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This study aimed to examine whether the combination of excimer laser coronary atherectomy (ELCA) and drug-coated balloon (DCB) angioplasty can provide feasible clinical outcome in patients with ST-segment elevation myocardial infarction (STEMI) with 8-month and 2-year scheduled follow-up angiography.Intracoronary thrombus elevates the risk of interventional treatment in patients with STEMI and hampers drug absorption into the vasculature released from DCB.Sixty-two patients with STEMI within 24 h after the onset of symptoms were enrolled in this prospective, single-center, single-arm study.The laser catheter was successfully crossed distal to the culprit lesion in all cases. No ELCA-related adverse events occurred. Bail-out stenting was required in two patients (3.2%) after adjunctive ballooning; thus, the remaining 60 patients were completed with DCB angioplasty without stenting. Scheduled angiography at 8 months and 2 years was completed in 100% and 85.2%, respectively, and minimal lumen diameters were 3.4 ± 0.5, 3.4 ± 0.6, and 3.4 ± 0.5 mm after the procedure, at 8 months and at 2 years, respectively. Binary restenosis was observed in five patients (8.1%) in whom target lesion revascularization was performed. The duration of dual antiplatelet therapy was 2.3 ± 2.2 months, and neither abrupt vessel closure, reinfarction, cardiac death nor major bleeding was observed.A combination of DCB angioplasty with ELCA is a feasible therapeutic option for STEMI.

How Epstein–Barr virus (EBV)‐positive diffuse large B‐cell lymphoma (DLBCL) occasionally occurs following chronic inflammation remains to be elucidated. The case of a 57‐year‐old man who developed pulmonary EBV‐positive DLBCL from underlying silicosis lesions is presented. Immunohistochemical examination of the resected silicosis lesions showed predominant helper T cells and M1/M2 macrophages, with a lack of B cells, regulatory T cells, and resident memory T cells. Two years later, EBV‐positive DLBCL emerged unexpectedly from the silicosis. The imbalance of the immune cells in the microenvironment, at least in part, may help explain how chronic inflammation contributes to EBV‐positive DLBCL., The underlying silicosis lesions showed predominant Th cells and M1/M2 macrophages, with a lack of B cells, Treg cells, and TRM cells. The imbalance of the immune cells in the microenvironment, at least in part, may help to explain how chronic inflammation contributes to EBV‐positive diffuse large B‐cell lymphoma.

Oxidative addition of CH

Binary alloy catalysts have the potential to exhibit higher activity than monometallic catalysts in nitrogen activation reactions. However, owing to the multiple possible combinations of metal elements constituting binary alloys, an exhaustive search for the optimal combination is difficult. In this study, we searched for the optimal binary alloy catalyst for nitrogen activation reactions using a combination of Bayesian optimization and density functional theory calculations. The optimal alloy catalyst proposed by Bayesian optimization had a surface energy of ∼0.2 eV/Å

Bonding dissimilar elements to provide synergistic effects is an effective way to improve the performance of metal catalysts. However, as the properties become more dissimilar, achieving synergistic effects effectively becomes more difficult due to phase separation. Here we describe a comprehensive study on how subnanoscale alloying is always effective for inter-elemental synergy. Thirty-six combinations of both bimetallic subnanoparticles (SNPs) and nanoparticles (NPs) were studied systematically using atomic-resolution imaging and catalyst benchmarking based on the hydrogen evolution reaction (HER). Results revealed that SNPs always produce greater synergistic effects than NPs, the greatest synergistic effect was found for the combination of Pt and Zr. The atomic-scale miscibility and the associated modulation of electronic states at the subnanoscale were much different from those at the nanoscale, which was observed by annular-dark-field scanning transmission electron microscopy (ADF-STEM) and X-ray photoelectron spectroscopy (XPS), respectively.

Sea turtles have well developed lacrimal glands for their electrolyte homeostasis. In turtles, stapedial artery and palatine artery send branches to supply orbital region, but supply artery for lacrimal glands was not identified. Micro-CT scans showed dorsoventrally large lacrimal glands of sea turtle are supplied by both stapedial artery and palatine artery. The circulatory pattern in cranial region was reconstructed based on the micro-CT scans, showing that sea turtle has basically similar pattern with the common snapping turtle: stapedial artery supplies orbital region and mandibular artery is ramified from stapedial artery. We also investigate the foramen stapedio-temporalis in turtles using osteological specimens. The foramen stapedio-temporalis, where the stapedial artery passes through, has different size among four families of turtles. We compared the sum of cross sections of left and right foramen stapedio-temporalis since homeostasis of one individual is maintained by a pair of lacrimal glands. The size difference may reflect primarily the share of stapedial artery against palatine artery in cranial circulation pattern and blood supply of orbital regions. Our observations confirmed a significantly larger cross-section in the foramen stapedio-temporalis of sea turtles than other freshwater/terrestrial turtles. Since the circulatory pattern is shared, the size difference of foramen stapedio-temporalis reflects the amount of arterial blood supply to lacrimal glands. Therefore, the size of the foramen stapedio-temporalis may indicate marine adaptation of turtles and are applicable to both fossil and osteological specimens.

BackgroundThe lack of precise information on the epidemiology of peripheral intravascular catheter (PIVC)-related phlebitis and complications in critically ill patients results in the absence of appropriate preventive measures. Therefore, we aimed to describe the epidemiology of the use of PIVCs and the incidence/occurrence of phlebitis and complications in the intensive care unit (ICU).MethodsThis prospective multicenter cohort study was conducted in 23 ICUs in Japan. All consecutive patients aged ≥ 18 years admitted to the ICU were enrolled. PIVCs inserted prior to ICU admission and those newly inserted after ICU admission were included in the analysis. Characteristics of the ICU, patients, and PIVCs were recorded. The primary and secondary outcomes were the occurrence and incidence rate of PIVC-related phlebitis and complications (catheter-related blood stream infection [CRBSI] and catheter failure) during the ICU stay.ResultsWe included 2741 patients and 7118 PIVCs, of which 48.2% were inserted in the ICU. PIVC-related phlebitis occurred in 7.5% (95% confidence interval [CI] 6.9–8.2%) of catheters (3.3 cases / 100 catheter-days) and 12.9% (95% CI 11.7–14.2%) of patients (6.3 cases / 100 catheter-days). Most PIVCs were removed immediately after diagnosis of phlebitis (71.9%). Grade 1 was the most common phlebitis (72.6%), while grade 4 was the least common (1.5%). The incidence rate of CRBSI was 0.8% (95% CI 0.4–1.2%). In cases of catheter failure, the proportion and incidence rate per 100 intravenous catheter-days of catheter failure were 21% (95% CI 20.0-21.9%) and 9.1 (95% CI 8.7–10.0), respectively.ConclusionPIVC-related phlebitis and complications were common in critically ill patients. The results suggest the importance of preventing PIVC-related complications, even in critically ill patients.Trial registrationUMIN-CTR, the Japanese clinical trial registry (registration number:UMIN000028019, July 1, 2017).

A 68-year-old Japanese man was admitted to our hospital for an acute febrile illness with shivering and impaired consciousness. He was a previous smoker and had a history of chronic obstructive pulmonary disease, for which he inhaled steroid with a long-acting bronchodilator. He had received a 23-valent pneumococcal polysaccharide vaccination 2 years previously. He was intubated and placed on a ventilator in intensive care unit because of acute respiratory failure and hypercapnia. Streptococcus pneumoniae was grown from his blood, sputum, and urine cultures, and he was diagnosed with invasive pneumococcal disease with acute renal failure. He was treated with intravenous beta-lactam and macrolide with continuous hemodiafiltration and was discharged 3 months later. The pneumococcus was identified as serotype 12F, and his serotype-specific IgG and opsonophagocytic index against serotype 12F indicating a lack of protection from IPD among PPV23 serotypes. This case highlights that some individuals may have a serotype-specific polysaccharide antibody failure that makes them susceptible to serotype 12F invasive pneumococcal disease. This case also illustrates the need for serotype-specific IgG and opsonophagocytic index titre cut-offs for each specific pneumococcal serotype in available vaccines to understand the vaccination protection for individual patients better.

The association between gut microbiota and the lung immune system has been attracting increasing interest. Here, we report a case of pancreatic cancer in which the dipeptidyl peptidase-4 inhibitor vildagliptin induced unusual manifestations of interstitial pneumonia, possibly under the influence of Lactobacillus paraplantarum probiotic supplementation. Chest computed tomography and positron emission tomography showed multiple ground-glass nodules (GGNs) mimicking metastatic lung cancer. Transbronchial biopsy specimens showed mild fibrosis and infiltration of lymphocytes consisting of more CD4+ than CD8+ cells. The CD4+ cells did not include FOXP3+ regulatory T cells. Bronchoalveolar lavage confirmed lymphocytosis with a markedly increased CD4+ /CD8+ ratio of 7.4. The nodules disappeared shortly after vildagliptin and probiotics were withheld. If unusual interstitial pneumonia is observed in some cancer patients, physicians should pay careful attention to their medication history, including probiotic supplements.

We studied the effects of mineral oil (MO) on the properties and structure of a spread monolayer of polar lipid constituents in meibum, by performing cyclic lateral compression-expansion experiments using a Langmuir trough. A meibum sample without nonpolar lipids (meibumΔnonpolar-lipid) was prepared by removing the nonpolar lipids from biological meibum extruded from rabbit eyelids and spread on a water surface for measuring the cyclic surface pressure (π)-film area (A) isotherms with in situ observation of the film morphology using a Brewster angle microscope. The meibumΔnonpolar-lipid formed a homogeneous fluid monolayer and underwent collapse upon compression. The π-A isotherm shifted to a smaller area upon repeating the compression-expansion cycles. These observations contrasted those obtained for meibum previously, which may have resulted from the absence of nonpolar lipids. The recovery of the film stability against the lateral compression-expansion cycles was analyzed by adding MO as a nonpolar compound to the film system. A spread film of 1:1 mixture (by weight) could recover the high reversibility of the π-A isotherms during the repeated compression and expansion processes.

Oral treatment for elderly outpatients with pneumonia is becoming increasingly important in this super-aged society from the perspective of cost-effectiveness and limited hospital capacities. We evaluated the efficacy and safety of two oral respiratory quinolones, sitafloxacin and garenoxacin, in elderly patients with pneumonia. This randomized, multicenter, open-label trial was conducted among patients aged ≥65 years with clinically and radiographically confirmed pneumonia in Japan. Patients were randomly assigned (1:1) to receive either sitafloxacin (100 mg/day) or garenoxacin (400 mg/day) for 3–10 days. The primary efficacy endpoint was the clinical cure rate at 5–10 days after the end of treatment. From December 2013 to November 2017, we enrolled 120 patients at 11 hospitals and randomly assigned 59 patients to the sitafloxacin group (1 patient withdrew) and 61 patients to the garenoxacin group. These included 30 patients with nursing and healthcare-associated pneumonia (NHCAP) (18 receiving sitafloxacin, 12 receiving garenoxacin) and 37 patients with aspiration pneumonia (16 receiving sitafloxacin, 21 receiving garenoxacin). The clinical cure rates in the sitafloxacin and garenoxacin groups were 88.5% (95% confidence interval: 76.6–95.6) and 88.9% (95% confidence interval: 77.4–95.8), respectively. No significant differences were observed in the incidence rates of drug-related adverse events between the sitafloxacin (20.7%; 12/58 patients) and garenoxacin (27.9%; 17/61 patients) groups. The most common adverse event was hepatic dysfunction, which occurred in seven patients in each group. We conclude that sitafloxacin and garenoxacin are comparably effective and safe for the treatment of pneumonia, including NHCAP and aspiration pneumonia, in elderly patients.

Coal preparation plants are under increasing pressure to reduce their consumption of fresh water leading to the use of recycle water. Recycled water generally contains a large quantity of dissolved inorganic electrolytes, which affect coal flotation. This paper reports the conductivity and pH measurements of water in the tailings stream of an industrial scale flotation cell covering a period of approximately two years. The different coal seams processed at the site were also compared and the influence the water quality on the overall yield of coal assessed. This study presents the large variation in inorganic content in recycled water observed for a wash plant and determines its possible effect on coal preparation. The maximum daily temperature was found to be an important factor controlling the amount of inorganic electrolytes in the water and, very significantly, the water management system implemented. The overall plant performance was somewhat affected by the use of water containing high concentrations of inorganic electrolytes. The effect of the quantity of ions in the water on the flotation process is explored in Part 2.

This manuscript is an extension of part 1 in which secondary data was acquired and analyzed to evaluate the effect of the water management system and recycling water on the performance of a coal preparation plant. Recycling water leads to an accumulation of inorganic electrolytes by dissolving some of the inorganic matters from the coals. The effect of water quality on the performance of a Jameson cell at a coal preparation plant was investigated using water conductivity and pH data monitored for approximately two years over a three year period. The concentration of inorganic electrolytes was found to strongly affect the gas dispersive properties in the flotation cell and the dosing of other reagents was modified in response to variations in the conductivity of the water. Flotation performances were assessed by the average particle density of the tailings stream. The results again highlight the significant effect of the presence of inorganic electrolytes. Specifically, the interaction of the conductivity with the frother concentration and the superficial gas velocity could lead to the increased flotation of coal particles as well as the entrainment of coal reject particles.

Semiaquatic walking has resulted in the evolution of functional and morphological changes in various hoofed mammals, such as hippopotamus and Brazilian tapir. The biomechanics of skilful walking in wetlands or at the bottom of a waterbody involve the medio-lateral opening and closing of the feet to effectively support and stabilize the body on soft ground and to reduce the water resistance during recovery stroke, respectively. We demonstrate that the opening and closing of the feet in hippopotamus and Brazilian tapir are mediated by the adduction and abduction of the most medial and lateral phalanges from the CT examination. The axial toes, metacarpals and metatarsals do not contribute to changes in the width and shape of the feet, unlike the medial and lateral toes. We suggest that this semiaquatic walking motion is derived from the original terrestrial mode of locomotion, in contrast to the highly functional swimming motion using webs or fins in morphologically modified feet and tail. From the present data we demonstrate that semiaquatic locomotion evolved due to the acquisition of adductor-abductor mobility in the phalanges of the most medial and lateral digits, as shown in hippopotamus and Brazilian tapir.

Mass migration of photo-isomeric azo-polymers occurs according to the light intensity gradient, and the morphological surface structure can be fabricated by the artificial distribution of light by applying the interference properties of coherent laser light. Recently, the optical radiation force has played an important role in the morphology for dielectric targets, and chiral structures have been fabricated according to the spirally gathering force distribution that arises due to the electric susceptibility. On the contrary, interference laser processing has been applied to process the surface or interior of the material, and nano- or micro-structures in the lattice have been fabricated in a single exposure to the interference pattern. The unit structures are mostly axisymmetric nanowhiskers, nanodrops and nanobumps, among others. In this experiment, interference laser processing of an azo-polymer dielectric target using a circularly polarised continuous-wave (CW) laser was examined, and a spiral structure was successfully fabricated. From the viewpoint of laser processing method, an optical spiral radiation force was introduced in interference laser processing for the first time.

Background The combination of PD-1 inhibitors and cytotoxic drugs is reported to enhance anti-tumor activity in non-small cell lung cancer; however, the underlying synergistic mechanisms remain uncertain. This retrospective case series was designed to investigate objective response and survival rates of salvage chemotherapy following nivolumab and explore the immunohistochemical profiles of tumor-infiltrating immune cells. Methods The medical records of 37 patients administered nivolumab were retrospectively reviewed. Overall response rate and progression-free survival were compared among three groups: salvage chemotherapy following nivolumab, nivolumab therapy alone, and chemotherapy preceding nivolumab. Results Eight cases met the study criteria. Salvage chemotherapy following nivolumab improved the overall response rate to 62.5% (95% confidence interval [CI] 34.4-90.6%; P = 0.004) and median progression-free survival to six months (95% CI 4.6-7.4; P = 0.016), compared to nivolumab alone and preceding chemotherapy. The response to salvage chemotherapy was not associated with tumor PD-L1 expression. A partial response was achieved in four cases with ≤ 5% and ≤ 2.9 cells/mm2 of PD-1+ immune cells, whereas stable disease and progressive disease were observed in three cases with ≥ 30% and ≥ 12.7 cells/mm2 . Responders had fewer PD-1+ immune cells than non-responders (percentage P = 0.028; density P = 0.034). Conclusion Salvage chemotherapy following nivolumab improved anti-tumor activity regardless of tumor PD-L1 status, but nivolumab following chemotherapy did not. The presence of few PD-1+ tumor-infiltrating immune cells may serve as a potential predictor of response to salvage chemotherapy. Further studies involving a large cohort are needed to clarify how nivolumab re-sensitizes the tumor immune microenvironment to chemotherapy.

Little is known about the anti-tumor activity of humoral immunity in lung cancer patients treated with nivolumab, an immune checkpoint inhibitor. Herein, we report a case of lung cancer with 5% expression of PD-L1, in which a partial response to nivolumab was sustained for > 7 months. Immunohistochemical analysis of the metastatic lymph node biopsy specimen showed prominent accumulation of plasma cells and immunoglobulin G. These findings suggest that pre-existing humoral immunity may be worth considering as a candidate therapeutic biomarker of nivolumab in some lung cancer patients.

Interference of six countering femtosecond (fs) laser beams at a wavelength of 785 nm has been utilized to fabricate nanostructures in a regular hexagonal lattice. A diffractive-optical element for six-beam splitting was introduced to a beam correlation system. The lattice structure was in accordance with the simulated structure based on the principle of superposition of electric fields. The unit structures fabricated on gold thin films were nanobit, nanodrop, and metallic hole array. The height and diameter of a representative nanodrop were 450 and 210 nm, respectively. Molten structures such as nanodrops are believed to have been fabricated via a solid–liquid–solid (SLS) mechanism, as in the case of previous experiments using four beams. In addition, multi-shot processing is examined to fabricate through-holes at lower fluences.

Molecular orientation with combinations of near-single-cycle THz and non-resonant laser pulses is studied by means of optimal control simulation with CO molecules at 5 K. We optimize non-resonant laser pulses with optimally determined final times while assuming fixed THz pulses and focusing on the carrier-envelope phase (CEP) effects. Although almost the same high degrees of orientation are achieved by the combined control independent of CEPs, the structures of the optimal non-resonant laser pulses considerably depend on CEPs and the central frequencies of the THz pulses. From a practical viewpoint, simplified treatments are also discussed.

In this study, we examined the hypothesis that the preferential conduction property along left lateral ridge (LLR) might affect the arrhythmogenicity of left pulmonary veins (LPVs).The study population included 40 consecutive AF patients. Radiofrequency energy (RF) was sequentially delivered along the LLR from a lower to upper manner during postero-lateral CS pacing during an isoproterenol infusion.The conduction time during pacing from the CS was significantly prolonged during radiofrequency (RF) deliveries (before vs. after, upper; 91±26ms vs. 127±38ms, p0.001, lower; 86±21ms vs. 103±22ms, p0.001). Remarkable prolongation of more than 30ms was observed in 19 of 40 patients (48%) (both LPVs, 6; only the upper LPVs, 12; and only the lower LPV, 1). Sites with a remarkable prolongation were observed at the carina between the LPVs,[4] anterior site of the upper LPV carina,[10] anterior wall of the lower LPV,[3] and bottom of the lower LPVs [2] Thirty-three arrhythmogenic foci (AMF) from the LPVs were observed in 23/40 patients (56%). The conduction time during pacing from the LPVs during the RF delivery was significantly longer in the patients with AMF from the upper LPV than in those patients without (107±36ms vs. 146±40ms, p0.01).The LLR includes the preferential conduction properties between the CS and LPVs, and the observation of the serial changes during the RF delivery could provide us information about the LPVs arrhythmogenicity.

A 28-year-old man arrived at our hospital complaining of severe dyspnea. Bronchoscopic findings demonstrated that a tumor was located approximately 4 cm distant from the vocal cord, occupying most of the tracheal lumen. To urgently relieve the dyspnea, some parts of the tumor were cauterized with the neodymium:yttrium-aluminum garnet laser. Histopathologic examination of the cauterized specimen revealed malignant hemangiopericytoma. During the operation, the tumor was resected en bloc with a tracheal segment containing four tracheal cartilages. The patient's postoperative course was uneventful with no evidence of recurrence 1 year after the operation.

Beta-adrenergic (BA) signaling including cAMP-protein kinase A (PKA) pathway has been implicated in the mechanism of ischemic preconditioning (IPC). However, effect of IPC on the failing heart, in which BA signaling is supposed to be altered, is left to be determined. To assess a role of BA signaling in IPC, levels of beta2-adrenergic receptor (B2AR) mRNA were quantified by real time RT-PCR, and in vivo intracardiac function was evaluated in post-MI heart. The effect of IPC on post-MI heart was then determined with an isolated heart perfusion system. Finally, cardioprotective effect of repetitive preischemic infusion of phosphodiesterase III inhibitor olprinone (30 microM), which is known to increase myocardial cAMP levels, was evaluated with/without PKA inhibitor H-89 (2 microM). B2AR mRNA levels in post-MI heart were significantly reduced compared to non-MI heart. IPC was not effective in post-MI heart. Repetitive preischemic infusion of olprinone increased peak developed pressure (94.6 +/- 6.3 vs. 62.8 +/- 4.9%, OLP vs. control, p0.05) and decreased infect size (15.2 +/- 0.4 vs. 33.5 +/- 2.5%, OLP vs. control, p0.01). These effects were abolished by H-89. These results may indicate that repetitive preischemic infusion of olprinone mimics IPC through cAMP-PKA pathway in post-MI heart, and that BA signaling plays a crucial role in IPC response.

Carperitide, a synthetic alpha-human atrial natriuretic peptide (ANP) is a newly developed drug for the treatment of heart failure. However, effects of carperitide on susceptibility to ischemia reperfusion injury are left to be determined. Isolated rat hearts were subjected to Langendorff perfusion. Six hearts received 0.1 microM of carperitide for 10 min, 6 hearts received 1 mM of a NO synthetase inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME) for 5 min before the infusion of carperitide, 6 hearts received 0.02 microM of a PKC synthetase inhibitor chelerythrine chloride for 5 min before the infusion of carperitide, 6 hearts received 100 microM of a selective mitochondrial ATP-sensitive potassium (KATP) channel blocker 5-dehydroxydecanoate (5HD) before the infusion of carperitide, 6 hearts received 10 microM of a soluble guanylate cyclase inhibitor methylene blue for 5 min before the infusion of carperitide, and 6 hearts served as a control with no drug infusion. All hearts were then subjected to 20 min of global ischemia followed by 120 min of reperfusion. Left ventricular pressures and coronary flow were measured throughout the experiment and infarct size was detected at the end of experiment. Both plasma and tissue cGMP levels were also determined. The results showed: (1) Carperitide significantly reduced infarct size compared to control (26.1 +/- 2.8 vs. 42.7 +/- 2.3%, carperitide vs. control, p0.05). This effect was reversed by L-NAME, chelerythrine and 5HD, but not methylene blue. (2) Plasma cGMP levels were increased in carperitide-treated group. This effect was reversed by L-NAME (0.16 +/- 0.03 vs. 1.04 +/- 0.09* vs. 0.28 +/- 0.02 nmol/L, control vs. carperitide vs. L-NAME, *p0.01 vs. control). We conclude that preischemic infusion of carperitide exerts cardioprotective effects possibly through NO-PKC dependent pathway followed by mitochondrial KATP channel activation.