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In sarcoidosis, granulomas develop in multiple organs including the liver and lungs. Although mechanistic target of rapamycin complex 1 (mTORC1) activation in macrophages drives granuloma development in sarcoidosis by enhancing macrophage proliferation, little is known about the macrophage subsets that proliferate and mature into granuloma macrophages. Here, we show that aberrantly increased monocytopoiesis gives rise to granulomas in a sarcoidosis model, in which Tsc2, a negative regulator of mTORC1, is conditionally deleted in CSF1R-expressing macrophages (Tsc2 csf1rΔ mice). In Tsc2 csf1rΔ mice, common myeloid progenitors (CMPs), granulocyte-monocyte progenitors (GMPs), common monocyte progenitors / monocyte progenitors (cMoPs / MPs), inducible monocyte progenitors (iMoPs), and Ly6Cint CX3CR1low CD14− immature monocytes (iMOs), but not monocyte-dendritic cell progenitors (MDPs) and common dendritic cell progenitors (CDPs), accumulated and proliferated in the spleen. Consistent with this, monocytes, neutrophils, and neutrophil-like monocytes increased in the spleens of Tsc2 csf1rΔ mice, whereas dendritic cells did not. The adoptive transfer of splenic iMOs into wild-type mice gave rise to granulomas in the liver and lungs. In these target organs, iMOs matured into Ly6Chi classical monocytes/macrophages (cMOs). Giant macrophages (gMAs) also accumulated in the liver and lungs, which were similar to granuloma macrophages in expression of cell surface markers such as MerTK and SLAMF7. Furthermore, the gMA-specific genes were expressed in human macrophages from sarcoidosis skin lesions. These results suggest that mTORC1 drives granuloma development by promoting the proliferation of monocyte/neutrophil progenitors and iMOs predominantly in the spleen, and that proliferating iMOs mature into cMOs and then gMAs to give rise to granuloma after migration into the liver and lungs in sarcoidosis. [ABSTRACT FROM AUTHOR]

Materials that intrinsically exhibit localized surface plasmon resonance (LSPR) in the visible region have been predominantly researched on nanoparticles (NPs) composed of coinage metals, namely Au, Ag, and Cu. Here, as a coinage metal‐free intermetallic NPs, colloidal PtIn2 NPs with a C1 (CaF2‐type) crystal structure are synthesized by the liquid phase method, which evidently exhibit LSPR at wavelengths similar to face‐centered cubic (fcc)‐Au NPs. Computational simulations pointed out differences in the electronic structure and photo‐excited electron dynamics between C1‐PtIn2 and fcc‐Au NPs; reduces interband transition and stronger screening with smaller number of bound d‐electrons compare with fcc‐Au are unique origins of the visible plasmonic nature of C1‐PtIn2 NPs. These results strongly indicate that the intermetallic NPs are expected to address the development of alternative plasmonic materials by tuning their crystal structure and composition. [ABSTRACT FROM AUTHOR]

Purpose: The prevalence of hyperdynamic left ventricular (LV) systolic function in septic patients and its impact on mortality remain controversial. In this systematic review and meta-analysis, we investigated the prevalence and association of hyperdynamic LV systolic function with mortality in patients with sepsis. Methods: We searched MEDLINE, Cochrane Central Register of Controlled Trials, and Embase. Primary outcomes were the prevalence of hyperdynamic LV systolic function in adult septic patients and the associated short-term mortality as compared to normal LV systolic function. Hyperdynamic LV systolic function was defined using LV ejection fraction (LVEF) of 70% as cutoff. Secondary outcomes were heart rate, LV end-diastolic diameter (LVEDD), and E/e' ratio. Results: Four studies were included, and the pooled prevalence of hyperdynamic LV systolic function was 18.2% ([95% confidence interval (CI) 12.5, 25.8]; I2 = 7.0%, P < 0.0001). Hyperdynamic LV systolic function was associated with higher mortality: odds ratio of 2.37 [95%CI 1.47, 3.80]; I2 = 79%, P < 0.01. No difference was found in E/e' (P = 0.43) between normal and hyperdynamic LV systolic function, while higher values of heart rate (mean difference: 6.14 beats/min [95%CI 3.59, 8.69]; I2 = 51%, P < 0.0001) and LVEDD (mean difference: − 0.21 cm [95%CI − 0.33, − 0.09]; I2 = 73%, P < 0.001) were detected in patients with hyperdynamic LV systolic function. Conclusion: The prevalence of hyperdynamic LV systolic function is not negligible in septic patients. Such a finding is associated with significantly higher short-term mortality as compared to normal LV systolic function. [ABSTRACT FROM AUTHOR]

To develop a method for predicting amyloid positron emission tomography (PET) positivity based on multiple regression analysis of quantitative susceptibility mapping (QSM). This prospective study included 39 patients with suspected dementia from four centers. QSM images were obtained through a 3-T, three-dimensional radiofrequency-spoiled gradient-echo sequence with multiple echoes. The cortical standard uptake value ratio (SUVR) was obtained using amyloid PET with 18F-flutemetamol, and susceptibility in the brain regions was obtained using QSM. A multiple regression model to predict cortical SUVR was constructed based on susceptibilities in multiple brain regions, with the constraint that cortical SUVR and susceptibility were positively correlated. The discrimination performance of the Aβ-positive and Aβ-negative cohorts was evaluated based on the predicted SUVR using the area under the receiver operating characteristic curve (AUC) and Mann–Whitney U test. The correlation coefficients between true and predicted SUVR were increased by incorporating the constraint, and the AUC to discriminate between the Aβ-positive and Aβ-negative cohorts reached to 0.79 (p < 0.01). These preliminary results suggest that a QSM-based multiple regression model can predict amyloid PET positivity with fair accuracy. [ABSTRACT FROM AUTHOR]

It is necessary to secure both the proximal and distal sides of the parent artery to prevent premature rupture when clipping cerebral aneurysms. Herein, we describe four cases in which the proximal internal carotid artery (ICA), affected by a paraclinoid aneurysm, was secured using an endoscopic endonasal approach. We used various tools, including a surgical video, cadaver dissection picture, artist's illustration, and intraoperative photographs, to elucidate the process. No patient experienced postoperative complications at our institution. Compared to the cervical or cavernous ICA, the ICA adjacent to the clivus (paraclival ICA) can be anatomically safely and easily exposed using an endoscopic endonasal approach because there is no need to consider cerebrospinal fluid leakage or hemorrhage from the cavernous sinus. Securing the proximal side of the parent artery using an endoscopic endonasal approach may be a viable method for clipping selected ICA aneurysms, such as paraclinoid aneurysms especially for upward or outward aneurysms of the C2 portion. [ABSTRACT FROM AUTHOR]

Background: Tissue Doppler-derived left ventricular systolic velocity (mitral S') has shown excellent correlation to left ventricular ejection fraction (LVEF) in non-critically patients. However, their correlation in septic patients remains poorly understood and its impact on mortality is undetermined. We investigated the relationship between mitral S' and LVEF in a large cohort of critically-ill septic patients. Methods: We conducted a retrospective cohort study between 01/2011 and 12/2020. All adult patients (≥ 18 years) who were admitted to the medical intensive care unit (MICU) with sepsis and septic shock that underwent a transthoracic echocardiogram (TTE) within 72 h were included. Pearson correlation test was used to assess correlation between average mitral S' and LVEF. Pearson correlation was used to assess correlation between average mitral S' and LVEF. We also assessed the association between mitral S', LVEF and 28-day mortality. Results: 2519 patients met the inclusion criteria. The study population included 1216 (48.3%) males with a median age of 64 (IQR: 53–73), and a median APACHE III score of 85 (IQR: 67, 108). The median septal, lateral, and average mitral S' were 8 cm/s (IQR): 6.0, 10.0], 9 cm/s (IQR: 6.0, 10.0), and 8.5 cm/s (IQR: 6.5, 10.5), respectively. Mitral S' was noted to have moderate correlation with LVEF (r = 0.46). In multivariable logistic regression analysis, average mitral S' was associated with an increase in both 28-day ICU and in-hospital mortality with odds ratio (OR) 1.04 (95% CI 1.01–1.08, p = 0.02) and OR 1.04 (95% CI 1.01–1.07, p = 0.02), respectively. Conclusions: Even though mitral S' and LVEF may be related, they are not exchangeable and were only found to have moderate correlation in this study. LVEF is U-shaped, while mitral S' has a linear relation with 28-day ICU mortality. An increase in average mitral S' was associated with higher 28-day mortality. [ABSTRACT FROM AUTHOR]

The impact of left ventricular (LV) systolic function on outcomes in patients with sepsis and septic shock remains uncertain. The association, if any, may be nonlinear. Is LV systolic dysfunction associated with increased mortality among patients with sepsis and septic shock? Retrospective cohort study comprising all adult patients admitted to the medical ICU from January 1, 2011, through December 31, 2020, with sepsis and septic shock as defined by the Third International Consensus Definitions for Sepsis and Septic Shock guidelines. All adult patients with sepsis or septic shock who underwent transthoracic echocardiography within 3 days from admission to the medical ICU were included. We divided patients into five groups based on LV ejection fraction (LVEF). In addition to univariate analysis, we also performed multivariate logistic regression analysis adjusting for patients' baseline characteristics and severity of illness. The primary outcome was the association between each classification of LVEF and in-hospital mortality. A total of 3,151 patients were included in this study (LVEF < 25%, 133 patients; 25% ≤ LVEF < 40%, 305 patients; 40% ≤ LVEF < 55%, 568 patients; 55% ≤ LVEF < 70%, 1,792 patients; and LVEF ≥ 70%, 353 patients). In-hospital mortalities in each LVEF category were 51.1%, 34.8%, 26.6%, 26.2%, and 41.9%, respectively. In the multivariate logistic regression analysis, LVEF of < 25% (OR, 2.75; 95% CI, 1.82-4.17; P <.001) and LVEF of ≥ 70% (OR, 1.70; 95% CI, 1.09-1.88; P =.010) were associated independently with significantly higher in-hospital mortality compared with the reference LVEF category of 55% to 70%. The association of LVEF to in-hospital mortality in sepsis and septic shock was U-shaped. Both severe LV systolic dysfunction (LVEF < 25%) and hyperdynamic LVEF (LVEF ≥ 70%) were associated independently with significantly higher in-hospital mortality. [ABSTRACT FROM AUTHOR]

Diphenylanthracene (DPA) and its derivatives are promising semiconducting materials for p‐type organic‐field‐effect transistors (OFETs). In this study, to develop n‐type semiconducting materials with an anthracene core, pentafluorobenzene was introduced into anthracene by C−H direct arylation, enabling the synthesis of various bis(pentafluorophenyl)anthracene (DPA−F) derivatives. The high reactivity of the pentafluorobenzene C−H bond allows direct arylation for synthesizing DPA−F derivatives in a single step. The introduction of strong electron‐withdrawing pentafluorophenyl groups provides the anthracene derivatives with n‐type semiconducting properties, in contrast to the p‐type properties of the parent DPAs. Among the synthesized compounds, 2,6‐bis(pentafluorophenyl)anthracene shows a high electron mobility of 0.12±0.02 cm2/Vs and an on/off ratio>106 in OFETs. The high crystallinity results in the smooth electron transport. This study provides a facile synthetic method for n‐type semiconducting materials and insights into the molecular design of the positional effects of aromatic substituents on anthracene. [ABSTRACT FROM AUTHOR]

Background: Ventricular-arterial coupling (V-A coupling) recently gathers attention from clinicians to evaluate the interaction between afterload and left ventricular systolic function. We aimed to describe the chronological demographics of V-A decoupling in patients with sepsis and septic shock through the clinical course. Method: We conducted a single-center prospective observational study comprising adult patients with sepsis and septic shock admitted to the tertiary care hospital between 04/2017 and 03/2019. Patients' characteristics, lab data on admission, and echocardiographic parameters including Ea and Ees on the day- 1, 2, 3, 7, and 14–28 were collected. V-A decoupling was defined as Ea/Ees ≥ 1.36. Results: Seventy-one patients with sepsis or septic shock were enrolled. The prevalence of V-A decoupling was as follows; day-1: 25.4%, day-2: 23.8%, day-3: 13.3%, day-7: 18.5%, day-14–28: 30.3%, respectively. Ea was higher in patients with V-A decoupling than those without throughout the clinical course (day1; 2.8 vs. 1.8, p < 0.01, day2; 2.7 vs. 1.9, p < 0.01, day3; 2.8 vs. 2.1, p = 0.06, day7; 2.7 vs. 1.9, p = 0.02, day14-28; 2.4 vs. 1.8, p = 0.08). This increase in Ea was mainly induced by reduced stroke volume (SV) as well as high systolic blood pressure (SBP) in the earlier course of sepsis but only by increased SBP in the later course of sepsis. Ees was lower in patients with V-A decoupling than those without throughout the clinical course (day1; 1.3 vs. 2.1, p < 0.01, day2; 1.5 vs. 2.3, p < 0.01, day3; 1.6 vs. 2.3, p = 0.02, day7; 1.8 vs. 2.3, p = 0.01, day14-28; 1.2 vs. 1.9, p = 0.07). Conclusion: We reported that V-A decoupling was commonly seen in patients with sepsis and septic shock. In patients with V-A decoupling, both Ea and Ees were significantly altered, but the causes of these alterations appeared to be changing over the clinical course of sepsis. [ABSTRACT FROM AUTHOR]

Objectives: Voxel-based morphometry (VBM) is widely used to quantify the progression of Alzheimer's disease (AD), but improvement is still needed for accurate early diagnosis. We evaluated the feasibility of a novel diagnosis index for early diagnosis of AD based on quantitative susceptibility mapping (QSM) and VBM. Methods: Thirty-seven patients with AD, 24 patients with mild cognitive impairment (MCI) due to AD, and 36 cognitively normal (NC) subjects from four centers were included. A hybrid sequence was performed by using 3-T MRI with a 3D multi-echo GRE sequence to obtain both a T1-weighted image for VBM and phase images for QSM. The index was calculated from specific voxels in QSM and VBM images by using a linear support vector machine. The method of voxel extraction was optimized to maximize diagnostic accuracy, and the optimized index was compared with the conventional VBM-based index using receiver operating characteristic analysis. Results: The index was optimal when voxels were extracted as increased susceptibility (AD > NC) in the parietal lobe and decreased gray matter volume (AD < NC) in the limbic system. The optimized proposed index showed excellent performance for discrimination between AD and NC (AUC = 0.94, p = 1.1 × 10−10) and good performance for MCI and NC (AUC = 0.87, p = 1.8 × 10−6), but poor performance for AD and MCI (AUC = 0.68, p = 0.018). Compared with the conventional index, AUCs were improved for all cases, especially for MCI and NC (p < 0.05). Conclusions: In this preliminary study, the proposed index based on QSM and VBM improved the diagnostic performance between MCI and NC groups compared with the VBM-based index. Key Points: • We developed a novel diagnostic index for Alzheimer's disease based on quantitative susceptibility mapping (QSM) and voxel-based morphometry (VBM). • QSM and VBM images can be acquired simultaneously in a single sequence with little increasing scan time. • In this preliminary study, the proposed diagnostic index improved the discriminative performance between mild cognitive impairment and normal control groups compared with the conventional VBM-based index. [ABSTRACT FROM AUTHOR]

Objectives: The aim of this study was to conduct a systematic review and meta-analysis of randomized controlled trials to investigate whether IV high-dose vitamin C improves the short-term mortality of patients with sepsis.Design: This study is a systematic review and meta-analysis of randomized controlled trials. We searched EMBASE, the Cochrane Central Register of Controlled Trials, and MEDLINE for randomized controlled trials that met inclusion criteria. The protocol was registered at the University hospital Medical Information Network Clinical Trials Registry (UMIN000040528). All analyses were presented with the use of random-effects models. The primary outcome was short-term mortality defined as 28-day, 30-day, or in-hospital mortality.Patients: Two authors independently evaluated the following eligibility criteria: 1) randomized controlled trial, 2) patients with sepsis aged ≥18 years, and 3) received intravenous high-dose vitamin C in addition to standard of care, or standard of care alone. Then, two authors independently extracted the selected patient and study characteristics and outcomes from studies that met above eligibility criteria.Measurements and Main Results: Eleven randomized controlled trials (n = 1,737 patients) were included in this meta-analysis. High-dose IV vitamin C was not associated with a significantly lower short-term mortality (risk ratio, 0.88; 95% CI, 0.73-1.06; p = 0.18; I2 = 29%) but was associated with a significantly shorter duration of vasopressor use (standardized mean difference, -0.35; 95% CI, -0.63 to -0.07; p < 0.01; I2 = 80%) and a significantly greater decline in the Sequential Organ Failure Assessment score at 72-96 hours (standardized mean difference, -0.20; 95% CI, -0.32 to -0.08; p < 0.01; I2 = 16%). One study reported significant association with hypernatremia, but adverse effects were rare, and high-dose vitamin C is deemed relatively safe.Conclusions: In this meta-analysis, the use of IV high-dose vitamin C in patients with sepsis was not associated with lower short-term mortality although it was associated with significantly shorter duration of vasopressor use and greater decline in the Sequential Organ Failure Assessment score at 72-96 hours. [ABSTRACT FROM AUTHOR]

Objectives: Reactive oxygen species generated by xanthine oxidoreductase (XOR) are associated with the progression of atherosclerosis. However, changes in plasma XOR (pXOR) activity after percutaneous coronary intervention (PCI) for stable coronary artery disease (CAD) remains unknown. Methods: Herein, we compared the change in the pXOR activity in patients undergoing PCI with that in patients undergoing coronary angiography (CAG) and further evaluated the relation between changes in pXOR activity and in-hospital and long-term outcomes of patients undergoing PCI. The pXOR activity of 80 consecutive patients who underwent PCI and 25 patients who underwent CAG during the hospitalization was analyzed daily. The percentage changes from baseline regulated time interval was evaluated. Results: We found that although pXOR activity decreased after PCI, and remained low until discharge, no significant changes were observed in patients undergoing CAG. Furthermore, among the patients undergoing PCI, those who experienced in-hospital adverse events, had a higher percentage of pXOR reduction 3 days after PCI. There was no association between these changes and long-term events. Conclusions: A significant change in pXOR activity was observed in patients undergoing PCI than in patients undergoing CAG, and there seems to be a correlation between the in-hospital outcomes and the percentage reduction from baseline in pXOR activity. [ABSTRACT FROM AUTHOR]

RNase T2, a ubiquitously expressed RNase, degrades RNAs in the endosomal compartments. RNA sensors, double-stranded RNA (dsRNA)-sensing Toll-like receptor 3 (TLR3) and single-stranded RNA (ssRNA)-sensing TLR7, are localized in the endosomal compartment in mouse macrophages. We here studied the role of RNase T2 in TLR3 and TLR7 responses in macrophages. Macrophages expressed RNase T2 and a member of the RNase A family RNase 4. RNase T2 was also expressed in plasmacytoid and conventional dendritic cells. Treatment with dsRNAs or type I interferon (IFN) up-regulated expression of RNase T2 but not RNase 4. RNase T2-deficiency in macrophages up-regulated TLR3 responses but impaired TLR7 responses. Mechanistically, RNase T2 degraded both dsRNAs and ssRNAs in vitro , and its mutants showed a positive correlation between RNA degradation and the rescue of altered TLR3 and TLR7 responses. H122A and C188R RNase T2 mutations, not H69A and E118V mutations, impaired both RNA degradation and the rescue of altered TLR3 and TLR7 responses. RNase T2 in bone marrow-derived macrophages was broadly distributed from early endosomes to lysosomes, and colocalized with the internalized TLR3 ligand poly(I:C). These results suggest that RNase T2-dependent RNA degradation in endosomes/lysosomes negatively and positively regulates TLR3 and TLR7 responses, respectively, in macrophages. [ABSTRACT FROM AUTHOR]

Polyaddition via the Co‐catalyzed hydroarylation of 1‐(2‐pyrimidinyl)pyrrole with aromatic diynes affords poly(arylenevinylene)s under mild conditions. This reaction avoids production of stoichiometric amounts of by‐products. Although structural analysis of the obtained polymers reveals the presence of 1,1‐vinylidene unit, switching the counter anion of the Co catalyst and steric hindrance of the diyne monomers improves the regioselectivity of the polymers. When a catalyst with bulky counter anions is used for the reaction of less hindered diyne monomers, 1,2‐vinylene linkages are formed dominantly over 1,1‐vinylidene linkages (93:7). The effect of the regioselectivity of the polymer on the optical and semiconducting properties is also evaluated. [ABSTRACT FROM AUTHOR]

Background: Historically, β-blockers have been considered to be relatively contraindicated for septic shock because they may cause cardiac suppression. On the other hand, there is an increasing interest in the use of β-blockers for treating patients with sepsis with persistent tachycardia despite initial resuscitation.Research Question: Do ultrashort-acting β-blockers such as esmolol and landiolol improve mortality in patients with sepsis with persistent tachycardia despite initial resuscitation?Study Design and Methods: This was a systematic review and meta-analysis. We searched MEDLINE, Cochrane Central Register of Controlled Trials, and Embase for randomized controlled trials (RCTs) that compared the mortality of patients with sepsis and septic shock treated with esmolol or landiolol. We updated our search on April 20, 2020. Two independent reviewers assessed whether titles and abstracts met the following eligibility criteria: (1) RCT, (2) patients with sepsis and septic shock ≥ 18 years of age, and (3) treatment with either esmolol/landiolol or placebo/no interventions. Two authors independently extracted selected patient and study characteristics and outcomes. The results of all analyses are presented using random effect models.Results: Seven RCTs with a pooled sample size of 613 patients were included. Of these, six RCTs with 572 patients reported 28-day mortality. Esmolol or landiolol use in patients with sepsis and septic shock was significantly associated with lower 28-day mortality (risk ratio, 0.68; 95% CI, 0.54-0.85; P < .001). Unimportant heterogeneity was observed (I2 = 31%). The absolute risk reduction and number of patients to be treated to prevent one death were 18.2% and 5.5, respectively.Interpretation: The use of ultrashort-acting β-blockers such as esmolol and landiolol in patients with sepsis with persistent tachycardia despite initial resuscitation was associated with significantly lower 28-day mortality.Trial Registry: UMIN Clinical Trials Registry; No.: UMIN000040174; URL: https://www.umin.ac.jp/ctr/index.htm. [ABSTRACT FROM AUTHOR]

Background: The use of ultrashort-acting β1-blockers recently has attracted attention in septic patients with non-compensatory tachycardia. We summarized the metabolic and hemodynamic effects and the clinical evidence of ultrashort-acting β1-blockers. Main body: A recent meta-analysis showed that ultrashort-acting β1-blockers reduced the mortality in septic patients with persistent tachycardia. However, its mechanism to improve mortality is not fully understood yet. We often use lactate as a marker of oxygen delivery, but an impaired oxygen use rather than reduced oxygen delivery has been recently proposed as a more reasonable explanation of hyperlactatemia in patients with sepsis, leading to a question of whether β1-blockers affect metabolic systems. While the stimulation of the β2-receptor accelerates glycolysis and lactate production, the role of β1-blocker in lactate production remains unclear and studies investigating the role of β1-blockers in lactate kinetics are warranted. A meta-analysis also reported that ultrashort-acting β1-blockers increased stroke volume index, while it reduced heart rate, resulting in unchanged cardiac index, mean arterial pressure, and norepinephrine requirement at 24 h, leading to an improvement of cardiovascular efficiency. On the other hand, a recent study reported that heart rate reduction using fast esmolol titration in the very early phase of septic shock caused hemodynamic instability, suggesting that ultrashort-acting β1-blockers should be started only after completing initial resuscitation. While many clinicians still do not feel comfortable controlling sinus tachycardia, one randomized controlled trial in which the majority had sinus tachycardia suggested the mortality benefit of ultrashort-acting β1-blockers. Therefore, it still deems to be reasonable to control sinus tachycardia with ultrashort-acting β1-blockers after completing initial resuscitation. Conclusion: Accumulating evidence is supporting the use of ultrashort-acting β1-blockers while larger randomized controlled trials to clarify the effect of ultrashort-acting β1-blockers are still warranted. [ABSTRACT FROM AUTHOR]

Toll-like receptors (TLRs) impact myeloid cell responsiveness to environmental cues such as pathogen components and metabolites. Although TLR protein expression in monocytes and tissue macrophages is thought to be optimized for microenvironments in each tissue, a comprehensive study has not been reported. We here examined protein expression of endogenous TLRs in tissue-resident myeloid cells. Neutrophils in peripheral blood, spleen, liver and lung expressed TLR2, TLR4 and TLR5 in all tissues. Ly6C+ MHC II‒ classical monocytes mature into Ly6C‒ MHC II+ monocyte-derived dendritic cells (moDCs) or Ly6C‒ MHC II‒ patrolling monocytes. These subsets were found in all the tissues studied. TLR2 and TLR4 were displayed on all of these subsets, regardless of location. In contrast, expression of endosomal TLRs did vary with tissues and subsets. moDCs expressed TLR9, but much less TLR7. In contrast, TLR7, not TLR3 or TLR9, was highly expressed in classical and patrolling monocytes. Tissue macrophages such as red pulp macrophages in the spleen, Kupffer cells in the liver, microglia in the brain, alveolar macrophages in the lung and adipose tissue macrophages all expressed TLR2, TLR4 and TLR3. TLR7 was also expressed in these tissue macrophages except Kupffer cells in the liver. TLR9 expression in tissue macrophages was much lower or hard to detect. These results suggest that expression of endosomal TLRs in myeloid cells is influenced by their differentiation status and tissue-specific microenvironments. [ABSTRACT FROM AUTHOR]

We have synthesised an air-stable Pd(0) catalyst bearing donor and acceptor phosphine ligands (Complex 1). This study revealed the long-term air stability and catalytic property of Complex 1 as a catalyst for cross-coupling reactions, where it was stable in air for eight months. DFT calculations revealed that the acceptor ligands in Complex 1 decreased the HOMO energy level, which provided the observed air stability. Complex 1 successfully served as a catalyst for direct C–H arylation reactions and Suzuki–Miyaura cross-coupling reactions, and catalysed the reaction of a relatively inactive substrate, 2-chrolopyridine, which could not be achieved by conventional, air-stable Pd(0) catalysts. Isolating the intermediates of the coupling reactions revealed that each intermediate possessed the donor ligand (PCy3), which was determined to be responsible for imparting the high catalytic activity exhibited by Complex 1. [ABSTRACT FROM AUTHOR]

Aluminum precipitates have long been used as adjuvants for human vaccines, but there is a clear need for safer and more effective adjuvants. Here we report in a mouse model that the psoriasis drug Oxarol ointment is a highly effective vaccine adjuvant. By applying Oxarol ointment onto skin, humoral responses and germinal center (GC) reactions were augmented, and the treated mice were protected from death caused by influenza virus infection. Keratinocyte-specific vitamin D3 receptor (Vdr) gene expression was required for these responses through induction of the thymic stromal lymphopoietin (Tslp) gene. Experiments involving administration of recombinant TSLP or, conversely, anti-TSLP antibody demonstrated that TSLP plays a key role in the GC reactions. Furthermore, cell-type-specific Tslpr gene deletion or diphtheria toxin-mediated deletion of specific cell types revealed that CD11c+ cells excluding Langerhans cells were responsible for the Oxarol-mediated GC reactions. These results indicate that active vitamin D3 is able to enhance the humoral response via Tslp induction in the skin and serves as a new vaccine adjuvant. [ABSTRACT FROM AUTHOR]

Objectives: Clinicians often encounter adult patients with septic shock who fail to respond to fluid therapy and vasopressors. There is an increasing interest in venoarterial extracorporeal membranous oxygenation in the treatment of patients with septic shock, but its outcomes and safety remain unclear. The aim of this study is to describe in-hospital mortality and complication rate in adult patients with septic shock who underwent venoarterial extracorporeal membranous oxygenation, and to identify patients who may potentially benefit from venoarterial extracorporeal membranous oxygenation.Data Sources: The protocol for this systematic review was registered at International Prospective Register of Systematic Reviews (CRD42018098848). We searched MEDLINE, Embase, and Igaku Chuo Zasshi for studies of any design in which patients with septic shock were treated with venoarterial extracorporeal membranous oxygenation. Our search was updated on October 6, 2019.Study Selection: Two independent reviewers assessed whether titles and abstracts met the eligibility criteria. Studies were included when patients met the following criteria: 1) age 18 years old or older; 2) septic shock; and 3) treated with venoarterial extracorporeal membranous oxygenation as hemodynamic support. When there were disagreements between reviewers, the full text was reviewed, and discussion was continued until a consensus was reached.Data Extraction: Two authors independently extracted the selected patient and study characteristics and outcomes.Data Synthesis: A total of 6,457 studies were screened. Six retrospective studies were included. The in-hospital mortality rate of patients with septic shock who underwent venoarterial extracorporeal membranous oxygenation was 76.7% (188/245). Four studies provided cardiac function with left ventricular ejection fraction and/or cardiac index. In two of these four studies where median left ventricular ejection fraction and cardiac index were 16.0% and 1.3 L/min/m and median left ventricular ejection fraction and mean cardiac index were 30.0% and 2.4 L/min/m, respectively, the in-hospital mortalities were markedly lower (14.8% and 28.6%, respectively) than the other two studies (78.1% and 91.5%, respectively) that included populations with median left ventricular ejection fraction of 25.0% and mean cardiac index of 2.1 L/min/m. Complications were reported in five studies (39 events/174 cases), hemorrhage (22 events/174 cases) being the most common.Conclusions: Venoarterial extracorporeal membranous oxygenation remains a controversial treatment strategy in septic shock. The reported in-hospital mortality rates in patients with sepsis-induced cardiogenic shock who underwent venoarterial extracorporeal membranous oxygenation were quite inconsistent. There is a need for well-designed studies to assess the benefit and safety of venoarterial extracorporeal membranous oxygenation in patients with sepsis-induced cardiogenic shock. [ABSTRACT FROM AUTHOR]

We propose a novel processing method for reducing shading artifacts in quantitative susceptibility mapping (QSM) for prostate imaging. In the conventional method, calculation errors in the boundary regions between water and fat cause shading artifacts that degrade the image quality for QSM. In the proposed method, water and fat regions are separated, and susceptibilities in these two regions are calculated separately and then combined. Susceptibility in the water regions is calculated by using the fat regions as a background susceptibility source to remove shading artifacts. Susceptibility in the fat regions is calculated by using the constraint that shading artifacts in the water regions are suppressed to improve accuracy. In quantitative evaluation of the method with a numerical simulation, calculation errors for the water and fat regions were reduced by 62% and 85%, respectively, compared with the conventional method. In visual evaluation using human prostate imaging, the proposed method also reduced the shading artifacts unlike the conventional method. The proposed method is expected to improve the performance of QSM in diagnosing such diseases as prostate cancer. [ABSTRACT FROM AUTHOR]

Abstract Investigation of the cyclization efficiency of N -methyl linear tetrapeptides using a molecular modeling study and chemical synthesis is described. The linear peptide with two N -methyl groups, MeAla-Leu-MePhe-Gly, forms γ-turn like conformation with the amine at N -terminus and the carbonyl at C-terminus in closer proximity to give the desired cyclic tetrapeptide, dihydrotentoxin. In addition, synthesis of tentoxin B by the combination of Fmoc solid-phase peptide synthesis and cyclization in solution phase has been reported. An unusual amino acid, an L- N -methyl-β-hydroxyphenylalanine derivative, which was assembled on solid support, was prepared from ethyl cinnamate. Cyclic tetrapeptide formation and cleavage of benzyl ether were optimized with DIPCI/HOBt/DIPEA and Et 3 SiH/Pd(OH) 2 , respectively. Graphical abstract Image 1 [ABSTRACT FROM AUTHOR]

Background: Pellagra, which is caused by a deficiency of niacin and tryptophan, the precursor of niacin, is a rare disease in developed countries where alcoholism is a major risk factor due to malnutrition and lack of B vitamins. Although pellagra involves treatable dementia and psychosis, it is often underdiagnosed, especially in developed countries.Case Report: In Japan, a 37-year-old man presented to the emergency department with altered mental status and seizures. Wernicke encephalopathy and alcohol withdrawal were suspected. The patient was treated with multivitamins, which did not include nicotinic acid amide, and oral diazepam. Despite medical treatment, his cognitive impairment progressively worsened, and eventually, pellagra was suspected. His response to treatment with nicotinic acid amide was substantial, and he was discharged without any long-term sequelae. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Despite the treatable dementia and psychosis, pellagra is often underdiagnosed, especially in developed countries and alcoholic patients. Pellagra should be routinely suspected in alcoholic patients because the response to appropriate treatment is typically dramatic. [ABSTRACT FROM AUTHOR]

Polycondensation of 1,2,4,5-tetrafluorobenzene (1) with 3,3′-dihexyl-2,2′-bithiophene via Pd/Ag dual-catalyzed cross-dehydrogenative coupling was examined. In situ deprotonation-metalation of 1 with Ag salt proceeded smoothly at 25 °C, and the subsequent transmetalation with a Pd catalyst provided a cross-coupling product. The sequential one-pot two-step reaction method effectively suppressed undesired homo-coupling defects during polymerization. The obtained highly regioregular polymer had a packing structure and exhibited strong fluorescence in the film state, which was also evaluated for use as an emitting material in organic light-emitting diodes. [Display omitted] • One-pot two-step cross-dehydrogenative-coupling polycondensation is demonstrated. • The sequential one-pot two-step reaction effectively suppressed undesired homo-coupling defects. • The regioregular polymer exhibits high crystallinity and strong fluorescence. [ABSTRACT FROM AUTHOR]

Background Jolt accentuation has been considered to be the most sensitive physical finding to predict meningitis. However, there are only a few studies assessing the diagnostic accuracy of jolt accentuation. Therefore, we aimed to evaluate the diagnostic accuracy of jolt accentuation and investigate whether it can be extended to patients with mild altered mental status. Methods We performed a single center, retrospective observational study on patients who presented to the emergency department in a Japanese tertiary care center from January 1, 2010 to March 31, 2016. Jolt accentuation evaluated in patients with fever, headache, and mild altered mental status with Glasgow Coma Scale no lower than E2 or M4 was defined as 'jolt accentuation in the broad sense.' Jolt accentuation evaluated in patients with fever, headache, and no altered mental status was defined as 'jolt accentuation in the narrow sense.' We evaluated the sensitivity and specificity in both groups. Results Among 118 patients, the sensitivity and specificity of jolt accentuation in the broad sense were 70.7% (95% confidence interval (CI): 58.0%-80.8%) and 36.7% (95% CI: 25.6%-49.3%). The positive likelihood ratio and negative likelihood ratio were 1.12 (95% CI: 0.87-1.44) and 0.80 (95% CI: 0.48-1.34), respectively. Among 108 patients, the sensitivity and specificity of jot accentuation in the narrow sense were 75.0% (95% CI: 61.8%-84.8%) and 35.1% (95% CI: 24.0%-48.0%). The positive likelihood ratio and negative likelihood ratio were 1.16 (95% CI: 0.90-1.48) and 0.71 (95% CI: 0.40-1.28), respectively. Conclusions Jolt accentuation itself has a limited value in the diagnosis of meningitis regardless of altered mental status. Therefore, meningitis should not be ruled out by negative jolt accentuation. [ABSTRACT FROM AUTHOR]

Sepsis, septic shock, and transthoracic echocardiogram (TTE) were identified using the International Classification of Diseases, Tenth Revision codes. B Introduction: b While the current Surviving Sepsis Campaign Guidelines suggests echocardiogram for the hemodynamic assessment in sepsis and septic shock, the evidence to support the utility of echocardiogram has been limited. B Conclusions: b This study using the large national database described that the use of TTE was associated with significantly lower in-hospital mortality in patients with septic shock while it was not in patients with sepsis without septic shock. [Extracted from the article]

Antheraea yamamai silk contains long poly(alanine) sequences that contribute to β-sheet crystals, which are responsible for the high tensile strength of silk fibers. We determined the crystal structure, physical properties, and morphology of A. yamamai cocoon silk fibers. The crystal lattice of A. yamamai silk fiber consists of antiparallel β-pleated sheets with an orthogonal unit cell ( a = 10.72 Å, b = 9.73 Å, c [fiber axis] = 6.80 ± 0.05 Å). Wide-angle X-ray scattering and birefringence measurements revealed that stretching deformation does not affect the crystal structure but contributes to alignment of silk molecules along the fiber axis in the partial amorphous phase. Crystallinity and amino acid sequence analyses suggested that the poly(alanine) region can be partially crystallized. The long poly(alanine) sequences therefore do not contribute to the mechanical, thermal, or structural properties of A. yamamai silk. Our results may aid the design and development of A. yamamai silk-based materials. [ABSTRACT FROM AUTHOR]

Background: Various complications are reported with Clostridium difficile infection (CDI), including fulminant CDI. Fulminant CDI is an underappreciated life-threatening condition associated with complications such as toxic megacolon and bowel perforation.Case Report: A 79-year-old woman presented to the Emergency Department with altered mental status. She was admitted and conservatively treated for a left thalamic hemorrhage. While hospitalized, she developed watery diarrhea due to Clostridium difficile. Although metronidazole was initiated, she developed altered mental status and septic shock. Abdominal x-ray study and computed tomography revealed a significantly dilatated colon and a massive pneumoperitoneum. She underwent subtotal colectomy with a 14-day course of intravenous meropenem. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: This case suggests that we must be aware of the complications that CDI may present and adequately consider surgical management because early diagnosis and surgical treatment is critical to reduce the mortality of fulminant CDI. [ABSTRACT FROM AUTHOR]

Rat-bite fever (RBF) is a challenging diagnosis transmitted by the bite of the rats. We present the first reported case of RBF complicated by vertebral osteomyelitis. It is important to consider performing the MRI to differentiate vertebral osteomyelitis from simple back pain to determine the appropriate duration of antibiotic therapy. [ABSTRACT FROM AUTHOR]

B Introduction: b Sedation is an essential component of critical care for patients undergoing mechanical ventilation. Thus, this systematic review and meta-analysis aimed to clarify whether treatment with dexmedetomidine could reduce the mortality on top of intensive care unit length of stay, and ventilator-free days in patients with sepsis. However, more recent large randomized-controlled trials (RCTs) in patients with sepsis reported that dexmedetomidine use was not associated with improved outcomes (Shehabi et al. 2019 and Hughes et al. 2021). [Extracted from the article]

After controlling for baseline characteristics, past medical history, and vasopressor requirements within the first 24 hours of septic shock, late-onset septic shock, compared to early-onset septic shock, was associated with significantly higher in-hospital mortality [odds ratio (OR): 2.22, 95% confidence interval (CI): 1.72 - 2.85, p < 0.01]. B Conclusion: b In this study, late-onset septic shock (> 7days) after hospital admission was associated with a significantly higher in-hospital mortality compared to early-onset septic shock. B Result: b A total of 3,508 patients with septic shock (2,821 early-onset and 687 late-onset septic shock) were included. [Extracted from the article]

This study aimed to compare the maximum VIS and norepinephrine equivalent (NEE) dose in the first 24 hours of septic shock for the prediction of in-hospital mortality and explore the optimal definition of refractory septic shock. NEE dose showed significantly better prediction accuracy than VIS for in-hospital mortality [NEE dose; area under the curve (AUC): 0.78, 95% confidence interval (CI): 0.76-0.79 versus. [Extracted from the article]

Abstract: Selective amine de-alkylation enables the conversion of Sommelet–Hauser rearrangement products into 2-aryl-2-bromoacetic acid derivatives. These compounds are valuable synthetic intermediates in the synthesis of α-aryl-α-amino or α-aryl-β-amino acid derivatives. The method presented herein is a formal de-N,N-dialkylation of Sommelet–Hauser rearrangement products. [Copyright &y& Elsevier]

Abstract: The effects of calcination temperature and surface area of ceria support on the propene oxidation over Pd/ceria were investigated. Very unique dependence of the oxidation activity of Pd/ceria on surface area was observed, i.e. lower surface area of ceria is more preferable for the higher catalytic activity depending on the pretreatment conditions. The structure of supported Pd species was characterized by Pd K-edge EXAFS. Isolated Pd ions were stable on ceria with high surface area after the propene oxidation, which was caused by the easy oxidation of Pd species and formation of Pd–O–Ce bond. On the other hand, moderately dispersed Pd metal particles were abundant on ceria with low surface area. It was suggested that the weaker interaction with sintered ceria is suggested to be preferable for the formation of active Pd metal particles by the reduction at low temperatures. [Copyright &y& Elsevier]

The article proposes a new front-projection system for large screens by diffusing only projected light towards the viewing-angle range and reflecting ambient light towards the other angle ranges. With this new front-projection system, a high-quality and large-sized front-projection display with a high contrast ration even in a bright room has been achieved. It highlights several features of the front-projection displays.

This study evaluated the hypothesis that LY374388, an inhibitor of secretory phospholipase A2 (sPLA2) activity, may exert a protective effect on lipopolysaccharide (LPS)-induced acute lung injury in male C57BL/6J mice. Intratracheal administration of LPS increased histopathological changes in lung tissue, lung wet to dry ratios, and the bronchoalveolar lavage fluid levels of neutrophil numbers, sPLA2 activity, leukotriene B4, and thromboxane B2. However, a simultaneous intraperitoneal treatment with LY374388 significantly attenuated these LPS-induced changes. Thus, inhibition of sPLA2 activity significantly attenuated the acute lung injury induced by LPS. sPLA2 played an important role in the pathogenesis of LPS-induced acute lung injury in mice. [ABSTRACT FROM AUTHOR]

Photoluminescence (PL) spectroscopy of individual semiconductor nanocrystals (NCs) is a powerful method for understanding the intrinsic optical properties of these materials. Here, we report the temperature dependence of the PL spectra of single perovskite FAPbBr3 and CsPbBr3 NCs [FA = HC(NH2)2]. The temperature dependences of the PL linewidths were mainly determined by the Fröhlich interaction between excitons and longitudinal optical phonons. For FAPbBr3 NCs, a redshift in the PL peak energy appeared between 100 and 150 K, which was because of the orthorhombic-to-tetragonal phase transition. We found that the phase transition temperature of FAPbBr3 NCs decreases with decreasing NC size. [ABSTRACT FROM AUTHOR]

Spinal cord sarcoidosis (SCS) is rare, and its diagnosis is challenging. We examined clinical, laboratory, and imaging features in patients with SCS to obtain useful clues for diagnosis and prognosis. Eleven consecutive patients (four males, seven females) at a single Japanese institution were investigated. Median age at onset was 66 years old. The most frequent site affected, other than the nervous system, was the respiratory system. While histological confirmation of non-caseating granulomas was often found there, no patient had respiratory symptoms. Peripheral nerve involvement was detected in 64% of patients. Soluble IL-2 receptor (sIL-2R) levels in serum and cerebrospinal fluid (CSF) were elevated in 64% and 45% of patients, respectively, and this finding was more common than elevation of angiotensin-converting enzyme (ACE). 18F-fluorodeoxyglucose (FDG) positron emission tomography showed abnormally high uptake in spinal lesions of all examined patients. Although corticosteroids were administrated to all patients, and immuno-suppressants were prescribed to six (55%), the modified Rankin Scale was unchanged or worsened in four (36%) patients during the follow-up period. Neurological exacerbation of myelopathy was seen in four (36%) patients. Complete response rate was only seen in 9%. High levels of cell count, protein, ACE, and sIL-2R in CSF were significantly more frequent in patients with a marked improvement after immunotherapy than in the other patients. These results suggest that high serum and CSF sIL-2R, high uptake of FDG, and peripheral nerve involvement are indicative of SCS. Given that SCS is commonly intractable, CSF abnormalities may predict efficacy of immunotherapies. [ABSTRACT FROM AUTHOR]

The crystallization behavior of halide perovskites is of great significance. Fractal structures, featured by self-similarity between local morphology and global structures, have consistently captivated scientists' interest across diverse disciplines. In this study, we realized the fractal patterns in lead-free zero-dimensional (0D) Cs2InBr5(H2O) perovskites. By depositing saturated precursor droplets on silicon or glass substrates, we initiated nucleation and crystallization of 0D Cs2InBr5(H2O) crystals on the liquid's upper surface. As the solution evaporated, the remaining high-concentration solution formed self-similar fractal patterns beneath the Cs2InBr5(H2O) crystals. This anisotropic growth mechanism imparted a unique self-assembly behavior to 0D Cs2InBr5(H2O). Additionally, X-ray diffraction results confirmed distinct preferential orientations of the fractal patterns. The findings of this work provide valuable insights into the controlled crystallization behavior of lead-free perovskites and inspire further exploration of novel optoelectronic properties arising from such a unique fractal pattern. [ABSTRACT FROM AUTHOR]

A succinct synthetic approach to mugineic acids and 2'‐hydroxynicotianamine was established. Unlike all other synthetic methods, this approach utilized epoxide ring‐opening reactions to form two C−N bonds and is characterized by the absence of redox reactions. Mugineic acid was synthesized from three readily available fragments on a gram scale in 6 steps. The protected 2'‐hydroxynicotianamine was also synthesized in 4 steps, and the dansyl group, serving as a fluorophore, was introduced through a click reaction after propargylation of the 2'‐hydroxy group. The dansyl‐labeled nicotianamine (NA) iron complexes were internalized by oocytes overexpressing ZmYS1 (from maize) or PAT1 (from human) transporters, indicating successful transport of the synthesized NA‐probe through these transporters. [ABSTRACT FROM AUTHOR]

A succinct synthetic approach to mugineic acids and 2'‐hydroxynicotianamine was established. Unlike all other synthetic methods, this approach utilized epoxide ring‐opening reactions to form two C−N bonds and is characterized by the absence of redox reactions. Mugineic acid was synthesized from three readily available fragments on a gram scale in 6 steps. The protected 2'‐hydroxynicotianamine was also synthesized in 4 steps, and the dansyl group, serving as a fluorophore, was introduced through a click reaction after propargylation of the 2'‐hydroxy group. The dansyl‐labeled nicotianamine (NA) iron complexes were internalized by oocytes overexpressing ZmYS1 (from maize) or PAT1 (from human) transporters, indicating successful transport of the synthesized NA‐probe through these transporters. [ABSTRACT FROM AUTHOR]

In diabetic peripheral neuropathy (DPN), metabolic disorder by hyperglycemia progresses in peripheral nerves. In addition to the direct damage to peripheral neural axons, the homeostatic mechanism of peripheral nerves is disrupted by dysfunction of the blood–nerve barrier (BNB) and Schwann cells. The disruption of the BNB, which is a crucial factor in DPN development and exacerbation, causes axonal degeneration via various pathways. Although many reports revealed that hyperglycemia and other important factors, such as dyslipidemia-induced dysfunction of Schwann cells, contributed to DPN, the molecular mechanisms underlying BNB disruption have not been sufficiently elucidated, mainly because of the lack of in vitro studies owing to difficulties in establishing human cell lines from vascular endothelial cells and pericytes that form the BNB. We have developed, for the first time, temperature-sensitive immortalized cell lines of vascular endothelial cells and pericytes originating from the BNB of human sciatic nerves, and we have elucidated the disruption to the BNB mainly in response to advanced glycation end products in DPN. Recently, we succeeded in developing an in vitro BNB model to reflect the anatomical characteristics of the BNB using cell sheet engineering, and we established immortalized cell lines originating from the human BNB. In this article, we review the pathologic evidence of the pathology of DPN in terms of BNB disruption, and we introduce the current in vitro BNB models. [ABSTRACT FROM AUTHOR]

Local transport properties of a carbon nanotube (CNT) thin-film transistor (TFT) have been investigated by conducting atomic force microscopy. The current in a CNT bundle is almost constant, whereas it drastically decreases at the contacts between CNTs. Current drops at the contacts are reduced with increasing negative gate voltage VG. The results show that the contact resistance between CNTs can be modified by VG, and the operation of CNT-TFT is mainly governed by the modulation of contact resistance. [ABSTRACT FROM AUTHOR]

While prognoses in relation to myocardial infarction (MI) type have been elucidated in past reports, the results were not consistent, perhaps due to occurrence of Type 2 MI with CVS and its mortality. The Japanese registry of acute Myocardial Infarction diagnosed by Universal Definition (J-MINUET) is a prospective multicenter registry in Japan. In contrast to thromboembolic event-related Type 1 myocardial infarction (MI), clinical features of Type 2 MI, including coronary vasospasm (CVS), are varied due to the heterogeneous nature of its development. To elucidate the MI type-related all-cause mortality, 2989 consecutive patients with AMI were stratified as Type 1 MI, Type 2 MI with CVS, and Type 2 MI with non-CVS. Most patients (n = 2834; 94.8%) were classified as Type 1 MI and 155 patients (5.2%) were classified as Type 2 MI. Of the Type 2 MI patients, 87 (56% of Type 2 MI) were diagnosed as MI with CVS. Although the 3-year mortality was comparable between Type 1 and Type 2 MI patients, significant differences were observed between Type 2 MI with CVS and with non-CVS (3.4% and 22.1%, p < 0.001). Among Japanese patients with AMI, mortality rates between Type 1 MI and Type 2 MI are comparable, but further stratification of Type 2 MI (with or without CVS) may be useful in predicting the prognosis of patients with Type 2 MI. [ABSTRACT FROM AUTHOR]

The authors have proposed a new combustion process called the Plume Ignition Combustion Concept (PCC), in which with an optimal combination of hydrogen injection timing and controlled jet geometry, the plume of the hydrogen jet is spark-ignited to accomplish combustion of a rich mixture. This combustion process markedly improves thermal efficiency by reducing cooling loss, which is essential for increasing thermal efficiency in a hydrogen engine while maintaining high power. In order to improve thermal efficiency and reduce NOx formation further, PCC was applied to a lean-burn regime to burn a leaner mixture globally. In this study, the effect of supercharging which was applied to recover the reduced output power due to the leaner mixture on improving thermal efficiency was confirmed along with clarifying the cause. [Display omitted] • Supercharging improves the thermal efficiency, high output, and NOx emissions of a direct-injection hydrogen engine. • Major factors that improve thermal efficiency by supercharge are reduction of cooling loss and unburned hydrogen. • Optimization of SOI timing and λ is important for achieving high efficiency and near-zero NOx emissions. [ABSTRACT FROM AUTHOR]

IgG4-related disease (IgG4-RD) is a systemic condition in which IgG4+ plasma cell infiltration and fibrosis cause organ swelling and lead to diverse clinical manifestations. Although IgG4-RD typically responds to glucocorticoids (GCs), relapse during tapering occurs and an early GC-sparing approach might therefore be beneficial. Systemic lupus erythematosus (SLE) is a chronic inflammatory disease with multiple symptoms that is also treated with GCs as a first-line therapy. Recently, belimumab, a recombinant human IgG-1λ monoclonal antibody that inhibits B-cell activating factor, was approved, but reports of use for IgG4-RD are scarce. Here, we present a rare case of IgG4-RD complicated with SLE which was successfully treated with belimumab. A 67-year-old man was diagnosed with IgG4-RD based on a high serum IgG4 level and histopathological findings. Furthermore, he had pericardial effusion on echocardiography, and laboratory tests revealed thrombocytopenia, autoimmune hemolysis, positive anti-nuclear antibodies, positive anti-DNA antibodies, and hypocomplementemia. These data led to an SLE diagnosis. Treatment was started with prednisolone at 40 mg/day, plus hydroxychloroquine, which initially improved both the SLE and IgG4-RD symptoms. During the GC tapering, belimumab was added and clinical symptoms resolved completely. Our case and the literature review summarize reported rare overlapping cases of IgG4-RD and SLE and suggest that belimumab is a promising candidate for the treatment of IgG4-RD. [ABSTRACT FROM AUTHOR]

Azimuthal asymmetry of atmospheric delay, coming from hydrostatic delay (dry air) and wet delay (water vapor), makes atmospheric delay gradients (MacMillan, 1995). Those gradients, unless properly treated, may cause GNSS positioning errors of up to a few centimeters, and its spatial and temporal changes help us study dynamics of tropospheric water vapor. We studied average atmospheric delay gradients in winter (January) and summer (July) at ~1300 continuous GNSS stations in Japan with time resolution of 4 hours using the GAMIT software. Gradients at the coastal stations in summer are dominated by changes in atmospheric water vapor and are made of diurnal landward components and stationary southward components. Those in winter, on the other hand, showed stationary southward components throughout the day. Diurnal landward gradients in summer show maximum in daytime (~0.5 mm). They correlate well with the strength of sea breeze (2-4 m/s) and would originate from the landward thickening of the atmospheric boundary layer due to landward winds and topographic slopes. We also found those at inland stations often show strong diurnal changes in gradient. They may come from mountain-valley breeze, but their pattern is not so clear as coastal stations. Surface pressure distribution and spatial changes in zenith total delays suggest that the stationary southward components in winter (~0.26 mm) come ~70 % from hydrostatic delay and ~30 % from wet delay. This reverses for stationary southward components in summer (~0.30 mm), i.e. they come ~30 % from hydrostatic delay and ~70 % from wet delay. [ABSTRACT FROM AUTHOR]