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

Simple Summary: Blood clots are formed when blood vessels are injured. They help stop bleeding and heal wounds, but can also cause serious problems if they block blood flow or break off and travel to other organs. This study investigates how blood clots differ in people with cancer compared to healthy or non-cancerous individuals. This study found that cancer patients have higher levels of histones in their blood, which make their clots stiffer and resistant to lysis. Further, clots formed in cancer patients have higher viscoelastic properties, and hence are harder to break down. These findings suggest that cancer patients have abnormal clotting properties that may increase their risk of developing thrombosis, and evaluating these properties can be helpful in detecting cancer. Background: Blood viscoelasticity and plasma protein levels can play an important role in the diagnosis and prognosis of cancer. However, the role of histones and DNA in modulating blood clot properties remains to be investigated. This study investigates the differences in blood viscoelasticity and plasma protein levels among cancer patients, individuals with other diseases, and healthy individuals. Methods: Blood samples were collected from 101 participants, including 45 cancer patients, 22 healthy individuals, and 34 individuals with other diseases. Rheological properties of clots formed in vitro by reconstituted elements of fibrinogen or plasma were analyzed with an Anton Paar Rheometer, USA. Plasma protein levels of D-dimer, TPA, EPCR, fibrinogen, and histone H3 were measured through ELISA. Blood clots were formed with or without DNA and histones (H3) by adding thrombin and calcium to plasma samples, and were evaluated for viscoelasticity, permeability, and degradation. Results: Cancer patients show higher blood viscoelasticity and plasma D-dimer levels compared to healthy individuals and individuals with other diseases. Our in vitro analysis showed that the addition of histone to the plasma results in a significant decrease in viscoelasticity and mean fiber thickness of the clot formed thereafter. In parallel studies, using plasma from patients, DNA and histones were detected in fibrin clots and were associated with less degradation by t-PA. Moreover, our results show that the presence of DNA and histones not only increases clots' permeability, but also makes them more prone to degradation. Conclusions: Plasma histones and DNA affect the structure of the clot formed and induce defective fibrinolysis. Moreover, the increased viscoelastic properties of plasma from cancer patients can be used as potential biomarkers in cancer prognosis. [ABSTRACT FROM AUTHOR]

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

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

Despite significant advances in the diagnosis and treatment of cardiovascular diseases, recent calls have emphasized the unmet need to improve precision-based approaches in cardiovascular disease. Although some studies provide preliminary evidence of the diagnostic and prognostic potential of circulating coding and non-coding RNAs, the complex RNA biology and lack of standardization have hampered the translation of these markers into clinical practice. In this position paper of the CardioRNA COST action CA17129, we provide recommendations to standardize the RNA development process in order to catalyse efforts to investigate novel RNAs for clinical use. We list the unmet clinical needs in cardiovascular disease, such as the identification of high-risk patients with ischaemic heart disease or heart failure who require more intensive therapies. The advantages and pitfalls of the different sample types, including RNAs from plasma, extracellular vesicles, and whole blood, are discussed in the sample matrix, together with their respective analytical methods. The effect of patient demographics and highly prevalent comorbidities, such as metabolic disorders, on the expression of the candidate RNA is presented and should be reported in biomarker studies. We discuss the statistical and regulatory aspects to translate a candidate RNA from a research use only assay to an in-vitro diagnostic test for clinical use. Optimal planning of this development track is required, with input from the researcher, statistician, industry, and regulatory partners. [ABSTRACT FROM AUTHOR]

Background: Harmful Alcohol use is frequent among opioid dependents patients undergoing agonist maintenance treatment. The objective assessment of harmful alcohol use can be done using laboratory measures of serum biomarkers. For community-based patients, there is often a requirement of an alternative method due to lack of onsite laboratory services. The aim of the study was to examine filter paper as a matrix to measure serum biomarkers of harmful alcohol use. Methods: The initial phase involved standardization of the filter-paper-based assay. Conditions were optimised for extraction and estimation of alcohol biomarkers (Aspartate Aminotransferase; AST, Alanine Aminotransferase; ALT, Gamma Glutamyl transferase; GGT and Carbohydrate Deficient Transferrin; CDT) from the filter paper. For clinical validation, serum samples were collected from community clinics. Biomarker levels obtained from both the methods were correlated using linear regression analysis. Limits of agreement between the two methods was estimated using the Intraclass Correlation Coefficient (ICC). Results: The extraction of enzymes (AST, ALT and GGT) from filter paper was carried out using the substrate buffer available with the reagent kit (Randox, UK). CDT was readily extracted from filter paper using deionised water. Serum biomarker levels measured from samples collected from community clinics correlated well with filter paper extracted levels (ICC 0.97-0.99). More than 90% of alcohol biomarker levels were recovered from the filter paper matrix using this method. Conclusion: Filter paper has the potential to be used as a matrix to objectively measure alcohol biomarkers among opioid-dependent patients from community settings lacking onsite laboratory facilities. [ABSTRACT FROM AUTHOR]

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

Few biomarker-based validation studies have examined error in online self-report dietary assessment instruments, and food records (FRs) have been considered less than food frequency questionnaires (FFQs) and 24-hour recalls (24HRs). We investigated measurement error in online and paper-based FFQs, online 24HRs, and paper-based FRs in 3 samples drawn primarily from 3 cohorts, comprising 1,393 women and 1,455 men aged 45–86 years. Data collection occurred from January 2011 to October 2013. Attenuation factors and correlation coefficients between reported and true usual intake for energy, protein, sodium, potassium, and respective densities were estimated using recovery biomarkers. Across studies, average attenuation factors for energy were 0.07, 0.07, and 0.19 for a single FFQ, 24HR, and FR, respectively. Correlation coefficients for energy were 0.24, 0.23, and 0.40, respectively. Excluding energy, the average attenuation factors across nutrients and studies were 0.22 for a single FFQ, 0.22 for a single 24HR, and 0.51 for a single FR. Corresponding correlation coefficients were 0.31, 0.34, and 0.53, respectively. For densities (nutrient expressed relative to energy), the average attenuation factors across studies were 0.37, 0.17, and 0.50, respectively. The findings support prior research suggesting different instruments have unique strengths that should be leveraged in epidemiologic research. [ABSTRACT FROM AUTHOR]

Enzyme-linked immunosorbent assay (ELISA) is widely used for the detection of disease biomarkers. However, it utilizes time-consuming procedures and expensive instruments, making it infeasible for point-of-care (POC) analysis especially in resource-limited settings. In this work, a multicolorimetric ELISA biosensor integrated on a paper/polymer hybrid microfluidic device was developed for rapid visual detection of disease biomarkers at point of care, without using costly equipment. This multicolormetric ELISA platform was built on multiple distinct color variants resulted from the catalytic oxidation of 3,3′,5,5′-tetramethylbenzidine (TMB) and the etching of gold nanorods (AuNRs). The vivid color changes could be easily distinguished by the naked eye, and their red mean values allowed quantitative biomarker detection, without using any sophisticated instruments. When this multicolorimetric ELISA was integrated on a paper/polymer hybrid analytical device, it not only provided integrated processing and high portability but also enabled fast assays in about 50 min due to the unique advantages of paper/polymer hybrid devices. The limit of detection of 9.1 ng/μL of the hepatitis C virus core antigen, a biomarker for hepatitis C, was achieved using this multicolorimetric ELISA platform. This multicolor ELISA analytical device provides a new versatile, user-friendly, affordable, and portable immunosensing platform with high potential for on-site detections of various viruses, proteins, and biomarkers for low-resource settings such as at home, public venues, rural areas, and developing nations. [ABSTRACT FROM AUTHOR]

Ovarian cancer has a poor cure rate and rates of relapse are high. Current recurrence detection is limited by non-specific methods such as blood testing and ultrasound. Based on reports that human epididymis four (HE4) / creatinine (CRE) ratios found in urine are elevated in ovarian cancers, we have developed a paper-based device that combines lateral flow technology and cell phone analysis to quantitatively measure HE4/CRE. Surrogate samples were used to test the performance over clinically expected HE4/CRE ratios. For HE4/CRE ratios of 2 to 47, the percent error was found to be 16.0% on average whether measured by a flatbed scanner or cell phone. There was not a significant difference between the results from the cell phone or scanner. Based on published studies, error in this method was less than the difference required to detect recurrence. This promising new tool, with further development, could be used at home or in low-resource settings to provide timely detection of ovarian cancer recurrence. [ABSTRACT FROM AUTHOR]

Urine is commonly used for clinical diagnosis and biomedical research. The discovery of extracellular vesicles (EV) in urine opened a new fast‐growing scientific field. In the last decade urinary extracellular vesicles (uEVs) were shown to mirror molecular processes as well as physiological and pathological conditions in kidney, urothelial and prostate tissue. Therefore, several methods to isolate and characterize uEVs have been developed. However, methodological aspects of EV separation and analysis, including normalization of results, need further optimization and standardization to foster scientific advances in uEV research and a subsequent successful translation into clinical practice. This position paper is written by the Urine Task Force of the Rigor and Standardization Subcommittee of ISEV consisting of nephrologists, urologists, cardiologists and biologists with active experience in uEV research. Our aim is to present the state of the art and identify challenges and gaps in current uEV‐based analyses for clinical applications. Finally, recommendations for improved rigor, reproducibility and interoperability in uEV research are provided in order to facilitate advances in the field. [ABSTRACT FROM AUTHOR]

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

The coronavirus disease 2019 (COVID-19) pandemic has been as unprecedented as unexpected, affecting more than 105 million people worldwide as of 8 February 2020 and causing more than 2.3 million deaths according to the World Health Organization (WHO). Not only affecting the lungs but also provoking acute respiratory distress, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is able to infect multiple cell types including cardiac and vascular cells. Hence a significant proportion of infected patients develop cardiac events, such as arrhythmias and heart failure. Patients with cardiovascular comorbidities are at highest risk of cardiac death. To face the pandemic and limit its burden, health authorities have launched several fast-track calls for research projects aiming to develop rapid strategies to combat the disease, as well as longer-term projects to prepare for the future. Biomarkers have the possibility to aid in clinical decision-making and tailoring healthcare in order to improve patient quality of life. The biomarker potential of circulating RNAs has been recognized in several disease conditions, including cardiovascular disease. RNA biomarkers may be useful in the current COVID-19 situation. The discovery, validation, and marketing of novel biomarkers, including RNA biomarkers, require multi-centre studies by large and interdisciplinary collaborative networks, involving both the academia and the industry. Here, members of the EU-CardioRNA COST Action CA17129 summarize the current knowledge about the strain that COVID-19 places on the cardiovascular system and discuss how RNA biomarkers can aid to limit this burden. They present the benefits and challenges of the discovery of novel RNA biomarkers, the need for networking efforts, and the added value of artificial intelligence to achieve reliable advances. [ABSTRACT FROM AUTHOR]

Elevated serum IgE levels are associated with allergic disorders, parasitosis and specific immunologic abnormalities. In addition, epidemiological and mechanistic evidence indicates an association between IgE-mediated immune surveillance and protection from tumour growth. Intriguingly, recent studies reveal a correlation between IgE deficiency and increased malignancy risk. This is the first review discussing IgE levels and links to pathological conditions, with special focus on the potential clinical significance of ultra-low serum IgE levels and risk of malignancy. In this Position Paper we discuss: (a) the utility of measuring total IgE levels in the management of allergies, parasitosis, and immunodeficiencies, (b) factors that may influence serum IgE levels, (c) IgE as a marker of different disorders, and d) the relationship between ultra-low IgE levels and malignancy susceptibility. While elevated serum IgE is generally associated with allergic/atopic conditions, very low or absent IgE may hamper anti-tumour surveillance, indicating the importance of a balanced IgE-mediated immune function. Ultra-low IgE may prove to be an unexpected biomarker for cancer risk. Nevertheless, given the early stage of investigations conducted mostly in patients with diseases that influence IgE levels, in-depth mechanistic studies and stratification of malignancy risk based on associated demographic, immunological and clinical co-factors are warranted. [ABSTRACT FROM AUTHOR]

Elevated serum IgE levels are associated with allergic disorders, parasitosis and specific immunologic abnormalities. In addition, epidemiological and mechanistic evidence indicates an association between IgE‐mediated immune surveillance and protection from tumour growth. Intriguingly, recent studies reveal a correlation between IgE deficiency and increased malignancy risk. This is the first review discussing IgE levels and links to pathological conditions, with special focus on the potential clinical significance of ultra‐low serum IgE levels and risk of malignancy. In this Position Paper we discuss: (a) the utility of measuring total IgE levels in the management of allergies, parasitosis, and immunodeficiencies, (b) factors that may influence serum IgE levels, (c) IgE as a marker of different disorders, and d) the relationship between ultra‐low IgE levels and malignancy susceptibility. While elevated serum IgE is generally associated with allergic/atopic conditions, very low or absent IgE may hamper anti‐tumour surveillance, indicating the importance of a balanced IgE‐mediated immune function. Ultra‐low IgE may prove to be an unexpected biomarker for cancer risk. Nevertheless, given the early stage of investigations conducted mostly in patients with diseases that influence IgE levels, in‐depth mechanistic studies and stratification of malignancy risk based on associated demographic, immunological and clinical co‐factors are warranted. [ABSTRACT FROM AUTHOR]

With more than 23 million infections and more than 814,000 deaths worldwide, the coronavirus disease-2019 (COVID-19) pandemic is still far from over. Several classes of drugs including antivirals, antiretrovirals, anti-inflammatory, immunomodulatory, and antibiotics have been tried with varying levels of success. Still, there is lack of any specific therapy to deal with this infection. Although less than 30% of these patients require intensive care unit admission, morbidity and mortality in this subgroup of patients remain high. Hence, it becomes imperative to have general principles to guide intensivists managing these patients. However, as the literature emerges, these recommendations may change and hence, frequent updates may be required. [ABSTRACT FROM AUTHOR]

In a resource-limited country like India, rationing of scarce critical care resources might be required to ensure appropriate delivery of care to the critically ill patients suffering from COVID-19 infection. Most of these patients require critical care support because of respiratory failure or presence of multiorgan dysfunction syndrome. As there is no pharmacological therapy available, respiratory support in the form of supplemental oxygen, noninvasive ventilation, and invasive mechanical ventilation remains mainstay of care in intensive care units. As there is still dearth of direct evidence, most of the data are extrapolated from the experience gained from the management of general critical care patients. [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]

Introduction: Alzheimer Disease (AD) is a neurodegenerative disorder characterized by the progressive loss of memory and other cognitive functions. Protein Kinase Cε (PKCε) is an isoform that most effectively suppresses Amyloid Beta (Aβ) production and synaptic loss. Methods: In this study, spatial learning and memory for treated rats were evaluated by the Morris water maze test. The activity (total PKC), mRNA expression, and protein level of PKCε in the platelet and hippocampal tissue were evaluated using immunosorbent assay, real-time qPCR, and western blotting analysis, respectively. Results: The traveled distance was significantly prolonged, and escape latency significantly increased in Aβ-treated groups. PKC activity assay showed that there was a remarkable difference between the Aβ-treated and sham-operated groups on days 10 and 30 in the hippocampus and also day 30 in platelet after the injection of Aβ. A significant effect in PKC activity was observed between days 0 and 10, days 0 and 30, as well as days 5 and 30. Aβ significantly downregulated the PKCε mRNA expression in the hippocampus of rats on day 30; however, no significant difference was observed in platelet. Western blot analysis demonstrated that Aβ significantly reduced PKCε protein expression in the hippocampus of treated groups on day 30. Conclusion: The expression level of PKCε was downregulated following the injection of Aβ in the hippocampus, but no significant difference was observed between the AD and sham groups in platelet that may be due to the low concentration of PKCε or duration of Aβ exposure in the rat brain. [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]

Glucose is the main source of energy for the human brain. This paper presents a non-invasive technique to study metabolic changes caused by glucose in human brain cell lines. In this paper we present the spectroscopic characterization of human normal brain (NHA; astrocytes) and human cancer brain (CRL-1718; astrocytoma and U-87 MG; glioblastoma) control cell lines and cell lines upon supplementation with glucose. Based on Raman techniques we have identified biomarkers that can monitor metabolic changes in lipid droplets, mitochondria and nucleus caused by glucose. We have studied the vibrations at 750 cm−1, 1444 cm−1, 1584 cm−1 and 1656 cm−1 as a function of malignancy grade. We have compared the concentration of cytochrome, lipids and proteins in the grade of cancer aggressiveness in normal and cancer human brain cell lines. Chemometric analysis has shown that control normal, control cancer brain cell lines and normal and cancer cell lines after supplementation with glucose can be distinguished based on their unique vibrational properties. PLSDA (Partial Least Squares Discriminant Analysis) and ANOVA tests have confirmed the main role of cytochromes, proteins and lipids in differentiation of control human brain cells and cells upon supplementation with glucose. We have shown that Raman techniques combined with chemometric analysis provide additional insight to monitor the biology of astrocytes, astrocytoma and glioblastoma after glucose supplementation. [ABSTRACT FROM AUTHOR]

Simple Summary: Achieving improved rates of overall survival remains a significant challenge in advanced-stage ovarian cancer; even if complete debulking is achieved, certain patients report poor results in terms of survival. Therefore, the aim of this paper is to investigate new prognostic markers that could point out which cases could benefit most from debulking surgery and which ones should be rather submitted to neoadjuvant therapies followed by debulking surgery. Background: Despite improving surgical techniques and achieving more often complete debulking procedures, certain patients with advanced-stage ovarian cancer still have a very poor prognosis. The aim of the current paper is to investigate whether inflammatory and nutritional status can predict the long-term outcomes of ovarian cancer patients. Methods: A retrospective analysis of 57 cases diagnosed with advanced-stage ovarian cancer submitted to surgery as first intent therapy was carried out. In all cases, the preoperative status was determined by calculating the CRP/albumin ratio, as well as the Glasgow score, the modified Glasgow score and the prognostic nutritional index. Results: Patients presenting higher values of the CRP/albumin ratio, with a higher Glasgow score, modified Glasgow score and prognostic nutritional index (PNI), were more frequently associated with incomplete debulking surgery, a higher peritoneal carcinomatosis index and poorer overall survival (20 months versus 9 months for the CRP/albumin ratio p = 0.011, 42 versus 27 versus 12 months for the Glasgow score p = 0.042, 50 versus 19 versus 12 months for the modified Glasgow score, p = 0.001, and 54 months versus 21 months, p = 0.011 for the prognostic nutritional index). Conclusions: A strong relationship between the nutritional and inflammatory status in advanced-stage ovarian cancer seems to exist. [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]

Collection of sufficient amounts of chemical residues and metabolites from skin in a non-invasive manner is challenging [1]. The available sampling methods are based on the use of various sampling techniques [2]: macroduct, solvent extraction, tape stripping, oil/membrane approach, implementing absorbing materials such as semipermeable skin patch, alcohol swab, cotton pad, textile, nitrocellulose membrane, or imprinting materials such as silica plate, polydimethylosiloxane film and derivatized silicon. In certain cases, specimen collection is invasive while some materials cause inconvenience due to the time-consuming sampling step. In the past few years, our laboratory developed hydrogel micropatch sampling method, which was successfully combined with mass spectrometry (MS) allowing for detection of skin metabolites [3], disease biomarkers [4], and topical drugs [5]. The previous method took advantage of an atmospheric pressure sample introduction to MS without pre-separation. In fact, such hassle-free interfaces are popular in the MS-related research work [6, 7]. However, eliminating the chromatographic separation step complicates quantitative analysis of complex samples by increasing the risk of isobaric interferences. Another drawback of our previous method was fast drying of the hydrogel (agarose), what put an additional burden on the analyst (preparation of the probes a few hours before sampling skin). In an attempt to address these issues, we have been searching for a better sampling material, and we intended to use it in combination with a hyphenated analytical technique. In principle, one could consider hundreds of synthetic materials (e.g. polymers) as potential sorbents for skin sampling. While a major limitation of implementing new synthetic materials in clinical applications is their biocompatibility [8], various commercially available skin-care products can potentially be used to collect molecules present on the surface of skin for chemical analysis. In this study, we show that oil-control blotting paper can lift chemical species originating from a topical agent from skin in the quantities sufficient for subsequent analysis by gas chromatography (GC) coupled with MS (Fig. 1A). Due to the great popularity of plant-based insect repellents [9], we exemplify the use of the proposed protocol by investigating retention of such a repellent on the surface of skin. The knowledge of the retention kinetics of the related topical agents on the skin can be useful for the development of more effective formulations with long retention times, and--in consequence--for more efficient protection against infectious diseases spread by insect vectors. [ABSTRACT FROM AUTHOR]

This paper shows that stacked sheets of paper preincubated with different biological reagents and skiving them into uniform test paper sheets allow mass manufacturing of multiplexed immunoassay devices and simultaneous detection of multiplex targets that can be read out by a barcode scanner. The thickness of one sheet of paper can form the width of a module for the barcode; when stacked, these sheets of paper can form a series of barcodes representing the targets, depending on the color contrast provided by a colored precipitate of an immunoassay. The uniform thickness of sheets of paper allows high-quality signal readout. The manufacturing method allows highly efficient fabrication of the materials and substrates for a straightforward assay of targets that range from drugs of abuse to biomarkers of blood-transmitted infections. In addition, as a novel alternative to the conventional point-of-care testing method, the paper-based barcode assay system can provide highly efficient, accurate, and objective diagnoses. [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]

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]

2,6-pyridine dicarboxylic acid (DPA) is an exceptional biomarker of notorious anthrax spores. Therefore, the rapid, sensitive, and selective quantitative detection of DPA is extremely significant and urgent. This paper reports a Zn(II) metal–organic framework with the formula of {[Zn6(NDA)6(DPBT)3] 2H2O·3DMF}n (MOF-1), which consists of 2,6-naphthalenedicarboxylic acid (2,6-NDA), 4,7-di(4-pyridyl)-2,1,3-benzothiadiazole (DPBT), and Zn(II) ions. Structural analysis indicated that MOF-1 is a three-dimensional (3D) network which crystallized in the monoclinic system with the C2/c space group, revealing high pH, solvent, and thermal stability. Luminescence sensing studies demonstrated that MOF-1 had the potential to be a highly selective, sensitive, and recyclable fluorescence sensor for the identification of DPA. Furthermore, fluorescent test paper was made to detect DPA promptly with color changes. The enhancement mechanism was established by the hydrogen-bonding interaction and photoinduced electron transfer transition between MOF-1 and DPA molecules. [ABSTRACT FROM AUTHOR]

Introduction: Personalised prevention aims to delay or avoid disease occurrence, progression, and recurrence of disease through the adoption of targeted interventions that consider the individual biological, including genetic data, environmental and behavioural characteristics, as well as the socio-cultural context. This protocol summarises the main features of a rapid scoping review to show the research landscape on biomarkers or a combination of biomarkers that may help to better identify subgroups of individuals with different risks of developing specific diseases in which specific preventive strategies could have an impact on clinical outcomes. This review is part of the "Personalised Prevention Roadmap for the future HEalThcare" (PROPHET) project, which seeks to highlight the gaps in current personalised preventive approaches, in order to develop a Strategic Research and Innovation Agenda for the European Union. Objective: To systematically map and review the evidence of biomarkers that are available or under development in cancer, cardiovascular and neurodegenerative diseases that are or can be used for personalised prevention in the general population, in clinical or public health settings. Methods: Three rapid scoping reviews are being conducted in parallel (February–June 2023), based on a common framework with some adjustments to suit each specific condition (cancer, cardiovascular or neurodegenerative diseases). Medline and Embase will be searched to identify publications between 2020 and 2023. To shorten the time frames, 10% of the papers will undergo screening by two reviewers and only English-language papers will be considered. The following information will be extracted by two reviewers from all the publications selected for inclusion: source type, citation details, country, inclusion/exclusion criteria (population, concept, context, type of evidence source), study methods, and key findings relevant to the review question/s. The selection criteria and the extraction sheet will be pre-tested. Relevant biomarkers for risk prediction and stratification will be recorded. Results will be presented graphically using an evidence map. Inclusion criteria: Population: general adult populations or adults from specific pre-defined high-risk subgroups; concept: all studies focusing on molecular, cellular, physiological, or imaging biomarkers used for individualised primary or secondary prevention of the diseases of interest; context: clinical or public health settings. Systematic review registration: https://doi.org/10.17605/OSF.IO/7JRWD (OSF registration DOI). [ABSTRACT FROM AUTHOR]

Intermediate filaments are one of three polymeric structures that form the cytoskeleton of epithelial cells. In the epithelium, these filaments are made up of a variety of keratin proteins. Intermediate filaments complete a wide range of functions in keratinocytes, including maintaining cell structure, cell growth, cell proliferation, cell migration, and more. Given that these functions are intimately associated with the carcinogenic process, and that hyperkeratinization is a quintessential feature of oral leukoplakias, the utility of keratins in oral leukoplakia is yet to be fully explored. This scoping review aims to outline the current knowledge founded on original studies on human tissues regarding the expression and utility of keratins as diagnostic, prognostic, and predictive biomarkers in oral leukoplakias. After using a search strategy developed for several scientific databases, namely, PubMed, Scopus, Web of Science, and OVID, 42 papers met the inclusion and exclusion criteria. One more article was added when it was identified through manually searching the list of references. The included papers were published between 1989 and 2024. Keratins 1–20 were investigated in the 43 included studies, and their expression was assessed in oral leukoplakia and dysplasia cases. Only five studies investigated the prognostic role of keratins in relation to malignant transformation. No studies evaluated keratins as a diagnostic adjunct or predictive tool. Evidence supports the idea that dysplasia disrupts the terminal differentiation pathway of primary keratins. Gain of keratin 17 expression and loss of keratin 13 were significantly observed in differentiated epithelial dysplasia. Also, the keratin 19 extension into suprabasal cells has been associated with the evolving features of dysplasia. The loss of keratin1/keratin 10 has been significantly associated with high-grade dysplasia. The prognostic value of cytokeratins has shown conflicting results, and further studies are required to ascertain their role in predicting the malignant transformation of oral leukoplakia. [ABSTRACT FROM AUTHOR]

Simple Summary: Immune checkpoint inhibitors have revolutionized cancer therapy and improved clinical outcomes. Immunotherapy is now increasingly combined with chemotherapy and other conventional treatments, such as radiation therapy, as part of the multimodal treatment of earlier-stage cancers. Although generally well tolerated and capable of inducing long-lasting responses, immunotherapy for thymic epithelial tumors can be challenging due to defects in immune self-tolerance, which increase the risk of immune-mediated toxicity. In order to improve the safety of immunotherapy and maximize clinical benefit in patients with thymic cancers, there is a pressing need to identify potential biomarkers of response and toxicity for this patient population. In this paper, we review the current role of immunotherapy for thymic cancers and discuss future applications across the spectrum of stage and histology of these diseases. Thymic epithelial tumors are a histologically diverse group of cancers arising from the epithelial compartment of the thymus. These tumors are characterized by a low tumor mutation burden, a lack of actionable genomic changes, and, especially with thymomas, defects in immune tolerance. Surgery is the mainstay of the management of resectable disease, whereas advanced, unresectable tumors are treated with platinum-based chemotherapy. Disease recurrence can occur months to years after frontline treatment. Although several options are available for conventional treatment of recurrent thymic tumors, response rates are generally low, and treatment-related toxicity can affect quality of life. A subset of patients benefit from biologic therapies, but there remains an unmet need for the development of new treatments. Immune checkpoint inhibitors are safe, clinically active, and have contributed to an improvement in survival for patients with a wide variety of cancers. However, the application of these revolutionary treatments for thymic cancers is limited to their use for the management of recurrent thymic carcinoma because of the risk of immune toxicity. In this paper, we review the current uses of immunotherapy for the management of thymic epithelial tumors and highlight potential strategies to improve safety and broaden the application of these treatments for patients with thymic cancers. [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]

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]

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]

Background: Adiponectin is an adipocyte-derived hormone that acts as a marker of insulin sensitivity. Bloodspot sampling by fingerstick onto filter paper may increase the feasibility of large-scale studies of the determinants of insulin sensitivity. We first describe the validation of an enzyme-linked immunoassay (ELISA) for quantifying adiponectin from dried blood spots and then demonstrate its application in a large trial (PROBIT). Methods: We quantified adiponectin from 3-mm diameter discs (≈3 µL of blood) punched from dried blood spots obtained from: i) whole blood standards (validation); and ii) PROBIT trial samples (application) in which paediatricians collected blood spots from 13,879 children aged 11.5 years from 31 sites across Belarus. We examined the distribution of bloodspot adiponectin by demographic and anthropometric factors, fasting insulin and glucose. Results: In the validation study, mean intra-assay coefficients of variation (n = 162) were 15%, 13% and 10% for ‘low’ (6.78 µg/ml), ‘medium’ (18.18 µg/ml) and 'high’ (33.13 µg/ml) internal quality control (IQC) samples, respectively; the respective inter-assay values (n = 40) were 23%, 21% and 14%. The correlation coefficient between 50 paired whole bloodspot versus plasma samples, collected simultaneously, was 0.87 (95% CI: 0.78 to 0.93). Recovery of known quantities of adiponectin (between 4.5 to 36 µg/ml) was 100.3–133%. Bloodspot adiponectin was stable for at least 30 months at −80°C. In PROBIT, we successfully quantified fasting adiponectin from dried blood spots in 13,329 of 13,879 (96%) children. Mean adiponectin (standard deviation) concentrations were 17.34 µg/ml (7.54) in boys and 18.41 µg/ml (7.92) in girls and were inversely associated with body mass index, fat mass, triceps and subscapular skin-fold thickness, waist circumference, height and fasting glucose. Conclusions: Bloodspot ELISA is suitable for measuring adiponectin in very small volumes of blood collected on filter paper and can be applied to large-scale studies. [ABSTRACT FROM AUTHOR]

This paper presents a portable paper-based microfluidic platform for multiplexed electrochemical detection of antibody markers of human immunodeficiency virus (HIV) and hepatitis C virus (HCV) in serum samples. To our best knowledge, this is the first paper-based electrochemical immunosensing platform, with multiplexing and telemedicine capabilities, for diagnosing HIV/HCV co-infection. The platform consists of an electrochemical microfluidic paper-based immunosensor array (E-μPIA) and a handheld multi-channel potentiostat, and is capable of performing enzyme-linked immunosorbent assays simultaneously on eight samples within 20 min (using a prepared E-μPIA). The multiplexing feature of the platform allows it to produce multiple measurement data for HIV and HCV markers from a single run, and its wireless communication module can transmit the results to a remote site for telemedicine. The unique integration of paper-based microfluidics and mobile instrumentation renders our platform portable, low-cost, user-friendly, and high-throughput. [ABSTRACT FROM AUTHOR]

Simple Summary: Proteomics can be very useful in identifying proteins, which helps find potential markers for diseases. Managing endometrial cancer can be difficult and finding reliable markers can contribute to an early diagnosis, to manage its evolution, and even predict the response to treatment. This paper reviews the current research on the proteins involved in endometrial cancer. Most studies used tissue, serum, and plasma samples and found potential diagnostic and prognostic markers. Eight studies were examined closely, with three showing strong similarities, sharing forty-five proteins. This review also identified the 10 most commonly reported proteins in these studies. While proteomics shows promise in finding diagnostic and prognostic markers for endometrial cancer, there is still a need for more research on new therapeutic targets. Proteomics can be a robust tool in protein identification and regulation, allowing the discovery of potential biomarkers. In clinical practice, the management of endometrial cancer can be challenging. Thus, identifying promising markers could be beneficial, helping both in diagnosis and prognostic stratification, even predicting the response to therapy. Therefore, this manuscript systematically reviews the existing evidence of the proteomic profile of human endometrial cancer. The literature search was conducted via Medline (through PubMed) and the Web of Science. The inclusion criteria were clinical, in vitro, and in vivo original studies reporting proteomic analysis using all types of samples to map the human endometrial cancer proteome. A total of 55 publications were included in this review. Most of the articles carried out a proteomic analysis on endometrial tissue, serum and plasma samples, which enabled the identification of several potential diagnostic and prognostic biomarkers. In addition, eight articles were analyzed regarding the identified proteins, where three studies showed a strong correlation, sharing forty-five proteins. This analysis also allowed the identification of the 10 most frequently reported proteins in these studies: EGFR, PGRMC1, CSE1L, MYDGF, STMN1, CASP3 ANXA2, YBX1, ANXA1, and MYH11. Proteomics-based approaches pointed out potential diagnostic and prognostic candidates for endometrial cancer. However, there is a lack of studies exploring novel therapeutic targets. [ABSTRACT FROM AUTHOR]

Simple Summary: This review outlines the use of metabolomics to detect biomarkers for bovine mastitis, offering insights into disease prediction and early diagnosis. It details the use of various biological samples for metabolomic analysis, including milk, blood, urine, rumen fluid, feces, and mammary tissue. Bovine mastitis is an inflammatory disease of the mammary glands, and its pathogenesis and diagnosis are complicated. Through qualitative and quantitative analysis of small-molecule metabolites, the metabolomics technique plays an important role in finding biomarkers and studying the metabolic mechanism of bovine mastitis. Therefore, this paper reviews the predictive and diagnostic biomarkers of bovine mastitis that have been identified using metabolomics techniques and that are present in samples such as milk, blood, urine, rumen fluid, feces, and mammary tissue. In addition, the metabolic pathways of mastitis-related biomarkers in milk and blood were analyzed; it was found that the tricarboxylic acid (TCA) cycle was the most significant (FDR = 0.0015767) pathway in milk fluid, and glyoxylate and dicarboxylate metabolism was the most significant (FDR = 0.0081994) pathway in blood. The purpose of this review is to provide useful information for the prediction and early diagnosis of bovine mastitis. [ABSTRACT FROM AUTHOR]

Type 2 diabetes mellitus (T2DM) is one of the most common metabolic diseases in the world and poses a significant public health challenge. Early detection and management of this metabolic disorder is crucial to prevent complications and improve outcomes. This paper aims to find core differences in male and female markers to detect T2DM by their clinic and anthropometric features, seeking out ranges in potential biomarkers identified to provide useful information as a pre-diagnostic tool whie excluding glucose-related biomarkers using machine learning (ML) models. We used a dataset containing clinical and anthropometric variables from patients diagnosed with T2DM and patients without TD2M as control. We applied feature selection with three different techniques to identify relevant biomarker models: an improved recursive feature elimination (RFE) evaluating each set from all the features to one feature with the Akaike information criterion (AIC) to find optimal outputs; Least Absolute Shrinkage and Selection Operator (LASSO) with glmnet; and Genetic Algorithms (GA) with GALGO and forward selection (FS) applied to GALGO output. We then used these for comparison with the AIC to measure the performance of each technique and collect the optimal set of global features. Then, an implementation and comparison of five different ML models was carried out to identify the most accurate and interpretable one, considering the following models: logistic regression (LR), artificial neural network (ANN), support vector machine (SVM), k-nearest neighbors (KNN), and nearest centroid (Nearcent). The models were then combined in an ensemble to provide a more robust approximation. The results showed that potential biomarkers such as systolic blood pressure (SBP) and triglycerides are together significantly associated with T2DM. This approach also identified triglycerides, cholesterol, and diastolic blood pressure as biomarkers with differences between male and female actors that have not been previously reported in the literature. The most accurate ML model was selection with RFE and random forest (RF) as the estimator improved with the AIC, which achieved an accuracy of 0.8820. In conclusion, this study demonstrates the potential of ML models in identifying potential biomarkers for early detection of T2DM, excluding glucose-related biomarkers as well as differences between male and female anthropometric and clinic profiles. These findings may help to improve early detection and management of the T2DM by accounting for differences between male and female subjects in terms of anthropometric and clinic profiles, potentially reducing healthcare costs and improving personalized patient attention. Further research is needed to validate these potential biomarkers ranges in other populations and clinical settings. [ABSTRACT FROM AUTHOR]

Reproductive management significantly impacts dairy farm productivity, necessitating accurate timely pregnancy detection in cattle. This paper presents a novel handheld and portable fluorescence imaging system designed for quantitative assessment of pregnancy-specific biomarkers, addressing the limitations of current detection methods. The objective was to develop a cost-effective, at-farm solution for detecting pregnancy-specific protein B (PSPB) in bovine plasma samples. The system integrates an imaging module and a custom software application, enabling image capture, data processing, and PSPB concentration determination. Calibration utilizing known PSPB concentrations achieved a 0.6 ng/mL limit of detection. Validation encompassed a comparison with a standard ELISA method using 100 bovine plasma samples; minimal bias and good agreement were observed within the linear range of the calibration curve for both methods. The system offers portability, user-friendliness, and potential for multiplex detection, promising real-time, at-farm reproductive management. This study demonstrates the successful development and validation of a portable fluorescence imaging system, offering an efficient and accurate approach to detecting pregnancy-specific biomarkers in cattle. Its implications extend to improving dairy farm productivity by enabling timely and reliable reproductive management practices. [ABSTRACT FROM AUTHOR]

Non-invasive continuous health monitoring has become feasible with the advancement of biosensors. While monitoring certain biomarkers such as heart rate or skin temperature are now at a certain maturity, monitoring molecular biomarkers is still challenging. Progress has been shown in sampling, measurement, and interpretation of data toward non-invasive molecular sensors that can be integrated into daily wearable items. Toward this goal, this paper explores the potential of embroidered interdigitated transducer (IDT)-based sensors for non-invasive, continuous monitoring of human biomarkers, particularly glucose levels, in human sweat. The study employs innovative embroidery techniques to create flexible fabric-based sensors with gold-coated IDTs. In controlled experiments, we have shown the variation of glucose concentration in water can be wirelessly detected by tracking the resonant frequency of the embroidered sensors. The current sensors operate at 1.8 GHz to 2 GHz and respond to the change in glucose concentration with a sensitivity of 0.17 MHz/(mg/dL). The embroidered IDT-based sensors with wireless sensing will be a new measurement modality for molecular wearable sensors. The establishment of a wireless sensing mechanism for embroidered IDT-based sensors will be followed by an investigation of sweat for molecular detection. This will require adding functionalities for sampling and interpretation of acquired data. We envisage the embroidered IDT-based sensors offer a unique approach for seamless integration into clothing, paving the way for personalised, continuous health data capture. [ABSTRACT FROM AUTHOR]

Background: Small RNA molecules known as microRNAs (miRNAs) regulate gene expression during the post-translational steps. miRNAs are essential for many physiological processes, such as cell division, growth, and proliferation, as well as development and metabolism. Aims: To review the developments in investigations on miR-155 and miR-146a as possible biomarkers for multiple sclerosis (MS) disease diagnosis and prognosis. Methods: A comprehensive analysis of the available literature was carried out by searching databases including PubMed, Scopus, and Web of Science for papers published between 2011 and 2023 years. Only original articles written in the English language were considered for inclusion in this review. Results: A total of 29 studies were initially identified, with 14 meeting the inclusion criteria. Conclusion: The present study underscores the crucial role of microRNAs, particularly miR-155 and miR-146a, in the etiology and progression of multiple sclerosis (MS). Through an extensive analysis of the literature, we have found compelling evidence linking aberrations in the expression and function of these microRNAs to MS pathogenesis. Specifically, our synthesis suggests that miR-155 and miR-146a hold promise as valuable biomarkers for both the diagnosis and prognosis of MS. Despite the challenges posed by the heterogeneity of MS subtypes, the non-invasive accessibility of miRNAs in various bodily fluids, including serum, peripheral blood, cerebrospinal fluid, and extracellular vesicles, presents a promising avenue for the development of robust diagnostic and prognostic tools. By elucidating the intricate roles of miR-155 and miR-146a in MS, our findings contribute to advancing our understanding of the disease mechanisms and pave the way for the development of more effective diagnostic and therapeutic strategies. [ABSTRACT FROM AUTHOR]

Introduction: Osteoarthritis (OA) is a common degenerative disorder of the synovial joints and is usually an age-related disease that occurs due to continuous wear and tear of the cartilage in the joints. Presently, there is no proven medical management to halt the progression of the disease in the early stages. The purpose of our systematic review is to analyze the possible metabolites and metabolic pathways that are specifically involved in OA pathogenesis and early treatment of the disease. Materials and Methods: The articles were collected from PubMed, Cochrane, Google Scholar, Embase, and Scopus databases. "Knee", "Osteoarthritis", "Proteomics", "Lipidomics", "Metabolomics", "Metabolic Methods", and metabolic* were employed for finding the articles. Only original articles with human or animal OA models with healthy controls were included. Results: From the initial screening, a total of 458 articles were identified from the 5 research databases. From these, 297 articles were selected in the end for screening, of which 53 papers were selected for full-text screening. Finally, 50 articles were taken for the review based on body fluid: 6 urine studies, 15 plasma studies, 16 synovial fluid studies, 11 serum studies, 4 joint tissue studies, and 1 fecal study. Many metabolites were found to be elevated in OA. Some of these metabolites can be used to stage the OA Three pathways that were found to be commonly involved are the TCA cycle, the glycolytic pathway, and the lipid metabolism. Conclusion: All these studies showed a vast array of metabolites and metabolic pathways associated with OA. Metabolites like lysophospholipids, phospholipids, arginine, BCCA, and histidine were identified as potential biomarkers of OA but a definite association was not identified, Three pathways (glycolytic pathway, TCA cycle, and lipid metabolic pathways) have been found as highly significant in OA pathogenesis. These metabolic pathways could provide novel therapeutic targets for the prevention and progression of the disease. [ABSTRACT FROM AUTHOR]

Understanding the origins of potential source rocks and unraveling the intricate connections between reservoir oils and their source formations in the Siwa Basin (Western Desert, Egypt) necessitate a thorough oil-source correlation investigation. This objective is achieved through a meticulous analysis of well-log responses, Rock-Eval pyrolysis, and biomarker data. The analysis of Total Organic Carbon across 31 samples representing Paleozoic formations in the Siwa A-1X well reveals a spectrum of organic richness ranging from 0.17 wt% to 2.04 wt%, thereby highlighting diverse levels of organic content and the presence of both Type II and Type III kerogen. Examination of the fingerprint characteristics of eight samples from the well suggests that the Dhiffah Formation comprises a blend of terrestrial and marine organic matter. Notably, a significant contribution from more oxidized residual organic matter and gasprone Type III kerogen is observed. Contrarily, the Desouky and Zeitoun formations exhibit mixed organic matter indicative of a transitional environment, and thus featuring a pronounced marine influence within a more reducing setting, which is associated with Type II kerogen. Through analysis of five oil samples from different wellsdSIWA L-1X, SIWA R-3X, SIWA D-1X, PTAH 5X, and PTAH 6X, it is evident that terrestrial organic matter, augmented by considerable marine input, was deposited in an oxidizing environment, and contains Type III kerogen. Geochemical scrutiny confirms the coexistence of mixed terrestrial organic matter within varying redox environments. Noteworthy is the uniformity of identified kerogen Types II and III across all samples, known to have potential for hydrocarbon generation. The discovery presented in this paper unveils captivating prospects concerning the genesis of oil in the Jurassic Safa reservoir, suggesting potential links to Paleozoic sources or even originating from the Safa Member itself. These revelations mark a substantial advancement in understanding source rock dynamics and their intricate relationship with reservoir oils within the Siwa Basin. By illuminating the processes of hydrocarbon genesis in the region, this study significantly enriches our knowledge base. [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]

Simple Summary: This research studied how three types of proteins, called interleukins (namely 8, 17A and 33), are present in the blood of healthy people and people with colon cancer. Colon cancer is a disease that affects the large intestine. The paper looked at 82 people, 42 of whom had colon cancer and 40 of whom did not. The researchers divided the cancer patients into four groups based on how severe their cancer was. The study measured the amount of interleukins in the blood of each person using a special test. The paper analyzed the results of the test, considering the age, gender, and cancer stage of each person. The results showed that younger people, and those with less severe cancer had more interleukins in their blood. The paper also found that two of the interleukins (8 and 17A) were higher in the cancer group, while one of them (33) was higher in the healthy group. The study also found that the interleukins were related to each other in both groups. This research concluded that the interleukins might help detect colon cancer and predict how it will progress. This paper could help improve the diagnosis and treatment of colon cancer. This research investigated the serum levels of three interleukins (IL8, IL17A, and IL33) and the possible relationships between them in healthy people and colon cancer patients at different stages. This study involved 82 participants, 42 of whom had colon cancer and 40 were healthy individuals. The cancer patients were classified into four groups according to the TNM staging classification of colon and rectal cancer. Serum levels of the interleukins were measured by the ELISA test. The data were analyzed statistically to compare the demographic characteristics, the interleukin levels across cancer stages, and the correlation between interleukins in both groups. The results showed that women had more early-stage colon cancer diagnoses, while men had more advanced-stage cancer diagnoses. Stage two colon cancer was more common in older people. Younger people, men, and those with early-stage colon cancer had higher levels of interleukins. The levels of IL8 and IL17A were higher in the cancer group, while the level of IL33 was higher in the healthy group. There was a strong correlation between IL8 and IL17A levels in both groups (p = 0.001). IL17A influenced the level of IL33 in the cancer group (p = 0.007). This study suggested that cytokine variation profiles could be useful for detecting colon cancer and predicting its outcome. [ABSTRACT FROM AUTHOR]

Colorectal cancer (CRC) is one of the most aggressive, heterogenous, and fatal types of human cancer for which screening, and more effective therapeutic drugs are urgently needed. Early-stage detection and treatment greatly improve the 5-year survival rate. In the era of targeted therapies for all types of cancer, a complete metabolomic profile is mandatory before neoadjuvant therapy to assign the correct drugs and check the response to the treatment given. The aim of this study is to discover specific metabolic biomarkers or a sequence of metabolomic indicators that possess precise diagnostic capabilities in predicting the efficacy of neoadjuvant therapy. After searching the keywords, a total of 108 articles were identified during a timeframe of 10 years (2013–2023). Within this set, one article was excluded due to the use of non-English language. Six scientific papers were qualified for this investigation after eliminating all duplicates, publications not referring to the subject matter, open access restriction papers, and those not applicable to humans. Biomolecular analysis found a correlation between metabolomic analysis of colorectal cancer samples and poor progression-free survival rates. Biomarkers are instrumental in predicting a patient's response to specific treatments, guiding the selection of targeted therapies, and indicating resistance to certain drugs. [ABSTRACT FROM AUTHOR]

Simple Summary: Ovarian cancer is still one of the deadliest malignancies affecting women worldwide which is associated with poor long-term outcomes even in certain cases in which complete debulking is achieved. In this respect, attention has been focused on identifying other prognostic factors which might indicate which cases are expected to have the best long-term outcomes such as the procoagulant or inflammatory status. The aim of the current paper is to analyse the correlation between the most frequently cited inflammatory and tumoral markers and the long-term outcomes of ovarian cancer patients. Ovarian cancer remains one of the most lethal gynaecological malignancies affecting women worldwide; therefore, attention has been focused on identifying new prognostic factors which might help the clinician to select cases who could benefit most from surgery versus cases in which neoadjuvant systemic therapy followed by interval debulking surgery should be performed. The aim of the current paper is to identify whether preoperative inflammation could serve as a prognostic factor for advanced-stage ovarian cancer. Material and methods: The data of 57 patients who underwent to surgery for advanced-stage ovarian cancer between 2014 and 2020 at the Cantacuzino Clinical Hospital were retrospectively reviewed. The receiver operating characteristic curve was used to determine the optimal cut-off value of different inflammatory markers for the overall survival analysis. The analysed parameters were the preoperative level of CA125, monocyte-to-lymphocyte ratio (MLR), platelet-to-lymphocyte ratio (PLR), neutrophil-to-lymphocyte ratio (NLR) and systemic inflammation index (SII). Results: Baseline CA125 > 780 µ/mL, NLR ≥ 2.7, MLR > 0.25, PLR > 200 and a systemic immune inflammation index (SII, defined as platelet × neutrophil–lymphocyte ratio) ≥ 84,1000 were associated with significantly worse disease-free and overall survival in a univariate analysis. In a multivariate analysis, MLR and SII were significantly associated with higher values of overall survival (p < 0.0001 and p = 0.0124); meanwhile, preoperative values of CA125, PLR and MLR were not associated with the overall survival values (p = 0.5612, p = 0.6137 and p = 0.1982, respectively). In conclusion, patients presenting higher levels of MLR and SII preoperatively are expected to have a poorer outcome even if complete debulking surgery is performed and should be instead considered candidates for neoadjuvant systemic therapy followed by interval surgery. [ABSTRACT FROM AUTHOR]