Low Concentration Levels Research Articles

Ethnic minorities and income inequality: the Albanian community in Italy

PurposeThis study explores whether ethnic minorities exhibit varying levels of income inequality compared to the host population.Design/methodology/approachThe research leverages a unique immigration event in Italy, specifically the settlement of multiple Albanian groups in southern Italy during the 16th century. This historical occurrence enables an investigation into the role of cultural traits in income inequality, as these groups are situated in the same geographical region and often share borders.FindingsThe results, which remain consistent after undergoing various robustness checks, indicate that Albanian villages, while still preserving their identity and tradition, tend to experience an approximately 2% lower level of income concentration compared to similar Italian municipalities.Originality/valueOur findings aim to provide supporting evidence for future policy considerations regarding the long-term impact of immigration on income inequality.

Microbial nanomaterials: Role in sustainable agricultural practices

The increased use of chemical fertilizers, pesticides, soil-based heavy metals to improve productivity in agriculture results into higher pollution level in agroecosystem. It has become a major issue on a global scale that seriously jeopardizes people’s health and welfare as well as affects society and overall economy. In view of this, there is an urgent need to detect pollutants in the agroecosystem so that remediation practices can be implemented in time. The evolution of more responsive, affordable and precise technology is needed to create nano-sensors or nanodevices that can be used to monitor agricultural pollution, and the processes involved in pollution control. Major focused ones are those that can detect pollutants at very low concentration levels, as well as point-to-point sensing, in situ, and uninterrupted monitoring devices that offer synchronized data. These sensors are readily available in the market for the detection of organic pollutants, gases, volatile organic molecules, heavy metal ions, hazardous metal ions, etc. but they consume a lot of power and lack sophisticated technologies for improved selectivity and sensitivity. Their precision, sensitivity, response speed and environmental stability under actual operating conditions can all be improved with the aid of nanotechnology. In this study an attempt was made to describe how microbial biosensors can be used to detect toxic materials in agroecosystems. Additionally, an application of nanomaterials as pesticides and antimicrobial agent has also been discussed.

Behavior of Thiamethoxam and Clothianidin in Young Oilseed Rape Plants before Flowering, Monitored by QuEChERS/LC–MS/MS Protocol

Behavior of Thiamethoxam and Clothianidin in Young Oilseed Rape Plants before Flowering, Monitored by QuEChERS/LC–MS/MS Protocol

Recovery of lead, iron, and copper from point-of-use-filters to examine performance

Over the last few decades, reliance on point-of-use (POU) treatment for removing actual or perceived contaminants in drinking water has increased within the United States. Understanding POU treatment removal performance, and accurately estimating metals exposure at the tap, is critical for understanding POU water treatment device effectiveness and potential reductions in contaminant exposure. Previous bench-scale efforts have documented significant removal of dissolved Pb using faucet-mounted POU filters; however, limited efforts have challenged these filters with extreme water quality conditions which are more common in homes reliant on private well water. Characterization of typical rates of metals uptake by POU filters would support: improved exposure estimates and predictions, a better understanding of long-term filter performance under different conditions, and identification of conditions where POU use is recommended. In the current study, standard faucet-mount activated carbon POU filters were tested in a laboratory setting in order to: 1) determine removal of Pb, Cu, and Fe under low and high concentration conditions designed to reflect previous observations of residential water quality; and 2) evaluate the effectiveness of an acid flow-through procedure in recovering metals from used POU filters exposed to varying concentrations of Pb, Cu, and Fe. Although the filters tested here successfully removed Pb and Cu from waters of both high and low-level concentrations (>91% removal), Fe removal varied considerably. The acid flow-through procedure yielded mixed results: while 25.1-70.4% of influent Pb mass was recovered, recovery of Cu and Fe from the dosed filters was unpredictable. This was attributed in part to leaching from the filter media itself; in addition to Cu and Fe, concentrations of several other elements (e.g., Ti, Si, Al) increased and appeared to leach from control filters during the acid flow-through procedure. Given these results, alternative methods for assessing uptake of metals to POU filters should be explored.

Unveiling the potential of machine learning in cost-effective degradation of pharmaceutically active compounds: A stirred photo-reactor study

In this study, neural networks and support vector regression (SVR) were employed to predict the degradation over three pharmaceutically active compounds (PhACs): Ibuprofen (IBP), diclofenac (DCF), and caffeine (CAF) within a stirred reactor featuring a flotation cell with two non-concentric ultraviolet lamps. A total of 438 datapoints were collected from published works and distributed into 70% training and 30% test datasets while cross-validation was utilized to assess the training reliability. The models incorporated 15 input variables concerning reaction kinetics, molecular properties, hydrodynamic information, presence of radiation, and catalytic properties. It was observed that the Support Vector Regression (SVR) presented a poor performance as the ε hyperparameter ignored large error over low concentration levels. Meanwhile, the Artificial Neural Networks (ANN) model was able to provide rough estimations on the expected degradation of the pollutants without requiring information regarding reaction rate constants. The multi-objective optimization analysis suggested a leading role due to ozone kinetic for a rapid degradation of the contaminants and most of the results required intensification with hydrogen peroxide and Fenton process. Although both models were affected by accuracy limitations, this work provided a lightweight model to evaluate different Advanced Oxidation Processes (AOPs) by providing general information regarding the process operational conditions as well as know molecular and catalytic properties.

Residual loads from tilapia farming on the sediment of a Brazilian reservoir

This study investigated the sediment geochemistry of a fish farming area in net cage tanks in the Rosário reservoir, Brazil. Three areas were investigated: reference (RA), fish farming (FFA), and dispersion (DA). The results were analyzed through correlation, similarity, principal component analysis, comparison with legislation, sediment quality guidelines, and sediment pollution indices. The mean concentrations for RA, FFA, and DA areas were respectively: Cu (mg.kg−1) 37.74, 62.23, and 71.83; Mn (mg.kg−1) 22.55, 66.48, and 55.90; Zn (mg.kg−1) 9.13, 114.83, and 94.27; Fe (%) 0.28, 0.40, and 0.43; OM (%) 15.84, 21.95, and 18.45; TOC (%) 1.86, 3.69, and 6.05; TN (mg.kg−1) 2365.00, 5015.00, and 3447.51; TP (mg.kg−1) 780.00, 6896.00, and 2585.50; ORP (mV) −95.50, −135.20, and −127.10; pH 6.60, 6.58, and 6.05; <63 μm 90.59, 78.68, and 87.30. Statistically, the influence of fish farming on sediment, organic matter, and pollutant sedimentation was demonstrated. Cu and Zn concentrations were below sediment quality guidelines. Regarding legal limits (resolution 454/2012/CONAMA), nutrients in the FFA area exceeded by 60% (TN) and 100% (TP), while in DA and RA areas they were 100% lower. TOC was 100% lower in all areas. Organic matter exceeded the limit by 100% in all areas. Pollution indices resulted in: low contamination factor 78%; unpolluted for 87% of pollution load and 83% of combined pollution; moderately polluted for 75% of the Nemerow index. The greatest impacts and influence of farming on pollutant sedimentation were more concentrated in the fish farming area. In terms of legal aspects and pollution indices, fish farming produced low levels of trace metal pollution and nutrient concentrations exceeded legal limits.

Do internal and external risk spillovers of the food system matter for national food security?

The COVID-19 pandemic and the Russia-Ukraine war raise concerns about food security, particularly in interconnected and vulnerable food systems. However, existing literature focuses mainly on food supply-chain linkages and less on systemic risk spillovers, namely system-wide risk contagion among food companies. We estimate countries' internal and external risk spillovers using the “Vector Auto-Regressive (VAR) for Value-at-Risk (VaR)” approach with an Elastic Net penalty and the stock returns of 528 food companies, and analyze their impacts on national food security using country-level panel data. Results reveal that both risk spillovers significantly threaten food security, especially for countries with low food self-sufficiency and high import concentration levels. Beyond non-financial channels like higher food consumer prices, fewer food imports, and lower food quality, these impacts also rely on financial channels (reduced credit flows to agriculture). Our study highlights enhancing food security for governments by monitoring and reducing risk contagion among food companies.

MOF-derived sandwich-structured dual Z-Scheme Co9S8@ZnIn2S4/CdSe hollow nanocages heterojunction: Target-induced ultrasensitive photoelectrochemical sensing of chlorpyrifos

Exploring efficient photoactive material presents an intriguing opportunity to enhance the analytical performance of photoelectrochemical (PEC) sensor in the environmental analysis. In this work, a sandwich-structured multi-interface Co9S8@ZnIn2S4/CdSe QDs dual Z-Scheme heterojunction, derived from metal-organic framework (MOF), was synthesized as a sensing platform for chlorpyrifos detection, by integrating with enzyme-induced in situ insoluble precipitates strategy. The meticulously designed Co9S8@ZnIn2S4/CdSe QDs exhibited enhanced charge separation efficiency and was proved to be a highly effective sensing platform for the immobilization of biomolecules, attributing to the intrinsic dual Z-Scheme heterojunction and the distinctive hollow structure. The proposed PEC sensing platform combined with enzyme-induced in situ precipitate signal amplification strategy achieved superior performance for sensing of chlorpyrifos (CPF), showing in wide linear range (1.0 pg mL−1–100 ng mL−1), with a limit of detection (0.6 pg mL−1), excellent selectivity, and stability. This work offers valuable insights for the design of novel advanced photoactive materials aimed at detecting environmental pollutants with low level concentration.

Removal of pesticide acetamiprid using KOH activated biochar derived from crayfish shell: Behavior and mechanism

Over the past few decades, the excessive use of pesticides has resulted in serious environment pollution, and residual pesticides prompt significant concern regarding their potential harm to both the ecological security and human health. In this study, KOH activated crayfish shell biochar (KBC) was successfully prepared and used to effectively remove acetamiprid (ACE) and triadimefon (TDM) from aqueous solutions. Batch experiments results indicated that, the adsorption process of ACE was predominantly by chemical reaction and controlled by multiple mechanisms, and ACE adsorption was a thermodynamically spontaneous and exothermic reaction. The KBC exhibited exceptional adsorption performance in removing ACE with a maximum adsorption capacity of 40.41 mg g−1. A superior adsorption capacity toward both ACE and TDM over KBC could be achieved at lower concentration levels, and KBC exhibited good reuse for the removal of ACE and TDM. Different adsorption models and characterization results revealed the adsorption mechanism of ACE and TDM by KBC, including van der Waals forces, pore filling, hydrogen bonding, and π-π electron donor-acceptor interactions. These findings suggested that KBC was an excellent adsorbent for removing pesticide-contaminated water.

Evaluation of acetanilide and antipyrine adsorption on lignin-derived activated carbons

In this study, the removal of two emerging pollutants (EPs), antipyrine and acetanilide, through adsorption on activated carbons (ACs) prepared by chemical activation of Organosolv lignin with H3PO4 were evaluated. ACs with different pore size distribution were obtained at different impregnation ratios (H3PO4/lignin, 0.5–3.0 w/w) and activating temperatures (500–900 °C). The porosity and surface chemistry of the ACs were determined, and a bimodal size distribution of micropores and narrow mesopores was observed for the different ACs. These ACs were tested for antipyrine and acetanilide adsorption in aqueous solutions in a batch system at 20 °C and low concentration levels (0.5–10 ppm). In general, the ACs exhibited higher adsorption affinity to acetanilide than to antipyrine due to its smaller molecular size. Langmuir adsorption isotherm was able to describe the adsorption equilibrium data. A new Linear Driving Force (2-LDF) kinetic model, based on the bimodal size distribution of micropores and narrow mesopores observed for the ACs has been developed. The new model provided a more accurate description of the batch adsorption rates than that obtained from conventional kinetic models, and also enabled to relate the pore size distribution of the adsorbent with the adsorption kinetics. The validity of this model was checked in small-scale column fixed bed adsorption for the AC showing the highest affinity for both EP. The kinetic model and equilibrium adsorption isotherm obtained from the batch experiments were successfully used to provide an accurate description of the bed service time and the full breakthrough profile of acetanilide and antipyrine.

Insights into adsorbable organic halogen analysis: Two overlooked factors impacting water quality assessment

Adsorbable organic halogen (AOX) represents the total amount of halogenated organics that can be adsorbed on activated carbon (AC) from samples. Measuring AOX is crucial for assessing water quality, and any erroneous estimation of AOX risks misleading decision-makers. This study demonstrated two overlooked factors that may introduce biases to AOX measurement. The first one relates to impurities in the gas transfer tubes of AOX combustion system and in the pressurized gas of AOX separation system, which resulted in significant fluctuations and high blank values (8.5–118.0 μg-Cl/L). The solutions of above issues are to warming up the combustor for several runs and replacing the pressurized air with argon gas in the separator, which could drop the blank AOX values to 9.1–10.0 μg-Cl/L. The second one involves coexisting chloride ion (Cl−) during AOX analysis, which interfered with AOX measurements (T. test, p < 0.05) even at low concentration levels (e.g., 10 mg/L Cl− in samples with 100 μg-Cl/L p-chlorophenol). Results show that AC captured 0.02–0.11 % of Cl−, resulting in 17.7–24.5 μg-Cl/L AOX responses in control samples containing 15–130 mg/L Cl− only. Furthermore, a significant mass imbalance of Cl− (3.58–8.39 %) during analysis process suggests a potential impact of residual Cl− on subsequent samples. By comparing synthetic and actual waters, samples with low dissolved organic carbon (DOC) were more susceptible to interference from Cl− on AOX measurement than those with high DOC. These findings underscore the pressing need to optimize existing AOX methods or develop alternative analytical methods to ensure accurate water quality assessment.

Determination of Ethanol in Vinegar and Beverage by Gas Chromatography: A Validated Method for Halal Verification

Validation of the method for determining ethanol in vinegar and beverages has been carried out in the linearity range of 0.05-1% using GC-FID. This research was carried out using an internal standard solution and without an internal standard solution. The research aims to validate the linearity of ethanol determination at low concentration levels. This validation is useful to ensure that the ethanol test method in the sample can be detected at low concentration levels. In the halal authentication process, the maximum limit for ethanol content is 5%. The method validation results confirm that in the concentration range 0.05-1% it has good linearity with a correlation coefficient (R) without the addition of internal standards and with the addition of standard solutions being 0.9972 (R2=0.9943) and 0.9952 (R2=0.9905). The results of the analysis of variance (ANOVA) test with a 95% confidence interval and 9 degrees of freedom F-count (0.0141) &lt; F-critical (0.3146) show that the range 0.05-1% corresponds to the limit of linearity. The results of the ANOVA test with a 95% confidence interval with df=6 show the F-test value (0.0879) &lt; F-critical (0.2334) indicating that the two proposed methods have high precision and no significant differences. Both methods also have high accuracy and no significant differences in accuracy as shown by the results of the ANOVA test with a 95% confidence interval and degrees of freedom = 6 showing the F-test value (1.5204) &lt; F-critical (4.2839). It is recommended that the results of this validation be useful in the halal verification process for vinegar and beverage products.

Study of the sensitivity of methicillin-resistant &lt;i&gt;Staphylococcus aureus&lt;/i&gt; to antibiotics and bacteriophage preparations

Objective. To evaluate the sensitivity of methicillin-resistant Staphylococcus aureus strains to antibiotics and therapeutic and prophylactic preparations of bacteriophages. Materials and methods. The antibiotic sensitivity of strains of methicillin-resistant S.aureus was studied by the disco-diffusion method, the determination of the minimum inhibitory concentrations of vancomycin and linezolid by broth microdilution method, and ceftaroline by E-tests. The sensitivity of methicillin-resistant S.aureus to bacteriophage preparations was studied. Results. It has been established that linezolid and vancomycin are quite active drugs against methicillin-resistant S.aureus (MRSA), however, resistance to them begins to develop. MRSA resistance to fluoroquinolones and cefoxitin was the highest of all antibiotics tested; the results obtained with cefoxitin can be interpreted for other cephalosporins (except ceftaroline) and all penicillins. Only 67.9% of MRSA strains retained sensitivity to ceftaroline, but ceftaroline-resistant strains had low levels of minimal inhibitory concentration. The preparations of the bacteriophages “Sextaphage” and “Piobacteriophage Phagio” showed their lytic activity only in relation to 35.8% and 18.9% of MRSA isolates, respectively. Conclusion. Monitoring the development of antibiotic resistance in methicillin-resistant S.aureus is an important part of the strategy of rational antibiotic therapy for staphylococcal infections. Only taking into account the preliminary step-by-step determination of the phage sensitivity of the causative agent of the disease, bacteriophage preparations can be considered as a completely possible alternative to antibiotics for the treatment of purulent inflammatory diseases caused by MRSA.

Deep eutectic solvents as green and sustainable diluents in headspace gas chromatography for the determination of trace level genotoxic impurities in pharmaceuticals

Genotoxic impurities (GTIs) are potential carcinogens that need to be controlled down to ppm or lower concentration levels in pharmaceuticals under strict regulations. The static headspace gas chromatography (HS-GC) coupled with electron capture detection (ECD) is an effective approach to monitor halogenated and nitroaromatic genotoxins. Deep eutectic solvents (DESs) possess tunable physico-chemical properties and low vapor pressure for HS-GC methods. In this study, zwitterionic and non-ionic DESs have been used for the first time to develop and validate a sensitive analytical method for the analysis of 24 genotoxins at sub-ppm concentrations. Compared to non-ionic diluents, zwitterionic DESs produced exceptional analytical performance and the betaine : 7 (1,4- butane diol) DES outperformed the betaine : 5 (1,4-butane diol) DES. Limits of detection (LOD) down to the 5-ppb concentration level were achieved in DESs. Wide linear ranges spanning over 5 orders of magnitude (0.005–100 µg g−1) were obtained for most analytes with exceptional sensitivities and high precision. The method accuracy and precision were validated using 3 commercially available drug substances and excellent recoveries were obtained. This study broadens the applicability of HS-GC in the determination of less volatile GTIs by establishing DESs as viable diluent substitutes for organic solvents in routine pharmaceutical analysis.

Electrical Activity Changes and Neurovascular Unit Markers in the Brains of Patients after Cardiac Surgery: Effects of Multi-Task Cognitive Training.

There is growing interest in finding methods to enhance cognitive function and comprehend the neurophysiological mechanisms that underlie these improvements. It is assumed that non-pharmacological interventions have better results in cognitive recovery. The aim of this study was to assess the effect of multi-task cognitive training (MTT) on electroencephalographic (EEG) changes and markers of the neurovascular unit in patients undergoing coronary artery bypass grafting (CABG). This prospective cohort study involved 62 CABG patients aged 45-75 years, 30 of whom underwent a 5-7-day MTT course. The groups of patients were comparable with respect to baseline clinical and anamnestic characteristics. An EEG study was performed before surgery and 11-12 days after CABG. Markers of the neurovascular unit (S100β, NSE, and BDNF) were examined at three time points: before surgery, within the first 24 h after surgery, and 11-12 days after CABG. Patients without training demonstrated higher relative theta power changes compared to the MTT patients. The course of MTT was associated with low plasma S100β concentration but high BDNF levels at the end of the training course. The theta activity changes and the markers of the neurovascular unit (S100β, BDNF) indicated that the severity of brain damage in cardiac surgery patients after a short course of MTT was slightly reduced. Electrical brain activity indicators and vascular markers can be informative for monitoring the process of cognitive rehabilitation in cardiac surgery patients.

Nutritional profile and risk assessment of inorganic elements in enteral and parenteral nutrition formulas

The contents of essential (Ca, Fe, K, Na, P, and Zn) and potentially toxic inorganic elements (As, Al, Cd, Cr, Cu, Mn, and Pb) in enteral and parenteral nutrition formulas were evaluated by inductively coupled plasma optical emission spectrometry (ICP OES) and graphite furnace atomic absorption spectrometry (GFAAS). A total of 30 enteral formulas, 23 parenteral solution components, and 3 parenteral solutions were analyzed. The elements Ca and K presented the higher contents (72–2918 mg L−1 and 235–2760 mg L−1) while the lowest concentration levels were found for As and Cd (<0.68 µg L−1 and <0.01–0.62 µg L−1) in the studied samples. The validated analytical methods presented an accuracy of 75–116% and RSD values lower than 9.8%. Calcium gluconate and magnesium sulfate, which are used as raw materials in parenteral solution, are potential sources of Al and Mn contamination. A Hazard Quotient (HQ) >1 was obtained for Al (27 ± 1 µg L−1) in one of the parenteral samples, whereas the established limit is 25 µg L−1. Enteral samples were considered safe for consumption regarding the Al, As, and Cd levels. One healing-specific and pediatric formula contained Pb at levels above 0.25 µg kg-day−1, too high for safe consumption. The enteral formulas (pediatric, diabetes-specific, renal-specific, healing-specific, and standard formula with addition of fiber) presented risks in relation to the consumption of Cr and Mn (>250 µg day−1 and >11 mg day−1). The results indicate the need for strict monitoring, considering that these formulations are often the single patient’s food source.

Unveiling the Molecular Characteristics, Origins, and Formation Mechanism of Reduced Nitrogen Organic Compounds in the Urban Atmosphere of Shanghai Using a Versatile Aerosol Concentration Enrichment System.

Reduced nitrogen-containing organic compounds (NOCs) in aerosols play a crucial role in altering their light-absorption properties, thereby impacting regional haze and climate. Due to the low concentration levels of individual NOCs in the air, the utilization of accurate detection and quantification technologies becomes essential. For the first time, this study investigated the diurnal variation, chemical characteristics, and potential formation pathways of NOCs in urban ambient aerosols in Shanghai using a versatile aerosol concentration enrichment system (VACES) coupled with HPLC-Q-TOF-MS. The results showed that NOCs accounted over 60% of identified components of urban organic aerosols, with O/N < 3 compounds being the major contributors (>70%). The predominance of the positive ionization mode suggested the prevalence of reduced NOCs. Higher relative intensities and number fractions of NOCs were observed during nighttime, while CHO compounds showed an opposite trend. Notably, a positive correlation between the intensity of NOCs and ammonium during the nighttime was observed, suggesting that the reaction of ammonium to form imines may be a potential pathway for the formation of reduced NOCs during the nighttime. Seven prevalent types of reduced NOCs in autumn and winter were identified and characterized by an enrichment of CH2 long-chain homologues. These NOCs included alkyl, cyclic, and aromatic amides in CHON compounds, as well as heterocyclic or cyclic amines and aniline homologue series in CHN compounds, which were associated with anthropogenic activities and may be capable of forming light-absorbing chromophores or posing harm to human health. The findings highlight the significant contributions of both primary emissions and ammonium chemistry, particularly amination processes, to the pollution of reduced NOCs in Shanghai's atmosphere.

Кислотно-щелочное состояние крови у пациентов с мочекаменной болезнью. Исследование II. Роль pH крови.

Introduction. We will try to show the place of acid-base balance (ABB) study in urolithiasis patients. There is the second article in a series of works devoted to the study of ABB in urolithiasis patients. This work is devoted to the study of the level of basic acid base indicators: blood pH, pCO2, pO2, BE. Materials and methods. The study was conducted prospectively at the N. Lopatkin Scientific Research Institute of Urology and Interventional Radiology – branch of the National Medical Research Radiological Center of the Ministry of Health of the Russian Federation. We analyzed data of 83 urolithiasis patients (39 men and 44 women). All patients underwent an analysis of the urinary stones chemical composition, biochemical analysis of blood and daily urine, blood acid-basic balance, blood parathyroid hormone. Urine pH morning was determined for all patients. Results. Patients with acidemia (blood pH &lt;7.32) had significantly higher concentrations of chlorine, creatinine and ionized calcium in the blood than in the group of patients with 7.32 &lt;blood pH &lt;7.42. The BE indicator is significantly lower than in the comparison group. There is a higher level of total blood calcium (p&lt;0.05) and magnesium excretion, a lower level of serum concentration of creatinine (p&lt;0.05), urea (p&lt;0.05) and chlorine (p&lt;0.05) in the group of patients with hypercapnia (pCO2 &gt;51 mmHg) than in patients with 41&lt; pCO2 &lt;51 mmHg. Patients with a BE level &lt;-2.5 had significantly higher levels of creatinine, urea and chlorine in the blood, and higher urine pH (p&lt;0.05) compared to patients with BE&gt;2.5. Patients with BE &lt; -2.5 also had significantly lower level of blood pH, pCO2 and ionized calcium compared to the group of patients with BE &gt;2.5. Conclusion. Normalization of blood pH is capable to correct the metabolism of the main lithogenic substances in urolithiasis patients.

Abstract 4696: ERBB2 signaling and inhibition in bladder cancer

Abstract The role of human epidermal growth factor receptor-2 (HER2) protein and the inhibition of its oncogenic signaling pathway, ERBB2, is well defined and found to be beneficial in combination with standard chemotherapies in breast and certain gastro-intestinal cancers. Targeting the ERBB2 pathway has had unclear or inconsistent results in early trials in bladder cancer (BLCA) and the efficacy of its combination with cisplatin, a standard BLCA chemotherapy, is not known. In this study, we identify the transcriptomic oncogenic signatures that correlate with ERBB2 signaling in BLCA, explore how HER2 expression in BLCA cell lines correlates with treatment response in vitro, and evaluate the potential of ERBB2 inhibition in combination with cisplatin for BLCA. We analyzed the tumor transcriptome from the Cancer Genome Atlas (TCGA) study of BLCA with single sample Gene Set Enrichment Analyses (ssGSEA) for Hallmark and Oncogenic gene sets. We performed multiple Pearson correlation analyses of HER2 protein levels and ERBB2 signaling with other signaling pathways in the TCGA BLCA tumors and adjusted the significance for multiple comparisons using the Benjamini-Hochberg method. Immunoblotting was used to assess HER2 protein levels across a panel of bladder cancer cell lines. We then assessed cell viability and colony formation upon exposure to the specific ERBB2 inhibitor, tucatinib. Synergy between cisplatin and tucatinib in BLCA cell lines was evaluated using the Chou-Talalay method. In the TCGA BLCA dataset, HER2 protein positively correlates with ERBB2 signaling with a Pearson correlation coefficient of 0.45 and an adjusted p-value of 1.73E-17. ERBB2 signaling has multiple significant positive and negative correlations. ERBB2 signaling negatively correlates with the DNA repair gene set with a Pearson coefficient of -0.5 and an adjusted p-value of 1.40E-22. HER2 protein expression varies greatly between bladder cancer cell lines: HT-1197 and UMUC3 have lower HER2 expression, with HT-1376, T24, RT4, 5637, and SW780 showing higher HER2 expression. HT-1197 and RT4 had the lowest IC50s for tucatinib and showed a strong response to low doses of tucatinib in the colony formation assay. Cisplatin and tucatinib have synergetic growth inhibition (combination index &amp;lt;1) at low concentration levels in the HT-1197 and SW780 cell lines. Multiple oncogenic pathways coexist with ERBB2 signaling in BLCA. The varied response to specific ERBB2 inhibition and the lack of correlation of the response with HER2 protein level in cell lines alludes to alternative oncogenic pathways. A strong negative correlation of ERBB2 signaling with the DNA response pathway in the TCGA BLCA dataset, combined with preclinical evidence of synergy between tucatinib and cisplatin, indicates a potential for development of the combination as a clinical treatment strategy and warrants further study. Citation Format: Constance Caparas-Spaugy, Chris Stubben, Ken Boucher, Bingjian Feng, Aaron Atkinson, David Nix, Bradley Cairns, Sumati Gupta. ERBB2 signaling and inhibition in bladder cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 4696.

Abstract 3498: A novel combination of tissue-informed, comprehensive genomic profiling (CGP) and non-bespoke blood-based profiling for quantifying circulating tumor DNA (ctDNA)

Abstract Background: Estimating quantitative circulating tumor fraction in liquid biopsy samples is a promising area of clinical development for monitoring therapeutic molecular response and correlates with patient outcomes. Here we introduce a sensitive measure of estimating ctDNA tumor fraction (ctDNA TF) using a novel combination of tissue-informed CGP with a non-bespoke, blood-based liquid biopsy panel. Methods: Advanced pan-solid tumor samples were sequenced with both the Tempus xF/xF+ (105/523 gene, liquid biopsy) and Tempus xT (648 genes, solid-tumor with matched buffy coat) NGS assays (samples collected within 90 days). A normal distribution was fit against the somatic variants detected in solid-tissue and variants with variant allele fractions (VAF) within two standard deviations were used as selected biomarkers in the corresponding liquid biopsy to calculate a tumor-informed ctDNA TF for each sample. Results: In the initial validation set (n=79 samples also sequenced with low-pass whole genome sequencing), the linearity of tumor-informed ctDNA TF was compared to mean VAF (R2=0.26, slope=0.55), ichorCNA (R2=0.84, slope=0.84), and tumor-naive ctDNA TF (R2=0.71, slope=0.90). In a larger validation set (n=12,080), 37.5% samples had no variants detected in both xF and/or xT. Of the remaining samples, the linearity of tumor-informed ctDNA TF was compared to mean VAF (R2=0.21, slope=0.55) and tumor-naive ctDNA TF (R2=0.65, slope=0.81). In a follow-up analysis, we required 5 or more variants be detected in both xF and xT (n=1,659 samples) and compared the linearity of tumor-informed ctDNA TF to mean VAF (R2=0.37, slope=0.64) and tumor-naive ctDNA TF (R2=0.68, slope=0.98). In samples that received xF+ profiling (n=567), 24.3% had no variants detected in both xF+ and xT. The linearity of tumor-informed ctDNA TF of the remaining samples was compared to mean VAF (R2=0.01, slope=0.26) and tumor-naive ctDNA TF (R2=0.63, slope=1.02). Increasing the required number of variants to 5 or more had marginal improvement in linearity of tumor-informed ctDNA TF to mean VAF (R2=0.12, slope=0.47) and tumor-naive ctDNA TF (R2=0.67, slope=1.13).The limit-of-blank of the tumor-informed ctDNA TF approach was established to be 0% in both xF and xF+, and the limit-of-detection was ≤0.1% demonstrating that tumor informed ctDNA TF is a sensitive measure in detecting tumor fraction at low concentration levels. Conclusion: Here we introduce a novel sensitive and specific tumor-informed, non-bespoke approach for estimating ctDNA TF. Linearity improves with increased panel size and increased variant number. These results suggest that a tumor-informed ctDNA TF can be utilized to improve the sensitivity of existing methods for estimating tumor fraction to help in treatment decisions using Tempus’ tissue and liquid comprehensive NGS genomic profiling platform. Citation Format: Terri Driessen, Christine Lo, Wei Zhu, Robert Tell, Jonathan Freaney, Halla Nimeiri, Kate Sasser. A novel combination of tissue-informed, comprehensive genomic profiling (CGP) and non-bespoke blood-based profiling for quantifying circulating tumor DNA (ctDNA) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3498.