Conversion map from quantitative parameter mapping to myelin water fraction: comparison with R1·R2* and myelin water fraction in white matter.

OBJECTIVE: To clarify the relationship between myelin water fraction (MWF) and R1⋅R2* and to develop a method to calculate MWF directly from parameters derived from QPM, i.e., MWF converted from QPM (MWFQPM). MATERIALS AND METHODS: Subjects were 12 healthy volunteers. On a 3 T MR scanner, dataset was acquired using spoiled gradient-echo sequence for QPM. MWF and R1⋅R2* maps were derived from the multi-gradient-echo (mGRE) dataset. Volume-of-interest (VOI) analysis using the JHU-white matter (WM) atlas was performed. All the data in the 48 WM regions measured VOI were plotted, and quadratic polynomial approximations of each region were derived from the relationship between R1·R2* and the two-pool model-MWF. The R1·R2* map was converted to MWFQPM map. MWF atlas template was generated using converted to MWF from R1·R2* per WM region. RESULTS: The mean MWF and R1·R2* values for the 48 WM regions were 11.96 ± 6.63%, and 19.94 ± 4.59 s-2, respectively. A non-linear relationship in 48 regions of the WM between MWF and R1·R2* values was observed by quadratic polynomial approximation (R2 ≥ 0.963, P < 0.0001). DISCUSSION: MWFQPM map improved image quality compared to the mGRE-MWF map. Myelin water atlas template derived from MWFQPM may be generated with combined multiple WM regions.

Read-through transcription of tRNA underlies the cell cycle-dependent dissociation of IHF from the DnaA-inactivating sequence datA.

Timely initiation of chromosomal DNA replication in Escherichia coli is achieved by cell cycle-coordinated regulation of the replication origin, oriC, and the replication initiator, ATP-DnaA. Cellular levels of ATP-DnaA increase and peak at the time for initiation at oriC, after which hydrolysis of DnaA-bound ATP causes those to fall, yielding initiation-inactive ADP-DnaA. This hydrolysis is facilitated by the chromosomal locus datA located downstream of the tRNA-Gly (glyV-X-Y) operon, which possesses a cluster of DnaA-binding sequences and a single binding site (IBS) for the DNA bending protein IHF (integration host factor). While IHF binding activates the datA function and is regulated to occur specifically at post-initiation time, the underlying regulatory mechanisms remain obscure. Here, we demonstrate that datA-IHF binding at pre-initiation time is down-regulated depending on the read-through transcription of datA IBS initiated at the glyV-X-Y promoter. During the cell cycle, the level of read-through transcription, but not promoter activity, fluctuated in a manner inversely related to datA-IHF binding. Transcription from the glyV-X-Y promoter was predominantly interrupted at datA IBS by IHF binding. The terminator/attenuator sequence of the glyV-X-Y operon, as well as DnaA binding within datA overall, contributed to attenuation of transcription upstream of datA IBS, preserving the timely fluctuation of read-through transcription. These findings provide a mechanistic insight of tRNA transcription-dependent datA-IHF regulation, in which an unidentified factor is additionally required for the timely datA-IHF dissociation, and support the significance of datA for controlling the cell cycle progression as a connecting hub of tRNA production and replication initiation.

4D Flow MRI Reflects Physiological Hemodynamics for the Diagnosis and Management of Portosystemic Shunts.

A woman in her sixties with portosystemic shunt and hepatic encephalopathy underwent open mesenteric vein ligation, resulting in improved portal flow and blood ammonia. In this case, 4D flow MRI was a valuable diagnostic and follow-up tool, visualizing and quantifying physiological portal hemodynamics with features distinct from those of contrast-enhanced CT and digital subtraction angiography. Our case study highlights the value of 4D flow MRI for managing portosystemic shunts.

An autopsy case of lung adenocarcinoma with immune checkpoint inhibitor-induced pneumonia and fulminant myocarditis following pembrolizumab administration: a case report.

Immune checkpoint inhibitors (ICIs) are the current standard of care for non-small-cell lung cancer (NSCLC). Myocarditis is a rare but serious immune-related adverse event (irAE) associated with ICI therapy. We present a patient who received a single dose of pembrolizumab for NSCLC and developed ICI-associated pneumonia. Although pneumonia improved with corticosteroid therapy, the patient subsequently developed ICI-associated fulminant myocarditis. Despite high-dose corticosteroid therapy, the patient died on day 30 after pembrolizumab initiation. Even if an observed irAE was effectively treated, clinicians should remain vigilant for other irAEs, especially those that are difficult to control with low-dose corticosteroids.

In vitro study of the embolic characteristics of imipenem/cilastatin particles.

BACKGROUND: Imipenem/cilastatin (IPM/CS) has long been administered intravenously as a carbapenem antibiotic. However, since this agent is poorly soluble in liquid, occasional reports have described its use as a short-acting, temporary embolic agent. The purpose of this study was to elucidate the characteristics of IPM/CS particles, which are thought to have pain-relieving effects against osteoarthritis-related pain, as an embolic agent. METHODS: Three aspects of IPM/CS as an embolic agent were evaluated in vitro: particle size; particle shape; and change in particle size over time. For particle size, the long diameter was measured. RESULTS: Mean particle size (n=244) was 29.2±12.0 µm (range, 1-60 µm). Shape (n=109) was round in 18.35%, elliptical in 11.93%, and polygonal in 69.72%, showing that most particles were polygonal. In observations of changes in particle size over time (n=9), particles had decreased to 75% of their original size at 82±10.7 min, 50% at 89.3±9.14 min, 25% at 91.3±8.74 min, complete dissolved at 91.8±9.02 min. A rapid shrinkage in diameter was seen in the final period. CONCLUSIONS: IPM/CS particles are ultrafine and the majority display a polygonal shape. This substance shows ultra-short embolic activity. This study revealed the characteristics of a substance that demonstrates an embolic effect not found in existing embolic materials.

Differences of white matter structure for diffusion kurtosis imaging using voxel-based morphometry and connectivity analysis.

Objectives: In a clinical study, diffusion kurtosis imaging (DKI) has been used to visualize and distinguish white matter (WM) structures' details. The purpose of our study is to evaluate and compare the diffusion tensor imaging (DTI) and DKI parameter values to obtain WM structure differences of healthy subjects. Methods: Thirteen healthy volunteers (mean age, 25.2 years) were examined in this study. On a 3-T MRI system, diffusion dataset for DKI was acquired using an echo-planner imaging sequence, and T1-weghted (T1w) images were acquired. Imaging analysis was performed using Functional MRI of the brain Software Library (FSL). First, registration analysis was performed using the T1w of each subject to MNI152. Second, DTI (eg, fractional anisotropy [FA] and each diffusivity) and DKI (eg, mean kurtosis [MK], radial kurtosis [RK], and axial kurtosis [AK]) datasets were applied to above computed spline coefficients and affine matrices. Each DTI and DKI parameter value for WM areas was compared. Finally, tract-based spatial statistics (TBSS) analysis was performed using each parameter. Results: The relationship between FA and kurtosis parameters (MK, RK, and AK) for WM areas had a strong positive correlation (FA-MK, R2 = 0.93; FA-RK, R2 = 0.89) and a strong negative correlation (FA-AK, R2 = 0.92). When comparing a TBSS connection, we found that this could be observed more clearly in MK than in RK and FA. Conclusions: WM analysis with DKI enable us to obtain more detailed information for connectivity between nerve structures. Advances in knowledge: Quantitative indices of neurological diseases were determined using segmenting WM regions using voxel-based morphometry processing of DKI images.

Three-dimensional simultaneous T1 and T2* relaxation times and quantitative susceptibility mapping at 3 T: A multicenter validation study.

We aimed to determine the intra-site repeatability and cross-site reproducibility of T1 and T2* relaxation times and quantitative susceptibility (χ) values obtained through quantitative parameter mapping (QPM) at 3 T. This prospective study included three 3-T scanners with the same hardware and software platform at three sites. The brains of twelve healthy volunteers were scanned three times using QPM at three sites. Intra-site repeatability and cross-site reproducibility were evaluated based on voxel-wise and region-of-interest analyses. The within-subject coefficient of variation (wCV), within-subject standard deviation (wSD), linear regression, Bland-Altman plot, and intraclass correlation coefficient (ICC) were used for evaluation. The intra-site repeatability wCV was 11.9 ± 6.86% for T1 and 3.15 ± 0.03% for T2*, and wSD of χ at 3.35 ± 0.10 parts per billion (ppb). Intra-site ICC(1,k) values for T1, T2*, and χ were 0.878-0.904, 0.972-0.976, and 0.966-0.972, respectively, indicating high consistency within the same scanner. Linear regression analysis revealed a strong agreement between measurements from each site and the site-average measurement, with R-squared values ranging from 0.79 to 0.83 for T1, 0.94-0.95 for T2*, and 0.95-0.96 for χ. The cross-site wCV was 13.4 ± 5.47% for T1 and 3.69 ± 2.25% for T2*, and cross-site wSD of χ at 4.08 ± 3.22 ppb. The cross-site ICC(2,1) was 0.707, 0.913, and 0.902 for T1, T2*, and χ, respectively. QPM provides T1, T2*, and χ values with an intra-site repeatability of <12% and cross-site reproducibility of <14%. These findings may contribute to the development of multisite studies.

Peculiar properties of tuber starch in a potato mutant lacking the α-glucan water dikinase 1 gene GWD1 created by targeted mutagenesis using the CRISPR/dMac3-Cas9 system.

Glucose chains in starch are phosphorylated and contribute to structural stabilization. Phosphate groups contained in starch also play a role in retaining moisture. α-Glucan water dikinase 1 (GWD1) is involved in the phosphorylation of glucose chains in starch. In this study, we generated potato mutants of the GWD1 gene using the CRISPR/dMac3-Cas9 system. Observation of the phenotypes of the GWD1-deficient mutants revealed their physiological roles in tuber starch formation. The 4-allele mutants showed growth retardation and a delay in tuber formation. A significant decrease in phosphorus content was detected in the tuber starch of the gwd1 mutant. This mutant starch showed a higher amylose content than the wild-type starch, whereas its gelatinization temperature was slightly lower than that of the WT starch. The peak viscosity of the mutant starch was lower than that of the WT starch. These observations revealed that the starch of the gwd1 mutants had peculiar and unique properties compared to those of WT, sbe3 and gbss1 mutant starches. The amount of tissue-released water due to freeze-thawing treatment was determined on tubers of the gwd1 mutant and compared with those of WT and the other mutants. Significantly less water loss was found in the gwd1, sbe3 and gbss1 mutant tubers than in the WT tubers. Our results indicate that the GWD1 gene is not only important for potato growth, but also largely effective for the traits of tuber starch.