Search

Abstract Background The prevalence and death rate arising from malaria infection, and emergence of other diseases showing similar symptoms to malaria require the development of malaria-specific and sensitive devices for its diagnosis. To address this, the design and fabrication of low-cost, rapid, paper-based analytical devices (µPAD) using surface-immobilized aptamers to detect the presence of a recombinant malarial biomarker—Plasmodium falciparum lactate dehydrogenase (rPfLDH)—is reported in this study. Methods Test zones on paper surfaces were created by covalently immobilizing streptavidin to the paper, subsequently attaching biotinylated aptamers to streptavidin. Aptamers selectively bound rPfLDH. The measurement of captured rPfLDH enzyme activity served as the means of detecting this biomarker. Enzyme activity across three replicate sensors was digitally quantified using the colorimetric Malstat assay. Results Screening of several different aptamers reported in the literature showed that aptamers rLDH7 and 2008s immobilized in this manner specifically recognised and captured PfLDH. Using rLDH7, the sensitivity of the µPAD sensor was evaluated and the µPAD sensor was applied for preferential detection of rPfLDH, both in buffered solutions of the protein and in spiked serum and red blood cell lysate samples. In buffered solutions, the test zone of the µPAD sensor exhibited a K D of 24 ± 11 nM and an empirical limit of detection of 17 nM, respectively, a limit similar to commercial antibody-based sensors exposed to rPfLDH. The specific recognition of 133 nM rPfLDH in undiluted serum and blood samples was demonstrated by the µPAD. Conclusion The reported µPAD demonstrates the potential of integrating aptamers into paper-based malarial rapid diagnostic tests. Graphical Abstract The assembly of µPAD sensors using APTEC assay principles for the detection the malarial biomarker, lactate dehydrogenase enzymes from Plasmodium falciparum (PfLDH). The aptamers immobilized at the test zones capture the PfLDH in samples. After washing the unbound sample components from the zones, Malstat assay reagents are added for colour development, proportional to the amount of captured PfLDH.

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

Total bilirubin values have been used as a potential marker to pre-screen and diagnose various liver-based diseases such as jaundice, bile obstruction, liver cancer, etc. A device known as KromaHealth Kit, composed of paper and an acrylic backbone, is developed to quantify total bilirubin in human serum using image processing and machine learning technology. The biochemical assays are deposited on absorbent paper pads that act as reaction zones when serum is added. A dedicated smartphone app captures images of the colorimetric changes on the pad and converts them into quantitative values of bilirubin. The range of bilirubin concentration that can be quantified using the device ranges from 0.5 mg/dl to 7.0 mg/dl. The precision, limit of detection, interference analysis, linearity, stability, and comparison with a predicate are studied in this paper in accordance with clinical and laboratory standards institute. The results indicate that the KromaHealth Kit can be used as an inexpensive alternative to conventional bilirubin testing in clinical settings. With its level of precision, ease-of-use, long shelf-life, and short turnaround time, it will prove to be invaluable in limited-resource settings.

This ENETS guidance paper for well‐differentiated nonfunctioning pancreatic neuroendocrine tumours (NF‐Pan‐NET) has been developed by a multidisciplinary working group, and provides up‐to‐date and practical advice on the management of these tumours. Using the extensive experience of centres treating patients with NF‐Pan‐NEN, the authors of this guidance paper discuss 10 troublesome questions in everyday clinical practice. Our many years of experience in this field are still being verified in the light of the results of new clinical, which set new ways of proceeding in NEN. The treatment of NF‐Pan‐NEN still requires a decision of a multidisciplinary team of specialists in the field of neuroendocrine neoplasms. This ENETS guidance paper provides up‐to‐date practical advice on the NF‐Pan‐NET diagnosis and treatment. Management of NF‐Pan‐NET patients requires a NET‐dedicated MDT decision. ENETS Centres of Excellence should be strongly considered to be involved in the diagnostic‐therapeutic strategy of these patients. Further studies are needed to fulfil the unmet needs in this field focusing on prognostic molecular markers, dilemmas concerning the selection of a therapeutic approach as well as the sequence of their use to achieve success in the management of NF‐Pan‐NETs patients. [ABSTRACT FROM AUTHOR]

Within the last decade, challenges of diagnosis have emerged on the global health agenda, accompanied by an expansion in the use of point-of-care and rapid detection devices in low-resource contexts where laboratory facilities are scarce. Few studies have explored how these changes are shaping people’s diagnostic journeys and their modes of accessing such technologies. In this paper I show how sick people and their families in a peri-urban area in Burkina Faso attempt to access diagnostic technologies and make themselves visible to the healthcare system through papers. In this context, I show how referral papers and diagnostic papers take on significance for people as they attempt to access care and diagnostic technologies and ‘carry’ knowledge between different levels of the healthcare system. The use of papers is often an uncertain undertaking, as they remain unintelligible to the sick and the layperson. I highlight how the form of the papers makes a crucial difference to the ways that sick people are able to use them. Papers and diagnostic technologies present both opportunities and challenges, and simultaneously engender hope, uncertainty, disappointment, and despair for the sick seeking a cure. Uncertainties, especially financial ones, arise with the possibility of new referrals and diagnostic tests, and along the way many give up or are immobilised when faced with diagnostic ambiguity.

Benign conditions of the lower urinary tract, including benign prostatic hyperplasia, overactive bladder syndrome, and stress urinary incontinence, are frequent in the general population. Despite their benign nature, they have major adverse effects on the quality of life of the afflicted patients and their partners. Despite major progress in the diagnosis and treatment of these conditions, improved understanding and management of these patients remain substantial medical needs. This editorial discusses some recent high-quality articles published in the Journal of Clinical Medicine on the understanding of the epidemiology, pathophysiology, diagnostic, and treatment of benign diseases of the lower urinary tract tissues such as the bladder and prostate.

Abstract Background Propensity scores are widely used to deal with confounding bias in medical research. An incorrectly specified propensity score model may lead to residual confounding bias; therefore it is essential to use diagnostics to assess propensity scores in a propensity score analysis. The current use of propensity score diagnostics in the medical literature is unknown. The objectives of this study are to (1) assess the use of propensity score diagnostics in medical studies published in high-ranking journals, and (2) assess whether the use of propensity score diagnostics differs between studies (a) in different research areas and (b) using different propensity score methods. Methods A PubMed search identified studies published in high-impact journals between Jan 1st 2014 and Dec 31st 2016 using propensity scores to answer an applied medical question. From each study we extracted information regarding how propensity scores were assessed and which propensity score method was used. Research area was defined using the journal categories from the Journal Citations Report. Results A total of 894 papers were included in the review. Of these, 187 (20.9%) failed to report whether the propensity score had been assessed. Commonly reported diagnostics were p-values from hypothesis tests (36.6%) and the standardised mean difference (34.6%). Statistical tests provided marginally stronger evidence for a difference in diagnostic use between studies in different research areas (p = 0.033) than studies using different propensity score methods (p = 0.061). Conclusions The use of diagnostics in the propensity score medical literature is far from optimal, with different diagnostics preferred in different areas of medicine. The propensity score literature may improve with focused efforts to change practice in areas where suboptimal practice is most common.

Male lower urinary tract dysfunction represents a common problem in the community. Physicians should approach these patients based on the best available evidence. This summary provides the up-to-date recommendations for the evaluation and the management of men with lower urinary tract symptoms. Lower urinary tract symptoms (LUTS) are common, often bothersome, and have multifactorial aetiology. To present a summary of the 2023 version of the European Association of Urology guidelines on the management of male LUTS. A structured literature search from 1966 to 2021 selected the articles with the highest certainty evidence. The Delphi technique consensus approach was used to develop the recommendations. The assessment of men with LUTS should be practical. A careful medical history and physical examination are essential. Validated symptom scores, urine test, uroflowmetry, and postvoid urine residual, as well as frequency-volume charts for patients with nocturia or predominately storage symptoms should be used. Prostate-specific antigen should be ordered if a diagnosis of prostate cancer changes the treatment plan. Urodynamics should be performed for selected patients. Men with mild symptoms are candidates for watchful waiting. Behavioural modification should be offered to men with LUTS prior to, or concurrent with, treatment. The choice of medical treatment depends on the assessment findings, predominant type of symptoms, ability of the treatment to change the findings, and the expectations to be met in terms of the speed of onset, efficacy, side effects, and disease progression. Surgery is reserved for men with absolute indications, and for patients who fail or prefer not to receive medical therapy. Surgical management has been divided into five sections: resection, enucleation, vaporisation, and alternative ablative and nonablative techniques. The choice of surgical technique depends on patient's characteristics, expectations, and preferences; surgeon's expertise; and availability of modalities. The guidelines provide an evidence-based approach for the management of male LUTS. A clinical assessment should identify the cause(s) of symptoms and define the clinical profile and patient's expectations. The treatment should aim to ameliorate symptoms and reduce the risk of complications. [ABSTRACT FROM AUTHOR]

Objective: This study evaluated the bibliometric data of the most common publication types of the neuroimaging literature.Methods: PubMed was searched to identify all published papers with “neuroimaging” as their MeSH Major Topics, and they were further searched by the following publication types: case report, clinical trial, comparative study, editorial, evaluation study, guideline, meta-analysis, multicenter study, randomized controlled trial, review, technical report, and validation study. The proportion of papers belonging to each publication type published in neuroimaging journals was calculated. Year-adjusted mean citation counts for each publication type were computed using data from Web of Science. Publication trend and its correlation with citation performance were assessed.Results: Review and comparative study were the most common publication types. Publication types with the highest proportion in neuroimaging journals were guideline, validation study, and technical reports. Since the year 2000, multicenter study, review, and meta-analysis showed the strongest linear increase in annual publication count. These publication types also had the highest year-adjusted citation counts (4.7–10.0). Publication types with the lowest year-adjusted citation counts were editorial and case report (0.5–1.0). It was estimated that 12.5% of the publications labeled as case reports were incorrectly labeled.Conclusions: Neuroimaging literature has been expanding with papers of higher levels of evidence, such as meta-analyses, multicenter studies, and randomized controlled trials.

The following article summarizes United States Patent Application No. US20180052155A1, titled ‘Assay Devices and Methods’ (filed 16 August 2016, published 22 February 2018). While lateral flow assays (LFAs) have revolutionized point-of-care diagnostics by enabling accurate, inexpensive, and rapid detection of biomarkers, they typically do not provide quantitative results. Hence, there is a significant need for quantitative assays at the point of care. This patent summary describes a novel method of chronometric biomarker quantitation via enzymatic degradation of a metastable gelatin-based biomatrix, principally suited for use in paper-based microfluidic devices (microPADs). This new quantitation mechanism was designed to meet the ASSURED criteria for point-of-care diagnostic devices laid forth by the World Health Organization and may ultimately provide increased access to healthcare, at a significantly reduced cost, around the world.

Listeria monocytogenes is the third most deadly foodborne pathogen in the United States. The bacterium is found in soil and water, contaminating raw food products and the processing environment, where it can persist for an extended period. Currently, testing of food contact and non-food contact surfaces is performed using an array of sampling devices and endpoint technologies, offering various levels of sensitivity, cost, user skill, and time to detection. Paper-based microfluidic devices (µPADs) are a rapid detection platform amenable to low-cost, user-friendly, and portable diagnostics. In this study, we developed and evaluated a µPAD platform specific for the colorimetric detection of the Listeria genus following recovery from food contact and non-food contact surfaces. For detection, four colorimetric substrates specific for the detection of β-glucosidase, two broths selective for the detection of Listeria spp., and a nonselective broth were evaluated to facilitate detection of Listeria spp. The limit of detection and time to detection were determined by using pure bacterial cultures. After 8 h enrichment, L. monocytogenes (102 Colony Forming Units (CFU)/coupon) was detected on every surface. After 18 h enrichment, L. monocytogenes (102 CFU/coupon) was detected on all surfaces with all swabbing devices. This study demonstrated the ability of the µPAD-based method to detect potentially stressed cells at low levels of environmental contamination.

Benign conditions of the lower urinary tract, including benign prostatic hyperplasia, overactive bladder syndrome, and stress urinary incontinence, are frequent in the general population. Despite their benign nature, they have major adverse effects on the quality of life of the afflicted patients and their partners. Despite major progress in the diagnosis and treatment of these conditions, improved understanding and management of these patients remain substantial medical needs. This editorial discusses some recent high-quality articles published in the Journal of Clinical Medicine on the understanding of the epidemiology, pathophysiology, diagnostic, and treatment of benign diseases of the lower urinary tract tissues such as the bladder and prostate. [ABSTRACT FROM AUTHOR]

Reagent pencils allow for solvent-free deposition of reagents onto paper-based microfluidic devices. The pencils are portable, easy to use, extend the shelf-life of reagents, and offer a platform for customizing diagnostic devices at the point of care. In this work, reagent pencils were characterized by measuring the wear resistance of pencil cores made from polyethylene glycols (PEGs) with different molecular weights and incorporating various concentrations of three different reagents using a standard pin abrasion test, as well as by measuring the efficiency of reagent delivery from the pencils to the test zones of paper-based microfluidic devices using absorption spectroscopy and digital image colorimetry. The molecular weight of the PEG, concentration of the reagent, and the molecular weight of the reagent were all found to have an inverse correlation with the wear of the pencil cores, but the amount of reagent delivered to the test zone of a device correlated most strongly with the concentration of the reagent in the pencil core. Up to 49% of the total reagent deposited on a device with a pencil was released into the test zone, compared to 58% for reagents deposited from a solution. The results suggest that reagent pencils can be prepared for a variety of reagents using PEGs with molecular weights in the range of 2000 to 6000 g/mol.

This paper presents a lateral flow assay (LFA) for the quantitative, fluorescence-based detection of the cardiac biomarker troponin I (cTnI) that features an analytical strip made of cellulose filter paper. The results show that the wicking and test time are comparable to those obtained with conventional nitrocellulose (NC)-based LFAs. Further, the cellulose paper provides an excellent background with no auto-fluorescence that is very adequate in detecting fluorescent lines. While fluorescence that was generated with cellulose strips was lower when compared to that generated in NC strips, signals could be improved by layering carbon nanofibers (CNF) on the cellulose. A nonlinear behavior of the concentration–response relationship was observed for the LFA architectures with NC, cellulose, and cellulose-CNF in the 0 to 200 ng/mL cTnI concentration range. The measurements were consistent and characterized by coefficients of variation lower than 2.5%. Detection and quantitation limits that were in the range 1.28–1.40 ng/mL and 2.10–2.75 ng/mL were obtained for LFA with cellulose and cellulose CNF strips that are equivalent to the limits obtained with the standard NC LFA. Overall, we showed that commercially available filter paper can be used in the analytical strip of LFA.

Objective: Computerized neglect tests could significantly deepen our disorder-specific knowledge by effortlessly providing additional behavioral markers that are hardly or not extractable from existing paper-and-pencil versions. This study investigated how testing format (paper versus digital), and screen size (small, medium, large) affect the Center of cancelation (CoC) in right-hemispheric stroke patients in the Letters and the Bells cancelation task. Our second objective was to determine whether a machine learning approach could reliably classify patients with and without neglect based on their search speed, search distance, and search strategy. Method: We compared the CoC measure of right hemisphere stroke patients with neglect in two cancelation tasks across different formats and display sizes. In addition, we evaluated whether three additional parameters of search behavior that became available through digitization are neglect-specific behavioral markers. Results: Patients' CoC was not affected by test format or screen size. Additional search parameters demonstrated lower search speed, increased search distance, and a more strategic search for neglect patients than for control patients without neglect. Conclusion: The CoC seems robust to both test digitization and display size adaptations. Machine learning classification based on the additional variables derived from computerized tests succeeded in distinguishing stroke patients with spatial neglect from those without. The investigated additional variables have the potential to aid in neglect diagnosis, in particular when the CoC cannot be validly assessed (e.g., when the test is not performed to completion). [ABSTRACT FROM AUTHOR]

[Display omitted] • A simple and user-friendly diagnostics to detect the hypervirulent K. pneumoniae. • CRISPR-assisted point-of-need tool that stands worthy of the ASSURED criteria. • Species-specific detection of solely the test-strains of K. pneumoniae. • No cross-reactivity observed when tested on different genera besides the test strains. • Instrument-free readout to extend the reach of the technology to remote locations. Klebsiella pneumoniae , a prevalent healthcare-associated pathogen, poses a significant challenge to diagnosis and treatment due to its virulence and antimicrobial resistance. The demand for more efficient, precise and accessible diagnostic methods is imperative, as current approaches are labor-intensive and resource-dependent. In this study, a CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats)-based diagnostic tool for rapid detection of hypervirulent K. pneumoniae infections was proposed. We integrated recombinase polymerase amplification (RPA) coupled with a lateral flow assay and Cas13a (CRISPR associated protein 13a) to target the housekeeping rpoB gene for species-specific detection and the capsular polysaccharide regulating gene rmpA for identification of hypervirulent strains of K. pneumoniae. Tested on 18 K. pneumoniae strains, the devised tool successfully detected hypervirulent strains K. pneumoniae M59 and K. pneumoniae KP109 showing presence of rmpA. This study allows to develop an instrument-free platform for routine diagnosis of K. pneumoniae from serum, urine, and saliva samples that would empower healthcare personnel to facilitate proper and timely treatment of infections caused by the K. pneumoniae. [ABSTRACT FROM AUTHOR]

Current centralised healthcare models pose many challenges, particularly for developing countries such as South Africa, where travel and time costs make it difficult for patients to seek healthcare, even when urgently needed. To address this issue, point-of-care (PoC) tests, which are performed at or near the site of clinical care, have gained popularity and are actively being developed. Microfluidic systems, in which small volumes of fluids can be processed, provide an ideal platform on which to develop PoC diagnostic solutions. Specifically, the emerging field of paper-based microfluidics, with advantages such as low-cost, disposability and minimal external equipment requirements, provides unique opportunities for addressing healthcare issues in developing countries. This work explores the field of paper-based microfluidics, with step-by-step instructions on the design, manufacture and testing processes to realise paper-based devices towards diagnostic applications. Paper-based microfluidic and electronic components are presented, as well as the integration of these components to provide smart paper-based devices. This serves as an educational tool, enabling both beginners and experts in the field to fast-track development of unique paper-based solutions towards PoC diagnostics, with emphasis on the South African context, where both the need for and impact of these solutions are great.

Due to their portability, versatility for supporting multiple assay formats, and potential for resulting in low-cost assays, paper-based analytical devices (PADs) are an increasingly popular format as a platform for the development of point-of-care tests. However, very few PADs have been translated successfully to their intended environments outside of academic settings. Often overlooked as a factor that inhibits translation, usability is a vital characteristic of any successful point-of-care test. Recent advancements in PAD design have demonstrated improved usability by simplifying various aspects of user operation, including sample collection, sample processing, device operation, detection, and readout/interpretation. Field testing at various stages of device design can offer critical feedback about device usability, especially when it involves the proposed end-user or other stakeholders. By highlighting advances in usability, we aim to encourage thoughtful and rigorous design at the academic prototyping stage to address one outstanding hurdle that limits the number of PADs that make it from the benchtop to the point-of-care. Image 1 • Paper-based devices have potential for use at the point-of-care. • Devices that are user-friendly are more likely to be translated to the field. • Additional user steps create additional opportunities for user error. • We discuss ways to streamline user operation of paper-based devices. • We highlight three case studies for devices deployed successfully to the field. [ABSTRACT FROM AUTHOR]

Abstract The severity and cost of wound infections strongly demands for simple and fast methods for wound infection determination. Point-of-care testing devices play a crucial role in order to achieve a fast diagnosis and early treatment. Myeloperoxidase (MPO) enzyme, detected in fluids of infected wounds has been postulated as a suitable biomarker for wound diagnostics. Here we present a new system for MPO detection, based on enzyme-catalysed oxidative synthesis of a dye that can be incorporated into paper-based point of care devices. Visual MPO detection has been achieved through the use of phenylenediamine, a common colourless hair dye precursor. MPO oxidation of these compounds yielded bright coloured products distinguishable from the colour of the wound environment. Immobilisation of the MPO substrates on paper strips was achieved through in situ interaction of the oxidised coloured product with branched polyethyleneimine. The colour reaction of the immobilized substrates, detectable by naked eye, responds to the MPO levels present in infected wound fluids revealing an easy system for incorporation of MPO detection in paper based diagnostic devices. Graphical abstract fx1 Highlights • A new sensitive MPO detection method for wound infection diagnose. • Fast visual detection of MPO levels corresponding to infected wounds avoiding haemoglobin cross-reaction. • A new detection method easily transferable to paper-based point of care diagnostic devices. [ABSTRACT FROM AUTHOR]

The disinfection of deteriogenic microorganisms and the removal of induced chromatic alterations in artworks are still open challenges in the field of conservation. For this purpose, a new alcoholic hydrogel was tested to remove an extensive fungal attack from a multimaterial collage by the artist Alessandro Kokocinski and to mitigate chromatic changes caused by the contamination of its poster paper and plywood support layers. A Gellan gum-based hydrogel was used, which was modified by adding a high concentration of alcohol (66.7% ethanol), to give the system an effective disinfecting agent in addition to the detergent capacity of the gel for water-sensitive works of art. It was successfully tested on samples mimicking the complex stratigraphy of the artwork under study. To create replica mock-ups, the artwork materials and stratigraphy were investigated through diagnostic and laboratory techniques such as multispectral imaging, X-ray fluorescence spectroscopy, Fourier transform infrared spectroscopy, and pyrolysis coupled with gas-chromatography-mass spectrometry. The treatment was shown to have a disinfecting effect on the test samples and did not alter their structure, allowing us to apply the method to the artwork. Here, the hydrogel successfully removed and inhibited fungal proliferation in addition to mitigating the color changes caused by fungi.

Staphylococcus argenteus and Staphylococcus schweitzeri, previously known as divergent Staphylococcus aureus clonal lineages, have been recently established as novel, difficult-to-delimit, coagulase-positive species within the S. aureus complex. Methicillin-resistant strains of S. argenteus are known from Australia and the UK. Knowledge of their epidemiology, medical significance and transmission risk is limited and partly contradictory, hampering definitive recommendations. There is mounting evidence that the pathogenicity of S. argenteus is similar to that of 'classical' S. aureus , while as yet no S. schweitzeri infections have been reported. To provide decision support on whether and how to distinguish and report both species. PubMed, searched for S. argenteus and S. schweitzeri. This position paper reviews the main characteristics of both species and draws conclusions for microbiological diagnostics and surveillance as well as infection prevention and control measures. We propose not distinguishing within the S. aureus complex for routine reporting purposes until there is evidence that pathogenicity or clinical outcome differ markedly between the different species. Primarily for research purposes, suitably equipped laboratories are encouraged to differentiate between S. argenteus and S. schweitzeri. Caution is urged if these novel species are explicitly reported. In such cases, a specific comment should be added (i.e. 'member of the S.aureus complex') to prevent confusion with less- or non-pathogenic staphylococci. Prioritizing aspects of patient safety, methicillin-resistant isolates should be handled as recommended for methicillin-resistant Staphylococcus aureus (MRSA). In these cases, the clinician responsible should be directly contacted and informed by the diagnosing microbiological laboratory, as they would be for MRSA. Research is warranted to clarify the epidemiology, clinical impact and implications for infection control of such isolates. [ABSTRACT FROM AUTHOR]

Listeria monocytogenes is the third most deadly foodborne pathogen in the United States. The bacterium is found in soil and water, contaminating raw food products and the processing environment, where it can persist for an extended period. Currently, testing of food contact and non-food contact surfaces is performed using an array of sampling devices and endpoint technologies, offering various levels of sensitivity, cost, user skill, and time to detection. Paper-based microfluidic devices (µPADs) are a rapid detection platform amenable to low-cost, user-friendly, and portable diagnostics. In this study, we developed and evaluated a µPAD platform specific for the colorimetric detection of the Listeria genus following recovery from food contact and non-food contact surfaces. For detection, four colorimetric substrates specific for the detection of β-glucosidase, two broths selective for the detection of Listeria spp., and a nonselective broth were evaluated to facilitate detection of Listeria spp. The limit of detection and time to detection were determined by using pure bacterial cultures. After 8 h enrichment, L. monocytogenes (102 Colony Forming Units (CFU)/coupon) was detected on every surface. After 18 h enrichment, L. monocytogenes (102 CFU/coupon) was detected on all surfaces with all swabbing devices. This study demonstrated the ability of the µPAD-based method to detect potentially stressed cells at low levels of environmental contamination. [ABSTRACT FROM AUTHOR]

This work demonstrates a stand-alone power source that integrates a paper-based hydrogen fuel cell with a customized chemical heater that produces hydrogen in-situ upon the addition of a liquid. The presented approach operates by capillary action and takes advantage of the hydrogen released as a by-product of an exothermic reaction used in point-of-care diagnostics. The paper-based fuel cell produces a maximum power of 25.8 mW (103.2 mW cm −2 ), which is suitable for powering a diversity of electrical devices such as commercially available digital pregnancy tests and glucometers. While device shape and dimensions can be customized, here it is shown that the fuel cell can be designed in a compact form factor and footprint comparable to a lateral flow test while providing a remarkable power output. This approach holds great promise for powering portable diagnostics, as the generated electric power could enable device functionalities required for advanced assays, such as device timing, actuation, and signal quantification. Part of the same liquid sample that is to be analyzed (urine, saliva, water, etc) could be used to trigger the hydrogen generation and start the fuel cell operation. [ABSTRACT FROM AUTHOR]

We demonstrate, for the first time, the multiplexed determination of microbial species from whole blood using the paper-folding technique of origami to enable the sequential steps of DNA extraction, loop-mediated isothermal amplification (LAMP), and array-based fluorescence detection. A low-cost handheld flashlight reveals the presence of the final DNA amplicon to the naked eye, providing a 'sample-to-answer' diagnosis from a finger-prick volume of human blood, within 45 min, with minimal user intervention. To demonstrate the method, we showed the identification of three species of Plasmodium, analyzing 80 patient samples benchmarked against the gold-standard polymerase chain reaction (PCR) assay in an operator-blinded study. We also show that the test retains its diagnostic accuracy when using stored or fixed reference samples. [ABSTRACT FROM AUTHOR]

Malaria elimination is a major goal to be reached in the next decade. Significant progress were made in the past, and the prevalence decreased in many areas while the positive trend stalled in the last years. The exact number of asymptomatic carriers of Plasmodium parasites is unknown since this population is not detected by conventional diagnosis methods and participate in the maintenance of transmission. Molecular methods to detect low parasitemia are not available at point-of-care in low-income countries of malaria endemic areas. Adaptation of molecular methods such as loop-mediated isothermal amplification of DNA may provide effective tools but it required simplification of DNA detection. Square waves voltammetry, easily imbedded in small device such as cell phone, was largely described for DNA detection but support for reaction was an issue to address. Here we used an efficient functionalization method of paper-based material to facilitate the interactions between isothermal amplification product and methylene blue for easy-to-use DNA detection. The proof-of-concept of qualitative detection of very low parasitemia from malaria infected patients using newly chemically treated paper for square waves voltammetry was obtained with a sensitivity and specificity of 100% and a limit-of-detection of 0.1 parasite. μL−1 corresponding to a parasitemia of 0.000002%. [Display omitted] • Asymptomatic carriers of Plasmodium parasites participate in the maintenance of malaria transmission. • Molecular methods to detect low parasitemia are not available at point-of-care in malaria endemic areas. • Detection of Plasmodium DNA using square waves voltammetry and methylene blue required innovative paper functionalization. • The proof-of-concept of low parasitemia diagnosis using chemically grafted paper for square waves voltammetry was obtained. [ABSTRACT FROM AUTHOR]

Addressing the pressing demand for rapid and inexpensive coagulation testing in cardiovascular care, this study introduces a novel application of repurposed COVID-19 rapid antigen tests (RATs) as paper-based lateral flow assays (LFAs) combined with machine learning for coagulation status evaluation. By further developing a mobile app prototype, we present a platform that enables clinicians to perform immediate and accurate anticoagulant dosing adjustments using existing post-pandemic resources. Our proof-of-concept employs a random forest machine learning classifier to interpret image feature variations on RAT NC membrane, correlating red blood cell (RBC) wicked diffusion distance in recalcified citrated whole blood with changes in coagulative viscosity, easily interpreted. Enhanced by confocal imaging studies of paper microfluidics, our approach provides insights into the mechanisms dissecting coagulation components, achieving high classification precision, recall, and F1-scores. The inverse relationship between RBC wicked diffusion distance and enoxaparin concentration paves the way for machine learning to inform real-time dose prescription adjustments, aligning with individual patient profiles to optimize therapeutic outcomes. This study not only demonstrates the potential of leveraging surplus RATs for coagulation management but also exemplifies a cost-effective, rapid, and smart strategy to enhance clinical decision-making in the post-pandemic era. Highlights: • Repurposed COVID-19 RATs provide an ideal platform for observing differences in blood coagulability. • Random Forest image classification algorithms can facilitate rapid coagulation status assessment on a paper-based LFA platform. [ABSTRACT FROM AUTHOR]

Current centralised healthcare models pose many challenges, particularly for developing countries such as South Africa, where travel and time costs make it difficult for patients to seek healthcare, even when urgently needed. To address this issue, point-of-care (PoC) tests, which are performed at or near the site of clinical care, have gained popularity and are actively being developed. Microfluidic systems, in which small volumes of fluids can be processed, provide an ideal platform on which to develop PoC diagnostic solutions. Specifically, the emerging field of paper-based microfluidics, with advantages such as low-cost, disposability and minimal external equipment requirements, provides unique opportunities for addressing healthcare issues in developing countries. This work explores the field of paper-based microfluidics, with step-by-step instructions on the design, manufacture and testing processes to realise paper-based devices towards diagnostic applications. Paper-based microfluidic and electronic components are presented, as well as the integration of these components to provide smart paper-based devices. This serves as an educational tool, enabling both beginners and experts in the field tofast-track development of unique paper-based solutions towards PoC diagnostics, with emphasis on the South African context, where both the need for and impact of these solutions are great. [ABSTRACT FROM AUTHOR]

Objective: To determine whether a smartphone‐obtained image can be used to extrapolate the PCV of canine blood samples. Design: Prospective study of surplus blood obtained from clinical cases. Setting: University teaching hospital. Interventions: Blood samples were placed on filter paper, and images were obtained with a smartphone in different environments. These results were then compared to the PCV measurements on the same samples following the World Health Organization guidelines. Measurements: Sixty‐nine samples were assessed and identified that smartphone images, obtained in a controlled environment, were able to predict the PCV of the samples. This prediction was most accurate when assessing samples of a normal erythroid mass or polycythemic samples. Conclusions: The results of this study suggest that smartphone‐obtained images do have a utility in predicting canine PCV. If this can be incorporated into a smartphone application, there would be scope to use this in low resource settings. [ABSTRACT FROM AUTHOR]

Objective: This study evaluated the bibliometric data of the most common publication types of the neuroimaging literature. Methods: PubMed was searched to identify all published papers with "neuroimaging" as their MeSH Major Topics, and they were further searched by the following publication types: case report, clinical trial, comparative study, editorial, evaluation study, guideline, meta-analysis, multicenter study, randomized controlled trial, review, technical report, and validation study. The proportion of papers belonging to each publication type published in neuroimaging journals was calculated. Year-adjusted mean citation counts for each publication type were computed using data from Web of Science. Publication trend and its correlation with citation performance were assessed. Results: Review and comparative study were the most common publication types. Publication types with the highest proportion in neuroimaging journals were guideline, validation study, and technical reports. Since the year 2000, multicenter study, review, and meta-analysis showed the strongest linear increase in annual publication count. These publication types also had the highest year-adjusted citation counts (4.7–10.0). Publication types with the lowest year-adjusted citation counts were editorial and case report (0.5–1.0). It was estimated that 12.5% of the publications labeled as case reports were incorrectly labeled. Conclusions: Neuroimaging literature has been expanding with papers of higher levels of evidence, such as meta-analyses, multicenter studies, and randomized controlled trials. [ABSTRACT FROM AUTHOR]

This paper presents a lateral flow assay (LFA) for the quantitative, fluorescence-based detection of the cardiac biomarker troponin I (cTnI) that features an analytical strip made of cellulose filter paper. The results show that the wicking and test time are comparable to those obtained with conventional nitrocellulose (NC)-based LFAs. Further, the cellulose paper provides an excellent background with no auto-fluorescence that is very adequate in detecting fluorescent lines. While fluorescence that was generated with cellulose strips was lower when compared to that generated in NC strips, signals could be improved by layering carbon nanofibers (CNF) on the cellulose. A nonlinear behavior of the concentration–response relationship was observed for the LFA architectures with NC, cellulose, and cellulose-CNF in the 0 to 200 ng/mL cTnI concentration range. The measurements were consistent and characterized by coefficients of variation lower than 2.5%. Detection and quantitation limits that were in the range 1.28–1.40 ng/mL and 2.10–2.75 ng/mL were obtained for LFA with cellulose and cellulose CNF strips that are equivalent to the limits obtained with the standard NC LFA. Overall, we showed that commercially available filter paper can be used in the analytical strip of LFA. [ABSTRACT FROM AUTHOR]

Abstract Phage‐inducible chromosomal islands (PICIs) are a family of phage satellites that hijack phage components to facilitate their mobility and spread. Recently, these genetic constructs are repurposed as antibacterial drones, enabling a new toolbox for unorthodox applications in biotechnology. To illustrate a new suite of functions, the authors have developed a user‐friendly diagnostic system, based upon PICI transduction to selectively enrich bacteria, allowing the detection and sequential recovery of Escherichia coli and Staphylococcus aureus. The system enables high transfer rates and sensitivities in comparison with phages, with detection down to ≈50 CFU mL−1. In contrast to conventional detection strategies, which often rely on nucleic acid molecular assays, and cannot differentiate between dead and live organisms, this approach enables visual sensing of viable pathogens only, through the expression of a reporter gene encoded in the PICI. The approach extends diagnostic sensing mechanisms beyond cell‐free synthetic biology strategies, enabling new synthetic biology/biosensing toolkits.

Paper is predominantly composed of cellulose fibers that have an inherent ability to wick fluids by capillary action; it provides an interesting diagnostic platform that is inexpensive, easily obtained, and eco-friendly. Paper has been used in various types of biologically relevant applications including paper-based molecular assays, paper-based ELISA (P-ELISA), paper-based nucleic acid assays, and paper-based cell assays. Based on recent successes with the use of paper as a platform, we contend that paper is not only very suitable for diagnostics but could provide a more advantageous platform than current plastics-based platforms for drug discovery, and would be useful for accomplishing in vitro pre-compound screening steps while offering a possible solution to several economic obstacles inherent in the pharmaceutical industry. [ABSTRACT FROM AUTHOR]

Ambient ionization mass spectrometry using paper spray is utilized for rapid discrimination of Candida species without sample preparation. The experiment is based on characteristic lipid profiles and is an extension to a procedure used for the discrimination of bacteria. Candida colonies were smeared onto filter paper pre-cut to a sharp tip, subsequently wetted with solvent and held at high potential. Charged droplets released by field emission were sucked into the mass spectrometer inlet and mass spectra were recorded. Eight closely related Candida species with clinical relevance and known phylogeny were investigated. Numerical data fusion of the positive and negative ion mass spectra and multivariate statistics (principal component analysis, followed by linear discriminant analysis) allowed species level discrimination with a prediction rate of ca. 90%. [ABSTRACT FROM AUTHOR]

[Display omitted] • Non-invasive and Invasive Body-fluids. • Frugal detection systems. • Colorimetric, Fluorimetric, SERS, Electro-chemical, Electrophoresis. • Electro-kinetics, Aptamers and body-fluid heterogeneity. Paper has been used for testing analytes since the advent of litmus paper. Also, the rapid growth of the human population in isolated areas of the world have engendered demand for testing and diagnostic methods that are not only easy to transport, but also have a low cost of fabrication and rapid results. Hormones are crucial biomarkers which can be used to detect certain physiological conditions. These hormones, present in non-invasive and invasive body fluids, hold major potential for detection using paper-based devices. This review paper aims to highlight the advancements in the creation of paper-based microfluidic devices to detect hormones in different body fluids. It exhaustively explains the current methods of detection for hormones in various body fluids like sweat, saliva and serum using paper-based microfluidic devices and the role of these devices in the future in terms of rapid detection, low cost, and ease of transport. By demonstrating the mechanisms of these devices, this paper shows a promising unconventional avenue for efficient hormone detection. [ABSTRACT FROM AUTHOR]

Biosensors integrated with artificial intelligence (AI) hold immense potential for transforming healthcare through rapid, automated diagnostics and precision therapeutics. This paper reviews the convergence of biosensing and AI towards developing smart biomedical systems. The fundamentals, historical evolution, and classification of biosensors are presented, highlighting key applications across infections, chronic illnesses, and environmental monitoring. Core AI concepts, including machine learning, neural networks, computer vision, and natural language processing, are discussed, along with their implementation to augment biosensor functionality, connectivity, point-of-care adoption, and laboratory automation. Promising research directions and real-world case studies applying AI-integrated biosensors for early diagnosis and drug delivery are discussed. The opportunities and challenges in advancing this synergistic technology are contemplated, underscoring the need for cross-disciplinary collaboration, clinical validation, ethical vigilance and supportive policy environments to successfully translate AI-biosensors into practical healthcare solutions. [ABSTRACT FROM AUTHOR]

Reagent pencils allow for solvent-free deposition of reagents onto paper-based microfluidic devices. The pencils are portable, easy to use, extend the shelf-life of reagents, and offer a platform for customizing diagnostic devices at the point of care. In this work, reagent pencils were characterized by measuring the wear resistance of pencil cores made from polyethylene glycols (PEGs) with different molecular weights and incorporating various concentrations of three different reagents using a standard pin abrasion test, as well as by measuring the efficiency of reagent delivery from the pencils to the test zones of paper-based microfluidic devices using absorption spectroscopy and digital image colorimetry. The molecular weight of the PEG, concentration of the reagent, and the molecular weight of the reagent were all found to have an inverse correlation with the wear of the pencil cores, but the amount of reagent delivered to the test zone of a device correlated most strongly with the concentration of the reagent in the pencil core. Up to 49% of the total reagent deposited on a device with a pencil was released into the test zone, compared to 58% for reagents deposited from a solution. The results suggest that reagent pencils can be prepared for a variety of reagents using PEGs with molecular weights in the range of 2000 to 6000 g/mol. [ABSTRACT FROM AUTHOR]

The pandemic of COVID-19 and its widespread transmission have made us realize the importance of early, quick diagnostic tests for facilitating effective cure and management. The primary obstacles encountered were accurately distinguishing COVID-19 from other illnesses including the flu, common cold, etc. While the polymerase chain reaction technique is a robust technique for the determination of SARS-CoV-2 in patients of COVID-19, there arises a high demand for affordable, quick, user-friendly, and precise point-of-care (POC) diagnostic in therapeutic settings. The necessity for available tests with rapid outcomes spurred the advancement of POC tests that are characterized by speed, automation, and high precision and accuracy. Paper-based POC devices have gained increasing interest in recent years because of rapid, low-cost detection without requiring external instruments. At present, microfluidic paper-based analysis devices have garnered public attention and accelerated the development of such POCT for efficient multistep assays. In the current review, our focus will be on the fabrication of detection modules for SARS-CoV-2. Here, we have included a discussion on various strategies for the detection of viral moieties. The compilation of these strategies would offer comprehensive insight into the detection of the causative agent preparedness for future pandemics. We also provide a descriptive outline for paper-based diagnostic platforms, involving the determination mechanisms, as well as a commercial kit for COVID-19 as well as their outlook. [ABSTRACT FROM AUTHOR]

Introduction: To contribute to addressing diagnostic health inequalities in the United Kingdom, this review aimed to investigate determinants of diagnostic service use amongst people experiencing high deprivation in the United Kingdom. Methods: A systematic review was conducted using three databases (EBSCO, Web of Science and SCOPUS) to search studies pertaining to diagnostic service use amongst people experiencing high deprivation. Search terms related to diagnostics, barriers and facilitators to access and deprivation. Articles were included if they discussed facilitators and/or barriers to diagnostic service access, contained participants' direct perspectives and focussed on individuals experiencing high deprivation in the United Kingdom. Articles were excluded if the full text was unretrievable, only abstracts were available, the research did not focus on adults experiencing high deprivation in the United Kingdom, those not including participants' direct perspectives (e.g., quantitative studies) and papers unavailable in English. Results: Of 14,717 initial papers, 18 were included in the final review. Determinants were grouped into three themes (Beliefs and Behaviours, Emotional and Psychological Factors and Practical Factors), made up of 15 sub‐themes. These were mapped to a conceptual model, which illustrates that Beliefs and Behaviours interact with Emotional and Psychological Factors to influence Motivation to access diagnostic services. Motivation then influences and is influenced by Practical Factors, resulting in a Decision to Access or Not. This decision influences Beliefs and Behaviours and/or Emotional and Psychological Factors such that the cycle begins again. Conclusion: Decision‐making regarding diagnostic service use for people experiencing high deprivation in the United Kingdom is complex. The conceptual model illustrates this complexity, as well as the mediative, interactive and iterative nature of the process. The model should be applied in policy and practice to enable understanding of the factors influencing access to diagnostic services and to design interventions that address identified determinants. Patient or Public Contribution: Consulting lived experience experts was imperative in understanding whether and how the existing literature captures the lived experience of those experiencing high deprivation in South England. The model was presented to lived experience experts, who corroborated findings, highlighted significant factors for them and introduced issues that were not identified in the review. [ABSTRACT FROM AUTHOR]

The disinfection of deteriogenic microorganisms and the removal of induced chromatic alterations in artworks are still open challenges in the field of conservation. For this purpose, a new alcoholic hydrogel was tested to remove an extensive fungal attack from a multimaterial collage by the artist Alessandro Kokocinski and to mitigate chromatic changes caused by the contamination of its poster paper and plywood support layers. A Gellan gum-based hydrogel was used, which was modified by adding a high concentration of alcohol (66.7% ethanol), to give the system an effective disinfecting agent in addition to the detergent capacity of the gel for water-sensitive works of art. It was successfully tested on samples mimicking the complex stratigraphy of the artwork under study. To create replica mock-ups, the artwork materials and stratigraphy were investigated through diagnostic and laboratory techniques such as multispectral imaging, X-ray fluorescence spectroscopy, Fourier transform infrared spectroscopy, and pyrolysis coupled with gas-chromatography-mass spectrometry. The treatment was shown to have a disinfecting effect on the test samples and did not alter their structure, allowing us to apply the method to the artwork. Here, the hydrogel successfully removed and inhibited fungal proliferation in addition to mitigating the color changes caused by fungi. [ABSTRACT FROM AUTHOR]

• Review of paper-based microfluidics. • Overview of current methods of fabrication. • Applications as diagnostic devices. • Limitations and opportunities. Paper-based microfluidics is the branch of microfluidics involving devices made out of paper, or other porous membranes, that wick fluids by capillary action. Paper-based microfluidic devices have several advantages over conventional microfluidic devices including simpler fabrication, lower cost, easier disposal, and the ability to operate without pumps or other supporting equipment. The most common application of paper-based microfluidic devices is in the development of point-of-care (POC) diagnostic devices, which could eliminate the need for costly and time-consuming laboratory-based analytical procedures. This review provides an overview of current methods of fabricating paper-based microfluidic devices, examples of applications of these devices, a discussion of their current limitations, and an outlook on their future. [ABSTRACT FROM AUTHOR]

This paper describes the need for technologies that improve analytical sensitivity to proteins to better define and monitor the progression from heath to disease over the course of an individual's life. These technologies have the potential to allow the early diagnosis of disease, and trigger treatments at the time when they have the greatest opportunity to be effective. We will describe a technology that we have developed for high sensitivity protein detection, namely, single molecule arrays (Simoa). Simoa is based on the capture of protein molecules on magnetic beads, labeling each protein with an enzyme, and counting of single enzyme labels on beads that are isolated in arrays of femtoliter wells. Simoa has enabled the detection of proteins at subfemtomolar concentrations in a variety of biological fluids. We describe the impact of higher sensitivity of proteins using Simoa on: less invasive testing; earlier detection of disease; providing biomarker baseline profiles for healthy individuals; testing of small sample volumes; monitoring of therapeutic efficacy; faster tests; and detection of proteins in complex samples. We also provide a perspective of how new technologies that allow the low-cost manufacture and miniaturization of Simoa could drive the next wave of analytical devices, including wearables. [ABSTRACT FROM AUTHOR]