterization of beta amyloid peptide samples

Alzheimer Disease (AD) is the most common cause of dementia. 46.8 million people live with AD worldwide, with numbers projected to almost double every 20 years. The etiological mechanisms underlying the neuropathological changes in AD remain unclear. The beta amyloid peptide Aβ is considered to be the main culprit of the pathological processes. NECTAR (NEutron Capture-enhanced Treatment of neurotoxic Amyloid aggRegates) project proposes an alternative and revolutionary strategy to address AD, investigating the safety, feasibility and effectiveness of a Capture-Enhanced Neutron Irradiation to structurally damage Aβ aggregates, by exploiting capture agent vectors containing B-10 and Gd-157.Among many others, one of the goals of the project is to perform calculations and measurements of microdosimetric and nanodosimetric quantities to characterize the effect of reaction products at local level and to link it to the fibrils depolymerization process. In this framework, a new low-pressure tissue-equivalent proportional counter (TEPC) was designed and developed. The system is a wall-free TEPC able to measure micro-nanometric dose deposition for different biological samples. It is characterized by two main features: i) a wall-less structure allows the charged particles produced by the sample to access the sensitive volume, where their effects are studied; ii) a trigger system enables the assessment of the number of ionizations induced in the sensitive volume related to a single primary particle for obtaining nandosimetric information.The prototype system was tested in the PGNAA (Prompt Gamma Neutron Activation Analysis) facility of the LENA reactor (Pavia) to directly study secondary particles from Aβ fibrils, loaded with Boron. Results of the micro-nanodosimetric characterization of high LET secondaries from Aβ-fibrils were compared to a reference Boron sample. For a 500 nm simulated site size, the presence of Boron in the Aβ sample greatly populates microdosimetric spectra at high lineal energy values. Instead, lower LET particles (photons, protons) from reactions on the other Aβ aggregate solution molecules populate the low lineal energy portion of the distribution.The nanodosimetric distributions highlights the presence of different field components on the nanodosimetric spectra: low LET particles (protons/electrons) produce small ionization clusters, while alpha and Lithium ions induce larger clusters, thus have a higher biological effect. The nanodosimetric measurements have been compared with Monte Carlo simulations performed with a track-structure code, showing a good agreement.This multi-level approach provides a deeper physical understanding of the mixed secondaries field coming from B-enriched target, as well as a reference for the biological effect on Aβ fibrils at nanometer level. These preliminary measurements represent the first microdosimetric and nanodosimetric characterization of the secondary mixed field directly emitted by a biological sample irradiated with neutrons.

Bioconcentration and translocation of elements from soil to vegetables and associated health risk

This study provides valuable insights into the bio-concentration and translocation of elements from soil to plants, addressing potential health risks associated by the neutron activation analysis. The results showed that arsenic (As) and Zinc (Zn) concentrations in the soil were higher than national regulations for heavy metals in agricultural soil in Vietnam but remained within permissible limits recommended by the World Health Organization (WHO). Different plant species show varying affinities for the accumulation of elements, indicating their potential use for specific remediation purposes. Rainbow beet (Beta vulgaris) were considered for phytoextraction of cesium (Cs), chromium (Cr), and aluminum (Al). Bioconcentration factors (BCF) for both root and shoot tissues for all elements were lower than unity (except manganese (Mn 1.04)). This suggests that green lollo rossa has the potential to accumulate Mn in its root system. The target hazard quotient ranged from 0.01 for antimony (Sb) to 0.26 for chromium (Cr). This study indicated that the vegetables investigated in the study area do not pose a risk to consumers for the analyzed potential toxic elements.

JAK/STAT signaling in rheumatoid arthritis leukocytes is uncoupled from serum cytokines in a subset of patients

ObjectiveRheumatoid Arthritis (RA) is a systemic autoimmune disease involving pro-inflammatory cytokines that can be therapeutically targeted by antibodies or kinase inhibitors. Nevertheless, these drugs fail in a subset of patients independent of the abundance of the targeted cytokines. We aim to explore the cellular basis of this phenomenon by analyzing the relation of cytokine abundance and activation of downstream signaling pathways in RA. MethodsThe study included 62 RA patients and 9 healthy controls (HC). Phosphorylation of STAT 1–6 in various immune cell subsets was determined ex vivo using a novel robust flow cytometry-based protocol. Serum concentrations of IL-6, IL-10, IL-12p70, IL-17 A, interferon gamma, and TNF-alpha in the same samples were measured using highly sensitive single molecule array (SIMOA). ResultsWe found an increase in circulating cytokines in RA patients, while STAT activity was lower in RA patients compared to HC. Based on STAT activity we determined three endotypes in active RA patients (cDAI>10, n = 28): 1) those with active STAT5a/b signaling in T cells (n = 7/28), 2) those with a low STAT activity in all assessed cell types (n = 14/28), and 3) those with active STAT1 and STAT3 signaling mainly in myeloid cells (n = 7/28). Integrating intracellular STAT activation and cytokine analysis revealed diminished JAK/STAT signaling in a subset of patients (n = 8/20) despite elevated serum cytokine concentrations. ConclusionDiminished JAK/STAT signaling in active RA may partly explain unresponsiveness to therapy targeting cytokine signaling. Analysis of JAK/STAT phosphorylation may identify patients at risk for non-response to these therapies.

Effect of propofol and isoflurane on NK Cells: A pilot study on perioperative breast cancer patients from Eastern India

Introduction: In onco-anesthesiology, the selection between intravenous and volatile anesthetics for maintaining NK cell response during cancer surgery has been an ambiguous area. In the absence of any such comparative Indian report, this pilot study aimed to investigate the effect of intravenous anesthetic, Propofol, and volatile anesthetic, Isoflurane on the NK cell-mediated immune-inflammatory response of perioperative breast cancer patients. Materials and Methods: Treatment naive breast cancer patients (N, 50) selected for surgery were randomly subjected to either Isoflurane (N, 25) or Propofol (N, 25) anesthetic group. The peripheral blood samples were collected 1 day before surgery (Pre), 1 h after incision (Intra) and 48 h after surgery (Post). The blood samples were subjected to immunophenotyping, activation, degranulation, and cytokine analysis. Results: The frequency of NK cell populations did not differ between the Isoflurane and Propofol groups irrespective of cancer stage II/III. NK cell degranulation marker CD107a and activation marker CD335 expression were significantly reduced in the postoperative period compared to the preoperative group in the Isoflurane group but Propofol did not inflict such alterations. Both Isoflurane/Propofol elicited similar trends in the cytokine profiles of interleukin (IL)-6, IL-15, interferon (IFN)-g and transforming growth factor (TGF)-β levels. Isoflurane significantly increased IL-8 during the intraoperative period and matrix metalloproteinase (MMP)-9 during the postoperative period whereas no such changes were observed with Propofol. Conclusion: This pilot study indicated that Propofol partially proved better over Isoflurane in maintaining the activation (CD335) and degranulation of NK cells (CD107a) and alleviating inflammation (IL-8 and MMP-9) during the perioperative period in the breast cancer patients.

Passive high explosive neutron inspection (PHENIX): a new method to confirm the presence or absence of high explosives for nuclear treaty verification

Advanced instruments and methods need to be developed now to create a technical basis to support the negotiation of future nuclear arms control treaties. One new capability that is anticipated is the ability to confirm either the declared presence or declared absence of high explosive (HE) material in the presence of special nuclear material (SNM). Towards this goal, Passive HE Neutron Inspection (PHENIX) has been developed and demonstrated as a method for confirming the presence or absence of HE in the presence of plutonium. The method exploits the inherent presence of neutrons associated with the decay of plutonium as an internal probe source for performing prompt gamma-ray neutron activation analysis (PGNAA), searching for the presence of HE as revealed by the emission of characteristic gamma rays following neutron absorption in hydrogen and nitrogen which are building blocks of present-day, military-grade HE. Tests using stoichiometrically-correct hemishells of mock HE with plutonium show that a system can be expected to positively confirm the presence or absence of these signatures, supporting determination of HE presence or absence with Pu, in a few hours. To protect other potentially sensitive gamma-ray signatures from a treaty accountable item, an analog information barrier has been conceptualized and tested which physically prevents the collection of gamma-ray spectral data outside of user selected energy windows strategically chosen to view only narrow spectral regions corresponding to the hydrogen (2223.2 keV) and nitrogen (9807.2 keV, 10,318.2 keV, and 10,829.2 keV) PGNAA signatures.

Numerical solution of a parameter estimation problem arising in Prompt-Gamma Neutron Activation Analysis

We study a parameter estimation problem which arises from measurements with QUANTOM, a measurement facility utilizing Prompt-Gamma Neutron Activation Analysis (PGNAA) to analyze elemental masses in 200-l nuclear waste drums. The presence of neutron flux measurements in QUANTOM offers additional information for elemental composition reconstruction, motivating an alternative to the standard iterative approach. Therefore, the measurement is modelled using approximate models for neutron and photon transport. We introduce a mathematical formulation for solving the resulting parameter estimation problem of QUANTOM measurements and employ an adjoint-based method to determine the elemental composition. Uniqueness of solutions in this context is studied, and the results offer novel insights for PGNAA applications.

Determination of strategic metals in graphitic formations by the methods of neutron activation analysis with a californium source

Determination of strategic metals in graphitic formations by the methods of neutron activation analysis with a californium source

Advancing 2D reaction rate measurements in BNCT: Validation of the indirect neutron radiography method

The precise characterization of neutron beams is a cornerstone of Boron Neutron Capture Therapy (BNCT). While Instrumental Neutron Activation Analysis (INAA) is the standard technique for neutron flux measurement, it is limited in its ability to capture two-dimensional (2D) reaction rate distributions. This study aims to validate the Indirect Neutron Radiography (INR) method for 2D reaction rate quantification, addressing critical variables such as temperature sensitivity and signal fading. We designed and constructed an optimized INR platform comprising an Imaging Plate (IP), readout device, activation detectors (copper foils), and real-time temperature monitoring. Comprehensive experiments were conducted to investigate the impact of ambient temperature and fading time on IP signal reliability. A robust calibration curve was formulated, linking IP signals to dose deposition metrics, thereby enabling precise reaction rate assessments. The study found that IP signals are minimally sensitive to temperature variations (less than 0.1% change per 1 °C), but are subjected to linear fading over time, necessitating stringent temperature control and time-dependent signal corrections. A mathematical relationship between IP signals and dose deposition was established, represented by Y = 20,500 × x0.01803-21103. Application of the INR method revealed that the depth-dependent reaction rates in copper strips closely aligned with those acquired through INAA, exhibiting a relative deviation of less than 5% within a 4cm depth range inside the phantom. Our findings demonstrate that the INR method offers a robust alternative to traditional INAA for capturing 2D reaction rates, effectively addressing complexities like temperature sensitivity and signal fading. While challenges persist, particularly in the realm of measurement errors, this study lays the groundwork for further methodological refinements and broadens the scope for future research in BNCT neutron beam characterization.

Pathway Activation Analysis for Pan-Cancer Personalized Characterization Based on Riemannian Manifold.

The pathogenesis of carcinoma is believed to come from the combined effect of polygenic variation, and the initiation and progression of malignant tumors are closely related to the dysregulation of biological pathways. Quantifying the alteration in pathway activation and identifying coordinated patterns of pathway dysfunction are the imperative part of understanding the malignancy process and distinguishing different tumor stages or clinical outcomes of individual patients. In this study, we have conducted in silico pathway activation analysis using Riemannian manifold (RiePath) toward pan-cancer personalized characterization, which is the first attempt to apply the Riemannian manifold theory to measure the extent of pathway dysregulation in individual patient on the tangent space of the Riemannian manifold. RiePath effectively integrates pathway and gene expression information, not only generating a relatively low-dimensional and biologically relevant representation, but also identifying a robust panel of biologically meaningful pathway signatures as biomarkers. The pan-cancer analysis across 16 cancer types reveals the capability of RiePath to evaluate pathway activation accurately and identify clinical outcome-related pathways. We believe that RiePath has the potential to provide new prospects in understanding the molecular mechanisms of complex diseases and may find broader applications in predicting biomarkers for other intricate diseases.

Seasonal and interannual variability of heavy metals and other microelements in wild and farmed mussels Mytilus galloprovincialis in Saldanha Bay (South Africa)

The temporal fluctuations of the levels of 21 of macro- and microelements including heavy metals in soft tissues and shells of mussels from waters of Saldanha Bay (South Africa) collected in the period of 2013–2019 were analyzed by using Neutron activation analysis. The wild and farmed sets of Mytilus galloprovincialis were selected from the bays with different hydrological conditions: from open ocean bay to the relatively closed site. It was concluded that the found features of elements’ distribution could be explained by hydrological regimes, influence of the coastal runoffs and mixing of waters, which led to higher levels of heavy metals and microelements. The farmed mussels demonstrated lower maxima for many elements during the study period but could show local increasing due to intense hydrological mixing with resuspending of bottom sediments and terrigenous runoff indicated by the non-volatile elements such as Sc, Cs, Th. The obtained data were not revealed high anthropogenic influence during studied period in comparison with the other water areas. The study proposed the indicative background levels for the heavy metals and other determined elements in the Saldanha Bay area based on the maximum values from the pristine water area obtained in the considered period.

Clinicopathologic Heterogeneity and Glial Activation Patterns in Alzheimer Disease.

Factors associated with clinical heterogeneity in Alzheimer disease (AD) lay along a continuum hypothesized to associate with tangle distribution and are relevant for understanding glial activation considerations in therapeutic advancement. To examine clinicopathologic and neuroimaging characteristics of disease heterogeneity in AD along a quantitative continuum using the corticolimbic index (CLix) to account for individuality of spatially distributed tangles found at autopsy. This cross-sectional study was a retrospective medical record review performed on the Florida Autopsied Multiethnic (FLAME) cohort accessioned from 1991 to 2020. Data were analyzed from December 2022 to December 2023. Structural magnetic resonance imaging (MRI) and tau positron emission tomography (PET) were evaluated in an independent neuroimaging group. The FLAME cohort includes 2809 autopsied individuals; included in this study were neuropathologically diagnosed AD cases (FLAME-AD). A digital pathology subgroup of FLAME-AD cases was derived for glial activation analyses. Clinicopathologic factors of heterogeneity that inform patient history and neuropathologic evaluation of AD; CLix score (lower, relative cortical predominance/hippocampal sparing vs higher, relative cortical sparing/limbic predominant cases); neuroimaging measures (ie, structural MRI and tau-PET). Of the 2809 autopsied individuals in the FLAME cohort, 1361 neuropathologically diagnosed AD cases were evaluated. A digital pathology subgroup included 60 FLAME-AD cases. The independent neuroimaging group included 93 cases. Among the 1361 FLAME-AD cases, 633 were male (47%; median [range] age at death, 81 [54-96] years) and 728 were female (53%; median [range] age at death, 81 [53-102] years). A younger symptomatic onset (Spearman ρ = 0.39, P < .001) and faster decline on the Mini-Mental State Examination (Spearman ρ = 0.27; P < .001) correlated with a lower CLix score in FLAME-AD series. Cases with a nonamnestic syndrome had lower CLix scores (median [IQR], 13 [9-18]) vs not (median [IQR], 21 [15-27]; P < .001). Hippocampal MRI volume (Spearman ρ = -0.45; P < .001) and flortaucipir tau-PET uptake in posterior cingulate and precuneus cortex (Spearman ρ = -0.74; P < .001) inversely correlated with CLix score. Although AD cases with a CLix score less than 10 had higher cortical tangle count, we found lower percentage of CD68-activated microglia/macrophage burden (median [IQR], 0.46% [0.32%-0.75%]) compared with cases with a CLix score of 10 to 30 (median [IQR], 0.75% [0.51%-0.98%]) and on par with a CLix score of 30 or greater (median [IQR], 0.40% [0.32%-0.57%]; P = .02). Findings show that AD heterogeneity exists along a continuum of corticolimbic tangle distribution. Reduced CD68 burden may signify an underappreciated association between tau accumulation and microglia/macrophages activation that should be considered in personalized therapy for immune dysregulation.

Fingerprinting Ceramics from the Chalcolithic Santa Vitória Enclosure (SW Iberia)

The Santa Vitória Chalcolithic site (southern Portugal) prompts several questions related to the provenance and production technology of artefacts. Archaeological ceramics from two sections of Ditch 1 of the Santa Vitória site were studied by neutron activation analysis and X-ray diffraction for the first time, with the main goal of contributing to the contextualization of the artefacts and better understanding their production processes/technologies and the provenance of raw materials. The results point to a local production of ceramics, since their mineral phases reflect the geological contexts around the archaeological site. The mineralogical assemblage indicates a firing temperature below 850 °C. Iron is the better discriminator of ceramics from both sections, which could be related to the addition of different proportions of temper grains during the ceramics’ production. Although trace elements do not serve as discriminating geochemical indicators for the analyzed samples, they do imply a slightly higher heterogeneity in the composition of the ceramic paste from section 2. The negative Eu anomaly found in two samples is in accordance with the lower contents of Na2O, related to plagioclase weathering. Detailed studies on ceramics and potential raw materials are foreseen to assist in discussing the role of this Chalcolithic archaeological site at a regional level.

Mosses as bioindicators of air pollution with potentially toxic elements in the Burabay State National Natural Park, Kazakhstan.

The Burabay State National Natural Park is a national park of the great natural and historical values located in the north of Kazakhstan, which has been exposed in recent years to significant anthropogenic impact. The moss biomonitoring was performed in the Borovoye resort community, an important tourist destination in the national park, to identify the level of air pollution. Mosses collected at 29 locations were subjected to neutron activation analysis to determine 36 elements and additionally to ICP-OES to detect the level of Cu and Pb. Factor analysis was applied to check if there are any associations between identified elements and to link them with possible emission sources. According to contamination factor and pollution load indices the investigated area belongs to three classes of pollution: unpolluted, suspected and moderate. Potential ecological risk index calculated for selected elements revealed harmless risk to human health. The level of element obtained in Burabay State National Natural Park was compared with the data available for other national parks.

Effects on brain structural and functional in deaf children after aerobic exercise training: a pilot cluster randomized controlled study

Purpose: To examine effects of aerobic exercise interventions on brain via the structural Magnetic Resonance Imaging (MRI), as well as functional change during working memory (WM) task using fMRI in deaf children.Method: The study applied a cluster randomized controlled design. Twelve deaf children in the intervention group were required to complete an eleven-week aerobic exercise intervention, while other twelve age and gender matched deaf children in the control group were required to keep their normal daily life. Task fMRI images of each participant were acquired in the baseline and post intervention period. The surface-based morphometry (SBM) analysis and functional activation analysis were employed to probe the effects of 11-week aerobic exercise on cerebral structural and functional in deaf children, respectively.Results: The 11-week aerobic exercise intervention did not change brain structure in deaf children. However, behavior performance (reaction time and mean accuracy rate) presented significant improvements after the 11-week aerobic exercise intervention. Compared to the control group, the intervention group showed decreased reaction time in the 2-back (p < 0.001) and 2-0 back (p < 0.001), and increased mean accuracy rate during 2-back (p = 0.034). Furthermore, enhanced brain activations in the left supplementary motor cortex (p < 0.05, FDR-corrected) and left paracentral lobule (p < 0.05, FDR-corrected) were observed in the intervention group.Conclusion: 11-week aerobic exercise intervention may not be able to modulate brain structure in deaf children, but may have significantly positive effects on behavior performance and brain functional activation during WM task.

ESTIMATION OF THE ELEMENTAL PROFILE OF LEAVES, ROOTS, SEEDS AND DRY EXTRACTS OF ARCTIUM LAPPA AND ARCTIUM TOMENTOSUM

The use of plant raw materials can be hindered due to concerns about their quality and safety for the human body, resulting from exceeding permissible limits of radionuclides, heavy metals, and other xenobiotics. Ensuring the quality and safety and guaranteeing the quality of raw materials and finished products is one of the tasks for researchers and practitioners. The composition and content of macro- and microelements in the seeds, roots, and leaves of A.lappa and A. tomentosum, cultivated and growing wild in the Tomsk region (Timiryazevskoye village) and Altai Territory (Altaiskoe village), have been determined, and samples a dry extracts of the roots and leaves of A. tomentosum produced by Visterra LLC, have been analyzed. The elemental composition was determined by using neutron activation analysis and flame photometry. The samples of wild and cultivated species, extracts revealed the presence of 31 chemical elements. According to the potassium content, Arctium lappa and Arctium tomentosum can be attributed to potassium concentrator plants. The leaves, roots, and seeds have the same elemental composition parts of the plant and species. In all samples of roots, seeds, leaves, and dry extracts, the levels of Cd, As complied with the requirements of the standards and sanitary norms.

Abstract LB435: Large panel organoid drug testing combined with biomarker analysis: Unveiling prospects for mechanism of action identification and preclinical patient stratification

Abstract Introduction The development of oncology drugs has a persistently high attrition rate of greater than 95%, requiring the development and implementation of novel models and technologies aimed at better predictive abilities during the preclinical phase. Among these, organoid technologies, which involve propagating tumor stem cells in a near-native state, have proven to markedly advance drug testing with enhanced precision. Our previously developed assay-ready organoid technology has paved the way for large panel organoid screening, allowing organoids to augment the efficiency of drug development pipelines, boost patient-derived model usage in preclinical studies, and facilitate accurate predictions of drug action mechanisms. Here, we present a proof-of-concept (POC) large scale organoid experiment, studying the responses of 50 models to the cytotoxic agent paclitaxel, using next generation sequencing data to analyze the drug mechanism of action (MOA) and identify biomarkers that predict drug responses. Methods A panel of 50 organoid models was characterized for paclitaxel response in 9-dose-response curves by measuring ATP levels after a 5-day exposure. Models were genomically profiled by whole-exome sequencing (n = 47) and whole-transcriptome sequencing (n = 44) to analyze the association between organoid pharmacology data and genomic information and elucidate genes and pathways that may be related with, or predictive of, the treatment responses. We performed biomarker analysis on gene expression, mutation, and copy number alteration levels. Results By assessing organoid sensitivity to paclitaxel, we observed no significant indication-specific difference in organoid responses across 7 cancer types. The 50 models were then categorized into responders (AUC &amp;lt; 1.5; n=15) and non-responders (AUC &amp;gt; 2.6; n=14) for biomarker discovery. Differential expression analysis and pathway activation analysis revealed genes and pathways involved in the cell cycle and DNA replication. DNA recombination differentiates responders from non-responders, while genes involved in epithelial cell proliferation, differentiation, and wound healing are associated with drug resistance. Mutation of proto-oncogene RB Transcriptional Corepressor 1, RB1 (a negative regulator of the cell cycle), was found to be a biomarker enriched in non-responders to paclitaxel, corroborating earlier clinical findings. Using the identified profile, we predicted responses for non-tested models in our biobank and validated our approach. Conclusion Large panel organoid drug screening in combination with biomarker analysis brings great opportunities for increasing drug pipeline efficiency. The POC here presented highlights how such a screen can identify MOAs and identify relevant biomarker profiles to be used in clinical trial patient stratification. Citation Format: Linda Xue, Liza Wijler, Marten Hornsveld, Sheng Guo, Leo Price, Marrit Putker, Ludovic Bourre. Large panel organoid drug testing combined with biomarker analysis: Unveiling prospects for mechanism of action identification and preclinical patient stratification [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr LB435.

Trace Elements Characterization in Rocks Using Neutron Activation Analysis, Northwestern Coast, Ras El-Hekma–Egypt

Trace Elements Characterization in Rocks Using Neutron Activation Analysis, Northwestern Coast, Ras El-Hekma–Egypt