Pathological analysis of Prader-Willi syndrome using adipocytes.

Prader-Willi syndrome (PWS) is a complex epigenetic disorder caused by the deficiency of paternally expressed genes in chromosome 15q11-q13. This syndrome also includes endocrine dysfunction, leading to short stature, hypogonadism, and obscure hyperphagia. Although recent progress has been made toward understanding the genetic basis for PWS, the molecular mechanisms underlying its pathology in obesity remain unclear. In this study, we examined the adipocytic characteristics of two PWS-induced pluripotent stem cell (iPSC) lines: those with the 15q11-q13 gene deletion (iPWS cells) and those with 15q11-q13 abnormal methylation (M-iPWS cells). The transcript levels of the lipid-binding protein aP2 were decreased in iPWS and M-iPWS adipocytes. Flow-cytometry analysis showed that PWS adipocytes accumulated more lipid droplets than did normal individual adipocytes. Furthermore, glucose uptake upon insulin stimulation was attenuated compared to that in normal adipocytes. Overall, our results suggest a significantly increased lipid content and defective in glucose metabolism in PWS adipocytes.

The Interaction between Anesthetic Isoflurane and Model-Biomembrane Monolayer Using Simultaneous Quartz Crystal Microbalance (QCM) and Quartz Crystal Impedance (QCI) Methods.

The interaction between anesthetic Isoflurane (Iso) and model-biomembrane on the water surface has been investigated using quartz crystal microbalance (QCM) and quartz crystal impedance (QCI) methods. The model-biomembranes used were dipalmitoyl phosphatidyl choline (DPPC), DPPC-palmitic acid (PA) mixture (DPPC:PA = 8:2), DPPC-Alamethicin (Al) mixture (DPPC:Al = 39:1), and DPPC-ß-Lactoglobulin (ßLG) mixture (DPPC:ßLG = 139:1) monolayers, respectively. The quartz crystal oscillator (QCO) was attached horizontally to each monolayer, and QCM and QCI measurements were performed simultaneously. It was found that Iso hydrate physisorbed on each monolayer/water interface from QCM and changed those interfacial viscosities from QCI. With an increase in Iso concentration, pure DPPC, DPPC-PA mixed, and DPPC-Al mixed monolayers showed a two-step process of Iso hydrate on both physisorption and viscosity, whereas it was a one-step for the DPPC-ßLG mixed monolayer. The viscosity change in the DPPC-ßLG mixed monolayer with the physisorption of Iso hydrate was much larger than that of other monolayers, in spite of the one-step process. From these results, the action mechanism of anesthetics and their relevance to the expression of anesthesia were discussed, based on the "release of interfacial hydrated water" hypothesis on the membrane/water interface.

Development of a suitable vibration pad for renal MR elastography.

The aim of this study was to develop a vibration pad suitable for renal MR elastography (MRE). Chronic kidney disease (CKD) is a progressive condition affecting >800 million people worldwide. Renal fibrosis is a common pathological feature of CKD that causes fibrotic regions to be much stiffer than those in normal renal tissues. Therefore, MRE can be used to diagnose CKD because it can image organ stiffness. In MRE, the shear modulus is obtained from the wavelength of the shear waves. Therefore, it is highly important to propagate shear waves with sufficient vibration strength in the tissue. By using a three-dimensional (3D) printer, we created a "Flexible Pad" suitable for renal MRE. The Flexible Pad was placed under the back of the participant in the supine position and deformed in response to the participant's weight, adhering closely to the body surface. Six healthy volunteers participated in this study. Our Flexible Pad allowed for coherent shear waves (clear waves with little scattering and interference) to be efficiently transmitted to the kidney deep-lying tissues in the abdomen. The shear moduli of the kidney (n = 6) were 8.95 ± 0.84 kPa in the right kidney and 9.70 ± 0.99 kPa in the left kidney. Our results indicate that using our Flexible Pad for renal MRE can provide a more reliable measurement of renal shear modulus.

Fast abdominal magnetic resonance elastography with simultaneous encoding of three-dimensional displacements.

Three-dimensional (3D) magnetic resonance elastography (MRE) is more accurate than two-dimensional (2D) MRE; however, it requires long-term acquisition. This study aimed to reduce the acquisition time of abdominal 3D MRE using a new sample interval modulation (short-SLIM) approach that can acquire all three motions faster while reducing the prolongation of echo time and flow compensation. To this end, two types of phantom studies and an in vivo test of the liver in three healthy volunteers were performed to compare the performances of conventional spin-echo echo-planar (SE-EPI) MRE, conventional SLIM and short-SLIM. One phantom study measured the mean amplitude and shear modulus within the overall region of a homogeneous phantom by changing the mechanical vibration power to assess the robustness to the lowered phase-to-noise ratio in short-SLIM. The other measured the mean shear modulus in the stiff and background materials of a phantom with an embedded stiffer rod to assess the performance of short-SLIM for complex wave patterns with wave interference. The Spearman's rank correlation coefficient was used to assess similarity of elastograms in the rod-embedded phantom and liver between methods. The results of the phantom study changing the vibration power indicated that there was little difference between conventional MRE and short-SLIM. Moreover, the elastogram pattern and the mean shear modulus in the rod-embedded phantom in conventional SLIM and short-SLIM did not change for conventional MRE; the liver test also showed a small difference between the acquisition techniques. This study demonstrates that short-SLIM can provide MRE results comparable to those of conventional MRE. Short-SLIM can reduce the total acquisition time by a factor of 2.25 compared to conventional 3D MRE time, leading to an improvement in the accuracy of shear modulus estimation by suppressing the patient movements.

Defects in early synaptic formation and neuronal function in Prader-Willi syndrome.

Prader-Willi syndrome (PWS), which is a complex epigenetic disorder caused by the deficiency of paternally expressed genes in chromosome 15q11-q13, is associated with several psychiatric dimensions, including autism spectrum disorder. We have previously reported that iPS cells derived from PWS patients exhibited aberrant differentiation and transcriptomic dysregulation in differentiated neural stem cells (NSCs) and neurons. Here, we identified SLITRK1 as a downregulated gene in NSCs differentiated from PWS patient iPS cells by RNA sequencing analysis. Because SLITRK1 is involved in synaptogenesis, we focused on the synaptic formation and function of neurons differentiated from PWS patient iPS cells and NDN or MAGEL2 single gene defect mutant iPS cells. Although ßIII tubulin expression levels in all the neurons were comparable to the level of differentiation in the control, pre- and postsynaptic markers were significantly lower in PWS and mutant neurons than in control neurons. PSD-95 puncta along ßIII tubulin neurites were also decreased. Membrane potential responses were measured while exposed to high K+ stimulation. The neuronal excitabilities in PWS and mutant neurons showed significantly lower intensity than that of control neurons. These functional defects in PWS neurons may reflect phenotypes of neurodevelopmental disorders in PWS.

Improving taxonomic classification of marine zooplankton by molecular approach: registration of taxonomically verified 18S and 28S rRNA gene sequences.

Background: Zooplankton plays an important role in the marine ecosystem. A high level of taxonomic expertise is necessary for accurate species identification based on morphological characteristics. As an alternative method to morphological classification, we focused on a molecular approach using 18S and 28S ribosomal RNA (rRNA) gene sequences. This study investigates how the accuracy of species identification by metabarcoding improves when taxonomically verified sequences of dominant zooplankton species are added to the public database. The improvement was tested by using natural zooplankton samples. Methods: rRNA gene sequences were obtained from dominant zooplankton species from six sea areas around Japan and registered in the public database for improving the accuracy of taxonomic classifications. Two reference databases with and without newly registered sequences were created. Comparison of detected OTUs associated with single species between the two references was done using field-collected zooplankton samples from the Sea of Okhotsk for metabarcoding analysis to verify whether or not the newly registered sequences improved the accuracy of taxonomic classifications. Results: A total of 166 sequences in 96 species based on the 18S marker and 165 sequences in 95 species based on the 28S marker belonging to Arthropoda (mostly Copepoda) and Chaetognatha were registered in the public database. The newly registered sequences were mainly composed of small non-calanoid copepods, such as species belonging to Oithona and Oncaea. Based on the metabarcoding analysis of field samples, a total of 18 out of 92 OTUs were identified at the species level based on newly registered sequences in the data obtained by the 18S marker. Based on the 28S marker, 42 out of 89 OTUs were classified at the species level based on taxonomically verified sequences. Thanks to the newly registered sequences, the number of OTUs associated with a single species based on the 18S marker increased by 16% in total and by 10% per sample. Based on the 28S marker, the number of OTUs associated with a single species increased by 39% in total and by 15% per sample. The improved accuracy of species identification was confirmed by comparing different sequences obtained from the same species. The newly registered sequences had higher similarity values (mean >0.003) than the pre-existing sequences based on both rRNA genes. These OTUs were identified at the species level based on sequences not only present in the Sea of Okhotsk but also in other areas. Discussion: The results of the registration of new taxonomically verified sequences and the subsequent comparison of databases based on metabarcoding data of natural zooplankton samples clearly showed an increase in accuracy in species identification. Continuous registration of sequence data covering various environmental conditions is necessary for further improvement of metabarcoding analysis of zooplankton for monitoring marine ecosystems.

A Versatile MR Elastography Research Tool with a Modified Motion Signal-to-noise Ratio Approach.

PURPOSE: This study aimed to facilitate research progress in MR elastography (MRE) by providing a versatile and convenient application for MRE reconstruction, namely the MRE research tool (MRE-rTool). It can be used for a series of MRE image analyses, including phase unwrapping, arbitrary bandpass and directional filtering, noise assessment of the wave propagation image (motion SNR), and reconstruction of the elastogram in both 2D and 3D MRE acquisitions. To reinforce the versatility of MRE-rTool, the conventional method of motion SNR was modified into a new method that reflects the effects of image filtering. METHODS: MRE tests of the phantom and liver were performed using different estimation algorithms for stiffness value (algebraic inversion of the differential equation [AIDE], local frequency estimation [LFE] in MRE-rTool, and multimodel direct inversion [MMDI] in clinical reconstruction) and acquiring dimensions (2D and 3D acquisitions). This study also tested the accuracy of masking low SNR regions using modified and conventional motion SNR under various mechanical vibration powers. RESULTS: The stiffness values estimated using AIDE/LFE in MRE-rTool were comparable to that of MMDI (phantom, 3.71 ± 0.74, 3.60 ± 0.32, and 3.60 ± 0.54 kPa in AIDE, LFE, and MMDI; liver, 2.26 ± 0.31, 2.74 ± 0.16, and 2.21 ± 0.26 kPa in AIDE, LFE, and MMDI). The stiffness value in 3D acquisition was independent of the direction of the motion-encoding gradient and was more accurate than that of 2D acquisition. The masking of low SNR regions using the modified motion SNR worked better than that in the conventional motion SNR for each vibration power, especially when using a directional filter. CONCLUSION: The performance of MRE-rTool on test data reached the level required in clinical MRE studies. MRE-rTool has the potential to facilitate MRE research, contribute to the future development of MRE, and has been freely released online.

pH response and mechanical properties of Fe2O3-TeO2-based glass/stainless steel enamel electrodes for pH sensors.

Glass pH sensors are unsuitable for in vivo biomedical, clinical, or food applications because of the brittleness of glass and the difficulty in measuring small volumes. Enamel structures such as glass/stainless steel are candidates for glass-based pH electrodes. In this study, new enamel electrodes for pH sensors using Fe2O3-TeO2-based glass/stainless steel were developed. The effect of NiO addition to Fe2O3-TeO2 glass on the pH sensitivity and the three-point bending strength of enamels were investigated. The effect of NiO addition to Fe2O3-TeO2 glass/stainless steel on the pH sensitivity was negligible. Fe2O3-TeO2-based glass/stainless steel showed pH sensitivity appropriate to a working electrode. Enameling at a lower temperature under an air atmosphere was desirable for narrowing the gap between pH 4-7 and pH 7-9 sensitivities. The NiO addition to Fe2O3-TeO2 glass/stainless steel decreased the three-point bending strength. Therefore, NiO did not serve as an adhesion oxide in the Fe2O3-TeO2 glass. Fe2O3-TeO2 glass/stainless steel possessed the highest three-point bending strength among all samples when prepared at 670 °C under an air atmosphere. Therefore, no NiO addition and enameling at a lower temperature under an air atmosphere are desirable for obtaining more robust Fe2O3-TeO2 glass/stainless steel than Li2O-SiO2-based glass electrodes for pH sensors.

A peptide derived from adaptor protein STAP-2 inhibits tumor progression by downregulating epidermal growth factor receptor signaling.

Signal-transducing adaptor family member-2 (STAP-2) is an adaptor protein that regulates various intracellular signals. We previously demonstrated that STAP-2 binds to epidermal growth factor receptor (EGFR) and facilitates its stability and activation of EGFR signaling in prostate cancer cells. Inhibition of this interaction may be a promising direction for cancer treatment. Here, we found that 2D5 peptide, a STAP-2-derived peptide, blocked STAP-2-EGFR interactions and suppressed EGFR-mediated proliferation in several cancer cell lines. 2D5 peptide inhibited tumor growth of human prostate cancer cell line DU145 and human lung cancer cell line A549 in murine xenograft models. Additionally, we determined that EGFR signaling and its stability were decreased by 2D5 peptide treatment during EGF stimulation. In conclusion, our study shows that 2D5 peptide is a novel anticancer peptide that inhibits STAP-2-mediated activation of EGFR signaling and suppresses prostate and lung cancer progression.

Time-course of physical properties of the psoas major muscle after exercise as assessed by MR elastography.

This study aimed to analyze the time-course of the physical properties of the psoas major muscle (PM) before and after exercise using magnetic resonance elastography (MRE). Muscle stiffness is one of the important properties associated with muscle function. However, there was no research on the stiffness of the PM after exercise. In this study, we investigated time-course changes of the shear modulus of the PM after exercise. Furthermore, T2 values and apparent diffusion coefficient (ADC), as the additional information associated with muscular physical properties, were also measured simultaneously. Healthy young male volunteers were recruited in this study (n = 9) and they were required to perform a hand-to-knee isometric and unilateral exercise (left side). At each time-point before and after exercise, a set of 3 types of MR scans to measure multiple physical properties of the PM [shear modulus (MRE), T2 values, and ADC] were repeatedly taken. On day 1, a single set MR scan was taken before exercise (pre-exercise MR scan), and 6 sets MR scans were taken (5.5 to 38.0 min after exercise). After about 10-min rest (46.0 to 56.0 min after exercise), 4 sets MR scans were taken (57.5 to 77.0 min after exercise). About 10-min rest was taken again (85.0-95.0 min after exercise), 4 sets MR scans were taken (96.5 to 116.0 min after exercise). On days 2 and 7, a single set MR scan (MRE, T2 value, and ADC) was taken on each experimental day. The data were analyzed as relative changes (%) of the given parameters to the pre-exercise values. The results indicated significant decreases in PM shear modulus up to about 30 min after exercise. Then, it gradually increased and showed significant increases at about 100 min after exercise compared to that before exercise. T2 values and ADC showed significant increases up to about 65 min after exercise compared to those before exercise, and then returned to the pre-exercise values. On days 2 and 7, all values showed no significant changes compared to the pre-exercise values. This study is the first to report the time-course of the physical properties of the PM after exercise.

A novel technique for automating stiffness measurement and emphasizing the main wave: Coherent-wave auto-selection (CHASE).

This study aims to develop and assess a new automated processing technique in MR elastography (MRE), namely coherent-wave auto-selection (CHASE). CHASE enables automatic selection of the region of interest (ROI) for stiffness measurement by extraction of the coherent wave region (CHASE ROI), and it improves the reconstruction of stiffness by a directional filter oriented along the main wave in each pixel (CHASE filtering). In this study, MRE of a phantom and of the liver of four healthy volunteers was performed. To investigate the potential of CHASE, this study assessed the CHASE according to three indices through the phantom study: 1) agreement on the ROI settings between CHASE and expert observers, 2) noise dependency, and 3) effect of the CHASE on stiffness variability within the CHASE ROI. The agreements on the ROI settings were analyzed by Cohen's kappa coefficient (κ). The noise dependency was analyzed by the mean absolute percentage errors (MAPEs) within the ROI between low (20%-80% amplitudes) and high vibration amplitudes (100% amplitude). The stiffness variability was assessed by standard deviation (SD) within the ROI. In the volunteer study, agreements on the ROI settings (or stiffness value) and stiffness variability within the CHASE ROI were assessed using κ-value (or intraclass correlation coefficient: ICC) and coefficient of variation, respectively. The results showed close agreement on the ROI settings and stiffness (κ-value: greater than 0.61 in both the phantom and volunteer studies, ICC: 0.97 in the volunteer study). The MAPEs within the CHASE ROI were much smaller than those in the whole region of the phantom (CHASE ROI vs. the whole region at 20% amplitude: 10.3% vs. 50.8%). Moreover, in both the phantom and volunteer studies, the stiffness variation within the CHASE ROI was smaller in the elastogram processed with CHASE filtering than in the unprocessed one. Our results demonstrated that the CHASE has high robustness against noise and the potential to provide ROI settings for stiffness measurement comparable to expert observers, as well as improve the reconstruction of stiffness.

Suppressive effect of dexamethasone on murine Th9 cell-mediated nasal eosinophilic inflammation.

BACKGROUND: Th9 cells have been implicated in the development of allergic inflammation, though its contribution to allergic rhinitis and the effect of steroid on Th9 cell-mediated nasal responses are unclear. OBJECTIVE: In this study, allergen-induced nasal inflammatory responses and their steroid responsiveness were investigated in ovalbumin (OVA)-specific Th9 cell-transferred mice. METHODS: BALB/c mice were transferred with in vitro-differentiated Th9 cells and challenged by intranasal injection of OVA with or without subcutaneous administration of dexamethasone (Dex). Then, the infiltration of inflammatory cells in the nasal mucosa and nasal hyperresponsiveness (NHR) was assessed. RESULTS: The significant NHR accompanied by nasal infiltration of eosinophils as well as allergen-specific T cells was induced in Th9 cell-transferred mice upon allergen challenge. These responses were strongly suppressed by the treatment with Dex. CONCLUSION: The participation of Th9 cells in the pathogenesis of allergic rhinitis was suggested.

L-type amino acid transporter 1 inhibitor suppresses murine Th2 cell-mediated bronchial hyperresponsiveness independently of eosinophil accumulation.

BACKGROUND: The activation of Th2 cells that play a pivotal role in the development of allergic eosinophilic inflammation is regulated by an L-type amino acid transporter (LAT) 1. However, the contribution of LAT1 to the pathogenesis of Th2 cell-mediated airway inflammation has not been investigated. OBJECTIVE: In this study, we investigated the effect of a LAT1 inhibitor, JPH203, on Th2 cell-mediated airway eosinophilic inflammation. METHODS: BALB/c mice were transferred with ovalbumin (OVA)-specific Th2 cell and challenged by corresponding allergen with or without administration of JPH203. Then, the infiltration of inflammatory cells including eosinophils and allergen-specific Th2 cells in the lungs and bronchial hyperresponsiveness (BHR) was assessed. RESULTS: Inflammatory responses in the lungs with massive accumulation of eosinophils and BHR were induced in Th2 cell-transferred mice upon challenge with OVA. The treatment with JPH203 significantly suppressed the allergen-induced BHR but not eosinophil infiltration. The infused Th2 cells were also accumulated in the lungs upon allergen challenge, though the response was not affected by JPH203 treatment. CONCLUSION: JPH203 suppressed Th2 cell-mediated BHR through the mechanisms independently of the lung accumulation of eosinophils and Th2 cells.

Deneddylation by SENP8 restricts hepatitis B virus propagation.

Proteins newly synthesized from messenger RNA undergo Posttranslational modifications (PTMs) such as phosphorylation, glycosylation, methylation, and ubiquitination. These PTMs have important roles in protein stability, localization, and conformation and have been reported to be involved in hepatitis B virus (HBV) propagation. Although ubiquitination plays an essential role in HBV life cycles, the involvement of ubiquitin-like proteins (UBLs) in HBV life cycles has been understudied. Through comprehensive gain- and loss-of-function screening of UBLs, we observed that neddylation, a PTM in which neural precursor cell, expressed developmentally downregulated 8 (NEDD8) is conjugated to substrate proteins, was required for efficient HBV propagation. We also found that overexpression of sentrin-specific protease 8 (SENP8), which cleaves conjugated NEDD8, suppressed HBV propagation. Further, the catalytic activity of SENP8 was required for the suppression of HBV propagation. These results indicated that the reduction of neddylation negatively regulated HBV propagation. In addition, we demonstrated that suppression of HBV propagation via SENP8 overexpression was independent of hepatitis B protein X (HBx) and HBV promoter activity. Therefore, our data suggested that neddylation plays an important role in the late stages of HBV life cycles.

Enhancement of Photosynthetic Iron-Use Efficiency Is an Important Trait of Hordeum vulgare for Adaptation of Photosystems to Iron Deficiency.

Leaf iron (Fe) contents in Fe-deficiency-tolerant plants are not necessarily higher than that in Fe-deficiency-susceptible ones, suggesting an unknown mechanism involved in saving and allowing the efficient use of minimal Fe. To quantitatively evaluate the difference in Fe economy for photosynthesis, we compared the ratio of CO2 assimilation rate to Fe content in newly developed leaves as a novel index of photosynthetic iron-use efficiency (PIUE) among 23 different barley (Hordeum vulgare L.) varieties. Notably, varieties originating from areas with alkaline soil increased PIUE in response to Fe-deficiency, suggesting that PIUE enhancement is a crucial and genetically inherent trait for acclimation to Fe-deficient environments. Multivariate analyses revealed that the ability to increase PIUE was correlated with photochemical quenching (qP), which is a coefficient of light energy used in photosynthesis. Nevertheless, the maximal quantum yield of photosystem II (PSII) photochemistry, non-photochemical quenching, and quantum yield of carbon assimilation showed a relatively low correlation with PIUE. This result suggests that the ability of Fe-deficiency-tolerant varieties of barley to increase PIUE is related to optimizing the electron flow downstream of PSII, including cytochrome b6f and photosystem I.

Modulation of Band Gaps toward Varying Conductivities in Heterometallic One-Dimensional Chains by Ligand Alteration and Third Metal Insertion.

A heterometallic one-dimensional (1-D) chain consisting of multiple kinds of metals, Rh, Pt, and Pd, with direct metal-metal bonds was successfully obtained by mixing a Rh dinuclear complex and Pt-Pd-Pt trinuclear complex. The Pt-Pd-Pt trinuclear complex can be reversibly one-electron-oxidized or -reduced, where the electron paramagnetic resonance spectrum of the one-electron-oxidized one shows an axially symmetric signal with hyperfine splitting by two Pt and Pd, indicating that an unpaired electron is delocalized to the d z 2 orbital of Pt-Pd-Pt. Utilized with the highest occupied molecular orbital and lowest unoccupied molecular orbital interaction at the d z 2 orbital, simple mixing of the Pt-Pd-Pt trinuclear complex and Rh dinuclear complex in adequate solvents afforded heterometallic 1-D chains, which are aligned as -Rh-Rh-Pt-Pd-Pt-. Several physical measurements revealed that the metal oxidation state is +2. Diffuse reflectance spectra and theoretical calculations show that heterometallic 1-D chains have σ-type conduction and valence bands where π*(Rh2) are lying between them, whose gaps become narrower than the prototype chains aligned as -Rh-Rh-Pt-Pt-Pt-Pt-. The narrower band gaps are induced by destabilization of the σ-type valence bands and accompanied by insertion of Pd ions because the d-orbital energy level of Pd is closer in value to Rh compared with Pt. Flash-photolysis time-resolved microwave conductivity measurements exhibited an increase in the product of charge carrier mobility and its generation efficiency (8.1 × 10-5 to 4.6 × 10-4 cm2 V-1 s-1) with narrowing the band gaps, suggesting that the better conductivity is attributed to shorter metal-metal distances in 1-D chains. These results imply the possibilities of controlling band gap with ligand modification and third metal insertion in heterometallic 1-D chains to show various conductivities.

Estimation and prediction of ellipsoidal molecular shapes in organic crystals based on ellipsoid packing.

Crystal structure prediction has been one of the fundamental and challenging problems in materials science. It is computationally exhaustive to identify molecular conformations and arrangements in organic molecular crystals due to complexity in intra- and inter-molecular interactions. From a geometrical viewpoint, specific types of organic crystal structures can be characterized by ellipsoid packing. In particular, we focus on aromatic systems which are important for organic semiconductor materials. In this study, we aim to estimate the ellipsoidal molecular shapes of such crystals and predict them from single molecular descriptors. First, we identify the molecular crystals with molecular centroid arrangements that correspond to affine transformations of four basic cubic lattices, through topological analysis of the dataset of crystalline polycyclic aromatic molecules. The novelty of our method is that the topological data analysis is applied to arrangements of molecular centroids intead of those of atoms. For each of the identified crystals, we estimate the intracrystalline molecular shape based on the ellipsoid packing assumption. Then, we show that the ellipsoidal shape can be predicted from single molecular descriptors using a machine learning method. The results suggest that topological characterization of molecular arrangements is useful for structure prediction of organic semiconductor materials.

Discontinuation of Cardiac Resynchronization Therapy for Heart Failure Due to Dilated Cardiomyopathy in a 61-Year-Old Female "-Super-Responder" with Return of a Reduced Left Ventricular Ejection Fraction to Normal.

BACKGROUND Although cardiac resynchronization therapy (CRT) is widely used, it has been validated only during active pacing. "Super-responders" are patients with normalized or markedly improved left ventricular (LV) systolic function with CRT who may experience a decline in cardiac function with CRT discontinuation. CASE REPORT A 61-year-old woman with a nonischemic cardiomyopathy was admitted to our hospital in September 2008 for the treatment of heart failure (HF). Cardiac assessment revealed impaired LV function with an ejection fraction of 18%, LV dilatation, and left bundle branch block (LBBB). Despite optimized medical treatment, her HF progressed, with a rapid increase in LV chamber size, mitral regurgitation, and widening of the QRS complex. In July 2011, the patient initially refused CRT, but later consented to the procedure; CRT pacemaker implantation was subsequently performed. Thereafter, the LVEF improved from 27% to 46%, LV diastolic dimension decreased rapidly from 79 mm to 56 mm, and LVEF (65%) and LV size (47 mm) normalized within 1 year later. As of August 2012, battery exchange was needed within 1 year because of high LV pacing thresholds. In October 2012, although CRT discontinuation was not recommended, we discontinued CRT to conserve battery life with the patient's consent, hoping to maintain her condition with pharmaceutical treatment. She remained stable through January 2020, with no indication of re-exacerbation. CONCLUSIONS We describe a female patient with a nonischemic cardiomyopathy and LBBB who demonstrated a super-response to CRT and maintained improvement in LV function and functional status for 8 years after discontinuing CRT.

Magnetic resonance elastography of the supraspinatus muscle: A preliminary study on test-retest repeatability and wave quality with different frequencies and image filtering.

The purpose of this study was to determine an optimal condition (vibration frequency and image filtering) for stiffness estimation with high accuracy and stiffness measurement with high repeatability in magnetic resonance elastography (MRE) of the supraspinatus muscle. Nine healthy volunteers underwent two MRE exams separated by at least a 30 min break, on the same day. MRE acquisitions were performed with a gradient-echo type multi-echo MR sequence at 75, 100, and 125 Hz pneumatic vibration. Wave images were processed by a bandpass filter or filter combining bandpass and directional filters (bandpass-directional filter). An observer specified the region of interest (ROI) on clear wave propagation in the supraspinatus muscle, within which the observer measured the stiffness. This study assessed wave image quality according to two indices, as a substitute for the assessment of the accuracy of the stiffness estimation. One is the size of the clear wave propagation area (ROI size used to measure the stiffness) and the other is the qualitative stiffness resolution score in that area. These measurements made by the observer were repeated twice at least one month apart after each MRE exam. This study assessed the intra-examiner and observer repeatability of the stiffness value, ROI size and resolution score in each combination of vibration frequency and image filter. Repeatability of the data was analyzed using the intraclass correlation coefficient (ICC) and 95% limits-of-agreement (LOA) in Bland-Altman analysis. The analyses on intra-examiner and observer repeatability of stiffness indicated that the ICC and 95% LOA were not varied greatly depending on vibration frequency and image filter (intra-examiner repeatability, ICC range, 0.79 to 0.88; 95% LOA range, ±23.95 to ±32.42%, intra-observer repeatability, ICC range, 0.98 to 1.00; 95% LOA range, ±5.10 to ±10.99%). In the analyses on intra-examiner repeatability of ROI size, ICCs were rather low (ranging from: 0.03 to 0.69) while 95% LOA was large in all the combinations of vibration frequency and image filter (ranging from: ±62.66 to ±83.33%). In the analyses on intra-observer repeatability of ROI size, ICCs were sufficiently high in the total combination of vibration frequency and image filter (ranging from 0.80 to 0.87) while the 95% LOAs were better (lower) in the bandpass-directional filter than the bandpass filter (bandpass directional filter vs. bandpass filter, ±28.81 vs. ±54.83% at 75 Hz; ±25.63 vs. ±37.83% at 100 Hz; ±34.51 vs. ±43.36% at 125 Hz). In the analyses on intra-examiner and observer repeatability of resolution score, the mean difference (bias) between the two exams (or observations) was significantly low and there was almost no difference across all the combinations of vibration frequency and image filter (range of bias: -0.11-0.11 and -0.17-0.00, respectively). Additionally, effects of vibration frequency and image filter on wave image quality (ROI size and resolution score) were assessed separately in each exam. Both mean ROI size and resolution score in the bandpass-directional filter were larger than those in the bandpass filter. Among the data in the bandpass-directional filter, mean ROI size was larger at 75 and 100 Hz, and mean resolution score was larger at 100 and 125 Hz. Taking into consideration with the results of repeatability and wave image quality, the present results suggest that optimal vibration frequency and image filter for MRE of the supraspinatus muscles is 100 Hz and bandpass-directional filter, respectively.