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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]

Abstract We present a QR code paper microfluidic colorimetric assay that can exploit the hardware and software on mobile devices, and circumvent sample preparation by directly targeting volatile biomarkers. Our platform is a printable microarray of well-defined reaction regions, which outputs an instant diagnosis by directing the user to a URL containing their test result, while simultaneously storing epidemiological data for remote access and bioinformatics. To assist in the rapid identification of Escherichia coli in bloodstream infections, we employed an existing colorimetric reagent (p -dimethylaminocinnamaldehyde) and adapted its use to detect volatile indole, a biomarker produced by E. coli. Our assay was able to quantitatively detect indole in the headspace of E. coli culture after 12 h of growth (27.0 ± 3.1 ppm), assisting in species-level identification hours earlier than existing methods. Results were confirmed with headspace solid-phase microextraction (HS-SPME) two-dimensional gas chromatography time-of-flight mass spectrometry (GC×GC-ToFMS), which estimated indole concentration in E. coli culture to average 32.3 ± 5.2 ppm after 12 h of growth. This QR paper microfluidic platform represents a novel development in both telemedicine and diagnostics using volatile biomarkers. We envision that our QR code platform can be extended to other colorimetric assays for real-time diagnostics in low-resource environments. Highlights • Volatile indole can be detected on a paper substrate with a colorimetric reagent. • Colorimetric signal correlates linearly with volatile indole concentration. • Indole can be colorimetrically detected in the headspace of E. coli culture. • Benchmarking with GCxGC-TOFMS showed that paper sensor measurements were accurate. • Digital QR code paper-based microfluidic sensors are feasible diagnostic platforms. [ABSTRACT FROM AUTHOR]

Abstract The early detection of acute myocardial infarction (AMI) upon the onset of chest pain symptoms is crucial for patient survival. However, this detection is challenging, particularly without a persistent elevation of ST-segment reflected in an electrocardiogram or in blood tests. A majority of the available point-of-care testing devices allow accurate and rapid diagnosis of AMI. However, AMI diagnosis is reliable only at intermediate and later stages, with myocardial injury (> 6 h) and MI, based on the expression of specific cardiac biomarkers including troponin I or T (cTnI or cTnT), creatine kinase-MB (CK−MB), and myoglobin. Diagnosis at the early myocardial ischemia stage is not possible. To overcome this limitation, a sensitive and rapid microfluidic paper-based device (µPAD) was developed for the simultaneous detection of multiple cardiac biomarkers for the early and late diagnosis of AMI. The glycogen phosphorylase isoenzyme BB (GPBB) was detected during early (within first 4 h) ischemic myocardial injury. On the same µPAD platform, detection of prolonged elevation of levels of cTnT and CK-MB, which are only produced 6 h after the onset of chest pain in human serum, was possible. Sandwich immunoassay performed on the µPAD achieved reproducibility (RSD approximately 10% and intra-and inter-day precision (CV 10–20%, 99th percentile), as well as consistently stable test results for 28 days, with strong correlation (r2 = 0.962), using the standard Siemens Centaur XPT Immunoassay system. The present findings indicate the potential of the µPAD platform as a point-of-care device for the early diagnosis and prognosis of AMI. Graphical abstract fx1 Highlights • The first POC device developed for early diagnosis and prognosis of AMI. • Wax printed µPAD allows rapid multiplex detection of GPBB, CK-MB and cTnT. • Developed µPAD has potential use in clinical testing. • Results obtained are well correlated with Siemens Centaur XPT Immunoassay system. [ABSTRACT FROM AUTHOR]

Personalized health care (PHC) is being appreciated globally to combat clinical complexities underlying various metabolic or infectious disorders including diabetes, cardiovascular, communicable diseases etc. Effective diagnoses majorly depend on initial identification of the causes which are nowadays being practiced in disease-oriented approach, where personal health profile is often overlooked. The adoption of PHC has shown significantly improved diagnoses in various conditions including emergency, ambulatory, and remote area. PHC includes personalized health monitoring (PHM), which is its integral part and may provide valuable information's on various clinical conditions. In PHC, bio-fluids are analyzed using various diagnostic devices including lab based equipment and biosensors. Among all types of biosensing systems, paper based biosensors are commercially attracted due to its portability, easy availability, cheaper manufacturing cost, and transportability. Not only these, various intrinsic properties of paper has facilitated the development of paper based miniaturized sensors, which has recently gained ASSURED (Affordable, Sensitive, Specific, User-friendly, Rapid and Robust, Equipment free, Deliverable to all end-users) status for point of care diagnosis in miniaturized settings. In this review, importance of paper based biosensors and their compatibility for affordable and low cost diagnostics has been elaborated with various examples. Limitations and strategies to overcome the challenges of paper biosensor have also been discussed. We have provided elaborated tables which describe the types, model specifications, sensing mechanisms, target biomarkers, and analytical performance of the paper biosensors with their respective applications in real sample matrices. Different commercial aspects of paper biosensor have also been explained using SWOT (Strength, Weakness, Opportunities, Threats) analysis. [ABSTRACT FROM AUTHOR]

Abstract Background Our current understanding of the pathophysiology and management of sepsis is associated with a lack of progress in clinical trials, which partly reflects insufficient appreciation of the heterogeneity of this syndrome. Consequently, more patient-specific approaches to treatment should be explored. Aims To summarize the current evidence on precision medicine in sepsis, with an emphasis on translation from theory to clinical practice. A secondary objective is to develop a framework enclosing recommendations on management and priorities for further research. Sources A global search strategy was performed in the MEDLINE database through the PubMed search engine (last search December 2017). No restrictions of study design, time, or language were imposed. Content The focus of this Position Paper is on the interplay between therapies, pathogens, and the host. Regarding the pathogen, microbiologic diagnostic approaches (such as blood cultures (BCs) and rapid diagnostic tests (RDTs)) are discussed, as well as targeted antibiotic treatment. Other topics include the disruption of host immune system and the use of biomarkers in sepsis management, patient stratification, and future clinical trial design. Lastly, personalized antibiotic treatment and stewardship are addressed (Fig. 1). Implications A road map provides recommendations and future perspectives. RDTs and identifying drug-response phenotypes are clear challenges. The next step will be the implementation of precision medicine to sepsis management, based on theranostic methodology. This highly individualized approach will be essential for the design of novel clinical trials and improvement of care pathways. [ABSTRACT FROM AUTHOR]

In this work, a novel time-resolved ratiometric fluorescent probe based on dual lanthanide (Tb: terbium, and Eu: europium)-doped complexes (Tb/DPA@SiO 2 -Eu/GMP) has been designed for detecting anthrax biomarker (dipicolinic acid, DPA), a unique and major component of anthrax spores. In such complexes-based probe, Tb/DPA@SiO 2 can serve as a stable reference signal with green fluorescence and Eu/GMP act as a sensitive response signal with red fluorescence for ratiometric fluorescent sensing DPA. Additionally, the probe exhibits long fluorescence lifetime, which can significantly reduce the autofluorescence interferences from biological samples by using time-resolved fluorescence measurement. More significantly, a paper-based visual sensor for DPA has been devised by using filter paper embedded with Tb/DPA@SiO 2 -Eu/GMP, and we have proved its utility for fluorescent detection of DPA, in which only a handheld UV lamp is used. In the presence of DPA, the paper-based visual sensor, illuminated by a handheld UV lamp, would result in an obvious fluorescence color change from green to red, which can be easily observed with naked eyes. The paper-based visual sensor is stable, portable, disposable, cost-effective and easy-to-use. The feasibility of using a smartphone with easy-to-access color-scanning APP as the detection platform for quantitative scanometric assays has been also demonstrated by coupled with our proposed paper-based visual sensor. This work unveils an effective method for accurate, sensitive and selective monitoring anthrax biomarker with backgroud-free and self-calibrating properties. [ABSTRACT FROM AUTHOR]

Food-borne pathogens have been recognized as a major cause of human infections worldwide. Their identification needs to be simpler, cheaper and more reliable than the traditional methods. Here, we constructed a low-cost paper platform for viable pathogenic bacteria detection with the naked eye. In this study, an effective isothermal amplification method was used to amplify the hlyA mRNA gene, a specific RNA marker in Listeria monocytogenes. The amplification products were applied to the paper-based platform to perform a visual test using sandwich hybridization assays. When the RNA products migrated along the platform by capillary action, the gold nanoparticles accumulated at the designated area. Under optimized experimental conditions, as little as 0.5pg/μL genomic RNA from L. monocytogenes could be detected. It could also be used to specifically detect 20CFU/mL L. monocytogenes from actual samples. The whole assay process, including RNA extraction, amplification, and visualization, can be completed within several hours. This method is suitable for point-of-care applications to detect food-borne pathogens, as it can overcome the false-positive results caused by amplifying nonviable L. monocytogenes. Furthermore, the results can be imaged and transformed into a two-dimensional bar code through an Android-based smart phone for further analysis or in-field food safety tracking. [ABSTRACT FROM AUTHOR]

Paper-based point-of-care (POC) devices exhibit the advantages of simplicity, rapidity, trim sizes, and low cost, which are of particular importance for food safety, biological analysis, and medical diagnosis. However, the materials utilized to make paper-based POC rarely produce multiple signals, hampering further applications in diverse situations. Herein, we present an appealing approach, namely Colorimetric-Temperature Dual-Signal Output Sensor (CTDSS), and construct a CTDSS based on coordinative self-assembly biomimetic nanozymes Fe-GMP-L-His CPNs as a proof of concept. These CPNs mimic the structure of horseradish peroxidase (HRP), in which Fe (II) is the center, nucleotide GMP and histidine are chosen as ligands to simulate metal coordination of the pyrrole ring and protein function in HRP, respectively. This strategy allows CPNs to show an excellent peroxidase-like activity, efficiently converting H 2 O 2 into •OH and oxidizing TMB to generate colorimetric-temperature dual-signal. As a proof-of-concept application, we exploited cholesterol as the target and successfully applied this CTDSS to detect cholesterol, displaying extraordinary features of rapidity, dramatic specificity, and high sensitivity. By utilizing the colorimetric test strip and temperature discoloration sticker, the paper-based POC tools were constructed to visualize the target. Meanwhile, two proposed test strip POC devices generating different signal outputs exhibited remarkable feasibility and were further employed to detect cholesterol in human serum. We anticipate that this CTDSS platform will inspire innovative concepts for future portable detection tools. [ABSTRACT FROM AUTHOR]

Chronic lymphocytic leukemia (CLL) mainly affects older people: the median age at diagnosis is>70 years. Elderly patients with CLL are heterogeneous with regard both to the biology of their disease and aging. Following the diagnosis of CLL in an elderly individual, careful risk assessment is essential when treatment options are evaluated. This includes not only clinical staging and evaluation of disease-specific prognostic biomarkers such as 17p deletion and TP53 mutation, but also of comorbidities, physical capacity, nutritional status, cognitive capacity, ability to perform activities of daily living and social support. Comorbidity scoring and geriatric assessment tools are helpful in achieving such multidimensional evaluation in a systematic manner. The introduction of new drugs including novel monoclonal antibodies and kinase inhibitors offers enhanced opportunities for the treatment of elderly patients with CLL. This position paper of a Task Force of the International Society of Geriatric Oncology (SIOG) reviews currently available evidence relevant to such patients. All types of elderly patient (i.e. chronological age>65-70 years) are considered, from robust (fit) to vulnerable (unfit) to the terminally ill. Among the topics covered are the following: (i) the relationship between chronological age, prognosis and survival, (ii) assessment of biological aging, (iii) biological age as a determinant of treatment feasibility and tolerance and (iv) tailoring of both first and further-line treatment to the circumstances of the individual patient. [ABSTRACT FROM AUTHOR]

In this work, we developed a cascade signal amplification strategy for detection of IgG antigen by combining the rolling circle amplification (RCA) technique with oligonucleotide functionalized carbon dots (CDs), based on a paper-based electrochemiluminescence (ECL) origami device (PECLOD) for the first time. In this PECLOD, three-dimensional (3D) macroporous Au-paper electrode was fabricated and employed as the working electrode for specific and efficient antibodies capture. The RCA product containing tandem-repeat sequences could serve as an excellent template for periodic assembly of CDs, which presented per protein recognition event to numerous CDs tags for ECL readout. Under the optimal conditions, the proposed strategy showed remarkable amplification efficiency, very little nonspecific adsorption with good stability, reproducibility, and accuracy. Using human IgG (H-IgG) as a model protein, the designed strategy was successfully demonstrated for the ultrasensitive detection of protein target. The results revealed that the strategy exhibited a dynamic response to H-IgG range from 1.0 fM to 25 pM with a limit of detection as low as 0.15 fM. Importantly, the methodology can be further extended to the detection of other proteins or biomarkers. [ABSTRACT FROM AUTHOR]

Paper, a cheap and ubiquitous material, has great potential to be used as low-cost, portable and biodegradable platform for chemical and biological sensing application. In this paper, we are exploring a low-cost, flexible and reliable method to effectively pattern paper for capturing optical dyes and for flow-based delivery of target samples for colorimetric chemical sensing. In this paper, we target the detection of ammonia (NH 3 ) and carbon dioxide (CO 2 ), two of the important environmental and health biomarkers. By functionalizing the paper platform with diverse cross-reactive dyes sensitive to NH 3 and CO 2 , their selective sensing within a certain pH range, as well as their detection at different concentrations can be achieved. The images of paper based device were captured by a flatbed scanner and processed in MATLAB ® using a RGB model and PCA for quantitative analysis. Paper based devices with readout using ubiquitous consumer electronic devices (e.g. smartphones, flatbed scanner) are considered promising approaches for disease screening in developing countries with limited resources. [ABSTRACT FROM AUTHOR]

Lake Baikal, a unique habitat for a great number of endemic species, is the largest freshwater reservoir in the world which is still largely unaffected by anthropogenic pollution, except for some shore regions with industrial activity. The expressions of a biomarker of exposure (heat shock protein Hsp70) and a biomarker of effect (DNA single-strand breaks) were measured for the first time in endemic Baikalian sponge species (Baikalospongia intermedia, Lubomirskia fusifera, and Lubomirskia abietina). Tissue cubes of B. intermedia and dissociated cells of L. fusifera and L. abietina reacted to temperature stress (10–16 °C above ambient temperature) with a time-dependent increase in expression of Hsp70. In B. intermedia, the effects of model pollutants (lead, copper, and zinc, and the organochlorines tetrachloroguaiacol, TCG, and pentachlorophenol, PCP) and of the wastewater from the final refinement and aeration reservoirs of the Baikalsk Pulp and Paper Plant (BPPP), located at the shore of the southern basin of Lake Baikal, on the expression of Hsp70 and the extent of DNA damage were investigated. It was found that lead and zinc but not copper cause a strong induction of Hsp70 in this sponge, while the frequency of DNA single-strand breaks increased after exposure to all these heavy metals tested. Induction of DNA single-strand breaks was also observed after exposure to TCG and PCP, but these compounds did not (consistently) enhance Hsp70 expression. Wastewater taken from the final water aeration pond of BPPP caused a concentration-dependent increase in Hsp70 expression in B. intermedia. However, there was no difference in the basal levels of Hsp70 between sponges collected in the shallow water at an unpolluted site near Baikalsk City and at a polluted site where the wastewaters of BPPP are discharged into the lake. There was also no clear difference in the wastewater concentration-dependent induction of Hsp70 expression between sponges collected at these sites, indicating no adaptation to continuous stress exposure. [Copyright &y& Elsevier]

Abstract: Paper based colorimetric biosensing platform utilizing cross-linked siloxane 3-aminopropyltriethoxysilane (APTMS) as probe was developed for the detection of a broad range of targets including H2O2, glucose and protein biomarker. APTMS was extensively used for the modification of filter papers to develop paper based analytical devices. We discovered when APTMS was cross-linked with glutaraldehyde (GA), the resulting complex (APTMS–GA) displays brick-red color, and a visual color change was observed when the complex reacted with H2O2. By integrating the APTMS–GA complex with filter paper, the modified paper enables quantitative detection of H2O2 through the monitoring of the color intensity change of the paper via software Image J. Then, with the immobilization of glucose oxidase (GOx) onto the modified paper, glucose can be detected through the detection of enzymatically generated H2O2. For protein biomarker prostate specific antigen (PSA) assay, we immobilized capture, not captured anti-PSA antibody (Ab1) onto the paper surface and using GOx modified gold nanorod (GNR) as detection anti-PSA antibody (Ab2) label. The detection of PSA was also achieved via the liberated H2O2 when the GOx label reacted with glucose. The results demonstrated the possibility of this paper based sensor for the detection of different analytes with wide linear range. The low cost and simplicity of this paper based sensor could be developed for “point-of-care” analysis and find wide application in different areas. [Copyright &y& Elsevier]

The article offers information on reduction of disease activity in axial spondyloarthritis from High intensity exercise for three months, as compared with standard care.

Abstract: In this work, electrochemiluminescence (ECL) immunoassay was introduced into the recently proposed microfluidic paper-based analytical device (μPADs) based on directly screen-printed electrodes on paper for the very first time. The screen-printed paper-electrodes will be more important for further development of this paper-based ECL device in simple, low-cost and disposable application than commercialized ones. To further perform high-performance, high-throughput, simple and inexpensive ECL immunoassay on μPAD for point-of-care testing, a wax-patterned three-dimensional (3D) paper-based ECL device was demonstrated for the very first time. In this 3D paper-based ECL device, eight carbon working electrodes including their conductive pads were screen-printed on a piece of square paper and shared the same Ag/AgCl reference and carbon counter electrodes on another piece of square paper after stacking. Using typical tris-(bipyridine)-ruthenium (Ⅱ) - tri-n-propylamine ECL system, the application test of this 3D paper-based ECL device was performed through the diagnosis of four tumor markers in real clinical serum samples. With the aid of a facile device-holder and a section-switch assembled on the analyzer, eight working electrodes were sequentially placed into the circuit to trigger the ECL reaction in the sweeping range from 0.5 to 1.1 V at room temperature. In addition, this 3D paper-based ECL device can be easily integrated and combined with the recently emerging paper electronics to further develop simple, sensitive, low-cost, disposable and portable μPAD for point-of-care testing, public health and environmental monitoring in remote regions, developing or developed countries. [Copyright &y& Elsevier]

Demand on the quick screening of gastric cancer (GC) has significantly stimulated the development of biomarker sensing techniques. Herein, we report the novel fluorescent paper-based analytical devices (PADs) for detections of GC-related microRNA-21 (miRNA-21) and circular RNA from Hippocampus Abundant Transcript 1 gene (circRNA-HIAT1) with prominent reliability and sensitivity. The PADs, constructed by in-situ synthesis of blue-emissive carbon dots (CDs) and conjugations of probe DNAs, exhibit the superior uniformity and stability. In the presence of targets, rolling circle amplifications (RCA) are triggered to generate long DNA strands for the assemblies of green-/red-emissive labels. Consequently, remarkable blue-to-green and blue-to-red emission color transitions of the PADs are achieved, implementing the color-analysis of miRNA-21 and circRNA-HIAT1, respectively. Benefited from the efficient RCA, coupled with the drastic ratiometric fluorescent changes, the limit of detections (LODs) of PADs are found to be several fM with the upper limit of the linear detection range at 1 nM. More importantly, the fluorescent PADs possess excellent specificity, as well as anti-interference capability in biological settings, enabling their applications in accurate GC screening with plasma samples. Overall, the proposed fluorescent PADs are featured with robust sensing platform, facile signal readout, and exceptional dual-type RNA sensing performance, holding high potential in point-of-care testing (POCT). [Display omitted] • In-situ synthesis of carbon dots on carboxylated cellulose paper is accomplished. • Fluorescent PADs are constructed by conjugating probe DNAs on fluorescent paper. • Dual-type RNA detection with ultra-sensitivity is realized with the PADs. • Emission color engineering of fluorescent labels enables the color-analysis of RNA. • Accurate gastric cancer screening by comparing abundances of dual-type RNA. [ABSTRACT FROM AUTHOR]

Abstract: An active biomonitoring study was performed in the vicinity of two pulp and paper mill effluents (PPMEs) released in two different streams in northeastern France. Freshwater gastropods, Radix peregra (=Lymnaea peregra or Lymnaea pereger), were transplanted for 0, 3, 14 and 21 days at two to three sites located upstream and downstream from the mill discharge points in both rivers. Lysosomal and peroxisomal systems, as well as lipofuscin and neutral lipids, were tested using histochemical methods on cryostat sections of digestive gland tissues, and stereological data were obtained by image analysis. Evidence of structural changes in the lysosomal system was found in animals exposed to both effluents, comprising general stress responses such as enlarged and more numerous lysosomes; and also possible specific pluri-phasic effects. Modifications of the lysosomal and cytoplasmic contents of lipid-related materials were also described, namely enhanced lipofuscin deposit and neutral lipid depletion. The peroxisomal proliferation in exposed snails seems to show its implication in oxidative stress detoxication, without preventing higher lipoperoxidation, as indicated by the increased amounts of digestive lipofuscin. Structural changes of the lysosomal and peroxisomal systems, digestive lipofuscin and neutral lipid contents have potential for use as early cellular biomarkers in Radix peregra exposed to environmental stressors, which deserve further investigations. [Copyright &y& Elsevier]

Electrochemical paper-based analytical devices (ePADs) are useful analytical devices that serve as point-of-care testing (POCT) devices for various clinical biomarkers in view of their simplicity, portability, and low-cost format. However, multistep reagent manipulation usually restricts the performance of the device for end users. Herein, we developed a sequential ePAD for sequential immunosensing fluid delivery by integrating dual flow behaviors (fast-flow/delayed) within a single paper platform for the simultaneous detection of hepatitis B surface antigen (HBsAg) and hepatitis C core antigen (HCVcAg). In the present work, a fast-flow channel was used for the automated washing of unbound antigens, while a delayed channel was created to store a redox reagent for further electrochemical analysis with a single buffer loading (the analysis time can be completed within 500 s). Hence, the undesirable complex procedure of multi-step reagent manipulation is scarcely needed by the user. The detection limit of the proposed ePAD was as low as 18.2 pg mL−1 for HBsAg and 1.19 pg mL−1 for HCVcAg. In addition, this proposed ePAD was also proven to be effective in real clinical sera from patients to verify its biological applicability. The ePAD sensor shows high promise as an easy-to-use, portable, and extendable sensor for other multiplex biological assays. [Display omitted] • ePAD for simultaneous HBsAg and HCVcAg was created. • First time employment of dual flow behaviors on ePAD for hepatitis markers sensing. • ePAD shows an easy to use, portability, and broad sensing applicability. • The sensor was applied to detect hepatitis markers in real clinical sera. [ABSTRACT FROM AUTHOR]

Currently colorimetric paper lateral flow strips (PLFS) encounter two major limitations, that is, low sensitivity and severe interference from complex sample matrices such as blood. These shortcomings limit their application in detection of low-concentration analytes in complex samples. To solve these problems, a PLFS has been developed by utilizing surface-enhanced Raman scattering (SERS) for sensing signal transduction. In particular, a hierarchical three-dimensional nanostructure has been designed to create "hot spots", which can significantly amplify the SERS sensing signal, leading to high sensitivity. As a result, this PLFS has demonstrated a limit of detection (LOD) of 5.0 pg mL−1 toward detection of S-100β, a traumatic brain injury (TBI) protein biomarker in blood plasma. The PLFS has been successfully used for rapid measurement of S-100β in clinical TBI patient samples taken in the emergency department. Availability of PLFS for blood testing would shift the paradigm of TBI patient management and clinical outcome in emergency departments. It is expected that this type of PLFS can be adapted for rapid detection of various human diseases due to its capability of measuring a low level of protein blood biomarkers in complex human fluids. • A paper biosensor for the detection of protein biomarker in blood plasma is proposed. • A hierarchical 3D plasmonic nanostructure is developed to improve detection sensitivity. • A two-order of magnitude improvement in detection sensitivity is obtained. • Test results from the proposed sensor are comparable to those by the standard ELISA in clinical samples. • The proposed sensor provides guidance for rational design of highly sensitive and anti-interference POC devices. [ABSTRACT FROM AUTHOR]

Early and accurate disease diagnosis is of great appeal for saving patients' life, but requires biomarkers to be sensitively detected with simplicity, convenience, and low cost. Exploring the development of a high-performance fluorescence biosensor for biomarkers solid, equipment-free and visual biosensing is highly urgent but faces enormous challenges. Herein, we proposed a brand-new fluorescence system by integrating a typical aggregation induced emission dye (TPE-BTD) with dopamine for multiple biomarkers sensitive detection based on target-induced catalyzing oxidation. The system comprising TPE-BTD and dopamine emits strong fluorescence; with horseradish peroxidase (HRP) or HRP-mimicking DNAzyme and H 2 O 2 being added, significant oxidation on dopamine occurs to generate dopachrome, which actuated the inner filter effect (IFE) due to the overlap of its absorbtion curve and emission spectrum of TPE-BTD, subsequently decreasing fluorescence emission and displaying a rapid and sensitive response to H 2 O 2 and G-quadruplex DNA. We further apply TPE-BTD/dopamine system in analysis of glucose and DNA adenine methylation methyltransferase (Dam MTase) based on target-initiated signal transduction. Finally, TPE-BTD was employed as emitters in fabrication of paper biosensors, which can achieve solid, equipment-free and visual detection of multiple biomarkers based on the high emission performance of TPE-BTD, opening up a new pathway to development of biosensors for practical application. We expect this sensing conception will be helpful in development of practical biosensors, and this sensor will find more applications in disease diagnosis. • AIEgen and dopamine were employed to develop label-free biosensors based on IFE. • It realized H 2 O 2 , G-quadruplex DNA, glucose, and Dam MTase sensitive detection. • It was applicable for paper biosensor for equipment-free and naked-eye sensing. [ABSTRACT FROM AUTHOR]

Pancreatic ductal adenocarcinoma is the predominant neoplastic disease of the pancreas and it represents the fourth most frequent cause of death in cancer-related disease, with only 8% of survivors after 5-year to the diagnosis. The main issues of this type of cancer rely on fast progress (i.e. 14 months from T1 to a T4 stage), nonspecific symptoms with delay in diagnosis, and the absence of effective screening strategies. To address the lack of early diagnosis, we report a cost-effective paper-based biosensor for the detection of miRNA-492, which is recognised as a biomarker for pancreatic ductal adenocarcinoma. To design a miniaturised, sensitive, and robust paper-based platform, an electrochemical sensor was screen-printed on office paper previously wax-patterned via wax-printing technique. The paper-based sensor was then engineered with a novel and highly specific peptide nucleic acid (PNA) as the recognition element. The formation of PNA/miRNA-492 adduct was evaluated by monitoring the interaction between the positively charged ruthenium (III) hexamine with uncharged PNA and/or negatively charged PNA/miRNA-492 duplex by differential pulse voltammetry. The paper-based biosensor provided a linear range up to 100 nM, with a LOD of 6 nM. Excellent selectivity towards one- and two-base mismatches (1MM, 2MM) or scrambled (SCR) sequences was highlighted and the applicability for biomedical analyses was demonstrated, measuring miRNA-492 in undiluted serum samples. • Paper-based electrochemical peptide nucleic acid (PNA) biosensor for the detection of miRNA-492. • miRNA-492 detection in undiluted serum samples by signal on strategy using charged redox mediator. • Wax/screen-printing, paper and nanomaterials for a laboratory-free platform. [ABSTRACT FROM AUTHOR]

Paper-based lateral-flow assays (LFAs) have achieved considerable commercial success and continue to have a significant impact on medical diagnostics and environmental monitoring. Conventional LFAs are typically performed by examining the color changes in the test bands by naked eye. However, for critical biochemical markers that are present in extremely small amounts in the clinical specimens, this readout method is not quantitative, and does not provide sufficient sensitivity or suitable detection limit for a reliable assay. Diverse technologies for high-sensitivity LFA detection have been developed and commercialization efforts are underway. In this review, we aim to provide a critical and objective overview of the recent progress in high-sensitivity LFA detection technologies, which involve the exploitation of the physical and chemical responses of transducing particles. The features and biomedical applications of the technologies, along with future prospects and challenges, are also discussed. • High-sensitivity detection methods for paper-based LFA are reviewed. • Operating principles, features, and applications of diverse LFA detection methods are described. • Future perspectives for high-sensitivity LFA detection methods are presented. [ABSTRACT FROM AUTHOR]

Portable, maneuverable and reliable versatile-integrated analytical devices are urgently demanded but still extremely challenging to meet the requirements of point-of-care testing in resource-limited areas. Herein, a multifunctional sensing platform with excellent photothermal performance was implanted into the miniature zone of a paper-based electrochemiluminescent (ECL) biosensor for accurate detection of interleukin-6, which could flexibly interconnect the visualized distance and temperature readout with ultrasensitive ECL response. Concretely, the multipurpose MBene and TaSe 2 composites (MBene@TaSe 2) prepared via self-assembly approach as target-associated photothermal element was introduced in the paper-based analytical device (PAD) and served as multi-signals trigger. Under the laser irradiation, MBene@TaSe 2 probe not only generated heat for rapid temperature output, but also triggered the phase transition behavior of thermoresponsive poly (N-isopropylacrylamide) (pNIPAM) hydrogel to release loaded malachite green (MG) dye for distance-based visual readout. Simultaneously, the released MG was also utilized as effective quencher to decrease the ECL signal of luminol. Benefitting from this dexterous architecture, the speedy preliminary screening and precise quantitative analysis could be subsequently obtained in single-drop sample through one-step sandwich immunoreaction, which avoids additional separation operations and greatly simplifies the analysis procedure. Undeniably, this work provides ingenious insights for advancing the development of convenient and fast multifunction-integrated PAD in family surveillance and intelligent diagnosis. [ABSTRACT FROM AUTHOR]

The article discusses the paper "Aβ and Apolipoprotein E/Amyloid-β Complex as Potential Mechanistic Biomarkers for Alzheimer Disease," by Mary Jo LaDu and colleagues at the University of Illinois at Chicago. It states that the researchers investigated the effects of APOE4 and APOE3 genotypes on levels of soluble apolipoprotein E (apoE)/Aβ and oligomeric amyloid-β (oAβ) complex. It adds that they developed novel enzyme-linked-immunosorbent serologic assays (ELISAs).

The article highlights a study in which the authors have derived islet cells by reprogramming human skin cells to resemble stem cells. The authors found that the induced pluripotent stem (iPS) cells can differentiate into islet-like clusters that contain cells positive for pancreatic biomarkers glucagon and C-peptide.

Objective: To summarize recent scientific advances in protein-derived soluble biomarkers of osteoarthritis.Design: A systematic search on the PubMed electronic database of clinical studies on protein-derived soluble biochemical markers of osteoarthritis in humans that were published between January 1st 2020 and March 31th 2021. The studies were selected on the basis of objective criteria and summarized in a table. Then they were described in a narrative review.Results: Out of 1971 publications, 48 fulfilled all selection criteria and 16 were selected by the author for the narrative review. The papers were classified according their clinical significance as defined in the BIPEDS classification. Two papers investigated the "burden of disease", two were dedicated to "investigative biomarkers", four papers question the "prognosis", three the "efficacy of treatment" and five the "diagnosis and phenotyping" value of protein-derived biomarkers.Conclusions: Currently, biomarkers research is focused on their use as tools to identify molecular endotypes and clinical phenotypes and to facilitate patient screening and monitoring in clinical trials. This approach should allow a more targeted management of patients suffering from osteoarthritis. [ABSTRACT FROM AUTHOR]

Lateral flow biosensors are a leading technology in point-of-care diagnostics due to their simplicity, rapidness and low cost. Their primacy in this arena continues through technological breakthroughs such as multiplexing: the detection of more than one biomarker in a single assay. Multiplexing capacity is critical for improving diagnostic efficiency, enhancing the diagnostic precision for specific diseases and reducing diagnostic cost. Here we review, for the first time, the various types and strategies employed for creating multiplexed lateral flow biosensors. These are classified into four main categories in terms of specific application or multiplexing level, namely linear, parameter, spatial and conceptual. We describe the practical applications and implications for each approach and compare their advantages and disadvantages. Importantly, multiplexing is still subject to limitations of the traditional lateral flow biosensor, such as sensitivity and specificity. However, by pushing the limitations of the traditional medium into the multiplex arena, several technological breakthroughs are emerging with novel solutions that further expand the utility of lateral flow biosensing for point-of-care applications. [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]

Abstract: The effects of two widely used insecticides – organophosphate pirimiphos-methyl and pyrethroid deltamethrin – were investigated under laboratory conditions following OECD guidelines using the epigeic earthworm Eisenia andrei as the test organism. The overall aim of this study was to evaluate the effects of these pesticides on molecular biomarkers of earthworm E. andrei using the in vitro, filter paper contact and artificial soil test. In this study for the first time the equivalent concentrations of investigated pesticide applied in different tests were calculated. Although the response of measured molecular biomarkers in different toxicity tests had certain similarities, some distinct differences were also evident. Both pesticides inhibited AChE and CES activities in all three applied toxicity tests; however only in the filter paper test the hormetic effect was recorded. The artificial soil test showed that duration of the exposure significantly changed the effects of the investigated pesticides on CAT and GST activities. Namely, after the initial increase, the prolongation of exposure caused the reduction of the CAT and GST activities. Both pesticides significantly inhibited the efflux pump activity. In the artificial soil test, the significant changes in measured biomarkers after application of doses lower than doses recommended for use in the agriculture indicate that the investigated pesticides could have a harmful effect on earthworms in the context of the realistic environment. [Copyright &y& Elsevier]

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]

Abstract Background Endometriosis is a gynaecological disease characterized by the presence of ectopic endometrial tissue that affects women during their reproductive years, having a strong impact on their lives, fertility and healthcare costs. The aetiology remains largely unknown, but current evidence suggests that it is multi-causal and oestrogen-dependent. Many epidemiologic studies have explored associations between organochlorine chemicals (OCCs) and endometriosis, but the findings are inconsistent. Objectives A systematic review (SR) and meta-analysis were conducted to gather and synthesize all the available evidence from human epidemiological studies about the associations between OCCs and endometriosis. Data sources The searches were conducted in PubMed and Web of Science in June 2016 with a final follow-up in August 2018. Study eligibility criteria Only human epidemiological studies were considered, independent of participant age, body mass index or life-stage. Studies reporting individual measures of exposure to OCCs were included, considering but not limited to polychlorinated dibenzodioxins and dibenzofurans (PCDD/Fs), polychlorinated biphenyls (PCBs), or organochlorine pesticides (OCPs). The primary health outcome was presence of endometriosis, including all sub-types. Eligibility criteria excluded articles not written in English, conference papers, reviews and studies with overlapping information. Study appraisal and synthesis methods A SR protocol pre-registered at PROSPERO was applied in duplicate to gather and extract all eligible original papers from PUBMED and Web of Science databases. Odds ratios were pooled using the inverse variance method for random effects meta-analysis for each group of OCCs. Risk of bias was assessed using the National Toxicology Program/Office of Health Assessment and Translation (NTP/OHAT) Risk of Bias Rating Tool for Human and Animal Studies adapted to the review question. The confidence in the body of evidence and related level of evidence was measured by using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) based NTP/OHAT framework. The results were structured and presented in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Results Of the 51 studies retained for the full-text screening, 17 provided effect sizes and metrics sufficient for pooling estimates through meta-analysis. The overall odds ratios and 95% confidence intervals were 1.65 (1.14; 2.39) for dioxins (n = 10), 1.70 (1.20; 2.39) for PCBs (n = 9), and 1.23 (1.13; 1.36) for OCPs (n = 5). Despite being statistically significant, these estimates should be considered with caution given the notable heterogeneity and small estimated effect size. Misclassification of exposure, due to varying laboratory detection rate capabilities, and disease status, due to varying definitions of endometriosis, were identified as major sources of uncertainty. Limitations, conclusions, and implications of key findings The level of evidence was considered to be "moderate" with "serious" risk of bias according the NTP/OHAT criteria, supporting the need for further well-designed epidemiological research to fill lingering data gaps. Given the complexity of endometriosis and lack of known biomarkers suitable for population-based research, carefully designed observational studies play an important role in better understanding the aetiology of endometriosis, as will evolving mixture modeling approaches capable of handling various environmental chemical exposures. Attention to critical windows of exposure will shed further light on the possible developmental origin of endometriosis. Considering the high economic and societal cost associated with endometriosis, further research on this field is urged. Systematic review registration number CRD42018080956 Highlights • A first systematic review was conducted on the link between POPs and endometriosis. • Meta-analysis revealed positive associations for dioxins, PCBs and pesticides. • The level of evidence was rated "moderate" with "serious" risk of bias. [ABSTRACT FROM AUTHOR]

Outer membrane vesicles (OMVs) are spherical, nano-sized particles of bilayer lipid structure secreted by Gram-negative bacteria. They contain a series of cargos from bacteria and are important messengers for communication between bacteria and their environment. OMVs play multiple roles in bacterial survival and adaptation and can affect host physiological functions and disease development by acting on host cell membranes and altering host cell signaling pathways. This paper summarizes the mechanisms of OMV genesis and the multiple roles of OMVs in the tumor microenvironment. Also, this paper discusses the prospects of OMVs for a wide range of applications in drug delivery, tumor diagnosis, and therapy. [Display omitted] • OMVs are generated through complex pathways. • OMVs carrying bacterial cargos have multiple roles in the tumor microenvironment. • OMVs carry specific cargos that can be used as tools for the diagnosis, prevention, and treatment of tumors. [ABSTRACT FROM AUTHOR]

[Display omitted] • Borophene quantum dots are fabricated via liquid-phase exfoliation-assisted ultrasonication. • Borophene quantum dots exhibited blue fluorescence at 428 nm when excited at 370 nm. • Borophene quantum dots acted as a sensor for the detection of dehydroepiandrosterone biomarker. • Borophene quantum dots loaded cellulose paper used as a sensor for DHEA detection. • Cell imaging of Saccharomyces cerevisiae and MTT assay of HeLa cells were performed using borophene quantum dots. A novel fluorescence approach is introduced for sensing of dehydroepiandrosterone (DHEA). The primary characteristic of pediatric adrenocortical carcinoma disease causes due to the excessive production of DHEA, a hormone whose levels in the bloodstream can potentially facilitate the early diagnosis of cancer. In this paper, a water-dispersed borophene quantum dots (BQDs) based sensor was developed for the detection of DHEA, marking the first instance of such an application. The as-synthesized BQDs display blue fluorescence under 365 nm of UV light and exhibit λ Ex/Em at 370/428 nm with a good quantum yield of 24.12%. The as-prepared BQDs acted as a fluorescent "turn-on" sensor for the detection of DHEA with a dynamic range from 0.1 to 125 μM with the detection limit of 18.72 nM. The BQDs-based paper strip was designed for visual detection of DHEA. In addition, BQDs were utilized as imaging probes to visualize Saccharomyces cerevisiae cells. The developed method was extended for DHEA assay in biofluids (plasma and urine). [ABSTRACT FROM AUTHOR]

Fingermark detection research aims to improve the quantity and quality of fingermarks detected through the development of novel techniques. Subsequently, there is a need to evaluate these methods to determine the quality of the developed mark. Since the 1980's there has been a significant number of publications, which utilise a variety of different quality assessment methods. The introduction of common practice methods from the International Fingerprint Research Group (IFRG) aimed to implement a more standardised approach. Although these schemes are recommended as common practice, they are only guidelines. Consequentially, there is currently no universally accepted method to evaluate the enhancement techniques implemented in research. Therefore, this study aimed to collate and analyse the published protocols being used within fingermark detection research in order to better understand their application and how research is currently analysing and interpreting fingermark quality. This study comprised of manual and automatic searches of over 2000 published papers within the fingermark detection area. After thorough analysis of the articles, 396 published papers were found to have used a scale within the years spanning 1998–2022. The number of publications that report the use of a scale to assess quality for fingermark detection research has considerably increased over the last decade. However, whilst the number of publications utilising scales has increased, it is not proportional to the number of papers using the IFRG scales. The choice of scale is often institution specific and even more specific to their location. There are also numerous different adaptations of the IFRG recommended scales, as well as novel scales, which do not associate with the IFRG recommended versions being introduced the more research continues to grow. One such reason for this is investigated here, as different quality parameters are utilised within each individual scale. There is underrepresentation of these quality parameters within some of the IFRG scales, in particular the Centre for Applied Science and Technology (CAST) scale. This correlates to the considerable number of tailored approaches as authors are forced to add these parameters within the descriptions. Until there is an introduction of clear guidelines surrounding all areas of fingermark quality, from definition to parameters chosen within phases, the research area will continue to face such issues. This article recommends areas of potential study, whilst also recommending procedures that may be employed to alleviate some of the issues seen with fingermark quality evaluation. • Critical meta-analysis of subjective fingermark quality evaluation methods in fingermark detection research. • Despite recommended scales, novel scales still dominate. • Scale choice dependent on author and location. [ABSTRACT FROM AUTHOR]

Breast cancer—a heterogeneous disease marked with a high mortality rate, necessitates early diagnosis and treatment. The availability of multi-omic data has revolutionized our understanding of how molecular changes mark the variations in different breast cancer subtypes. Epigenomic changes in the form of DNA methylation differentially impact the expression level of the genes that play a vital role in the onset and spread of these subtypes. So, in this paper, we study the role of these variations in distinguishing between the various breast cancer subtypes. The cardinality of the existing biomarker sets is often too large to be interpreted clinically, and their relevance in classification remains unclear. In this paper, we propose a two-stage XAI-MethylMarker—an explainable AI-based biomarker discovery framework applied to DNA methylation data to arrive at a small set of biomarkers for breast cancer classification. In the first stage, we build a deep-learning network M e t h y l N e t that employs an autoencoder for dimensionality reduction and a feed-forward neural network to classify breast cancer subtypes. In the second stage, we propose a biomarker discovery algorithm, M e t h y l B D A , which employs different explainable techniques for analyzing M e t h y l N e t model and discovers a small set of 52 biomarkers. Using 5-fold cross-validation, we achieved a classification accuracy of 0.8145 ± 0.07 at a 95% confidence interval. To establish the clinical relevance of the discovered biomarkers, we performed a gene set analysis that revealed 14 druggable genes, nine genes linked to prognostic outcomes, and several enriched pathways are known to be significantly associated with distinct breast cancer subtypes. [ABSTRACT FROM AUTHOR]

Low accuracy of diagnosing prostate cancer (PCa) was easily caused by only assaying single prostate specific antigen (PSA) biomarker. Although conventional reported methods for simultaneous detection of two specific PCa biomarkers could improve the diagnostic efficiency and accuracy, low detection sensitivity restrained their use in extreme early-stage PCa clinical assay applications. In order to overcome above drawbacks, this paper herein proposed a multiplexed dual optical microfibers separately functionalized with gold nanorods (GNRs) and Au nanobipyramids (Au NBPs) nanointerfaces with strong localized surface plasmon resonance (LSPR) effects. The sensors could simultaneously detect PSA protein biomarker and long noncoding RNA prostate cancer antigen 3 (lncRNA PCA3) with ultrahigh sensitivity and remarkable specificity. Consequently, the proposed dual optical microfibers multiplexed biosensors could detect the PSA protein and lncRNA PCA3 with ultra-low limit-of-detections (LODs) of 3.97 × 10−15 mol/L and 1.56 × 10−14 mol/L in pure phosphorus buffer solution (PBS), respectively, in which the obtained LODs were three orders of magnitude lower than existed state-of-the-art PCa assay technologies. Additionally, the sensors could discriminate target components from complicated physiological environment, that showing noticeable biosensing specificity of the sensors. With good performances of the sensors, they could successfully assay PSA and lncRNA PCA3 in undiluted human serum and urine simultaneously, respectively. Consequently, our proposed multiplexed sensors could real-time high-sensitivity simultaneously detect complicated human samples, that providing a novel valuable approach for the high-accurate diagnosis of early-stage PCa individuals. [ABSTRACT FROM AUTHOR]

The liver is a frequent site of metastasis in advanced gastric cancer (GC). Despite significant advancements in diagnostic and therapeutic techniques, the overall survival rate for patients afflicted with gastric cancer liver metastasis (GCLM) remains dismally low. Precision oncology has made significant progress in identifying therapeutic targets and enhancing our understanding of metastasis mechanisms through genome sequencing and molecular characterization. Therefore, it is crucial to have a comprehensive understanding of the various molecular processes involved in GCLM and the fundamental principles of systemic therapy to develop new treatment approaches. This paper aims to review recent findings on the diagnosis, potential biomarkers, and therapies targeting the multiple molecular processes of GCLM, with the goal of improving treatment strategies for patients with GCLM. [Display omitted] • Liver metastasis is the most common form of hematologic metastasis in GC. • Molecular characterization and genomic sequencing have deepened our understanding of GCLM. • The biomarkers capable of predicting GCLM occurrence and recurrence are discussed. • A comprehensive summary of diverse treatment strategies for GCLM and prediction of potential therapeutic targets. [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]