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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. The methodological validation revealed the resolution (Rs) as 1.78, the limit of detection (S/N = 3) as 20.83 fmol, good linearity (R2 ≥ 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. 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. [Display omitted] • A dried sweat spot paper method for estimating DL-LA enantiomers in human sweat. • The D/L and L/D ratios of LA in diabetic patient sweat are significantly different. • The D/L-LA ratio in human sweat is positively correlated with fasting blood glucose levels. • DSSP combined with UHPLC-MS/MS accurately quantified D/L-LA ratio is a non-invasive preventive method for screening for diabetes. [ABSTRACT FROM AUTHOR]

Schematic diagram depicting the synthesis process of the intelligent paper-based biosensor and its colorimetric detection application for biomarkers in urine. (FP: filter paper; CPBA: Carboxyphenylboric acid; HRP: horseradish peroxidase; TMB: 3,3′,5,5′-tetramethylbenzidine; GLU: glusose; UA: uric acid; SAR: sarcosine; GOx: glucose oxidase; UOx: urate oxidase; SOx: urate oxidase.) [Display omitted] • A green, low-cost, portable and visual intelligent paper-based biosensor was created. • This sensor immobilized HRP in horseradish by a borate-modified filter paper. • This sensor can detect many substances simultaneously and improve detection efficiency. • This sensor boasts the advantages of superior sensitivity, stability and selectivity. In the increasing demand for real-time testing, the imperative for a straightforward, rapid, portable, and effective biosensor is evident. In this study, an intelligent paper-based biosensor was developed, employing cost-effective and readily available filter paper as a matrix to prepare boronate affinity paper-based materials. The immobilization of horseradish peroxidase (HRP) from crude horseradish extract onto the material surface was realized. Ultimately, a cold assembly technique was employed to construct this intelligent paper-based biosensor, which combined with a smartphone APP, facilitated the easy, accurate, and simultaneous detection of the content of glucose (GLU), uric acid (UA), and sarcosine (SAR) in urine, significantly enhancing the convenience and practicality of real-time monitoring. Additionally, UV spectroscopy served as an auxiliary method to affirm the reliability of the detection outcomes. For the detection of GLU, UA, and SAR, the biosensor exhibited linear ranges of 2–200, 2–500, and 2–500 µmol L–1, respectively, with detection limits (LODs) of 1 µmol L–1 for all analytes. In practical urine sample analysis, the recovery rates of GLU, UA, and SAR detected by the intelligent paper-based biosensors were within a reasonable range, with relative standard deviations below 3.5 %. This fully demonstrates the high accuracy and reliability of the intelligent paper-based biosensor. The development of this low-cost, portable biosensor provides a new method for the detection of biomarkers related to H 2 O 2. [ABSTRACT FROM AUTHOR]

A novel CuS grafted PEDOT:PSS conducting paper-based electrochemical immunosensor has been successfully fabricated for the detection of EpCAM antigen. Electrical conductivity is further improved by doping the CuS@PEDOT:PSS/WP electrode with different organic solvents such as N,N-dimethyl formamide (DMF), N,N-dimethyl acetamide (DMA), ethylene glycol (EG) and dimetyl sulfoxide (DMSO). It is observed that DMSO doped conducting paper shows the highest conductivity (6.1 × 10−2 S/cm) among all these solvents. This low cost, biodegradable electrochemical paper-based immunosensor (BSA/anti-EpCAM/EP) possesses a broad linear range from 0.01 pg/mL to 1000 ng/mL for EpCAM antigen detection. The immunosensor is found to have high sensitivity of 104.31 μA pg−1 mL. This conducting paper based immunosensor is further used to detect EpCAM antigen in human serum samples, thereby confirming a cost effective clinical tool over other costly conventional techniques. • An electrochemical paper-based immunosensor has been designed using CuS and PEDOT:PSS. • This low cost and flexible platform may be a promising candidate over other costly conventional electrodes. • It exhibits high sensitivity of 104.31 μA pg−1 mL in broad range of 0.01 pg/mL to 1000 ng/mL, for EpCAM detection. • The clinical applicability and validity has been checked with human serum sample. [ABSTRACT FROM AUTHOR]

Development of the portable device is significant for sensitive and rapid detection of an anthrax biomarker dipicolinic acid (DPA), existing in the B. anthracis. In this work, a novel HAp:Tb-EDTA paper-based ratiometric fluorescent sensor was obtained by a simple one-pot method for rapid and sensitive DPA detection. With the increased DPA concentration, the luminescence intensity of HAp (hydroxyapatite) remained constant, and thus applied as the stable reference signal, while the luminescence signal of Tb3+-EDTA was significantly enhanced due to the antenna effect. Therefore, the HAp:Tb-EDTA paper-based sensor was endowed with self-calibrated and ratiometric fluorescent detection performance for DPA. The proposed sensor showed excellent detection performance with a detection limit as low as 10.8 nM in the linear range of 0.5–30 μM. After combination with a smartphone, rapid visual and fluorescent detection of DPA was achieved. The proposed sensor was successfully applied to detect DPA from B. subtilis spore real samples, showing the application prospects of the paper-based sensors and opening a new horizon to develop novel paper-based point-of-care testing (POCT) devices. A sensing platform was constructed by a HAp:Tb-EDTA paper-based ratiometric fluorescent probe prepared by a one-pot method and combined with a smartphone. The sensing platform has good stability and can be used for sensitive detection of DPA released from Bacillus subtilis spores. [Display omitted] • A novel HAp:Tb-EDTA paper-based ratiometric fluorescent probe was facilely constructed. • The Tb3+-EDTA recognition unit uniformly distributed on HAp with a paper-like structure, making it superior to that based on commercial test papers. • A portable platform was constructed through combining with smartphones for real samples detection, showing widespread application prospects. • Opening a new horizon to develop novel paper-based point-of-care testing (POCT) devices. [ABSTRACT FROM AUTHOR]

Paper-based analytical devices (PADs), thanks to the versatility, cheapness, availability, biodegradability, and porosity of paper, have emerged as flexible sensing platforms for determining various analytes. However, lack of selectivity can be a problem in complex analysis conditions and samples. To improve the selectivity and specificity of PADs, they can be integrated with molecularly imprinted polymers (MIPs). The high selectivity of the sensor is the essential feature for biomarker analysis because the reliable and accurate determination of biomarkers provides valuable information about various diseases, especially cancer. Therefore, MIP-PAD systems offer a good option for biomarker analysis. This way, it is possible to achieve point-of-care tests, early diagnosis, and affordability. This review points out the significant processes of MIP-PAD fabrication and characterization (paper selection and fabrication, synthesis of MIP). The most recent applications of MIP-PADs for biological samples are explained and discussed in detail. Lastly, the commercialization of MIP-PADs is evaluated. This study is the first in the literature to assess MIP-PADs for biomarkers analysis. • The evaluation of MIP-PADs for biomarker detection. • Comprehensive research for fabrication and characterization of MIP-PADs. • The successful sensor applications of MIP-PADs for biological samples. • The place of MIP-PADs in commercial applications. [ABSTRACT FROM AUTHOR]

• IFCC position paper about CDT outlining caveats, key points, and recommendations. • Alcohol intake versus CDT is discussed as well as the cut-off and expected range. • Comparison studies using inadequate study populations will lead to wrong outcome. • Standardisation has led to test accuracy improvements in national EQAS. Carbohydrate deficient transferrin (CDT) is a biomarker for excessive alcohol consumption utilized in clinical and forensic medicine and workplace testing. Previously, many different analytical methods for CDT were used and the measurand varied considerably, making direct comparison of test results difficult. To end this confusion, the IFCC established a working group on CDT standardisation (WG-CDT) which completed its tasks in 2017. This IFCC position paper by the WG-CDT summarizes state of the art information about the measurand and the analytical methods and gives concise recommendations for its utilization. The results achieved by the CDT standardisation process led to accuracy improvements in national external quality assessment schemes over the years. A brief review of ROC based comparison studies with the traditional biomarkers (GGT, MCV, ALT and AST) discusses the bias resulting from inadequate study populations. In large groups of the general population the superior diagnostic performance of CDT is confirmed. The relationship between alcohol intake versus resulting CDT is discussed as well as the cutoff and measurement uncertainty. Concerning the application in practice, potential pitfalls are considered and recommendations handling both analytical and preanalytical caveats are given. Finally, some examples of serious misunderstandings in publications about CDT are addressed. [ABSTRACT FROM AUTHOR]

The use of microfluidic paper-based analytical devices (μPADs) for aiding medical diagnosis is a growing trend in the literature mainly due to their low cost, easy use, simple manufacturing, and great potential for application in low-resource settings. Many important biomarkers (proteins, ions, lipids, hormones, DNA, RNA, drugs, whole cells, and more) and biofluids are available for precise detection and diagnosis. We have reviewed the advances μPADs in medical diagnostics have achieved in the last few years, focusing on the most common human biofluids (whole blood/plasma, sweat, urine, tears, and saliva). The challenges of detecting specific biomarkers in each sample are discussed, along with innovative techniques that overcome such limitations. Finally, the difficulties of commercializing μPADs are considered, and future trends are presented, including wearable devices and integrating multiple steps in a single platform. • μPADs can be applied for simple and low-cost diagnosis in low-resource settings. • The challenges of applying μPADs to human biofluids are analyzed. • Recent advancements to overcome specific drawbacks for each fluid are discussed. • Difficulties in commercializing μPADs and future tendencies are presented. [ABSTRACT FROM AUTHOR]

The accurate detection of glucose and cholesterol plays a pivotal role in disease diagnosis and home care. To this end, biochemical analyzers have become extensively utilized tools for measuring disease biomarkers. Nonetheless, their poor portability and high cost have restricted their accessibility, limiting their use to laboratory settings and hindering the adoption of point-of-care testing (POCT). In contrast, the emergence of portable and affordable paper-based testing platform has revolutionized diagnostic testing by providing distance signals, enhancing intuitiveness and visual accessibility. Consequently, these platforms have become increasingly suitable for POCT. We have developed a POCT platform that integrated AuNS@Ag, stimulus-responsive hydrogel and test strips, enabling visual distance reading of glucose. The silver-coated AuNS and enzyme were encapsulated within a temperature-responsive N-isopropylacrylamide-acrylamide (NIPAM-AcAm) hydrogel to act as target recognition and reaction units respectively. Glucose can diffuse freely within the hydrogel porous matrix, thereby instigating enzyme-catalyzed reaction that induce alterations in the photothermal effect of the system. This dynamic process ensures efficient and responsive modulation of the system's photothermal properties. By ingeniously capturing distance signals induced by the photothermal effect-mediated water release the visualization and quantification of target substances are achieved, with a linear range spanning from 0 to 30 mM. The consistency between distance-based POCT platform and commercial blood glucose meter demonstrates that the platform provides a portable, affordable and reliable method for visual reading biomarkers. The proposed strategy enables direct, visual quantitative analysis of the target without the need for additional analytical instruments. Particularly, this method holds significant promise as an efficient platform for cholesterol and other disease markers measurement. [Display omitted] • A POCT platform was constructed for visible distance-readout of disease marker. • AuNS@Ag was employed as target recognition unit for photothermal signal output. • Temperature-responsive hydrogel as carrier and framework for the platform. [ABSTRACT FROM AUTHOR]

General physicians misclassify depression in more than half of the cases. Researchers have explored the feasibility of leveraging passively collected data points, also called digital biomarkers, to provide more granular understanding of depression phenotypes as well as a more objective assessment of disease. This paper provides a systematic review following the PRISMA guidelines (Page et al., 2021) to understand which digital biomarkers might be relevant for passive screening of depression. Pubmed and PsycInfo were systematically searched for studies published from 2019 to early 2024, resulting in 161 records assessed for eligibility. Excluded were intervention studies, studies focusing on a different disease or those with a lack of passive data collection. 74 studies remained for a quality assessment, after which 27 studies were included. The review shows that depressed participants' real-life behavior such as reduced communication with others can be tracked by passive data. Machine learning models for the classification of depression have shown accuracies up to 0.98, surpassing the quality of many standardized assessment methods. Inconsistency of outcome reporting of current studies does not allow for drawing statistical conclusions regarding effectiveness of individual included features. The Covid-19 pandemic might have impacted the ongoing studies between 2020 and 2022. While digital biomarkers allow real-life tracking of participant's behavior and symptoms, further work is required to align the feature engineering of digital biomarkers. With shown high accuracies of assessments, connecting digital biomarkers with clinical practice can be a promising method of detecting symptoms of depression automatically. • This paper provides a PRISMA-guided systematic review of studies (2019-2024), showing model accuracy ranges of 0.52-0.98. • The review summarises constructs related to mood, location, smartphone use, communication, sleep quality and heart rate. • To be integrated into clinical practice, captured data needs to be reduced to the most relevant features. [ABSTRACT FROM AUTHOR]

Guanosine is an essential biomarker that enacts an important role in neuroprotection against brain-related activities, influences the metabolism of fatty acids, and assists in the improvement of the gastrointestinal tract. A facile and selective electrochemical sensor has been developed for the sensing of guanosine based on a hierarchical porous covalent organic framework. Owing to the distinctive 2D porous architecture and ordered framework of TpBD-COF, the irreversible electrooxidation of guanosine occurred at 1.03 V (vs. SCE) in phosphate buffer solution at pH 6. The anodic peak currents under optimal conditions were linear with guanosine concentration within the range of 0.123–720 μM with a LOD of 40.63 nM under various optimal conditions. Moreover, the developed biosensor was used to determine guanosine in pharmaceutical tablets to confirm its potential application in the healthcare industry. [Display omitted] • Hierarchical porous covalent organic framework-based sensor for guanosine detection. • The heteroatom functionalized structure boosted the electrochemical sensing ability. • It exhibited a broad linear detection range from 0.123 to 720 μM and achieved a low detection limit of 40.63 nM. • The sensor demonstrated excellent repeatability and reproducibility, indicating its reliability for guanosine detection. [ABSTRACT FROM AUTHOR]

• Survivin as an effective diagnostic marker of bladder cancer was confirmed. • Sensitivity of survivin mRNA was higher than that of survivin protein. • Immunohistochemical detection of survivin is more effective for diagnosis. Early detection, diagnosis, and treatment take on critical significance in preventing and treating bladder cancer. As indicated by numerous studies, survivin can serve as a biomarker of bladder cancer, whereas the results of a wide variety of studies have been controversial. This paper is to assess the accuracy of survivin in the diagnosis of bladder cancer by a meta-analysis. The studies regarding the diagnosis of bladder cancer using survivin were systematically retrieved from the CNKI, WanFang, CBM, VIP, Web of science, cochrane library and pubmed were extracted, and the literature quality was assessed. Meta-analysis was conducted using STATA 16.0 MP. 2,082 relevant studies were searched, and 40 studies were finally covered for meta-analysis. The pooled specificity and pooled sensitivity of survivin mRNA was 0.95 (95% CI : 0.91, 0.97) and 0.94 (95% CI : 0.88, 0.97). The pooled specificity and pooled sensitivity of survivin protein reached 0.95 (95% CI : 0.90, 0.97) and 0.87 (95% CI : 0.78, 0.92). The pooled positive likelihood ratio, pooled negative likelihood ratio, the area under the curve, and diagnostic odds ratio for survivin mRNA reached 17.7 (95% CI : 10.3, 30.6), 0.07 (95% CI : 0.04, 0.12), 0.98 (95% CI : 0.97, 0.99) and 266 (95% CI : 114, 621), respectively. For survivin protein was 16.4 (95% CI : 7.9, 33.9), 0.14 (95% CI : 0.08, 0.24), 0.97 (95% CI : 0.95, 0.98) and 117 (95% CI : 38, 357), respectively. Survivin takes on great significance in diagnosing bladder cancer. However, due to some limitations in the number and quality of covered studies, this conclusion should be validated through additional higher quality clinical studies. [ABSTRACT FROM AUTHOR]

This paper analyzes diverse features extracted from spoken language to select the most discriminative ones for dementia detection. We present a two-step feature selection (FS) approach: Step 1 utilizes filter methods to pre-screen features, and Step 2 uses a novel feature ranking (FR) method, referred to as dual dropout ranking (DDR), to rank the screened features and select spoken language biomarkers. The proposed DDR is based on a dual-net architecture that separates FS and dementia detection into two neural networks (namely, the operator and selector). The operator is trained on features obtained from the selector to reduce classification or regression loss. The selector is optimized to predict the operator's performance based on automatic regularization. Results show that the approach significantly reduces feature dimensionality while identifying small feature subsets that achieve comparable or superior performance compared with the full, default feature set. The Python codes are available at https://github.com/kexquan/dual-dropout-ranking. • Dual-net architecture enables automatic regularization. • Ensemble from multiple cross-validations stabilizes detection performance. • Two-step feature selection significantly reduces feature dimensions. • Identified spoken language biomarkers boost detection performance. • Codes are available at https://github.com/kexquan/dual-dropout-ranking. [ABSTRACT FROM AUTHOR]

Smart wound dressings aim to enable early diagnosis and treatment of wound infections to accelerate wound healing. This paper summarizes the latest research progress of smart wound dressings, including smart dressings for monitoring different parameters of wounds, smart dressings that can realize wound management, and advanced smart wound dressings that integrate monitoring and treatment into one, and systematically discusses and analyzes them. [Display omitted] • A comprehensive review of the latest developments in intelligent wound dressings. • Explored various wound dressing design concepts and developed applications. • Discussed the future prospects and challenges of intelligent wound dressings. Wound management has long been a significant concern within the healthcare industry. However, conventional passive wound dressings often fail to meet the requirements for effective wound management. As a result, there is a growing emergence of intelligent wound dressings that aim to address this issue. These smart wound dressings incorporate one or more electrochemical or optical sensors, enabling real-time monitoring of wound conditions. Furthermore, they also integrate various stimulation techniques, including photostimulation, electrostimulation, and pharmacological stimulation, in order to facilitate accelerated wound healing. This integration of sensing and stimulation capabilities holds immense potential for personalized wound care. This paper offers a comprehensive review of recent advancements in the field of wearable, novel dressings designed for the purpose of chronic wound monitoring and management. It examines various design concepts and applications that have been developed. Additionally, the paper discusses the future prospects and challenges associated with wearable bioelectronics in wound care, as well as their potential for clinical utilization. Furthermore, it explores the areas in which further development and research are needed, with a focus on establishing the priorities for the next generation of wound dressings. [ABSTRACT FROM AUTHOR]

Breast cancer has become the most diagnosed cancer worldwide in 2020 with high morbidity and mortality rates. The alarming increase in breast cancer incidence has sprung many researchers to focus on developing novel screening tests to identify early breast cancer which will allow clinicians to provide timely and effective treatments. With much evidence supporting the notion that the deregulation of miRNAs (a class of non-coding RNA) greatly contributes to cancer initiation and progression, the promising role of miRNAs as cancer biomarkers is gaining traction in the research world. Among the upregulated miRNAs identified in breast carcinogenesis, miR-21 was shown to be significantly expressed in breast cancer tissues and bodily fluids of breast cancer patients. Therein, this review paper aims to provide an overview of breast cancer, the role and significance of miR-21 in breast cancer pathogenesis, and its potential as a breast cancer biomarker. The paper also discusses the current types of tumor biomarkers and their limitations, the presence of miR-21 in extracellular vesicles and plasma, screening methods available for miRNA detection along with some challenges faced in developing diagnostic miR-21 testing for breast cancer to provide readers with a comprehensive outlook based on using miR-21 in clinical settings. [ABSTRACT FROM AUTHOR]

[Display omitted] • Nanomaterials possess exceptional optoelectric and electromagnetic properties due to their small size and large surface area • Nanomaterials have been extensively utilized in the biomedical and bioengineering fields, ranging from diagnostics to therapeutics. • Surface modifications of nanomaterials are essential to enhance their adsorbing capability for biomarkers on the nanomaterial surface. • The study explores surface modifications of diverse nanomaterials, encompassing metallic nanoparticles, carbon-based nanomaterials, and self-assembled materials. • The emphasis of the paper is on different surface modification techniques to improve the functionality and applicability of nanomaterials in medical diagnosis. Ranging from diagnostics to therapeutics, nanomaterials have been widely exploited in the fields of biomedicine and bioengineering. The past few decades have witnessed the development of a number of nanomaterials for bringing out the best results in the field of medical diagnosis. However, despite possessing extremely unique material properties, many of them lack surface heterogenic reactivity, which is a crucial factor for the specific binding of biomarkers on the nanomaterial surface. For this reason, nanomaterials have to undergo surface modifications so as to increase the adsorbing capability of biomarkers over the functionalized nanomaterial surface. Keeping in mind the importance of surface modification for successful application of nanomaterials in medical diagnosis, different surface modifications of a number of nanomaterials like metallic nanoparticles (metal and metal oxide nanoparticles, binary compounds), carbon-based nanomaterials (graphene-based nanomaterials, carbon dots, carbon nanotubes), and self-assembled materials have been discussed in this paper. Different types of interactions, such as covalent and non-covalent forces such as electrostatic force, hydrogen bonds, and Vander Waals, have been reported in the literature, which lead to the functionalization of nanoparticles. It has been found that organic molecules such as phosphates, citrates, thiols, amines, and various polymer molecules such as dextran, chitosan, PEG, etc. and inorganic compounds such as metallic elements and ligands are significant in the surface functionalization process of freshly synthesized nanoparticles. The self-assembly of nanostructures has also been found to be beneficial in terms of compatibility in biological media and to be a promising technique for biosensing-related applications of these nanostructures. This study aims at throwing light on the technology prevalent in the field of making nanostructures more advantageous in the field of biosensing by functionalizing their surface, and it indicates that by collaborating nanotechnology with different disciplines such as chemistry, biology, physics, and medicine, it will emerge as the most preferred and commercialized platform for biomedical functions such as biosensing, bioengineering, gene therapy, drug delivery, etc. [ABSTRACT FROM AUTHOR]

The end Permian to Middle Triassic interval (∼252–242 Ma) witnessed the largest marine mass extinction and the most delayed recovery in the Phanerozoic. The nature and mechanism of these biotic and environmental changes remain unclear. This special issue focuses on the Triassic marine sediments in South China, which provide unique documentation of the collapse and recovery of marine ecosystems. Six papers focus on biotic changes and their ecological significance in Early and Middle Triassic times, documenting evidence from bivalves, marine reptiles, stromatolites, hybodontid teeth, vertebrate coprolites, and other putative fossils. Two papers study conodont biostratigraphy across the Permian-Triassic boundary (PTB) and Induan-Olenekian boundary. Two papers reconstruct the palaeoenvironments of the Early Triassic Chaohu Fauna and Middle Triassic Luoping Biota. Two further papers present new marine δ13C records and biomarker data and link them to volcanic eruptions in Early Triassic times. These new findings are important for understanding the co-evolution between biotic and environmental changes in the aftermath of Permian-Triassic boundary mass extinction. [ABSTRACT FROM AUTHOR]

[Display omitted] • A fluorescence sensing system of Tb3+ functionalized HOF uniting CdTe QDs (Tb@HOF/CdTe QDs) was engineered. • Establishment of a sensitive, visual, accurate and stable fluorescence sensing system. • Fluorescence sensing system achieved the visual detection of bilirubin and HSA. • The sensing strategy provides a new method for the early diagnosis of HCC. Abnormal levels of bilirubin and human serum albumin are precursors to hepatocellular carcinoma and many fatal diseases. Establishing a portable, highly sensitive and intuitive dual biomarker detection method for bilirubin and human serum albumin is important to protect human health. Combined with the excellent photoluminescence properties of lanthanide functionalized hydrogen bond organic framework, a novel ratiometric fluorescence intelligent sensing system was engineered with the outstanding features of large Stokes shifts, high luminous stability and the self-calibration effect of dual emission centers in this paper. With the advantage of high sensitivity, strong stability and strong anti-interference, the simultaneous detection of dual biomarkers was realized successfully. The developed fluorescence sensing system had a wide detection range of bilirubin and human serum albumin (13.5 nM ∼ 30.0 μM and 448 nM ∼ 15.0 μM), low detection limits (7.20 nM and 15.6 nM). Furthermore, the developed sensing system realized the smartphone-assisted fluorescence visual detection of bilirubin and human serum albumin in serum and urine successfully with the detection limit of 85 nM and 163 nM, providing a promising detection strategy for the early diagnosis of hepatocellular carcinoma. [ABSTRACT FROM AUTHOR]

Triple-negative breast carcinoma (TNBC) is one of the most challenging subtypes of breast carcinoma and it has very limited therapeutic options as it is highly aggressive. The prognostic biomarkers are crucial for early diagnosis of the tumor, it also helps in anticipating the trajectory of the illness and optimizing the therapy options. Several therapeutic biomarkers are being used. Among them, the next-generation biomarkers that include Circulating tumor (ct) DNA, glycogen, lipid, and exosome biomarkers provide intriguing opportunities for enhancing the prognosis of TNBC. Lipid and glycogen biomarkers serve as essential details on the development of the tumor along with the efficacy of the treatment, as it exhibits metabolic alteration linked to TNBC. Several types of biomarkers have predictive abilities in TNBC. Elevated levels are associated with worse outcomes. ctDNA being a noninvasive biomarker reveals the genetic composition of the tumor, as well as helps to monitor the progression of the disease. Traditional therapies are ineffective in TNBC due to a lack of receptors, targeted drug delivery provides a tailored approach to overcome drug resistance and site-specific action by minimizing the side effects in TNBC treatment. This enhances therapeutic outcomes against the aggressive nature of breast cancer. This paper includes all the recent biomarkers which has been researched so far in TNBC and the state of art for TNBC which is explored. [Display omitted] • The Role of GSK3ꞵ as an Emerging Biomarker in TNBC. • Current state-of -art in the biomarkers for TNBC. • The next generation biomarker researched till date for TNBC. • New insight to the glycogen and lipid markers. [ABSTRACT FROM AUTHOR]

• Sensor array on tongue depressor detects salivary levels of GLU, UA, NO 2 –, and SCN- • Multianalyte determination using a convenient tool for saliva sampling and POC testing. • Tracking 4 clinically relevant biomarkers using an affordable (U$0.10) testing device. • Smartphone-enabled diagnostics of salivary biomarkers toward personalized medicine. • Cytotoxicity of sensing materials was evaluated to ensure the test's biocompatibility. The clinical tests usually make use of blood samples, requiring invasive sample collection protocols, which are not appropriate for decentralized, frequent, and point-of-care (POC) applications. Here, we report disposable (bio)sensors combining electrochemical and colorimetric technologies on an accessible and lightweight wooden tongue depressor platform. The array of (bio)sensors on this commonly used medical tool enables rapid, and safe saliva sampling and showed promise to be used for frequent self-testing of four clinically relevant biomarkers (glucose, uric acid, nitrite, and thiocyanate) in saliva. The electrochemical system was designed to detect uric acid and glucose by chronoamperometric measurements in clinically relevant concentrations ranging from 50 to 500 µmol L−1 and from 10 to 5000 µmol L−1, respectively. Meanwhile, the colorimetric paper-based spot tests were optimized to detect nitrite and thiocyanate in concentrations ranging from 5 to 200 µmol L−1 and 0.5 to 2.1 mmol L−1, respectively, using digital image colorimetry. Our affordable tongue depressor (bio)sensors provide results within 5 min and achieve limits of detection in the µmol L−1 range. Importantly, the results provided by our tests when applied to human saliva samples presented excellent concordance with the traditional spectrophotometric method (at a 95 % confidence level), demonstrating the reliability and robustness of our method. In addition, the toxicity and biocompatibility studies of the tongue depressor (bio)sensors were evaluated using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), Calcein acetoxymethyl ester (Calcein AM), and Calcein Propidium Iodide Hoechst (Calcein PI) Analysis, confirming the safety use of the test. Therefore, our tongue depressor (bio)sensor facilitates frequent testing of several biomarkers and can contribute to personalized medicine. [ABSTRACT FROM AUTHOR]

The significant proliferation of AI-empowered systems and machine learning (ML) across various examined domains underscores the vital necessity for comprehensive and customised explainability frameworks to lead to usable and trustworthy systems. Especially in the medical domain, where validation of methodologies and outcomes is as important as the adoption rate of such systems, the requirements of the depth and the level of abstraction of the explainability are particularly important and necessitate a systemic approach to ensure a proper definition. Explainability and interpretability are important usability and trustworthiness properties of AI-empowered systems and, as such, constitute important factors for technology acceptance. In this paper, we propose a novel framework for explainability requirements in AI-empowered systems using the Technology Acceptance Model (TAM). This framework employs targeted ML (hierarchical clustering, k-means or other) to acquire a user model for personalised, multi-layered explainability. Our novel framework integrates a rule-based system, which guides the degree of trustworthiness to be achieved based on user perception and AI literacy level. We test this methodology in the case of AI-empowered medical systems to (1) assess and quantify the doctors' abilities and familiarisation with technology and AI, (2) generate layers of personalised explainability based on user ability and user needs in terms of trustworthiness and (3) provide the necessary environment for transparency and validation. To assess and quantify the doctors' abilities we have considered Rapid Estimate of Adult Literacy in Medicine (REALM) a tool commonly used in the medical domain to bridge the communication gap between patients and doctors. • Framework for personalised explainability in Artificial intelligence, based on Levels. • Levels refer to AI literacy level and level of abstraction. • Behavioural models were used that measure perception towards an innovation. • Framework is evaluated and implemented in an AI-empowered medical application. [ABSTRACT FROM AUTHOR]

In this paper, a metal strip loaded doping less TFET (MS-DLTFET) biomarker with four cavities is proposed for SARs-CoV-2 detection virus. The results demonstrate that the proposed device offers an improved biomarker performance by introducing the charged plasma concept and the metal strips. The electrical parameters such as electron tunneling rate, drain current (I ds), current ratio (I ON /I OFF), threshold voltage (V th) are evaluated through simulations by immobilized dielectric constant (k) and charge density (ρ) of the bioelements in the nano-gap cavities. In addition, their sensitivity is also calculated with respect to air. The results depict that the proposed device tenders better performance in terms of I ds , I ON /I OFF and V th sensitivity as compared to existing devices. The device's response time under varying k and ρ values are investigated. The non-uniform cavity configurations formed due to steric hindrance effect are studied. It is found that concave configuration offers the best performance compared to other. Furthermore, the cavity size analysis is also performed to optimize the device performance. • The proposed device uses four nano-gap cavities to effectively detect the proteins and DNA charged bioelements of SARs-CoV-2. • This detection capability is attributed to the charged plasma concept, GaSb-source, and metal strip integration. • The effect of cavity thickness is examined. The proposed device shows an optimize performance of cavity thickness of 10 nm. • The device's response time under varying k and ρ values are investigated. It is found 4.1 ps for k = 12. • The result of threshold voltage and response time validates that proposed device has a potential of Corona virus detection. [ABSTRACT FROM AUTHOR]

Extracellular vesicles (EVs) represent a heterogeneous group of particles secreted by cells to transfer information from the cell of origin to recipient cells by carrying various bioactive molecules. Numerous PubMed records on EVs reveal a burgeoning interest in EV-research, with a notable subset focusing on the potential diagnostic and therapeutic applications of EVs for diverse diseases, including cardiovascular disease (CVD), currently a globally leading cause of mortality. However, this great diagnostic and clinical potential has not yet been translated into clinical practice. No EV-based biomarkers and EV-therapeutic products have been approved, and EV-based therapy for CVD has not yet been shown to be effective. Therefore, this paper aims to scrutinize available data and identify what is needed to translate the underlying potential of EVs into specific EV-biomarkers and EV-therapeutic tools applicable in clinical practice. [ABSTRACT FROM AUTHOR]

Osteosarcoma (OS) is a bone cancer which stems from several sources and presents with diverse clinical features, making evaluation and treatment difficult. Chemotherapy tolerance and restricted treatment regimens hinder progress in survival rates, requiring new and creative therapeutic strategies. The Wnt/β-catenin system has been recognised as an essential driver of OS development, providing potential avenues for therapy. Non-coding RNAs (ncRNAs), such as circular RNAs (circRNAs), long non-coding RNAs (lncRNAs), and microRNAs (miRNAs), are essential in modulating the Wnt/β-catenin cascade in OS. MiRNAs control the system by targeting vital elements, while lncRNAs and circRNAs interact with system genes, impacting OS growth and advancement. This paper thoroughly analyses the intricate interplay between ncRNAs and the Wnt/β-catenin cascade in OS. We examine how uncontrolled levels of miRNAs, lncRNAs, and circRNAs lead to an abnormal Wnt/β-catenin network, which elevates the development, spread, and susceptibility to the treatment of OS. We emphasise the potential of ncRNAs as diagnostic indicators and avenues for treatment in OS care. The review offers valuable insights for academics and clinicians studying OS aetiology and creating new treatment techniques for the ncRNA-Wnt/β-catenin cascade. Utilising the oversight roles of ncRNAs in the Wnt/β-catenin system shows potential for enhancing the outcomes of patients and progressing precision medicine in OS therapy. [ABSTRACT FROM AUTHOR]

Treatment options and survival chances are enhanced with early detection of uterine cancer. In this work, an electrochemical paper analytical device (ePAD) for detecting Epidermal growth factor receptor (EGFR), a biomarker for uterine cancer, was demonstrated. The objective of this study is to develop a rapid nano-biosensing method for early detection of fatal uterine cancer. The proposed ePAD is inexpensive, disposable, easy, and repeatable, among other advantageous qualities. The ePAD's Working electrode comprises of silver nanowires. In addition, the use of aptamers has enhanced the performance of the biosensor. The silver nanowires' morphological, optical, elemental content, and phase characteristics were assessed by employing several analytical techniques: transmission electron microscopy (TEM), Fourier transform infrared (FTIR), Scanning electron microscopy (SEM), X-ray diffraction (XRD), and UV–vis spectroscopy. This aptamer-modified ePAD assists in amplifying the signal of the developed platform to identify EGFR. The biosensor utilized the voltametric detection of EGFR in a solution of 0.5 mM potassium ferro/ferri cyanide, which acts as a redox pair by applying a potential of 50 mV/s at the working electrode yielded the highest performance. The designed sensor demonstrated an optimum response broad linearity of 0.01 ng/ml – 1 μg/ml for EGFR, with limit of detection (LOD) of 0.01ng/ml. • The proposed sensor proved good sensitivity and reproducibility. • Silver nanowires that were chemically synthesized and thoroughly characterized were used. • The usage of the PDGF confirmed no cross-reactivity. • The constructed electrochemical sensor worked efficiently in artificial serum and urine sample. • This sensor could be used to detect the wide range of EGFR biomarker for detecting uterine cancer. [ABSTRACT FROM AUTHOR]

[Display omitted] • All the types of biofluids are compared on the basis of constituent biomarkers for human health monitoring. • Explore the mechanism of sweat sensing and recent biosensor advancements in this comprehensive discussion. • Various biomarkers for fitness monitoring, drug abuse, and health status tracking are reported. • Discover key features of sweat sensing modalities for optimized performance and explore suitable sensing options. • Finally, the challenges and future scope of sweat-sensing systems are discussed. The demand for non-invasive real-time health monitoring devices has increased in the last few decades. Healthcare communities claim an increase in the average lifetime of human beings by 10 to 15 years through regular monitoring of the physical status of one's health. Hence, researchers are rigorously focusing on developing optimized wearable biosensors for real-time health status monitoring. However, a few brands like Apple Watch and FitBit have come up with a new class of health monitoring wearables but have yet to succeed in providing more profound insights. As biological fluids consist of molecules secreted from the various body parts, the variation in the concentration of such constituents reveals the health status at the molecular level. Among all the biofluids, sweat can be extracted continuously and also non-invasively. In some health issues, such as diabetes and cystic fibrosis, continuous and real-time diagnosis is required. In such cases, sweat analysis is proven as a gold standard. In this article, we have discussed different biomarkers, their concentration in sweat, and their relative health parameters. This article sheds light on various sweat sampling techniques, different wearable sweat sensing methodologies, and the significance of wearable sweat sensors in the healthcare sector and in the sports community. Adopting safe signaling and data handling techniques and high-throughput manufacturing methods may lead to a more comprehensive picture of health and its broader commercial utility. This article critically reviews the recent developments, technological challenges, and requirements for future advancements in wearable sweat sensors. This review paper comprises a detailed discussion of wearable sweat sensors with an aim to cover all the most important aspects of this system. This piece of study provides all the basic as well as advanced information to the new researchers interested in this field. The future scope discussed here suggests novel possibilities and developments in the healthcare sector. [ABSTRACT FROM AUTHOR]

Human epidemiological studies with biomarkers of effect play an invaluable role in identifying health effects with chemical exposures and in disease prevention. Effect biomarkers that measure genetic damage are potent tools to address the carcinogenic and/or mutagenic potential of chemical exposures, increasing confidence in regulatory risk assessment decision-making processes. The micronucleus (MN) test is recognized as one of the most successful and reliable assays to assess genotoxic events, which are associated with exposures that may cause cancer. To move towards the next generation risk assessment is crucial to establish bridges between standard approaches, new approach methodologies (NAMs) and tools for increase the mechanistically-based biological plausibility in human studies, such as the adverse outcome pathways (AOPs) framework. This paper aims to highlight the still active role of MN as biomarker of effect in the evolution and applicability of new methods and approaches in human risk assessment, with the positive consequence, that the new methods provide a deeper knowledge of the mechanistically-based biology of these endpoints. • Chemical mixture exposure is real-life exposure. • Effect biomarkers are used in disease prevention. • Micronucleus gives reliable information of genotoxicity. • Classical effect biomarkers serve as comparators for novel biomarkers research. [ABSTRACT FROM AUTHOR]

The aim of this paper is to evaluate the position of the Holocene transgression on the coast of the Valencia Gulf. To achieve this goal, a sedimentological and micropaleontological analysis of samples of fossil benthic foraminifera in cores from six boreholes drilled in three different wetlands (Almenara marsh, Moro marsh and Valencia lagoon) was carried out. In order to assess the extent of sea level change, at least three factors must be taken into account: 1) eustatic rise (global scale) 2) neotectonics (regional scale) and 3) the sedimentary factor (local and regional scale). Regarding the first factor, some authors have noted that the Holocene transgression reached +1 m above the current sea level in this area. As for the second factor, while the Valencia lagoon is located on a subsiding coast the northernmost marshes are located on a tectonically stable coast. Finally, sedimentation rates are highly variable depending on the area; whereas in the Valencia lagoon the shoreline generally shifts seawards (progradation) in the northernmost areas the coast is currently undergoing retrogradation, although the anthropic factor clearly interferes with this pattern. One of the main conclusions is that in the Valencian coast the Holocene maximum relative sea level did not exceed the present-day one, except in the case of the subsiding area of the Valencia lagoon. The calculation of sedimentation rates, the relative sea-level curve and the evolution of the water column in the different wetlands seem to corroborate it. Radiocarbon and AAR analyses allowed us to date the maximum extent of the Holocene transgression on the Valencian coast at around 5500 cal yr BP in all cases. Despite the different subsidence the three studied wetlands reflected the predominant marine influence until 5500–5200 BP, which was later followed by a growing fluvial or continental incidence, when glacioeustatic adjustments defined the patterns of coastal progradation. [Display omitted] • Location of the MIS 1 coastline position in three West Mediterranean wetlands. • The global Holocene eustatic rise invaded the three wetlands at least 5300 years BP. • Subsidence rate determined different MIS 1 relative sea-level rise in the wetlands. • Tectonic stability in the northern wetlands involved slower relative sea-level rise. [ABSTRACT FROM AUTHOR]

• The review focuses on Aβ, p-tau, NfL, GFAP, NDEs, and TDP-43 as blood AD biomarkers. • Progress in the area was accelerated in part due to advanced analytic platforms. • Blood biomarkers enable broad initial screening, succeeded by in-depth assessments. • Blood biomarkers can evaluate the impact of AD-modifying treatments. • Equitable diagnosis across socioeconomics is needed to mitigate disparities. The field of blood-based biomarkers for Alzheimer's disease (AD) has advanced at an incredible pace, especially after the development of sensitive analytic platforms that can facilitate large-scale screening. Such screening will be important when more sophisticated diagnostic methods are scarce and expensive. Thus, blood-based biomarkers can potentially reduce diagnosis inequities among populations from different socioeconomic contexts. This large-scale screening can be performed so that older adults at risk of cognitive decline assessed using these methods can then undergo more complete assessments with classic biomarkers, increasing diagnosis efficiency and reducing costs to the health systems. Blood-based biomarkers can also aid in assessing the effect of new disease-modifying treatments. This paper reviews recent advances in the area, focusing on the following leading candidates for blood-based biomarkers: amyloid-beta (Aβ), phosphorylated tau isoforms (p-tau), neurofilament light (NfL), and glial fibrillary acidic (GFAP) proteins, as well as on new candidates, Neuron-Derived Exosomes contents (NDEs) and Transactive response DNA-binding protein-43 (TDP-43), based on data from longitudinal observational cohort studies. The underlying challenges of validating and incorporating these biomarkers into routine clinical practice and primary care settings are also discussed. Importantly, challenges related to the underrepresentation of ethnic minorities and socioeconomically disadvantaged persons must be considered. If these challenges are overcome, a new time of cost-effective blood-based biomarkers for AD could represent the future of clinical procedures in the field and, together with continued prevention strategies, the beginning of an era with a lower incidence of dementia worldwide. [ABSTRACT FROM AUTHOR]

Tire impression evidence can be a valuable tool during a crime scene investigation—it can link vehicles to scenes or secondary locations, and reveal information about the series of events surrounding a crime. The interpretation of tire impression evidence relies on the expertise of forensic tire examiners. To date, there have not been any studies published that empirically evaluate the accuracy and reproducibility of decisions made by tire impression examiners. This paper presents the results of a study in which 17 tire impression examiners and trainees conducted 238 comparisons on 77 distinct questioned impression-known tire comparison sets (QKsets). This study was conducted digitally and addressed examinations based solely upon the characteristics of the tire impression images provided. The quality and characteristics of the impressions were selected to be broadly representative of those encountered in casework. Participants reported their decisions using a multi-level conclusion scale: 68% of responses were class associations (Association of Class Characteristics or Limited Association of Class), 21% were definitive decisions (ID or Exclusion), 8% were probable decisions (High Degree of Association or Indications of Non-Association), and 3% were neutral responses (Not Suitable or Inconclusive). Although class associations were the most reported response type, when definitive decisions were reported, they were often correct: 96% of IDs and 89% of Exclusions were consistent with ground truth regarding the source of the known tire in the QKset. Overall, we observed 4 erroneous definitive decisions (3 Exclusions on mated QKsets; 1 ID on a nonmated QKset) and 1 incorrect probable decision (Indications of Non-Association on a mated QKset). Decision rates were notably associated with both quality (lower quality questioned impressions were more likely to result in class associations) and dimensionality (2D questioned impressions were more likely to result in definitive decisions), which were correlated factors. Although the study size limits the precision of the measured rates, the results of this study remain valuable to the forensic science and legal communities and provide empirical data regarding examiner performance for a discipline that previously did not have any such estimates. • First formal black box evaluation of forensic tire examiner decisions. • Evaluated overall decision rates as well as accuracy and reproducibility. • Class associations comprised 68% of decisions reported in this study. • Definitive decisions were often correct: 96% of IDs and 89% of Excls were correct. [ABSTRACT FROM AUTHOR]

Providing reliable diagnostic evidence to doctors while minimizing financial and physical burdens on patients is a prominent focus of current research. Gait features show potential as a clinical marker for dementia diagnosis. Radar is capable of efficient, contactless collecting human motion. This paper proposes a novel radar-based gait analysis strategy with a Transformer-liked network for dementia diagnosis. The gait data are collected by Micro-Doppler radar. Then Welch's power spectral density estimation is adopted to obtain the frequency features while unifying and compressing data size. The network is designed to explore the relationship between dementia and gait features. In the network, 1D convolution is crucial in extracting local features and encoding features into deeper dimensions. The attention-based module, inspired by the encoder of the Transformer, possesses an edge in capturing long-sequence dependencies. The dual-stage gating mechanism enhances the discriminative power of the learned representations by fine-tuning the weights of extracted features. To validate the effectiveness of the proposed strategy, comparative experiments are performed with prevailing networks in both time and frequency domains. Experimental results demonstrate the superiority of the frequency domain processing method over the time domain processing method and fusion time-frequency processing method. Notably, the proposed model outperforms others, achieving the highest accuracy of 94.93% in frequency domain processing-based experiments — 5.91% and 4.25% higher than the highest accuracies in time domain processing-based experiments and fusion time-frequency processing-based experiments respectively. The overall findings illustrate that our proposal can provide a reliable reference for dementia diagnosis effectively. • Gait of dementia and non-afflicted individuals is collected using Doppler radar. • Power spectral density unifies data size and reduces data length by over 63.51%. • The proposed model aims to obtain the link between gait data and dementia. [ABSTRACT FROM AUTHOR]

[Display omitted] • Fluorescent Zn based metal organic framework (MOF) synthesized. • MOF showed the ultra-sensitive detection of hyperprolinemia biomarker. • Colorimetric response was extremely fast (within 5 s). • The sensing mechanism was rationalized by electron transfer, ACE and further DFT study. • MOF showed the detection hyperprolinemia biomarker in biological sample (human saliva). A hydrogen bonded ability metal organic framework (MOF, 1 Zn) is used for the ultra-sensitive "turn-on" detection of hyperprolinemia biomarker with ultrafast (within 5 s) colorimetric response making the first MOF based hyperprolinemia biomarker sensor. The detection limit (4.46 ppb) is outperformed compared to all contemporary hyperprolinemia biomarker based sensors. Further, the sensor showed the recognition of biomarker in biological sample (human saliva). The detection of biomarker is also realized through colorimetric response (solution based and paper strip method). The mechanism of sensing is established through the electron transfer and the absorption caused emission (ACE). Moreover, the theoretical study is performed to support the sensing mechanism. The control titration of 1 Zn suggest that the free –NH 2 group of linker in 1 Zn is involved in supramolecular interaction (hydrogen bonding) with the carboxylic group present on biomarker results the facile occurrence of electron transfer and ACE. Consequently, the luminescence "turn-on" effect of 1 Zn for hyperprolinemia biomarker is observed. [ABSTRACT FROM AUTHOR]

Archaeological excavations in urban and rural contexts often uncover dark homogeneous anthropogenic deposits, soils and soil horizons, known as Dark Earths, Cultural Layers and Anthrosols. Major scientific questions arise about the processes that lead to the formation of these soils and deposits, as they are often related to a complex combination of environmental, climatic, and anthropogenic factors. Many studies focused on the morphological and physical-chemical investigation of the archaeological remains found as well as the inorganic constituent of the soil. The organic fraction has been only roughly investigated and studies carried out on a molecular level are very limited. However, a more refined investigation of the chemical constituents of these soils can potentially reveal pivotal insights on the archaeological context such as past domestic habits and/or urban organization. It has been demonstrated that, among organic matter constituents, fecal steroids are promising biomarkers to track fecal input in many environmental matrixes such as water, soils, and sediments. In this paper we determine the fecal sterols and stanols content in dark homogeneous anthropogenic deposits and soils found in seven archaeological sites in Italy (from Verona, Como, Florence, Mel and Conegliano) dated from the Late Bronze Age and the Medieval Period, aiming to assess the major contribution of the fecal input using diagnostic fecal indexes obtained from specific fecal sterol proportions. To this purpose, a baseline was established by identifying the fecal fingerprint of domestic herbivores (caprids, ovines, equines and bovines) and omnivores (pigs). Based on their fecal fingerprint, we classified the deposits of seven studied sites into four distinct categories: i) the medieval sites of Verona, presented a strong mixed fecal input from both herbivores and humans; ii) the medieval sites of Como and Florence which showed a similar pattern, with a predominance of human fecal input over livestock; iii) the late medieval soils of Mel and the late bronze age Cultural Layers of Castellar di Leppia (Verona) which exhibited a generally scarce fecal contamination while iv) the final bronze age site of Conegliano (Treviso), a strong fecal contamination from herbivores was detected. These results thus demonstrate that for the Medieval Dark Earth the socio-cultural processes leading to the formation of the Dark Earth differ in terms of sewage and waste management and/or in animal husbandry practices. • The molecular fecal fingerprint of domestic animals was established. • Seven archaeological sites in north-central Italy were analyzed for fecal input. • The diverse fecal contamination patterns reveal past habits of sewage and water management. [ABSTRACT FROM AUTHOR]

Mitochondria are bioenergetic, biosynthetic, and signaling organelles in eukaryotes, and contain their own genomes, mitochondrial DNA (mtDNA), to supply energy to cells by generating ATP via oxidative phosphorylation. Therefore, the threat to mitochondria' integrity and health resulting from environmental exposure could induce adverse health effects in organisms. In this review, we summarized the association between mtDNA copy number (mtDNAcn), and environmental exposures as reported in the literature. We conducted a literature search in the Web of Science using [Mitochondrial DNA copy number] and [Exposure] as two keywords and employed three selection criteria for the final inclusion of 97 papers for review. The consensus of data was that mtDNAcn could be used as a plausible biomarker for cumulative exposures to environmental chemical and physical agents. In order to furtherly expand the application of mtDNAcn in ecological and environmental health research, we suggested a series of algorithms aiming to standardize the calculation of mtDNAcn based on the PCR results in this review. We also discussed the pitfalls of using whole blood/plasma samples for mtDNAcn measurements and regard buccal cells a plausible and practical alternative. Finally, we recognized the importance of better understanding the mechanistic analysis and regulatory mechanism of mtDNAcn, in particular the signals release and regulation pathways. We believe that the development of using mtDNAcn as an exposure biomarker will revolutionize the evaluation of chronic sub-lethal toxicity of chemicals to organisms in ecological and environmental health research that has not yet been implemented. [Display omitted] • We summarized the associations of mtDNAcn and environmental exposures. • The consensus was that mtDNAcn could be a plausible exposure biomarker. • We suggested algorithms aiming to standardize the quantification of mtDNAcn. • We discussed the importance of proper specimens for mtDNAcn measurements. • We recognized the needs of better understanding the mechanistic of mtDNAcn. [ABSTRACT FROM AUTHOR]

Fructose is one of the most important monosaccharides in the human diet that the human body needs for proper metabolism. This paper presents an approach to study biochemical changes caused by sugars in human normal bronchial cells (BEpiC) and human cancer lung cells (A549) by Raman spectroscopy and Raman imaging. Results after supplementation of human bronchial and lung cells with fructose are also discussed and compared with results obtained for pure human bronchial and lung cells. Based on Raman techniques we have proved that peaks at 750 cm−1, 1126 cm−1, 1444 cm−1, 1584 cm−1 and 2845 cm−1 can be treated as biomarkers to monitor fructose changes in cells. Results for fructose have been compared with results for glucose. Raman analysis of the bands at 750 cm−1, 1126 cm−1, 1584 cm−1 and 2845 cm−1 for pure BEpiC and A549 cells and BEpiC and A549 after supplementation with fructose and glucose are higher after supplementation with fructose in comparison to glucose. The obtained results shed light on the uninvestigated influence of glucose and fructose on lipid droplet metabolism by Raman spectroscopy methods. [Display omitted] • Raman spectroscopy allows to identify the biomarkers in BEpiC and A549 cells caused by incubation with fructose and glucose. • Raman bands at 750 cm-1, 1126 cm-1, 1444 cm-1, 1584 cm-1 and 2845 cm-1 can be treated as biomarkers to monitor fructose changes in BEpiC and A549 cells. • Raman spectroscopy allows to monitor the metabolism of lipid droplets after supplementation with glucose and fructose. [ABSTRACT FROM AUTHOR]

In this paper, we explore the challenges associated with biomarker identification for diagnosis purpose in biomedical experiments, and propose a novel approach to handle the above challenging scenario via the generalization of the Dantzig selector. To improve the efficiency of the regularization method, we introduce a transformation from an inherent nonlinear programming due to its nonlinear link function into a linear programming framework under a reasonable assumption on the logistic probability range. We illustrate the use of our method on an experiment with binary response, showing superior performance on biomarker identification studies when compared to their conventional analysis. Our proposed method does not merely serve as a variable/biomarker selection tool, its ranking of variable importance provides valuable reference information for practitioners to reach informed decisions regarding the prioritization of factors for further investigations. [ABSTRACT FROM AUTHOR]

This systematic review aimed at synthesizing current evidence on biomarkers associated with cognitive impairment (CI) in Post-Traumatic Stress Disorder (PTSD). A systematic literature search was conducted for studies assessing biomarkers associated with CI in PTSD. Of the 10,149 titles screened, 8 studies met our inclusion criteria. In a single longitudinal study, MRI volumes, Aβ and tau accumulation were not associated with CI in PTSD. Studies on structural imaging reported no significant association between morphological changes and CI. Two studies on diffusion neuroimaging showed abnormalities in white matter tracts which were cross-sectionally associated with CI in PTSD. Similarly, lower resting-state functional connectivity in neocortical networks, and elevated tau in the neocortex were also cross sectionally associated with CI. Two single studies on biochemical biomarkers showed that sixteen novel plasma proteins and lower BDNF, indicative of genetic vulnerabilities associated with neural and synaptic dysfunctions commonly observed in neurodegeneration, were cross-sectionally associated with CI in PTSD. Overall, evidence is of low quality. Longitudinal research utilizing large representative samples of trauma exposed populations are needed to establish the utility of specific biomarkers in monitoring cognitive decline in PTSD. • A systematic review on biomarkers of cognitive impairment (CI) in PTSD was conducted; 8 studies met inclusion criteria. • Despite their potential importance, no biomarker has as yet been validated. • In a single longitudinal study identified, MRI volumes, Aβ and tau accumulation were not associated with CI in PTSD. • Diffusion neuroimaging showed abnormalities in white matter tracts which were cross-sectionally associated with CI in PTSD. • This paper provides clear recommendations on how to overcome the current issues in this research field. [ABSTRACT FROM AUTHOR]

Occupational asthma covers a group of work-related diseases whose clinical manifestations include airway hyperresponsiveness and airflow limitation. Although the chemical respiratory allergy (CRA) induced by Low Molecular Weight (LMW) sensitizers is a major concern, especially in terms of the regulatory framework, to date there are no methods available for preclinically addressing this toxicological outcome, as its mechanistic background is not fully understood at molecular or cellular levels. This paper proposes a mechanistic study applying New Approach Methodologies (NAM) of the pro-inflammatory and functional effects triggered by LMW respiratory allergens in different respiratory tract cell lines, including bronchial epithelial (BEAS-2B), lung fibroblast (MRC-5), and endothelial cells (EA.hy926), and an analysis of the capacity of such chemicals to interact with the mucin protein, to address certain toxicodynamic aspects of such compounds. The results showed that some of the sensitizers evaluated interact with mucin, the main protein mucus component, but the toxicant-mucin complex formation does not seem to be a common feature of different chemical classes of allergens. At a cellular level, sensitizers promoted an increase in IL-8, IL-6, and IL-1β production in the evaluated cell types. It also impaired the MUC1 expression by bronchial cells and activated endothelial cells, thereby increasing the ICAM-I surface expression. Taken together, our results showed that these aforementioned cell types participate in the CRA Adverse Outcome Pathway and must be considered when developing preclinical testing strategies, particularly investigating danger signal production after exposure to LMW sensitizers in different tissue compartments. [ABSTRACT FROM AUTHOR]

Gastrointestinal (GI) malignancies, encompassing gastric, hepatic, colonic, and rectal cancers, are prevalent forms of cancer globally and contribute substantially to cancer-related mortality. Although there have been improvements in methods for diagnosing and treating GI cancers, the chances of survival for these types of cancers are still extremely low. According to the World Cancer Research International Fund's most recent figures, stomach cancer was responsible for roughly one million deaths worldwide in 2020. This emphasizes the importance of developing more effective tools for detecting, diagnosing, and predicting the outcome of these cancers at an early stage. Biomarkers, quantitative indications of biological processes or disease states, have emerged as promising techniques for enhancing the diagnosis and prognosis of GI malignancies. Recently, there has been a considerable endeavor to discover and authenticate biomarkers for various GI cancers by the utilization of diverse methodologies, including genomics, proteomics, and metabolomics. This review provides a thorough examination of the current state of biomarker research in the field of gastrointestinal malignancies, with a specific emphasis on colorectal, stomach, and liver cancers. A thorough literature search was performed on prominent databases such as PubMed, Scopus, and Web of Science to find pertinent papers published until November, 2023 for the purpose of compiling this review. The diverse categories of biomarkers, encompassing genetic, epigenetic, and protein-based biomarkers, and their potential utility in the fields of diagnosis, prognosis, and treatment selection, are explored. Recent progress in identifying and confirming biomarkers, as well as the obstacles that persist in employing biomarkers in clinical settings are emphasized. The utilization of biomarkers in GI cancers has significant potential in enhancing patient outcomes. Ongoing research is expected to uncover more efficient biomarkers for the diagnosis and prognosis of these cancers. [ABSTRACT FROM AUTHOR]

Serum prostate-specific antigen (PSA) is thought to be the most vital indicator for early identification, staging and monitoring of prostate cancer (PCa). Although lateral flow immunoassay (LFA) has demonstrated limitless promise for point-of-care testing (POCT) and has drawn increasing interest and attention, there are significant restrictions on the assay's sensitivity and quantitative capability. Surface-enhanced Raman spectroscopy-based LFA (SERS-LFA) technique integrates the great sensitivity of SERS with the simplicity, rapidity, and usability of the LFA technique, making it ideal for POCT. In this paper, we propose a sensitive self-calibrating SERS-LFA platform, which uses Au@MBN@Ag@PSA NPs as a SERS immunoprobe for the specific recognition of PSA and loads graphene oxide/gold nanoparticles (GO/Au NPs) on nitrocellulose (NC) membranes as an internal standard (IS) molecule. The SERS-LFA platform's detection accuracy is increased through dynamic calibration of the characteristic signals, which is accomplished by detecting the immunoprobe and IS signals simultaneously and computing their respective signal intensity ratios. The self-calibrated SERS-LFA platform demonstrated a 1.65-fold improvement in reproducibility over the conventional SERS-LFA, and PSA could only be detected to a limit of 0.08 ng/mL, meaning that it was 3.5-fold lower than the conventional SERS-LFA platform. The spike recovery experiments yielded recoveries of 96.16∼104.53% with RSD values of 9.37%, 8.66%, and 3.49%, respectively, demonstrating that our self-calibrated SERS-LFA platform for PSA quantification has an acceptable level of precision and has great prospect for early screening of PCa and other diseases. [Display omitted] • A SERS-LFA platform with self-calibration was developed. • The self-calibrating SERS-LFA platform significantly corrects for linear correlation and improves quantitative accuracy. • The self-calibrating SERS-LFA platform offers lower LOD and higher reproducibility than traditional SERS-LFA. [ABSTRACT FROM AUTHOR]

• This review provides a pioneering systematic and detailed explanation of breath marker generation mechanisms in diseases, the relevance of these markers to diseases, and the diverse methods for detecting various types of markers. • It introduces the core constituents of typical exhaled breath, shedding light on microscopic mechanisms and associated diseases, encompassing both the oral cavity and common systemic conditions. • The paper deliberates on recent research strides in gas sensors, with a focus on their existing or potential roles in diagnosing and assessing oral diseases and pathologies. • It offers an overview of strategies to overcome the present limitations of different gas sensor types, which holds significance for the swift and structured advancement of the field. As society advances and social status improves, oral odor's impact on psychological well-being and social interactions gains recognition. Exhaled breath, regardless of clinical bad breath, contains valuable biomarkers linked to oral diseases. Analyzing breath enables early clinical diagnosis and non-invasive health management, facilitating swift detection of exhaled gas biomarkers. This review spotlights significant oral volatile biomarkers and their formation mechanisms in diseases. It also summarizes recent advancements in gas sensors with stomatology applications. The first section explores typical exhaled breath constituents, micro-mechanisms, and associated oral and systemic conditions. The subsequent section examines gas sensing device progress in the past five years, emphasizing their use in diagnosing oral diseases and pathological states. These devices evaluate various gas biomarkers, holding promise for bedside detection and routine monitoring, ultimately enhancing future quality of life. [ABSTRACT FROM AUTHOR]

[Display omitted] • Two colorimetric aptasensor reproducible, accurate and specific are manufactured for IL-6 and CRP quantification to detect sepsis. • µpads are incredible tools for stabilizing result of gold nanoparticle in aptasensors. In addition to stabilizing reaction results, the pads were shown to improve the limit and linear range of detection. • By using the µpads, we were able to use color histogram analyzing instead of UV–Vis spectroscopy to analyze results. Histogram analysis was done by taking a picture with a smart phone and did not need a complicated device. Point-of-care testing is defined as medical diagnostic testing at or near the time and place of a patient. The integration of microfluidics with functionalized nanomaterials provides a rapid and sensitive detection method for biomarkers. Due to their optical characteristics, gold nanoparticles (GNPs) and aptamers can be used in a colorimetric technique. In this research, accurate and quick aptasensors were created using aptamers for two sepsis biomarkers, interleukin-6 (IL-6) and C-reactive protein (CRP). Aptamers were combined with GNPs to create aptasensors, which were then used to analyze various biomarker concentrations after aptamer-protein docking on the online HDOCK server to verify aptamer-protein interactions. To improve the results' stability and ease of use during the reaction time, microfluidic paper-based analytical devices (µPAD) was employed. The linear diagnostic ranges in this method were 50–1000 mg L−1 and 1–25 ng/L, and limit of detection values were 1.9 mg L−1 and 0.07 ng/L for CRP and IL-6, respectively; These values decreased when µPADs were used and became more suitable to diagnosis of sepsis. Two aptasensors were highly stable, reproducible, accurate, and recoverable. Our result suggests that colorimetric GNPs can be used to detect a specific analyte through color changes visible to the naked eye for monitoring purposes or as simple optical detectors for quantitative measurements. [ABSTRACT FROM AUTHOR]

Erigeron breviscapus is a common medicine of eight ethnic minorities, including Miao, Naxi, and Yi. As early as the Ming Dynasty (AD 1368–1644), Lanmao's Materia Medica of Southern Yunnan (AD 1436) recorded that the medicine is used for the treatment of "Zuo tan you huan." In modern pharmacological research, Erigeron breviscapus injection is the most commonly used preparation in the treatment of ischemic stroke caused by acute cerebral infarction, but its mechanism of action in the treatment of ischemic stroke is not well understood. In this study, a metabonomics study based on ultraperformance liquid chromatography–quadrupole time-of-flight tandem mass spectrometry (UPLC-QTOF-MS) was used in investigating the effect of a traditional Chinese medicine preparation Erigeron breviscapus injection on the rat model of focal cerebral ischemia-reperfusion and the affinity of its main components with the targets of mitochondrial apoptotic pathways. This study used molecular docking technology to verify the effective binding ability of main effective components of Erigeron breviscapus injection to target proteins related to mitochondrial apoptosis pathway. This study developed a metabonomics method based on the ultra-performance liquid chromatography combined with quadrupole time-of-flight tandem mass spectrometry (UPLC Q-TOF MS) to evaluate the efficacy and study the mechanism of traditional Chinese medicine preparation. With pattern recognition analysis (principal component analysis and partial least squares-discriminate analysis) of urinary metabolites, a clear separation of focal cerebral ischemia-reperfusion model group and healthy control group was achieved. Erigeron breviscapus injection can significantly reduce the area of cerebral infarction, improve tissue morphological lesion in rats, and can increase the number of Nissl bodies. It may be a promoting factor by inhibiting hippocampal nerve cell apoptosis and Bax protein expression and by exerting effects against ischemia reperfusion after the induction of apoptosis. Thus, it plays a role in brain protection. Moreover, it can considerably promote the recovery of neurological deficiency signs in advance. Meanwhile, Erigeron breviscapus decreased malondialdehyde content and T-NOS activity. Its curative effect from strong to weak order: low dose > high dose > medium dose. The representative components of Erigeron breviscapus have good affinity with the active sites of mitochondrial apoptosis-related proteins. Metabolomics found that the potential biomarkers regulated by breviscapine are kynurequinolinic acid, succinylornithine, and leucine proline. It is speculated that it may participate in TRP–kynurequinolinic acid and succinylornithine–urea cycle–NO metabolic pathways. This paper revealed the potential biomarkers and metabolic pathways regulated by Erigeron breviscapus. It was speculated that the mechanism is related to its inhibition of mitochondrion-mediated apoptosis. Erigeron breviscapus could restore the metabolic profiles of the model animals to normal animal levels. The mechanism may be related to the potential biomarkers of quinolinic acid, succinylornithine, and leucine proline and the metabolic pathways involved. However, the exact mechanism by which Erigeron breviscapus inhibits mitochondrion-mediated apoptosis remains to be further explored. [Display omitted] • The metabolic profile of cerebral ischemia-reperfusion injury model rats regulated by Breviscapus injection were revealed. • A new method of metabolomics combined with pharmacodynamics to evaluate the effectiveness of ethnomedicine was explored. • Erigeron breviscapus has high research value. • Erigeron breviscapus is a common medicine of eight ethnic minorities, such as the Miao, Naxi and Yi nationalities. [ABSTRACT FROM AUTHOR]

• Ti 3 C 2 T x MXene based sensor for determination of Vitamin B 6. • High electrocatalytic activity of MnO 2 -Pi/MXene/CFP towards oxidation of Vitamin B 6. • The fabricated electrochemical sensor showcased low LOD and wide linear dynamic range. • Selective quantification of Vitamin B 6 in pharmaceutical samples. MXenes are 2D nanomaterials that are considered the materials of the future generation due to their high electrical conductivity, good biocompatibility, and ease of functionalization. This research work reports the electrochemical sensing of Vitamin B 6 using the Manganese dioxide-inorganic phosphate/MXene brush-coated Carbon fiber paper electrode (MnO 2 -Pi/MXene/CFP) electrode for the first time. The three-dimensional Ti 3 C 2 T x MXene nanosheets consisting of highly ordered, vertically aligned nanosheets with electrochemically deposited MnO 2 -Pi are capable of yielding a synergistic effect in combination with high electrochemical performance and large surface area of MnO 2 -Pi. The reported electrochemical sensor exhibited a wide linear dynamic range (0.06–650 µM) and a low-level detection limit of 0.021 µM. An increase in the anodic peak current confirms the rapid transfer of electrons transfer arising between the Ti 3 C 2 T x MXene and MnO 2 -Pi. The results attained substantiate that the fabricated sensor has enhanced selectivity, reproducibility, and stability toward the electrochemical determination of Vitamin B 6 in real samples. This research work describes the utilization of Manganese dioxide-Phosphate/MXene brush-coated CFP electrode (MnO 2 -Pi/MXene/CFP) electrode for the electrochemical sensing of Vitamin B 6. The fabricated electrochemical sensor could exhibit a low-level detection limit of 35.44 µM and wide linear dynamic range (5–650 µM). The rapid transferance of electrons between the Ti 3 C 2 T x MXene and MnO 2 -Pi was responsible for an increase in the anodic peak current. [Display omitted] [ABSTRACT FROM AUTHOR]

Studies of prenatal substance exposure often rely on self-report, urine drug screens, and/or analyses of blood or meconium biomarkers. Accuracy of these measures is limited when assessing exposure over many weeks or months of gestation. Nails are increasingly being considered as a matrix from which to assess substance exposure. This systematic review synthesizes data on the validity of detecting alcohol, nicotine, cannabis, and opioid from nail clippings, with an emphasis on prenatal exposure assessment. The systematic review was conducted using PRISMA 2020 guidelines. Seven databases were searched with keywords relevant to the four substances of interest. Results were summarized grouping manuscripts by the exposure of interest with focus on accuracy and feasibility. Of 2384 papers initially identified, 35 manuscripts were included in our qualitative synthesis. Only a few studies specifically looked at pregnant individuals or mother-child dyads. Across the four substances, many studies demonstrated a dose-response relationship between exposure and concentration of analytes in nails. Nail assays appear to detect lower level of exposure compared to hair; however, sample insufficiency, especially for multi-substance assays, remains a limitation. Based on the reviewed studies, nail clippings are an acceptable and potentially preferable matrix for the evaluation of these four prenatal substances when sampling frequency and/or study design necessitates assessment of past exposures over an extended period. Nails have the advantage of infrequent sampling and minimal invasiveness to assess a broad exposure period. Future studies should examine validity of analytes in toenail versus fingernail clippings. • We performed a systematic review of substance exposures in nail clipping samples. • Exposures of interest were alcohol, nicotine, opioids and cannabinoids. • Many studies demonstrated a dose-response relationship. • Nails were an acceptable matrix for evaluating prenatal exposures. [ABSTRACT FROM AUTHOR]

Repetitive transcranial magnetic stimulation (rTMS) is a safe, effective and non-invasive form of neuromodulatory therapy in patients with major depressive disorder (MDD). MDD is associated with increased peripheral and brain inflammation. The current paper aims to provide an overview of research examining the relationship between immune and inflammatory markers and response to rTMS in MDD. A scoping review method was adopted in keeping with the PRISMA-ScR guidelines. Twelve relevant studies were retrieved from the PubMed and Scopus databases and rated for study quality using a modified version of the BIOCROSS tool. Response to rTMS in MDD was associated with basal and post-treatment levels of the inflammatory markers amyloid A, antithrombin III, oxidised phosphatidylcholine, and the microRNA miR-146a-5p. Inconsistent results were observed for the cytokines interleukin-1β, interleukin-2 and tumour necrosis factor-α. Increased baseline levels of interleukin-6 and C-reactive protein were linked to a poorer response to rTMS. These results suggest that rTMS may have effects on immune-inflammatory pathways that are distinct from those of antidepressants and electroconvulsive therapy. Because of certain methodological limitations in the included studies, these results should be interpreted with caution. [Display omitted] [ABSTRACT FROM AUTHOR]

The mesopelagic zooplankton community plays an important role in the cycling and sequestration of carbon via the biological pump. However, little is known about the physiology and ecology of key taxa found within this region, hindering our understanding of their influence on the pathways of energy and organic matter cycling. We sampled the eight most abundant zooplankton (Calanoides acutus, Rhincalanus gigas, Paraeuchaeta spp., Chaetognatha , Euphausia triacantha, Thysanoessa spp., Themisto gaudichaudii and Salpa thompsoni) from within the mesopelagic zone in the Scotia Sea during a sinking diatom bloom and investigated their physiological ecology using lipid biomarkers and stable isotopic signatures of nitrogen. Data suggest that the large calanoid copepods, C. acutus and R. gigas , were in, or emerging from, a period of metabolic inactivity during the study period (November 15th – December 15th, 2017). Abundant, but decreasing lipid reserves in the predominantly herbivorous calanoid copepods, suggest these animals may have been metabolising previously stored lipids at the time of sampling, rather than deriving energy solely from the diatom bloom. This highlights the importance of understanding the timing of diapause of overwintering species as their feeding is likely to have an impact on the turnover of particulate organic matter (POM) in the upper mesopelagic. The δ15N signatures of POM became enriched with increasing depth, whereas all species of zooplankton except T. gaudichaudii did not. This suggests that animals were feeding on fresher, surface-derived POM, rather than reworked particles at depth, likely influencing the quantity and quality of organic matter leaving the upper mesopelagic. Our study highlights the complexity of mesopelagic food webs and suggests that the application of broad trophic functional types may lead to an incorrect understanding of ecosystem dynamics. • Calanoides acutus and Rhincalanus gigas use stored lipids for energy not ingestion. • Actively feeding zooplankton consumed fresh POM, not reworked particles at depth. • Decoupling between zooplankton feeding dynamics and ambient POM in the upper 500m. [ABSTRACT FROM AUTHOR]