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Background: Human sweat can be collected non-invasively with low infectivity; however, its application as a determination method has been challenged due to the presence of trace amounts of chiral metabolites. Moreover, its application as a biological fluid for disease diagnosis has not been previously reported. In this study, the human dried sweat spot paper (DSSP) method was proposed for the derivatization of a novel mass spectrometric chiral probe, N-[1-Oxo-5-(triphenylphosphonium) pentyl]-(S)-3-aminopyrrolidine (OTPA), determination and resolution of DL-lactic acid (DL-LA) enantiomers in human elbow sweat., Results: The methodological validation revealed the resolution (Rs) as 1.78, the limit of detection (S/N = 3) as 20.83 fmol, good linearity (R 2  ≥ 0.9996), and the intra-day and intra-day stability with RSD ranging from 0.53 to 10.85 %, while the average recovery rate of D-LA and L-LA were 104.00 % ± 4.68 % and 107.41 % ± 8.34 %, respectively, with high accuracy. In addition, the method was applied for the determination of DL-LA in the sweat on elbow of 10 healthy volunteers and 30 diabetic patients. The results demonstrated that the D/L ratio and L/D ratio were significantly different (p < 0.0001). In addition, a moderate positive linear correlation between the D/L-LA ratio in human sweat and fasting blood glucose level (r = 0.7744, p < 0.0001) was observed, thereby suggesting that the D/L ratio of lactate in human sweat correlate the glucose level in human fasting blood., Significance and Novelty: The D/L lactate ratio in human sweat could be used as a potential biomarker for diabetes screening. The method can be used to screen for diabetes by providing a dry sweat paper to test equipment and has the potential to be a non-invasive early-warning diagnostic tool for diabetes., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Alzheimer's disease (AD) is a prevalent neurodegenerative disease with no effective treatment. Efficient and rapid detection plays a crucial role in mitigating and managing AD progression. Deep learning-assisted smartphone-based microfluidic paper analysis devices (μPADs) offer the advantages of low cost, good sensitivity, and rapid detection, providing a strategic pathway to address large-scale disease screening in resource-limited areas. However, existing smartphone-based detection platforms usually rely on large devices or cloud servers for data transfer and processing. Additionally, the implementation of automated colorimetric enzyme-linked immunoassay (c-ELISA) on μPADs can further facilitate the realization of smartphone μPADs platforms for efficient disease detection., Results: This paper introduces a new deep learning-assisted offline smartphone platform for early AD screening, offering rapid disease detection in low-resource areas. The proposed platform features a simple mechanical rotating structure controlled by a smartphone, enabling fully automated c-ELISA on μPADs. Our platform successfully applied sandwich c-ELISA for detecting the β-amyloid peptide 1-42 (Aβ 1-42, a crucial AD biomarker) and demonstrated its efficacy in 38 artificial plasma samples (healthy: 19, unhealthy: 19, N = 6). Moreover, we employed the YOLOv5 deep learning model and achieved an impressive 97 % accuracy on a dataset of 1824 images, which is 10.16 % higher than the traditional method of curve-fitting results. The trained YOLOv5 model was seamlessly integrated into the smartphone using the NCNN (Tencent's Neural Network Inference Framework), enabling deep learning-assisted offline detection. A user-friendly smartphone application was developed to control the entire process, realizing a streamlined "samples in, answers out" approach., Significance: This deep learning-assisted, low-cost, user-friendly, highly stable, and rapid-response automated offline smartphone-based detection platform represents a good advancement in point-of-care testing (POCT). Moreover, our platform provides a feasible approach for efficient AD detection by examining the level of Aβ 1-42, particularly in areas with low resources and limited communication infrastructure., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The exploration into nanomaterial-based nonenzymatic biosensors with superb performance in terms of good sensitivity and anti-interference ability in disease marker monitoring has always attained undoubted priority in sensing systems. In this work, we report the design and synthesis of a highly active nanocatalyst, i.e., palladium and platinum nanoparticles (Pt&Pd-NPs) decorated ultrathin nanoporous gold (NPG) film, which is modified on a homemade graphene paper (GP) to develop a high-performance freestanding and flexible nanohybrid electrode. Owing to the structural characteristics the robust GP electrode substrate, and high electrochemically catalytic activities and durability of the permeable NPG support and ultrafine and high-density Pt&Pd-NPs on it, the resultant Pt&Pd-NPs-NPG/GP electrode exhibits excellent sensing performance of low detection limitation, high sensitivity and anti-interference capability, good reproducibility and long-term stability for the detection of small molecular biomarkers hydrogen peroxide (H 2 O 2 ) and glucose (Glu), and has been applied to the monitoring of H 2 O 2 in different types of live cells and Glu in body fluids such as urine and fingertip blood, which is of great significance for the clinical diagnosis and prognosis in point-of-care testing.

Background: Total joint arthroplasty (TJA) has significantly improved the quality of life for millions suffering from end-stage arthritis. However, periprosthetic joint infections (PJI) remain a serious complication, necessitating extensive interventions and prolonged antimicrobial treatments. The aging population is expected to lead to a rise in TJA cases, subsequently increasing the incidence of PJI, particularly in the elderly who face higher mortality rates. Current diagnostic methods for suspected PJI, such as radiographs and biochemical markers like CRP and ESR, exhibit limited sensitivity. Therefore, there is a critical need for a specific synovial fluid biomarker assay to enhance PJI diagnosis using specific SF-based assay., Results: This study introduces a novel microfluidic chip with a paper-based aptamer-sandwich assay for the quantitative detection of HNP 1, a crucial PJI biomarker, in synovial fluid. The assay leverages the advantages of aptamers over antibodies, demonstrating high selectivity and affinity for target molecules. The integration of a nitrocellulose (NC) membrane onto the microfluidic platform represents a significant advancement, reducing background signals and simplifying the assay procedure without intricate procedure and pre-treatment. The NC membrane-based microfluidic device offers rapid, cost-effective, and highly sensitive detection of HNP 1, with a limit of detection of 0.5 mg L -1 . The microfluidic device demonstrates exceptional performance, detecting up to four clinical samples in approximately 42 min on a single chip with 100 % accuracy, as confirmed by analysis of 12 clinical samples and comparison with "gold-standard". Moreover, the assay exhibits a wide dynamic range of 0.5-100 mg L-1, underscoring its potential as a powerful tool for PJI diagnosis in clinical settings., Significance: This work introduces a paper-based microfluidic system tailored for rapid HNP 1 detection using synovial fluid near joint region (and not serum via blood) for better diagnosis. The innovative paper-based aptamer-sandwich assay yields results within 42-min. Significantly, it boasts a wide dynamic range, detecting levels from an impressive 0.5 mg L-1, crucial in the 2.6 mg L-1 threshold region. This heightened sensitivity and expansive detection capability establish our assay as a leader in PJI diagnostics, promising unmatched precision and efficiency in clinical applications., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Epidemiological studies have explored the relationship between allergic diseases and cancer risk or prognosis in AllergoOncology. Some studies suggest an inverse association, but uncertainties remain, including in IgE-mediated diseases and glioma. Allergic disease stems from a Th2-biased immune response to allergens in predisposed atopic individuals. Allergic disorders vary in phenotype, genotype and endotype, affecting their pathophysiology. Beyond clinical manifestation and commonly used clinical markers, there is ongoing research to identify novel biomarkers for allergy diagnosis, monitoring, severity assessment and treatment. Gliomas, the most common and diverse brain tumours, have in parallel undergone changes in classification over time, with specific molecular biomarkers defining glioma subtypes. Gliomas exhibit a complex tumour-immune interphase and distinct immune microenvironment features. Immunotherapy and targeted therapy hold promise for primary brain tumour treatment, but require more specific and effective approaches. Animal studies indicate allergic airway inflammation may delay glioma progression. This collaborative European Academy of Allergy and Clinical Immunology (EAACI) and European Association of Neuro-Oncology (EANO) Position Paper summarizes recent advances and emerging biomarkers for refined allergy and adult-type diffuse glioma classification to inform future epidemiological and clinical studies. Future research is needed to enhance our understanding of immune-glioma interactions to ultimately improve patient prognosis and survival., (© 2024 European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

Low-density lipoprotein cholesterol has been established as a powerful cardiovascular risk factor; its reduction provides a clinical benefit in primary cardiovascular prevention, irrespective of the characteristics of the patients treated. It is useful to tailor low-density lipoprotein cholesterol targets according to the magnitude of cardiovascular risk (low, high or very high) in order to reduce the cardiovascular risk as fully as possible. In order to provide a uniform approach, it is necessary to propose recommendations for good practice, defining strategies for reducing low-density lipoprotein cholesterol. It is also necessary to know their merits, to analyse their practical limits and to propose adaptations, taking into account limitations and national specifics. This position paper aims to analyse the contribution and limits, as well as the adaptation to French practice, of 2019 and 2021 European Society of Cardiology recommendations for the management of lipid variables and cardiovascular prevention., (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)

The 17 th Workshop on Recent Issues in Bioanalysis (17 th WRIB) took place in Orlando, FL, USA on 19-23 June 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 17 th 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 17 th 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 2) covers the recommendations on Biomarkers, IVD/CDx, LBA and Cell-Based Assays. Part 1A (Mass Spectrometry Assays and Regulated Bioanalysis/BMV), P1B (Regulatory Inputs) and Part 3 (Gene Therapy, Cell therapy, Vaccines and Biotherapeutics Immunogenicity) are published in volume 16 of Bioanalysis, issues 9 and 7 (2024), respectively.

Aβ 42 is one of the most extensively studied blood and Cerebrospinal fluid (CSF) biomarkers for the diagnosis of symptomatic and prodromal Alzheimer's disease (AD). Because of the heterogeneity and transient nature of Aβ 42 oligomers (Aβ 42 Os), the development of technologies for dynamically detecting changes in the blood or CSF levels of Aβ 42 monomers (Aβ 42 Ms) and Aβ 42 Os is essential for the accurate diagnosis of AD. The currently commonly used Aβ 42 ELISA test kits usually mis-detected the elevated Aβ 42 Os, leading to incomplete analysis and underestimation of soluble Aβ 42 , resulting in a comprised performance in AD diagnosis. Herein, we developed a dual-target lateral flow immunoassay (dLFI) using anti-Aβ 42 monoclonal antibodies 1F12 and 2C6 for the rapid and point-of-care detection of Aβ 42 Ms and Aβ 42 Os in blood samples within 30 min for AD diagnosis. By naked eye observation, the visual detection limit of Aβ 42 Ms or/and Aβ 42 Os in dLFI was 154 pg/mL. The test results for dLFI were similar to those observed in the enzyme-linked immunosorbent assay (ELISA). Therefore, this paper-based dLFI provides a practical and rapid method for the on-site detection of two biomarkers in blood or CSF samples without the need for additional expertise or equipment., (© 2021. The Author(s).)

Paper-based sensors have received increasing attention in the last decade, their use has spread to various application fields, such as clinical diagnostic, food safety, environmental monitoring, etc. Feature inherent to on-side detection is suitable to be used as point-of-care (POC) testing, including avoided sampling, sample preparation, and laborious procedure in the classical clinical lab, which is undoubtedly driving many developments of this lab-on-paper technology. The detection of biomarkers that are related to human health conditions has to play important role in the indication of the risk of diseases. In this review, the development of paper-based sensors for the detection of important biomarkers is presented. The also emphasis on recognition elements, such as chromophores/fluorophores, plasmonic nanoparticles, metal nanoclusters, etc., used to serve suitable selectivity and sensitivity. The performance of paper-based sensors using various techniques, including optical and electrochemical and other detection techniques are addressed. Furthermore, their limitations and prospects are discussed. The review also highlights cutting-edge technologies for further enhancement in the sensor performances for biomarkers detection.

This article introduces distance-based paper analytical devices (dPADs) integrated with molecularly imprinted polymers (MIPs) and carbon dots (CDs) for simultaneous quantification of cytokine biomarkers, namely C-reactive protein (CRP), tumor necrosis factor-alpha (TNF-a), and interleukin-6 (IL-6) in human biological samples for diagnosis of cytokine syndrome. Using fluorescent CDs and MIP technology, the dPAD exhibits high selectivity and sensitivity. Detection is based on fluorescence quenching of CDs achieved through the interaction of the target analytes with the MIP layer on the paper substrate. Quantitative analysis is easily accomplished by measuring the distance length of quenched fluorescence with a traditional ruler and naked eye readout enabling rapid diagnosis of cytokine syndrome and the underlying infection. Our sensor demonstrated linear ranges of 2.50-24.0 pg mL-1 (R2 = 0.9974), 0.25-3.20 pg mL-1 (R2 = 0.9985), and 1.50-16.0 pg mL-1 (R2 = 0.9966) with detection limits (LODs) of 2.50, 0.25, and 1.50 pg mL-1 for CRP, TNF-a, and IL-6, respectively. This sensor also demonstrated remarkable selectivity compared to a sensor employing a non-imprinted polymer (NIP), and precision with the highest relative standard deviation (RSD) of 5.14%. The sensor is more accessible compared to prior methods relying on expensive reagents and instruments and complex fabrication methods. Furthermore, the assay provided notable accuracy for monitoring these biomarkers in various human samples with recovery percentages ranging between 99.22% and 103.58%. By integrating microfluidic systems, nanosensing, and MIPs technology, our developed dPADs hold significant potential as a cost-effective and user-friendly analytical method for point-of-care diagnostics (POC) of cytokine-related disorders. This concept can be further extended to developing diagnostic devices for other biomarkers. [ABSTRACT FROM AUTHOR]

The World Health Organization (WHO) calls for the development of a rapid, biomarker-based, non-sputum test capable of detecting all forms of tuberculosis (TB) at the point-of-care to enable immediate treatment initiation. Lipoarabinomannan (LAM) is the only WHO-endorsed TB biomarker that can be detected in urine, an easily collected sample matrix. For obtaining optimal sensitivity, we and others have shown that some form of sample pretreatment is necessary to remove background from patient urine samples. A number of systems are paper-based often destined for resource limited settings. Our current work presents incorporation of one such sample pretreatment, proteinase K (ProK) immobilized on paper (IPK) and test its performance in comparison to standard proteinase K (SPK) treatment that involves addition and deactivation at high temperature prior to performing a capture ELISA. Herein, a simple and economical method was developed for using ProK immobilized strips to pretreat urine samples. Simplification and cost reduction of the proposed pretreatment strip were achieved by using Whatman no.1 paper and by minimizing the concentration of ProK (an expensive but necessary reagent) used to pretreat the clinical samples prior to ELISA. To test the applicability of IPK, capture ELISA was carried out on either LAM-spiked urine or the clinical samples after pretreatment with ProK at 400 μg/mL for 30 minutes at room temperature. The optimal conditions and stability of the IPK were tested and validation was performed on a set of 25 previously analyzed archived clinical urine samples with known TB and HIV status. The results of IPK and SPK treated samples were in agreement showing that the urine LAM test currently under development has the potential to reach adult and pediatric patients regardless of HIV status or site of infection, and to facilitate global TB control to improve assay performance and ultimately treatment outcomes., Competing Interests: The authors have declared that no competing interests exist.

Mass spectrometry (MS) has become a powerful technique for clinical applications with high sensitivity and specificity. Different from conventional MS diagnosis in laboratory, point-of-care (POC) analyses in clinics require mass spectrometers and analytical procedures to be friendly for novice users and applicable for on-site clinical diagnosis. The recent decades have seen the progress in the development of miniature mass spectrometers, providing a promising solution for clinical POC applications. In this review, we report recent advances of miniature mass spectrometers and their exploration in clinical applications, mainly including the rapid analysis of illegal drugs, on-site monitoring of therapeutic drugs, and detection of biomarkers. With improved analytical performance, miniature mass spectrometers are also expected to apply to more and more clinical applications. Some promising POC analyses that can be performed by miniature mass spectrometers in the future are discussed. Lastly, we also provide our perspectives on the challenges in technical development of miniature mass spectrometers for clinical POC analysis., (© 2023 John Wiley & Sons Ltd.)

Plasmodium falciparum malaria remains a dominant infectious disease that affects Africa than the rest of the world, considering its associated cases and death rates. It's a febrile illness that produces several reliable biomarkers, for example, P. falciparum lactate dehydrogenase (PfLDH), P. falciparum Plasmodium glutamate dehydrogenase (PfGDH), and P. falciparum histidine-rich proteins (HRP-II) in blood circulatory system that can easily be employed as targets in rapid diagnostic tests (RDTs). In recent times, several DNA aptamers have been developed via SELEX technology to detect some specific malaria biomarkers (PfLDH, PvLDH, HRP-II, PfGDH) in a biosensor mode with good binding affinity properties to overcome the trend of cross-reactivity, limited sensitivity and stability problems that have been observed with immunodiagnostics. In this review, we summarized existing diagnostic methods and relevant biomarkers to suggest promising approaches to develop sensitive and species-specific multiplexed diagnostic devices enabling effective detection of malaria in complex biological matrices and surveillance in the endemic region., (© 2024 John Wiley & Sons Ltd.)

The adult heart is a complex, multicellular organ that is subjected to a series of regulatory stimuli and circuits and has poor reparative potential. Despite progress in our understanding of disease mechanisms and in the quality of health care, ischaemic heart disease remains the leading cause of death globally, owing to adverse cardiac remodelling, leading to ischaemic cardiomyopathy and heart failure. Therapeutic targets are urgently required for the protection and repair of the ischaemic heart. Moreover, personalized clinical biomarkers are necessary for clinical diagnosis, medical management and to inform the individual response to treatment. Non-coding RNAs (ncRNAs) deeply influence cardiovascular functions and contribute to communication between cells in the cardiac microenvironment and between the heart and other organs. As such, ncRNAs are candidates for translation into clinical practice. However, ncRNA biology has not yet been completely deciphered, given that classes and modes of action have emerged only in the past 5 years. In this Review, we discuss the latest discoveries from basic research on ncRNAs and highlight both the clinical value and the challenges underscoring the translation of these molecules as biomarkers and therapeutic regulators of the processes contributing to the initiation, progression and potentially the prevention or resolution of ischaemic heart disease and heart failure., (© 2024. Springer Nature Limited.)

Background: Chronic rhinosinusitis with nasal polyps (CRSwNP) may have a heterogeneous response to medical/surgical treatments based on endotypes. Data correlating biomarkers and severity of the disease are lacking. We aimed to determine if IL-5 and calprotectin may be useful in defining severity of disease and identifying uncontrolled patients., Methods: This was a case-control study including 81 patients with diffuse CRSwNP who underwent at least one previous surgery and treated with intranasal steroids. We enrolled 39 uncontrolled patients (SNOT-22 ≥ 40 and two or more cycles of systemic corticosteroids in last year) (Group A) and 42 controlled one (SNOT-22 < 40 and less than two cycles of systemic corticosteroids in last year) (Group B). We analyzed IL-5 and calprotectin in both nasal secretions and nasal polyp tissue., Results: Calprotectin and IL-5 were significantly higher in Group A in both secretions and tissue, and the higher the number of previous surgeries, the higher the levels detected in nasal secretions. At univariate analyses, smoking, asthma, non-steroidal anti-inflammatory drugs-exacerbated respiratory disease (NSAID-ERD), blood eosinophilia, neutrophils, and eosinophils at nasal cytology were significantly associated with uncontrolled disease. Multivariate analyses showed that asthma, NSAID-ERD, and IL-5 in nasal secretion/polyp tissue were significantly related to the risk of uncontrolled disease., Conclusions: Our data suggest that asthma, NSAID-ERD, and IL-5 in nasal secretions/tissue may be helpful to identify more severe patients, as they are related to the risk of uncontrolled disease. Nonetheless, high levels of calprotectin and neutrophilia were also observed in uncontrolled patients, especially after multiple surgeries., (© 2024 The Authors. International Forum of Allergy & Rhinology published by Wiley Periodicals LLC on behalf of American Academy of Otolaryngic Allergy and American Rhinologic Society.)

Background: Uterine fibroids are benign monoclonal tumors originating from the smooth muscle cells of the myometrium, constituting the most prevalent pathology within the female genital tract. Uterine sarcomas, although rare, still represent a diagnostic challenge and should be managed in centers with adequate expertise in gynecological oncology. Objectives: This article is aimed to summarize and discuss cutting-edge elements about the diagnosis and management of uterine fibroids and sarcomas. Methods: This paper is a report of the lectures presented in an expert meeting about uterine fibroids and sarcomas held in Palermo in February 2023. Outcome: Overall, the combination of novel molecular pathways may help combine biomarkers and expert ultrasound for the differential diagnosis of uterine fibroids and sarcomas. On the one hand, molecular and cellular maps of uterine fibroids and matched myometrium may enhance our understanding of tumor development compared to histologic analysis and whole tissue transcriptomics, and support the development of minimally invasive treatment strategies; on the other hand, ultrasound imaging allows in most of the cases a proper mapping the fibroids and to differentiate between benign and malignant lesions, which need appropriate management. Conclusions and Outlook: The choice of uterine fibroid management, including pharmacological approaches, surgical treatment, or other strategies, such as high-intensity focused ultrasound (HIFU), should be carefully considered, taking into account the characteristics of the patient and reproductive prognosis. [ABSTRACT FROM AUTHOR]

Background: The Taiwan Oncology Society (TOS) and the Taiwan Society of Pathology (TSP) have collaborated to present a joint position paper on the molecular tumor boards (MTBs) within the medical institutions of Taiwan. Materials and Methods: To raise awareness of MTBs among health-care professionals, policymakers, and the public, a total of 20 experts from TOS and TSP formulated a joint consensus statement through a voting process. Results: The joint statement proposes key recommendations: (1) MTB discussions encompass diverse molecular analyses including next-generation sequencing (NGS), RNA sequencing, whole-exon sequencing, and whole-genomic sequencing addressing relevant genomic changes, tumor mutation burden, microsatellite instability, and specific biomarkers for certain cancers. (2) MTB meetings should involve multidisciplinary participants who receive regular updates on NGS-related clinical trials. (3) Prioritize discussing cases with unique clinical needs, gene alterations lacking treatments, untreatable neoplasms, or oncogenes unresponsive to targeted therapies. (4) Base MTB discussions on comprehensive patient data, including genetics, pathology, timing of specimen collection, and NGS outcomes. (5) MTBs offer treatment recommendations: standard therapies, off-label use, clinical trials, genetic counseling, and multidisciplinary reviews. (6) MTB effectiveness can be gauged by member composition, case reviews, treatment suggestions, and patient outcomes. Encourage government incentives for MTB engagement. Conclusion: The primary aim of this initiative is to promote the advancement of precision oncology in Taiwan. [ABSTRACT FROM AUTHOR]

Sepsis is an immune response to a microbial invasion that causes organ injury and dysfunction due to a systemic inflammatory response. Sepsis is a serious, life-threatening condition and a widely recognized global health challenge. Given its high death rate, it is critical to diagnose sepsis and start treatment as early as possible. There is an urgent need for a sensitive and rapid screening method for detecting sepsis. In this study, we investigated the use of MMP-9 as a biomarker for sepsis. A colorimetric paper-based biosensor was used for the detection of MMP-9 utilizing peptide-magnetic nanoparticle conjugates. The method is based on the cleavage of the MMP-9-specific peptide by the protease leading to the detaching of the magnetic beads from the sensor surface and changing of color. A fecal intraperitoneal (FIP) challenge was used to induce sepsis in mice, and an MMP-9 secretion was measured by taking blood and Bronchoalveolar Lavage (BAL) fluid samples at 1 h, 2 h, 4 h, and 20 h (early sepsis) post-challenge intervals. The results of the paper-based sensor for the detection of MMP-9 levels in blood samples and BAL samples were compared with ELISA and Western Blot. We found that both blood and BAL levels of MMP-9 increased immediately and could be detected as early as 1 h in FIP mice post-challenge. Our work adds evidence to the assertion that MMP-9 is a reliable biomarker for the detection of sepsis at early stages.

Based on surface biomolecular imprinting technology, a rotary microfluidic electrochemical paper-based chip (MIP-ePADs) was proposed for sensitive and selective detection of human interleukin 6 (IL-6) and procalcitonin (PCT). Compared with the traditional method, the sample can be added directly on the MIP-ePAD by rotating the working electrode, which avoids the loss of the liquid to be tested and greatly simplifies the process of electropolymerization imprinting and template elution. Our experimental results show that linear concentration ranges of IL-6 and PCT in the electrochemical molecularly imprinted microfluidic paper-based chip ranged from 0.01 to 5 ng mL−1, with their detection limits being 3.5 and 2.1 pg mL−1, respectively. For the detection of actual serum samples, there was no significant difference between the results of MIP-ePADs and the traditional electrochemiluminescence method used in hospitals, indicating that the paper-based chip can be used for stable and accurate analysis and detection. The chip greatly reduces the cost of clinical trials due to its advantages of easy preparation and low cost. The chip can be used for the analysis of non-antibody inflammation markers and can be widely used in home and hospital treatment detection. This method will not only play an important role in rapid detection, but also provide new ideas for the improvement of rapid detection technology. [ABSTRACT FROM AUTHOR]

Introduction: When the body experiences a change in its internal environment due to factors such as mood (euphoria, stress) and illness, it releases biomarkers in large quantities. These biomarkers are used for detecting a disease at its early stages. This involves the detection of insufficient quantities of biocomponents, which can be done by using nanomaterials, conventional materials, and biotechnology; thus, scientists can increase the sensitivity of electrochemical sensors. According to studies conducted in this area, electrochemical sensors have shown promise as a diagnostic tool due to their ability to identify and pinpoint illness biomarkers. The present review article was compiled to gather the latest information on electrochemical biosensors targeting stress markers., Materials and Methods: The authors searched scholarly databases like ScienceDirect, Pubmed, Medline, and Scopus for information on electrochemical biosensors targeting stress markers., Results: In this article, we looked at the recent developments in electrochemical sensors for stress monitoring. Because of advances in nanomaterial and biomolecule processes, electrochemical biosensors have been developed with the sensitivity to detect several biomarkers in real-time in therapeutically relevant materials., Conclusion: This biomarker sensor strategy can analyze various biofluids (sweat, plasma, urine, and saliva)., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

In a large proportion of individuals with fronto-temporal lobar degeneration (FTLD), the underlying pathology is associated with the misfolding and aggregation of the microtubule associated protein tau (FTLD-tau). With disease progression, widespread protein accumulation throughout cortical and subcortical brain regions may be responsible for neurodegeneration. One of the syndromes of FTLD is the behavioral variant of frontotemporal dementia (bvFTD), in which the underlying pathology is heterogenous, with half of the cases being related to FTLD-tau. Currently, there are no approved disease-modifying treatments for FTLD-tau, therefore representing a major unmet therapeutic need. These descriptive, preliminary findings of the phase 1 open-label trial provide data to support the potential of sodium selenate to halt the cognitive and behavioral decline, as well as to reduce tau levels in a small group of participants with bvFTD (N = 11). All participants were treated with sodium selenate over a period of 52 weeks. Cognition was assessed with the Neuropsychiatry Unit Cognitive Assessment Tool (NUCOG, total scores), social cognition with the Revised Self-Monitoring Scale (RSMS, total scores), behavior with the Cambridge Behavioral Inventory (CBI), and carer burden with the Caregiver Buden Scale (CBS). Fluid biomarker measures include cerebrospinal fluid of total tau (t-tau), phosphorylated tau (p-tau181), NfL, p-tau181/t-tau, t-tau/Aβ1–42, and p-tau181/Aβ1–42 levels. After treatment at follow-up, cognition and behavior showed further negative change (based on a reliable change criterion cut-off of annual NUCOG decline) in the “progressors,” but not in the “non-progressors.” “Non-progressors” also showed elevated baseline CSF tau levels and no increase after treatment, indicating underlying tau pathology and a positive response to sodium selenate treatment. Significant changes in MRI were not observed. The findings provide useful information for future clinical trials to systematically assess the disease-modifying treatment effects of sodium selenate in randomized controlled designs for bvFTD and FTLD-tau pathologies.

Paper-based sensors overcome the drawbacks of conventional sensors in terms of their flexibility, portability, and stability compared to conventional sensors. Moreover, as a noninvasive bodily fluid, saliva contains various biomarkers related to physical status, which makes it perfectly matched with to use of paper-based sensors to manufacture a convenient and inexpensive disposable sensing device. This review focuses on the recent advances and progress in the design of paper-based salivary sensors and their applications. The first part mainly discusses various paper-based sensors and their advanced compositions, including dipstick assay, lateral flow assay, and microfluidic analytical device. Different detection methods in salivary biomarker detection are specially introduced in the secondary section, then their multiple potential applications and prospects are summarized. The sensor has excellent advantages for saliva detection, provides a reliable platform for point-of-care tests and telemedicine, and epically promotes the development of the medical Internet of Things. [ABSTRACT FROM AUTHOR]

In this study, a paper-based sensor was developed for the detection of hydrogen-peroxide-related biomarkers, with glucose oxidase catalyzing as an example. Potassium iodide can catalyze the oxidation of 3,3′,5,5′-tetramethylbenzidine in the presence of hydrogen peroxide to colorize the paper-based biosensor detection area, which was imaged by a scanner, and the color intensity was analyzed by the Adobe Photoshop. Under the optimal conditions, the color intensity shows a good linear relationship with hydrogen peroxide and glucose concentrations in the ranges of 0.1–5.0 mM and 0.5–6.0 mM, respectively. The detection limit of hydrogen peroxide is 0.03 mM and the limit of quantification of glucose is 0.5 mM. Besides, the method was employed in measuring glucose concentration in fruit samples, and the spiked recoveries are in the range of 95.4–106.1%. This method is cost-effective, environmentally friendly, and easy to be operated, which is expected to realize the point-of-care testing of more hydrogen-peroxide-related biomarkers. [ABSTRACT FROM AUTHOR]

Soluble urokinase plasminogen activator receptor (suPAR) is a marker of systemic chronic inflammation. Elevated suPAR levels are associated with adverse clinical outcomes, but a small subset of patients with low suPAR also experience poor outcomes. Therefore, we aimed to characterize patients presenting to the emergency department with low suPAR (<3 ng/mL) who died within 90 days after discharge in a registry-based study. Compared to patients with low suPAR who survived (n = 15 122), those who died within 90 days (n = 87) had higher age (75.4 years), higher medication use (7.0; 71.3% with polypharmacy) and more blood tests outside reference intervals (5.0) (including C-reactive protein, neutrophils and albumin), and the most common diagnoses were chronic pulmonary disease (27.6%), cerebrovascular disease (18.4%) and dementia (11.5%). Patients with low suPAR were more morbid than what was reflected by suPAR alone. Future studies must determine which factors that contribute the most to potential algorithms when stratifying patients based on their risk of adverse clinical outcomes. These data indicate that inclusion of medication data could be relevant., (© 2024 The Author(s). Basic & Clinical Pharmacology & Toxicology published by John Wiley & Sons Ltd on behalf of Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).)

Purpose: The purpose of this study is to optimize a dMS-based urinary proteomic technique and evaluate the relationship between urinary proteome content and adaptive changes in bone microarchitecture during BCT., Methods: Urinary proteomes were analyzed with an optimized dMS technique in two groups of 13 recruits ( N = 26) at the beginning (Pre) and end (Post) of BCT. Matched by age (21 ± 4 yr), sex (16 W), and baseline tibial trabecular bone volume fractions (Tb.BV/TV), these groups were distinguished by the most substantial (High) and minimal (Low) improvements in Tb.BV/TV. Differential protein expression was analyzed with mixed permutation ANOVA and false discovery proportion-based adjustment for multiple comparisons., Results: Tibial Tb.BV/TV increased from pre- to post-BCT in High (3.30 ± 1.64%, P < 0.0001) but not Low (-0.35 ± 1.25%, P = 0.4707). The optimized dMS technique identified 10,431 peptides from 1368 protein groups that represented 165 integrative biological processes. Seventy-four urinary proteins changed from pre- to post-BCT ( P = 0.0019), and neutrophil-mediated immunity was the most prominent ontology. Two proteins (immunoglobulin heavy constant gamma 4 and C-type lectin domain family 4 member G) differed from pre- to post-BCT in High and Low ( P = 0.0006)., Conclusions: The dMS technique can identify more than 1000 urinary proteins. At least 74 proteins are responsive to BCT, and other principally immune system-related proteins show differential expression patterns that coincide with adaptive bone formation., (Copyright © 2024 by the American College of Sports Medicine.)

Objective: Identifying the biomarkers for uncontrolled chronic rhinosinusitis (CRS) is important for directing treatment decisions. Eosinophilia has been reported to be involved in the poor disease control of CRS and mucus eosinophil-derived neurotoxin (EDN) is potentially a biomarker of intense eosinophil activation. This study aimed to assess the relationship between mucus EDN levels, disease severity, and degree of CRS control., Methods: A total of 150 adult patients with CRS and 25 healthy controls were prospectively enrolled. The nasal mucus and tissue specimens were collected to analyze EDN levels. Disease severity was assessed by Lund-Mackay score and 22-item Sino-Nasal Outcome Test (SNOT-22) score. Five CRS symptom severities during the prior month (nasal blockage, rhinorrhoea/postnasal drip, facial pain/pressure, smell, sleep disturbance or fatigue), use of rescue medications in the last six months, and the presence of diseased mucosa on nasal endoscopy were obtained. Consistent with the European Position Paper on Rhinosinusitis and Nasal Polyps 2020 CRS control criteria, uncontrolled CRS was defined as meeting at least three items., Results: 40% of patients with CRS presented with uncontrolled status. Patients with uncontrolled CRS had significantly higher nasal mucus EDN levels (P = 0.010), percentage of blood eosinophil (P = 0.015), SNOT-22 score (P < 0.001), Lund-Mackay score (P = 0.008), and a more eosinophilic dominant phenotype of CRS (P < 0.001) than patients with controlled CRS. Furthermore, mucus EDN levels were positively correlated with blood eosinophils (r = 0.541, P = 0.005), SNOT-22 score (r = 0.460, P = 0.021), and Lund-Mackay score (r = 0.387, P = 0.039). Mucus EDN levels were the significant parameter related to uncontrolled CRS in multivariable analysis after adjusting for patient demographics and comorbidities (odds ratio = 1.323; P = 0.004)., Conclusions: Mucus EDN levels may be a potential biomarker for identifying the CRS control status., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: The vocal biomarkers market was worth $1.9B in 2021 and is projected to exceed $5.1B by 2028, for a compound annual growth rate of 15.15%. The investment growth demonstrates a blossoming interest in voice and artificial intelligence (AI) as it relates to human health. The objective of this study was to map the current landscape of start-ups utilizing voice as a biomarker in health-tech., Data Sources: A comprehensive search for start-ups was conducted using Google, LinkedIn, Twitter, and Facebook. A review of the research was performed using company website, PubMed, and Google Scholar., Review Methods: A 3-pronged approach was taken to thoroughly map the landscape. First, an internet search was conducted to identify current start-ups focusing on products relating to voice as a biomarker of health. Second, Crunchbase was utilized to collect financial and organizational information. Third, a review of the literature was conducted to analyze publications associated with the identified start-ups., Results: A total of 27 start-up start-ups with a focus in the utilization of AI for developing biomarkers of health from the human voice were identified. Twenty-four of these start-ups garnered $178,808,039 in investments. The 27 start-ups published 194 publications combined, 128 (66%) of which were peer reviewed., Conclusion: There is growing enthusiasm surrounding voice as a biomarker in health-tech. Academic drive may complement commercialization to best achieve progress in this arena. More research is needed to accurately capture the entirety of the field, including larger industry players, academic institutions, and non-English content., (© 2024 American Academy of Otolaryngology–Head and Neck Surgery Foundation.)

This study aimed to evaluate the association between maternal liver biomarkers in early pregnancy and the risk of hypertensive disorders of pregnancy (HDP), as well as to evaluate interaction between liver enzymes and BMI on the development of HDP. Pregnant women in our study were recruited from the Zhoushan Pregnant Women Cohort. Participants who had their first prenatal follow-up and the blood pressure follow-up records, and measured liver biomarkers in the first trimester were eligible for inclusion in the study. A total of 10,610 pregnant women were included in the analysis, and 305 (2.87%) developed the HDP. There were positive associations between AST, GGT, ALP, HSI and SBP, as well as between ALT, GGT, ALP, HSI and DBP. In addition, AST/ALT level was negatively associated with DBP. The highest quartile of GGT, ALP, AST/ALT and HSI were significantly associated with 1.71-fold (95% Cl: 1.23-2.41), 1.53-fold (95% Cl: 1.10-2.14), 0.62-fold (95% Cl: 0.43-0.90) and 1.67-fold (95% Cl: 1.05-2.67) increased risk of HDP, respectively. There was no significant association between ALT, AST and HDP. These associations remained consistent in pregnant women with liver enzymes within the clinical reference range. Besides, we found an interaction between GGT and BMI (P interaction  = 0.013) in the development of HDP. In summary, the level of GGT, ALP, AST/ALT and HSI were associated with the subsequent risk of HDP, even within the clinical reference range. And there was an interaction between liver biomarkers and BMI in the development of HDP. Our study showed the level of GGT, ALP, AST/ALT and HSI were associated with the subsequent risk of HDP. And there was an interaction between GGT and BMI in the risk of HDP., (© 2024. The Author(s), under exclusive licence to The Japanese Society of Hypertension.)

Introduction: Longitudinal metabolomics data from a meal challenge test contains both fasting and dynamic signals, that may be related to metabolic health and diseases. Recent work has explored the multiway structure of time-resolved metabolomics data by arranging it as a three-way array with modes: subjects, metabolites, and time. The analysis of such dynamic data (where the fasting data is subtracted from postprandial states) reveals dynamic markers of various phenotypes, and differences between fasting and dynamic states. However, there is still limited success in terms of extracting static and dynamic biomarkers for the same subject stratifications., Objectives: Through joint analysis of fasting and dynamic metabolomics data, our goal is to capture static and dynamic biomarkers of a phenotype for the same subject stratifications providing a complete picture, that will be more effective for precision health., Methods: We jointly analyze fasting and dynamic metabolomics data collected during a meal challenge test from the COPSAC 2000 cohort using coupled matrix and tensor factorizations (CMTF), where the dynamic data (subjects by metabolites by time) is coupled with the fasting data (subjects by metabolites) in the subjects mode., Results: The proposed data fusion approach extracts shared subject stratifications in terms of BMI (body mass index) from fasting and dynamic signals as well as the static and dynamic metabolic biomarker patterns corresponding to those stratifications. Specifically, we observe a subject stratification showing the positive association with all fasting VLDLs and higher BMI. For the same subject stratification, a subset of dynamic VLDLs (mainly the smaller sizes) correlates negatively with higher BMI. Higher correlations of the subject quantifications with the phenotype of interest are observed using such a data fusion approach compared to individual analyses of the fasting and postprandial state., Conclusion: The CMTF-based approach provides a complete picture of static and dynamic biomarkers for the same subject stratifications-when markers are present in both fasting and dynamic states., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

➤ No single test has demonstrated absolute accuracy for the diagnosis of periprosthetic joint infection (PJI).➤ Physicians rely on a combination of serological tests, synovial markers, and clinical findings plus clinical judgment to help to guide preoperative decision-making.➤ Several organizations have proposed criteria for the diagnosis of hip or knee PJI on which we now rely.➤ Given that shoulder arthroplasty has only recently become popular, it is possible that a shoulder-specific definition of PJI will be introduced in the coming years.➤ Although a number of serum and synovial markers have demonstrated high accuracy for the diagnosis of PJI of the hip and knee, further research is needed in order to identify markers that may be more suitable for the diagnosis of shoulder PJI and for the potential development and identification of specific serological tests as screening tools for PJI., Competing Interests: Disclosure: The Disclosure of Potential Conflicts of Interest forms are provided with the online version of the article ( http://links.lww.com/JBJS/I24 )., (Copyright © 2024 by The Journal of Bone and Joint Surgery, Incorporated.)

Potatoes (Solanum tuberosum L.) are one of the world's major staple crops. In stored potatoes, Pectobacterium carotovorum subsp carotovorum causes soft rot. As a result of the rapid spread of the disease during post-harvest storage, potato production suffers huge losses. By detecting disease early and controlling it promptly, losses can be minimized. The profile of volatiles of plants can be altered by phytopathogens. Identifying unique volatile organic compounds (VOCs) as biomarkers for early disease detection has attracted considerable research attention. This study compared the VOC profiles of healthy and soft rot inoculated potatoes (cv. "Kufri Pukhraj") over a time course using gas chromatography-mass spectrometry (GC-MS). It was found that there was a differential emission of 27 VOCs between healthy non-inoculated potatoes and soft rot inoculated potatoes. Among 27 VOCs, only five (1-octen-3-ol, 2-methylisoborneol, 3-octanone, 1,4-dimethyladamantane, and 2-methyl-2-bornene) were found exclusively in soft rot inoculated potatoes, suggesting them potential biomarker for non-destructive prediction of soft rot disease in potatoes. Reactive oxygen species (H 2 O 2 ) and phytohormone methyl-jasmonate (MeJa) levels increased transiently on infection with soft rot. The analysis of the primary metabolism of soft rot infected tubers at three different stages suggests metabolic reprogramming that occurs at the early stage of infection, possibly leading to biomarker volatile emission. Based on these results, it appears that the initial potato-soft rot bacteria interaction initiates metabolic reprogramming mainly through H 2 O 2 and the MeJa signalling pathway. In asymptomatic potatoes, these biomarkers may be promising candidates for non-destructive detection of soft rot at an early stage. These biomarkers can be used to develop an e-nose sensor to predict soft rot in the future., (© 2024 Scandinavian Plant Physiology Society.)

In recently conducted phase III trials in a rare disease area, patients received monthly treatment at a high dose of the drug, which targets to lower a specific biomarker level, closely associated with the efficacy endpoint, to around 10% across patients. Although this high dose demonstrated strong efficacy, treatments were withheld due to the reports of serious adverse events. Dosing in these studies were later resumed at a reduced dosage which targets to lower the biomarker level to 15%-35% across patients. Two questions arose after this disruption. The first is whether the efficacy of this revised regimen as measured by the reduction in annualized event rate is adequate to support the continuation of the development and the second is whether the potential bias due to the loss of patients during this dosing gap process can be gauged. To address these questions, we built a prediction model that quantitatively characterizes biomarker vs. endpoint relationship and predicts efficacy at the 15%-35% range of the biomarker level using the available data from the original high dose. This model predicts favorable event rate in the target biomarker level and shows that the bias due to the loss of patients is limited. These results support the continued development of the revised regimen, however, given the limitation of the data available, this prediction is planned to be validated further when data under the revised regimen become available., (© 2024 John Wiley & Sons Ltd.)

Introduction: Ethnic and gender differences in plasma lipid composition have been widely reported among the general population, but there are scarce data on athletes., Aim: To assess ethnic and gender differences in lipid profile across a large cohort of Olympic athletes practicing different sport disciplines METHODS: We enrolled 1165 Olympic athletes divided into power, endurance, and mixed disciplines according to European Society of Cardiology classification. Sixty-two (5.3%) were Afro-Caribbean. Body composition and fat mass percentage were measured. Blood samples were collected and lipid profile was investigated., Results: Compared to Caucasians, Afro-Caribbeans had better lipid profile characterized by lower LDL (90 ± 25 mg/dL vs. 97.1 ± 26.2 mg/dL, p = 0.032) lower LDL/HDL ratio (1.39 ± 0.5 vs. 1.58 ± 0.6, p = 0.012), lower non-HDL-cholesterol (102.5 ± 27.4 mg/dL vs. 111.5 ± 28.5 mg/dL, p = 0.015) and lower TC/HDL (2.59 ± 0.6 vs. 2.82 ± 0.7, p = 0.010). Female Afro-Caribbeans showed lower TG/HDL ratio (p = 0.045) and TC/HDL ratio (p = 0.028), due to higher HDL (p = 0.005) compared to male Afro-Caribbeans. In Caucasian athletes, females showed even more evident differences with lower TC, LDL, and higher HDL with subsequent lower ratios compared to men. Moreover, endurance Caucasian athletes had lower LDL (p = 0.003) and TG (p = 0.017) plasmatic levels and higher HDL levels compared to non-endurance Caucasian athletes (p< 0.0001) CONCLUSIONS: Ethnicity and gender have a significant influence on plasmatic lipid balance in elite athletes and Afro-Caribbeans have favorable lipid profiles compared to Caucasians. Moreover, endurance sports, particularly in Caucasian athletes, are associated with better lipid profile compared to other type of sports., (© 2024. The Author(s).)

Objective: Irisin, released by muscles during exercise, was recently identified as a neuroprotective factor in mouse models of Alzheimer disease (AD). In a cohort of AD patients, we studied cerebrospinal fluid (CSF) and plasma irisin levels, sex interactions, and correlations with disease biomarkers., Methods: Correlations between CSF and plasma irisin levels and AD biomarkers (amyloid β 1-42, hyperphosphorylated tau, and total tau [t-tau]) and Clinical Dementia Rating Scale Sum of Boxes (CDR-SOB) were analyzed in a cohort of patients with Alzheimer dementia (n = 82), mild cognitive impairment (n = 44), and subjective memory complaint (n = 20) biologically characterized according to the recent amyloid/tau/neurodegeneration classification., Results: CSF irisin was reduced in Alzheimer dementia patients (p < 0.0001), with lower levels in female patients. Moreover, CSF irisin correlated positively with Aβ42 in both female (r = 0.379, p < 0.001) and male (r = 0.262, p < 0.05) patients, and negatively with CDR-SOB (r = -0.234, p < 0.05) only in female patients. A negative trend was also observed between CSF irisin and t-tau levels in all patients (r = -0.144, p = 0.082) and in the female subgroup (r = -0.189, p = 0.084)., Interpretation: The results highlight the relationship between irisin and biomarkers of AD pathology, especially in females. Our findings also offer perspectives toward the use of irisin as a marker of the AD continuum. ANN NEUROL 2024;96:61-73., (© 2024 The Authors. Annals of Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.)

Pancreatic cancer remains one of the most challenging malignancies to diagnose and treat effectively, resulting in poor patient outcomes due to late-stage detection and limited therapeutic options. The emergence of biosensors has revolutionized cancer diagnosis and therapy, providing new avenues for early detection and personalized treatment. This paper explores the development and integration of biosensors within a unique expert system for pancreatic cancer diagnosis and drug delivery automation. It discusses the principles, types, and applications of biosensors in pancreatic cancer diagnosis, their role in automating drug delivery, and the design of an expert system that leverages these technologies to enhance patient outcomes. [ABSTRACT FROM AUTHOR]

The modification of an easily available resource like paper to circumvent expensive or intensive sample pretreatment could be the answer to sample analysis in resource-poor regions. Therefore, a novel on-paper device combining sample collection with affinity sample pretreatment is introduced here. Universal smart affinity samplers are produced by a simple KIO4-mediated oxidation of cellulose, which functionalizes the paper. This is followed by immobilization of streptavidin. Streptavidin serves as a universal anchor for biotinylated antibodies, enabling simple preparation of tailor-made affinity samplers. The functionality of the device was tested using a model protein (human chorionic gonadotropin, hCG) and biotinylated anti-hCG antibodies for affinity capture. In a laboratory setting, the performance was demonstrated, and a 14-fold increase of target binding compared to binding without bmAb was achieved. The recovery of hCG captured with bmAb-treated samplers was determined to be 33% and comparable to previously described affinity capture approaches. Application of the smart affinity samplers to human serum containing hCG showed an R2 of 0.98 (200–1000 pg mL−1), precision of ≤ 9.1% RSD, and estimated limit of detection of 65 pg mL−1. Although further optimization and validation are necessary prior to application to real samples in clinical settings, the potential of the device for use in determination of low abundant biomarkers in complex samples has been demonstrated. [ABSTRACT FROM AUTHOR]

Rapid, simple, and sensitive analysis of relevant proteins is crucial in many research areas, such as clinical diagnosis and biomarker detection. In particular, clinical data on cancer biomarkers show great promise in forming reliable predictions for early cancer diagnostics, although the current analytical systems are difficult to implement in regions of limited recourses. Paper-based biosensors, in particular, have recently received great interest because they meet the criteria for point-of-care (PoC) devices; the main drawbacks with these devices are the low sensitivity and efficiency in performing quantitative measurements. In this work, we design a low-cost paper-based nanosensor through plasmonic calligraphy by directly drawing individual plasmonic lines on filter paper using a ballpoint pen filled with gold nanorods (AuNR) as the colloidal ink. The plasmonic arrays were further successively coated with negatively and positively charged polyelectrolyte layers employed as dielectric spacers to promote the enhancement of the emission of carboxyl-functionalized quantum dots (QD)—previously conjugated with specific antibodies—for indirect detection of the carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5). The efficiency, sensitivity, as well as the specificity of our portable nanosensor were validated by recording the luminescence of the QD@Ab complex when different concentrations of CEACAM5 were added dropwise onto the calligraphed plasmonic arrays. [ABSTRACT FROM AUTHOR]

Background: Multi-arm, multi-stage (MAMS) platform trials can accelerate the identification of disease-modifying treatments for Parkinson's disease (PD) but there is no current consensus on the optimal outcome measures (OM) for this approach. Objective: To provide an up-to-date inventory of OM for disease-modifying PD trials, and a framework for future selection of OM for such trials. Methods: As part of the Edmond J Safra Accelerating Clinical Trials in Parkinson Disease (EJS ACT-PD) initiative, an expert group with Patient and Public Involvement and Engagement (PPIE) representatives' input reviewed and evaluated available evidence on OM for potential use in trials to delay progression of PD. Each OM was ranked based on aspects such as validity, sensitivity to change, participant burden and practicality for a multi-site trial. Review of evidence and expert opinion led to the present inventory. Results: An extensive inventory of OM was created, divided into: general, motor and non-motor scales, diaries and fluctuation questionnaires, cognitive, disability and health-related quality of life, capability, quantitative motor, wearable and digital, combined, resource use, imaging and wet biomarkers, and milestone-based. A framework for evaluation of OM is presented to update the inventory in the future. PPIE input highlighted the need for OM which reflect their experience of disease progression and are applicable to diverse populations and disease stages. Conclusion: We present a range of OM, classified according to a transparent framework, to aid selection of OM for disease-modifying PD trials, whilst allowing for inclusion or re-classification of relevant OM as new evidence emerges. [ABSTRACT FROM AUTHOR]