Biomarkers Of Disease Severity Research Articles

Racial and ethnic differences in diagnosis age and blood biomarkers in a pediatric inflammatory bowel disease cohort.

Prompt diagnosis of pediatric-onset inflammatory bowel disease (IBD) is crucial for preventing a complicated disease course; however, it is not well understood how social determinants of health might affect pediatric IBD diagnosis. This study examined differences in diagnosis age, biomarkers of disease severity, and anthropometrics with sociodemographic factors in a pediatric IBD cohort. Pediatric IBD patients (n = 114) and their parents/caregivers were enrolled from the Children's of Alabama Pediatric IBD Clinic in Birmingham, Alabama. Primary analyses examined associations of child race and ethnicity, parental income, parental education, single-parent household status, insurance type, and distance to a tertiary pediatric gastroenterology referral center with diagnosis age. Secondary analyses examined differences in biomarker levels, height, and body mass index at the time of diagnosis. Racial and ethnic minority children were diagnosed at an older age compared to Non-Hispanic White children (14.4 ± 0.40 vs. 11.7 ± 0.38 years; p < 0.001), and this trend was robust to adjustment with other sociodemographic variables. Parental attainment of a college education attenuated the link between minority race and ethnicity and the likelihood of older age at diagnosis, while other sociodemographic variables had no moderating effect. Racial and ethnic minority children were 5.7 times more likely to have clinically elevated erythrocyte sedimentation rate at diagnosis compared to Non-Hispanic White children (p = .024). These results suggest that child race and ethnicity may exert a primary effect on the age at diagnosis with pediatric-onset IBD. This study highlights the need for further research on racial and ethnic disparities to promote health equity in pediatric-onset IBD.

Plasma proteomic profiles of UK Biobank participants with multiple sclerosis.

We aimed to describe plasma protein biomarkers of multiple sclerosis risk and to explore protein biomarkers of disease severity using radiological outcome measures. Multiple sclerosis cases and controls were identified in UK Biobank, a longitudinal cohort study of ~500,000 British adults. Plasma proteins were assayed in ~50,000 UK Biobank participants using the Olink proximity extension assay. We performed case-control association testing to examine the association between 2911 proteins and multiple sclerosis, using linear models adjusted for confounding covariates. Associations with radiological lesion burden and brain volume were determined in a subset of the cohort with available magnetic resonance imaging, using normalized T2-hyperintensity volume or whole brain volume as the outcome measure. In total, 407 prevalent multiple sclerosis cases and 39,979 healthy controls were included. We discovered 72 proteins associated with multiple sclerosis at a Bonferroni-adjusted p value of 0.05, including established markers such as neurofilament light chain and glial fibrillary acidic protein. We observed a decrease in plasma Granzyme A, a marker of T cell and NK cell degranulation, which was specific to multiple sclerosis. Higher levels of plasma proteins involved in coagulation were associated with lower T2 lesion burden and preserved brain volume. We report the largest plasma proteomic screen of multiple sclerosis, replicating important known associations and suggesting novel markers, such as the reduction in granzyme A. While these findings require external validation, they demonstrate the power of biobank-scale datasets for discovering new biomarkers for multiple sclerosis.

Quantitative muscle ultrasound as a disease biomarker in hereditary transthyretin amyloidosis with polyneuropathy.

There is an increasing need for a reproducible and sensitive outcome measure in patients with hereditary transthyretin amyloidosis (ATTRv) with polyneuropathy (PN) due to the emergence of disease modifying therapies. In the current study, we aimed to investigate the role of quantitative muscle ultrasound (QMUS) as a disease biomarker in ATTRv-PN. Twenty genetically confirmed ATTRv amyloidosis patients (nine symptomatic, 11 pre-symptomatic) were enrolled prospectively between January to March 2023. Muscle ultrasound was performed on six muscles at standardized locations. QMUS parameters included muscle thickness (MT) and muscle echo intensity (EI). Twenty-five age- and sex-matched healthy controls were recruited for comparison. Significant QMUS parameters were correlated with clinical outcome measures. Muscle volume of first dorsal interosseus (FDI) muscle [measured as cross-sectional area (CSA)] was significantly lower in symptomatic patients compared to healthy controls and pre-symptomatic carriers (98.3 ± 58.0 vs. 184.4 ± 42.5 vs. 198.3 ± 56.8, p < 0.001). EI of biceps and FDI for symptomatic ATTRv-PN patients were significantly higher compared to the other two groups (biceps: 76.4 ± 10.8 vs. 63.2 ± 11.5 vs. 59.2 ± 9.0, p = 0.002; FDI: 48.2 ± 7.5 vs. 38.8 ± 7.5 vs. 33.0 ± 5.3, p < 0.001). CSA of FDI and EI of biceps and FDI correlated with previous validated outcome measures [polyneuropathy disability score, neuropathy impairment score, Karnofsky performance scale, Rasch-built overall disability scale, European quality of life (QoL)-5 dimensions and Norfolk QoL questionnaire-diabetic neuropathy]. QMUS revealed significant difference between ATTRv amyloidosis patients and healthy controls and showed strong correlation with clinical outcome measures. QMUS serves as a sensitive and reliable biomarker of disease severity in ATTRv-PN.

A Genome-Wide Association Study of Respiratory Syncytial Virus Infection Severity in Infants.

Respiratory syncytial virus (RSV) is a significant cause of infant morbidity and mortality worldwide. Most children experience at least one 1 RSV infection by the age of two 2 years, but not all develop severe disease. However, the understanding of genetic risk factors for severe RSV is incomplete. Consequently, we conducted a genome-wide association study of RSV severity. Disease severity was assessed by the ReSVinet scale, in a cohort of 251 infants aged 1 week to 1 year. Genotyping data were collected from multiple European study sites as part of the RESCEU Consortium. Linear regression models were used to assess the impact of genotype on RSV severity and gene expression as measured by microarray. While no SNPs reached the genome-wide statistical significance threshold (P < 5 × 10-8), we identified 816 candidate SNPs with a P-value of <1 × 10-4. Functional annotation of candidate SNPs highlighted genes relevant to neutrophil trafficking and cytoskeletal functions, including LSP1 and RAB27A. Moreover, SNPs within the RAB27A locus significantly altered gene expression (false discovery rate, FDR P < .05). These findings may provide insights into genetic mechanisms driving severe RSV infection, offering biologically relevant information for future investigations.

P824 Association between visceral adipose tissue and disease duration, clinical activity, and response to various biological agents in inflammatory bowel disease

Abstract Background The relationship between body fat composition and inflammatory bowel disease (IBD) progression, medical response, and prognosis is widely acknowledged. Visceral adipose tissue (VAT) has been shown to be profoundly responsible of most of the obesity-associated metabolic derangements, however it is also related to severity of inflammation. Although VAT can be estimated using computerized tomography, abdominal bioimpedance is a new and reliable technique without expense and radiation exposure. We investigated whether VAT is linked to the disease activity in severe IBD and the short-term response to biological therapies. Methods We prospectively evaluated 65 IBD patients, (n=26 with ulcerative colitis (UC) and n=39 with Crohn’s disease (CD) who had moderate-severe disease activity) at baseline before the initiation of biological therapy. We quantified VAT using abdominal bioimpedance (ViScan). VAT and other body fat metric measures (BMI, total and free fat mass, abdominal fat mass) were also analyzed. The response to biological agents was assessed by clinical (Mayo and CDAI) and endoscopical (mucosal healing) scores at 3 months. Results Out of the 65 patients, 22 individuals (33.8%) exhibited clinical and/or endoscopic response after 3 months. Among responders and non-responders, there was a comparable approximation of disease location (p=0.321) and behavior (p=0.239). Patients with CD had slightly lower levels of VAT, BMI, and free fat mass compared to those with UC. In non-responders with UC, VAT levels were lower than in responders, whereas in non-responders with CD, VAT levels were higher than in responders. No distinction was observed in the VAT response among other classes of biologics, including anti-TNF, ustekinumab, and vedolizumab. Conclusion In summary, VAT parameters using bioimpedance (ViScan) were found to be correlated with the disease activity and reliably identified IBD patients who responded well to various biological treatment in the short-term. Therefore, human fat indices might be novel biomarkers for disease severity and response to therapy.

Circulating miRNAs and Preeclampsia: From Implantation to Epigenetics.

In this review, we comprehensively present the literature on circulating microRNAs (miRNAs) associated with preeclampsia, a pregnancy-specific disease considered the primary reason for maternal and fetal mortality and morbidity. miRNAs are single-stranded non-coding RNAs, 20-24 nt long, which control mRNA expression. Changes in miRNA expression can induce a variation in the relative mRNA level and influence cellular homeostasis, and the strong presence of miRNAs in all body fluids has made them useful biomarkers of several diseases. Preeclampsia is a multifactorial disease, but the etiopathogenesis remains unclear. The functions of trophoblasts, including differentiation, proliferation, migration, invasion and apoptosis, are essential for a successful pregnancy. During the early stages of placental development, trophoblasts are strictly regulated by several molecular pathways; however, an imbalance in these molecular pathways can lead to severe placental lesions and pregnancy complications. We then discuss the role of miRNAs in trophoblast invasion and in the pathogenesis, diagnosis and prediction of preeclampsia. We also discuss the potential role of miRNAs from an epigenetic perspective with possible future therapeutic implications.

The Soluble Urokinase Plasminogen Activator Receptor as a Severity Biomarker in Children With Acute COVID-19 or Multisystem Inflammatory Syndrome.

Elevated soluble urokinase plasminogen activator receptor (suPAR) has been associated with a poor prognosis in serious infections. The aim of this study was to evaluate the clinical value of suPAR in children with acute coronavirus disease 2019 (COVID-19) or multisystem inflammatory syndrome (MIS-C). Serum suPAR was measured using the suPARnostic AUTO Flex enzyme-linked immunosorbent assay in hospitalized children with COVID-19, MIS-C, bacterial pneumonia, and healthy controls. A total of 211 children with a mean (±SD) age of 6.9 ± 4.96 years were tested; with COVID-19: 59 (28%), MIS-C: 36 (17%), pneumonia: 78 (37%) and healthy controls: 38 (18%). In the acute phase, the levels of suPAR (mean ± SD) were: MIS-C: 8.11 ± 2.80 ng/mL, COVID-19: 4.91 ± 1.90 ng/mL, pneumonia: 4.25 ± 1.44 ng/mL and controls: 2.09 ± 0.47 ng/mL ( P < 0.001). Children with acute COVID-19 and a severe or moderate clinical presentation had higher values than those with mild symptoms: 5.79 ± 1.58 versus 5.40 ± 1.94 versus 3.19 ± 0.73 ng/mL, respectively ( P < 0.001). In the MIS-C group, children hospitalized in the intensive care unit and in need of mechanical ventilation had higher suPAR than those who were not admitted to an intensive care unit: 9.32 ± 3.06 versus 7.13 ± 2.19 ng/mL, respectively ( P = 0.023). In children with COVID-19 or MIS-C, a correlation was detected between suPAR values and length of hospitalization ( rs = 0.418, P < 0.001). The findings suggest that suPAR may be a valuable biomarker of disease severity in children with COVID-19 or MIS-C. This could facilitate the identification of children in need of intensive anti-inflammatory treatment, as it has been shown in adults with severe COVID-19.

Neurofilament light protein as a biomarker for spinal muscular atrophy: a review and reference ranges.

Spinal muscular atrophy (SMA) is the leading genetic cause of infant mortality, characterized by progressive neuromuscular degeneration resulting from mutations in the survival motor neuron (SMN1) gene. The availability of disease-modifying therapies for SMA therapies highlights the pressing need for easily accessible and cost-effective blood biomarkers to monitor treatment response and for better disease management. Additionally, the wide implementation of newborn genetic screening programs in Western countries enables presymptomatic diagnosis of SMA and immediate treatment administration. However, the absence of monitoring and prognostic blood biomarkers for neurodegeneration in SMA hinders effective disease management. Neurofilament light protein (NfL) is a promising biomarker of neuroaxonal damage in SMA and reflects disease progression in children with SMA undergoing treatment. Recently, the European Medicines Agency issued a letter of support endorsing the potential utilization of NfL as a biomarker of pediatric neurological diseases, including SMA. Within this review, we comprehensively assess the potential applications of NfL as a monitoring biomarker for disease severity and treatment response in pediatric-onset SMA. We provide reference ranges for normal levels of serum based NfL in neurologically healthy children aged 0-18 years. These reference ranges enable accurate interpretation of NfL levels in children and can accelerate the implementation of NfL into clinical practice.

Achieving One Part Per Billion Hydrogen Sulfide (H2S) Level Detection through Optimizing Composition and Crystallinity of Gold-Decorated Tungsten Trioxide (Au-WO3) Nanofibers.

As a common environmental pollutant and an important breath biomarker for several diseases, it is essential to develop a hydrogen sulfide gas sensor with a low-ppb level detection limit to prevent harmful gas exposure and allow early diagnoses of diseases in low-resource settings. Gold doped/decorated tungsten trioxide (Au-WO3) nanofibers with various compositions and crystallinities were synthesized to optimize H2S-sensing performance. Systematically experimental results demonstrated the ability to detect 1 ppb H2S with a response value (Rair/Rgas) of 2.01 using a 5 at % Au-WO3 nanofibers with average grain sizes of around 15 nm. Additionally, energy barrier difference of sensing materials in air and nitrogen (ΔEb) and power law exponent (n) were determined to be 0.36 eV and 0.7, respectively, at 450 °C indicating that O- is predominately ionic oxygen species and adsorption of O- significantly altered the Schottky barrier between the grain. Such quantitative analysis provides a comprehensive understanding of H2S detection mechanism.

A prospective observational study correlating possible novel biomarkers with disease severity and antihistamine response in chronic spontaneous urticaria.

Role of complement fraction 5a (C5a), interleukin (IL)-9, and apolipoprotein (apo) A-IV as biomarkers of disease severity and antihistamine response in chronic spontaneous urticaria (CSU) remains elusive. To identify the role of C5a, IL-9, and apo A-IV as potential biomarkers in predicting disease severity and antihistamine response in CSU patients. This was a prospective observational study of 95 patients and 42 controls. Serum analysis of C5a, IL-9, and apo A-IV was done using enyzme linked immunosorbent assay kits. Also, serum IgE and anti-thyroid peroxidase (TPO) levels were assessed in all patients. All patients were started on oral levocetirizine 5 mg at baseline and dose was titrated upwards to maximum of 20 mg based on response. Patients were categorized into antihistamine responders or nonresponders as per their disease response. Serological markers, serum IgE, and anti-TPO were correlated with baseline disease severity and antihistamine response. C5a levels were significantly higher in cases as compared to controls (P = 0.004). Significantly higher IL-9 levels were observed in antihistamine responders than nonresponders (P = 0.008). Baseline urticaria severity demonstrated a statistically significant positive and negative correlations with IL-9 (ρ = 0.277, P = 0.007) and apo A-IV (ρ = -0.271, P = 0.008) levels, respectively. Levels of serum IgE (P = 0.031) and anti-TPO (P = 0.039) were significantly higher in antihistamine nonresponders compared to responders. IL-9 and apo A-IV might be potential novel biomarkers to predict urticaria severity. Higher IL-9 might be a predictor of antihistamine response. Elevated anti-TPO and serum IgE might predict poor antihistamine response.

Plasma neurofilament light as a promising biomarker in neuronal intranuclear inclusion disease.

Neuronal intranuclear inclusion disease (NIID) is a rare neurodegenerative disorder lacking reliable biomarkers. This study investigates plasma protein levels as potential biomarkers of disease severity and progression in NIID. In this study, we enrolled 30 NIID patients and 36 age- and sex-matched controls, following them for 1-2years. Plasma neurofilament light (NfL), glial fibrillary acidic protein (GFAP), ubiquitin carboxy-terminal hydrolase L1 (UCH-L1), and tau were measured using ultrasensitive single molecule array (Simoa) assays. Disease severity was evaluated with the Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), Activities of Daily Living (ADL), and CNS symptom counts, in addition to neuroimaging data. Our study revealed that NIID patients has significantly higher plasma NfL (median, 35.2 vs. 8.61pg/mL, p < 0.001) and GFAP (102 vs. 79.0pg/mL, p = 0.010) levels compared to controls, with NfL emerging as a robust diagnostic marker (AUC = 0.956). NfL levels were notably higher in acute-onset NIID (77.5 vs. 28.8pg/mL, p = 0.001). NfL correlated strongly with disease severity, including MMSE (ρ = - 0.687, p < 0.001), MoCA (ρ = - 0.670, p < 0.001), ADL (ρ = 0.587, p = 0.001), CNS symptoms (ρ = 0.369, p = 0.045), and white matter hyperintensity volume (ρ = 0.620, p = 0.004). Higher baseline NfL (≥ 35.2pg/mL) associated with increased ADL scores, CNS symptoms, and white matter hyperintensity at follow-up. UCH-L1 and total tau levels showed no significant differences. Our results suggested the potential of NfL as a promising biomarker of disease severity and progression in NIID.

Greater reduction in hyperreflective foci with faricimab compared to aflibercept in patients with diabetic macular oedema

Aims/Purpose: In diabetic macular oedema (DME), hyperreflective foci (HRF) may be a biomarker for disease severity and progression. This post hoc analysis aimed to test if faricimab, a dual‐action therapeutic inhibiting both vascular endothelial growth factor (VEGF)‐A and angiopoietin‐2 (Ang‐2), yields improved resolution of retinal HRF in DME compared to aflibercept.Methods: Phase 3 YOSEMITE/RHINE (NCT03622580/NCT03622593) spectral‐domain optical coherence tomography (SD‐OCT) volumes from 1527 DME patients were automatically segmented using a deep learning‐based HRF model trained with manually‐annotated B‐scans from phase 2 BOULEVARD (NCT02699450). Bright objects ≤50 μm in diameter were classified as retinal HRF. HRF volumes were assessed within the 1‐ and 3‐mm diameter Early Treatment Diabetic Retinopathy Study (ETDRS) rings, separated into inner and outer retina. Treatment groups were compared using a Mixed Model for Repeated Measures.Results: In the inner retina at 1 mm diameter, adjusted mean HRF volumes reduced more markedly from baseline to week 48 for faricimab every 8 weeks (Q8W; −118.29 pL) and faricimab treat&amp;extend (T&amp;E; −130.05 pL) than aflibercept Q8W (−58.67 pL; p = 0.0006 and p &lt; 0.0001, for comparison of each faricimab arm vs aflibercept, averaged across all visits, respectively). In the inner retina at 3‐mm diameter, reductions from baseline to week 48 were − 406.76 pL (faricimab Q8W), −533.01 pL (faricimab T&amp;E) and − 397.67 pL (aflibercept Q8W; p = 0.0142 and p = 0.0034, for comparison to aflibercept averaged across all visits, respectively). Similar, statistically significant results were obtained for the outer retina.Conclusions: Significantly greater retinal HRF volume reductions were observed with faricimab compared to aflibercept. Our findings of better resolution of the pathological manifestations of DME with faricimab support the therapeutic potential of dual Ang‐2/VEGF‐A inhibition.

The Role of Uromodulin in Chronic Kidney Disease – A Systematic Review and Meta-Analysis

Background: Numerous studies have investigated the function of the biomarker uromodulin (UMD), which has shown promise in the diagnosis and severity assessment of chronic kidney disease (CKD). However, the results continue to be contradictory and inconclusive. Consequently, our goal was to investigate the connection between UMD and CKD patients, with a focus on their diagnostic utility and association with the severity of CKD based on the Kidney Disease Improving Global Outcomes (KDIGO) classification. Methods: We systematically searched PubMed, EMBASE, and Scopus using a predefined string to identify relevant studies. Included studies diagnosed CKD based on GFR according to Kidney Disease Outcomes Quality Initiative KDOQI guidelines or by calculating eGFR using the MDRD formula, meeting predefined criteria. Quality assessment was conducted using the Newcastle Ottawa Scale (NOS). The main outcome was the mean difference (MD) in serum UMD levels across CKD stages. Results: A total of 5 articles involving 1,094 subjects fulfilled our inclusion criteria and were included in our systematic review and meta-analysis. Significant differences in UMD levels were observed across multiple comparisons. When comparing CKD patients to controls, UMD levels showed a substantial MD of –115.719 (95% CI –163.297, -68.141). Similarly, UMD levels exhibited significant MDs when comparing controls vs. CKD 1 71.185 (95% CI 39.572, 102.798), controls vs. CKD 2 81.531 (95% CI 40.570, 122.491), controls vs. CKD 3 130.886 (95% CI 99.095, 162.677), controls vs. CKD 4 180.317 (95% CI 141.373, 219.262), controls vs. CKD 5 198.033 (95% CI 155.573, 240.494) and CKD 1-2-3 vs. CKD 4-5 89.540 (95% CI 47.561, 131.518). Conclusions: In conclusion, our systematic review and meta-analysis highlights pronounced differences in UMD levels across multiple comparisons in CKD. When comparing CKD patients with controls, a significant decrease in UMD levels is evident, indicative of potential implications in renal pathology. Moreover, the observed variations in UMD levels between different CKD stages underscore its potential utility as a biomarker for disease severity and progression. These findings contribute to our understanding of UMD dynamics in CKD and suggest avenues for further research into its diagnostic and prognostic significance in clinical practice.

Single-step colorimetric detection of acid phosphatase in human urine using an oxidase-mimic platinum nanozyme

A nanozyme sensor for rapid detection of urinary acid phosphatase with high sensitivity and a broad dynamic range that is relevant to human pathophysiology is proposed.

Mn-ferrite nanoparticles as promising magnetic tags for radiofrequency inductive detection and quantification in lateral flow assays.

Lateral flow assays are low-cost point-of-care devices that are stable, easy to use, and provide quick results. They are mostly used as qualitative screening tests to detect biomarkers for several diseases. Quantification of the biomarkers is sometimes desirable but challenging to achieve. Magnetic nanoparticles can be used as tags, providing both visual and magnetic signals that can be detected and quantified by magnetic sensors. In the present work, we synthesized superparamagnetic MnFe2O4 nanoparticles using the hydrothermal coprecipitation route. MnFe2O4 presents low magnetic anisotropy and high saturation magnetization, resulting in larger initial magnetic susceptibility, which is crucial for optimizing the signal in inductive sensors. We functionalized the coprecipitated nanoparticles with citric acid to achieve colloidal stability in a neutral pH and to provide carboxyl groups to their surface to bioconjugate with biomolecules, such as proteins and antibodies. The nanomaterials were characterized by several techniques, and we correlated their magnetic properties with their sensitivity and resolution for magnetic detection in radiofrequency inductive sensors. We considered the NeutrAvidin/biotin model of biorecognition to explore their potential as magnetic labels in lateral flow assays. Our results show that MnFe2O4 nanoparticles are more sensitive to inductive detection than magnetite nanoparticles, the most used nanotags in magnetic lateral flow assays. These nanoparticles present high potential as magnetic tags for the development of sensitive lateral flow immunoassays for detecting and quantifying biomarkers.

Isolation of Extracellular Vesicles Using Titanium Dioxide Microspheres.

Extracellular vesicles (EVs) are bilayer membrane particles released from several cell types to the extracellular environment. EVs have a crucial role in cell-cell communication, involving different biological processes in health and diseases. Due to the potential of biomarkers for several diseases as diagnostic and therapeutic tools, it is relevant to understand the biology of the EVs and their content. One of the current challenges involving EVs is regarding the purification method, which is a critical step for EV's functional and characterization studies. Ultracentrifugation is the most used method for EV isolation, where the nanoparticles are separated in sequential centrifugation to isolate the EVs based on their size. However, for viscous biofluids such as plasma, there is a co-isolation of the most abundant proteins, which can impair the EV's protein identification due to the low abundance of these proteins and signal suppression by the most abundant plasma proteins. Emerging techniques have gained attention in recent years. Titanium dioxide (TiO2) is one of the most promising techniques due to its property for selective isolation based on the interaction with phospholipids in the EV membrane. Using a small amount of TiO2 beads and a low volume of plasma, it is possible to isolate EVs with reduced plasma protein co-isolation. This study describes a comprehensive workflow for the isolation and characterization of plasma extracellular vesicles (EVs) using mass spectrometry-based proteomics techniques. The aim of this chapter is describe the EV isolation using TiO2 beads enrichment and high-throughput mass spectrometry techniques to efficiently identify the protein composition of EVs in a fast and straightforward manner.

Contrast enhanced photoacoustic detection of fibrillar collagen in the near infrared region-I.

Fibrillar collagen accumulation emerges as a promising biomarker in several diseases, such as desmoplastic tumors and unstable atherosclerotic plaque. Gold nanorods (GNRs) hold great potential as contrast agents in high-resolution, biomedically safe, and non-invasive photoacoustic imaging (PAI). This study presents the design and characterization of a specialized imaging tool which exploits GNR assisted targeted photoacoustic imaging that is tailored for the identification of fibrillar collagen. In addition to the photoacoustic characterization of collagen in the NIR 1 and 2 regions, we demonstrate the detailed steps of conjugating a decoy to GNRs. This study serves as a proof of concept, that demonstrates that conjugated collagenase-1 (MMP-1) generates a distinct and collagen-specific photoacoustic signal, facilitating real-time visualization in the wavelength range of 700-970 nm (NIR I). As most of the reported studies utilized the endogenous contrast of collagen in the NIR II wavelength that has major limitations to perform in vivo deep tissue imaging, the approach that we are proposing is unique and it highlights the promise of MMP-1 decoy-functionalized GNRs as novel contrast agents for photoacoustic imaging of collagen in the NIR 1 region. To our knowledge this is the first time functionalized GNRs are optimized for the detection of fibrillar collagen and utilized in the field of non-invasive photoacoustic imaging that can facilitate a better prognosis of desmoplastic tumors and broken atherosclerotic plaques.

D-Dimer a biomarker for disease severity in COVID-19 patients

D-Dimer a biomarker for disease severity in COVID-19 patients

Quantitative muscle ultrasound in adult spinal muscular atrophy. A pilot study.

Muscle ultrasound has been investigated in children with spinal muscular atrophy (SMA) and proposed as a potential biomarker of disease severity. We studied the ultrasound properties in adults with SMA to see whether they also have potential as markers of disease severity in older patients. Thickness and quantitative echogenicity of muscle and subcutaneous tissue were compared between eight prospectively recruited adult patients with SMA and eight age, sex and body mass index-matched controls. Measurements were made in the dominant deltoid, biceps, triceps, forearm extensors, first dorsal interosseous, quadriceps, tibialis anterior, and gastrocnemius muscles. The muscle-to-subcutaneous (M:S) thickness and echogenicity ratios were also calculated. A mean value across all muscles as well as the individual values for each muscle were then calculated for each parameter in each subject and compared between the two groups. Significance was set at 0.05 after Bonferroni correction. In the SMA patients, mean muscle thickness was significantly smaller (1.3 vs. 1.9 cm), muscle echogenicity higher (106 vs. 67 on the grayscale level), and subcutaneous thickness larger (0.9 vs. 0.3 cm) than in controls; M:S echogenicity ratio was significantly increased and M:S thickness ratio reduced in the patients. The most abnormal scores were found in the nonambulatory patients and the least abnormal in the ambulatory patients. Ultrasound can detect and quantify the severity of muscle atrophy and structure in adult SMA, suggesting a potential role as a marker of disease severity, which will require validation by larger studies.

A novel coupling technique based on thermal desorption gas chromatography with mass spectrometry and ion mobility spectrometry for breath analysis

Exhaled breath analysis is evolving into an increasingly important non-invasive diagnostic tool. Volatile organic compounds (VOCs) in breath contain information about health status and are promising biomarkers for several diseases, including respiratory infections caused by bacteria. To monitor the composition of VOCs in breath or the emission of VOCs from bacteria, sensitive analytical techniques are required. Next to mass spectrometry, ion mobility spectrometry (IMS) is considered a promising analytical tool for detecting gaseous analytes in the parts per billion by volume to parts per trillion by volume range. This work presents a new, dual coupling of thermal desorption gas chromatography to a quadrupole mass spectrometer (MS) and an IMS by operating a simple splitter. Nearly identical retention times can be reached in the range of up to 30 min with slight deviations of 0.06 min–0.24 min. This enables the identification of unknown compounds in the IMS chromatogram using unambiguous mass spectral identification, as there are still no commercially available databases for IMS. It is also possible to discriminate one of the detectors using the splitter to improve detection limits. Using a test liquid mixture of seven ketones, namely 2-butanone, 2-pentanone, 2-hexanone, 2-heptanone, 2-octanone, 2-nonanone, and 2-decanone with a concentration of 0.01 g l−1 reproducibilities ranging from 3.0% to 7.6% for MS and 2.2%–5.3%, for IMS were obtained, respectively. In order to test the system optimized here for the field of breath analysis, characteristic VOCs such as ethanol, isoprene, acetone, 2-propanol, and 1-propanol were successfully identified in exhaled air using the dual detector system due to the match of the corresponding IMS, and MS spectra. The presented results may be considered to be a starting point for the greater use of IMS in combination with MS within the medical field.