Validation Study Research Articles

A Proteomics Pipeline for Generating Clinical Grade Biomarker Candidates from Data-Independent Acquisition Mass Spectrometry (DIA-MS) Discovery.

Clinical biomarker development has been stymied by inaccurate protein quantification from mass spectrometry (MS) discovery data and a prolonged validation process. To mitigate these issues, we created the Targeted Extraction Assessment of Quantification (TEAQ) software package that uses data-independent acquisition analysis from a discovery cohort to select precursors, peptides, and proteins that adhere to analytical criteria required for established targeted assays. TEAQ was applied to DIA-MS data from plasma samples acquired on a new high resolution accurate mass (HRAM) mass spectrometry platform where precursors were evaluated for linearity, specificity, repeatability, reproducibility, and intra-protein correlation based on 8- or 11-point loading curves at three throughputs. This data can be used as a general resource for developing other targeted assays. TEAQ analysis of data from a case and control cohort for inflammatory bowel disease (n=492) identified 1110 signature peptides for 326 quantifiable proteins from the 1179 identified proteins. Applying TEAQ analysis to discovery data will streamline targeted assay development and the transition to validation and clinical studies.

A Proteomics Pipeline for Generating Clinical Grade Biomarker Candidates from Data‐Independent Acquisition Mass Spectrometry (DIA‐MS) Discovery

Clinical biomarker development has been stymied by inaccurate protein quantification from mass spectrometry (MS) discovery data and a prolonged validation process. To mitigate these issues, we created the Targeted Extraction Assessment of Quantification (TEAQ) software package that uses data‐independent acquisition analysis from a discovery cohort to select precursors, peptides, and proteins that adhere to analytical criteria required for established targeted assays. TEAQ was applied to DIA‐MS data from plasma samples acquired on a new high resolution accurate mass (HRAM) mass spectrometry platform where precursors were evaluated for linearity, specificity, repeatability, reproducibility, and intra‐protein correlation based on 8‐ or 11‐point loading curves at three throughputs. This data can be used as a general resource for developing other targeted assays. TEAQ analysis of data from a case and control cohort for inflammatory bowel disease (n=492) identified 1110 signature peptides for 326 quantifiable proteins from the 1179 identified proteins. Applying TEAQ analysis to discovery data will streamline targeted assay development and the transition to validation and clinical studies.

A virtue-based measurement of leadership education: The LID questionnaire

This article presents the validation of a virtue-based leadership development questionnaire (LID). Leadership is defined as the human action of guiding others toward a common good, which requires the exercise of personal competencies and virtues. The theoretical and factorial structure of LID has three domains: intellectual, relational and performative. The LID was administered to a sample of 1759 university students from Mexico and Spain for factor analysis. Subsequently, it was applied to a sample of 1906 students from a Mexican university for confirmatory factor analysis and to 171 Mexican students for a convergent validity study with the Socially Responsible Leadership Scale (SRLS). Psychometric analyses indicate that the questionnaire is reliable and valid. Confirmatory factor analysis indicates that the questionnaire fits the theoretical model and has convergent validity with the SRLS. This questionnaire aims to contribute to the leadership education of university students.

Turkish adaptation of the fear of cancer scale: validity, measurement invariance and reliability study.

The aim of this study was to evaluate the Turkish cultural and psychometric properties of the cancer fear scale developed by Feng et al. This methodological study was conducted between January and April 2024 with students from a university in eastern Turkey. Data were collected from two different sample groups (sample 1:350, sample 2:245). Personal information form and cancer fear scale were used. In the adaptation process of the scale, language validity, content validity, construct validity, and reliability were examined. Exploratory factor analysis, confirmatory factor analysis, measurement invariance and convergent-divergent validity were used to determine construct validity. Cronbach alpha internal consistency coefficient, test-retest and corrected item-total correlation were used for reliability. According to the results of exploratory factor analysis, it was determined that the fear of cancer scale had a two-factor structure with factor loadings between 0.58 and 0.70. As a result of the confirmatory factor analysis performed on the two-factor structure of the fear of cancer scale, it was determined that the model goodness-of-fit indices were acceptable and had an excellent fit. It has been determined that measurement invariance findings across genders support configural, metric and scalar invariance. The Cronbach alpha internal consistency coefficient of the fear of cancer scale was 0.93, and the corrected item total correlation values were between 0.45 and 0.73. The Turkish version of the fear of cancer scale was found to be a valid and reliable measurement tool.

Lactobacillus reuteri or Lactobacillus rhamnosus GG intervention facilitates gut barrier function, decreases corticosterone and ameliorates social behavior in LPS-exposed offspring

Probiotic therapy with Lactobacillus reuteri and Lactobacillus rhamnosus (LGG) demonstrates potential as an adjunctive treatment for autism spectrum disorder (ASD). In a rat model of ASD induced by lipopolysaccharide (LPS) injection during pregnancy, we evaluated the effects of these probiotics on offspring. Administration of L. reuteri or LGG for three weeks post-birth improved social deficits and reduced anxiety in LPS-exposed rats. Additionally, probiotics significantly modified short-chain fatty acid profiles, increasing butyric acid levels and decreasing propionic acid levels. They also enhanced colonic barrier integrity by upregulating tight junction proteins, including ZO-1, Occludin, and Claudin4. RNA sequencing identified differential gene expression in pathways related to inflammation, the HPA axis, and reactive oxygen species metabolism, with NADPH oxidase 1 (NOX1) emerging as a crucial gene. Validation studies confirmed that Lactobacillus strains reduced inflammatory cytokines, inhibited corticosterone secretion, increased antioxidant levels, and suppressed the NF-κB/NOX1 pathway. In an H2O2-induced oxidative stress model using Caco-2 cells, pre-treatment with L. reuteri, LGG, or NF-κB inhibitors enhanced cellular antioxidants, inhibited NF-κB/NOX1 activation, and improved barrier function. Overall, L. reuteri and LGG administration improved social behavior, bolstered colonic barrier function, and mitigated HPA axis overactivation in LPS-exposed rats, while also alleviating oxidative stress in the colon and Caco-2 cells. These findings suggest that L. reuteri and LGG have substantial clinical potential for ASD treatment by targeting multiple pathophysiological mechanisms, including inflammation, HPA axis dysregulation, and oxidative stress, thereby presenting a promising adjunctive therapeutic strategy for enhancing social behavior and gut health in ASD.

The use of a novel toe-thumb pressure index for assessing arterial status in the lower limb. A reliability and validity study.

This study explored the reliability, validity and perceived comfort of a novel thumb pressure measure and calculation of a toe-thumb index to identify their suitability as an adjunct or alternatives to ankle-brachial and toe-brachial indices. Repeated manual thumb and toe systolic blood pressures were conducted using two raters, over two time points, on 34 healthy participants. Concurrent automated toe, thumb and brachial systolic blood pressures as well as comfort ratings for these measures (using a 10mm visual analogue scale) were captured once by a research assistant. Automated thumb and brachial measures showed fair correlation (ρ=0.36, p=0.03) and a toe-thumb index and toe-brachial index good correlation (ρ=0.62, p<0.01). Intraclass correlation coefficients (ICC) identified moderate intra-rater reliability for manual thumb pressures for Rater 1 and 2 (ICC 0.57, 95% CI [0.14, 0.79] and ICC 0.74, 95% CI [0.49, 0.87], respectively), while inter-rater reliability was poor (ICC=0.16, 95% CI [-0.85, 0.47]). Concurrent validity comparing manual and automated measures for thumb pressure was also poor (ICC -0.05, 95% CI [-1.06, 0.72] and ICC 0.42, 95% CI [-0.16, 0.72] Rater 1 and 2 respectively). Thumb measures were significantly more comfortable than brachial measures (5mm, p<0.00). Thumb systolic pressures are correlated with brachial systolic pressures, with reasonable intra-rater reliability, however, correlation is only fair and measurement error wider than clinically acceptable. Furthermore, manual measures are poorly correlated with automated units. Consequently, caution is required in applying these techniques. As thumb measures were perceived as significantly more comfortable than brachial measures and have an advantage where brachial pressures cannot, or should not, be obtained, further evaluation is warranted.

Hippocampal recording with a soft microelectrode array in a cranial window imaging scheme: a validation study

The hippocampus has a crucial role in the formation, consolidation and recall of memories as well as in navigation related processes. These functions are in the focus of neuroscience and different disciplines have contributed to this research field for decades. Two-photon imaging in awake animals is a valuable new aspect for these observations, especially when it is supported by electrophysiology. In this study, we applied high speed two-photon hippocampal imaging through a chronically implanted, soft, transparent microelectrode (STM) device incorporated into a cranial window chamber in awake mice. We monitored the impedance of the recording sites over the course of the experiments to observe long-term changes in recording quality. The large-scale ipsilateral local field potential (LFP) recordings from the dorsal hippocampus provided reliable sharp wave-ripples (SPW-Rs), multi-unit activity (MUA) and single-unit activity (SUA) for up to two months. Calcium imaging of GCaMP6f. labeled cells from the CA1 pyramidal layer under the transparent device was possible even after six months in thy1-GCaMP6f. transgenic mice. We investigated the immune response with GFAP staining after the end of the long-term experiments. Based on our results, this dedicated transparent electrode device proved to be suitable for simultaneous two-photon imaging and large-scale electrophysiological measurements in chronic experiments in mice.

Functionalization of cellulose nanocrystals with a potent antimalarial compound: Synthesis, characterization, and biological studies

Cellulosic materials, such as cellulose nanocrystals (CNCs), are biocompatible, biodegradable and have unique and fascinating biomedical applications. Calxinin (CXN), a potent multistage antimalarial compound was functionalised with CNCs to improve biocompatibility and enhance the bioactivity of the resulting CNC-CXN nano-conjugate. Elemental analysis, powder X-ray, SEM, AFM, Infrared, and solid-state NMR spectroscopic techniques confirmed the composition of novel CNC-CXN nano-conjugate. Next, CNC-CXN nano-conjugate did not exhibit apparent cytotoxic effects on the sensitive Vero E6 cell line up to a concentration of 4.66 μg/μl. The CNC-CXN nano-conjugate was also evaluated for its preliminary efficacy on Plasmodium falciparum (3D7) malaria parasite and showed a 50 % inhibitory concentration value of 0.02 μg/μl. Overall, the selectivity index (SI) of the CNC-CXN nano-conjugate significantly improved to 233, indicating its suitability for further validation studies in animal models.

Surface Quality Evaluation of 3D-Printed Carbon-Fiber-Reinforced PETG Polymer During Turning: Experimental Analysis, ANN Modeling and Optimization

This work presents an experimental analysis related to 3D-printed carbon-fiber-reinforced-polymer (CFRP) machining. A polyethylene-terephthalate-glycol (PETG)-based composite, reinforced with 20% carbon fibers, was selected as the test material. The aim of the study was to evaluate the influence of cutting conditions used in light operations on the generated surface quality of the 3D-printed specimens. For this purpose, nine specimens were fabricated and machined under a wide range of cutting parameters, including cutting speed, feed, and depth of cut. The generated surface roughness was measured with a mechanical gauge and the acquired data were used to develop a shallow artificial neural network (ANN) for prediction purposes, showing that a 3-6-1 structure is the best solution. Following this, a genetic algorithm (GA) was utilized to minimize the response, revealing that the optimal combination is 205 m/min speed, 0.0578 mm/rev feed, and 0.523 mm depth of cut, contributing to the fabrication of low friction parts and shafts with a high quality surface, as well as to the reduction of resource waste. A validation study supported the accuracy of the developed model, by exhibiting errors below 10%. Finally, a set of enhanced images were taken to assess the machined surfaces. It was found that 1.50 mm depth of cut is responsible for the generation of defects across the circumference of the specimens. Especially, combined with 150 m/min cutting speed and 0.11 mm/rev feed, more flaws are produced.

Faecal Volatile Organic Compounds to Detect Colorectal Neoplasia in Lynch Syndrome-A Prospective Longitudinal Multicentre Study.

Non-invasive biomarkers may reduce post-colonoscopy colorectal cancer (CRC) rates and colonoscopy overuse in Lynch syndrome. Unlike faecal immunochemical test (FIT), faecal volatile organic compounds (VOCs) may accurately detect both advanced and non-advanced colorectal neoplasia. The aim of this study was to evaluate the potential of faecal VOCs-separately and with FIT-to guide optimal colonoscopy intervals in Lynch syndrome. Prospective longitudinal multicentre study in which individuals with Lynch syndrome collected faeces before and after high-quality surveillance colonoscopy. VOC-patterns were analysed using field asymmetric ion mobility spectrometry (FAIMS) and gas chromatography-ion mobility spectrometry (GC-IMS) followed by machine learning pipelines, and combined with FIT at 2.55 μg Hb/g faeces. Gas chromatography time-of-flight mass spectrometry analysed individual VOC abundance. Among 200 included individuals (57% female, median 51 years), 62 had relevant neoplasia at colonoscopy: 3 CRC, 6 advanced adenoma (AA), 3 advanced serrated lesion (ASL), and 50 non-advanced adenoma (NAA). Respective sensitivity and negative predictive value for CRC and AA (and also ASL in case of FAIMS) were 100% and 100% using FAIMS (54% specificity), and 89% and 99% using GC-IMS (58% specificity). Respective sensitivity and specificity for any relevant neoplasia were 88% and 44% (FAIMS) and 84% and 28% (GC-IMS); accuracy did not significantly improve upon VOC-FIT. VOC-patterns differed before and after polypectomy (AUC 0.70). NAA showed decreased faecal abundance of butanal, 2-oxohexane, dimethyldisulphide and dimethyltrisulphide. In Lynch syndrome, faecal VOCs may be a promising strategy for postponing colonoscopy and for follow-up after polypectomy. Our results serve as a stepping stone for large validation studies. NL8749.

Effects of poultry by-product meal and complete replacement of fish oil with alternative oils on growth performance and gut health of rainbow trout (Oncorhynchus mykiss): a FEEDNETICS™ validation study

BackgroundAquaculture, traditionally a form of biotechnology, has evolved to integrate innovative biotechnological applications, such as advanced feed formulations, aimed at improving the growth performance and health of farmed fish species. In the present study, the effects of feeding rainbow trout with novel feed formulations were investigated. Fish growth, gut and liver morphology, the concentration of fatty acids in the fillet, and volatile fatty acids in the gut were assessed. The study also validated scenarios from in vivo experiments using a nutrient-based model called FEEDNETICS™. This globally used model serves as a tool for data interpretation and decision support in the context of precision fish farming.MethodsAlternative protein and oil sources, including poultry by-product meal (PBM) and natural algae oil, were explored as sustainable replacements for fishmeal (FM) and fish oil (FO). A 90-day feeding trial was conducted using rainbow trout, comparing two isoproteic, isolipidic and isoenergetic diets. The control diet contained 15% FM, 5% PBM, and 8% FO, while the test diet replaced FM with 15% PBM and 5% feather meal hydrolysate (FMH), and fully substituted FO with VeraMaris® natural algae oil and rapeseed oil.ResultsPBM successfully replaced FM protein without negatively affecting feed intake, growth performance or feed utilization in trout. The combination of PBM and natural algae oil was well tolerated by the trout and showed no negative effects on gut health. A detailed analysis of fatty acids in the fillet revealed that PUFAs of the n3 and n6 series were significantly higher in the PBM group than in the FM group. Values of fatty acid-related health indexes, including atherogenicity index, and thrombogenicity index, confirmed the high nutritional value of trout filet, thus representing a healthy product for human. In addition, the predictions using the FEEDNETICS™ indicated that the tested novel alternative formulations are economically viable. The validation of the model for fish growth resulted in a Mean Absolute Percentage Error (MAPE) of 8%.ConclusionsThe FEEDNETICS™ application enhances our ability to optimize feeding strategies and improve production efficiency in the aquaculture industry. VeraMaris® algae oil and PBM could serve as viable and sustainable raw materials for fish feed, promoting environmentally friendly aquaculture practices.

The Multidimensional Scale of Perceived Social Support (MSPSS-SK): Validation Study of the Slovak Version for Adolescents

The Multidimensional Scale of Perceived Social Support (MSPSS-SK): Validation Study of the Slovak Version for Adolescents

How Culture and Musical Engagement Shape Musical Reward Sensitivity in Danish Teens: A Validation Study of the Danish Barcelona Musical Reward Questionnaire With 4641 Adolescents.

The ability to convey emotions and induce pleasure is one of the most important aspects of the way that music becomes meaningful to humans. Affective responses to music are specific to both cultural and personal preferences, but little is known about the individual variability in adolescence. The Barcelona Music Reward Questionnaire (BMRQ) is a psychometric measure that identifies five factors associated with musical pleasure: Musical Seeking, Emotional Evocation, Mood Regulation, Social Reward, and Sensory-Motor. With this study, we aimed to validate the BMRQ in Danish teens and to explore the differences in music reward experiences in relation to the amount of musical activity, between genders and over ages. Approximately 30,000 Danish adolescents participated in a mass experiment with a subset (N = 4641, 51.2% girls, age range = 13-19 years old) responding to (1) a Danish adaptation of the BMRQ and (2) the Concurrent Musical Activities (CCM) Questionnaire. Both exploratory and confirmatory factor analyses were applied, and a seven-factor model of the BMRQ was found to fit the Danish adolescent population. The seven-factor version of the Danish BMRQ was due to the split of the dimensions "Sensory-Motor" and "Social Reward" into two further subfactors. The students with a higher amount of musical engagement scored higher across all dimensions. In particular, the higher the musical engagement, the higher scores were found for the facet of musical pleasure related to the sharing of musical activities, especially in the earliest stages of adolescence. Furthermore, we found that sensitivity to music generally tends to increase with age, and that girls reported overall to be more sensitive to music than boys in the dimension related to evocation of emotions. A slightly different model of the BMRQ has to be taken into account when testing the Danish adolescent population. In addition to utilizing the Danish version of the BMRQ on a large sample of adolescents, this study may provide insight into the relationship between changes in the level of musical reward depending on amount of musical engagement and how musical reward unfolds within and between genders and across age groups during this developmental stage.

Benefit of dual bronchodilator therapy on exacerbations in former and current smokers with chronic obstructive pulmonary disease in real-world clinical practice: a multicenter validation study (TOReTO)

BackgroundDual bronchodilator therapy, consisting of a long-acting beta-agonist (LABA) and a long-acting muscarinic antagonist (LAMA), has proven effective for patients with chronic obstructive pulmonary disease (COPD). However, it remains uncertain whether there are efficacy differences between current and former smokers with COPD. This study aims to explore the effectiveness of LABA/LAMA therapies in both these groups.MethodsThe TOReTO trial assessed lung function, symptoms, health status, the occurrence of exacerbations, clinically significant exacerbations, and the use of LABA/LAMA therapies. These therapies include Tio/Olo, umeclidinium/vilanterol (Umec/Vi), and umeclidinium/vilanterol (Umec/Vi) are used in patients with COPD. The study examined the differences in outcomes between current and former smokers. To balance the baseline characteristics, propensity score matching (PSM) was employed.ResultsData from 967 patients were collected. After PSM, the time to the first acute exacerbation in current smokers was analyzed separately for the three treatment groups and was significantly different between them (p = 0.0457). Among, there are differences in the occurrence of acute exacerbation between treatment and smoking status in Umec/Vi (p = 0.0114). There is no significant difference in the treatment of former smokers among the three different groups of LABA/LAMA fixed-dose combinations (p = 0.3079). COPD-related symptoms remained stable throughout the treatment period. There were no significant differences in symptom scores, including CAT and mMRC, among the three groups at the end of the study.ConclusionsThe three fixed-dose combinations of LABA/LAMA showed no difference in reducing exacerbations in former smokers but did show differences in current smokers. This trend has clinical significance, and future research will be conducted to control influencing variables to validate this point. However, due to the non-randomized study design, these findings should be interpreted with caution.

Electrochemical Analysis of Amyloid Plaques and ApoE4 with Chitosan-Coated Gold Nanostars for Alzheimer's Detection.

Monitoring the progression of Alzheimer's disease (AD) is crucial for mitigating dementia symptoms, alleviating pain, and improving mobility. Traditionally, AD biomarkers like amyloid plaques are predominantly identified in cerebrospinal fluid (CSF) due to their concentrated presence. However, detecting these markers in blood is hindered by the blood-brain barrier (BBB), resulting in lower concentrations. To address this challenge and identify pertinent AD biomarkers-specifically amyloid plaques and apolipoprotein E4 (ApoE4)-in blood plasma, we propose an innovative approach. This involves enhancing a screen-printed carbon electrode (SPCE) with an immobilization matrix comprising gold nanostars (AuNSs) coated with chitosan. Morphological and electrical analyses confirmed superior dispersion and conductivity with 0.5% chitosan, supported by UV-Vis spectroscopy, cyclic voltammetry, and Nyquist plots. Subsequent clinical assays measured electrical responses to quantify amyloid-β 42 (Aβ42) (15.63-1000 pg/mL) and APoE4 levels (0.41 to 40 ng/mL) in human blood plasma samples. Differential pulse voltammetry (DPV) responses exhibited peak currents proportional to biomarker concentrations, demonstrating high linear correlations (0.985 for Aβ42 and 0.919 for APoE4) with minimal error bars. Cross-reactivity tests with mixed solutions of amyloid-β 40 (Aβ40), Aβ42, and ApoE4 indicated minimal interference between biomarkers (<3% variation), further confirming the high specificity of the developed sensor. Validation studies demonstrated a strong concurrence with the gold-standard enzyme-linked immunosorbent assay (ELISA), while interference tests indicated a minimal variation in peak currents. This improved device presents promising potential as a point-of-care system, offering a less invasive, cost-effective, and simplified approach to detecting and tracking the progression of AD. The substantial surface binding area further supports the efficacy of our method, offering a promising avenue for advancing AD diagnostics.

The translation and validation of the surgical anxiety questionnaire into the modern standard Arabic language: results from classical test theory and item response theory analyses

BackgroundPreoperative anxiety is commonly found in patients who are waiting for surgery and can lead to negative surgical outcomes. Understanding the sources of surgical anxiety allows healthcare providers to identify at-risk patients and implement psychosocial interventions such as counseling, relaxation techniques, and cognitive‒behavioral therapy to minimize anxiety. Few comprehensive psychiatric measures are available to assess preoperative anxiety in Arabic.ObjectiveOur study aimed to translate, adapt, and validate the Surgical Anxiety Questionnaire (SAQ) into the modern standard Arabic language, also known as Fusha al-Asr Arabic.MethodsTo translate the questionnaire, the research team used the gold standard process of forward translation by two independent translators along with back translation evaluation by four trained medical doctors. A cross-sectional study was conducted using an online survey completed by 208 Arabic speakers (mean age 38 years, 44% women) from four countries. Psychometric analyses, which included internal consistency, test-retest reliability, convergent validity, confirmatory factor analysis, and item response analysis, were performed. Convergent validity tests were performed against the Generalized Anxiety Disorder 2-item Scale (GAD-2), Patient Health Questionnaire-4 (PHQ-2), Perceived Stress Scale 4 (PSS-4), and Arabic version of the Visual Analog Scale for anxiety (VAS-A).ResultsThe mean SAQ of our sample was 19.38 ± 12.63 (possible range 0–68). The Arabic SAQ translation demonstrated excellent internal consistency, with McDonald’s omega and a Cronbach’s alpha of approximately 0.90. The test-retest reliability was also high, with an intraclass coefficient of 0.94. The SAQ showed strong convergent validity against the GAD-2 (r = 0.94, p < 0.01). The SAQ also showed weak-moderate correlations with the PHQ-2 (r = 0.26, p < 0.01), PSS-4 (r = 43, p < 0.01), and VAS-A (r = 0.36, p < 0.01) scores. The original three-factor structure was supported by confirmatory factor analysis, confirming the original structure reported in the original English language version. The results for fitness indices showed acceptable preliminary results (CFI/TLI approximately 0.90), and deleting some items improved the model fit (CFI/TLI > 0.90, RMSEA < 0.08). We suggest retaining the original factorial solution until further validation studies can be conducted. The item response theory (IRT) results identified no items that were excessively difficult or subject to guessing. The multidimensional IRT provided evidence that the SAQ items form a multidimensional scale assessing surgical anxiety that fits the classical model reasonably well.ConclusionThe SAQ has demonstrated acceptable reliability and validity; thus, it is a trustworthy and valid tool for evaluating preoperative anxiety in Arabic speakers. Future research could benefit from using the SAQ in both surgical and psychiatric research.

Bladder Cancer detection by urinary methylation markers GHSR/MAL: a validation study

PurposeAlthough cystoscopy is a reliable tool for detecting bladder cancer, it poses a high burden on patients and entails high costs. This highlights the need for non-invasive and cost-effective alternatives. This study aimed to validate a previously developed urinary methylation marker panel containing GHSR and MAL.MethodsWe enrolled 134 patients who underwent cystoscopy because of hematuria, including 63 individuals with primary bladder cancer and 71 with non-malignant findings. Urine samples were self-collected at home and sent via regular mail. Subsequently, DNA was extracted and the hypermethylation of GHSR and MAL was evaluated using quantitative methylation-specific polymerase chain reaction. The performance of methylation markers was assessed using area-under-the-curve (AUC) analysis and sensitivity and specificity based on pre-established cut-off values.ResultsValidation of the marker panel GHSR/MAL resulted in an AUC of 0.87 at 79% sensitivity and 80% specificity. Sensitivity was comparable to the previous investigation (P > 0.9), though specificity was significantly lower (P = 0.026). Sensitivity was higher for high-grade tumors compared to low-grade tumors (94% vs. 60%, P = 0.002).ConclusionValidation of the GHSR/MAL methylation marker panel on at home collected urine samples confirms its robust performance for bladder cancer detection in a hematuria population, and underscores the diagnostic potential for future clinical application.

Commercial devices for monitoring symptoms in Parkinson's disease: benefits, limitations and trends

Parkinson's disease (PD) is a neurodegenerative disorder that significantly affects patients' quality of life. Treatment of PD requires accurate assessment of motor and non-motor symptoms, which is often complicated by subjectivity in reporting symptoms, and the limited availability of neurologists. Commercial wearable devices, which monitor PD symptoms continuously and outside the clinical setting, have appeared to address these challenges. These devices include PKG™, Kinesia 360™, Kinesia U™, PDMonitor™ and STAT-ON™. These devices use advanced technologies, including accelerometers, gyroscopes and specific algorithms to provide objective data on motor symptoms, such as tremor, dyskinesia and bradykinesia. Despite their potential, the adoption of these devices has been limited, due to concerns about their accuracy, complexity of use and the lack of independent validation. The correlation between the measurements obtained from these devices and traditional clinical observations varies, and their usability and patient adherence are critical areas for improvement. Validation and usability studies with a sufficient number of patients, standardised protocols and integration with hospitals' IT systems are essential to optimise their usefulness and improve patient outcomes.

An Investigation into the Viability of Cell-Level Temperature Control in Lithium-Ion Battery Packs

Abstract This article focuses on the thermal management and temperature balancing of lithium-ion battery packs. As society transitions to relying more heavily on renewable energy, the need for energy storage rises considerably, as storage facilitates power regulation between these sources and the grid. Lithium-ion batteries are leading the market for energy storage options, but their properties are temperature sensitive, with thermal abuse resulting in shortened pack lifetime and possible safety issues. Current battery thermal management systems (BTMS) are implemented in a number of ways to ensure consistent and reliable operation. However, they are typically limited in architecture and restricted in ability to attend to temperature gradients. This work proposes a BTMS topology that permits control of the individual cooling received by a cell in a pack. First, an analysis is done using timescale separation to confirm that cell-level temperature control is capable of extending the lifetime of a pack as compared to pack-level control. The analysis is used to guide the gain tuning of a state feedback controller, which directs more cooling effort to cells of higher temperatures. Validation of the BTMS topology and control is performed through the simulation of a battery pack, with variations in total cooling power and resistance heterogeneity. The outcome of the validation studies indicates that the proposed BTMS configuration is better equipped to reduce temperature differences and extend pack life. This benefit increases as total input power increases, giving the controller more freedom to cool unhealthy cells while remaining within power constraints.

Rasch analysis of quality of life in children with vernal keratoconjunctivitis (QUICK) questionnaire

ABSTRACT Clinical relevance A validated questionnaire measures the construct accurately, helps clinician to support decision making, facilitates assessment and monitoring of patients, guides clinical trial and promotes patient-centred care. Background To assess the psychometric properties of the Quality of Life in Children with Vernal Keratoconjunctivitis (QUICK) questionnaire among Indian children with Vernal Keratoconjuntivitis (VKC) using Rasch analysis. Methods This study used a questionnaire validation study design. The QUICK questionnaire for VKC was translated to two local languages using back translation process and administered to the Indian children (aged 5–15 years) diagnosed with VKC between June 2021 and March 2022. The study took place at a tertiary eye care hospital in Chennai, India. The psychometric properties were assessed based on six indicators namely rating scale behaviour, measurement precision, item fit, unidimensionality, targeting and Differential Item Functioning (DIF). Results Fifty six children with VKC (mean age 10.5 years and 77.8% males) filled the questionnaire. The analysis of overall QUICK questionnaire (16 items) revealed an ordered threshold for the rating scale, no noticeable DIF and excellent person-item targeting (0.15). However, the questionnaire showed inadequate person separation (PSI 1.82 and PSR 0.77), four misfit items and lack of unidimensionality (eigenvalue 2.80). Eliminating misfit items and contrasting items resolved multidimensionality, leaving nine items related to the symptoms domain in the questionnaire. However, the person separation (PSI 1.52 and PSR 0.70) remained below 2.0. Conclusion The resultant 9-item QUICK questionnaire discriminates only low and high performers among VKC patients. Thus, it may be used solely to assess the symptoms domain in Health Related Quality of Life (HRQoL). This questionnaire requires addition of items in other domains pertaining to HRQoL to make it holistic.