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Discordance between fractional flow reserve (FFR) and instantaneous wave-free ratio (iFR) occurs in approximately 20 % of cases. However, no studies have reported the discordance in patients with severe aortic stenosis (AS). We aimed to evaluate the diagnostic discordance between FFR and iFR in patients with severe AS.We examined 140 consecutive patients with severe AS (164 intermediate coronary artery stenosis vessels). FFR and iFR were calculated in four quadrants based on threshold FFR and iFR values of ≤0.8 and ≤0.89, respectively (Group 1: iFR0.89, FFR0.80; Group 2: iFR ≤0.89, FFR0.80; Group 3: iFR0.89, FFR ≤0.80; and Group 4: iFR ≤0.89, FFR ≤0.80). Concordant groups were Groups 1 and 4, and discordant groups were Groups 2 and 3. Positive and negative discordant groups were Groups 3 and 2, respectively.The median (Q1, Q3) FFR and iFR were 0.84 (0.76, 0.88) and 0.85 (0.76, 0.91), respectively. Discordance was observed in 48 vessels (29.3 %). In the discordant group, negative discordance (Group 2: iFR ≤0.89 and FFR0.80) was predominant (45 cases, 93.6 %). Multivariate analysis showed that the left anterior descending artery [odds ratio (OR), 3.88; 95 % confidence interval (CI): 1.54-9.79, p = 0.004] and peak velocity ≥5.0 m/s (OR, 3.21; 95%CI: 1.36-7.57, p = 0.008) were independently associated with negative discordance (FFR0.8 and iFR ≤0.89).In patients with severe AS, discordance between FFR and iFR was predominantly negative and observed in 29.3 % of vessels. The left anterior descending artery and peak velocity ≥5.0 m/s were independently associated with negative discordance.

A new strategy for the convergent synthesis of the ABCD ring system of indole terpene alkaloids has been developed based on a Sonogashira coupling of an o-iodoaniline (the A ring) with an alkyne bearing the D ring. After a tandem palladium-catalyzed cyclization, the tetracyclic ABCD ring structure found in the terpene indole alkaloids was obtained in good yield.

Sandwich freezing is a method of rapid freezing by sandwiching specimens between two metal disks and has been used for observing exquisite the close-to-native ultrastructure of living yeast and bacteria. Recently, this method has been found to be useful for preserving cell images of glutaraldehyde-fixed animal and human tissues. In the present study, this method was applied to observe the fine structure of mouse glomerular capillary loops. Morphometry was then performed, and the results were compared with the data obtained by an in vivo cryotechnique, which may provide the closest ultrastructure to the native state of living tissue. The results show that the ultrastructure of glomerular capillary loops obtained by sandwich freezing–freeze-substitution after glutaraldehyde fixation was close to that of the ultrastructure obtained by in vivo cryotechnique not only in the quality of cell image but also in quantitative morphometry. They indicate that the ultrastructure obtained by sandwich freezing–freeze-substitution after glutaraldehyde fixation may more closely reflect the living state of cells and tissues than conventional chemical fixation and dehydration at room temperature and conventional rapid freezing–freeze-substitution of excised tissues without glutaraldehyde fixation. Sandwich freezing–freeze-substitution techniques should be used routinely as a standard method for observing the close-to-native ultrastructure of biological specimens.

BACKGROUND/PURPOSE Data on the feasibility of coronary access (CA) through above or outside of the cylindrical shaped-transcatheter heart valve (THV) are very limited. The aims of the present study were to assess the feasibility of CA after transcatheter aortic valve replacement (TAVR) with the LOTUS using multi detector computed tomography (MDCT) and the reliability of algorithm detecting unfavorable CA. METHODS/MATERIALS Post-TAVR MDCT of 41 patients with 82 coronary arteries were evaluated. The relationship and distance between the THV flame and sinotubular junction (STJ) and coronary ostia were assessed. Unfavorable CA was defined as the valve-to-STJ distance < 2-mm or the valve-to-coronary ostia distance < 2-mm if the THV flame was above STJ or coronary ostia. RESULTS MDCT-identified unfavorable CA was observed in 29.3% for the left coronary artery and 41.5% for the right coronary artery. In total, 53.7% of patients had at least one unfavorable CA and 14.6% of those had unfavorable CA for both left and right coronary artery. While patients underwent coronary angiography after TAVR, the success rates of selective coronary cannulation were significantly lower in patients with MDCT-identified unfavorable CA in comparison to those with favorable CA for left (20.0% vs. 100%, P = 0.002) and right coronary artery (0% vs. 100%, P < 0.001). CONCLUSIONS Future CA through above or outside of a cylindrical shaped THV may be challenging with a significant probability. Our algorithm identifying unfavorable CA using post-MDCT seems to be useful for estimating the risk of unsuccessful selective cannulation.

The fungal cell wall is the initial barrier for the fungi against diverse external stresses, such as osmolarity changes, harmful drugs, and mechanical injuries. This study explores the roles of osmoregulation and the cell wall integrity (CWI) pathway in response to high hydrostatic pressure in the yeastSaccharomyces cerevisiae. We demonstrate the roles of the transmembrane mechanosensor Wsc1 and aquaglyceroporin Fps1 in a general mechanism to maintain cell growth under high-pressure regimes. The promotion of water influx into cells at 25 MPa, as evident by an increase in cell volume and a loss of the plasma membrane eisosome structure, promotes the activation of Wsc1, an activator of the CWI pathway. The downstream mitogen-activated protein kinase Slt2 was hyperphosphorylated at 25 MPa. Glycerol efflux increases via Fps1 phosphorylation, which is initiated by downstream components of the CWI pathway and contributes to the reduction in intracellular osmolarity under high pressure. The elucidation of the mechanisms underlying adaption to high pressure through the well-established CWI pathway could potentially translate to mammalian cells and provide novel insights into cellular mechanosensation.

This paper provides a possible solution to the issue of whether functional projections are necessary for secondary predicates. Focusing on manner adverbs and resultative predicates in Japanese because they have the same particles -ni or -ku, I will present several pieces of evidence that these two kinds of phrases are of the same syntactic category but should be given different treatments. As a proposal, I argue that, although in Japanese, resultative predicates are syntactic adjuncts, both manner adverbs and resultative predicates are headed by functional projections that take adjectival phrases in their complements and are responsible for the result meaning. I further claim that particles of Japanese resultative predicates are realizations of the functional projection, while adverbial categorizers in the sense of Distributed Morphology are realized as the particles of manner adverbs. It will also be shown that the functional projection is obligatorily realized as -ni or -ku, but this restriction is not imposed on the adverbial categorizer, which undergoes various realizations. The differences between these two phrases can be accounted for by assuming different syntactic structures for these phrases, leading to the conclusion that functional projections are necessary with respect to resultative predicates in Japanese.

Background Difficulties are often encountered while controlling atrial fibrillation (AF), especially in hemodialysis (HD) patients. Previous data revealed that cryoballoon ablation (CBA) for treating paroxysmal atrial fibrillation (PAF) was not inferior to radiofrequency ablation (RFA); however, HD patients were excluded in this prior trial. Thus, the efficacy of CBA for HD patients is still unknown. Methods This retrospective study analyzed HD patients who underwent catheter ablation (CA) for AF from August 2011 to June 2019. Patients who received CBA (CBA group) and those who received RFA (RFA group) were compared. The primary endpoint was defined as freedom from a composite outcome (a documented recurrence of any atrial tachyarrhythmia or a prescription of antiarrhythmic drugs) at one year after CA. Results The RFA and CBA groups were composed of 21 and 23 patients, respectively. Freedom from a composite outcome was 58.4% in the RFA group and 68.2% in the CBA group (Log-rank: p = 0.571). Conclusion Our results suggest that patients on HD with AF who were treated with CBA tended to have better outcomes than patients treated with RFA. Therefore, CBA could be a suitable ablation method for HD patients.

We herein report the cytokine expression at different stages for three patients who developed cardiac complications after immune checkpoint inhibitor (ICI) therapy. Case 1 with biopsy-proven myocarditis showed increased levels of interleukin (IL)-8, monocyte chemotactic and activating factor, and granulocyte macrophage colony-stimulating factor (GM-CSF) when he developed Takotsubo cardiomyopathy. Case 2 with subclinical myocarditis showed predominant activation of IL-8 during the progressive clinical course. Case 3 with cytokine-releasing syndrome showed substantial activations of IL-6, IL-8, GM-CSF, and interferon-γ. Our data suggest the development of unique cytokine activation in individual patients with cardiac complications after ICI therapy.

We have been using sandwich freezing of living yeast and bacteria followed by freeze-substitution for observing close-to-native ultrastructure of cells. Recently, sandwich freezing of glutaraldehyde-fixed cultured cells and human tissues have been found to give excellent preservation of ultrastructure of cells and tissues. These studies, however, have been conducted using a handmade sandwich freezing device and have been limited in a few laboratories. To spread the use of this method to other laboratories, we fabricated and commercialized a new sandwich freezing device. The new device is inexpensive, portable and sterilizable. It can be used to rapid-freeze viruses, bacteria, yeast, cultured cells and animal and human tissues to a depth of 0.2 mm if tissues are prefixed with glutaraldehyde. The commercial availability of this device will expand application of rapid freezing to wide range of biological materials.

Many advances in PET/CT technology can potentially improve image quality and the ability to detect small lesions. A new digital TOF-PET/CT scanner based on silicon photomultipliers (SiPM) integrated with a Bayesian penalized likelihood (BPL) PET reconstruction algorithm (Q.Clear; GE Healthcare) has been introduced into clinical practice. The present study aimed to quantify the ability of a digital TOF-PET/CT scanner combined with BPL reconstruction to detect small lesions, and to determine the optimal penalization factor (β) in BPL to accurately detect such lesions. All PET data were acquired from a NEMA body phantom using a Discovery MI (DMI) PET/CT system (GE Healthcare). The phantom included six spheres with diameters of 4, 5, 6, 8, 10, and 13 mm, and contained a background activity level of 5.3 kBq/mL, with target-to-background ratios (TBR) of 4:1 and 8:1. Images were reconstructed using a baseline OSEM algorithm, with OSEM + PSF, OSEM + TOF, OSEM + PSF + TOF, and BPL + PSF + TOF (β: 50–400). The matrix size was 192 × 192 and 384 × 384. Data acquired in 100-min list mode were re-binned into acquisition times ranging from 2 to 100 min. The quantitative accuracy and detectability of small hot spheres were evaluated by physical assessment of a recovery coefficient (RC) and a detectability index (DI), as well as visual assessment of PET images at each acquisition time. The RC and DI of sub-centimeter spheres were improved, because the digital TOF-PET/CT scanner has a larger TOF performance gain due to better timing resolution. The RC and DI were higher with BPL in sub-centimeter spheres, than with other OSEM-based types of reconstruction. The BPL for an 8-mm sphere overestimated uptake due to edge artifact overshoot induced by PSF modeling. The variability of RC and DI for acquisition times and TBR differed considerably according to β values. The RC for ~ 8-mm spheres were > 1 at β values between 50 and 100, but were close to 1 at β value of 200. The visual scores for β = 200 in BPL were maximal, whereas those for spheres that were ≥ 6 mm exceeded the criterion of 3. The BPL in the digital TOF-PET/CT scanner improved the quantitation and detectability of sub-centimeter spheres compared with OSEM-based reconstruction. Optimization of the β value in BPL might allow the detection of lesions ≤ 6 mm, although detectability depended on the TBR of lesions. A β value of 200 seemed optimal for detecting sub-centimeter lesions.

This paper explores a theoretical account for depictive constructions in Japanese. Some previous analyses claim that depictive predicates in Japanese and their semantic DPs form a constituent, based on ellipsis phenomena. However, this paper provides several pieces of evidence showing that Japanese depictive predicates are independent of their semantic subjects. Therefore, an independent analysis should be applied to depictive constructions in Japanese. This paper argues that adjunction sites of depictive predicates are different, depending on the types of the predicates; object-oriented depictive predicates are adjoined to VP, and subject-oriented depictive predicates are either to vP or to TP. With this proposal, this paper demonstrates that all of the syntactic properties of depictive constructions can be accounted for, showing the plausibility of an independent constituent analysis of depictive constructions.

The uptake of cholesterol from the host is closely linked to the proliferation of pathogenic fungi and protozoa during infection. For some pathogenic fungi

This retrospective study was aimed (i) at elucidating the correlation between fatty liver diagnoses based on the plain computed tomography (CT) value and those based on the attenuation coefficient (AC) value determined with the ultrasound-guided attenuation parameter (UGAP) and (ii) at evaluating the diagnostic power of AC values. We included 125 patients who underwent blood tests, abdominal ultrasonography and abdominal CT at our department between April 2020 and March 2021. Hepatic fat infiltration was categorized as S0 (5%), S1 (≥5 and 30%), S2 (≥30 and50%) or S3 (≥50%). The diagnostic ability of UGAP-determined AC was evaluated using receiver operating characteristic (ROC) curve analysis, and the correlation between AC value and fatty liver grade by CT value. The coefficient of correlation (r) between the AC value and plain CT value was -0.6188, indicating a moderate relationship. For diagnosing grade ≥S1 (n = 44), the area under the ROC curve (AUROC) was 0.8541, sensitivity 84.1%, specificity 81.5% and cutoff value 0.676 dB/cm/MHz. In diagnosing grade ≥S2 (n = 35), the AUROC was 0.8603, sensitivity 88.6%, specificity 81.1% and cutoff value 0.694 dB/cm/MHz. In diagnosing grade = S3 (n = 18), the AUROC was 0.9016, sensitivity 94.5%, specificity 81.9% and cutoff value, 0.704 dB/cm/MHz. The AC value is useful in diagnosing fatty liver.

Background Giant cell myocarditis (GCM) is a rare cause of fulminant heart failure (HF). The most common presentation is progressive hemodynamic deterioration, and a few cases present with idiopathic complete atrioventricular block (cAVB). The prognosis of GCM is poor, and GCM patients usually die of HF and ventricular arrhythmia unless cardiac transplantation is performed. Few reports have described the effects of treatments such as immunosuppression and detailed reverse remodelling in GCM patients. Case summary A 69-year-old female presented with cAVB. Transvenous pacemaker was implanted via the left subclavian vein. One and a half months later, she exhibited left ventricular dyssynchrony and lower left ventricular ejection fraction (LVEF), resulting in hospitalization for HF. She received cardiac resynchronization therapy; however, this had no apparently positive effects on her cardiac function. To investigate the cause of the lower LVEF, an endomyocardial biopsy was taken from the right ventricular septum. She was diagnosed with GCM and immediately received immunosuppression therapy with prednisolone and ciclosporin. This resulted in the functional recovery of the right ventricle; on the other hand, the left ventricle had still not recovered based on transthoracic echocardiography. Fortunately, she successfully recovered from severe HF without recurrence. Discussion This is a case of fulminant HF due to GCM which initially presented as cAVB. Moreover, this case demonstrates the quite difference of the functional recovery between the left ventricle and the right ventricle with immunosuppression therapy.

The neutron-emission spectrum from a 197Au target excited with a 16.6 ±0.2 MeV, monoenergetic, linearly polarized photon beam was measured using the time-of-flight method at the NewSUBARU-BL01. Two...

Chemical fixation has been used for observing the ultrastructure of cells and tissues. However, this method does not adequately preserve the ultrastructure of cells; artifacts and extraction of cell contents are usually observed. Rapid freezing is a better alternative for the preservation of cell structure. Sandwich freezing of living yeast or bacteria followed by freeze-substitution has been used for observing the exquisite natural ultrastructure of cells. Recently, sandwich freezing of glutaraldehyde-fixed cultured cells or human tissues has also been used to reveal the ultrastructure of cells and tissues. These studies have thus far been carried out with a handmade sandwich freezing device, and applications to studies in other laboratories have been limited. A new sandwich freezing device has recently been fabricated and is now commercially available. The present paper shows how to use the sandwich freezing device for rapid freezing of biological specimens, including bacteria, yeast, cultured cells, isolated cells, animal and human tissues, and viruses. Also shown is the preparation of specimens for ultrathin sectioning after rapid freezing and procedures for freeze-substitution, resin embedding, trimming of blocks, cutting of ultrathin sections, recovering of sections, staining, and covering of grids with support films.

We present the case of a 56-year-old woman diagnosed with primary biliary cholangitis (PBC). She has continuously taken 600 mg/day of ursodeoxycholic acid. Edema of the lower limbs manifested on July 20, 20XX; after 2 weeks, she manifested rapid weight gain and nettle rash on the limbs and trunk. She was admitted to our hospital on August 22. She had marked eosinophilia, hypoalbuminemia, anemia, non-pitting lower limbs edema, and nettle rash of the limbs and the trunk. We ruled out other diseases that may have caused the edema and suspected her with episodic angioedema with eosinophilia (EAE). The peripheral blood eosinophil count rapidly decreased after the administration of 30 mg prednisolone. The edema and nettle rash improved on the 7th day of admission, and the hypoalbuminemia and anemia improved on the 14th day. Prednisolone was tapered and discontinued, and there was no relapse of edema. We revised our diagnosis to non-recurrent EAE. She was diagnosed with asymptomatic PBC; therefore, anemia and hypoalbuminemia were considered not PBC but chronic inflammation and decrease in appetite. In this case, elevation of serum IgG4 was observed at onset and at remission. This suggests that IgG4 may be involved in the development of EAE in patients with chronic liver disease.

Background The Bayesian penalized likelihood (BPL) algorithm Q.Clear (GE Healthcare) allows fully convergent iterative reconstruction that results in better image quality and quantitative accuracy, while limiting image noise. The present study aimed to optimize BPL reconstruction parameters for 18F-NaF PET/CT images and to determine the feasibility of 18F-NaF PET/CT image acquisition over shorter durations in clinical practice. Methods A custom-designed thoracic spine phantom consisting of several inserts, soft tissue, normal spine, and metastatic bone tumor, was scanned using a Discovery MI PET/CT scanner (GE Healthcare). The phantom allows optional adjustment of activity distribution, tumor size, and attenuation. We reconstructed PET images using OSEM + PSF + TOF (2 iterations, 17 subsets, and a 4-mm Gaussian filter), BPL + TOF (β = 200 to 700), and scan durations of 30–120 s. Signal-to-noise ratios (SNR), contrast, and coefficients of variance (CV) as image quality indicators were calculated, whereas the quantitative measures were recovery coefficients (RC) and RC linearity over a range of activity. We retrospectively analyzed images from five persons without bone metastases (male, n = 1; female, n = 4), then standardized uptake values (SUV), CV, and SNR at the 4th, 5th, and 6th thoracic vertebra were calculated in BPL + TOF (β = 400) images. Results The optimal reconstruction parameter of the BPL was β = 400 when images were acquired at 120 s/bed. At 90 s/bed, the BPL with a β value of 400 yielded 24% and 18% higher SNR and contrast, respectively, than OSEM (2 iterations; 120 s acquisitions). The BPL was superior to OSEM in terms of RC and the RC linearity over a range of activity, regardless of scan duration. The SUVmax were lower in BPL, than in OSEM. The CV and vertebral SNR in BPL were superior to those in OSEM. Conclusions The optimal reconstruction parameters of 18F-NaF PET/CT images acquired over different durations were determined. The BPL can reduce PET acquisition to 90 s/bed in 18F-NaF PET/CT imaging. Our results suggest that BPL (β = 400) on SiPM-based TOF PET/CT scanner maintained high image quality and quantitative accuracy even for shorter acquisition durations.

We previously reported that Candida albicans responded to mild heat stress in a range of temperature elevations simulating fever, and concluded that mild heat stress increases susceptibility to antifungal drugs. In this study, we show that mild heat stress causes a morphological change in hyphae during the process of biofilm formation. We found that mild heat stress extended the period of hyphal stage maintenance in C. albicans biofilm. Although the rate of hyphal change from yeast form to hyphal form reached the maximum within 3 hr, later, almost every cell quickly reverted to the yeast growth phase within 6 hr at 37°C but not at 39°C, or under mild heat stress. Electron microscopy using a smart specimen preparation technique revealed that mild heat stress significantly increased the thickness of the inner cell wall accompanied by a decrease in density of the outer cell wall in the hyphae of C. albicans biofilm. To identify the gene responsible for the morphological changes associated with mild heat stress, we performed microarray gene expression analysis. Eleven genes were upregulated and 17 genes were downregulated under mild heat stress in biofilm cells. The increased PHR1 gene expression in response to mild heat stress was confirmed in quantitative RT-PCR analysis. The mutant upregulated PHR1 expression showed the same sensitivity against antifungal drug micafungin as dependent on mild heat stress. Our findings point to possible therapeutic effects of hyperthermia as well as to the effect of fever during infections.

A calibration scheme of position and orientation errors of rotary axis average lines based on touch-trigger probing is widely available on many commercial five-axis machine tools. Such a measurement is influenced by error motions of both linear and rotary axes. This paper proposes a novel scheme to separately identify linear and rotary axis geometric errors by using a touch-trigger probe and an uncalibrated test piece. Whereas the proposed scheme is based on well-developed self-calibration schemes for the circularity measurement, an original contribution is that it is applied to separate linear and rotary axis geometric errors. Two case studies are presented. First, the proposed tests are performed on the same five-axis machine tool for half a year to observe a long-term change in linear and rotary axis geometric errors. The second case study investigates the influence of room temperature change on linear axis and rotary axis error motions.