Diagnostic ability of Japanese version of high bleeding risk criteria for ischemic outcomes in patients with acute myocardial infarction.

The Japanese version of high bleeding risk (J-HBR) criteria was domestically proposed to identify patients at HBR after percutaneous coronary intervention (PCI). The applicability of J-HBR on bleeding events has been validated, while whether J-HBR predicts ischemic events is uncertain. This bi-center registry included 904 patients with acute myocardial infarction (MI) undergoing primary PCI. Patients were stratified by the J-HBR major (1 point) and minor (0.5 point) criteria. Patients with J-HBR ≥ 1 point were diagnosed as having HBR. The primary endpoint was major adverse cardiovascular events (MACE), a composite of cardiovascular death, recurrent MI, and ischemic stroke, after discharge. Of the 904 patients, 451 (49.9%) had the J-HBR. The primary endpoint more frequently occurred in patients with J-HBR than in those without (10.9% vs. 4.9%, p < 0.001) during the median follow-up period of 522 days. Probability of MACE was progressively increased with the increase in the number of J-HBR major and minor criteria, in which severe anemia, severe chronic kidney disease, prior heart failure, peripheral artery disease, and prior ischemic stroke were identified as significant factors associated with MACE. In patients with acute MI undergoing PCI, the J-HBR criteria were predictive for ischemic outcomes after discharge, suggesting that the J-HBR criteria may be useful to identify patients at high bleeding and ischemic risks.

Design of silica-PLC LP11 mode rotator based on adiabatic mode conversion.

A silica-based LP11 mode rotator, which is one of the basic and indispensable optical components for space division multiplexing, with multiple tapered trenches is proposed. Compared with the conventional interference-based LP11 mode rotator with a simple L-shape waveguide, the proposed LP11 mode rotator has many advantages in a mode conversion efficiency, an insertion loss, and a fabrication tolerance because the operation principle is based on the adiabatic mode conversion. By using an approach of the shortcut to adiabaticity, the proposed device is effectively miniaturized rather than the standard tapered structures. Among the LP11 mode rotators in the silica-based mode multi/demultiplexers, the proposed type will be a considerably promising candidate.

Bayesian design of mosaic-based mode multiplexers for various wavelength bands.

Ultracompact mode multiplexers based on mosaic structure for various wavelength bands designed by Bayesian technique are investigated. C-, O-, and C + O band, TE0-TE1 2-mode multiplexers can be designed with the same footprint, by only changing the mosaic-pattern, showing the great flexibility of mosaic-based devices. Bayesian direct binary search method is used for the design, and it is demonstrated that the Bayesian technique is superior to conventional design method in terms of the best-structure search for the same number of iterations. The designed devices are fabricated for Si-waveguide platform, and the proof-of-concept results are obtained. These results indicate that the mosaic-based devices are promising candidates for future compact optical transceivers.

Broadband design of silica-PLC mode-dependent-loss equalizer for 2LP-mode transmission systems.

A new configuration of mode-dependent-loss (MDL) equalizer for two linearly-polarized mode transmission systems using the silica planar lightwave circuit platform is proposed. This device acts as an LP01-mode attenuator (precisely, LP01/LP21 mode converter) to adjust the MDL keeping a high transmission of the LP11 modes. Almost all components constructing the device are based on the adiabatic mode conversion, which brings broadband operation. Especially, a newly proposed E12/E22 mode converter plays a key role in broadband MDL equalization. It is numerically revealed that the flattened spectra with designated transmission can be obtained for the wavelength from 1200 nm to 1650 nm.

Effect of admission in the stroke care unit versus intensive care unit on in-hospital mortality in patients with acute ischemic stroke.

BACKGROUND/OBJECTIVE: Few reports have directly compared the outcomes of patients with acute ischemic stroke (AIS) who are managed in a stroke care unit (SCU) with those who are managed in an intensive care units (ICU). This large database study in Japan aimed to compare in-hospital mortality between patients with AIS admitted into SCU and those admitted into ICU. METHODS: Patients with AIS who were admitted between April 1, 2014, and March 31, 2019, were selected from the administrative database and divided into the SCU and ICU groups. We calculated the propensity score to match groups for which the admission unit assignment was independent of confounding factors, including the modified Rankin scale (mRS) score. The primary outcome was in-hospital mortality, and secondary outcomes were the mRS score at discharge, length of stay (LOS), and total hospitalization cost. RESULTS: Overall, 8,683 patients were included, and 960 pairs were matched. After matching, the in-hospital mortality rates of the SCU and ICU groups were not significantly different (5.9% vs. 7.9%, P = 0.106). LOS was significantly shorter (SCU = 20.9 vs. ICU = 26.2 days, P < 0.001) and expenses were significantly lower in the SCU group than in the ICU group (SCU = 1,686,588 vs. ICU = 1,998,260 yen, P < 0.001). mRS scores (score of 1-3 or 4-6) at discharge were not significantly different after matching. Stratified analysis showed that the in-hospital mortality rate was lower in the ICU group than in the SCU group among patients who underwent thrombectomy. CONCLUSIONS: In-hospital mortality was not significantly different between the ICU and SCU groups, with significantly lower costs and shorter LOS in the SCU group than in the ICU group.

Prognostic Value of Natriuretic Peptide Levels and In-Hospital Heart Failure Events in Patients With Acute Myocardial Infarction.

BACKGROUND: In patients with acute myocardial infarction (AMI), elevated natriuretic peptide (NP) concentrations are reportedly associated with worse clinical outcomes. This study evaluated the prognostic value of NP concentrations and in-hospital heart failure (HF) events after AMI.Methods and Results: The present bicenter registry included 600 patients with AMI undergoing percutaneous coronary intervention. HF was evaluated at 3 different time points after AMI: on admission, during hospitalization, and at the short-term follow-up at 1 month. When HF was present at each time point, 1 point was assigned to the "HF time points" (HFTP) risk scoring system; possible total scores on this system ranged from 0 to 3. The primary endpoint was a composite of all-cause death and HF rehospitalization after discharge. Among the 600 patients who survived to discharge, the primary outcome occurred in 69 (11.5%) during a mean follow-up period of 488 days. HF on admission, during hospitalization, and at the short-term follow-up were all significantly associated with subsequent clinical outcomes. Higher scores on the HFTP scoring system were related to an increased risk of the primary endpoint. Multivariable analysis indicated scores of 2 and 3 were independently associated with outcome events in a stepwise manner. CONCLUSIONS: Among patients with AMI, HF evaluation at different time points was useful in stratifying risks of mortality and HF rehospitalization after discharge.

Potential of Z-100, extracted from Mycobacterium tuberculosis strain Aoyama B, as a hot tumor inducer.

The tumor microenvironment is one of the most important factors determining the efficacy of cancer immunotherapy. In particular, variability in efficacy has been linked to whether tumors are hot or cold, with hot tumors exhibiting greater T cell infiltration and responding better to immunotherapy. Z-100 extracted from Mycobacterium tuberculosis Aoyama B strain has been reported to increase cytokine production from immune cells. In this study, we examined its effect on the tumor microenvironment and its potential as a hot tumor inducer. The antitumor effect of Z-100 was confirmed in a mouse oral squamous cell carcinoma (Sq-1979) tumor model by starting administration before tumor injection. Treated tumors were collected to identify infiltrating CD8+ T cells. The antitumor effects of Z-100 were additionally examined in mice treated with anti-CD8 antibody and in IL-12p40 knockout (KO) mice. We found that Z-100 had strong antitumor effects and increased the proportion of CD8+ T cells in tumors. Moreover, the CD8+ T cells infiltrating tumors were identified as effector memory CD8+ T cells. Furthermore, the antitumor effects of Z-100 were abolished in mice treated with an anti-CD8 antibody and in IL-12p40 KO mice. Thus, Z-100 induces its antitumor effects by increasing tumor-infiltrating CD8+ T cells, suggesting that Z-100 may be a useful cancer therapy by acting as a hot tumor inducer.

Impact of PARIS and CREDO-Kyoto Thrombotic and Bleeding Risk Scores on Clinical Outcomes in Patients With Acute Myocardial Infarction.

BACKGROUND: The PARIS and CREDO-Kyoto risk scores were developed to identify patients at risks of thrombotic and bleeding events individually after percutaneous coronary intervention (PCI). However, these scores have not been well validated in different cohorts.Methods and Results:This 2-center registry enrolled 905 patients with acute myocardial infarction (MI) undergoing primary PCI. Patients were divided into 3 groups according to the PARIS and CREDO-Kyoto thrombotic and bleeding risk scores. The study endpoints included ischemic (cardiovascular death, recurrent MI, and ischemic stroke) and major bleeding events. Of 905 patients, 230 (25%) and 219 (24%) had high thrombotic and bleeding risks, respectively, with the PARIS scores, compared with 78 (9%) and 50 (6%) patients, respectively, with the CREDO-Kyoto scores. According to the 2 scores, >50% of patients with high bleeding risk had concomitant high thrombotic risk. During the mean follow-up period of 714 days, 163 (18.0%) and 95 (10.5%) patients experienced ischemic and bleeding events, respectively. Both PARIS and CREDO-Kyoto scores were significantly associated with ischemic and bleeding events after primary PCI. For ischemic events, the CREDO-Kyoto rather than PARIS thrombotic risk score had better diagnostic ability. CONCLUSIONS: In the present Japanese cohort of acute MI patients undergoing contemporary primary PCI, the PARIS and CREDO-Kyoto thrombotic and bleeding risk scores were discriminative for predicting ischemic and bleeding events.

Clinical Characteristics and Prognosis of Patients With No Standard Modifiable Risk Factors in Acute Myocardial Infarction.

BACKGROUND: Recently, the impact of the lack of standard modifiable risk factors, including hypertension, diabetes, dyslipidaemia, and current smoking, has been investigated in ST-segment elevation myocardial infarction (MI). The present study aimed to evaluate clinical characteristics and prognosis of the patients with no standard risk factors in acute MI. METHODS: This bi-centre registry included 1,093 patients with acute MI undergoing percutaneous coronary intervention. The participants were divided into two groups: patients having at least one of the four standard risk factors and those having none of the risk factors. The study endpoints included major adverse cardiovascular events (MACE) (death, recurrent MI, and stroke) and major bleeding events during hospitalisation. Any MACE and major bleeding events after discharge were also evaluated as an exploratory analysis. RESULTS: Of 1,093 patients, 64 (5.9%) had none of the four standard risk factors. The patients with no standard risk factors were likely to present with Killip class IV and cardiac arrest. The rate of in-hospital MACE was higher in patients with no risk factors than in their counterparts (25.0% vs 9.9%; p<0.001), whereas the incidence of in-hospital major bleeding was not significantly different between the two groups (9.4% vs 6.7%; p=0.44). Active cancer and autoimmune/inflammatory diseases were often found in patients with no standard risk factors. After discharge, no significant differences were observed in the risks of MACE and major bleeding events between the two groups. CONCLUSIONS: No standard modifiable risk factors were not uncommon and were associated with poor short-term outcomes in patients with acute MI.

Broadband silicon four-mode multi/demultiplexer designed by a wavefront matching method.

We propose a broadband silicon four-mode multi/demultiplexer which consists of three asymmetric directional couplers, and the asymmetric directional couplers were designed by a wavefront matching method to operate as mode multi/demultiplexers for TE1, TE2, and TE3 modes, respectively. Simulated results show that the -0.5-dB bandwidths of normalized transmission of the couplers designed by a wavefront matching method are 112, 114, and 134 nm, respectively. Those for the conventional couplers are 80, 72, 65 nm, respectively. The superiority of asymmetric directional couplers designed by a wavefront matching method are experimentally demonstrated. In the additional investigation, ultrabroadband tapered asymmetric directional couplers are theoretically demonstrated.

Genetic variation analyses indicate conserved SARS-CoV-2-host interaction and varied genetic adaptation in immune response factors in modern human evolution.

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a pandemic as of early 2020. Upon infection, SARS-CoV-2 attaches to its receptor, that is, angiotensin-converting enzyme 2 (ACE2), on the surface of host cells and is then internalized into host cells via enzymatic machineries. This subsequently stimulates immune response factors. Since the host immune response and severity of COVID-19 vary among individuals, genetic risk factors for severe COVID-19 cases have been investigated. Our research group recently conducted a survey of genetic variants among SARS-CoV-2-interacting molecules across populations, noting near absence of difference in allele frequency spectrum between populations in these genes. Recent genome-wide association studies have identified genetic risk factors for severe COVID-19 cases in a segment of chromosome 3 that involves six genes encoding three immune-regulatory chemokine receptors and another three molecules. The risk haplotype seemed to be inherited from Neanderthals, suggesting genetic adaptation against pathogens in modern human evolution. Therefore, SARS-CoV-2 uses highly conserved molecules as its virion interaction, whereas its immune response appears to be genetically biased in individuals to some extent. We herein review the molecular process of SARS-CoV-2 infection as well as our further survey of genetic variants of its related immune effectors. We also discuss aspects of modern human evolution.

Effect of plyometric training on the fascicle length of the gastrocnemius medialis muscle.

[Purpose] The present study aimed to determine the effects of eccentric calf raise exercise, which has the characteristics of plyometric training, on the fascicle length and muscle thickness of the gastrocnemius medialis muscle and range of motion of the ankle using ultrasonography. [Participants and Methods] Twenty-one healthy volunteers were randomly assigned to the eccentric calf raise exercise group or normal calf raise exercise group. Measurements were performed before training and at 3, 6, 9, and 12 weeks after training. [Results] In the eccentric calf raise exercise group, the fascicle length significantly increased after 6 weeks compared to that at baseline and at 3 weeks after training. The dorsiflexion angle and muscle thickness after three weeks significantly increased compared to that at baseline, but the pennation angle was not significantly different. The fascicle length, pennation angle, dorsiflexion angle, and muscle thickness showed no significant difference at all time points in the NCR group. [Conclusion] The results of this study showed that continued stretching of the gastrocnemius medialis muscle during eccentric calf raise exercise enhanced the morphological structures, such as the a fascicle length and muscle thickness. Eccentric calf raise exercise training may aid in injury prevention.

Ultrasmall design of a universal linear circuit based on microring resonators.

We designed a universal linear circuit by using microring resonators instead of conventional Mach-Zehnder interferometers and phase shifters. We illustrated that the footprint of the universal linear circuit can be drastically reduced (∼ 1/10). In addition, power consumption can also be reduced by using the sensitivity of the phase change in the vicinity of the resonant peak. Furthermore, as an important example of the application for optical communication, MIMO compensation operation is numerically demonstrated by our proposed universal linear circuit. The proposed design can be adapted to other experimentally reported devices, which will accelerate the integration of the universal linear circuit.

Optimum index profile of few-mode coupled multicore fibers for reducing the group delay spread.

We numerically investigate the group delay spread (GDS) characteristics in few-mode coupled multicore fibers (FM-CMCFs) in weak random-bending conditions by using a coupled-wave theory. We qualitatively show the modal coupling between modes in the intra- and the inter-mode group generated by bending. The results indicate that the modes of FM-CMCFs are less likely to couple with each other in weak random-bending conditions in contradiction to single-mode coupled multicore fibers. To resolve this problem, we demonstrate an optimum index profile and core pitch, where the GDS can be reduced even if the different mode groups do not couple strongly.

Breaking the icosahedra in boron carbide.

Findings of laser-assisted atom probe tomography experiments on boron carbide elucidate an approach for characterizing the atomic structure and interatomic bonding of molecules associated with extraordinary structural stability. The discovery of crystallographic planes in these boron carbide datasets substantiates that crystallinity is maintained to the point of field evaporation, and characterization of individual ionization events gives unexpected evidence of the destruction of individual icosahedra. Statistical analyses of the ions created during the field evaporation process have been used to deduce relative atomic bond strengths and show that the icosahedra in boron carbide are not as stable as anticipated. Combined with quantum mechanics simulations, this result provides insight into the structural instability and amorphization of boron carbide. The temporal, spatial, and compositional information provided by atom probe tomography makes it a unique platform for elucidating the relative stability and interactions of primary building blocks in hierarchically crystalline materials.

Low-loss, compact, and fabrication-tolerant Si-wire 90° waveguide bend using clothoid and normal curves for large scale photonic integrated circuits.

Ultimately low-loss 90° waveguide bend composed of clothoid and normal curves is proposed for dense optical interconnect photonic integrated circuits. By using clothoid curves at the input and output of 90° waveguide bend, straight and bent waveguides are smoothly connected without increasing the footprint. We found that there is an optimum ratio of clothoid curves in the bend and the bending loss can be significantly reduced compared with normal bend. 90% reduction of the bending loss for the bending radius of 4 µm is experimentally demonstrated with excellent agreement between theory and experiment. The performance is compared with the waveguide bend with offset, and the proposed bend is superior to the waveguide bend with offset in terms of fabrication tolerance.

Reduction of global interference of scalp-hemodynamics in functional near-infrared spectroscopy using short distance probes.

Functional near-infrared spectroscopy (fNIRS) is used to measure cerebral activity because it is simple and portable. However, scalp-hemodynamics often contaminates fNIRS signals, leading to detection of cortical activity in regions that are actually inactive. Methods for removing these artifacts using standard source-detector distance channels (Long-channel) tend to over-estimate the artifacts, while methods using additional short source-detector distance channels (Short-channel) require numerous probes to cover broad cortical areas, which leads to a high cost and prolonged experimental time. Here, we propose a new method that effectively combines the existing techniques, preserving the accuracy of estimating cerebral activity and avoiding the disadvantages inherent when applying the techniques individually. Our new method accomplishes this by estimating a global scalp-hemodynamic component from a small number of Short-channels, and removing its influence from the Long-channels using a general linear model (GLM). To demonstrate the feasibility of this method, we collected fNIRS and functional magnetic resonance imaging (fMRI) measurements during a motor task. First, we measured changes in oxygenated hemoglobin concentration (∆Oxy-Hb) from 18 Short-channels placed over motor-related areas, and confirmed that the majority of scalp-hemodynamics was globally consistent and could be estimated from as few as four Short-channels using principal component analysis. We then measured ∆Oxy-Hb from 4 Short- and 43 Long-channels. The GLM identified cerebral activity comparable to that measured separately by fMRI, even when scalp-hemodynamics exhibited substantial task-related modulation. These results suggest that combining measurements from four Short-channels with a GLM provides robust estimation of cerebral activity at a low cost.

Time course of left ventricular reverse remodeling in response to pharmacotherapy: clinical implication for heart failure prognosis in patients with idiopathic dilated cardiomyopathy.

The present study aimed to identify the clinical significance of differences in detection timings of left ventricular reverse remodeling (LVRR) on heart failure (HF) prognosis in patients with idiopathic dilated cardiomyopathy (IDCM). We investigated 207 patients with IDCM who underwent pharmacotherapeutic treatment. LVRR was defined as improvements in both LV ejection fraction ≥10 % and indexed LV end-diastolic dimension (LVEDDi) ≥10 %. Patients were stratified into 3 groups by LVRR timing: patients with LVRR <24 months (Early LVRR), those with LVRR ≥24 months (Delayed LVRR), and those without LVRR during the entire follow-up period (No LVRR). The major endpoint was first detection of composite event including readmission for decompensated HF, major ventricular arrhythmias, or all-cause mortality. LVRR was recognized in 108 patients (52 %): Early LVRR in 83 (40 %), Delayed LVRR in 25 (12 %), and No LVRR in 99 (48 %). The survival rate for the major endpoint was significantly higher for Delayed LVRR than for No LVRR (P = 0.001); there was no significant difference between Early and Delayed LVRR. Among patients without LVRR <24 months (Delayed + No LVRR), receiver operating characteristic curve analysis showed that the area under the curve for improvement in LVEDDi during the first 6 months for predicting subsequent LVRR (Delayed LVRR) [0.822 (95 % confidence interval, 0.740-0.916; P = 0.038)] was greater than that for improvement in LVEF. In conclusion, LVRR was a favorable prognostic indicator in patients with IDCM irrespective of its detection timing. Reduced LVEDDi during the first 6 months was predictive for subsequent LVRR in the later phase.

Determination of the fascicle length of the gastrocnemius muscle during calf raise exercise using ultrasonography.

[Purpose] The purpose of this study was to find a strength training protocol which maintains isometric contraction of the triceps surae during dorsal flexion of the ankle. [Subjects] The left feet of 22 young normal volunteers who did not have orthopedic injuries or lower limb pain participated in this study. [Methods] All subjects performed four sets of five repetitions of four sets calf-raise (CR) exercise at were (1) 60 bpm without a pedestal, (2) 60 bpm with a pedestal, (3) 90 bpm without a pedestal, and (4) 90 bpm with a pedestal. The fascicle length of the lateral head of the gastrocnemius and ankle angle were measured using ultrasonography and a video camera. The CR exercise was divided into two or three phases using the kinematics of the ankle. The average change in fascicle length over the five repetitions of each phase were compared. [Results] The change of the fascicle length during the hyper-dorsiflexion phase was significantly smaller than during the other two phases. [Conclusion] It is possible that eccentric CR exercises have progressed to motor learning of the isometric contraction during counter movement, and improved the release of elastic energy of the Achilles tendon during running, jumping, and other athletic activities.

Synthesis and evaluation of effective photoaffinity probe molecule of furospinosulin-1, a hypoxia-selective growth inhibitor.

The synthesis and evaluation of a photoaffinity probe molecule for furospinosulin-1, a hypoxia-selective growth inhibitor that we identified from marine sponge, was studied. An analogue carrying an alkyne tail showed potent hypoxia-selective inhibitory activity exceeding that of the parent molecule, and exhibited in vivo anti-tumor activity following oral administration. The alkyne moiety in the analogue was also found to be a good anchoring group for the preparation of probe molecules; a photoaffinity probe molecule having an optimized spacer length was selected through the systematic synthesis of several probes and the evaluation of their hypoxia-selective growth inhibitory activity and electrophoretic mobility shift properties.