Novel point-of-care cytokine biomarker lateral flow test for the screening for sexually transmitted infections and bacterial vaginosis: study protocol of a multicentre multidisciplinary prospective observational clinical study to evaluate the performance and feasibility of the Genital InFlammation Test (GIFT).

INTRODUCTION: A prototype lateral flow device detecting cytokine biomarkers interleukin (IL)-1α and IL-1ß has been developed as a point-of-care test-called the Genital InFlammation Test (GIFT)-for detecting genital inflammation associated with sexually transmitted infections (STIs) and/or bacterial vaginosis (BV) in women. In this paper, we describe the rationale and design for studies that will be conducted in South Africa, Zimbabwe and Madagascar to evaluate the performance of GIFT and how it could be integrated into routine care. METHODS AND ANALYSIS: We will conduct a prospective, multidisciplinary, multicentre, cross-sectional and observational clinical study comprising two distinct components: a biomedical ('diagnostic study') and a qualitative, modelling and economic ('an integration into care study') part. The diagnostic study aims to evaluate GIFT's performance in identifying asymptomatic women with discharge-causing STIs (Chlamydia trachomatis (CT), Neisseria gonorrhoeae (NG), Trichomonas vaginalis (TV) and Mycoplasma genitalium (MG)) and BV. Study participants will be recruited from women attending research sites and family planning services. Several vaginal swabs will be collected for the evaluation of cytokine concentrations (ELISA), STIs (nucleic acid amplification tests), BV (Nugent score) and vaginal microbiome characteristics (16S rRNA gene sequencing). The first collected vaginal swab will be used for the GIFT assay which will be performed in parallel by a healthcare worker in the clinic near the participant, and by a technician in the laboratory. The integration into care study aims to explore how GIFT could be integrated into routine care. Four activities will be conducted: user experiences and/or perceptions of the GIFT device involving qualitative focus group discussions and in-depth interviews with key stakeholders; discrete choice experiments; development of a decision tree classification algorithm; and economic evaluation of defined management algorithms. ETHICS AND DISSEMINATION: Findings will be reported to participants, collaborators and local government for the three sites, presented at national and international conferences, and disseminated in peer-reviewed publications.The protocol and all study documents such as informed consent forms were reviewed and approved by the University of Cape Town Human Research Ethics Committee (HREC reference 366/2022), Medical Research Council of Zimbabwe (MRCZ/A/2966), Comité d'Ethique pour la Recherche Biomédicale de Madagascar (N° 143 MNSAP/SG/AMM/CERBM) and the London School of Hygiene and Tropical Medicine ethics committee (LSHTM reference 28046).Before the start, this study was submitted to the Clinicaltrials.gov public registry (NCT05723484). TRIAL REGISTRATION NUMBER: NCT05723484.

Biosensors for psychiatric biomarkers in mental health monitoring.

Psychiatric disorders are associated with serve disturbances in cognition, emotional control, and/or behavior regulation, yet few routine clinical tools are available for the real-time evaluation and early-stage diagnosis of mental health. Abnormal levels of relevant biomarkers may imply biological, neurological, and developmental dysfunctions of psychiatric patients. Exploring biosensors that can provide rapid, in-situ, and real-time monitoring of psychiatric biomarkers is therefore vital for prevention, diagnosis, treatment, and prognosis of mental disorders. Recently, psychiatric biosensors with high sensitivity, selectivity, and reproducibility have been widely developed, which are mainly based on electrochemical and optical sensing technologies. This review presented psychiatric disorders with high morbidity, disability, and mortality, followed by describing pathophysiology in a biomarker-implying manner. The latest biosensors developed for the detection of representative psychiatric biomarkers (e.g., cortisol, dopamine, and serotonin) were comprehensively summarized and compared in their sensitivities, sensing technologies, applicable biological platforms, and integrative readouts. These well-developed biosensors are promising for facilitating the clinical utility and commercialization of point-of-care diagnostics. It is anticipated that mental healthcare could be gradually improved in multiple perspectives, ranging from innovations in psychiatric biosensors in terms of biometric elements, transducing principles, and flexible readouts, to the construction of 'Big-Data' networks utilized for sharing intractable psychiatric indicators and cases.

Biomarker-guided drug development provides value for patients, payers and drug developers: lessons learned from 25 years in the biomarker industry.

INTRODUCTION: There is an urgent, persistent, need for better biomarkers in clinical drug development. More informative biomarkers can increase the likelihood of drug advancement or approval, and implementing biomarkers increases the success rate in drug development. Biomarkers may guide decisions and allow resources to be directed to the projects most likely to succeed. However, biomarkers that are validated to high standards are needed, reflecting biological and pathological processes accurately. Such biomarkers are needed to develop treatments faster, and to improve and guide clinical trial design by selecting and de-selecting patients. METHODS: In this review based on the authors' previous published experience and interaction with pharmaceutical- and biomarker stakeholders, we highlight the use and value of biomarkers in clinical development according to the BEST guidelines. We highlight the value of 3 types of biomarkers that may provide optimal value to stakeholders: diagnostic, prognostic and pharmacodynamic biomarkers. RESULTS: A more appropriate clinical trial design, increasing the ratio between benefits and side effects, may come from a more tailored biomarker-approach identifying suitable molecular endotypes of patients to treat. DISCUSSION: Biomarkers may guide drug developers in selecting the optimal projects to progress, when designing clinical studies and development paths. Biomarkers may aid in the diagnosis and prognostic assessment of patients and assist in matching the molecular endotype to the selected treatment, which improves the success rate of clinical development progression. The aim of this paper is to provide a comprehensive ideation framework for how to utilize biomarkers in clinical development, with a focus on utility for patients, payers and drug developers.

2023 White Paper on Recent Issues in Bioanalysis: ISR for ADA Assays, the Rise of dPCR vs qPCR, International Reference Standards for Vaccine Assays, Anti-AAV TAb Post-Dose Assessment, NanoString Validation, ELISpot as Gold Standard (Part 3 - Recommendations on Gene Therapy, Cell Therapy, Vaccines Immunogenicity & Technologies; Biotherapeutics Immunogenicity & Risk Assessment; ADA/NAb Assay/Reporting Harmonization).

The 17th Workshop on Recent Issues in Bioanalysis (17th WRIB) took place in Orlando, FL, USA on June 19-23, 2023. Over 1000 professionals representing pharma/biotech companies, CROs, and multiple regulatory agencies convened to actively discuss the most current topics of interest in bioanalysis. The 17th WRIB included 3 Main Workshops and 7 Specialized Workshops that together spanned 1 week to allow an exhaustive and thorough coverage of all major issues in bioanalysis of biomarkers, immunogenicity, gene therapy, cell therapy and vaccines. Moreover, in-depth workshops on "EU IVDR 2017/746 Implementation and impact for the Global Biomarker Community: How to Comply with these NEW Regulations" and on "US FDA/OSIS Remote Regulatory Assessments (RRAs)" were the special features of the 17th edition. As in previous years, WRIB continued to gather a wide diversity of international, industry opinion leaders and regulatory authority experts working on both small and large molecules as well as gene, cell therapies and vaccines to facilitate sharing and discussions focused on improving quality, increasing regulatory compliance, and achieving scientific excellence on bioanalytical issues. This 2023 White Paper encompasses recommendations emerging from the extensive discussions held during the workshop and is aimed to provide the bioanalytical community with key information and practical solutions on topics and issues addressed, in an effort to enable advances in scientific excellence, improved quality and better regulatory compliance. Due to its length, the 2023 edition of this comprehensive White Paper has been divided into three parts for editorial reasons. This publication (Part 3) covers the recommendations on Gene Therapy, Cell therapy, Vaccines and Biotherapeutics Immunogenicity. Part 1A (Mass Spectrometry Assays and Regulated Bioanalysis/BMV), P1B (Regulatory Inputs) and Part 2 (Biomarkers, IVD/CDx, LBA and Cell-Based Assays) are published in volume 16 of Bioanalysis, issues 8 and 9 (2024), respectively.

Quantitative Assessment of Fungal Biomarkers in Clinical Samples via an Interface-Modulated Optical Fiber Biosensor.

Invasive fungal infections pose a significant public health threat. The lack of precise and timely diagnosis is a primary factor contributing to the significant increase in patient mortality rates. Here, an interface-modulated biosensor utilizing an optical fiber for quantitative analysis of fungal biomarkers at the early stage of point-of-care testing (POCT), is reported. By integrating surface refractive index (RI) modulation and plasmon enhancement, the sensor to achieve high sensitivity in a directional response to the target analytes, is successfully optimized. As a result, a compact fiber-optic sensor with rapid response time, cost-effectiveness, exceptional sensitivity, stability, and specificity, is developed. This sensor can successfully identify the biomarkers of specific pathogens from blood or other tissue specimens in animal models. It quantifies clinical blood samples with precision and effectively discriminates between negative and positive cases, thereby providing timely alerts to potential patients. It significantly reduces the detection time of fungal infection to only 30 min. Additionally, this approach exhibits remarkable stability and achieves a limit of detection (LOD) three orders of magnitude lower than existing methods. It overcomes the limitations of existing detection methods, including a high rate of misdiagnosis, prolonged detection time, elevated costs, and the requirement for stringent laboratory conditions.

Influence of controlled environmental conditions in potential salivary ocular pain biomarkers for enhancing the assessment of ocular pain.

PURPOSE: We endeavored to identify objective salivary biomarkers for pain, a subjective sensation with a biological basis, using molecules already described related to pain. The study aimed to analyze inter-individual differences and intersession variability in salivary potential ocular pain biomarkers on healthy subjects, in samples obtained under the influence of controlled environmental conditions. METHODS: Thirty-four healthy subjects, 20 male, 14 female, median age 35.44 years (range 30-40) were exposed for 30 minutes under standard environmental conditions (T: 22°C, 50% relative humidity) in the Controlled Environmental Research Laboratory (CE-Lab, Vision R&D, Valladolid Spain) in two separate visits (V1, V2) at least 24 hours apart. Saliva was collected after the exposure in each of the visits, and cortisol, α-amylase (sAA), secretory IgA (sIgA), testosterone, and soluble fraction of TNFα receptor II (sTNFαRII) were analyzed by ELISA. Repeatability of inter-subject inter-session measurements was assayed by intraclass correlation coefficient (ICC). RESULTS: There were no significant inter-session differences in testosterone (p = 0.2497), sTNFαRII (p = 0.6451) and sIgA (p = 0.9689) salivary levels. The reproducibility for salivary cortisol, sAA, testosterone, sTNFαRII and sIgA were 0.98 ng/ml, 20.58 U/ml, 21.07 µg/ml, 24.68 pg/ml and 0.19 pg/ml, respectively. Salivary cortisol, sAA, testosterone, sTNFαRII and sIgA yielded the following ICCs: 0.506, 0.569, 0.824, 0.870 and 0.4295, respectively; all these ICCs (except that for cortisol and sIgA) were found to be improved compared to those found previously by our group in a previous study in salivary samples obtained from healthy subjects under non-controlled environmental conditions; Cortisol´s ICC didn´t improve and was in both cases at the limit of acceptability. CONCLUSION: Environmental factors such as temperature and relative humidity affect the reproducibility of measurement of some salivary molecules which have been proposed as potential pain biomarkers. The exposure of subjects to standard controlled environmental conditions before salivary sample obtention would improve the reproducibility of these molecule measures' as potential biomarkers of chronic ocular pain.

Composite Assessment Using Intestinal Ultrasound and Calprotectin Is Accurate in Predicting Histological Activity in Ulcerative Colitis: A Cohort Study.

BACKGROUND: Beyond endoscopic remission, histological remission in ulcerative colitis (UC) is predictive of clinical outcomes. Intestinal ultrasound (IUS) may offer a noninvasive surrogate marker for histological activity; however, there are limited data correlating validated ultrasound and histological indices. AIM: Our aim was to determine the correlation of IUS activity in UC with a validated histological activity index. METHODS: Twenty-nine prospective, paired, same-day IUS/endoscopy/histology/fecal calprotectin (FC) cases were included. Intestinal ultrasound activity was determined using the Milan Ultrasound Criteria, histological activity using the Nancy Histological Index, endoscopic activity using Mayo endoscopic subscore and Ulcerative Colitis Endoscopic Index of Severity, and clinical activity using the Simple Clinical Colitis Activity Score. RESULTS: Histological activity demonstrated a significant linear association with overall IUS activity (coefficient 0.14; 95% CI, 0.03-0.25; P = .011). Intestinal ultrasound activity was also significantly associated with endoscopic activity (0.32; 95% CI, 0.14-0.49; P < 0.001), total Mayo score (0.31; 95% CI, 0.02-0.60; P = .036) but not FC (0.10; 95% CI, -0.01 to 0.21; P = .064) or clinical disease activity (0.04; 95% CI, -0.21 to 0.28; P = .768). A composite of IUS and FC showed the greatest association (1.31; 95% CI, 0.43-2.18; P = .003) and accurately predicted histological activity in 88% of cases (P = .007), with sensitivity of 88%, specificity 80%, positive predictive value 95%, and negative predictive value 57%. CONCLUSIONS: Intestinal ultrasound is an accurate noninvasive marker of histological disease activity in UC, the accuracy of which is further enhanced when used in composite with FC. This can reduce the need for colonoscopy in routine care by supporting accurate point-of-care decision-making in patients with UC.

An integrated biological effects assessment of the discharge water into the Sunndalsfjord from an aluminium smelter.

An integrated biological effects study using field transplanted mussels was applied to determine the potential biological effects of an effluent discharge from an aluminium smelter into a Norwegian fjord. Chemical body burden and biological effects were measured in mussels positioned downstream (1, 2, 5, 10 and 20 km) from the aluminium smelters discharge for a period of 6 weeks. A suite of biomarkers, from whole organism to subcellular responses were measured. Chemical concentrations in mussel tissues were low; however, a change in the PAC (polyaromatic compound) profile from high to low pyrogenic influence provided evidence of exposure to the smelter's effluent. Overall, the biological responses observed where greater in the mussels positioned closest to the smelter (1-5 km). Lowest chemical accumulation and biomarker responses were observed in mussels positioned 10 km from the smelter and were considered as the reference field population. Mussels located furthest from the smelter (20 km) exhibited significant biomarker responses and suggested a different contaminant source within the fjord. The integrated biological response index (IBR) was applied and reflected the expected level of exposure to the smelters discharge, with highest IBR calculated in mussels positioned closest to the discharge (1-5 km). Principal component analysis (PCA) also differentiated among mussel groups, with the most impacted located closest to the smelter. Not one chemical factor could explain the biological responses observed in mussels, but the presence of PAH16, PAH41 and metals Mn, Ni and Cr were the main contributors measured to the higher stress seen in the mussels from the 1 and 5 km groups.

2022 White Paper on Recent Issues in Bioanalysis: FDA Draft Guidance on Immunogenicity Information in Prescription Drug Labeling, LNP & Viral Vectors Therapeutics/Vaccines Immunogenicity, Prolongation Effect, ADA Affinity, Risk-based Approaches, NGS, qPCR, ddPCR Assays (Part 3 - Recommendations on Gene Therapy, Cell Therapy, Vaccines Immunogenicity & Technologies; Immunogenicity & Risk Assessment of Biotherapeutics and Novel Modalities; NAb Assays Integrated Approach).

The 2022 16th Workshop on Recent Issues in Bioanalysis (WRIB) took place in Atlanta, GA, USA on September 26-30, 2022. Over 1000 professionals representing pharma/biotech companies, CROs, and multiple regulatory agencies convened to actively discuss the most current topics of interest in bioanalysis. The 16th WRIB included 3 Main Workshops and 7 Specialized Workshops that together spanned 1 week in order to allow exhaustive and thorough coverage of all major issues in bioanalysis, biomarkers, immunogenicity, gene therapy, cell therapy and vaccines. Moreover, in-depth workshops on ICH M10 BMV final guideline (focused on this guideline training, interpretation, adoption and transition); mass spectrometry innovation (focused on novel technologies, novel modalities, and novel challenges); and flow cytometry bioanalysis (rising of the 3rd most common/important technology in bioanalytical labs) were the special features of the 16th edition. As in previous years, WRIB continued to gather a wide diversity of international, industry opinion leaders and regulatory authority experts working on both small and large molecules as well as gene, cell therapies and vaccines to facilitate sharing and discussions focused on improving quality, increasing regulatory compliance, and achieving scientific excellence on bioanalytical issues. This 2022 White Paper encompasses recommendations emerging from the extensive discussions held during the workshop and is aimed to provide the bioanalytical community with key information and practical solutions on topics and issues addressed, in an effort to enable advances in scientific excellence, improved quality and better regulatory compliance. Due to its length, the 2022 edition of this comprehensive White Paper has been divided into three parts for editorial reasons. This publication (Part 3) covers the recommendations on Gene Therapy, Cell therapy, Vaccines and Biotherapeutics Immunogenicity. Part 1 (Mass Spectrometry and ICH M10) and Part 2 (LBA, Biomarkers/CDx and Cytometry) are published in volume 15 of Bioanalysis, issues 16 and 15 (2023), respectively.

Assessment of intensive periurban agriculture soil quality applying biomarkers in earthworms.

Periurban agriculture in Argentina is carried out by farmers without adequate control. The indiscriminate agrochemical application for productivity improvement negatively impacts the environment. The objective of this work was to test the quality of periurban agricultural soils by performing bioassays with Eisenia andrei as an indicator. Soils belonging to two orchards with intensive production (S: strawberry/broccoli crop plot and G: tomato/pepper crop greenhouse - Moreno District, Buenos Aires, Argentina) were sampled during 2015 and 2016. As subcellular biomarkers, cholinesterases (ChE), carboxylesterases (CaE), and glutathione-S-transferases (GST) activities were analysed in E. andrei (7-day exposure). While no effect on ChE activities was observed, CaE activities were significantly reduced 18% (S-2016 soil). GST activities were increased 35% and 30% by S-2016 and G-2016, respectively. CaE decrease together with GST increase could be indicative of a negative disturbance. Concerning whole organism biomarkers, reproduction (56-day exposure), avoidance (3-day exposure), and feeding activity (bait-lamina test, 3-day exposure) were analysed. A reduced cocoons' viability (50%), hatchability (55%), accompanied by a low number of juveniles (50%) were observed in all cases. Additionally, the earthworms exhibited significant avoidance responses to S-2015, S-2016 and G-2016 whereas G-2015 soil induced migration. No significant effect on the feeding activity was registered in any case. Most of the E. andrei biomarkers tested could constitute an early warning of harmful effects produced by polluted periurban soils, even if the agrochemical treatment applied remains unknown. The results reveal the need to develop an action plan to avoid further deterioration of the productive soil.

Assessment of the diagnostic accuracy of noninvasive scoring tools in predicting moderate-to-severe steatohepatitis via ultrasonography in asymptomatic healthy subjects admitted to family medicine outpatient clinics.

OBJECTIVE: Efficacies of the noninvasive scoring tools in screening and diagnosing nonalcoholic fatty liver disease (NAFLD) remain controversial. Aspartate aminotransferase/alanine aminotransferase (AST/ALT) ratio, AST-to-platelet ratio index (APRI), and fibrosis-4 (FIB-4) index are the most frequently used parameters for differentiating moderate and severe steatohepatitis. In this context, the objective of this study is to evaluate the diagnostic accuracy of noninvasive tools in predicting moderate-to-severe steatohepatitis via ultrasonography in asymptomatic healthy subjects admitted to family medicine outpatient clinics. PATIENTS AND METHODS: The population of this retrospective study consisted of healthy individuals tested within the scope of a medical check-up program between January and July 2021. All participants included in the study underwent relevant laboratory tests and liver ultrasonography (US). Steatohepatitis was graded using the US images as normal (grade 0), mild (grade 1), moderate (grade 2), and severe (grade 3). The participants with grade 0 and 1 steatohepatitis were categorized as Group 1, whereas those with grade 2 and 3 steatohepatitis (NAFLD) were categorized as Group 2. Any relationship between the aminotransferase/alanine aminotransferase (AST/ALT), AST-to-platelet ratio index (APRI), and fibrosis-4 index (FIB-4) parameters and the diagnostic powers thereof were analyzed based on the collected data. RESULTS: The mean age of the study sample (n=408) was 46.1±12.7 years. There were 352 (86.3%) and 56 individuals in Groups 1 and 2, respectively. Platelet-to-lymphocyte ratio (PLR) and AST/ALT values were significantly higher, whereas APRI values were significantly lower in Group 1 than in Group 2 (p=0.004, p<0.001, and p<0.001, respectively). There were significant correlations between the presence of NAFLD and PLR values of ≤90.78 [area under the curve (AUC)=0.619, 95% confidence interval (CI): 0.570-0.666, p=0.007], AST/ALT values of ≤0.91 (AUC=0.802, 95% CI: 0.760-0.840, p<0.001), and APRI values of >0.22 (AUC=0.687, 95% CI: 0.640-0.732, p<0.001). CONCLUSIONS: The composite noninvasive indices, including PLR, AST/ALT, and APRI, can be beneficial in predicting NAFLD in healthy individuals.

Seminal plasma testis expressed sequence (TEX)-101 as a biomarker for the qualitative assessment of male factor infertility: A case-control study.

OBJECTIVE: The study was conducted to assess the role of seminal plasma Testis Expressed Sequence (TEX)-101 as a biomarker of male infertility. STUDY DESIGN: The study was conducted on 180 men (20-50 years) with 90 having abnormal semen reports as cases and 90 with normal reports as controls in a rural tertiary care center in Southern India over two years. After the enrolment of cases and control, semen samples were cryopreserved till the desired sample size was achieved and a biochemical test for TEX-101 was run using Human Testis-expressed Protein 101 ELISA Kit. The results of TEX-101 were compared between cases and controls and correlated with various semen parameters. Statistical analysis was done using SPSS software version 22.0, a p-value < 0.05 was considered statistically significant. RESULTS: Mean ± SD age of all participants was 29.94 ± 4.91 years. Of 90 cases, 48.9% had asthenospermia, 24.4% oligoasthenospermia, 15.6% oligospermia, 11.1% azoospermia. A statistically significant difference was observed in mean values of seminal plasma TEX-101 between cases (1.45 ± 0.08 ng/mL) and controls (2.26 ± 0.18 ng/mL), p = 0.001. A significant correlation (p = 0.001) was found between seminal TEX-101, semen volume, sperm concentration, progressive motility, and morphology. The area under the Receiver Operating Characteristic curve of TEX-101 between cases and controls was 1.00 (p = 0.001), indicating TEX-101 as a potential biomarker for distinguishing men with abnormal semen parameters from those with normal semen parameters. At a cut-off value of 1.84 ng/mL, seminal plasma TEX-101 had a sensitivity, specificity, and negative and positive predictive values of 100% for male infertility prediction. CONCLUSION: Seminal TEX-101 is a potential seminal biomarker and can be used in the qualitative assessment of male factor infertility.

Assessment of alcohol consumption in mexican pregnant women by hair testing of ethyl glucuronide.

There are no studies that have utilized both biomarkers and self-reported data to evaluate maternal alcohol use during pregnancy in Mexico. Therefore, we aimed to describe the prevalence of alcohol consumption in a cohort of 300 Mexican pregnant women. We used a validated ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method to measure hair ethyl glucuronide (EtG) in hair segments that corresponded to the first and second half of pregnancy. We compared the hair EtG values to a self-reported questionnaire on maternal drinking habits and evaluated whether the gestational alcohol use was associated with psychotropic drug use. Based on the EtG measurements, 263 women (87.7%) were alcohol-abstinent during the entire pregnancy, while 37 (12.3%) had used alcohol at least once during the pregnancy. Of these, only two women were found to have problematic alcoholic behavior during the entire pregnancy. No significant differences in sociodemographic characteristics were observed between alcohol-abstinent women and women with drinking habits. The self-reporting data and hair EtG gave heterogeneous results: although 37 women had self-reported alcohol use during pregnancy, only 54.1% of these women tested positive for hair EtG. Of the women who tested positive for hair EtG, 54.1% tested positive for psychoactive substances. In our cohort, the use of drugs of abuse was independent of gestational drinking. This study provided the first objective evidence of prenatal ethanol consumption in a cohort of Mexican pregnant women.

Quality assessment of traditional Chinese medicine using quality biomarkers: Compound DanShen dripping pills as an example.

BACKGROUND: The quality control of traditional Chinese medicine (TCM) is one of the main topics in TCM modernisation research. To date, the overwhelming majority of research has focused on chemical ingredients in the quality control of TCM. However, detecting a single or multiple chemical components cannot fully demonstrate the specificity and correlation between quality and efficacy. PURPOSE: To solve the problem that the association between quality control and efficacy is lacking. The present study was designed to establish a methodology for quality control based on quality biomarkers (Q-biomarkers) and the vasodilatation efficacy of compound DanShen dripping pills (CDDP) as a case. METHODS: Guided by the basic principles of Q-biomarkers, the compounds in TCM were determined by ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry. Predicted targets were screened through network pharmacology. The potential Q-biomarkers were further screened through proteomics and partial least squares regression analysis. The protein-protein interaction network that combines both predicted targets and potential Q-biomarkers was constructed to screen Q-biomarkers. RESULTS: There were 32 components and 79 predictive targets for CDDP. Proteomic results indicated that the expression of 23 differential proteins changed as pharmacodynamic and componential changes. CPSF6, RILP11, TMEM209, COQ7, VPS18, PPPP1CA, NF2, and ARFRP1 highly correlated with vasodilation. Protein interaction network analysis showed that NF2 and PPPP1CA were closely related to predicted proteins. Thus, NF2 and PPPP1CA could be considered as Q-biomarkers of CDDP. CONCLUSION: Our preliminary study suggested the feasibility of the Q-biomarkers theory in the quality of TCM. The concept of Q-biomarkers provided a powerful method to strengthen the link between clinical efficacy and the quality of TCM. In conclusion, a novel, more scientific, and standard quality control method was established in this study.

GC-MS analysis of soil faecal biomarkers uncovers mammalian species and the economic management of the archeological site "Le Colombare di Negrar".

The identification of the mammalian species based on faecal sediments in modern and ancient environments is the aim of the research of archaeologists, forensic scientists and ecologists. Here, we set up and validated an optimized gas chromatography-mass spectrometry (GC-MS) method, characterized by a time-saving sample preparation protocol, for the simultaneous analysis of faecal biomarkers (6 sterols/stanols and 5 bile acids) in 14 soil samples from the archaeological site of "Le Colombare di Negrar" in northern Italy. Although the archaeological sediment samples examined are numerically exiguous, a comparative reading of our faecal biomarkers findings with new studies on faunal materials collected in the same stratigraphic detail during recent excavation campaigns will allow to better clarify the economic interest of the animal species farmed in the Colombare site (such as bovines, goats, sheep and pigs) and to shed light on the management of breeding. Together with archaeozoological and archaeobotanical analyses, the investigation of faecal biomarkers can increase our knowledge of how ancient local communities exploited natural resources and may allow us to deduce what their impact on the landscape was.

Wastewater-based epidemiology for the assessment of population exposure to chemicals: The need for integration with human biomonitoring for global One Health actions.

WBE has now become a complimentary tool in SARS-CoV-2 surveillance. This was preceded by the established application of WBE to assess the consumption of illicit drugs in communities. It is now timely to build on this and take the opportunity to expand WBE to enable comprehensive assessment of community exposure to chemical stressors and their mixtures. The goal of WBE is to quantify community exposure, discover exposure-outcome associations, and trigger policy, technological or societal intervention strategies with the overarching aim of exposure prevention and public health promotion. To achieve WBE's full potential, the following key aspects require further action: (1) Integration of WBE-HBM (human biomonitoring) initiatives that provide comprehensive community-individual multichemical exposure assessment. (2) Global WBE monitoring campaigns to provide much needed data on exposure in low- and middle-income countries (LMICs) and fill in the gaps in knowledge especially in the underrepresented highly urbanised as well as rural settings in LMICs. (3) Combining WBE with One Health actions to enable effective interventions. (4) Advancements in new analytical tools and methodologies for WBE progression to enable biomarker selection for exposure studies, and to provide sensitive and selective multiresidue analysis for trace multi-biomarker quantification in a complex wastewater matrix. Most of all, further developments of WBE needs to be undertaken by co-design with key stakeholder groups: government organisations, health authorities and private sector.

Assessment of an e-nose performance for the detection of COVID-19 specific biomarkers.

Early, rapid and non-invasive diagnosis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is needed for the prevention and control of coronavirus disease 2019 (COVID-19). COVID-19 mainly affects the respiratory tract and lungs. Therefore, analysis of exhaled breath could be an alternative scalable method for reliable SARS-CoV-2 screening. In the current study, an experimental protocol using an electronic-nose ('e-nose') for attempting to identify a specific respiratory imprint in COVID-19 patients was optimized. Thus the analytical performances of the Cyranose®, a commercial e-nose device, were characterized under various controlled conditions. In addition, the effect of various experimental conditions on its sensor array response was assessed, including relative humidity, sampling time and flow rate, aiming to select the optimal parameters. A statistical data analysis was applied to e-nose sensor response using common statistical analysis algorithms in an attempt to demonstrate the possibility to detect the presence of low concentrations of spiked acetone and nonanal in the breath samples of a healthy volunteer. Cyranose®reveals a possible detection of low concentrations of these two compounds, in particular of 25 ppm nonanal, a possible marker of SARS-CoV-2 in the breath.

Noninvasive Assessment of Postoperative Disease Recurrence in Crohn's Disease: A Multicenter, Prospective Cohort Study on Behalf of the Italian Group for Inflammatory Bowel Disease.

BACKGROUND & AIMS: Colonoscopy (CS) is the gold standard to assess postoperative recurrence (POR) in Crohn's disease (CD). However, CS is invasive and may be poorly tolerated by patients. The aim of this study was to prospectively assess the diagnostic accuracy of a noninvasive approach in detecting POR, using the endoscopic Rutgeerts' score (RS) as the reference standard. METHODS: Consecutive patients with CD who underwent ileo-cecal resection were prospectively enrolled in 3 referral Italian centers. Patients underwent CS and bowel ultrasound within 1 year of surgery. Uni- and multivariable analyses were used to assess the correlation between noninvasive parameters and endoscopic recurrence, defined by a RS ≥2. RESULTS: Ninety-one patients were enrolled. Sixty patients (66%) experienced endoscopic POR. The multivariable analysis identified bowel wall thickness (BWT) per 1-mm increase (odds ratio [OR], 2.43; 95% confidence interval [CI], 1.21-4.89; P = .012), the presence of mesenteric lymph nodes (OR, 15.63; 95% CI, 1.48-164.54; P = .022), and fecal calprotectin (FC) values ≥50 mcg/g (OR, 8.58; 95% CI, 2.45-29.99; P < .001) as independent predictors for endoscopic recurrence. The presence of lymph nodes or the combination of BWT ≥3 mm and FC values ≥50 mcg/g correctly classified 56% and 75% of patients, with less than 5% of patients falsely classified as having endoscopic recurrence. Conversely, the combination of BWT <3 mm and FC <50 mcg/g correctly classified 74% of patients with only 4.5% of patients falsely classified as not having endoscopic recurrence. CONCLUSIONS: A noninvasive approach combining bowel ultrasound and FC can be used with confidence for detecting POR in patients with CD without the requirement for CS.

Field validated biomarker (ValidBIO) based assessment of impacts of various pollutants in water.

The sensitivity of fish towards pollutants serves as an excellent tool for the analysis of water pollution. The effluents generated from various anthropogenic activities may contain heavy metals, pesticides, microplastics, and persistent organic pollutants (POPs) and ultimately find its way to aquatic environment. The enzymatic activities of fish collected from water bodies near major cities, oil spillage sites, agricultural land, and intensively industrialized areas have been reported to be significantly impacted in various field studies. These significant alterations in enzymatic activities act as a biomarker for monitoring purposes. The use of biomarkers not only helps in the identification of known and unknown pollutants and their detrimental health impacts, but also identifies the interaction between pollutants and organisms. The conventional method majorly used is physicochemical analysis, which is recognized as the backbone of the system for monitoring water quality. In physicochemical monitoring, major problems exist in assessing or predicting biological effects from chemical or physical data. Xenobiotic-induced enzymatic changes in fish may serve as an intuitive and efficient biomarker for determining contaminants in water bodies. Therefore, field validated biomarker (ValidBIO) approach needs to be integrated in water quality monitoring program for environmental health risk assessment of aquatic life impacted due to various point and non-point sources of water pollution.

Assessment and prediction of glioblastoma therapy response: challenges and opportunities.

Glioblastoma is the most aggressive type of primary adult brain tumour. The median survival of patients with glioblastoma remains approximately 15 months, and the 5-year survival rate is <10%. Current treatment options are limited, and the standard of care has remained relatively constant since 2011. Over the last decade, a range of different treatment regimens have been investigated with very limited success. Tumour recurrence is almost inevitable with the current treatment strategies, as glioblastoma tumours are highly heterogeneous and invasive. Additionally, another challenging issue facing patients with glioblastoma is how to distinguish between tumour progression and treatment effects, especially when relying on routine diagnostic imaging techniques in the clinic. The specificity of routine imaging for identifying tumour progression early or in a timely manner is poor due to the appearance similarity of post-treatment effects. Here, we concisely describe the current status and challenges in the assessment and early prediction of therapy response and the early detection of tumour progression or recurrence. We also summarize and discuss studies of advanced approaches such as quantitative imaging, liquid biomarker discovery and machine intelligence that hold exceptional potential to aid in the therapy monitoring of this malignancy and early prediction of therapy response, which may decisively transform the conventional detection methods in the era of precision medicine.