van der Waals Decoration of Ultra-High-Q Silica Microcavities for χ(2)-χ(3) Hybrid Nonlinear Photonics.

Optical nonlinear processes are indispensable in a wide range of applications, including ultrafast lasers, microscopy, and quantum information technologies. Among the diverse nonlinear processes, second-order effects usually overwhelm the higher-order ones, except in centrosymmetric systems, where the second-order susceptibility vanishes to allow the use of the third-order nonlinearity. Here we demonstrate a hybrid photonic platform whereby the balance between second- and third-order susceptibilities can be tuned flexibly. By decorating ultra-high-Q silica microcavities with atomically thin tungsten diselenide, we observe cavity-enhanced second-harmonic generation and sum-frequency generation with continuous-wave excitation at a power level of only a few hundred microwatts. We show that the coexistence of second- and third-order nonlinearities in a single device can be achieved by carefully choosing the size and location of the two-dimensional material. Our approach can be generalized to other types of cavities, unlocking the potential of hybrid systems with controlled nonlinear susceptibilities for novel applications.

Reproducibility of cardiopulmonary exercise testing between one after and 1-3 weeks after elective percutaneous coronary intervention.

Prompt prescription and early initiation of exercise training are essential for patients undergoing elective percutaneous coronary intervention (PCI). We hypothesized that cardiopulmonary exercise testing (CPET) parameters determined the day after elective PCI during hospitalization would not differ from those obtained 1-3 weeks post-PCI in patients with stable coronary heart disease (CHD). CPET was performed the day after and 1-3 weeks (13±4.6; 7-21 days) after PCI. CPET was performed with a bicycle ergometer up to the ventilatory aerobic threshold (VAT) on the day after PCI. Symptom-limited CPET was conducted 1-3 weeks after PCI. No complications arose from the tests. There were no significant differences in %VAT (next day: 88.6±16.7 vs. 1-3 weeks later: 91.4%±18.7%), the workload at the VAT (51.8±11.0 W vs. 52.9± 11.6 W), heart rate (HR) at the VAT (95.3±105 beats/min vs. 94.1±11.3 beats/min), or metabolic equivalent (METs) at the VAT (3.69±0.69 vs. 3.84±0.78) between the two sessions. The slope of linear regression for two repeated measurements was close to 1 (%VAT, 1.02; workload at the VAT, 0.95; METs at the VAT, 1.03), except for HR (0.70). Bland-Altman plots revealed the reproducibility of all four CPET measurements between the two sessions. In conclusion, CPET up to the VAT can be performed safely 1-day post-PCI in patients with stable CHD. CPET parameters do not significantly differ between testing performed the day after and 1-3 weeks after PCI. Next-day CPET during hospitalization after PCI may enable prompt exercise prescription without the need for another CPET 1-3 weeks later.

A Japanese retrospective study of non-tuberculous mycobacterial infection in children, adolescents, and young adult patients with hematologic-oncologic diseases.

Non-tuberculous mycobacterial infection (NTM) is rare in healthy children, with lymphadenitis being the most common presentation. Immunocompromised populations are known to be at high risk, but the clinical picture of NTM infection in pediatric hematology/oncology patients is unclear. In this nationwide retrospective analysis of patients under the age of 40 treated in Japanese pediatric hematology/oncology departments who developed NTM infection between January 2010 and December 2020, 36 patients (21 patients with hematopoietic stem cell transplantation (HSCT) and 15 nontransplant patients) were identified. Post-transplant patients were infected with NTM at 24 sites, including the lungs (n = 12), skin and soft tissues (n = 6), bloodstream (n = 4), and others (n = 2). Nine of twelve patients with pulmonary NTM infection had a history of pulmonary graft-versus-host disease (GVHD), and rapid-growing mycobacteria (RGM) were isolated from five of them. In nontransplant patients, the primary diseases were acute lymphoblastic leukemia (ALL; n = 5), inborn errors of immunity (IEI; n = 6), and others (n = 4). All cases of ALL had bloodstream infections with RGM, whereas all cases of IEI were infected with slow-growing mycobacteria (SGM). In summary, three typical clinical scenarios for pediatric hematology/oncology patients have been established: RGM-induced pulmonary disease in patients with pulmonary GVHD, RGM bloodstream infection in patients with ALL, and SGM infection in patients with IEI. Our findings suggest that NTM must be regarded as a pathogen for infections in these high-risk patients, especially those with pulmonary GVHD, who may require active screening for NTM.

Clinical Outcomes and Predictors of All-Cause Mortality After Complex High-Risk and Indicated Revascularization Using Percutaneous Coronary Intervention.

The concept of complex and high-risk indicated procedures using percutaneous coronary intervention (CHIP-PCI) has recently been defined. However, few studies have investigated the prognosis of patients after CHIP-PCI. We enrolled 322 consecutive patients who underwent CHIP-PCI. CHIP-PCI was defined as a procedure satisfying at least one criterion each for both patient and procedure characteristics, as follows: patient characteristics [age ≥ 75 years old, low left ventricular ejection fraction (LVEF), diabetes mellitus, acute coronary syndrome, previous coronary artery bypass surgery, peripheral arterial disease, severe chronic kidney disease (CKD), chronic obstructive pulmonary disease (COPD), and severe valvular disease] and procedure characteristics [unprotected left main disease, degenerated saphenous or radial artery grafts, severely calcified lesions, last patent conduit, chronic total occlusions, multivessel disease, and use of mechanical circulatory support]. On Kaplan-Meier analysis, 1-, 2-, and 3-year survival rates following CHIP-PCI was 93.8%, 89.2%, and 85.4%, respectively. Moreover, on Cox multivariate hazard analysis, age (≥ 75 years old) (hazard ratio: 4.01, 95% confidence interval: 1.92-8.38, P < 0.01), COPD (hazard ratio: 2.95, 95% confidence interval: 1.38-6.32, P < 0.01), low LVEF (hazard ratio: 3.35, 95% confidence interval: 1.55-7.22, P < 0.01), severe CKD (hazard ratio: 3.02, 95% confidence interval: 1.44-6.36, P < 0.01), and use of mechanical circulatory support (hazard ratio: 5.97, 95% confidence interval: 2.72-13.10, P < 0.01) remained significant predictors of mortality. In conclusion, we revealed the clinical outcomes after CHIP-PCI. The presence of advanced age, COPD, low LVEF, severe CKD, and mechanical circulatory support use might lead to worse clinical outcomes.

Dopamine is involved in reparative dentin formation through odontoblastic differentiation of dental pulp stem cells.

Conventional direct pulp-capping materials induce pulp cells to secrete various biomolecules in pulp tissues that promote reparative dentin formation through induction of odontoblastic differentiation of dental pulp stem cells (DPSCs). However, these biomolecules sometimes induce bone-like dentin with poor sealing properties. Therefore, exploration of biomolecules that allow tight sealing by tubular reparative dentin is required. We recently reported that dopamine (DA) is involved in dentinogenesis. Hence, we investigated the effect of DA on odontoblastic differentiation of DPSCs and reparative dentin formation. Both tyrosine hydroxylase (TH), a DA synthetase, and DA were expressed in odontoblast-like cells in vivo. In vitro, their expression was increased during odontoblastic differentiation of DPSCs. Furthermore, TH-overexpressing DPSCs had promoted odontoblastic differentiation and DA production. Moreover, DA stimulation promoted their differentiation and induced tubular reparative dentin. These results suggest that DA produced by TH is involved in odontoblastic differentiation of DPSCs and has an inductive capacity for reparative dentin formation similar to primary dentin. This study may lead to the development of therapy to preserve vital pulp tissues.

Vedolizumab for children with intestinal graft-versus-host disease: a case report and literature review.

Acute graft-versus-host disease (aGVHD) is a challenging complication of allogeneic hematopoietic stem cell transplantation, and alternative therapies for patients showing inadequate response to steroids are limited. Vedolizumab, an anti-α4ß7 integrin antibody widely used for treating inflammatory bowel diseases, has recently been studied in adult patients with steroid-refractory intestinal aGVHD. However, few studies have examined its safety and effectiveness in pediatric patients with intestinal aGVHD. We report the case of a male patient with intestinal late-onset aGVHD treated with vedolizumab. He underwent allogeneic cord blood transplantation for warts, hypogammaglobulinemia, infections, and myelokathexis (WHIM) syndrome and developed intestinal late-onset aGVHD 31 months after transplantation. The patient was refractory to steroids; however, vedolizumab was initiated 43 months after transplantation (at the age of 7 years) and the symptoms of intestinal aGVHD were alleviated. Additionally, favorable endoscopic findings were observed, such as reduction of erosion and regenerative epithelial growth. We also evaluated the efficacy of vedolizumab in 10 patients with intestinal aGVHD (9 from the literature review and the present case). Six patients (60%) showed an objective response to vedolizumab. No serious adverse events were observed in any patients. Vedolizumab is a potential treatment option for steroid-refractory intestinal aGVHD in pediatric patients.

Current Application of iPS Cells in the Dental Tissue Regeneration.

When teeth and periodontal tissues are severely damaged by severe caries, trauma, and periodontal disease, such cases may be subject to tooth extraction. As tooth loss leads to the deterioration of quality of life, the development of regenerative medicine for tooth and periodontal tissue is desired. Induced pluripotent stem cells (iPS cells) are promising cell resources for dental tissue regeneration because they offer high self-renewal and pluripotency, along with fewer ethical issues than embryonic stem cells. As iPS cells retain the epigenetic memory of donor cells, they have been established from various dental tissues for dental tissue regeneration. This review describes the regeneration of dental tissue using iPS cells. It is important to mimic the process of tooth development in dental tissue regeneration using iPS cells. Although iPS cells had safety issues in clinical applications, they have been overcome in recent years. Dental tissue regeneration using iPS cells has not yet been established, but it is expected in the future.

ortho-Substituted Aryldiazonium Design for the Defect Configuration-Controlled Photoluminescent Functionalization of Chiral Single-Walled Carbon Nanotubes.

Defect functionalization of single-walled carbon nanotubes (SWCNTs) by chemical modification is a promising strategy for near-infrared photoluminescence (NIR PL) generation at >1000 nm, which has advanced telecom and bio/medical applications. The covalent attachment of molecular reagents generates sp3-carbon defects in the sp2-carbon lattice of SWCNTs with bright red-shifted PL generation. Although the positional difference between proximal sp3-carbon defects, labeled as the defect binding configuration, can dominate NIR PL properties, the defect arrangement chemistry remains unexplored. Here, aryldiazonium reagents with π-conjugated ortho-substituents (phenyl and acetylene groups) were developed to introduce molecular interactions with nanotube sidewalls into the defect-formation chemical reaction. The functionalized chiral SWCNTs selectively emitted single defect PL in the wavelength range of ∼1230-1270 nm for (6,5) tubes, indicating the formation of an atypical binding configuration, different from those exhibited by typical aryl- or alkyl-functionalized chiral tubes emitting ∼1150 nm PL. Moreover, the acetylene-based substituent design enabled PL brightening and a subsequent molecular modification of the doped sites using click chemistry.

Impact of the Coronavirus Disease 2019 Pandemic on the Clinical Features of Pediatric Respiratory Syncytial Virus Infection in Japan.

Background: Mitigation measures implemented during the coronavirus disease 2019 (COVID-19) pandemic remarkably reduced the incidence of infectious diseases among children. However, a re-emergence of respiratory syncytial virus (RSV) infection was observed in 2021 in Japan. We compared the clinical characteristics of hospitalized patients with RSV infection before and during COVID-19. Methods: We retrospectively enrolled children aged <6 years who were hospitalized with RSV infection in 18 hospitals and compared their clinical characteristics before (January 2019 to April 2020, 1675 patients) and during COVID-19 (September 2020 to December 2021, 1297 patients). Results: The mean age of patients with RSV infection was significantly higher during COVID-19 than before (17.4 vs 13.7 months, P < .001). Compared with before COVID-19, a 2.6-fold increase in RSV cases in the 2-5 years age group was observed from sentinel surveillance during COVID-19, whereas a 1.2-fold increase was noted in the same age group among hospitalized patients. On average for all patients, consolidation shadows obtained on radiography were less frequently observed (26.1 vs 29.6%, P = .04), and reduced respiratory assistance (42.2% vs 48.7%, P < .001) and hospitalization stay (5.7 vs 6.0 days, P < .001) was required in patients with RSV infection during COVID-19. Conclusions: Coronavirus disease 2019 and social activity restriction caused epidemiological changes in pediatric RSV infections, and a majority of patients with RSV infection aged ≥2 years did not develop severe symptoms requiring hospitalization. The RSV symptoms during the COVID-19 outbreak were equivalent to or milder than in the previous seasons.

PAX9 Is Involved in Periodontal Ligament Stem Cell-like Differentiation of Human-Induced Pluripotent Stem Cells by Regulating Extracellular Matrix.

Periodontal ligament stem cells (PDLSCs) play central roles in periodontal ligament (PDL) tissue homeostasis, repair, and regeneration. Previously, we established a protocol to differentiate human-induced pluripotent stem cell-derived neural crest-like cells (iNCs) into PDLSC-like cells (iPDLSCs) using human PDL cell-derived extracellular matrix (ECM). However, it remained unclear what factors principally regulate the differentiation of iNCs into iPDLSCs. In this study, we aimed to identify the transcription factor regulating production of human PDL cell-derived ECM, which is responsible for the generation of iPDLSCs. We cultured iNCs on ECMs of two human PDL cell lines (HPDLC-3S and HPDLC-3U) and of human dermal fibroblasts (HDF). iNCs cultured on HPDLC-3U demonstrated higher iPDLSC-associated gene expression and mesenchymal differentiation capacity than cells cultured on HDF or HPDLC-3S. The transcription factor PAX9 was highly expressed in HPDLC-3U compared with HDF and HPDLC-3S. iNCs cultured on siPAX9-transfected HPDLC-3U displayed downregulation of iPDLSC-associated marker expression and adipocytic differentiation capacity relative to controls. Our findings suggest that PAX9 is one of the transcription factors regulating ECM production in human PDL cells, which is responsible for the differentiation of iNCs into iPDLSCs.

Usefulness of the Snare Technique During Leadless Pacemaker Implantation for a Patient with a Severely Dilated Right Atrium.

We report here the case of a 92-year-old woman with atrial fibrillation bradycardia in which leadless pacemaker implantation was performed with a difficult delivery of the catheter sheath due to an extremely large right atrium. Using a snare technique with correction of the direction of the force on the catheter toward the right ventricle (RV) can result in successful delivery of the pacemaker catheter and stable placement of the pacemaker system in the RV septum. This specific snare technique has the potential to facilitate leadless pacemaker implantation safely in a severely dilated chamber of the heart, making this technique effective to use in clinical practice.

Cryoballoon ablation for atrial fibrillation without the use of a contrast medium: a combination of the intracardiac echocardiography and pressure wave monitoring guided approach.

In cryoballoon ablation (CBA), a contrast medium is commonly used to confirm balloon occlusion of the pulmonary veins (PVs). However, a contrast medium cannot always be used in patients with renal dysfunction and allergy. The present study aimed to assess the efficacy and safety of CBA without the use of a contrast medium. We retrospectively examined consecutive patients with paroxysmal atrial fibrillation (PAF) who underwent first-time CBA. We compared the procedural results and outcomes in patients for whom a contrast medium was used (contrast group) and those from whom a contrast medium was not used (non-contrast group). In the non-contrast group, we used saline injection on the intracardiac echocardiography and pressure wave monitoring for PV occlusion. Fifty patients (200 PVs) and 22 patients (88 PVs) underwent CBA with and without a contrast medium, respectively. The success rate of PV isolation with CBA alone was 93% and 90% in the non-contrast and contrast groups, respectively (p = 0.40). The fluoroscopy time and nadir temperature were significantly lower in the non-contrast group as compared to that in the contrast group. The recurrence rate 1 year after ablation did not differ between the two groups (18% vs. 18%, p > 0.99). Furthermore, the number of reconnected PVs in patients with recurrence was significantly lower in the non-contrast group than in the contrast group (6% vs. 36%, p = 0.017). In conclusion, CBA using the intracardiac echocardiography and pressure monitoring approach without the use of a contrast medium was safe and efficient.

Earliest pulmonary vein potential-guided cryoballoon ablation is associated with better clinical outcomes than conventional cryoballoon ablation: A result from two randomized clinical studies.

INTRODUCTION: With regard to short-term outcome in atrial fibrillation (AF), the benefit of cryoballoon ablation (CBA) by pressing a balloon against the earliest pulmonary vein (PV) potential site during PV isolation (earliest potential [EP]-guided CBA) has been previously demonstrated. The present study aimed to evaluate the long-term outcome of the EP-guided CBA. METHODS AND RESULTS: This study included 136 patients from two randomized studies, who underwent CBA for paroxysmal AF for the first time. Patients were randomly assigned to the EP-guided and conventional CBA groups in each study. In the EP-guided CBA group, we pressed a balloon against the EP site when the time-to-isolation (TTI) after cryoapplication exceeded 60 and 45 s in the first and second studies, respectively. We compared the clinical outcomes for 1 year after the procedure between the EP-guided CBA group (68 patients) and the conventional CBA group (68 patients). The primary endpoint was the recurrence of atrial arrhythmia after ablation. No significant differences in baseline characteristics were observed between the two groups. Compared with the conventional CBA group, the EP-guided CBA group had a significantly higher success rate at TTI ≤ 90 s (98.5% vs. 90.0%, p < .001); lower touch-up rate and total cryoapplication; and shorter procedure time, and fluoroscopy time. The recurrence at 1 year after ablation was significantly lower in the EP-guided CBA group than in the conventional CBA group (6.0% vs. 19.4%; p = .019). CONCLUSIONS: The EP-guided CBA approach can facilitate the ablation procedure and achieve low recurrence at 1 year after ablation.

Acute pancreatitis following allogeneic hematopoietic stem cell transplantation in children.

Acute pancreatitis (AP) is a potential complication of hematopoietic stem cell transplantation (HSCT), but its incidence and risk factors remain unclear. Thus, we reviewed the cases of 259 consecutive children who received allogeneic HSCT at our institution between January 2000 and December 2017 to determine the incidence and risk factors of AP. Thirteen patients developed AP during a median follow-up period of 4.4 years. The median time from HSCT to AP onset was 80 days (range 29-2426 days), and cumulative incidence (CI) at 4 years was 5.0% [95% confidence interval (95% CI) 2.7-8.3%]. The CI of AP was significantly higher in patients who received bone marrow or peripheral blood stem cells than in those who received cord blood (7.2% versus 0.0% at 4 years, P = 0.02) and was higher in patients who developed grade II-IV acute graft-versus-host disease (GVHD) than in those who did not (31.4% versus 1.4% at 4 years, P < 0.001). Multivariate analysis showed that grade II-IV acute GVHD was an independent risk factor for AP [hazard ratio 15.2 (95% CI 4.1-55.8), P < 0.001] and was strongly associated with post-HSCT AP in children.

Detection of negatively ionized air by using a Raman silicon nanocavity laser.

The performance of a Raman silicon laser based on a high quality-factor nanocavity depends on the degree of free-carrier absorption, and this characteristic may be useful for certain applications. Here we demonstrate that laser oscillation in a Raman silicon nanocavity laser stops abruptly after an exposure to a weak flux of negatively ionized air for a few seconds. Spectral measurements reveal that the laser interruption is mainly caused by the transfer of extra electrons from the negatively ionized air molecules to the silicon nanocavity. These electrons affect the efficiency of the Raman laser by free carrier absorption. We find that the laser output gradually recovers as the extra electrons escape from the nanocavity and confirm that such a detection of ionized air is repeatable. These results show that a Raman silicon nanocavity laser can be used for the detection of ionized air with a high spatial resolution.

Deterministic transfer of optical-quality carbon nanotubes for atomically defined technology.

When continued device scaling reaches the ultimate limit imposed by atoms, technology based on atomically precise structures is expected to emerge. Device fabrication will then require building blocks with identified atomic arrangements and assembly of the components without contamination. Here we report on a versatile dry transfer technique for deterministic placement of optical-quality carbon nanotubes. Single-crystalline anthracene is used as a medium which readily sublimes by mild heating, leaving behind clean nanotubes and thus enabling bright photoluminescence. We are able to position nanotubes of a desired chirality with a sub-micron accuracy under in-situ optical monitoring, thereby demonstrating deterministic coupling of a nanotube to a photonic crystal nanobeam cavity. A cross junction structure is also designed and constructed by repeating the nanotube transfer, where intertube exciton transfer is observed. Our results represent an important step towards development of devices consisting of atomically precise components and interfaces.