Semi-quantitative group testing for efficient and accurate qPCR screening of pathogens with a wide range of loads.

BACKGROUND: Pathogenic infections pose a significant threat to global health, affecting millions of people every year and presenting substantial challenges to healthcare systems worldwide. Efficient and timely testing plays a critical role in disease control and transmission prevention. Group testing is a well-established method for reducing the number of tests needed to screen large populations when the disease prevalence is low. However, it does not fully utilize the quantitative information provided by qPCR methods, nor is it able to accommodate a wide range of pathogen loads. RESULTS: To address these issues, we introduce a novel adaptive semi-quantitative group testing (SQGT) scheme to efficiently screen populations via two-stage qPCR testing. The SQGT method quantizes cycle threshold (Ct) values into multiple bins, leveraging the information from the first stage of screening to improve the detection sensitivity. Dynamic Ct threshold adjustments mitigate dilution effects and enhance test accuracy. Comparisons with traditional binary outcome GT methods show that SQGT reduces the number of tests by 24% on the only complete real-world qPCR group testing dataset from Israel, while maintaining a negligible false negative rate. CONCLUSION: In conclusion, our adaptive SQGT approach, utilizing qPCR data and dynamic threshold adjustments, offers a promising solution for efficient population screening. With a reduction in the number of tests and minimal false negatives, SQGT holds potential to enhance disease control and testing strategies on a global scale.

A perspective on the evolution of semi-quantitative MRI assessment of osteoarthritis: Past, present and future.

OBJECTIVE: This perspective describes the evolution of semi-quantitative (SQ) magnetic resonance imaging (MRI) in characterizing structural tissue pathologies in osteoarthritis (OA) imaging research over the last 30 years. METHODS: Authors selected representative articles from a PubMed search to illustrate key steps in SQ MRI development, validation, and application. Topics include main scoring systems, reading techniques, responsiveness, reliability, technical considerations, and potential impact of artificial intelligence (AI). RESULTS: Based on original research published between 1993 and 2023, this article introduces available scoring systems, including but not limited to Whole-Organ Magnetic Resonance Imaging Score (WORMS) as the first system for whole-organ assessment of the knee and the now commonly used MRI Osteoarthritis Knee Score (MOAKS) instrument. Specific systems for distinct OA subtypes or applications have been developed as well as MRI scoring instruments for other joints such as the hip, the fingers or thumb base. SQ assessment has proven to be valid, reliable, and responsive, aiding OA investigators in understanding the natural history of the disease and helping to detect response to treatment. AI may aid phenotypic characterization in the future. SQ MRI assessment's role is increasing in eligibility and safety evaluation in knee OA clinical trials. CONCLUSIONS: Evidence supports the validity, reliability, and responsiveness of SQ MRI assessment in understanding structural aspects of disease onset and progression. SQ scoring has helped explain associations between structural tissue damage and clinical manifestations, as well as disease progression. While AI may support human readers to more efficiently perform SQ assessment in the future, its current application in clinical trials still requires validation and regulatory approval.

Isolation, in vitro, and in vivo pathogenicity test of Tilapia lake virus (TiLV) and development of a prognostic semi-quantitative lesion scoring system for differentiating clinical/subclinical infection in farmed tilapia (Oreochromis niloticus L.).

Tilapia lake virus ('TiLV-MH-2022') was recently recovered from the naturally infected farmed tilapia. Reverse transcription-polymerase chain reaction (RT-PCR) using segment 1 specific primers, followed by Sanger sequencing, confirmed the infection. The pairwise sequence homology of segment 1 showed its close relationship with the previous isolates. The virus was successfully detected from the mucus, which emphasised the possibility of non-invasive screening of tilapia on a large scale. The virus inoculum prepared from the infected tissues was tested for in vivo and in vitro pathogenicity. Around 100-140 nm-sized electron-dense virus particles were observed in the infected OnlL cells. Based on the onset of symptoms and lesions, all RT-PCR-positive fish were categorised into two groups, 'clinical' and 'subclinical'. A lesion-scoring technique was developed for assessing the pathogenicity of the virus isolate. The external and internal gross lesions and histopathological alterations in the critical organs of the fish, such as the brain, kidney, gills, and liver, were assessed on a scale of 0 (no gross lesion) to 5 (most severe lesions). Overall lesion score was significantly high in the clinical and subclinical groups for gross and histopathology, respectively. This study is the first such attempt to standardise a semi-quantitative lesion scoring technique for TiLV infection, which establishes a clinical relevance and prognostic ability to distinguish between the apparent and inapparent infection.

Radiofrequency Echographic Multispectrometry (REMS) can Overcome the Effects of Structural Internal Artifacts and Evaluate Bone Fragility Accurately.

PURPOSE: This study measured bone mineral density (BMD) in a Japanese population using the novel non-ionizing system using radiofrequency echographic multispectrometry (REMS) and compared the results with those obtained using traditional dual-energy X-ray absorptiometry (DXA). We aimed to identify any discrepancies between measurements obtained using these instruments and identify the influencing factors. METHODS: This cross-sectional study examined patients with osteoporosis treated at a single center from April to August 2023. We examined BMD assessment by DXA and REMS in lumbar spine and proximal femur. Patients were categorized into two groups: those with discrepancies between lumbar spine BMD measured by DXA and REMS, and those without. Semiquantitative evaluation of vertebral fractures and abdominal aortic calcification scoring were also performed and compared between the two groups, along with various patient characteristics. RESULTS: A total of 70 patients (88.6% female; mean age 78.39 ± 9.50 years) undergoing osteoporosis treatment were included in the study. A significant difference was noted between DXA and REMS measurement of BMD and T-scores, with REMS recording consistently lower values. The discrepancy group exhibited a higher incidence of multiple vertebral fractures and increased vascular calcification than the non-discrepancy group. Multivariate analysis indicated that diabetes mellitus, severe vertebral fractures, and increased abdominal aortic calcification scores were significantly associated with discrepancies in lumbar spine T-scores. CONCLUSION: This study suggests that REMS may offer a more accurate measurement of BMD, overcoming the overestimation of BMD by DXA owing to factors such as vertebral deformities, abdominal aortic calcification, and diabetes mellitus.

Evaluation of semi-quantitative colorimetric assays based on loop-mediated isothermal amplification indicators by using image analysis.

Colorimetric assays are some of the most convenient detection methods, creating discoloration in solutions that is visible to the naked eye. However, colorimetric reactions have some limitations regarding the variability in the color perception of individuals caused by factors such as color blindness, experience, and gender. Semi-quantitative chromatic analysis has been used as an alternative method to differentiate between two colors and accurately interpret the results from a numerical value, with high confidence. Therefore, we developed and determined the optimal model between Red-Green-Blue (RGB) and Commission Internationale de l'Eclairage (CIE) Lab color spaces to establish a semi-quantitative colorimetric assay via image analysis by the ImageJ program for loop-mediated isothermal amplification (LAMP), using the dyes malachite green and phenol red. The semi-quantitative colorimetric assays using the color distance values of the CIELab color space (ΔEab) were more suitable than those using the RGB color space (ΔERGB) for chromatic differentiation between positive and negative reactions in both indicator dyes, demonstrating the feasibility of this assay to be applied in the detection of a wide range of pathogens and infectious diseases.

Insights into the methodological perspectives for screening polyunsaturated fatty acids-containing bacteria.

Polyunsaturated fatty acids (PUFA) are vital molecules in the pharmaceutical, medical, and nutritional industries. Exploration of bacterial strains capable of producing significant amounts of PUFAs offers a promising avenue for biotechnological applications and industrial-scale production. However, an extensive screening of several samples from diverse sources is highly needed to identify a potential strain. The present study provides the results of the evaluation of 15 different screening methodologies (including changes in existing protocols in terms of reagent concentration, incubation temperature and time) for identifying PUFA-producing bacteria in comparison to the gold standard method (Gas chromatography-mass spectrometry), for the first time. The results determined the most effective techniques for each critical PUFA, leading to an optimized screening process that saves time and resources. The H2O2 plate assay using 0.5% or 1% H2O2 for 72 & 96 h of incubation at 15 °C consistently outperformed others for finding bacteria containing total nutritionally important long chain-PUFA (LC-PUFA), linoleic acid, and arachidonic acid. Whereas the 2,3,5-triphenyl tetrazolium chloride broth assay at 10-15 °C was the most effective and semiquantitative screening methodology for eicosapentaenoic acid (EPA) and alpha-linolenic acid-containing bacteria. Apart from the methodological perspectives, the study also revealed certain potential strains to be targeted in the ongoing research on PUFA-containing bacteria. Further, the manuscript forms the first report on the presence of docosahexaenoic acid (DHA) in Shewanella decolorationis, EPA in Psychrobacter maritimus and Micrococcus aloeverae, and both EPA and DHA in Arthrobacter rhombi. Altogether, the paper generates several thought-provoking insights on the methodological perspectives and identifies potential PUFA-containing bacteria with practical applications in future bacteria-based PUFA research.

Interplay between polygenic variants related immune response and lifestyle factors mitigate the chances of stroke in a genome-wide association study.

We aimed to investigate the intricate interplay between genetic predisposition and lifestyle factors on stroke. We conducted a comprehensive genome-wide association study to identify the genetic variants linked to stroke in the participants who experienced a stroke event (cases; n 672) and those with no stroke history (non-stroke; n 58 029) in a large hospital-based cohort. Using generalised multifactor dimensionality reduction, we identified genetic variants with interactive effects and constructed polygenic risk scores (PRS) by summing up the risk alleles from the genetic variants. Food intake was measured with a validated semi-quantitative FFQ. No significant differences in stroke incidence were seen in demographic variables between the two groups. Among the metabolic indicators, only serum TAG levels were higher in males with stroke than those without stroke. The daily nutrient intake, dietary inflammation index, glycaemic index, dietary patterns, alcohol consumption, exercise and smoking did not display associations with the OR for stroke. The stroke-linked genetic variants were related to the IL-18 pathway. After accounting for covariates, the PRS derived from the 5-, 6- and 7-SNP models were positively associated with stroke chance with 2·5-, 2·9- and 2·8-fold. Furthermore, interactions between genetic predisposition and dietary components, including energy, carbohydrates, n-3 fatty acids and branched-chain amino acids (BCAA), that affected OR for stroke were observed. A high intake of energy, carbohydrates and BCAA and a low intake of n-3 fatty acids were positively associated with the chances of stroke occurrence. In conclusion, understanding the interaction between genetic variants and lifestyle factors can assist in developing stroke prevention and management strategies.

Clinical value of the semi-quantitative parameters of 18F-fluorodeoxyglucose PET/CT in the classification of hepatic echinococcosis in the Qinghai Tibetan area of China.

BACKGROUND: To investigate the value of 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT) semi-quantitative parameters, including the lesion diameter, maximum standardized uptake value (SUVmax), maximum standardized uptake value corrected for lean body mass (SULmax), metabolic lesion volume (MLV), and total lesion glycolysis (TLG), for classifying hepatic echinococcosis. METHODS: In total, 20 patients with 36 hepatic echinococcosis lesions were included in the study. Overall, these lesions were categorized as hepatic cystic echinococcosis (HCE) or hepatic alveolar echinococcosis (HAE) according to the pathological results. Multiple semi-parameters including the maximum diameter, SUVmax, SULmax, MLV, and TLG were measured to classify HCE and HAE compared with the pathological results. The receiver operator characteristic curve and area under the curve (AUC) of each quantitative parameter were calculated. The Mann-Whitney U test was used to compare data between the two groups. RESULTS: In total, 12 cystic lesions and 24 alveolar lesions were identified after surgery. There were significant differences in SUV max, SUL max, MLV, and TLG between the HAE and HCE groups (Z = - 4.70, - 4.77, - 3.36, and - 4.23, respectively, all P < 0.05). There was no significant difference in the maximum lesion diameter between the two groups (Z = - 0.77, P > 0.05). The best cutoffs of SUV max, SUL max, MLV, and TLG for the differential diagnosis of HAE and HCE were 2.09, 2.67, 27.12, and 18.79, respectively. The AUCs of the four parameters were 0.99, 0.99, 0.85, and 0.94, respectively. The sensitivities were 91.7%, 87.5%, 66.7%, and 85.6%, respectively, and the specificities were 90.1%, 91.7%, 83.3%, and 90.9%, respectively. CONCLUSION: 18F-FDG PET/CT semi-quantitative parameters had significant clinical value in the diagnosis and pathological classification of hepatic echinococcosis and evaluation of clinical treatment.

Defining hip osteoarthritis feature prevalence, severity, and change using the Scoring of Hip Osteoarthritis with MRI (SHOMRI).

OBJECTIVE: To define the reporting of Scoring Hip Osteoarthritis with MRI (SHOMRI) feature prevalence and severity, and to develop criteria to monitor feature change in longitudinal investigations. METHODS: Twenty-five participants (50 hips) of the femoroacetabular impingement and hip osteoarthritis cohort study underwent baseline and 2-year follow-up 3 T hip MRIs. Eight hip OA features were assessed using the SHOMRI. All MRIs were read paired with knowledge of timepoint by two blinded musculoskeletal radiologists. We provide definitions to report SHOMRI feature prevalence, severity, and longitudinal change. RESULTS: We report clear definitions for SHOMRI feature prevalence, severity, and change. When we applied the definitions to the studied cohort, we could detect the prevalence, severity, and change of hip OA features. For example, 88% of hips had labral tears (34% graded as severe tears) and 76% had cartilage defects (42% graded as full thickness). Over 70% of hips had feature change over 2 years, highlighting the sensitivity of SHOMRI definitions to assess longitudinal change of hip OA features. Intra-reader reliability was almost perfect (weighted (w)-kappa 0.86 to 1.00), with inter-reader reliability substantial to almost perfect (w-kappa 0.80 to 1.00). CONCLUSION: This study is the first to provide definitions to report SHOMRI feature prevalence, severity, and change. The proposed definitions will enable comparison between hip MRI studies and improve our understanding of hip OA pathogenesis.

A simple color absorption analysis of colorimetric loop-mediated isothermal amplification for detection of Raillietina spp. in clinical samples using a 3D-printed tube holder coupled with a smartphone camera and notebook screen.

A simple method has been developed for semi-quantitative analysis of the colorimetric output of loop-mediated isothermal amplification (LAMP) using a 3D-printed tube holder with a smartphone and notebook for the detection of Raillietina, which is the cause of Raillietiniasis affecting free-range chicken farming. In this method, a light is directed from a notebook screen to the LAMP products in the tube holder and the color absorption of the LAMP products is measured by using the appropriate smartphone application. It was found that the malachite green dye-coupled LAMP (MaG-LAMP) assay showed the highest sensitivity and specificity for detecting Raillietina without any cross-reaction with other related parasites and hosts. The limit of detection was 10 fg/µL of DNA. A total of 60 fecal samples were infectively confirmed by microscopic examination and the results of microscopy compared with those of MaG-LAMP and triplex PCR assays. Microscopy and MaG-LAMP based on the color absorption demonstrated high agreement in Raillietina detection with kappa = 1. Rapid, simple, cost-effective, and easy interpretation of colorimetric LAMP assays and their high sensitivity make them superior to PCR and morphological investigation, demonstrating the feasibility of this assay in point-of-care screening to support farm management and solve chicken health problems. Our study presents is an alternative diagnostic method using semi-quantitative analysis of colorimetric LAMP based on the differing solution color absorptions between positive and negative reactions for infectious disease diagnosis.

Semi-quantitative health risk assessment of heavy metal dust exposure among nail technicians using the SQRA technique and Monte Carlo simulation.

Nail technology, including the application of artificial nails and nail care, is a developing sector of the global beauty industry. Nail technicians are exposed to a variety of chemical substances through inhalation, as they spend extended periods of time in close proximity to these materials. This study aimed to evaluate the semi-quantitative health risk of dust-containing heavy metals among nail technicians. This analytical descriptive study employed the risk assessment method provided by the Singapore Occupational Health Department to evaluate the health hazards of lead, cadmium, nickel, chromium, and manganese. Dust samples from nail filing were collected from the respiratory zone of 20 nail technicians following the NIOSH 7300 method. The samples were analyzed using ICP-OES instrumentation. Monte Carlo simulation was utilized to characterize the risk and its uncertainties. Manganese and cadmium had the highest and lowest mean concentrations, respectively. The risk scores of the metals ranked from highest to lowest were as follows: Ni>Cr>Cd>Mn>Pb. All five metals had risk rankings below 2.8, signifying a minimal risk level. Sensitivity analysis using Spearman's correlation coefficient demonstrated a positive relationship between concentration, daily hours of exposure, and the number of workdays per week with the risk score (RR) and exposure level (ER). Conversely, the variable of weekly working hours (W) showed a negative correlation with these parameters. Despite the low-risk level of the examined metals, continuous exposure and potential long-term effects on nail technicians warrant preventive measures. Recommendations include implementing local exhaust ventilation systems, using table fans, establishing work-rest cycles, wearing N95 dust masks, and using reputable and high-quality nail polishes.

[Expert recommendations for magnetic resonance imaging of muscle disorders]. / Expertenempfehlung zur Magnetresonanztomographie bei Muskelerkrankungen.

BACKGROUND: Magnetic resonance (MRI) imaging of the skeletal muscles (muscle MRI for short) is increasingly being used in clinical routine for diagnosis and longitudinal assessment of muscle disorders. However, cross-centre standards for measurement protocol and radiological assessment are still lacking. OBJECTIVES: The aim of this expert recommendation is to present standards for the application and interpretation of muscle MRI in hereditary and inflammatory muscle disorders. METHODS: This work was developed in collaboration between neurologists, neuroradiologists, radiologists, neuropaediatricians, neuroscientists and MR physicists from different university hospitals in Germany. The recommendations are based on expert knowledge and a focused literature search. RESULTS: The indications for muscle MRI are explained, including the detection and monitoring of structural tissue changes and oedema in the muscle, as well as the identification of a suitable biopsy site. Recommendations for the examination procedure and selection of appropriate MRI sequences are given. Finally, steps for a structured radiological assessment are presented. CONCLUSIONS: The present work provides concrete recommendations for the indication, implementation and interpretation of muscle MRI in muscle disorders. Furthermore, it provides a possible basis for the standardisation of the measurement protocols at all clinical centres in Germany.

A Robust Method for the Unsupervised Scoring of Immunohistochemical Staining.

Immunohistochemistry is a powerful technique that is widely used in biomedical research and clinics; it allows one to determine the expression levels of some proteins of interest in tissue samples using color intensity due to the expression of biomarkers with specific antibodies. As such, immunohistochemical images are complex and their features are difficult to quantify. Recently, we proposed a novel method, including a first separation stage based on non-negative matrix factorization (NMF), that achieved good results. However, this method was highly dependent on the parameters that control sparseness and non-negativity, as well as on algorithm initialization. Furthermore, the previously proposed method required a reference image as a starting point for the NMF algorithm. In the present work, we propose a new, simpler and more robust method for the automated, unsupervised scoring of immunohistochemical images based on bright field. Our work is focused on images from tumor tissues marked with blue (nuclei) and brown (protein of interest) stains. The new proposed method represents a simpler approach that, on the one hand, avoids the use of NMF in the separation stage and, on the other hand, circumvents the need for a control image. This new approach determines the subspace spanned by the two colors of interest using principal component analysis (PCA) with dimension reduction. This subspace is a two-dimensional space, allowing for color vector determination by considering the point density peaks. A new scoring stage is also developed in our method that, again, avoids reference images, making the procedure more robust and less dependent on parameters. Semi-quantitative image scoring experiments using five categories exhibit promising and consistent results when compared to manual scoring carried out by experts.

Association between sleep slow-wave activity and in-vivo estimates of myelin in healthy young men.

Sleep has been suggested to contribute to myelinogenesis and associated structural changes in the brain. As a principal hallmark of sleep, slow-wave activity (SWA) is homeostatically regulated but also differs between individuals. Besides its homeostatic function, SWA topography is suggested to reflect processes of brain maturation. Here, we assessed whether interindividual differences in sleep SWA and its homeostatic response to sleep manipulations are associated with in-vivo myelin estimates in a sample of healthy young men. Two hundred twenty-six participants (18-31 y.) underwent an in-lab protocol in which SWA was assessed at baseline (BAS), after sleep deprivation (high homeostatic sleep pressure, HSP) and after sleep saturation (low homeostatic sleep pressure, LSP). Early-night frontal SWA, the frontal-occipital SWA ratio, as well as the overnight exponential SWA decay were computed over sleep conditions. Semi-quantitative magnetization transfer saturation maps (MTsat), providing markers for myelin content, were acquired during a separate laboratory visit. Early-night frontal SWA was negatively associated with regional myelin estimates in the temporal portion of the inferior longitudinal fasciculus. By contrast, neither the responsiveness of SWA to sleep saturation or deprivation, its overnight dynamics, nor the frontal/occipital SWA ratio were associated with brain structural indices. Our results indicate that frontal SWA generation tracks inter-individual differences in continued structural brain re-organization during early adulthood. This stage of life is not only characterized by ongoing region-specific changes in myelin content, but also by a sharp decrease and a shift towards frontal predominance in SWA generation.

Impact of Sustained Synovitis on Knee Joint Structural Degeneration: 4-Year MRI Data from the Osteoarthritis Initiative.

BACKGROUND: Synovial inflammation is a risk factor for osteoarthritis (OA). But to date, there is limited information on how inflammation impacts progression of knee OA. PURPOSE: To investigate how sustained synovitis, assessed with semi-quantitative magnetic resonance imaging (MRI) scores, impacts progression of knee degenerative changes over 4 years. STUDY TYPE: Retrospective cohort study. SUBJECTS: In 249 participants (N = 132 women [53%]), from the Osteoarthritis Initiative (OAI) two definitions for synovitis were used resulting in two groups of participants with sustained synovitis at baseline, 2-year, and 4-year follow-up (N = 80 and N = 132), and two groups without synovitis at all three time points (N = 81 and N = 47). FIELD STRENGTH/SEQUENCE: 3 T intermediate-weighted (IW) turbo spin-echo (TSE) sequence and three-dimensional (3D) dual-echo steady-state (DESS) sequence. ASSESSMENT: Synovitis was scored semi-quantitatively using the Anterior Cruciate Ligament Osteoarthritis Score (ACLOAS), MRI Osteoarthritis Knee Score (MOAKS), and synovial proliferation score (SPS). Two MRI-based definitions of synovitis were used: (i) score ≥2 based on cumulative score of MOAKS and ACLOAS, and (ii) score ≥3 based on the cumulative score of ACLOAS, MOAKS, and SPS. Changes in structural abnormalities from baseline to year 4 measured using the whole-organ MRI score (WORMS) were defined as outcomes. STATISTICAL TESTS: Linear regression models were used to compare the differences in longitudinal changes in WORMS scores between participants with and without sustained synovitis for each definition of sustained synovitis. A P-value of <0.05 was considered statistically significant. RESULTS: Significantly higher rates of progression were found in participants with synovitis for patellar (Beta coeff. = 0.29) and medial tibial cartilage abnormalities (Beta coeff. = 0.29) for definition (i). For definition (ii), patellar (Beta coeff. = 0.36) and medial femoral cartilage (Beta coeff. = 0.30) abnormalities demonstrated significant differences. DATA CONCLUSION: Greater progression of structural degenerative disease was observed in individuals with sustained synovitis compared to those without sustained synovitis, suggesting that sustained synovitis is associated with progressive OA. LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY: Stage 2.

Analysis of urinary oligosaccharide excretion patterns by UHPLC/HRAM mass spectrometry for screening of lysosomal storage disorders.

Oligosaccharidoses, sphingolipidoses and mucolipidoses are lysosomal storage disorders (LSDs) in which defective breakdown of glycan-side chains of glycosylated proteins and glycolipids leads to the accumulation of incompletely degraded oligosaccharides within lysosomes. In metabolic laboratories, these disorders are commonly diagnosed by thin-layer chromatography (TLC) but more recently also mass spectrometry-based approaches have been published. To expand the possibilities to screen for these diseases, we developed an ultra-high-performance liquid chromatography (UHPLC) with a high-resolution accurate mass (HRAM) mass spectrometry (MS) screening platform, together with an open-source iterative bioinformatics pipeline. This pipeline generates comprehensive biomarker profiles and allows for extensive quality control (QC) monitoring. Using this platform, we were able to identify α-mannosidosis, ß-mannosidosis, α-N-acetylgalactosaminidase deficiency, sialidosis, galactosialidosis, fucosidosis, aspartylglucosaminuria, GM1 gangliosidosis, GM2 gangliosidosis (M. Sandhoff) and mucolipidosis II/III in patient samples. Aberrant urinary oligosaccharide excretions were also detected for other disorders, including NGLY1 congenital disorder of deglycosylation, sialic acid storage disease, MPS type IV B and GSD II (Pompe disease). For the latter disorder, we identified heptahexose (Hex7), as a potential urinary biomarker, in addition to glucose tetrasaccharide (Glc4), for the diagnosis and monitoring of young onset cases of Pompe disease. Occasionally, so-called "neonate" biomarker profiles were observed in young patients, which were probably due to nutrition. Our UHPLC/HRAM-MS screening platform can easily be adopted in biochemical laboratories and allows for simple and robust screening and straightforward interpretation of the screening results to detect disorders in which aberrant oligosaccharides accumulate.

The More Extensive the Spread through Air Spaces, the Worse the Prognosis Is: Semi-Quantitative Evaluation of Spread through Air Spaces in Pulmonary Adenocarcinomas.

INTRODUCTION: The extent of spread through air spaces (STAS) is less investigated among patients with lung adenocarcinoma who underwent sublobar resection. Therefore, we aimed to evaluate the extent of STAS semi-quantitatively, to assess its prognostic impact on overall survival (OS) and recurrence-free survival (RFS), and to investigate the reproducibility of this assessment. METHODS: The number of tumour cell clusters and single tumour cells within air spaces was recorded in three different most prominent areas (200x field of view). The extent of STAS was categorized into three groups, and the presence of free tumour cluster (FTC) was recorded. RESULTS: Sixty-one patients were included. Recurrence was more frequent with higher grade (p = 0.003), presence of lymphovascular invasion (p = 0.027), and presence of STAS of any extent (p = 0.007). In multivariate analysis, presence of FTC (HR: 5.89; 95% CI: 1.63-21.26; p = 0.005) and more pronounced STAS (HR: 7.46; 95% CI: 1.60-34.6; p = 0.01) had adverse impact on OS and RFS, respectively. Concerning reproducibility, excellent agreement was found among STAS parameters (ICC range: 0.92-0.94). DISCUSSION: More extensive STAS is an unfavourable prognostic factor in adenocarcinomas treated with sublobar resection. As the evaluation of extent of STAS is reproducible, further investigation is required to gather more evidence.

Arterial occlusion duration affects the cuff-induced hyperemic response in skeletal muscle BOLD perfusion imaging as shown in young healthy subjects.

OBJECTIVE: Dynamic BOLD MRI with cuff compression, inducing ischemia and post-occlusive hyperemia in skeletal muscle, has been pointed out as a potential diagnostic tool to assess peripheral limb perfusion. The objective was to explore the robustness of this technique and its sensitivity to the occlusion duration. MATERIALS AND METHODS: BOLD images were acquired at 3 T in 14 healthy volunteers. [Formula: see text]-imaging with 5- and 1.5-min occlusions were acquired and several semi-quantitative BOLD parameters were derived from ROI-based [Formula: see text]-time curves. Differences in parameters from the two different occlusion durations were evaluated in the gastrocnemius and soleus muscles using non-parametrical tests. Intra- and inter-scan repeatability were evaluated with coefficient of variation. RESULTS: Longer occlusion duration resulted in an increased hyperemic signal effect yielding significantly different values (p < 0.05) in gastrocnemius for all parameters describing the hyperemic response, and in soleus for two of these parameters. Specifically, 5-min occlusion yielded steeper hyperemic upslope in gastrocnemius (41.0%; p < 0.05) and soleus (59.7%; p = 0.03), shorter time to half peak in gastrocnemius (46.9%; p = 0.00008) and soleus (33.5%; p = 0.0003), and shorter time to peak in gastrocnemius (13.5%; p = 0.02). Coefficients of variation were lower than percentage differences that were found significant. DISCUSSION: Findings show that the occlusion duration indeed influences the hyperemic response and thus should play a part in future methodological developments.

Value of the modified semiquantitative classification in predicting outcomes in children with Henoch-Schönlein purpura nephritis.

BACKGROUND: The modified semiquantitative classification (SQC) is a new pathological classification for Henoch-Schönlein purpura nephritis (HSPN), and its prognostic value with regard to the outcomes of HSPN is unclear. METHODS: We performed a retrospective review of 249 patients with biopsy-proven HSPN admitted to the Children's Hospital of Chongqing Medical University. In addition to the International Study of Kidney Disease in Children (ISKDC) classification, renal biopsy specimens were also reevaluated according to the SQC. RESULTS: During the follow-up period of 2.9 (1.0-6.9) years, 14 (5.6%) patients reached the poor outcome at the end of follow-up. The SQC activity and chronicity indexes were positively correlated with the clinical manifestations, conventional pathology grades, and 24-h urinary protein (24hUP). The difference in the areas under the curve between the total biopsy SQC scores and ISKDC classification was 0.12 (p = .001, 95% CI: 0.0485-0.192). In the receiver operating characteristic (ROC) curve analysis of 1-year, 3-year, and 5-year poor outcomes and total biopsy SQC scores, a total biopsy score ≥10 was associated with a higher risk of an adverse outcome. CONCLUSION: Our study suggests that the SQC indexes are clearly correlated with the clinical and pathological findings of HSPN. The SQC is more sensitive than ISKDC classification for the prediction of the long-term outcomes of HSPN in children.

Assessment of cardiopulmonary manifestations and its correlation with semi-quantitative scoring of high-resolution computed tomography in patients with autoimmune rheumatic diseases.

PURPOSE: Autoimmune rheumatic diseases (ARD) are groups of diseases that are commonly associated with cardiac and pulmonary manifestations and may affect the morbidity and mortality of the patients. The study aimed to the assessment of cardiopulmonary manifestations and their correlation with the semi-quantitative scoring of high-resolution computed tomography (HRCT) in ARD patients. METHODS AND PATIENTS: 30 patients with ARD were included in the study (mean age 42.2 ± 9.76 years) [10 patients were scleroderma (SSc), 10 patients were rheumatoid arthritis (RA), and 10 patients were systemic lupus erythematosus (SLE)]. They all met the diagnostic criteria of the American College of Rheumatology and underwent spirometry, echocardiography, and chest HRCT. The HRCT was assessed by a semi-quantitative score for parenchymal abnormalities. Correlation between HRCT lung scores and: inflammatory markers, lung volumes in spirometry, and echocardiographic indices has been performed. RESULTS: The total lung score (TLS) by HRCT was 14.8 ± 8.78 (mean ± SD), ground glass opacity score (GGO) was 7.20 ± 5.79 (mean ± SD) and fibrosis lung score (F) was 7.63 ± 6.05 (mean ± SD). TLS correlated significantly with ESR (r 0.528, p 0.003), CRP (r 0.439, p 0.015), PaO2 (r -0.395, P 0.031) FVC% (r -0.687, p 0.001), and echocardiographic Tricuspid E (r -0.370, p 0.044), Tricuspid E/è (r -0.397,p 0.03), ESPAP (r 0.459,p 0.011), TAPSE (r -0.405, p 0.027), MPI-TDI (r -0.428, p 0.018) and RV Global strain(r -0.567, p 0.001). GGO score correlated significantly with ESR (r 0.597, p 0.001), CRP (r 0.473, p 0.008), FVC% (r -0.558, p 0.001), and RV Global strain(r -0.496, p 0.005). F score correlated significantly with FVC% (r -0.397, p 0.030), Tricuspid E/è (r -0.445, p 0.014), ESPAP (r 0.402, p 0.028), and MPI-TDI (r -0.448, p 0.013). CONCLUSION: The total lung score and GGO score in ARD were found to be consistently significantly correlated with FVC% predicted, PaO2, inflammatory markers, and RV functions. Fibrotic score correlated with ESPAP. Therefore, in a clinical setting, most clinicians who monitor patients suffering from ARD should concern with the applicability of semiquantitative HRCT scoring in clinical practice.