Development of an orthotopic medulloblastoma zebrafish model for rapid drug testing.

BACKGROUND: Medulloblastoma (MB) is one of the most common malignant brain tumors in children. Current preclinical in vivo model systems for MB have increased our understanding of molecular mechanisms regulating MB development. However, they may not be suitable for large-scale studies. The aim of this study was to investigate if a zebrafish-based xenograft model can recapitulate MB growth and enable rapid drug testing. METHODS: Nine different MB cell lines or patient-derived cells were transplanted into blastula-stage zebrafish embryos. Tumor development and migration were then monitored using live imaging. RNA sequencing was performed to investigate transcriptome changes after conditioning cells in neural stem cell-like medium. Furthermore, drug treatments were tested in a 96-well format. RESULTS: We demonstrate here that transplantation of MB cells into the blastula stage of zebrafish embryos leads to orthotopic tumor growth that can be observed within 24 hours after transplantation. Importantly, the homing of transplanted cells to the hindbrain region and the aggressiveness of tumor growth are enhanced by pre-culturing cells in a neural stem cell-like medium. The change in culture conditions rewires the transcriptome towards a more migratory and neuronal phenotype, including the expression of guidance molecules SEMA3A and EFNB1, both of which correlate with lower overall survival in MB patients. Furthermore, we highlight that the orthotopic zebrafish MB model has the potential to be used for rapid drug testing. CONCLUSION: Blastula-stage zebrafish MB xenografts present an alternative to current MB mouse xenograft models, enabling quick evaluation of tumor cell growth, neurotropism, and drug efficacy.

Development of a Microfluidic Vascularized Osteochondral Model as a Drug Testing Platform for Osteoarthritis.

Osteoarthritis (OA) is a degenerative joint disease characterized by changes in cartilage and subchondral bone. To date, there are no available drugs that can counteract the progression of OA, partly due to the inadequacy of current models to recapitulate the relevant cellular complexity. In this study, an osteochondral microfluidic model is developed using human primary cells to mimic an OA-like microenvironment and this study validates it as a drug testing platform. In the model, the cartilage compartment is created by embedding articular chondrocytes in fibrin hydrogel while the bone compartment is obtained by embedding osteoblasts, osteoclasts, endothelial cells, and mesenchymal stem cells in a fibrin hydrogel enriched with calcium phosphate nanoparticles. After developing and characterizing the model, Interleukin-1ß is applied to induce OA-like conditions. Subsequently, the model potential is evaluated as a drug testing platform by assessing the effect of two anti-inflammatory drugs (Interleukin-1 Receptor antagonist and Celecoxib) on the regulation of inflammation- and matrix degradation-related markers. The model responded to inflammation and demonstrated differences in drug efficacy. Finally, it compares the behavior of the "Cartilage" and "Cartilage+Bone" models, emphasizing the necessity of incorporating both cartilage and bone compartments to capture the complex pathophysiology of OA.

In vitro drug testing using patient-derived ovarian cancer organoids.

BACKGROUND: Ovarian cancer is the most lethal gynecological cancer. As the primary treatment, chemotherapy has a response rate of only 60-70% in advanced stages, and even lower as a second-line treatment. Despite guideline recommendations, which drugs will be most effective remains unclear. Thus, a strategy to prioritize chemotherapy options is urgently needed. Cancer organoids have recently emerged as a method for in vitro drug testing. However, limited clinical correlations have been assessed with test results from cancer organoids, particularly in gynecological cancers. We therefore aimed to generate patient-derived organoids (PDOs) of ovarian cancer, to assess their drug sensitivities and correlations with patient clinical outcomes. METHODS: PDOs were generated from fresh tumors obtained during surgical resection, which was then cultured under matrix gel and appropriate growth factors. Morphological and molecular characterization of PDOs were assessed by phase contrast microscopy and paraffin-embedded histopathology. Expressions of PAX8, TP53, WT1, CK7, and CK20 were tested by immunohistochemical staining and compared with parental tumor tissues and the human protein atlas database. PDOs were subjected to in vitro drug testing to determine drug sensitivity using Titer-Glo® 3D Cell Viability Assay. PDO viability was measured, and area under the curve calculated, to compare responses to various compounds. Correlations were calculated between selected patients' clinical outcomes and in vitro drug testing results. RESULTS: We established 31 PDOs. Among them, 28 PDOs can be expanded, including 15, 11, and 2 from ovarian, endometrial, and cervical cancers, respectively. The PDOs preserved the histopathological profiles of their originating tumors. In vitro drug testing of 10 ovarian cancer PDOs revealed individual differential responses to recommended drugs, and interpersonal heterogeneity in drug sensitivity, even with the same histology type. Among four patients who were platinum sensitive, resistant, or refractory, PDO drug responses correlated well with their clinical courses. CONCLUSION: In vitro drug testing using ovarian cancer organoids is feasible and correlates well with patient clinical responses. These results may facilitate development of precision chemotherapy and personalized screening for repurposed or new drugs.

Recent applications of three-dimensional bioprinting in drug discovery and development.

The ability of three-dimensional (3D) bioprinting to fabricate biomimetic organ and disease models has been recognised to be promising for drug discovery and development as 3D bioprinted models can better mimic human physiology compared to two-dimensional (2D) cultures and animal models. This is useful for target selection where disease models can be studied to understand disease pathophysiology and identify disease-linked compounds. Lead identification and preclinical studies also benefit from 3D bioprinting as 3D bioprinted models can be utilised in high-throughput screening (HTS) systems and to produce efficacy and safety data that closely resembles clinical observations. Although no published applications of 3D bioprinting in clinical trials were found, there are two clinical trials planning to evaluate the predictive ability of 3D bioprinted models by comparing human and model responses to the same chemotherapy. Overall, this review provides a comprehensive summary of the latest applications of 3D bioprinting in drug discovery and development.

Prevalence and Misreporting of Illicit Drug Use among Electronic Dance Music Festivals Attendees: A Comparative Study between Sweden and Belgium.

Illicit drug use is common among attendees of electronic dance music (EDM) festivals, but is often significantly underreported by participants. The current study aimed to compare the prevalence and over- and under-reporting of illicit drug use among attendees at EDM festivals in two European countries with distinct drug laws and cultures. Self-reported data regarding recent drug use were collected through interviews. Participants' blood alcohol concentrations were measured using a breathalyzer. Recent illicit drug use was assessed through sampling microparticles in the breath and consequent off-site analysis through liquid chromatography and tandem mass spectroscopy. Illicit drug use was higher in Belgium than in Sweden as indicated by self-reports (56.8 vs. 4.3%) and drug testing (37.2 vs. 12.5%). Underreporting was higher in Sweden than in Belgium; in Sweden, only 2.6% reported taking an illicit drug other than cannabis, whereas 11.6% tested positive, while the corresponding figures in Belgium were 36.5% and 36.9%. In both countries, results from self-reporting and drug testing for specific drugs matched poorly at the individual level, indicating unwitting consumption of substances. This study indicates that the drug use prevalence and the likelihood of disclosure may differ between countries or cultures, which should be considered when choosing methods to investigate drug use prevalence.

Repeated lyophilization: A neo-method for urine-based reference materials preparation.

In urine drug testing, a cut-off value is often imposed to determine whether the sample is negative or positive. A matrix containing a reference substance helps counteract the adverse effects of the urine matrix across different laboratories to improve the consistency of final results. However, as a biological matrix, urine is prone to corruption and other problems that make it difficult to use as a reference sample. In this study, morphine, nitrazepam, lorazepam, buprenorphine, zolpidem, midazolam, diazepam, and clozapine commonly used in clinical practice were selected as target analytes, and the preparation process was further optimized to repeated lyophilization, in order to obtain more effective, stable, and accurate urine matrix reference materials (mRMs). The appropriate urine density (1.010-1.017 kg/m3) for preparing lyophilized samples was investigated through density determination. Conducting repeated lyophilizations resulted in a denser powder with reduced susceptibility to collapse and improved the quality of lyophilized urine samples. Lyophilized urine mRMs could be stored at room temperature for one month or under refrigeration conditions (4 ℃) for six months.

The Current State of Realistic Heart Models for Disease Modelling and Cardiotoxicity.

One of the many unresolved obstacles in the field of cardiovascular research is an uncompromising in vitro cardiac model. While primary cell sources from animal models offer both advantages and disadvantages, efforts over the past half-century have aimed to reduce their use. Additionally, obtaining a sufficient quantity of human primary cardiomyocytes faces ethical and legal challenges. As the practically unlimited source of human cardiomyocytes from induced pluripotent stem cells (hiPSC-CM) is now mostly resolved, there are great efforts to improve their quality and applicability by overcoming their intrinsic limitations. The greatest bottleneck in the field is the in vitro ageing of hiPSC-CMs to reach a maturity status that closely resembles that of the adult heart, thereby allowing for more appropriate drug developmental procedures as there is a clear correlation between ageing and developing cardiovascular diseases. Here, we review the current state-of-the-art techniques in the most realistic heart models used in disease modelling and toxicity evaluations from hiPSC-CM maturation through heart-on-a-chip platforms and in silico models to the in vitro models of certain cardiovascular diseases.

How do perceptions of procedural justice, police legitimacy, and legitimacy of laws influence intentions to drug drive?

INTRODUCTION: There is a need for improved drug driving enforcement to promote greater driver compliance with drug driving laws. In Australia, Roadside Drug Testing (RDT) suffers from operational challenges that undermine its effectiveness in reducing drug driving. OBJECTIVE: To identify potential improvements to RDT, this study investigated the extent to which drivers perceive RDT to be procedurally just and that the policing of drug driving and the associated laws are legitimate. These perceptions were then compared with those applying to Random Breath Testing (RBT) and examined in relation to their respective influence on intentions to drug and drink drive in the future. METHOD: A sample of 1,483 licensed drivers from three Australian states completed an online survey. RESULTS: Those participants who reported engaging in drug driving perceived RDT to be less procedurally just than non-drug drivers. Similarly, drug drivers perceived the police and associated drug driving laws to be less legitimate than non-drug drivers. Furthermore, drug drivers who had been tested at an RDT operation in the past perceived RDT to be less procedurally just and considered drug driving policing and laws to be less legitimate, compared with the corresponding perceptions of drink drivers who had been tested at an RBT operation. A regression analysis indicated that stronger intentions to drug drive in the future were associated with lower perceptions of police legitimacy and the legitimacy of drug driving laws, but not with the elements of procedural justice. However, follow-up analyses indicated that the influence of procedural justice on intentions was mediated by the two legitimacy variables, thus weakening its direct impact on intentions. PRACTICAL APPLICATIONS: The results highlight the need for road safety authorities to enhance the perceived legitimacy of drug driving enforcement and associated laws. Changes to current police practices and/or drug-driving laws may also be needed to enhance the effectiveness of RDT.

Trends in polysubstance use among patients in methadone maintenance treatment in Ireland: Evidence from urine drug testing 2010-2020.

INTRODUCTION: The benefits of methadone maintenance treatment (MMT) may be compromised by the continued use of other substances during treatment. Polysubstance use has been identified as a major contributing factor to treatment discontinuation, a known risk factor for drug overdose. We examined trends in immunoassay drug positivity rates for amphetamines, benzodiazepines, cannabis, cocaine and opioids, and (2) trends in polysubstance positivity rates for drug combinations associated with increased risk of drug overdose among patients attending the national drug treatment centre in Ireland for MMT between 2010 and 2020. METHODS: Repeated cross-sectional study of patients attending the national drug treatment centre (NDTC) for MMT (total N = 1942) between 2010 and 2020, focused on urine drug samples provided for testing to the NDTC clinical testing laboratory (n = 221,564). Samples were analysed using immunoassay during the study period. Mixed-effects logistic regression models evaluate time trends in drug positivity. A random intercept accounts for repeat testing of individual patients. The study reports Adjusted Odds Ratios (AOR) for time (per year) with 95 % Confidence Intervals (95 % CI). RESULTS: Drug positivity rates increased over time for benzodiazepines (AOR 1.02, 95 % CI 1.01-1.03, p < .0001), cannabis (AOR 1.06, 95 % CI 1.05-1.08, p < .0001) and cocaine (AOR 1.28, 95 % CI 1.27-1.29, p < .0001), with decreasing trends for opioids (AOR 0.91, 95 % CI 0.91-0.92, p < .0001). Methadone and benzodiazepines were co-detected in over two-thirds of all samples during the study period. Co-detection of methadone and benzodiazepines with cocaine was also found to be increasing (AOR 1.24, 95 % CI 1.23-1.25, p < .0001), with weighted polysubstance positivity rates reaching 29.2 % in 2020. The co-detection of methadone and benzodiazepines with opioids decreased over the study period (AOR 0.92, 95 % CI 0.91-0.92, p < .0001), ranging from 36.7 % in 2010 to 26.9 % in 2020. CONCLUSION: Interventions are needed to target the persistently high use of benzodiazepines among patients in receipt of methadone due to their synergistic effects with opioids on respiratory depression, enhancing the risk of overdose. The growing use of cocaine among people in MMT also needs to be addressed.

X-ray absorption spectroscopy combined with deep learning for auto and rapid illicit drug detection.

Background: X-ray absorption spectroscopy (XAS) is a widely used substance analysis technique. It bases on the different absorption coefficients at different energy level to achieve material identification. Additionally, the combination of spectral technology and deep learning can achieve auto detection and high accuracy in material identification.Objectives: Current methods are difficult to identify drugs quickly and nondestructively. Therefore, we explore a novel approach utilizing XAS for the detection of prohibited drugs with common X-ray tube source and photon-counting (PC) detector.Method: To achieve automatic, rapid, and accurate detection of drugs. A CdTe detector and a common X-ray source were used to collect data, then dividing the data into training and testing sets. Finally, the improved transformer encoder model was used for classification. LSTM and ResU-net models are selected for comparation.Result: Fifty substances, which are isomers or compounds with similar molecular formulas of drugs, were selected for experiment substances. The results showed that the improved transformer model achieving 1.4 hours for training time and 96.73% for accuracy, which is better than the LSTM (2.6 hours and 65%) and ResU-net (1.5 hours and 92.7%).Conclusion: It can be concluded that the attention mechanism is more accurate for spectral material identification. XAS combined with deep learning can achieve efficient and accurate drug identification, offering promising application in clinical drug testing and drug enforcement.

New Psychoactive Substances: A Canadian perspective on emerging trends and challenges for the clinical laboratory.

The production and use of New Psychoactive Substances (NPS) has skyrocketed over the last decade, causing major challenges for government authorities, public health agencies, and laboratories across the world. NPS are designed to mimic the psychoactive effects of unregulated or controlled drugs, while constantly being modified to evade drug control regulation. Hence, they are referred to as "legal highs", as they are technically legal to sell, possess, and use. NPS can be classified by their pharmacological mechanism of action and include cannabimimetic, depressants, dissociatives, hallucinogens, opioids, and stimulants. There is significant structural diversity within each NPS class, leading to variable detection using traditional clinical laboratory testing and complicating the interpretation of results. In this article, we review each of the NPS classes and summarize their associated mechanism of action, common structures, and metabolic pathways, and provide examples of recent drugs and emerging threats with a focus on Canadian drug trends. We also explore the current analytical advantages and limitations commonly faced by the clinical laboratory and provide insight on how toxicosurveillance can improve detection of NPS in the ever-changing NPS landscape.

Perfused In Vitro Intestine Tissue Model to Evaluate the Role of Stromal and Immune Cells in Epithelial Response to Inflammatory Cues and Drug Therapies.

We establish an in vitro perfusion intestinal tissue bioreactor system tailored to study drug responses related to inflammatory bowel disease (IBD). The system includes key components including multiple human intestinal cell types (colonoids, myofibroblasts, and macrophages), a three-dimensional (3D) intestinal architecture, and fluid flow. Inclusion of myofibroblasts resulted in increased secretion of cytokines such as glypican-1 (GCP-1), granulocyte-macrophage colony-stimulating factor (GM-CSF), and interleukin 1-α (IL-1α), whereas inclusion of macrophages resulted in increased secretion of monocyte chemoattractant proteins (MCPs) demonstrating a significant role of both stromal and immune cell types in intestinal inflammation. The system is responsive to drug treatments, as reflected in the reduction of pro-inflammatory cytokine production in tissue in some treatment scenarios. While future studies are needed to evaluate more nuanced responses in an IBD context, the present study demonstrates the ability to establish a 3D intestinal model with multiple relevant cell types and flow that is responsive to both inflammatory cues and various drug treatment options.

Incorporation of suvorexant and lemborexant into hair and their distributions after a single intake.

PURPOSE: This study examined the applicability of hair analysis as an approach to identify suvorexant (SUV) and lemborexant (LEM) intake by analyzing black hair specimens collected from study participants after a single oral administration. METHODS: Hair specimens were collected form participants who took a single dose of 10 mg SUV or 5 mg LEM. Identification of the dual orexin receptor antagonists (DORAs) and their metabolites was performed by liquid chromatography-tandem mass spectrometry. Reference standards of S-M9 and L-M4, the metabolites of SUV and LEM, respectively, were synthesized in our laboratory. Sectional analysis of 1-mm segments of the single-hair strands was also performed to investigate the incorporation behavior of the drugs into hair. RESULTS: Unchanged SUV and LEM, and their metabolites S-M9 and L-M4 were detected even in the single-hair specimens. Results of the segmental hair analysis showed predominant incorporation of the drugs into hair through the hair bulb region rather than through the upper dermis zone of the hair root. The drug concentrations in the hair specimens, collected about 1 month after intake, were 0.033-0.037 pg/hair strand (0.17-0.19 pg/mg) for SUV and 0.054-0.28 pg/hair strand (0.28-1.5 pg/mg) for LEM. The calculated distribution ratios of the DORAs into hair to the oral doses were much lower than those of benzodiazepines and zolpidem reported in a previous study. CONCLUSIONS: This is the first report of the detection of the DORAs in hair. The incorporation behavior of the DORAs into hair revealed herein are crucial for proper interpretation of hair test results.

Drug sensitivity tumor cell clusters in malignant peritoneal mesothelioma.

BACKGROUND: To explore the most effective adjuvant chemotherapy regimen for malignant peritoneal mesothelioma (MPM) through patient derived tumor-like cell clusters (PTC) drug sensitivity test. METHODS: PTC were cultured in vitro with intraoperative specimens, and drug sensitivity test was performed to calculate the most effective chemotherapy regimen for MPM. The patients were divided into conventional and individualized chemotherapy group according to whether they received PTC drug testing. Univariate and multivariate analyses were conducted to identify independent prognostic factors. RESULTS: Among 186 MPM patients included, 63 underwent PTC culture and drug sensitivity test. The results showed that the most effective chemotherapy regimen was oxaliplatin + gemcitabine. After propensity score matching, a total of 64 patients were enrolled in the following study, including 32 patients receiving individualized chemotherapy guided by PTC drug results as group 1 and 32 patients receiving conventional chemotherapy as group 2. Survival analysis showed that the median OS of group 1 was not reached, significantly longer than that of group 2 (23.5 months) (p < 0.05). CONCLUSIONS: Compared with conventional chemotherapy, individualized chemotherapy guided by PTC drug sensitivity tests can prolong patient survival, and oxaliplatin + gemcitabine + apatinib could be the optimal adjuvant treatment regimen for MPM.

Enthesitis on Chip - A Model for Studying Acute and Chronic Inflammation of the Enthesis and its Pharmacological Treatment.

Enthesitis, the inflammation of the enthesis, which is the point of attachment of tendons and ligaments to bones, is a common musculoskeletal disease. The inflammation often originates from the fibrocartilage region of the enthesis as a consequence of mechanical overuse or -load and consequently tissue damage. During enthesitis, waves of inflammatory cytokines propagate in(to) the fibrocartilage, resulting in detrimental, heterotopic bone formation. Understanding of human enthesitis and its treatment options is limited, also because of lacking in vitro model systems that can closely mimic the pathophysiology of the enthesis and can be used to develop therapies. In this study, an enthes(it)is-on-chip model is developed. On opposite sides of a porous culture membrane separating the chip's two microfluidic compartments, human mesenchymal stromal cells are selectively differentiated into tenocytes and fibrochondrocytes. By introducing an inflammatory cytokine cocktail into the fibrochondrocyte compartment, key aspects of acute and chronic enthesitis, measured as increased expression of inflammatory markers, can be recapitulated. Upon inducing chronic inflammatory conditions, hydroxyapatite deposition, enhanced osteogenic marker expression and reduced secretion of tissue-related extracellular matrix components are observed. Adding the anti-inflammatory drug celecoxib to the fibrochondrocyte compartment mitigates the inflammatory state, demonstrating the potential of the enthesitis-on-chip model for drug testing.

Size and shape control of microgel-encapsulating tumor spheroid via a user-friendly solenoid valve-based sorter and its application on precise drug testing.

The precision of previous cancer research based on tumor spheroids, especially the microgel-encapsulating tumor spheroids, was limited by the high heterogeneity in the tumor spheroid size and shape. Here, we reported a user-friendly solenoid valve-based sorter to reduce this heterogeneity. The artificial intelligence algorithm was employed to detect and segmentate the tumor spheroids in real-time for the size and shape calculation. A simple off-chip solenoid valve-based sorting actuation module was proposed to sort out target tumor spheroids with the desired size and shape. Utilizing the developed sorter, we successfully uncovered the drug response variations on cisplatin of lung tumor spheroids in the same population but with different sizes and shapes. Moreover, with this sorter, the precision of drug testing on the spheroid population level was improved to a level comparable to the precise but complex single spheroid analysis. The developed sorter also exhibits significant potential for organoid morphology and sorting for precision medicine research.

Δ9-tetrahydrocannabinol and 11-hydroxy-Δ9-tetrahydrocannabinol as markers of cannabis use in urinary drug testing.

With some exceptions, California Assembly Bill 2188 will preclude the use of ∆9-tetrahydrocannabinol-9-carboxylic acid (Δ9-THC-COOH) as a marker of cannabis use in urinary workplace drug testing. The bill allows for the use of psychoactive cannabis markers, which include Δ9-tetrahydrocannabinol (Δ9-THC) and the metabolite 11-hydroxy-Δ9-tetrahydrocannabinol (11-OH-Δ9-THC). Both analytes are present in urine mainly as conjugated metabolites and will require hydrolysis prior to analysis, but very little is known about expected concentrations in urine. The aim of this study was to report concentrations from two large data sets comprising 1,411 workplace drug testing urine specimens positive by immunoassay (50 ng/mL cutoff) and discuss strategies for using 11-OH-Δ9-THC and/or Δ9-THC to detect cannabis use. Median 11-OH-Δ9-THC and Δ9-THC concentrations were 28-35% and 1.1-1.6% of those of Δ9-THC-COOH and correlations between analytes were observed. To avoid the risk of positives from passive exposure, laboratories could use a cutoff with equivalent sensitivity to cannabis exposure. A 5 ng/mL cutoff for 11-OH-Δ9-THC showed 92% agreement with a 15 ng/mL cutoff for Δ9-THC-COOH, with only 0.9% of specimens being positive only for 11-OH-Δ9-THC. It was not possible to propose an estimated cutoff for Δ9-THC, due to the constraints of the limit of detection used in this study.

Development and evaluation of portable NIR technology for the identification and quantification of Australian illicit drugs.

The efficient and accurate analysis of illicit drugs remains a constant challenge in Australia given the high volume of drugs trafficked into and around the country. Portable drug testing technologies facilitate the decentralisation of the forensic laboratory and enable analytical data to be acted upon more efficiently. Near-infrared (NIR) spectroscopy combined with chemometric modelling (machine learning algorithms) has been highlighted as a portable drug testing technology that is rapid and accurate. However, its effectiveness depends upon a database of chemically relevant specimens that are representative of the market. There are chemical differences between drugs in different countries that need to be incorporated into the database to ensure accurate chemometric model prediction. This study aimed to optimise and assess the implementation of NIR spectroscopy combined with machine learning models to rapidly identify and quantify illicit drugs within an Australian context. The MicroNIR (Viavi Solutions Inc.) was used to scan 608 illicit drug specimens seized by the Australian Federal Police comprising of mainly crystalline methamphetamine hydrochloride (HCl), cocaine HCl, and heroin HCl. A number of other traditional drugs, new psychoactive substances and adulterants were also scanned to assess selectivity. The 3673 NIR scans were compared to the identity and quantification values obtained from a reference laboratory in order to assess the proficiency of the chemometric models. The identification of crystalline methamphetamine HCl, cocaine HCl, and heroin HCl specimens was highly accurate, with accuracy rates of 98.4 %, 97.5 %, and 99.2 %, respectively. The sensitivity of these three drugs was more varied with heroin HCl identification being the least sensitive (methamphetamine = 96.6 %, cocaine = 93.5 % and heroin = 91.3 %). For these three drugs, the NIR technology provided accurate quantification, with 99 % of values falling within the relative uncertainty of ±15 %. The MicroNIR with NIRLAB infrastructure has demonstrated to provide accurate results in real-time with clear operational applications. There is potential to improve informed decision-making, safety, efficiency and effectiveness of frontline and proactive policing within Australia.

Intelligence-based anti-doping via an Intelligence and Drug Testing Management (IDTM) system.

The Intelligence and Drug Testing Management (IDTM), a system that can enhance drug testing analytics with related horse information and intelligence in a single platform, can help identify and mitigate potential doping and other threats.

A 3D Pancreatic Cancer Model with Integrated Optical Sensors for Noninvasive Metabolism Monitoring and Drug Screening.

A distinct feature of pancreatic ductal adenocarcinoma (PDAC) is a prominent tumor microenvironment (TME) with remarkable cellular and spatial heterogeneity that meaningfully impacts disease biology and treatment resistance. The dynamic crosstalk between cancer cells and the dense stromal compartment leads to spatially and temporally heterogeneous metabolic alterations, such as acidic pH that contributes to drug resistance in PDAC. Thus, monitoring the extracellular pH metabolic fluctuations within the TME is crucial to predict and to quantify anticancer drug efficacy. Here, a simple and reliable alginate-based 3D PDAC model embedding ratiometric optical pH sensors and cocultures of tumor (AsPC-1) and stromal cells for simultaneously monitoring metabolic pH variations and quantify drug response is presented. By means of time-lapse confocal laser scanning microscopy (CLSM) coupled with a fully automated computational analysis, the extracellular pH metabolic variations are monitored and quantified over time during drug testing with gemcitabine, folfirinox, and paclitaxel, commonly used in PDAC therapy. In particular, the extracellular acidification is more pronounced after drugs treatment, resulting in increased antitumor effect correlated with apoptotic cell death. These findings highlight the importance of studying the influence of cellular metabolic mechanisms on tumor response to therapy in 3D tumor models, this being crucial for the development of personalized medicine approaches.