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The di(9-anthryl)methyl (DAntM) radical was synthesized and investigated to elucidate its optical, electrical properties, and reactivity. The generation of the DAntM radical was confirmed by its ESR spectrum, which showed two broad signals. The unpaired electron is primarily localized on the central sp2 carbon and slightly delocalized over the two anthryl moieties. Although the DAntM radical undergoes dimerization in solution, the radical still remains even at 190 K due to the bulky nature of the two anthryl groups. Interestingly, upon exposure to air, the purple color of the radical solution quickly fades to orange, resulting in decomposition to give 9-anthryl aldehyde and anthroxyl radical derivatives.

Dedifferentiated liposarcoma (DDLPS) comprises a high-grade dedifferentiated (DD) component and a juxtaposed well-differentiated (WD) component. The DD component is believed to originate from the WD component by acquiring additional genomic alterations. In this study, we performed multiregion genome, epigenome, and transcriptome analyses of three patients with DDLPS. In two patients, there were few common genomic alterations across all samples, but many common alterations within DD or WD component samples. Phylogenetic trees predicted from the genomic alterations were consistent with those predicted from DNA methylation patterns. The expression patterns of adipogenesis-related genes differed between DD and WD components and also among patients in connection with their CpG island methylation status. These results indicate that in some patients, WD and DD components are evolutionarily separated at very early stages of tumorigenesis, and are formed through relatively long clonal selection with acquisition of different driver genomic alterations and DNA methylation changes.

Abstract Synthesis of one-dimensional molecular arrays with tailored stereoisomers is challenging yet has great potential for application in molecular opto-, electronic- and magnetic-devices, where the local array structure plays a decisive role in the functional properties. Here, we demonstrate the construction and characterization of dehydroazulene isomer and diradical units in three-dimensional organometallic compounds on Ag(111) with a combination of low-temperature scanning tunneling microscopy and density functional theory calculations. Tip-induced voltage pulses firstly result in the formation of a diradical species via successive homolytic fission of two C-Br bonds in the naphthyl groups, which are subsequently transformed into chiral dehydroazulene moieties. The delicate balance of the reaction rates among the diradical and two stereoisomers, arising from an in-line configuration of tip and molecular unit, allows directional azulene-to-azulene and azulene-to-diradical local probe structural isomerization in a controlled manner. Furthermore, our theoretical calculations suggest that the diradical moiety hosts an open-shell singlet with antiferromagnetic coupling between the unpaired electrons, which can undergo an inelastic spin transition of 91 meV to the ferromagnetically coupled triplet state.

Abstract Acute myocardial infarction (AMI) can rarely arise from non-lipid-rich coronary plaques. This study sought to compare the clinical outcomes after percutaneous coronary intervention (PCI) between AMI showing maximum lipid-core burden index in 4 mm (maxLCBI4mm)

Abstract Patient-derived xenograft (PDX) tumor models are known to maintain the genomic and phenotypic profiles, including the histopathological structures, of the parental tumors. On the other hand, unique enrichment of single-nucleotide variants or copy number aberrations has been reported in several types of tumors. However, an understanding of endometrial carcinoma PDXs is limited. The purpose of the present study was to clarify the presence or absence of the molecular properties of endometrial carcinomas in PDXs passaged up to eight times. Established PDXs of endometrioid carcinomas maintained their histopathological characteristics, but those of carcinosarcomas predominantly consisted of sarcomatous components when compared to the parental tumors. Alterations in the proportion of cells with positive/negative immunohistochemical staining for estrogen receptor, PTEN, PAX8, and PAX2 were observed, whereas the proportions of cells with AE1/AE3, TP53, ARID1A, PMS2, and MSH6 staining were unchanged. Variants of cancer-associated genes were compared between PDXs and parental tumors. Mutations in POLE and a frameshift deletion in BRCA1 were observed in the parental tumor tissue in each of the six cases, and additional genomic alterations, which were not apparently related to histopathological and immunohistochemical alterations, were found in the PDXs of these cases. The genomic and phenotypic alterations observed between endometrial carcinoma PDXs and parental tumors were partly associated with endometrial cancer-specific characteristics related to cellular differentiation and gene mutations.

Knowledge about electronic structures is important to gain an understanding of the unique functional properties of diradicaloids. In this study, we synthesized and characterized a diradicaloid in which two phenalenyl radical sites are coupled antiferromagnetically via a through-space interaction. The results of quantum chemical, physicochemical (1H NMR, electronic absorption, cyclic voltammetry, SQUID, ESR), and chemical reactivity studies show that this diradicaloid has singlet diradical character. An assessment of the nature of the bonding interaction between two radical sites in this species using DFT calculations demonstrates that a small spatial overlap between the two SOMOs in this diradicaloid provides an efficient electron exchange path for the singlet state to be substantially lower in energy than the triplet state.

Abstract Since U.S. President Barack Obama announced the Precision Medicine Initiative in his New Year’s State of the Union address in 2015, the establishment of a precision medicine system has been emphasized worldwide, particularly in the field of oncology. With the advent of next-generation sequencers specifically, genome analysis technology has made remarkable progress, and there are active efforts to apply genome information to diagnosis and treatment. Generally, in the process of feeding back the results of next-generation sequencing analysis to patients, a molecular tumor board (MTB), consisting of experts in clinical oncology, genetic medicine, etc., is established to discuss the results. On the other hand, an MTB currently involves a large amount of work, with humans searching through vast databases and literature, selecting the best drug candidates, and manually confirming the status of available clinical trials. In addition, as personalized medicine advances, the burden on MTB members is expected to increase in the future. Under these circumstances, introducing cutting-edge artificial intelligence (AI) technology and information and communication technology to MTBs while reducing the burden on MTB members and building a platform that enables more accurate and personalized medical care would be of great benefit to patients. In this review, we introduced the latest status of elemental technologies that have potential for AI utilization in MTB, and discussed issues that may arise in the future as we progress with AI implementation.

Abstract This study sought to develop a deep learning-based diagnostic algorithm for plaque vulnerability by analyzing intravascular optical coherence tomography (OCT) images and to investigate the relation between AI-plaque vulnerability and clinical outcomes in patients with coronary artery disease (CAD). A total of 1791 study patients who underwent OCT examinations were recruited from a multicenter clinical database, and the OCT images were first labeled as either normal, a stable plaque, or a vulnerable plaque by expert cardiologists. A DenseNet-121-based deep learning algorithm for plaque characterization was developed by training with 44,947 prelabeled OCT images, and demonstrated excellent differentiation among normal, stable plaques, and vulnerable plaques. Patients who were diagnosed with vulnerable plaques by the algorithm had a significantly higher rate of both events from the OCT-observed segments and clinical events than the patients with normal and stable plaque (log-rank p

Abstract Cavotricuspid isthmus (CTI) linear ablation has been established as the treatment for typical atrial flutter. Recently, ablation index (AI) has emerged as a novel marker for estimating ablation lesions. We investigated the relationship between CTI depth and ablation parameters on the procedural results of typical atrial flutter ablation. A total of 107 patients who underwent CTI ablation were retrospectively enrolled in this study. All patients underwent computed tomography before catheter ablation. From the receiver-operating curve, the best cut-off value of CTI depth was 420 and > 386, respectively. Among patients with these cut-off values, the first-pass success rate was 89% in the SC and 50% in the DC (p

Abstract The Quaternary Kurobegawa Granite, central Japan, is not only the youngest known granitic pluton exposed on the Earth’s surface, it is one of few localities where both Quaternary volcanics and related plutons are well exposed. Here, we present new zircon U–Pb ages together with whole rock and mineral geochemical data, revealing that the Kurobegawa Granite is a resurgent pluton that was emplaced following the caldera-forming eruption of the Jiigatake Volcanics at 1.55 ± 0.09 Ma. Following the eruption, the remnant magma chamber progressively cooled forming the voluminous Kurobegawa pluton in the upper crust (~ 6 km depth) until ~ 0.7 Ma when resurgence caused rapid uplift and erosion in the region. This is the first study to document the detailed spatiotemporal evolution of resurgent pluton for a Quaternary caldera system. Our new findings may contribute significantly to understanding the fate of active caldera systems that can produce supereruptions.

Background: In the resting conditions, narrowing the window of coronary pressure measurements from the whole cardiac cycle to diastole improves diagnostic performance of coronary pressure–derived physiological index. However, whether this also applies to the hyperemic conditions has not yet been thoroughly evaluated. Objectives: The purpose of this study was to assess whether diastolic fractional flow reserve (diastolic FFR) has better diagnostic performance in identifying ischemia-causing coronary lesions than conventional FFR in a prospective, multicenter, and independent core laboratory–based environment. Methods: In this prospective multicenter registry at 29 Japanese centers, we compared the diagnostic performance of FFR, diastolic FFR, resting distal to aortic coronary pressure (Pd/Pa), and diastolic pressure ratio (dPR) using myocardial perfusion scintigraphy (MPS) as the reference standard in 378 patients with single-vessel coronary disease. Results: Inducible myocardial ischemia was found on MPS in the relevant myocardial territory of the target vessel in 85 patients (22%). In the receiver-operating curve analyses, diastolic FFR had comparable area under the curve (AUC) compared with FFR (AUCdiastolic FFR: 0.66; 95% confidence interval [CI]: 0.58-0.73, vs AUCFFR: 0.66; 95% CI: 0.58-0.74, P = 0.624). FFR and diastolic FFR showed significantly larger AUCs than resting Pd/Pa (0.62; 95% CI: 0.54-0.70; P = 0.033 and P = 0.046) but did not show significantly larger AUCs than dPR (0.62; 95% CI: 0.55-0.70; P = 0.102 and P = 0.113). Conclusions: Diastolic FFR showed a similar diagnostic performance to FFR as compared with MPS. This result reaffirms the use of FFR as the most accurate invasive physiological lesion assessment. (Diagnostic accuracy of diastolic fractional flow reserve (d-FFR) for functional evaluation of coronary stenosis; UMIN000015906)

This study sought to evaluate a novel approach for automatic coregistration of optical coherence tomography (OCT) and coronary angiography. Lumen diameters and side branches from both coronary angiography and OCT were used to create 2 feature sets. Subsequently, a 2-step coregistration approach was performed on the feature sets for matching of each OCT cross section on the angiographic centerline. For validation, all side branches with ≥1.0 mm diameter were identified and used as paired fiduciary landmarks. Geographical error was defined as the distance between the automatically coregistered and the true-paired landmarks. Altogether 212 vessels from 181 patients were analyzed. Mismatch of coronary angiography and OCT occurred in 64 of 1,530 reference landmarks. Median geographical error was 0.32 (interquartile range: 0.00-0.56) mm. The mean time for coregistration was 20.69 ± 1.07 seconds. In conclusion, fast and automatic coregistration of OCT and angiography using a single standard angiographic loop is feasible and accurate.

Abstract Background Coronary artery aneurysm (CAA) is an important complication of Kawasaki disease (KD) that is associated with arterial structure damage. However, few studies have examined structural changes in coronary arteries that are not associated with CAA. Methods We examined coronary arteries in KD patients with CAAs who underwent follow-up coronary angiography (CAG) and optical coherence tomography (OCT). Coronary arterial branches with no abnormal findings during the most recent CAG were classified into two groups. Arteries with an acute-phase CAA that later regressed were classified as group R; arteries with no abnormal findings on either acute or convalescent phase CAG were classified as group N. Coronary arterial wall structural changes were compared between groups using OCT. Results Fifty-seven coronary arterial branches in 23 patients were evaluated by OCT. Thirty-six branches showed no abnormality during the most recent CAG. Both groups R and N comprised 18 branches. Maximum intimal thicknesses in groups R and N were 475 and 355 µm, respectively (p = 0.007). The incidences of media disruption were 100% and 67%, respectively (p = 0.02). Calcification, macrophage accumulation, and thrombus were not found in either group. Conclusions Intimal thickening and disruption of the media occur in coronary arteries with acute phase CAAs that later regress in the convalescent phase, as well as in arteries with normal CAG findings in the acute and convalescent phases.

Abstract Organoids derived from epithelial tumors have recently been utilized as a preclinical model in basic and translational studies. This model is considered to represent the original tumor in terms of 3D structure, genetic and cellular heterogeneity, but not tumor microenvironment. In this study, we established organoids and paired cancer-associated fibroblasts (CAFs) from surgical specimens of colorectal carcinomas (CRCs), and evaluated gene expression profiles in organoids with and without co-culture with CAFs to assess interactions between tumor cells and CAFs in tumor tissues. We found that the expression levels of several genes, which are highly expressed in original CRC tissues, were downregulated in organoids but re-expressed in organoids by co-culturing with CAFs. They comprised immune response- and external stimulus-related genes, e.g., REG family and dual oxidases (DUOXs), which are known to have malignant functions, leading tumor cells to proliferative and/or anti-apoptotic states and drug resistant phenotypes. In addition, the degree of differential induction of REG1 and DUOX2 in the co-culture system varied depending on CAFs from each CRC case. In conclusion, the co-culture system of CRC organoids with paired CAFs was able to partially reproduce the tumor microenvironment.

Recent advances in intravascular imaging techniques have made it possible to assess the culprit lesions of acute coronary syndrome (ACS) in the clinical setting. Intravascular ultrasound (IVUS) is the most commonly used intravascular imaging technique that provides cross-sectional images of coronary arteries. IVUS can assess plaque burden and vessel remodeling. Optical coherence tomography (OCT) is a high-resolution (10 μm) intravascular imaging technique that uses near-infrared light. OCT can identify key features of atheroma, such as lipid core and thin fibrous cap. Near-infrared spectroscopy (NIRS) can detect lipid composition by analyzing the near-infrared absorption properties of coronary plaques. NIRS provides a chemogram of the coronary artery wall, which allows for specific quantification of lipid accumulation. These intravascular imaging techniques can depict histological features of plaque rupture, plaque erosion, and calcified nodule in ACS culprit lesions. However, no single imaging technique is perfect and each has its respective strengths and limitations. In this review, we summarize the implications of combined use of multiple intravascular imaging techniques to assess the pathology of ACS and guide lesion-specific treatment.

Abstract Since the discovery of the triphenylmethyl (trityl) cation 120 years ago, a variety of aromatic cations having various colors and luminescence properties have been rigorously studied. Many, differently substituted trityl cations have been synthesized, and their optical properties have been elucidated. However, the optical properties of the parent, non‐substituted and highly reactive trityl cation, which was observed to be very weakly luminescent, have not been subjected to detailed investigation. In the effort described herein, we explored the optical nature of non‐substituted trityl hexafluorophosphate (PF6) in the crystalline state. Trityl PF6 was found to exist as two crystal polymorphs including a yellow (Y) and an orange (O) form. Moreover, we observed that these crystalline forms display crystalline‐state emission with different colors. The results of X‐ray crystallographic analysis showed that the two polymorphs have totally different molecular packing arrangements. Furthermore, an investigation of their optical properties revealed that the O‐crystal undergoes a distinct color change to yellow upon cooling as a consequence of a change in the nature of the charge transfer interaction between the cation and PF6 anion, and that both the Y‐ and O‐crystal exhibit phosphorescence.

PurposePatients with advanced/relapsed rare cancers have few treatment options. Analysis of circulating tumor DNA in plasma may identify actionable genomic biomarkers using a non-invasive approach.Patients and MethodsRare cancer patients underwent prospective plasma-based NGS testing. Tissue NGS to test concordance was also conducted. Plasma DNA alterations were assessed for incidence, functional impact, therapeutic implications, correlation to survival, and comparison with tissue NGS.ResultsNinety-eight patients were analyzed. Diseases included soft-tissue sarcoma, ovarian carcinoma, and others. Mean turn-around-time for results was 9.5 days. Seventy-six patients had detectable gene alterations in plasma, with a median of 2.8 alterations/patient. Sixty patients had a likely pathogenic alteration. Five received matched-therapy based on plasma NGS results. Two developed known resistance mutations while on targeted therapy. Patients with an alteration having VAF ≥5% had a significantly shorter survival compared to those of lower VAF. Tissue NGS results from eleven of 22 patients showed complete or partial concordance with plasma NGS.ConclusionPlasma NGS testing is less invasive and capable of identifying alterations in advanced rare cancers in a clinically meaningful timeframe. It should be further studied as a prospective enrollment assay in interventional studies for patients with rare advanced stage cancers.Clinical Registration[https://www.umin.ac.jp/ctr/index-j.htm], identifier UMIN000034394.

Background: Association among local hemodynamic parameters and their implications in development of acute coronary syndrome (ACS) have not been fully investigated.Methods: A total of 216 lesions in ACS patients undergoing coronary CT angiography (CCTA) before 1–24 months from ACS event were analyzed. High-risk plaque on CCTA was defined as a plaque with ≥2 of low-attenuation plaque, positive remodeling, spotty calcification, and napkin-ring sign. With the use of computational fluid dynamics analysis, fractional flow reserve (FFR) derived from CCTA (FFRCT) and local hemodynamic parameters including wall shear stress (WSS), axial plaque stress (APS), pressure gradient (PG) across the lesion, and delta FFRCT across the lesion (ΔFFRCT) were obtained. The association among local hemodynamics and their discrimination ability for culprit lesions from non-culprit lesions were compared.Results: A total of 66 culprit lesions for later ACS and 150 non-culprit lesions were identified. WSS, APS, PG, and ΔFFRCT were strongly correlated with each other (all p < 0.001). This association was persistent in all lesion subtypes according to a vessel, lesion location, anatomical severity, high-risk plaque, or FFRCT ≤ 0.80. In discrimination of culprit lesions causing ACS from non-culprit lesions, WSS, PG, APS, and ΔFFRCT were independent predictors after adjustment for lesion characteristics, high-risk plaque, and FFRCT ≤ 0.80; and all local hemodynamic parameters significantly improved the predictive value for culprit lesions of high-risk plaque and FFRCT ≤ 0.80 (all p < 0.05). The risk prediction model for culprit lesions with FFRCT ≤ 0.80, high-risk plaque, and ΔFFRCT had a similar or superior discrimination ability to that with FFRCT ≤ 0.80, high-risk plaque, and WSS, APS, or PG; and the addition of WSS, APS, or PG into ΔFFRCT did not improve the model performance.Conclusions: Local hemodynamic indices were significantly intercorrelated, and all indices similarly provided additive and independent predictive values for ACS risk over high-risk plaque and impaired FFRCT.

Ambient aerosol particles at forest and suburban sites in western Japan were analyzed for imidazole compounds, such as 4 (5)-Methylimidazole (4-MI), 1-ethylimidazole (1-EI), 2-ethylimidazole (2-EI), and imidazole-2-carboxaldehyde (IC). The aerosols were collected on quartz fiber filters and extracted by the solid phase extraction method. The extract was analyzed by HPLC/Q-TOF-MS using an ion-pairing agent. The concentration of 4-MI in winter was higher than those in summer at the forest site; its concentration was highest among the analyzed imidazoles. The concentration of 4-MI in the suburban site was several times higher than the forest site. Anthropogenic activities, such as vehicle emissions, are considered to be the major source of 4-MI in this region.

Aims: The demand for specimen collection for genomic profiling is rapidly increasing in the era of personalized medicine. Percutaneous needle biopsy is recognized as minimally invasive, but the feasibility of comprehensive genomic analysis using next-generation sequencing (NGS) is not yet clear. The purpose of this study was to evaluate the feasibility of genomic analysis using NGS with specimens obtained by image-guided percutaneous needle biopsy with 18-G needles. Patients and methods: Forty-eight patients who participated in a clinical study of genomic profiling with NGS with the specimen obtained by image-guided needle biopsy were included. All biopsies were performed under local anesthesia, with imaging guidance, using an 18-G cutting needle. A retrospective chart review was performed to determine the rate of successful genomic analysis, technical success rate of biopsy procedure, adverse events, rate of success in pathological diagnosis, and cause of failed genomic analysis. Results: The success rate of genomic analysis was 79.2% (38/48). The causes of failure were unprocessed for DNA extraction due to insufficient specimen volume (6/10), insufficient DNA volume (2/10), and deteriorated DNA quality (2/10). The rate of successful genomic analysis excluding NGS analysis that failed for reasons unrelated to the biopsy procedures was 95.2% (40/42). Technical success of biopsy was achieved in all patients without severe adverse events. The rate of success in the pathological diagnosis was 97.9% (47/48). Conclusions: Image-guided needle biopsy specimens using an 18-G cutting needle yielded a successful NGS genomic analysis rate with no severe adverse events and could be an adoptable method for tissue sampling for NGS.

In order to determine recent behaviors in atmospheric polycyclic aromatic hydrocarbon (PAH) concentrations at the west end of Japan and to reveal the causes of these behaviors, atmospheric PAH concentrations were measured in suburban and forest sites of Nagasaki, Japan from 2017 to 2021. The results showed that the total concentration of PAHs decreased considerably by 60% and 57% in suburban and forest sites, respectively, over this period. When analyzed by season, the rate of decrease in winter was markedly high. Therefore, the decreasing behavior in PAH concentrations in Nagasaki in recent years was considered to be mainly due to less PAHs originating from cold continental regions such as northern China. In particular, the reduction in coal and biomass combustion for winter heating in households, the efforts to improve air quality, and the limitation of economic activities in response to COVID-19 were likely responsible for the decrease in atmospheric PAH concentrations. In addition, although the PAH concentrations decreased, there was no significant change in the breakdown of the number of benzene rings in the PAH or in the attributes of their sources.

The unique characteristics of patients with chronic coronary syndrome (CCS) in the Asia-Pacific region, heterogeneous approaches because of differences in accesses and resources and low number of patients from the Asia-Pacific region in pivotal studies, mean that international guidelines cannot be routinely applied to these populations. The Asian Pacific Society of Cardiology developed these consensus recommendations to summarise current evidence on the management of CCS and provide recommendations to assist clinicians treat patients from the region. The consensus recommendations were developed by an expert consensus panel who reviewed and appraised the available literature, with focus on data from patients in Asia-Pacific. Consensus statements were developed then put to an online vote. The resulting recommendations provide guidance on the assessment and management of bleeding and ischaemic risks in Asian CCS patients. Furthermore, the selection of long-term antithrombotic therapy is discussed, including the role of single antiplatelet therapy, dual antiplatelet therapy and dual pathway inhibition therapy.

Background The major underlying mechanisms contributing to acute coronary syndrome are plaque rupture, plaque erosion, and calcified nodule. Artery‐to‐artery embolic myocardial infarction (AAEMI) was defined as ST‐segment–elevation myocardial infarction caused by migrating thrombus formed at the proximal ruptured plaque. The aim of this study was to investigate the prevalence and clinical features of AAEMI by using optical coherence tomography. Methods and Results This study retrospectively enrolled 297 patients with ST‐segment–elevation myocardial infarction who underwent optical coherence tomography before percutaneous coronary intervention. Patients were divided into 4 groups consisting of plaque rupture, plaque erosion, calcified nodule, and AAEMI according to optical coherence tomography findings. The prevalence of AAEMI was 3.4%. The culprit vessel in 60% of patients with AAEMI was right coronary artery. Minimum lumen area at the culprit site was larger in AAEMI compared with plaque rupture, plaque erosion, and calcified nodule (4.0 mm2 [interquartile range (IQR), 2.2–4.9] versus 1.0 mm2 [IQR, 0.8–1.3] versus 1.0 mm2 [IQR, 0.8–1.2] versus 1.1 mm2 [IQR, 0.7–1.6], P

Abstract Background Even in the current drug-eluting stent era, revascularization for coronary stenosis with fractional flow reserve (FFR) between 0.75 and 0.80, the so-called “gray zone,” is a matter of debate. Previous studies have reported conflicting results regarding outcomes of revascularization versus deferral for coronary stenosis when FFR values are in the gray zone, but these studies have had differing designs and populations. We therefore will investigate whether medical therapy plus percutaneous coronary intervention (PCI) is superior to medical therapy alone in reducing major cardiovascular events in patients presenting with coronary stenosis with gray zone FFR values. Methods/design This is a prospective, multicenter, open-label, parallel group, randomized, controlled, superiority study. A total of 410 eligible participants will be recruited and randomized to either the medical therapy plus PCI group or the medical therapy alone group. The primary endpoint is 1-year major adverse cardiac events (MACEs), defined as a combined endpoint of all-cause death, nonfatal myocardial infarction (MI), or unplanned target vessel revascularization (TVR). Secondary endpoints include MACE at 2 and 5 years. Moreover, each individual component of the primary endpoint, cardiovascular death, target vessel-related and non-target vessel-related MI, all MI, clinically driven TVR or non-TVR, all revascularization, stent thrombosis, and angina symptom status will be evaluated at 1, 2, and 5 years. Discussion This is the first prospective, multicenter, randomized, controlled study to investigate the superiority of medical therapy plus PCI over medical therapy by itself in reducing major cardiovascular events in patients presenting with coronary stenosis with “gray zone” FFR values. The results will help interventional cardiologists in making revascularization decisions regarding coronary stenosis with gray zone FFR values. Trial registration University Hospital Medical Information Network Clinical Trials Registry, UMIN000031526. Registered on 1 March 2018.

Background: Although previous studies demonstrated that microcatheter-derived fractional flow reserve (mc-FFR) tends to overestimate lesion severity compared to pressure wire-derived FFR (pw-FFR), the clinical utility of mc-FFR remains obscure. The extent of differences between the two FFR systems and its relation to a lesion-specific parameter remain unknown. In this study, we sought to compare mc-FFR with pw-FFR and determine the lower and upper mc-FFR cut-offs predicting ischemic and non-ischemic stenosis, using an ischemic and a clinical FFR threshold of 0.75 and 0.80 as references, respectively. We further explored optical coherence tomography (OCT) parameters influencing the difference in FFR between the two systems. Methods and results: In this study, 44 target vessels with intermediate de novo coronary artery lesion in 36 patients with stable ischemic heart disease were evaluated with mc-FFR, pw-FFR and OCT. Bland-Altman plots for mc-FFR versus pw-FFR showed a bias of −0.04 for lower mc-FFR values compared to pw-FFR values. The mc-FFR cut-off values of 0.73 and 0.79 corresponded to the 0.75 ischemic pw-FFR and 0.80 clinical pw-FFR thresholds with high predictive values, respectively. The differences in the two FFR measurements (pw-FFR minus mc-FFR) were negatively correlated with OCT-derived minimum lumen area (MLA) (R = −0.359, p = 0.011). The OCT-derived MLA of 1.36 mm2 was a cut-off value for predicting the clinically significant difference between the two FFR measurements defined as >0.03. Conclusion: Mc-FFR is clinically useful when the specific cut-offs are applied. An OCT-derived MLA accounts for the clinically significant difference in FFR between the two systems. Keywords: Fractional flow reserve, Microcatheter, Pressure wire, Optical coherence tomography, Decision-making, Minimum lumen area

Abstract Advanced cancer genomics technologies are now being employed in clinical sequencing, where next-generation sequencers are used to simultaneously identify multiple types of DNA alterations for prescription of molecularly targeted drugs. However, no computational tool is available to accurately detect DNA alterations in formalin-fixed paraffin-embedded (FFPE) samples commonly used in hospitals. Here, we developed a computational tool tailored to the detection of single nucleotide variations, indels, fusions, and copy number alterations in FFPE samples. Elaborated multilayer noise filters reduced the inherent noise while maintaining high sensitivity, as evaluated in tumor-unmatched normal samples using orthogonal technologies. This tool, cisCall, should facilitate clinical sequencing in everyday diagnostics. It is available at https://www.ciscall.org.

Reliable and accurate next generation sequencing (NGS) technologies are important in precision medicine. Analysis using currently available NGS genomic tests is conducted on cancer-derived DNA collected from tumor tissue, blood, or both. Clonal hematopoiesis (CH) produces a detectable somatic clonal mutation that is commonly associated with clonal expansion of hematopoietic cells with age and genomic analysis of blood samples can be used to detect CH. A 74-year-old Korean male had lung adenocarcinoma with a metastasis to the left scapula. He underwent palliative radiotherapy to the left scapula and received multi-line chemotherapies. After disease progression, he underwent re-biopsy of the metastatic tumor tissue from lung cancer and concomitant blood sampling. NGS genomic testing revealed no significant genomic mutation in the tumor tissue DNA but showed the TP53 mutation C135Y in peripheral blood DNA. To investigate the discordance between the genotyping results in tumor tissue and blood, we tested for the TP53 mutation using a target sequencing test in blood and normal oral mucosa. The TP53 mutation C135Y was only detected in the blood sample, confirming the presence of TP53-mutated CH. We should be aware of different characteristics in NGS genomic testing including sample type such as tumor, blood, or paired specimens. Performing genomic testing on paired tumor and blood samples is effective for discriminating mutations derived from CH from germline mutations and somatic mutations in tumor cells.

In this study, we compare the flow and temperature fields of a heated impinging jet interfering with a Couette flow and a Poiseuille flow through numerical simulations. We find that the instantaneous vortex structure in the Couette main flow has some periodicity and affects the heat transfer on the jet impinging surface. In time-averaged flow and temperature fields, the Nusselt number shows unique distributions. Further, a counter-rotating vortex pair is extracted, similar to the previously reported studies on a jet in a cross flow. It is found that this vortex pair involves the main flow fluid and causes a unique Nusselt number distribution. The overall heat transfer in the Couette main flow is lower than that in the Poiseuille main flow. From the mean velocity field, a back current occurs behind the jet inlet, which is similar to the separation in the wake flow of a cylinder crossing the main flow. In addition, the fluctuation velocity in the Couette main flow does not spread wider than that in the Poiseuille main flow, and high velocity fluctuations concentrate on the front edge of the jet flow. The distributions of both mean and fluctuation velocities of the Couette flow interfering with the jet are similar to those of the turbulent Couette flow.

Background: Oncologists increasingly rely on clinical genome sequencing to pursue effective, molecularly targeted therapies. This study assesses the validity and utility of the artificial intelligence Watson for Genomics (WfG) for analyzing clinical sequencing results.Methods: This study identified patients with solid tumors who participated in in-house genome sequencing projects at a single cancer specialty hospital between April 2013 and October 2016. Targeted genome sequencing results of these patients' tumors, previously analyzed by multidisciplinary specialists at the hospital, were reanalyzed by WfG. This study measures the concordance between the two evaluations.Results: In 198 patients, in-house genome sequencing detected 785 gene mutations, 40 amplifications, and 22 fusions after eliminating single nucleotide polymorphisms. Breast cancer (n = 40) was the most frequent diagnosis in this analysis, followed by gastric cancer (n = 31), and lung cancer (n = 30). Frequently detected single nucleotide variants were found in TP53 (n = 107), BRCA2 (n = 24), and NOTCH2 (n = 23). MYC (n = 10) was the most frequently detected gene amplification, followed by ERBB2 (n = 9) and CCND1 (n = 6). Concordant pathogenic classifications (i.e., pathogenic, benign, or variant of unknown significance) between in-house specialists and WfG included 705 mutations (89.8%; 95% CI, 87.5%−91.8%), 39 amplifications (97.5%; 95% CI, 86.8–99.9%), and 17 fusions (77.3%; 95% CI, 54.6–92.2%). After about 12 months, reanalysis using a more recent version of WfG demonstrated a better concordance rate of 94.5% (95% CI, 92.7–96.0%) for gene mutations. Across the 249 gene alterations determined to be pathogenic by both methods, including mutations, amplifications, and fusions, WfG covered 84.6% (88 of 104) of all targeted therapies that experts proposed and offered an additional 225 therapeutic options.Conclusions: WfG was able to scour large volumes of data from scientific studies and databases to analyze in-house clinical genome sequencing results and demonstrated the potential for application to clinical practice; however, we must train WfG in clinical trial settings.

OBJECTIVE:The current guideline recommends lowering low-density lipoprotein cholesterol (LDL-C) for the primary management of dyslipidemia in patients at high-risk of cardiovascular events. Patients who have achieved LDL-C levels below the recommended targets may still experience cardiovascular events, suggesting additional therapeutic targets beyond LDL-C. The aim of this study was to investigate whether high-density lipoprotein cholesterol (HDL-C) levels had an impact on plaque stabilization in patients with acute coronary syndrome (ACS). METHODS:This study consisted of 90 ACS patients with untreated dyslipidemia. In optical coherence tomography (OCT) analysis, a plaque with fibrous cap thickness ≦160 μm was defined as a high-risk plaque. We registered one high-risk plaque per one patient by baseline OCT imaging, and then administrated high-intensity statin. Based on the follow-up OCT results, patients whose registered plaque was no longer high-risk plaque were classified into a responder group and the remains into a non-responder group. RESULTS:No differences were observed in the baseline LDL-C and HDL-C levels between the two groups. Reduction of LDL-C levels (δ LDL-C: -53 ± 21 mg/dL vs. -42 ± 29 mg/dL, p = 0.036) and increase of HDL-C levels (δ HDL-C: 2.5 ± 5.9 mg/dL vs. -0.3 ± 6.7 mg/dL, p = 0.039) were greater in the responder group. On multivariate logistic regression analysis, δ LDL-C levels (OR: 0.956, 95% CI: 0.921-0.993; p = 0.020) and δ HDL-C levels (OR: 1.143; 95% CI: 1.005-1.300, p = 0.041) were independent contributors for plaque stabilization. CONCLUSIONS:Increase of HDL-C levels is associated with plaque stabilization in patients with ACS. HDL-C could be a therapeutic target for residual risk management.

In this study, we developed a simultaneous measurement system for measuring the concentration fluctuations of two species using pulsed laser diodes in the light absorption spectrometric method. Conventional methods utilize halogen lamps or continuous laser diodes as light sources for concentration measurements. These light sources require multi-monochrometers or dichroic mirrors, which makes these methods rather expensive. However, using pulsed laser diodes as the light sources eliminates the need for additional multi-monochrometers and dichroic mirrors. A diffusion field consisting of two dye species in an axisymmetric turbulent jet was measured using the developed concentration measurement system. To ascertain the validity of our concentration measurements, we compared the present measurement results with those of a single dye species and previous studies. It was observed that the concentrations of the two dye species were measured accurately by the present measuring system. Therefore, such low-cost concentration measurement systems can be developed and applied in various simultaneous measurements of concentration fluctuations of multiple species such as in turbulent reactive flows.

A turbulent plane jet with a chemical reaction (A + B → R) in a liquid is investigated experimentally. The instantaneous concentrations of all species (A, B, and R) are measured simultaneously by using the light absorption spectrometric method and the mass conservation law. Statistics of the reactive scalar field are compared with those of the nonreactive scalar (frozen limit) and instantaneous reaction (equilibrium limit) fields. It is ascertained that, in comparison with the frozen limit, the mean concentrations of reactants A and B decrease while the mean concentration of product R increases in the downstream direction because of the chemical reaction. With regard to scalar fluctuations, it is also observed that in the region near the exit of the jet, the r.m.s. values of species A become larger than those in the frozen limit, whereas the r.m.s. values of species B become smaller than those in the frozen limit; the reverse situation is observed in the downstream and outer regions. Furthermore, the concentration correlations between species A and B have negative values. The segregation coefficients have values between 0 and -0.3 on the jet centerline and have minimum values at the location separated from the centerline in the cross-stream direction. The data obtained in the present study provide very useful and important information for modeling concentration correlation and the chemical source term in a turbulent reactive flow.

Recently, long-lived, organic radical species have attracted much attention from chemists and material scientists because of their unique electronic properties derived from their magnetic spin and singly occupied molecular orbitals. Most stable and persistent organic radicals are heteroatom-centered radicals, whereas carbon-centered radicals are generally very reactive and therefore have had limited applications. Because the physical properties of carbon-centered radicals depend predominantly on the topology of the π-electron array, the development of new carbon-centered radicals is key to new basic molecular skeletons that promise novel and diverse applications of spin materials. This account summarizes our recent studies on the development of novel carbon-centered radicals, including phenalenyl, fluorenyl, and triarylmethyl radicals.

A turbulent plane jet with a one-step reaction (R + B → S) in a liquid is investigated experimentally. The instantaneous concentrations of species R and S are measured simultaneously by using the light absorption spectrometric method, while the concentration of species B is determined by the conservation law. Statistics of reactive scalar field are compared with those of nonreactive scalar field. It is ascertained that, in comparison with the nonreactive case (frozen limit), the mean concentrations of reactants R and B decrease while the mean concentration of product S increases in the downstream direction because of the chemical reaction. With regard to scalar fluctuations, it is also observed that the change in the r.m.s. values of species R is small but these values become slightly small in comparison with those in the frozen limit, whereas the r.m.s. values of species B become apparently larger than those in the frozen limit. Furthermore, the segregation coefficients of species R and B in the frozen limit increase in the downstream direction because of the progress in mixing. In contrast, the segregation coefficients in the reactive case become slightly smaller than those in the frozen limit and lie between -0.14 and -0.02 in the measurement region. The present data show that the scalar covariance can not be neglected for modeling reactive flow, and provide very useful and important information for modeling concentration correlation and the chemical source term in a turbulent reactive flow.

The relationships between large-scale bulge and valley structures and bursting events in a zero-pressure-gradient turbulent boundary layer (TBL) are investigated by means of laboratory experiments carried out in a wind tunnel. To investigate the spatiotemporal structures of coherent motions in a TBL, multipoint instantaneous streamwise velocities and instantaneous wall static pressures are simultaneously measured using a combination of a rake of 23 I-type hot-wire probes, which covers entire TBL, and a microphone pressure sensor. The KL (Karhunen-Loève) expansion is applied to the measured velocity signals. The flow field is reconstructed by using lower- or higher-order modes to investigate the coherent motions in the TBL. The bursting events are detected by applying the VITA (Variable Interval Time Average) technique to the instantaneous velocity signals in the original flow. The bulge and valley structures are detected by using the newly proposed conditional sampling method, which is applied to both the original flow and the reconstructed flow by using the KL expansion. The results show that at lower modes, only the large-scale motions rotating against the mean shear stress accompany the bursting events. At higher modes, however, the large-scale motions are found to be poorly related to the bursting events.

In this study, special attention is directed to static pressure fluctuation in a sirocco fan for a car air-conditioning system, because it is expected that there is a close connection between the fluid noise and the pressure fluctuation. The final purpose of this study is to clarify the relationship between the static pressure fluctuation between fan blades and the sound noise emitted to the outside of the fan, and to develop an air-conditioning system with highly low noise level. For this purpose, first of all, a new micro probe for the measurement of static pressure fluctuation has been developed. This new micro probe is composed of an L-type static pressure tube (the outer diameter is 0.5 mm and the inner diameter is 0.34 mm) and a very small pressure transducer. This probe exhibits a flat frequency response until approximately 2,000 Hz, and it is set between the blades of the fan rotating at 1,500 rpm. The measurements of the static pressure fluctuation between the blades have been performed, and the intensity of sound source was quantified from the second derivative of the phase-averaged static pressure fluctuation signals on the basis of Ribner's formula (Ribner 1962). The experiments have been made in two different modes, i.e., the cooling mode (FACE MODE) and the heating mode (FOOT MODE). It is shown that the static pressure increases rapidly as the blade approaches to the nose of the casing. It is also found that the sound source for FACE MODE shows the larger value than that for FOOT MODE as a whole. In particular, the largest intensity of sound source is observed when the blade approaches to the nose. From these results, it is confirmed that the present new static pressure probe is useful to specify the distributions of sound source in a sirocco fan.

For the development of an active control of a turbulent jet, measurements of an axisymmetric turbulent jet were performed with multiple “moving delta tabs.” Five computercontrolled delta tabs, which can be driven independently, were installed at the skimmer. Two modes were tested; in the first mode, all the delta tabs were stationary (i.e., conventional way), and in the second mode, the delta tabs were oscillated in phase at a frequency of 4 Hz. Simultaneous multipoint measurements of instantaneous velocity were performed using a rake of 21 I-type hot wires, specially designed and manufactured for this study. The results are compared with those in a canonical axisymmetric jet without tabs. The results show that the turbulence quantities, such as mean and rms velocities, skewness, kurtosis, probability density function, and power spectra are significantly altered by the stationary and oscillating delta tabs. The effects of the oscillation of delta tabs are found to modify the large-scale structure in the near field of the jet. The results confirm the effectiveness of the active control of an axisymmetric jet using the oscillating delta tabs.

In this study, a water solution of dye (whose Schmidt number Sc is about 3,800) was issued into the quiescent water as an axisymmetric turbulent jet and the simultaneous measurements of axial velocity and concentration have been performed using the combined probe of I-type hot-film and fiber-optic concentration sensor based on the Lambert-Beer's law. Then we calculated the PDF (Probability Density Function) for the streamwise velocity derivative ∂u/∂x and streamwise concentration derivative ∂c/∂x. It was confirmed that the PDFs for ∂u/∂x skew negatively, and the values of skewness (S∂u/∂x) and flatness factor (F∂u/∂x) are consistent with the other researcher's data (see Sreenivasan and Antonia, Annual Review of Fluid Mechanics, Vol. 29, 1997, where the extensive past data of turbulent velocity and temperature (whose Prandtl number is Pr=0.7) fields are summarized). However, with regard to the PDFs for ∂c/∂x, the skewness (S∂c/∂x) show the values very close to zero, unlikely the past other data of the temperature fields which show the magnitude of 0.5∼1.0. On the other hand, the flatness factor (F∂c/∂x) show the values of 7.0∼8.0 which are consistent with the temperature fields. This result suggests that the fine-scale structure of a high-Schmidt-number diffusion field is almost isotropic although it is intermittent.

Fluctuating static pressure is closely related with fluctuating velocity in a turbulent flow, and it plays an important role in the energy balance and anisotropy of turbulence. Thus, the measurement of the fluctuating static pressure is significantly effective for the clarification of the organized structure of the turbulent flow. In this study, a static probe that is less sensitive to the yaw angle and having a good frequency response was developed, and the simultaneous measurement of velocity and pressure field was performed in a two-dimensional jet flow by a combination of this static pressure probe and an I-type hot-wire probe. In the pressure spectrum, the κ-7/3 power law range could be clearly observed, and the distribution of the cross-correlation between streamwise velocity and static pressure is demonstrated to be consistent with the previous model of coherent vortex structure.

The effects of stable and unstable thermal stratifications on the cross spectra between passive scalar (dye concentration) fluctuation c and vertical velocity fluctuation υ in shear-free grid turbulence are investigated using previously published data. The results show that cospectra in the neutral stratification have a slope close to -7/3, as predicted by Lumley (1964). The coherences of υ and c in the neutral stratification have a slope close to -4/3, which implies the absence of a phase shift between υ and c. In the weakly stable stratification, both the cospectrum and the coherence decay due to stable buoyancy force. In the moderately stable stratification, the scaling laws of the cospectrum and coherence collapse in the downstream region. However, in the strongly stable stratification, the negative cospectrum in the countergradient region reconstructs a small but distinct region close to -7/3 after the collapse. In the unstable stratification, despite strong convective motions due to the unstable buoyancy force, the cospectra and the coherences exhibit -7/3 and -4/3 power decay regions, respectively.

We developed a valve hybrid fractal stent to treat the cerebral aneurysm what is one of a cerebrovascular disease. The stent has a valve part to path through a coil. The valves have fractal structures. So, the blood flowing into cerebral aneurysm is prevented. We performed a Particle Image Velocimetry (PIV) experiment to evaluate the inflow into cerebral aneurysm. By the experiment result, we visualized the stream line by using the cerebral aneurysm. By calculation, we succeeded in a reduction in the inflow by using the valve fractal stent.

Turbulent reactive jet in liquid has been simulated by the “semi-empirical” Lagrangian probability density function (PDF) method, by which the velocity field consistent to the specified moments of the Eulerian PDF of velocity can be reproduced. The chemical reaction treated in this study is a second-order irreversible reaction, R + B → S, where a solution of species R is ejected from the nozzle into the main stream that includes species B. The Lagrangian velocities of the stochastic particles are modeled by a generalized Langevin equation in the cylindrical coordinate system. This model is constructed to satisfy the consistency condition of a velocity field and the thermodynamic constraint. For the molecular mixing of reactive scalar concentrations, the most fundamental IEM (interaction by exchange with the mean) was adopted. The simulation results are compared with the experimental data. It is found that the velocity field simulated by the present model satisfies the consistency condition up to the second-order moment and the thermodynamic constraint. The simulated reactive scalar concentration field shows almost the same distribution, on the whole, as the experimental data. Therefore, the models used in this study are useful for a turbulent reactive jet.

Optical coherence tomography (OCT) is a high-resolution imaging technique that offers microscopic visualization of coronary plaques. The clear and detailed images of OCT generate an intense interest in adopting this technique for both clinical and research purposes. Recent studies have shown that OCT is useful for the assessment of coronary atherosclerotic plaques, in particular the assessment of plaque rupture, erosion, and intracoronary thrombus in patients with acute coronary syndrome. In addition, OCT may enable identifying thin-cap fibroatheroma, the proliferation of vasa vasorum, and the distribution of macrophages surrounding vulnerable plaques. With its ability to view atherosclerotic lesions in vivo with such high resolution, OCT provides cardiologists with the tool they need to better understand the thrombosis-prone vulnerable plaques and acute coronary syndromes. This paper reviews the possibility of OCT for identification of vulnerable plaques in vivo.

Background. Recent intravascular ultrasound (IVUS) studies have demonstrated that hypoechoic plaque with deep ultrasound attenuation despite absence of bright calcium is common in acute coronary syndrome. Such “attenuated plaque” may be an IVUS characteristic of unstable lesion. Methods. We used optical coherence tomography (OCT) in 104 patients with unstable angina to compare lesion characteristics between IVUS-detected attenuated plaque and nonattenuated plaque. Results. IVUS-detected attenuated plaque was observed in 41 (39%) patients. OCT-detected lipidic plaque (88% versus 49%, 𝑃