Semi-quantitative Measurements Research Articles

Experimental investigation of unsteady nature of shock waves induced by various ramps

The ramp induced shock wave boundary layer interaction (RI-SWBLI) has been investigated experimentally at different ramp angles in a Ma = 3 flow. The shock unsteady nature has been examined in detail by using a semi-quantitative processing of Schlieren images. The shock-wave locations are extracted to allow spectral analysis of the shock-wave oscillations. Results show that the shock motion is associated with the state of separation, which has been categorized into three classifications based on semi-quantitative Schlieren measurements, namely, unseparated, initially separated, and fully separated. The statistical analysis of the shock oscillation illustrates that the probability distribution function and power spectral density (PSD) along two locations of a certain height follow almost the same principles in the time–frequency domain. The PSD results show that significant variations of shock motion of lower location occur at 30° ramp interaction flow according to the PSD, which is characterized by a lower energy, wide range, and uniformly distributed motion. The probability of the reattachment shock events first rises at 24° ramp interaction flow. With increase in ramp angle, the axial position at the peak of the probability of shock events slowly transfers to upstream positions. Moreover, a conceptual model of the shock motion is proposed to preliminarily reveal the unsteady nature of shock induced by a RI-SWBLI, including three scenarios: In nonseparating interaction flows, the shock motion is mainly affected by the upstream turbulent boundary layer and the shear layer on the ramp. During the initial separation process, the shock wave motion is mainly affected by the pulsations of separation bubble. With full separation, impact movement is primarily controlled by newly designed aerodynamic ramp.

Interrogating post-transplant donor HLA-specific antibody characteristics and effector functions using clinical bead assays

Single antigen bead (SAB) assays are the most common and sensitive method used to detect and monitor post-transplant donor specific HLA antibodies (DSA). However, a direct comparison across traditional and modified SAB assays to improve routine DSA monitoring using pre-treated IgG sera to eliminate interference has not been performed. We performed a technical comparison of 251 post-transplant DSA from n = 91 serum samples tested neat (pre-treated, undiluted), at a single 1:16 dilution, in the C1q bead assay, and for IgG subclasses (IgG1, IgG2, IgG3, IgG4) with IgG-enriched sera. We found that DSAs that are detectable by 1:16 dilution and/or C1q are associated with higher IgG MFI values and results could be predicted by testing neat sera. DSA detected at 1:16 dilution correlated with >7000 IgG MFI in neat sera and identified DSA that exceeded the SAB linear range for semiquantitative measurements. C1q positive DSA correlated with >15,000 IgG MFI in neat sera. C1q binding correlated most strongly with total IgG MFI (Spearman r = 0.82, p = 0.002) and not specific subclasses, demonstrating that DSA C1q binding capacity in this cohort is driven by HLA-specific IgG concentration. Evaluation of engineered pan-HLA class I-specific human IgG1 and IgG2 subclass monoclonal antibodies by SAB C1q and C3d assays revealed that IgG2 antibodies can bind complement at higher concentrations. The strengths and limitations of modified SAB assays must be considered to optimize efficient testing and accurate clinical interpretation.

N-coordinated iron sites dispersed in porous carbon frameworks to activate peroxymonosulfate for efficient sulfisoxazole degradation and real hospital wastewater decontamination

Herein, an N-coordinated Fe site dispersed in porous carbon frameworks (Fe-NC) fabricated from zeolitic imidazolate frameworks encapsulated with iron acetylacetonate (Fe(acac)3 @ZIFs) was employed to activate peroxymonosulfate (PMS) for the attenuation of sulfisoxazole (SIZ) and treating real hospital wastewater. The constructed Fe-NC/PMS system exhibited good catalytic stability for SIZ degradation, maintaining excellent degradation performance over multiple cycles with virtually no leaching. The quenching experiments, electron paramagnetic resonance (EPR) capture analyses, and semi-quantitative measurements showed that singlet oxygen (1O2) and high-valent metal-oxo species were mainly responsible for SIZ degradation by Fe-NC/PMS. Significantly, ultra-performance liquid chromatography coupled to quadrupole time-of-flight mass spectrometry (UHPLC-Q-TOF-MS/MS) was used to trace 134 pharmaceutical contaminants in real hospital wastewater. Effective degradation was achieved for 87 % of the pharmaceutical contaminants by the Fe-NC/PMS process. Seventy-four pharmaceutical contaminants were eliminated. Taken together, this work successfully established the Fe-NC/PMS technology using the developed iron-based materials and explored its application to real hospital wastewater treatment, providing an eco-friendly and effective strategy for treating wastewater.

Ultrasounds outperform magnetic resonance imaging in quantifying meniscal extrusion in patients with knee osteoarthritis.

The aim of this study was to quantify meniscal extrusion through ultrasound (US) evaluation in supine and standing positions and to compare the results with those documented through magnetic resonance (MR) imaging in patients affected by knee osteoarthritis (OA). Sixty patients (38 men, 22 women, mean age 60.8 ± 9.7 years) with knee OA were enrolled and underwent a 1.5 T MR evaluation and an US examination of the symptomatic OA knee for the evaluation of the medial and lateral meniscus extrusion both in the supine clinostatic position (clino-US) with the knee fully extended and in the standing weight-bearing orthostatic position (ortho-US). For the three imaging evaluations (MR, clino-US and ortho-US), both semi-quantitative and quantitative measurements were performed. The quantitative analysis documented higher values of medial meniscal extrusion at the ortho-US evaluation (5.2 ± 2.3 mm) compared to MR (4.2 ± 2.2, p < 0.0005) and clino-US (4.5 ± 2.3, p < 0.0005) and of the lateral meniscus at the ortho-US evaluation (4.3 ± 1.8) compared to MR (3.3 ± 1.6, p < 0.0005) and clino-US (3.8 ± 1.6, p < 0.0005). The semi-quantitative analysis confirmed the same trend for both menisci. Higher extrusion values were documented in women and more advanced OA, as well as in older patients with higher body mass index, the latter being underestimated the most by the MR approach. US outperforms MR imaging in quantifying meniscal extrusion in patients with knee OA. Moreover, the highest values of meniscal extrusion have been documented using US in standing position compared to the supine position, underlining the importance of the weight-bearing assessment of meniscal extrusion in knee OA patients. II.

The effect of reconstruction algorithms on semi-quantitative measurements in 18F-FDG PET/CT imaging.

This study was carried out to understand whether Q.Clear and ordered subset expectation maximization (OSEM), reconstruction algorithms used in fluorine-18-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) applications, and parameters such as time of flight (TOF) and point spread function (PSF) cause different results in semi-quantitative measurements. Raw PET data of 264 patients who were referred to 18F-FDG PET/CT imaging with the purpose of evaluation of known or suspicious malignant disease were reconstructed separately with Q.Clear (GE Healthcare), a BPL, an OSEM algorithm, PSF (SharpIR®) and TOF (VUE Point FX®) methods. Each patient's liver, mediastinal blood pool, metabolic tumor volume (MTV), total lesion glycolysis (TLG), and standardized uptake values (SUV) (SUVmax, SUVmean, and SUVpeak) of a total of 264 lesions selected from the patients were performed. β350+ToF yielded higher measurement results than all other variables for all of the lesion SUVmax, lesion SUVmean, L/AP SUVmax, and L/AP SUVmean parameters. OSEM+ToF and OSEM+TOF+PSF algorithms yielded higher mean and median SUVmax values for the reference structures (liver and mediastinum) and for lesions SUVmax and SUVmean values were statistically significantly lower than the β350+ToF method. The method with the lowest mean value for the L/Liver SUVmax variable was OSEM+ToF 4iter16ss (mean=1.76), while the method with the highest mean value was β350+ToF (mean=2.26). β350+ToF was the reconstruction method with the highest ratios for L/AP SUVmax and SUVmean for both lesions below and above 1 cm. β350+ToF algorithm had also statistically significantly higher results for these variables compared to all other parameters in malignant lesions. When comparing 18F-FDG PET/CT images, the use of different reconstruction algorithms may lead to misleading results, especially in the evaluation of response to treatment of malignancies.

64 Cu]Copper chloride PET-CT: a comparative evaluation of fasting and non-fasting states in patients of prostate carcinoma.

Altered copper metabolism in cancer has been linked to increased intracellular copper uptake mediated by human copper transporter 1, with [ 64 Cu]Cu 2+ as a potential biomarker for cancer theranostics. [ 64 Cu]CuCl 2 PET-CT though explored in various malignancies, a lack of standardized protocol exists, particularly regarding fasting status before imaging. This analysis aimed to evaluate the requirement of fasting for [ 64 Cu]CuCl 2 PET-CT along with temporal changes in physiological organ uptake in delayed scans. A total of 26 patients of prostate carcinoma who underwent [ 64 Cu]CuCl 2 PET-CT imaging were divided into two groups: (1) nonfasting ( n = 12) and (2) fasting ( n = 14). The nonfasting group received an average dose of 350 MBq, while the fasting group received 300 MBq of [ 64 Cu]CuCl 2 , and PET-CT images acquired approximately 60-90 min (1 h image) and 3-3.5 h (delayed image) after intravenous injection of the tracer. An experienced nuclear medicine physician evaluated the images for qualitative assessment between the groups. Multiple spherical regions of interest were placed at sites of physiological organ uptake of the tracer and over the diseased lesions to measure the mean SUV max . No significant difference was observed in the qualitative assessment of the images between the two groups (except for a slight predilection towards more hepatic tracer retention observed in the fasting group), including in the delayed images. The liver demonstrated the highest tracer uptake in all patients, with a mean SUV max of 21.5 in the fasting group and 19.7 in the nonfasting group, showing no significant difference ( P = 0.32). The kidneys, intestines, and salivary glands also showed similar trends of tracer uptake in both groups. The study illustrated that the fasting or nonfasting status did not affect image quality or semiquantitative measurements significantly in physiological organs and diseased lesions in patients with carcinoma prostate.

A Radioactivity-mass Spectrometry Calibration Method Coupled with Biosynthesis to Generate a Metabolite Standard for Enzyme Kinetics Studies

In early stages of drug development, the absence of authentic metabolite standards often results in semi-quantitative measurements of metabolite formation in reaction phenotyping studies using mass spectrometry (MS), leading to inaccuracies in the determination of enzyme kinetic parameters, such as the Michaelis constant (Km). Moreover, it is impossible to ascertain the maximum rate of enzyme-catalyzed reactions (kcat or Vmax). The use of radiolabeled parent compounds can circumvent this problem. However, radiometric detection exhibits significantly lower sensitivity compared to MS. To address these challenges, we have developed a stepwise approach that leverages biosynthesized radiolabeled and non-radiolabeled metabolites as standards, enabling accurate determination of Km, kcat or Vmax without the need for authentic metabolite standards. This approach, using the carbon-14 [14C] labeled metabolite to calibrate the unlabeled metabolite (14C calibration method), combines radiometric with LC-MS/MS detection to generate both [14C]-labeled and unlabeled metabolite standard curves to ensure that the sample concentrations measured are accurately quantitated. Two case studies were presented to demonstrate the utility of this method. We first compared the accuracy of the 14C calibration method to the use of authentic standards for quantitating imipramine metabolites. Next, we biosynthesized and quantitated the metabolites of BI 894416 using 14C calibration method and evaluated the enzyme kinetics of metabolite formation. The Km values of the metabolite formation demonstrated substantially improved accuracy compared to MS semi-quantitation. Moreover, the 14C calibration method offers a streamlined approach to prepare multiple metabolite standards from a single biosynthesis, reducing the time required for structure elucidation and metabolite synthesis.

Intraoperative Doppler flowmetry evaluation of humeral head perfusion after proximal humerus fracture

Understanding vascularity and assessing the risk of post-traumatic avascular necrosis are crucial for predicting outcomes and identifying optimal treatment options in proximal humerus fractures (PHFs). Until now, Hertel etal have been the only researchers to evaluate the intraoperative perfusion of the humeral head after fracture using Doppler flowmetry in a central single drill hole within the head. This pilot study aims to standardize the evaluation of intraoperative perfusion measurements in different areas of the humeral head in patients with PHF. In this prospective pilot study, intraoperative semiquantitative Doppler perfusion measurements were conducted during plate osteosynthesis for PHF treatment in our institution between July 2021 and May 2022. The fracture morphology was classified radiologically according to Resch's criteria. Quality of reduction was determined postoperatively to be either anatomical, minor malreduced, or major malreduced according to Peters etal in conventional and computed tomography examinations. Medial hinge integrity and medial metaphyseal extension were assessed radiographically according to Hertel etal. Intraoperatively, after drilling screw holes through the plate, a Doppler probe was inserted through all nine drill holes on the humeral head and at least one on the humeral shaft to successively measure the presence of a pulse to indicate if perfusion is present. A total of ten patients (mean age 59 years, range, 36-83) with a humeral head fracture (2× 2GL, 3× 3G, 2× 4G, 2× 4GL, 1× 5aG according to Resch) were included. Nine of the ten patients showed a pulse signal on the humeral shaft. Overall, pulse-synchronous perfusion was detected using Doppler sonography in at least one hole in the humeral head of all patients. In patients with an intact medial hinge (N=6), pulse-synchronous perfusion could be measured in almost twice as many humeral head holes on average (5.7 vs. 3.0 drill holes) compared to patients with a dislocated medial hinge (N=4). In patients with metaphyseal extension (N=3), pulse-synchronous perfusion was measured in an average of 6.7 humeral head holes compared to 3.7 holes in patients without metaphyseal extension (N=7). Semiquantitative, intraoperative Doppler flowmetry offers a noninvasive and rapid assessment of humeral perfusion which allows an understanding of humeral head perfusion, when used in a standardized fashion to measure flow in different areas of the humeral head.

Brain and Ventricle Volume Alterations in Idiopathic Normal Pressure Hydrocephalus Determined by Artificial Intelligence-Based MRI Volumetry.

The aim of this study was to employ artificial intelligence (AI)-based magnetic resonance imaging (MRI) brain volumetry to potentially distinguish between idiopathic normal pressure hydrocephalus (iNPH), Alzheimer's disease (AD), and age- and sex-matched healthy controls (CG) by evaluating cortical, subcortical, and ventricular volumes. Additionally, correlations between the measured brain and ventricle volumes and two established semi-quantitative radiologic markers for iNPH were examined. An IRB-approved retrospective analysis was conducted on 123 age- and sex-matched subjects (41 iNPH, 41 AD, and 41 controls), with all of the iNPH patients undergoing routine clinical brain MRI prior to ventriculoperitoneal shunt implantation. Automated AI-based determination of different cortical and subcortical brain and ventricular volumes in mL, as well as calculation of population-based normalized percentiles according to an embedded database, was performed; the CE-certified software mdbrain v4.4.1 or above was used with a standardized T1-weighted 3D magnetization-prepared rapid gradient echo (MPRAGE) sequence. Measured brain volumes and percentiles were analyzed for between-group differences and correlated with semi-quantitative measurements of the Evans' index and corpus callosal angle: iNPH patients exhibited ventricular enlargement and changes in gray and white matter compared to AD patients and controls, with the most significant differences observed in total ventricular volume (+67%) and the lateral (+68%), third (+38%), and fourth (+31%) ventricles compared to controls. Global ventriculomegaly and marked white matter reduction with concomitant preservation of gray matter compared to AD and CG were characteristic of iNPH, whereas global and frontoparietally accentuated gray matter reductions were characteristic of AD. Evans' index and corpus callosal angle differed significantly between the three groups and moderately correlated with the lateral ventricular volumes in iNPH patients [Evans' index (r > 0.83, p ≤ 0.001), corpus callosal angle (r < -0.74, p ≤ 0.001)]. AI-based MRI volumetry in iNPH patients revealed global ventricular enlargement and focal brain atrophy, which, in contrast to healthy controls and AD patients, primarily involved the supratentorial white matter and was marked temporomesially and in the midbrain, while largely preserving gray matter. Integrating AI volumetry in conjunction with traditional radiologic measures could enhance iNPH identification and differentiation, potentially improving patient management and therapy response assessment.

Associations of Urine and Plasma Metabolites With Kidney Failure and Death in a Chronic Kidney Disease Cohort

Rationale & ObjectiveBiomarkers that enable better identification of persons with chronic kidney disease (CKD) who are at higher risk for disease progression and adverse events are needed. This study sought to identify urine and plasma metabolites associated with progression of kidney disease. Study DesignProspective metabolome-wide association study. Setting & ParticipantsPersons with CKD enrolled in the German CKD Study (GCKD) with metabolite measurements; with external validation within the Atherosclerosis Risk in Communities Study. Exposures1,513 urine and 1,416 plasma metabolites (Metabolon, Inc.) measured at study entry using untargeted mass spectrometry. OutcomesMain endpoints were kidney failure (KF), and a composite endpoint of KF, eGFR <15 mL/min/1.73m2, or 40% decline in eGFR (CKE). Death from any cause was a secondary endpoint. After a median of 6.5 years follow-up, 500 persons experienced KF, 1,083 experienced CKE and 680 died. Analytical ApproachTime-to-event analyses using multivariable proportional hazard regression models in a discovery-replication design, with external validation. Results5,088 GCKD participants were included in analyses of urine metabolites and 5,144 in analyses of plasma metabolites. Among 182 unique metabolites, 30 were significantly associated with KF, 49 with CKE, and 163 with death. The strongest association with KF was observed for plasma hydroxyasparagine (hazard ratio: 1.95, 95% confidence interval: 1.68-2.25). An unnamed metabolite measured in plasma and urine was significantly associated with KF, CKE, and death. External validation of the identified associations of metabolites with KF or CKE revealed direction-consistency for 88% of observed associations. Selected associations of 18 metabolites with study outcomes have not been previously reported. LimitationsUse of observational data and semi-quantitative metabolite measurements at a single time point. ConclusionsThe observed associations between metabolites and KF, CKE or death in persons with CKD confirmed previously reported findings and also revealed several associations not previously described. These findings warrant confirmatory research in other study cohorts.

Neuropathological assessment of the olfactory bulb and tract in individuals with COVID-19

The majority of patients with Parkinson disease (PD) experience a loss in their sense of smell and accumulate insoluble α-synuclein aggregates in their olfactory bulbs (OB). Subjects affected by a SARS-CoV-2-linked illness (COVID-19) also frequently experience hyposmia. We previously postulated that microglial activation as well as α-synuclein and tau misprocessing can occur during host responses following microbial encounters. Using semiquantitative measurements of immunohistochemical signals, we examined OB and olfactory tract specimens collected serially at autopsies between 2020 and 2023. Deceased subjects comprised 50 adults, which included COVID19 + patients (n = 22), individuals with Lewy body disease (e.g., PD; dementia with Lewy bodies (n = 6)), Alzheimer disease (AD; n = 3), and other neurodegenerative disorders (e.g., progressive supranuclear palsy (n = 2); multisystem atrophy (n = 1)). Further, we included neurologically healthy controls (n = 9), and added subjects with an inflammation-rich brain disorder as neurological controls (NCO; n = 7). When probing for microglial and histiocytic reactivity in the anterior olfactory nuclei (AON) by anti-CD68 immunostaining, scores were consistently elevated in NCO and AD cases. In contrast, microglial signals on average were not significantly altered in COVID19 + patients relative to healthy controls, although anti-CD68 reactivity in their OB and tracts declined with progression in age. Mild-to-moderate increases in phospho-α-synuclein and phospho-tau signals were detected in the AON of tauopathy- and synucleinopathy-afflicted brains, respectively, consistent with mixed pathology, as described by others. Lastly, when both sides were available for comparison in our case series, we saw no asymmetry in the degree of pathology of the left versus right OB and tracts. We concluded from our autopsy series that after a fatal course of COVID-19, microscopic changes in the rostral, intracranial portion of the olfactory circuitry -when present- reflected neurodegenerative processes seen elsewhere in the brain. In general, microglial reactivity correlated best with the degree of Alzheimer’s-linked tauopathy and declined with progression of age in COVID19 + patients.

11C-CFT PET brain imaging in Parkinson’s disease using a total-body PET/CT scanner

PurposeThis study aimed to evaluate the feasibility of 11C-CFT PET brain imaging in Parkinson’s Disease using a total-body PET/CT scanner and explore the optimal scan duration to guide the clinical practice.MethodsThirty-two patients with Parkinson’s disease (PD) performing 11C-CFT PET/CT brain imaging using a total-body PET/CT scanner were retrospectively enrolled. The PET data acquired over a period of 900 s were reconstructed into groups of different durations: 900-s, 720-s, 600-s, 480-s, 300-s, 180-s, 120-s, 60-s, and 30-s (G900 to G30). The subjective image quality analysis was performed using 5-point scales. Semi-quantitative measurements were analyzed by SUVmean and dopamine transporter (DAT) binding of key brain regions implicated in PD, including the caudate nucleus and putamen. The full-time images (G900) were served as reference.ResultsThe overall G900, G720, and G600 image quality scores were 5.0 ± 0.0, 5.0 ± 0.0, and 4.9 ± 0.3 points, respectively, and there was no significant difference among these groups (P > 0.05). A significant decrease in these scores at durations shorter than 600 s was observed when compared to G900 images (P < 0.05). However, all G300 image quality was clinically acceptable (≥ 3 points). As the scan duration reduced, the SUVmean and DAT binding of caudate nucleus and putamen decreased progressively, while there were no statistically significant variations in the SUVmean of the background among the different groups. Moreover, the changes in the lesion DAT binding (ΔDAT-binding) between the full-time reference G900 image and other reconstructed group G720 to G30 images generally increased along with the reduced scan time.ConclusionSufficient image quality and lesion conspicuity could be achieved at 600-s scan duration for 11C-CFT PET brain imaging in PD assessment using a total-body PET/CT scanner, while the image quality of G300 was acceptable to meet clinical diagnosis, contributing to improve patient compliance and throughput of PET brain imaging.

Phytosterols in human serum as measured using a liquid chromatography tandem mass spectrometry

Phytosterols are lipophilic compounds found in plants with structural similarity to mammalian cholesterol. They cannot be endogenously produced by mammals and therefore always originate from diet. There has been increased interest in dietary phytosterols over the last few decades due to their association with a variety of beneficial health effects including low-density lipoprotein cholesterol lowering, anti-inflammatory and anti-cancerous effects. They are proposed as potential moderators for diseases associated with the central nervous system where cholesterol homeostasis is found to be imperative (multiple sclerosis, dementia, etc.) due to their ability to reach the brain. Here we utilised an enzyme-assisted derivatisation for sterol analysis (EADSA) in combination with a liquid chromatography tandem mass spectrometry (LC-MSn) to characterise phytosterol content in human serum. As little as 100 fg of plant sterol was injected on a reversed phase LC column. The method allows semi-quantitative measurements of phytosterols and their derivatives simultaneously with measurement of cholesterol metabolites. The identification of phytosterols in human serum was based on comparison of their LC retention times and MS2, MS3 spectra with a library of authentic standards. Free campesterol serum concentration was in the range from 0.30-4.10 µg/mL, β-sitosterol 0.16-3.37 µg/mL and fucosterol was at lowest concentration range from 0.05-0.38 µg/mL in ten individuals. This analytical methodology could be applied to the analysis of other biological fluids and tissues.

Semiquantitative 18F-FDG PET/CT in monitoring glucocorticoid response of immunoglobulin G4-related effusive constrictive pericarditis: a case report

BackgroundImmunoglobulin G4 (IgG4)-related effusive constrictive pericarditis (ECP) is a rare manifestation of IgG4-related disease (IgG4-RD). It can lead to persistent pericardial fibrosis, resulting in cardiac tamponade, diastolic dysfunction, and heart failure. Glucocorticoids are the primary treatment for effectively reducing inflammation and preventing fibrosis. However, guidelines for monitoring treatment response are lacking and tapering glucocorticoid therapy for specific target organs remains a challenge. Recent studies on IgG4-RD have demonstrated that semiquantitative measurements of fluorine-18 fluorodeoxyglucose (18F-FDG) uptake in the main involved organs in positron emission tomography/computed tomography (PET/CT) scanning are correlated to disease activity. We present a case of IgG4-related ECP to demonstrate the usefulness of 18F-FDG PET/CT for diagnosing and treatment follow-up of IgG4-related ECP.Case presentationHerein, a 66-year-old woman diagnosed with IgG4-related ECP presented with breathlessness, leg swelling, rales, and fever. Laboratory tests revealed markedly elevated levels of C-reactive protein, and transthoracic echocardiography revealed constrictive physiology with effusion. High IgG4 levels suggested an immune-related pathogenesis, while viral and malignant causes were excluded. Subsequent pericardial biopsy revealed lymphocyte and plasma cell infiltration in the pericardium, confirming the diagnosis of IgG4-related ECP. 18F-FDG PET/CT revealed increased uptake of 18F-FDG in the pericardium, indicating isolated cardiac involvement of IgG4-RD. Treatment with prednisolone and colchicine led to a rapid improvement in the patient’s condition within a few weeks. Follow-up imaging with 18F-FDG PET/CT after 3 months revealed reduced inflammation and improved constrictive physiology on echocardiography, leading to successful tapering of the prednisolone dose and discontinuation of colchicine.ConclusionThe rarity of IgG4-related ECP and possibility of multiorgan involvement in IgG4-RD necessitates a comprehensive diagnostic approach and personalized management. This case report highlights the usefulness of 18F-FDG PET/CT in the diagnosis and treatment follow-up of isolated pericardial involvement in IgG4-RD.

High-Throughput Lipidomic and Metabolomic Profiling for Brain Tissue and Biofluid Samples in Neurodegenerative Disorders.

Recent research has revealed the potential of lipidomics and metabolomics in identifying new biomarkers and mechanistic insights for neurodegenerative disorders. To contribute to this promising area, we present a detailed protocol for conducting an integrated lipidomic and metabolomic profiling of brain tissue and biofluid samples. In this method, a single-phase methanol extraction is employed for extracting both nonpolar and highly polar lipids and metabolites from each biological sample. The extracted samples are then subjected to liquid chromatography-mass spectrometry-based assays to provide relative or semiquantitative measurements for hundreds of selected lipids and metabolites per sample. This high-throughput approach enables the generation of new hypotheses regarding the mechanistic and functional significance of lipid and metabolite alterations in neurodegenerative disorders while also facilitating the discovery of new biomarkers to support drug development.

A novel approach to guide GD2-targeted therapy in pediatric tumors by PET and [64Cu]Cu-NOTA-ch14.18/CHO.

Background: The tumor-associated disialoganglioside GD2 is a bona fide immunotherapy target in neuroblastoma and other childhood tumors, including Ewing sarcoma and osteosarcoma. GD2-targeting antibodies proved to be effective in neuroblastoma and GD2-targeting chimeric antigen receptors (CAR)- expressing T cells as well as natural killer T cells (NKTs) are emerging. However, assessment of intra- and intertumoral heterogeneity has been complicated by ineffective immunohistochemistry as well as sampling bias in disseminated disease. Therefore, a non-invasive approach for the assessment and visualization of GD2 expression in-vivo is of upmost interest and might enable a more appropriate treatment stratification. Methods: Recently, [64Cu]Cu-NOTA-ch14.18/CHO (64Cu-GD2), a radiolabeled GD2-antibody for imaging with Positron-Emission-Tomography (PET) was developed. We here report our first clinical patients' series (n = 11) in different pediatric tumors assessed with 64Cu-GD2 PET/MRI. GD2-expression in tumors and tissue uptake in organs was evaluated by semiquantitative measurements of standardized uptake values (SUV) with PET/MRI on day 1 p.i. (n = 11) as well as on day 2 p.i. (n = 6). Results: In 8 of 9 patients with suspicious tumor lesions on PET/MRI at least one metastasis showed an increased 64Cu-GD2 uptake and a high tracer uptake (SUVmax > 10) was measured in 4 of those 8 patients. Of note, sufficient image quality with high tumor to background contrast was readily achieved on day 1. In case of 64Cu-GD2-positive lesions, an excellent tumor to background ratio (at least 6:1) was observed in bones, muscles or lungs, while lower tumor to background contrast was seen in the spleen, liver and kidneys. Furthermore, we demonstrated extensive tumor heterogeneity between patients as well as among different metastatic sites in individual patients. Dosimetry assessment revealed a whole-body dose of only 0.03 mGy/MBq (range 0.02-0.04). Conclusion: 64Cu-GD2 PET/MRI enables the non-invasive assessment of individual heterogeneity of GD2 expression, which challenges our current clinical practice of patient selection, stratification and immunotherapy application scheme for treatment with anti-GD2 directed therapies.

Tectonic-sedimentary evolution in a Palaeocene rifted Lishui Sag, East China Sea Shelf Basin

Influenced by episodic tectonic activity and multiple sediment sources, the source-to-sink systems in rifted basins are relatively complex. Based on seismic data, well logging, cores, thin sections, and heavy mineral data, the growth and linkage of the Lingfeng fault were reconstructed and its influence on the sedimentary responses of the Palaeocene-rifted Lishui Sag in the East China Sea Shelf Basin was examined. The researchers conducted a fault throw-distance analysis on the Lingfeng fault and found that it displayed an overall weak-strong-weak evolutionary process. During the early syn-rift stage, the Lingfeng fault exhibited a segmented geometry consisting of seven fault segments with low fault activity along its strike, and small-scale source-to-sink systems developed in both the hanging wall dip-slope and footwall. As the main syn-rift stage progressed, strong fault activity induced large-scale exposure of the source area, resulting in a high sediment-supply rate and large-scale source-to-sink systems. During the late syn-rift stage, the fault weakened and evolved into a connected basin-boundary fault, and proximal source-to-sink systems in the footwall gradually disappeared. Semi-quantitative measurements of the geomorphic parameters of these source-to-sink systems indicated wide and shallow sediment transport pathways in hanging wall dip-slope areas (average width and depth of approximately 6.34 kmand 0.13 km, respectively) and narrow and deep sediment transport pathways in the footwall (average width and depth of approximately 3.75 km and 0.15 km, respectively). The semi-quantitative statistical analysis implies that the cross-sectional area of the transport channels was positively correlated with the corresponding fan/delta complexes in a rift basin.

Duvelisib for Critically Ill Patients With Coronavirus Disease 2019: An Investigator-Initiated, Randomized, Placebo-Controlled, Double-Blind Pilot Trial.

Despite improvements in prevention and treatment, severe coronavirus disease 2019 (COVID-19) is associated with high mortality. Phosphoinositide 3-kinase (PI3K) pathways contribute to cytokine and cell-mediated lung inflammation. We conducted a randomized, placebo-controlled, double-blind pilot trial to determine the feasibility, safety, and preliminary activity of duvelisib, a PI3Kδγ inhibitor, for the treatment of COVID-19 critical illness. We enrolled adults aged ≥18 years with a primary diagnosis of COVID-19 with hypoxic respiratory failure, shock, and/or new cardiac disease, without improvement after at least 48 hours of corticosteroid. Participants received duvelisib (25 mg) or placebo for up to 10 days. Participants had daily semi-quantitative viral load measurements performed. Dose modifications were protocol driven due to adverse events (AEs) or logarithmic change in viral load. The primary endpoint was 28-day overall survival (OS). Secondary endpoints included hospital and intensive care unit length of stay, 60-day OS, and duration of critical care interventions. Safety endpoints included viral kinetics and AEs. Exploratory endpoints included serial cytokine measurements and cytometric analysis. Fifteen patients were treated in the duvelisib cohort, and 13 in the placebo cohort. OS at 28 days was 67% (95% confidence interval [CI], 38%-88%) compared to 62% (95% CI, 32%-86%) for placebo (P = .544). Sixty-day OS was 60% versus 46%, respectively (hazard ratio, 0.66 [95% CI, .22-1.96]; P = .454). Other secondary outcomes were comparable. Duvelisib was associated with lower inflammatory cytokines. In this pilot study, duvelisib did not significantly improve 28-day OS compared to placebo for severe COVID-19. Duvelisib appeared safe in this critically ill population and was associated with reduction in cytokines implicated in COVID-19 and acute respiratory distress syndrome, supporting further investigation. NCT04372602.

A flexible gradient lateral flow immunochromatographic assay for qualitative, semi-quantitative, and quantitative determination of serum amyloid A

Serum amyloid A (SAA) is an acute-phase protein produced in response to inflammatory proteins during infections, inflammation, trauma, surgery, cancer, and other conditions. Early and accurate detection of SAA is necessary for diagnosis and monitoring of disease progression. To meet this need, we developed a gradient lateral flow immunoassay test strip using Au nanoparticles as signal reporters. The test strip has three test (T1, T2, and T3) lines with progressively decreasing concentrations of SAA antibody, enabling the determination of high, medium, and low concentrations of SAA in serum. The test strip results were analyzed using three distinct readout methods, each with different sensitivity, accuracy, and precision for SAA concentration measurements. Qualitative judgment is based on the color of the T1 line. Semi-quantitative assessment of SAA concentration is determined by the number of colored T-lines. Specifically, color development in T1 line alone indicates a concentration range of 10–50 μg/mL, while T1 and T2 lines together indicate a range of 50–100 μg/mL, and development in all three lines (T1, T2, and T3) indicates a concentration of >100 μg/mL. Quantitative analysis was performed using either smartphone imaging or image scanning with ImageJ software. By using a five-parameter logistic function, we found a strong correlation (R2 = 0.998) between the ratio of signal intensities of (T1 + T2 + T3) to the control (C) line and SAA concentrations ranging from 5 to 1000 μg/mL. At lower concentrations (0–100 μg/mL), we observed a proportional relationship between the value of (T1 + T2 + T3)/C and SAA concentration. The limit of detection for SAA was 9.33 ng/mL (or 6.53 μg/mL of SAA in undiluted serum samples) for the smartphone method and 3.06 ng/mL (or 2.14 μg/mL of SAA in undiluted serum samples) for the scanner method. The gradient test strip was highly consistent with a commercially available SAA immunochromatographic test strip when tested with real human serum samples. Passing-Bablok regression indicated that results obtained using the smartphone app and scanner methods of the gradient test strip were comparable to those obtained using the commercial test strip. The gradient test strip is flexible and adaptable, providing solutions for qualitative, semi-quantitative, and quantitative SAA measurements.

Can lung semi-quantitative measurements and mediastinal adipose tissue volume predict prognosis in patients with idiopathic pulmonary fibrosis (IPF)? A CT-based preliminary study.

The aim of this study was to assess the potential of subcutaneous adipose tissue volume, mediastinal adipose tissue volume, lung density, and lung volume (as measured on high-resolution computed tomography) to predict disease progression in patients with idiopathic pulmonary fibrosis (IPF). Additionally, the study aimed to evaluate the changes in these semiquantitative measures over time. The HRCT images of 57 patients diagnosed with IPF were retrospectively screened. Subcutaneous adipose tissue volume, mediastinal adipose tissue volume, and mean lung density and volume were measured at the time of diagnosis and at the 12th month. The ability of these parameters to predict progression was evaluated using the univariate and multivariate Cox regression analyses. Low mediastinal adipose tissue volume at diagnosis had a 0.991-fold effect [odds ratio (OR)= 0.991, 95% confidence interval (CI)= 0.984-0.997, p< 0.001] on progression. Low mediastinal adipose tissue volume at diagnosis had a 0.993-fold effect [odds ratio (OR)= 0.993, 95% confidence interval (CI)= 0.975-1.011, p< 0.001] and progression development at the 12th month had a 6.5-fold effect [odds ratio (OR)= 6.516, 95% confidence interval (CI)= 1.594-26.639, p< 0.009] on mortality. This study indicate that the prognosis was better in those with a large mediastinal adipose tissue volume among the patients with IPF.