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Short-term preoperative methionine restriction (MetR) is a promising translatable strategy to mitigate surgical injury response. However, its application to improve post-interventional vascular remodeling remains underexplored. Here we find that MetR protects from arterial intimal hyperplasia in a focal stenosis model and pathologic vascular remodeling following vein graft surgery in male mice. RNA sequencing reveals that MetR enhances browning in arterial (thoracic aorta) perivascular adipose tissue (PVAT) and induces it in venous (caval vein) PVAT. Specifically, Ppara is highly upregulated in PVAT-adipocytes upon MetR. Furthermore, MetR dampens the postoperative pro-inflammatory response to surgery in PVAT-macrophages in vivo and in vitro. This study shows that the detrimental effects of dysfunctional PVAT on vascular remodeling can be reversed by MetR, and identifies pathways involved in MetR-induced browning of PVAT. Furthermore, we demonstrate the potential of short-term preoperative MetR as a simple intervention to ameliorate vascular remodeling after vascular surgery. Utilizing short-term dietary interventions for surgical preconditioning stands as an emerging approach to enhance surgical outcomes. Here, the authors show the potential of short-term preoperative methionine restriction as a simple intervention to ameliorate postinterventional vascular remodelling. [ABSTRACT FROM AUTHOR]

PINN, or physics-informed neural network, is a partial differential equation (PDE) solver realized as a neural network by incorporating the target PDE into the network as physical constraints. In this study, our focus lies in optimizing collocation point selection. We propose an active learning method to enhance the efficiency of PINN learning. The proposed method leverages variational inference based on dropout learning to assess the uncertainty inherent in the solution estimates provided by the PINN. Subsequently, it formulates an acquisition function for active learning grounded in this uncertainty assessment. By employing this acquisition function to probabilistically select collocation points, we can achieve a more expedited convergence to a reasonable solution, as opposed to relying on random sampling. The efficacy of our approach is empirically demonstrated using both Burgers' equation and the convection equation. We also show experimentally that the choice of the collocation points can affect the loss function, the fitting of initial and boundary conditions, and the sensible balance of PDE constraints. [ABSTRACT FROM AUTHOR]

Pathological neovascularization in retinopathy of prematurity (ROP) can cause visual impairment in preterm infants. Current ROP treatments which are not preventative and only address late neovascular ROP, are costly and can lead to severe complications. We showed that topical 0.1% dexamethasone eye drops administered prior to peak neovessel formation prevented neovascularization in five extremely preterm infants at high risk for ROP and suppressed neovascularization by 30% in mouse oxygen-induced retinopathy (OIR) modeling ROP. In contrast, in OIR, topical dexamethasone treatment before any neovessel formation had limited efficacy in preventing later neovascularization, while treatment after peak neovessel formation had a non-statistically significant trend to exacerbating disease. Optimally timed topical dexamethasone suppression of neovascularization in OIR was associated with increased retinal mitochondrial gene expression and decreased inflammatory marker expression, predominantly found in immune cells. Blocking mitochondrial ATP synthetase reversed the inhibitory effect of dexamethasone on neovascularization in OIR. This study provides new insights into topical steroid effects in retinal neovascularization and into mitochondrial function in phase II ROP, and suggests a simple clinical approach to prevent severe ROP. [ABSTRACT FROM AUTHOR]

Objective: Pathological retinal neovascularization is vision-threatening. In mouse oxygen-induced retinopathy (OIR) we sought to define mitochondrial respiration changes longitudinally during hyperoxia-induced vessel loss and hypoxia-induced neovascularization, and to test interventions addressing those changes to prevent neovascularization. Methods: OIR was induced in C57BL/6J mice and retinal vasculature was examined at maximum neovessel formation. We assessed total proteome changes and the ratio of mitochondrial to nuclear DNA copy numbers (mtDNA/nDNA) of OIR vs. control retinas, and mitochondrial oxygen consumption rates (OCR) in ex vivo OIR vs. control retinas (BaroFuse). Pyruvate vs. vehicle control was supplemented to OIR mice either prior to or during neovessel formation. Results: In OIR vs. control retinas, global proteomics showed decreased retinal mitochondrial respiration at peak neovascularization. OCR and mtDNA/nDNA were also decreased at peak neovascularization suggesting impaired mitochondrial respiration. In vivo pyruvate administration during but not prior to neovessel formation (in line with mitochondrial activity time course) suppressed NV. Conclusions: Mitochondrial energetics were suppressed during retinal NV in OIR. Appropriately timed supplementation of pyruvate may be a novel approach in neovascular retinal diseases. [ABSTRACT FROM AUTHOR]

The isomeric ratios of 198 Au, 197 Hg and 195 Hg produced by α -particle induced reactions on natural platinum were investigated experimentally up to 29 MeV by using the standard stacked foil activation technique and γ -ray spectrometry. The isomeric ratios of 197 Hg and 195 Hg determined by the conventional activation cross section formula showed strong cooling time dependence. The time dependence was resolved by adjusting the isomeric transition branching ratios for the two isotopes within a simultaneous decay curve analysis framework. Our analysis suggests 94.5±0.7% and 48.9±1.8% as the isomeric transition branching ratios of 197 m Hg (24 h) and 195 m Hg (42 h), respectively. The isomeric ratios and independent production cross sections of 198 Au, 197 Hg, 195 Hg and some other Hg, Au and Pt isotopes were also measured down to 6 MeV with these corrected isomeric transition branching ratios, and compared with predictions of statistical and pre-equilibrium models by TALYS-2.0 to discuss spin cutoff parameter dependence. We found the measured isomeric ratios are better predicted if we reduce the spin cutoff parameter to half or less from that estimated with the rigid body moment of inertia. [ABSTRACT FROM AUTHOR]

Lignocellulosic biomass is a valuable, renewable substrate for the synthesis of polyhydroxybutyrate (PHB), an ecofriendly biopolymer. In this study, bacterial strain E5-3 was isolated from soil in Japan; it was identified as Burkholderia ambifaria strain E5-3 by 16 S rRNA gene sequencing. The strain showed optimal growth at 37 °C with an initial pH of 9. It demonstrated diverse metabolic ability, processing a broad range of carbon substrates, including xylose, glucose, sucrose, glycerol, cellobiose, and, notably, palm oil. Palm oil induced the highest cellular growth, with a PHB content of 65% wt. The strain exhibited inherent tolerance to potential fermentation inhibitors derived from lignocellulosic hydrolysate, withstanding 3 g/L 5-hydroxymethylfurfural and 1.25 g/L acetic acid. Employing a fed-batch fermentation strategy with a combination of glucose, xylose, and cellobiose resulted in PHB production 2.7-times that in traditional batch fermentation. The use of oil palm trunk hydrolysate, without inhibitor pretreatment, in a fed-batch fermentation setup led to significant cell growth with a PHB content of 45% wt, equivalent to 10 g/L. The physicochemical attributes of xylose-derived PHB produced by strain E5-3 included a molecular weight of 722 kDa, a number-average molecular weight of 191 kDa, and a polydispersity index of 3.78. The amorphous structure of this PHB displayed a glass transition temperature of 4.59 °C, while its crystalline counterpart had a melting point of 171.03 °C. This research highlights the potential of lignocellulosic feedstocks, especially oil palm trunk hydrolysate, for PHB production through fed-batch fermentation by B. ambifaria strain E5-3, which has high inhibitor tolerance. [ABSTRACT FROM AUTHOR]

Background: Laparoscopic liver resection (LLR) is rapidly gaining popularity; however, its efficacy for nonalcoholic fatty liver disease (NAFLD)-associated hepatocellular carcinoma (HCC) (NAFLD-HCC) has been not evaluated. The purpose of this study was to compare short- and long-term outcomes between LLR and open liver resection (OLR) among patients with NAFLD-HCC. Methods: We used a single-institution database to analyze data for patients who underwent LLR or OLR for NAFLD-HCC from January 2007 to December 2022. We performed propensity score-matching analyses to compare overall postoperative complications, major morbidities, duration of surgery, blood loss, transfusion, length of stay, recurrence, and survival between the two groups. Results: Among 210 eligible patients, 46 pairs were created by propensity score matching. Complication rates were 28% for OLR and 11% for LLR (p = 0.036). There were no significant differences in major morbidities (15% vs. 8.7%, p = 0.522) or duration of surgery (199 min vs. 189 min, p = 0.785). LLR was associated with a lower incidence of blood transfusion (22% vs. 4.4%, p = 0.013), less blood loss (415 vs. 54 mL, p < 0.001), and shorter postoperative hospital stay (9 vs. 6 days, p < 0.001). Differences in recurrence-free survival and overall survival between the two groups were not statistically significant (p = 0.222 and 0.301, respectively). Conclusions: LLR was superior to OLR for NAFLD-HCC in terms of overall postoperative complications, blood loss, blood transfusion, and postoperative length of stay. Moreover, recurrence-free survival and overall survival were comparable between LLR and OLR. Although there is a need for careful LLR candidate selection according to tumor size and location, LLR can be regarded as a preferred treatment for NAFLD-HCC over OLR. [ABSTRACT FROM AUTHOR]

The International Maritime Organization (IMO) has formulated stringent ship emission regulations, and the global fuel sulfur limit of 0.50% became effective in 2020. Kitakyushu City is in the coastal suburbs of western Japan, and PM2.5 had already decreased prior to the global low-sulfur regulation, with concentrations in 2017, 2018, and 2019 of 12.2, 13.4, and 8.1 µg·m−3, respectively. The loading particles of the air masses passing through the Bohai Sea, Yellow Sea, and East China Sea in 2019 decreased to 3.4 µg·m−3, which was obviously higher than that of other air masses (0.5 µg·m−3), and the contribution of nss-SO42− could reach 56%, followed by OC (23%) and NH4+ (21%). Moreover, the characteristics of typical ship-emitted metals (V, Ni, As, Sb, W, and Cd) also changed greatly. Their sum concentrations in 2017, 2018, and 2019 were 10.6, 11.1, and 6.9 ng·m−3, respectively, which showed an annual variation similar to that of nss-SO42−. As for the particle exposure risk, the lowest chronic effect and carcinogenic risk were observed in 2019, with hazard indices (HI) for adults and children of 0.9 and 7.6, and carcinogenic risks (CRs) of 3.8 × 10−5 and 8.4 × 10−5, respectively. In this study, the health risks as well as air quality prior to the enforcement of the MARPOL Treaty in the leeward area of the Asian continent were totally and more precisely studied and evaluated based on the annual dataset; revealing the influence of trans-boundary transportation under individual Chinese regulations on the particle characteristic variations in Kitakyushu, Japan. [ABSTRACT FROM AUTHOR]

Hydroxychloroquine (HCQ) has been used to treat Sjögren's disease (SjD) patients. However, there are no studies evaluating drug adherence through HCQ blood levels, pharmacy refill (PR) and medication adherence questionnaires. The relationship of HCQ blood levels with glandular/extraglandular disease parameters was also poorly assessed. This cross-sectional observational study included 74 adult SjD patients, who were receiving a stable HCQ dose (4-5.5 mg/kg/day, actual weight) for at least 3 months before study inclusion. HCQ blood levels were quantified by high-performance liquid chromatography coupled to mass spectrometry. Adherence was assessed by PR and Medida de Adesão aos Tratamentos (MAT) questionnaire. The following parameters were evaluated: Xerostomia Inventory, Ocular Surface Disease Index, EULAR (European League Against Rheumatism) Sjögren's Syndrome Disease Activity Index, EULAR Sjögren's Syndrome Patient Reported Index, Schirmer's I test and non-stimulated/stimulated salivary flow rates. HCQ blood levels were 775.3(25.0–2,568.6)ng/mL. Eleven patients (14.9%) had HCQ blood levels < 200ng/mL (non-adherent group); 11(14.9%), 200-499ng/mL (sub-therapeutic levels group); and 52(70.2%), ≥ 500ng/mL (adherent group). PR classified incorrectly all non-adherent/sub-therapeutic patients and 2/52(3.9%) adherent patients. Using MAT, the overall misclassification was 24/52(46.2%) in the adherent group, and were correctly identified 9/11(81.8%) patients in non-adherent and 7/11(63.6%) in sub-therapeutic groups. MAT sensitivity and specificity to identify non-adherent/sub-therapeutic patients were 72.7% and 53.9%, respectively. The three groups were comparable regarding glandular/extraglandular disease parameters (p > 0.05). The assessment of HCQ blood levels is a promising tool for evaluating drug adherence in SjD. This is particularly crucial as one-third of patients exhibited non-adherence/sub-therapeutic levels, and neither PR nor MAT reliably identified these patients. [ABSTRACT FROM AUTHOR]

Recent advancements in machine learning and deep learning have revolutionized various computer vision applications, including object detection, tracking, and classification. This research investigates the application of deep learning for cattle lameness detection in dairy farming. Our study employs image processing techniques and deep learning methods for cattle detection, tracking, and lameness classification. We utilize two powerful object detection algorithms: Mask-RCNN from Detectron2 and the popular YOLOv8. Their performance is compared to identify the most effective approach for this application. Bounding boxes are drawn around detected cattle to assign unique local IDs, enabling individual tracking and isolation throughout the video sequence. Additionally, mask regions generated by the chosen detection algorithm provide valuable data for feature extraction, which is crucial for subsequent lameness classification. The extracted cattle mask region values serve as the basis for feature extraction, capturing relevant information indicative of lameness. These features, combined with the local IDs assigned during tracking, are used to compute a lameness score for each cattle. We explore the efficacy of various established machine learning algorithms, such as Support Vector Machines (SVM), AdaBoost and so on, in analyzing the extracted lameness features. Evaluation of the proposed system was conducted across three key domains: detection, tracking, and lameness classification. Notably, the detection module employing Detectron2 achieved an impressive accuracy of 98.98%. Similarly, the tracking module attained a high accuracy of 99.50%. In lameness classification, AdaBoost emerged as the most effective algorithm, yielding the highest overall average accuracy (77.9%). Other established machine learning algorithms, including Decision Trees (DT), Support Vector Machines (SVM), and Random Forests, also demonstrated promising performance (DT: 75.32%, SVM: 75.20%, Random Forest: 74.9%). The presented approach demonstrates the successful implementation for cattle lameness detection. The proposed system has the potential to revolutionize dairy farm management by enabling early lameness detection and facilitating effective monitoring of cattle health. Our findings contribute valuable insights into the application of advanced computer vision methods for livestock health management. [ABSTRACT FROM AUTHOR]

Low-density lipoprotein cholesterol (LDL-C) levels are recommended according to the patient's risk factors based on guidelines. In patients achieving low LDL-C levels, the need for statins is uncertain, and the plaque characteristics of patients not treated with statins are unclear. In addition, the difference in plaque characteristics with and without statins is unclear in similarly high LDL levels. We evaluate the impact of statins on plaque characteristics on optical coherence tomography (OCT) in patients with very low LDL-C levels and high LDL-C levels. A total of 173 stable angina pectoris patients with 173 lesions undergoing OCT before percutaneous coronary intervention were evaluated. We divided the LDL-C levels into three groups: < 70 mg/dL (n = 48), 70 mg/dL ≤ LDL-C < 100 mg/dL (n = 71), and ≥ 100 mg/dL (n = 54). Among patients with LDL-C < 70 mg/dL, patients not treated with statins showed a significantly higher C-reactive protein level (0.27 ± 0.22 mg/dL vs. 0.15 ± 0.19 mg/dL, p = 0.049), and higher incidence of thin-cap fibroatheromas (TCFAs; 44% [7/16] vs. 13% [4/32], p = 0.021) than those treated with statins. Among patients with LDL-C level ≥ 100 mg/dL, patients treated with statins showed a significantly higher prevalence of familial hypercholesterolemia (FH) (38% [6/16] vs. 5% [2/38], p = 0.004), lower incidence of TCFAs (6% [1/16] vs. 39% [15/38], p = 0.013), healed plaques (13% [2/16] vs. 47% [18/38], p = 0.015), and higher incidence of fibrous plaques (75% [12/16] vs. 42% [16/38], p = 0.027) than patients not treated with statins. While patients achieved a low LDL-C, patients not treated with statins had high plaque vulnerability and high systemic inflammation. While patients had a high LDL-C level with a high prevalence of FH, patients treated with statins had stable plaque characteristics. [ABSTRACT FROM AUTHOR]

The rupture of an atherosclerotic plaque cap overlying a lipid pool and/or necrotic core can lead to thrombotic cardiovascular events. In essence, the rupture of the plaque cap is a mechanical event, which occurs when the local stress exceeds the local tissue strength. However, due to inter- and intra-cap heterogeneity, the resulting ultimate cap strength varies, causing proper assessment of the plaque at risk of rupture to be lacking. Important players involved in tissue strength include the load-bearing collagenous matrix, macrophages, as major promoters of extracellular matrix degradation, and microcalcifications, deposits that can exacerbate local stress, increasing tissue propensity for rupture. This review summarizes the role of these components individually in tissue mechanics, along with the interplay between them. We argue that to be able to improve risk assessment, a better understanding of the effect of these individual components, as well as their reciprocal relationships on cap mechanics, is required. Finally, we discuss potential future steps, including a holistic multidisciplinary approach, multifactorial 3D in vitro model systems, and advancements in imaging techniques. The obtained knowledge will ultimately serve as input to help diagnose, prevent, and treat atherosclerotic cap rupture. [ABSTRACT FROM AUTHOR]

Manipulating the rotational as well as the translational degrees of freedom of rigid bodies has been a crucial ingredient in diverse areas, from optically controlled micro-robots, navigation, and precision measurements at macroscale to artificial and biological Brownian motors at nanoscale. Here, we demonstrate feedback cooling of all the angular motions of a near-spherical neutral nanoparticle with all the translational motions feedback-cooled to near the ground state. The occupation numbers of the three translational motions are 6 ± 1, 6 ± 1, and 0.69 ± 0.18. A tight, anisotropic optical confinement allows us to clearly observe three angular oscillations and to identify the ratio of two radii to the longest radius with a precision of 0.08 %. We develop a thermometry for three angular oscillations and realize feedback cooling of them to temperatures of lower than 0.03 K by electrically controlling the electric dipole moment of the nanoparticle. Levitated nanoparticles are a new platform for exploring quantum mechanics at macroscopic scales. The authors realize feedback controls of all external degrees of freedom of a nanoparticle, with one translational degree in the quantum ground state. [ABSTRACT FROM AUTHOR]

Heart valve disease is a major cause of mortality and morbidity worldwide with no effective medical therapy and no ideal valve substitute emulating the extremely sophisticated functions of a living heart valve. These functions influence survival and quality of life. This has stimulated extensive attempts at tissue engineering "living" heart valves. These attempts utilised combinations of allogeneic/ autologous cells and biological scaffolds with practical, regulatory, and ethical issues. In situ regeneration depends on scaffolds that attract, house and instruct cells and promote connective tissue formation. We describe a surgical, tissue-engineered, anatomically precise, novel off-the-shelf, acellular, synthetic scaffold inducing a rapid process of morphogenesis involving relevant cell types, extracellular matrix, regulatory elements including nerves and humoral components. This process relies on specific material characteristics, design and "morphodynamism". This study describes a method for in situ recruitment of relevant cells and extracellular matrix using a novel acellular scaffold to produce a living pulmonary root. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to compare the contribution of 18F-fluorodepxyglucose (FDG) positron (PET)/ computed tomography (CT) acquisition of early and delayed scans in patients with cardiac sarcoidosis (CS). Methods: Twenty-three patients with CS (median age: 69 years; 11 women) were retrospectively evaluated using dual-phase FDG PET/CT. All patients were instructed to consume a low-carbohydrate diet followed by fasting for 18 h before FDG injection to reduce physiological myocardial uptake. PET/CT was acquired at 60 min (early) and 100 min (delayed) after FDG administration. Focal and focal on diffuse uptake on visual analysis was considered positive for CS. A semi-quantitative analysis was performed using the maximum standardized uptake value (SUVmax) of the cardiac lesion and the mean SUV (SUVmean) of the blood pool. Results: Significant myocardial FDG uptake was observed in 21 patients (91.3%) in the early acquisition group and in 23 patients in the delayed scan group (100%). Compared to the early scan, the delayed scan showed a significantly higher SUVmax of the cardiac lesion [median, 4.0; IQR (interquartile range, 2.9 to 7.0) vs. 5.8 (IQR 3.7 to 10.1); P = 0.0030] and a significantly lower SUVmean of blood pool [median, 1.3 (IQR, 1.2 to 1.4) vs. 1.1 (IQR, 0.9 to 1.2); P < 0.0001]. Conclusion: Delayed FDG PET/CT acquisition improves detection accuracy in patients with CS compared to early scans with washout of the blood pool activity. Therefore, it can contribute to a more accurate assessment of CS. [ABSTRACT FROM AUTHOR]

The document titled "Correction: Mitochondrial control of hypoxia-induced pathological retinal angiogenesis" in the journal Angiogenesis has been corrected to replace the wrong supplementary file originally published. The corrected version of the article is now available online. The correction was made by a group of authors including Hitomi Yagi, Myriam Boeck, Shen Nian, Katherine Neilsen, Chaomei Wang, Jeff Lee, Yan Zeng, Matthew Grumbine, Ian R. Sweet, Taku Kasai, Kazuno Negishi, Sasha A. Singh, Masanori Aikawa, Ann Hellström, Lois E. H. Smith, and Zhongjie Fu. [Extracted from the article]

The daily mean concentration of gaseous mercury (Hg0) in an industrialized city in Japan was determined during almost 2 years. The Hg concentration largely fluctuated daily. By applying fast Fourier transform (FFT) analysis, different annual and seasonal variation were clarified. In spite of the large daily fluctuation and different annual and seasonal variations, it was noteworthy that an increasing trend was shown; however, it was strongly suggested that it is necessary to continue the determination for a longer duration. The daily fluctuation also implied the possibility that the precipitation was related to the variation in the Hg concentration. We introduced two new parameters for understanding and evaluating the actual potential risk, potential exposure, as well as the calculated—not actual—probability of risk to be suffered, the strength of the potential risk. At our observation site, the potential exposure was mainly controlled by the frequency of the wind from each direction; in contrast, the strength of the potential exposure was compositely determined by the Hg concentration as well as the wind speed. [ABSTRACT FROM AUTHOR]

The equilibrium between nitric acid gas (HNO3(g)) and ammonium nitrate aerosol (NH4NO3(p)) in ambient air was studied based on the monitoring data obtained using a five-stage filter-pack system, in which the fine aerosol and the coarse aerosol were separately collected; this made it possible to evaluate the actual situation of the equilibrium more accurately. The partition between HNO3(g) and coarse particulate nitrate (c-NO3-(p)), as well as that between HNO3(g) and fine particulate nitrate (f-NO3-(p)), could be evaluated individually thanks to the classification separation of the aerosol by size. The c-particle proportion c-NO3-(p)/(c-NO3-(p) + HNO3(g)) between HNO3(g) and c-NO3-(p) had a weak negative correlation (r = -0.46, p<0.001) with air temperature; in contrast, the f-particle proportion f-NO3-(p)/(f-NO3-(p) + HNO3(g)) between HNO3(g) and f-NO3-(p) had a moderate negative correlation (r = -0.80, p<0.001) with air temperature in total; furthermore, the f-particle proportion had an interesting and discriminative dependence on air temperature which could be divided into two regions by an air temperature around 15°C. The condition of high air temperature accompanied by high relative humidity frequently resulted in the deliquescent state of NH4NO3(p), providing the disconnect from the theoretical prediction for the products of [NH3(g)] and [HNO3(g)] ([NH3(g)][HNO3(g)]) by Seinfeld and Pandis (1998). [ABSTRACT FROM AUTHOR]

Introduction: Influenza A (H3N2) virus is the major cause of morbidity/mortality due to seasonal influenza over 50 years. Data about the safety/immunogenicity of influenza A/Singapore (H3N2) vaccine are scarce in primary Sjögren syndrome (pSS). Methods: Twenty-one consecutive pSS patients and 42 HC (healthy control individuals) were immunized with influenza A/Singapore/INFIMH-16–0019/2016 (H3N2)-like virus. Rates of SP (seroprotection) and SC (seroconversion), GMT (geometric mean titers), FI-GMT (factor increase in GMT), ESSDAI (EULAR Sjögren's Syndrome Disease Activity Index), and adverse events were appraised before and 4 weeks post-vaccination. Results: pSS and HC had similar mean age (51.2 ± 14.2 vs. 50.6 ± 12.1 years, p = 0.886). Pre-vaccination SP rates were high in pSS and HC (90.5% vs. 71.4%, p = 0.114), and GMT were higher in pSS [80.0 (52.4–160.0) vs. 40.0 (20.0–80.0), p = 0.001]. The percentage of influenza vaccination in the preceding two years was elevated and similar in pSS and HC (94.1% vs. 94.6%, p = 1.000). GMT values augmented in both groups four weeks after vaccination and persisted higher in the first group [160.0 (80.0–320.0) vs. 80.0 (40.0–80.0), p < 0.001] with equivalent FI-GMT [1.4 (1.0–2.8) vs. 1.4 (1.0–2.0), p = 0.410]. Both groups had low and similar SC rates (19.0% vs. 9.5%, p = 0.423). ESSDAI values persisted steadily during the study (p = 0.313). No serious adverse events have occurred. Conclusion: The novel demonstration that the influenza A/Singapore (H3N2) vaccine induces a different pattern of immunogenicity from other influenza A constituents in pSS, featured by a desirable high pre- and post-vaccination immunogenicity, is in line with reported differences in immune responses between strains in trivalent vaccines and may be related to pre-existing immunity. Clinicaltrials.gov: #NCT03540823. Key Points • This prospective study demonstrated a robust pre- and post-vaccination immunogenicity to influenza A/Singapore/INFIMH-16–0019/2016 (H3N2)-like virus in primary Sjögren's syndrome (pSS). • This high immunogenicity pattern may be related to pre-existing immunization, or else it is related to immunogenicity differences of each strain. • This vaccine had an adequate safety profile in pSS, with no impact on disease activity. [ABSTRACT FROM AUTHOR]

The local anesthetic (LA) systemic toxicity of trunk blocks is a major concern. Recently, modified thoracoabdominal nerve block through perichondrial approach (M-TAPA) has attracted attention; however, plasma LA level is unknown. We tested whether the peak plasma LA concentration following M-TAPA, using 25 mL of 0.25% levobupivacaine mixed with epinephrine on each side, would be below the toxic level (2.6 μg/mL). We recruited 10 patients undergoing abdominal surgery with planned M-TAPA between November 2021 and February 2022. In all patients, 25 mL of 0.25% levobupivacaine mixed with 1:200,000 epinephrine was administered on each side. Blood samples were obtained at 10, 20, 30, 45, 60, and 120 min after the block. The highest individual peak and the mean peak plasma LA concentrations were 1.03 and 0.73 μg/mL, respectively. We could not capture the peak in five patients; however, the highest concentrations in all patients were significantly lower than the toxic level. A negative correlation between the peak level and body weight was observed. Our results indicated that the plasma LA concentration following M-TAPA using total of 50 mL of 0.25% levobupivacaine with epinephrine remains below the toxic level. Further research is required due to the small sample size of this study. Trial registry number: UMIN000045406. [ABSTRACT FROM AUTHOR]

Ambient ammonia gas (NH3(g)) was continuously measured for one year, from March 2018 to February 2019, using a passive sampling method in a source-specific monitoring campaign in Hanoi, Vietnam, providing an unprecedented picture of the spatiotemporal characteristics of NH3(g) in this city. The four survey sites (three urban and one rural) were representative of a typical downtown area, a polluted river, a crossroad, and a rural area. Regarding spatial distribution, a distinctly high concentration (79.8 ± 61.2 ppb) was indicated at the polluted river, an important source unheard of in urban areas, followed by the crossroad (38.6 ± 18.8 ppb) and the downtown (36.5 ± 20.0 ppb); the lowest concentration (35.6 ± 36.0 ppb) was observed in the rural area. Seasonal variation was thoroughly discussed, together with meteorological parameters as driving factors. The strong dependence of NH3(g) concentration on the change in temperature and relative humidity at polluted river and rural area due to the strong impact of these meteorological factors on the volatilization of NH3(g) from wastewater and agriculture, respectively, causes the highest concentration in summer at these sites. The NH3(g) intensely emitted from the polluted river in summer was, furthermore, transferred to the surrounding area under the impact of the local wind direction. However, basically, in downtown, the concentration was higher in the cooler seasons than in the warmer seasons, which was found different compared with the conventional results in most of former studies, suggesting the major impact of vehicular emission on the rise of NH3(g) in urban area. [ABSTRACT FROM AUTHOR]

A novel colorimetric probe for Mn2+ was easily prepared by mixing negatively charged alizarin complexone (ALC) with positively charged poly[bis(2-chloroethyl)ether-alt-1,3-bis[3-(dimethylamino)propyl]urea] (PQ-2) in aqueous solutions at pH 6.0. Upon adding Mn2+ to ALC alone, the solution underwent no distinct color change, while the mixture displayed selective detection of Mn2+ over different physiological and environmentally significant metal ions by an efficient naked-eye color change from red to purple. The detection of Mn2+ by the mixture was achieved from the electrostatic interactions between ALC and PQ-2. The quantitative determination of Mn2+ was obtained by spectrophotometric measurement and naked-eye observation. This sensing strategy can be an attractive approach for the development of new colorimetric probes due to the advantages such as no organic synthesis, facile fabrication, and simple visual detection. [ABSTRACT FROM AUTHOR]

Methionine restriction (MetR) extends lifespan in various organisms, but its mechanistic understanding remains incomplete. Whether MetR during a specific period of adulthood increases lifespan is not known. In Drosophila, MetR is reported to extend lifespan only when amino acid levels are low. Here, by using an exome-matched holidic medium, we show that decreasing Met levels to 10% extends Drosophila lifespan with or without decreasing total amino acid levels. MetR during the first four weeks of adult life only robustly extends lifespan. MetR in young flies induces the expression of many longevity-related genes, including Methionine sulfoxide reductase A (MsrA), which reduces oxidatively-damaged Met. MsrA induction is foxo-dependent and persists for two weeks after cessation of the MetR diet. Loss of MsrA attenuates lifespan extension by early-adulthood MetR. Our study highlights the age-dependency of the organismal response to specific nutrients and suggests that nutrient restriction during a particular period of life is sufficient for healthspan extension.Dietary methionine restriction extends lifespans in many organisms. Here, the authors show in Drosophila that methionine restriction in early adulthood can increase lifespan and that the beneficial effect of the dietary manipulation declines with age. [ABSTRACT FROM AUTHOR]

Introduction: Recently, modified thoracoabdominal nerve block through perichondrial approach (M-TAPA) has been introduced as a novel trunk block. To date, studies comparing its clinical advantages with those of existing local anesthetic techniques are scarce. We aimed to compare the analgesic efficacy of M-TAPA to that of wound infiltration analgesia (WIA) in patients who underwent gynecological laparoscopic surgeries. Methods: We studied medical records from January 2020 to July 2021 at Hokkaido University Hospital. The primary outcome was the number of analgesic requirements in the first 24 h postoperatively. Secondary outcomes were the time until the first analgesic requirement and adverse events regarding local anesthetic techniques. To address confounding, a regression model was used. Results: Data from 90 of 231 patients were analyzed (M-TAPA group, n = 40; WIA group, n = 50). For the primary outcome, means and 95% confidence intervals for each group and between-group differences were as follows: 2.25 (1.74, 2.76), 2.28 (1.81, 2.75), and −0.03 (−0.72, 0.66), respectively. Adjusted mean difference was 0.39 (−0.32, 1.11). There were no significant differences in means between groups, with or without adjustment for covariates (p = 0.93, 0.28). Furthermore, no significant difference was detected in the time until the first analgesic requirement and adverse events related to local anesthesia. Conclusion: Our results demonstrate that M-TAPA did not reduce postoperative analgesic requirements compared to WIA. In a future clinical trial, sufficient visceral pain control may be required to evaluate the effectiveness of M-TAPA over WIA in patients undergoing laparoscopic gynecological surgery. [ABSTRACT FROM AUTHOR]

This work presents a new design method for nth-order infinite impulse response (IIR) differentiators. First, the cost function of the IIR differentiator is derived in closed form without frequency sampling. Next, a new optimization scheme is proposed to minimize the cost function under the pole radius constraint. Here, the magnitude and phase specifications are approximated simultaneously with a stability margin. Furthermore, discrete optimization for the IIR differentiator is presented for a specified word length constraint. The discrete optimization results in a stable IIR differentiator with finite word length coefficients owing to the stability margin. Finally, several design examples are demonstrated to evaluate the efficiency of the proposed method. [ABSTRACT FROM AUTHOR]

Background: Lupus nephritis (LN) is a frequent manifestation of childhood-onset systemic lupus erythematosus (cSLE) with a potential risk for kidney failure and poor outcomes. This study aimed to evaluate stages III, IV, and V of chronic kidney disease (CKD) and investigate risk factors for CKD in cSLE patients. Methods: We performed a nationwide observational cohort study in 27 pediatric rheumatology centers, including medical charts of 1528 cSLE patients. Data were collected at cSLE diagnosis, during follow-up, and at last visit or death, between September 2016 and May 2019. Results: Of 1077 patients with LN, 59 (5.4%) presented with CKD, 36/59 (61%) needed dialysis, and 7/59 (11.8%) were submitted for kidney transplantation. After Bonferroni's correction for multiple comparisons (p < 0.0013), determinants associated with CKD were higher age at last visit, urinary biomarker abnormalities, neuropsychiatric involvement, higher scores of disease activity at last visit and damage index, and more frequent use of methylprednisolone, cyclosporine, cyclophosphamide, and rituximab. In the regression model analysis, arterial hypertension (HR = 15.42, 95% CI = 6.12–38.83, p ≤ 0.001) and biopsy-proven proliferative nephritis (HR = 2.83, 95%CI = 1.70–4.72, p ≤ 0.001) increased the risk of CKD, while children using antimalarials had 71.0% lower CKD risk ((1.00–0.29) × 100%) than children not using them. The Kaplan–Meier comparison showed lower survival in cSLE patients with biopsy-proven proliferative nephritis (p = 0.02) and CKD (p ≤ 0.001). Conclusions: A small number of patients manifested CKD; however, frequencies of dialysis and kidney transplantation were relevant. This study reveals that patients with cSLE with hypertension, proliferative nephritis, and absence of use of antimalarials exhibited higher hazard rates of progression to CKD. [ABSTRACT FROM AUTHOR]

Recognition of nucleic acids as pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs) promotes an inflammatory response. On the other hand, LL-37, an antimicrobial peptide, is a multifunctional modulator of immune response, though whether it modulates inflammatory responses induced by nucleic acids in oral keratinocytes is unknown. In this study, we firstly investigated the effect of LL-37 on CXCL10 induced by DAMPs and PAMPs in immortalized oral keratinocytes, RT7. Furthermore, the effects of LL-37 on translocation of exogenous nucleic acids into cytoplasm as well as cytosolic receptor, RIG-I on immune responses mediated by LL-37-nucleic acid complexes were examined. From these results, LL-37 enhanced necrotic cell supernatant (NCS)–induced CXCL10 expression in RT7, while the response was decreased by RNase. Complexes of LL-37 and double-stranded (ds) RNA, Poly(I:C) enhanced CXCL10 expression in comparison with each alone, which were associated with NF-κB activation. Furthermore, LL-37 was shown to bind with ds nucleotides and translocate into cytoplasm. Knockdown of RIG-I decreased expression of CXCL10 induced by LL-37-Poly(I:C) complexes, and RIG-I were co-localized with Poly(I:C) entered by LL-37 in cytoplasm. LL-37 modulates dsRNA-mediated inflammatory response via RIG-I in oral keratinocytes, which may play an important role in the pathogenesis of oral inflammatory diseases. [ABSTRACT FROM AUTHOR]

We investigated hydrographic conditions in Tokyo Bay recorded from 1992 to 2019 by the training vessel Seiyo Maru (retired in October 2021). We reviewed the basic features of hydrographic conditions discussed in the literature. The long-term trend of temperature differed from that reported in previous studies. The rates of temperature increase estimated in this study were 0.04–0.07 °C /year in the inner bay of Tokyo Bay. These rates were the same as those reported in other areas worldwide. The heat budget in the inner bay of Tokyo Bay also increased significantly from 2004 to 2019; this increase was related to the decrease in the loss of latent heat because of the increases of the atmospheric temperature and the decreases of wind speed. Because formation of the Tokyo Bay thermohaline front has been affected by the increase of water temperature and because the temperature increases have differed between months, the program of monthly monitoring should be continued to document future environmental changes in Tokyo Bay. [ABSTRACT FROM AUTHOR]

To scout for an entomopathogenic nematode (EPN) that effectively controls the pine sawyer beetle, Monochamus alternatus Hope (Coleoptera: Cerambycidae), we screened EPNs from soil samples using M. alternatus larvae as bait. A population of the nematode obtained was named isolate SOz01, and molecularly identified as Heterorhabditis megidis Poinar, Jackson and Klein (Nematoda: Heterorhabditidae). In the inoculation test of the infective juveniles (IJs) of SOz01 onto mature larvae of M. alternatus under laboratory conditions, a mortality of 86–100% occurred when more than 20 IJs were inoculated. Even when the larvae were inoculated with only five IJs, one-third of them died. This finding suggests that H. megidis SOz01 has a strong insecticidal effect on M. alternatus. [ABSTRACT FROM AUTHOR]

The Candiota region, located in the extreme south of Brazil, has the largest mineral coal deposit in the country, and this activity is capable of releasing pollutants in which they are associated with the contamination of different matrices (soil, water, and air). The present study aimed to carry out a risk assessment to human health of atmospheric pollutants NO2 and SO2 and PM10-bound metal(loid)s in the municipality of Candiota, in addition to evaluating the correlation of meteorological parameters for the dynamics and potential risk of these pollutants. Pollutants were sampled from stations located almost 4 km from coal exploration activities, and the trace elements As, Cd, Se, Pb, and Ni, in addition to NO2 and SO2, were evaluated. Risk assessment was conducted taking into account the risk to adults via the inhalation route. During the sampling period, all pollutants presented values lower than national legislation or internationally accepted values, and Pb was the element that presented the highest values throughout the sampled period. The risk assessment showed no carcinogenic and non-carcinogenic risks, even when considering the sum of the risk of all analyzed pollutants. It can be observed that the highest levels of Pb, As, and Se occurred in the winter season, while the levels of Ni and Cd were higher in the spring, and the meteorological parameters were correlated with the pollutants, even using a temporal lag of 5 days. Although the air pollutants evaluated did not present a risk to human health, continuous monitoring of regions with strong mineral exploration activity must be carried out with a view to maintaining the well-being of exposed populations, mainly because there are people living in areas closer to sources of coal pollution than distance to air quality monitoring stations. [ABSTRACT FROM AUTHOR]

The colorimetric sensing system for glutathione (GSH) was constructed by the mixture of three components, an anionic dye 2-(5-bromo-2-pyridylazo)-5-(N-propyl-N-sulfopropylamino)phenol (BrPAPS), a cationic polyelectrolyte poly(diallyldimethylammonium chloride) (PDADMAC), and Cu2+ in an aqueous solution. BrPAPS was complexed with Cu2+ in a 2:1 molar ratio via the electrostatic interaction with PDADMAC (BrPAPS2-Cu2+-PDADMAC). The addition of GSH to the complex caused a hypsochromic shift with a distinct colorimetric response from red to yellow since the regeneration of the original BrPAPS through the interaction between GSH and Cu2+ in a 1:1 stoichiometry. BrPAPS2-Cu2+-PDADMAC allowed the selective recognition of GSH over other amino acids and the detection suffer little interference from them. Hence, BrPAPS2-Cu2+-PDADMAC provides efficient colorimetric sensing of GSH with high selectivity and sensitivity in pure aqueous media. [ABSTRACT FROM AUTHOR]

There are various techniques used for tendon lengthening, of which Z-lengthening and sliding-lengthening are the most frequently performed. In patients with cerebral palsy, tendon lengthening may often be necessary at multiple sites. However, they can cause various complications, such as inaccurate extension, overextension, and a lack of tendon continuity. We modified the sliding-lengthening technique with a locking mechanism to address these issues. This technical note aims to describe the surgical technique and pitfalls associated with the modified sliding-lengthening approach and suture locking mechanism. The tendon was exposed and stabilized using sterilized spitz tubes and was then threaded so that each loop length was equivalent to the amount of tendon extension. Symmetrical hemisection of both ends of the tendon was performed, and the tendon was carefully extended to create a tense loop. The modified sliding-lengthening technique with the locking suture mechanism may be an advantageous method that accurately addresses extension volume, prevents hyperextension, and maintains tendon continuity, even when smaller incisions are used. [ABSTRACT FROM AUTHOR]

The cardiac prognosis of patients with frailty and malnutrition remains poorly investigated. This study aimed to investigate the impact of frailty and malnutrition on cardiac prognosis by combining the clinical frailty scale (CFS) and the geriatric nutritional risk index (GNRI) in patients who underwent percutaneous coronary intervention (PCI). In this study, 608 patients who underwent PCI for stable angina pectoris between January 2018 and December 2020 were included. CFS scores of ≥ 4 were defined as high CFS and patients with these scores were considered frail. GNRI scores of ≤ 98.0 were defined as low GNRI and patients with these scores were considered to have malnutrition. Patients were categorized into low-risk (n = 267, low CFS and high GNRI), intermediate-risk (n = 200, high CFS or low GNRI), and high-risk (n = 141, high CFS and low GNRI) groups. Major adverse clinical events (MACEs), including all-cause death, nonfatal myocardial infarction, revascularization, hospitalization for heart failure, and stroke, were assessed. The median follow-up period was 529 days. During the follow-up, MACEs were found in 135 patients. The high-risk group were older (77.0 ± 9.2 vs 71.4 ± 10.7 vs 65.0 ± 10.1 years, p < 0.001), had higher prevalence rates of chronic kidney disease [61.7% (87/141) vs 37.5% (75/200) vs 16.9% (45/267); p < 0.001] and heart failure [47.5% (67/141) vs 22.5% (45/200) vs 12.4% (33/267), p < 0.001], and had higher C-reactive protein levels (1.64 ± 2.66 vs 1.00 ± 2.02 vs 0.34 ± 0.90 mg/dL; p < 0.001) than the intermediate-risk and low-risk groups. The high-risk group [hazard ratio (HR), 4.39; 95% confidence interval (CI), 2.87–6.72; p < 0.001] was an independent predictor of MACEs. In conclusion, patients with both frailty and malnutrition had a higher risk of MACEs after PCI than patients with frailty or malnutrition. Post-PCI patients should be evaluated for combined frailty and malnutrition. [ABSTRACT FROM AUTHOR]

Background: Laparoscopic liver resection for hepatocellular carcinoma (HCC) in patients with Child–Pugh A cirrhosis has been shown to be beneficial. However, less is known regarding the outcomes of such treatment in patients with Child–Pugh B cirrhosis. We conducted a retrospective study to evaluate the outcomes of laparoscopic liver resection for HCC in patients with Child–Pugh B cirrhosis, focusing on surgical risks, recurrence, and survival. Methods: 357 patients with HCC who underwent laparoscopic liver resection from 2007 to 2021 were identified from our single-institute database. The patients were divided into three groups by their Child–Pugh score: the Child–Pugh A (n = 280), Child–Pugh B7 (n = 42), and Child–Pugh B8/9 groups (n = 35). Multivariable Cox regression models for recurrence-free survival (RFS) and overall survival (OS) were constructed with adjustment for preoperative and postoperative clinicopathological factors. Results: The Child–Pugh B8/9 group had a significantly higher complication rate, but the complication rates were comparable between the Child–Pugh B7 and Child–Pugh A groups (Child–Pugh A vs. B7 vs. B8/9: 8.2% vs. 9.6% vs. 26%, respectively; P = 0.010). Compared with the Child–Pugh A group, the risk-adjusted hazard ratios (95% confidence intervals) in the Child–Pugh B7 and B8/9 groups for RFS were 1.39 (0.77–2.50) and 3.15 (1.87–5.31), respectively, and those for OS were 0.60 (0.21–1.73) and 1.80 (0.86–3.74), respectively. There were no significant differences in major morbidities (Clavien–Dindo grade > II) (P = 0.117) or the proportion of retreatment after HCC recurrence (P = 0.367) among the three groups. Conclusion: Among patients with HCC, those with Child–Pugh A and B7 cirrhosis can be good candidates for laparoscopic liver resection in terms of complications and recurrence. Despite poor postoperative outcomes in patients with Child–Pugh B8/9 cirrhosis, laparoscopic liver resection is less likely to interfere with retreatment and can be performed as part of multidisciplinary treatment. [ABSTRACT FROM AUTHOR]

Under ovarian hormone control, dormant blastocysts obtain implantation capacity (known as blastocyst activation) through their global gene expression. After the activated blastocysts communicate with the receptive uterus, the implantation-competent blastocysts start the implantation. Although dormant and activated blastocysts have different gene expression levels, the regulatory mechanisms underlying these transcriptions remain unclear. Hence, this study aimed to analyze epigenetic marks in dormant and activated blastocysts. In mice, blastocyst dormancy is artificially induced by daily progesterone injection without estrogen supplementation after peri-implantation ovariectomy; when estrogen is administered concomitantly, blastocyst activation and implantation occur. These phenomena demonstrate a mouse model of delayed implantation. We collected dormant and activated blastocysts from a delayed implantation mouse model. RNA-seq, methylated DNA immunoprecipitation (MeDIP)-seq, and chromatin immunoprecipitation (ChIP)-seq for H3K4 me3 and H3K27 me3 were performed using dormant and activated blastocysts. Cell cycle–related transcripts were affected during blastocyst activation. DNA methylations were accumulated in downregulated genes in the activated blastocysts. Histone H3 trimethylations were globally altered between the dormant and activated blastocysts. Dormant and activated blastocysts have unique methylation patterns on DNA and histone H3, with high correlation to gene expression. DNA methylation and histone modification can regulate preimplantation blastocyst activation. [ABSTRACT FROM AUTHOR]

Purpose: During surgical resection of malignant tumors in the hepatobiliary pancreatic region, portal vein resection and reconstruction may be needed. However, there is no alternative to the portal vein. We therefore developed an artificial portal vein that could be used in the abdominal cavity. Methods: In the experiments, hybrid pigs (n = 8) were included. An artificial portal vein was created using a bioabsorbable polymer sheet (BAPS). Subsequently, the portal vein's anterior wall was excised into an elliptical shape. A BAPS in the form of a patch was implanted at the same site. At 2 weeks (n = 3) and 3 months (n = 5) after the implantation, the BAPS implantation site was resected and evaluated macroscopically and histopathologically. Results: Immediately after the implantation, blood leakage was not detected. Two weeks after implantation, the BAPS remained, and endothelial cells were observed. Thrombus formation was not observed. Three months after implantation, the BAPS had been completely absorbed and was indistinguishable from the surrounding portal vein. Stenosis and aneurysms were not observed. Conclusions: BAPS can replace a defective portal vein from the early stage of implantation to BAPS absorption. These results suggest that it can be an alternative material to the portal vein in surgical reconstruction. [ABSTRACT FROM AUTHOR]

Objectives: The purpose of this study was to examine the diagnostic value of planar 99mTc-pyrophosphate (PYP) imaging at 1 and 3 h after tracer administration in patients with suspected transthyretin cardiac amyloidosis (ATTR-CA) using SPECT as a reference standard. We also tested whether blood pool activity of PYP is associated with renal dysfunction. Methods: PYP images of 109 consecutive patients with suspected ATTR-CA were retrospectively reviewed. The myocardial PYP uptake was visually graded on a scale of 0 to 3 and quantified with the heart-to-contralateral (H/CL) ratio in accordance with the current expert consensus recommendations. The diagnostic value of planar images for identifying positive PYP SPECT was assessed by a receiver-operating characteristic curve analysis with the area under the curve (AUC). The uptake ratios of the ascending and descending aorta, left atrium, and trapezius muscle divided by the liver uptake were measured on SPECT images and compared to the renal function. Results: A total of 41 patients (38%) had myocardial PYP uptake on SPECT images. In comparison with the visual scores on 1-h anterior planar images, those on 3-h anterior planar images had lower sensitivity (80.5% vs. 97.6%) and higher specificity (86.8% vs. 55.9%) for identifying positive PYP SPECT. The ROC analysis showed that the combination of visual scores on both 1-h and 3-h anterior planar images had significantly higher AUC values in comparison with 1-h anterior planar images alone (0.90 [95% CI 0.83–0.94] vs. 0.83 [95% CI 0.75–0.88]; P < 0.001), which was comparable to the AUC values on 3-h anterior planar images alone (0.88 [95% CI 0.80–0.92]; P = 0.071). In comparison with visual scores on 1-h or 3-h anterior planar images alone, the combination of visual scores and H/CL ratio did not significantly improve the diagnostic value for identifying positive PYP SPECT (P = 0.73 and P = 0.50, respectively). The uptake ratios of ascending aorta/liver, descending aorta/liver, left atrium/liver, and trapezius muscle/liver were not significantly associated with the serum creatinine level or estimated glomerular filtration rate (P > 0.05 for all). Conclusions: In the assessment of ATTR-CA using PYP imaging, visual scores on 3-h anterior planar images for identifying positive PYP SPECT had lower sensitivity and higher specificity in comparison with those on 1-h anterior planar images. The diagnostic value of the visual scores on 1-h and 3-h anterior planar images was not improved by adding the H/CL ratio. Blood pool activity of PYP was not significantly associated with renal dysfunction. [ABSTRACT FROM AUTHOR]

Lipoprotein(a) [Lp(a)] is a reliable lipid marker for atherosclerosis. However, the clinical relevance of Lp(a) to lower-extremity peripheral artery disease (LE-PAD) and coronary artery disease (CAD) in the same patient has not been investigated. Patients who received primary percutaneous coronary intervention for the acute coronary syndrome (ACS) were enrolled. Patients who received hemodialysis, required multidisciplinary treatments, or had incomplete medical history were excluded. A total of 175 patients were divided into two groups according to whether they had LE-PAD (n = 21) or did not (n = 154), and three multivariable logistic regression models were used to assess if Lp(a) level is associated with LE-PAD prevalence. In addition, serum Lp(a) levels were compared among three groups according to the severity of LE-PAD (none, unilateral, or bilateral) and CAD. Serum Lp(a) levels were significantly higher in patients with LE-PAD than in those without (31.0 mg/dL vs. 13.5 mg/dL, p = 0.002). After adjusting for confounding factors, higher Lp(a) levels were independently associated with the prevalence of LE-PAD in all three models (p < 0.001 for all). With respect to LE-PAD severity, serum Lp(a) levels were significantly higher in the bilateral LE-PAD groups than in the group with no LE-PAD (p = 0.005 for all), whereas Lp(a) was not associated with CAD severity. Though Lp(a) levels are associated with the prevalence and severity of LE-PAD, are not associated with the severity of CAD among patients with ACS. [ABSTRACT FROM AUTHOR]

Introduction: Patients with antineutrophil cytoplasmic antibody (ANCA)–associated vasculitis and idiopathic interstitial lung diseases (IIPs) are positive for myeloperoxidase (MPO)–ANCA. MPO–ANCA-positive vasculitis mainly comprises microscopic polyangiitis (MPA) and unclassifiable vasculitis. These diseases are frequently complicated by interstitial lung disease (ILD). Few studies have reported the clinical differences between the subtypes of MPO–ANCA-positive ILD. Therefore, this study aimed to examine the clinical findings and courses of MPO–ANCA-positive ILD. Method: This retrospective study enrolled 100 patients with MPO–ANCA-positive ILD who were categorized into three groups: MPA (n = 44), unclassifiable vasculitis (n = 29), and IIP (n = 27). Our study compared the clinical findings and prognosis of these patients and analyzed the poor prognostic factors. Furthermore, we assessed the association between the patients with and without acute exacerbation of ILD (AE-ILD). Results: Our study found clinical differences in serum markers, clinical symptoms, and treatment regimens among the three groups. ILD complications, as the main cause of death, differed among the three groups (P = 0.04). Patients with unclassifiable vasculitis showed higher survival rates than those with IIP (P = 0.046). Patients with AE-ILD showed fewer general symptoms (P = 0.02) and lower survival rates (P < 0.01) than those without AE-ILD. In multivariate analysis, AE-ILD development was a strong poor prognostic factor for MPO–ANCA-positive ILD. Conclusions: The subtypes of MPO–ANCA-positive ILD have different clinical features and prognoses. Patients who develop AE-ILD require careful evaluation of clinical courses. Key Points • In myeloperoxidase (MPO)–antineutrophil cytoplasmic antibody (ANCA)–positive interstitial lung disease (ILD), patients with unclassifiable vasculitis showed a better prognosis than those with idiopathic ILD.. • Development of acute exacerbation in ILD was a strong poor prognostic factor in patients with MPO–ANCA-positive ILD.. [ABSTRACT FROM AUTHOR]

A simple and effective colorimetric detection of adenosine 5-triphosphate (ATP) in 100% aqueous media was developed based on an indicator displacement approach (IDA). A commercially available dye, Chlorophosphonazo III (CPA), was utilized as the indicator and the ATP detection was achieved using the complex of CPA with Mg2+ in a 2:1 stoichiometric ratio (CPA2-Mg2+) through the regeneration of CPA by the binding of ATP to Mg2+. Upon addition of a series of anions to the CPA2-Mg2+ complex, only the appearance of the solution of the complex with ATP exhibited a color change from blue to purple which can be detected by the naked eye. Moreover, the ATP recognition was not hampered by the presence of other anions. Hence, CPA2-Mg2+ is efficient in ATP highly selective and sensitive colorimetric detection in 100% aqueous media. [ABSTRACT FROM AUTHOR]

Disease-risk stratification and development of intensified chemotherapy protocols have substantially improved the outcome of acute lymphoblastic leukemia (ALL). However, outcomes of relapsed or refractory cases remain poor. Previous studies have discussed the oncogenic role of enhancer of zeste homolog 1 and 2 (EZH1/2), and the efficacy of dual inhibition of EZH1/2 as a treatment for hematological malignancy. Here, we investigated whether an EZH1/2 dual inhibitor, DS-3201 (valemetostat), has antitumor effects on B cell ALL (B-ALL). DS-3201 inhibited growth of B-ALL cell lines more significantly and strongly than the EZH2-specific inhibitor EPZ-6438, and induced cell cycle arrest and apoptosis in vitro. RNA-seq analysis to determine the effect of DS-3201 on cell cycle arrest-related genes expressed by B-ALL cell lines showed that DS-3201 upregulated CDKN1C and TP53INP1. CRIPSR/Cas9 knockout confirmed that CDKN1C and TP53INP1 are direct targets of EZH1/2 and are responsible for the antitumor effects of DS-3201 against B-ALL. Furthermore, a patient-derived xenograft (PDX) mouse model showed that DS-3201 inhibited the growth of B-ALL harboring MLL-AF4 significantly. Thus, DS-3201 provides another option for treatment of B-ALL. [ABSTRACT FROM AUTHOR]

Purpose: Integrin αvβ3 is an essential molecule for tumor angiogenesis. This study aimed to investigate the anti-tumor effect of MK-0429, an integrin αvβ3 antagonist, on oral squamous cell carcinoma (OSCC) through its inhibitory effect on angiogenesis. Methods: In this study, we investigated the effect of MK-0429 on cellular function and angiogenesis in vitro with the use of an immortalized human umbilical vein endothelial cell, HUEhT-1, which is immortalized by the electroporatic transfection of hTERT. The effect of MK-0429 on the integrin αvβ3 signaling pathway was examined by FAK, MEK1/2 and ERK 1/2 phosphorylation. The anti-angiogenic effect of MK-0429 was evaluated by in vitro tube formation assay. The anti-tumor effect on OSCC was assessed by administrating MK-0429 to mouse oral cancer xenografts. Results: MK-0429 inhibited cell proliferation, migration, and adhesion of HUEhT-1 in a dose-dependent manner. FAK, MEK and ERK phosphorylation were significantly blocked by MK-0429 treatment. Tube formation was suppressed by MK-0429 in dose-dependent manner. Tumor progression was significantly suppressed by MK-0429 administration in mouse oral cancer xenografts. Histological study revealed that MK-0429 decreased tumor vascularization. Conclusion: These results indicated integrin αvβ3 as a therapeutic target for OSCC and suggested that MK-0429 might be clinically applicable as an anti-tumor agent with potent anti-angiogenic activity. [ABSTRACT FROM AUTHOR]

Fog water, throughfall, and bulk precipitation were collected at the site neighboring to coastal and urbanized area in Japan. Fog water was collected by using string type passive fog collector. Fog water was strongly influenced by the sea salt components presumably due to drizzle. Furthermore, fog water would be acidified by acid-related nitrate species like HNO3 gas in ambient air; however, fog water was neutralized well as shown below. Throughfall selectively included non-sea salt chloride (nss-Cl−) among the three media: fog water, throughfall, and bulk precipitation, likely due to a dry deposition of nss-Cl− species on canopy. The pH values for fog water, throughfall, and bulk precipitation, were 5.28, 5.97, and 5.73, respectively. Those were typically higher compared with other previous observations, meaning that all media were neutralized well. In particular, fog water was dominantly neutralized by nss-Mg2+ and nss-Ca2+. The supply of nitrogen (NO3−-N + NH4+-N) via throughfall showed the seasonality, higher in winter and summer. We considered a new and simple methodology to evaluate/estimate the deposition amount of fog water. We applied our new methodology to our present observation and obtained a good agreement with the result heretofore used. [ABSTRACT FROM AUTHOR]

Optical fibre communication is the backbone of the internet. As essential core technologies are approaching their limits of size, speed and energy-efficiency, there is a need for new technologies that offer further scaling of data transmission capacity. Here we show that a single optical frequency-comb source based on a silicon nitride ring resonator supports data capacities in the petabit-per-second regime. We experimentally demonstrate transmission of 1.84 Pbit s–1 over a 37-core, 7.9-km-long fibre using 223 wavelength channels derived from a single microcomb ring resonator producing a stabilized dark-pulse Kerr frequency comb. We also present a theoretical analysis that indicates that a single, chip-scale light source should be able to support 100 Pbit s–1 in massively parallel space-and-wavelength multiplexed data transmission systems. Our findings could mark a shift in the design of future communication systems, targeting device-efficient transmitters and receivers. A microcomb source based on a silicon nitride ring resonator is shown to support petabit-per-second data transmission over a multicore optical fibre. [ABSTRACT FROM AUTHOR]

Antimicrobial surfactants contained in mouthrinse have excellent efficacy, but are not retained on the tooth surface (are rinsed away) due to their low water resistance and thus do not exhibit sustained antibacterial activity. We have developed a new coating method using graphene oxide (GO) that retains the surfactant on the tooth surface even after rinsing with water, thus providing a sustained antibacterial effect. Ultra-thin films of GO and an antimicrobial agent were prepared by (1) applying GO to the substrate surface, drying, and thoroughly rinsing with water to remove excess GO to form an ultrathin film (almost a monolayer, transparent) on the substrate surface, then (2) applying antimicrobial cationic surface active agents (CSAAs) on the GO film to form a composite coating film (GO/CSAA). GO/CSAA formation was verified by scanning electron microscopy, Raman spectroscopy, X-ray photoelectron spectroscopy, and ζ-potential and contact angle measurements. GO/CSAA was effective at inhibiting the growth of oral pathogens for up to 7 days of storage in water, and antibacterial activity was recovered by reapplication of the CSAA. Antibacterial GO/CSAA films were also formed on a tooth substrate. The results suggest that GO/CSAA coatings are effective in preventing oral infections. [ABSTRACT FROM AUTHOR]

Objectives: To assess mental health and life conditions in adolescents with autoimmune rheumatic diseases (ARDs) and healthy controls quarantined during COVID-19 pandemic. Method: A cross-sectional study included 155 ARD adolescents and 105 healthy controls. Online survey included self-reported strengths and difficulties questionnaire (SDQ), and a semi-structured questionnaire with demographic data, daily home and school routine, physical activities, and COVID-19 information during the pandemic. Results: Among patients, 56% had juvenile idiopathic arthritis (JIA), 29% juvenile systemic lupus erythematosus (JSLE), and 15% juvenile dermatomyositis (JDM). No differences were found regarding sex, ethnicity, and current age between ARD patients and controls (p > 0.05). Abnormal emotional SDQ (38% vs. 35%, p = 0.653) were similar in both groups. Logistic regression analyses in ARD patients demonstrated that female (OR = 2.4; 95%CI 1.0–6.0; p = 0.044) was associated with severe emotional SDQ dysfunction, whereas sleep problems were considered as a risk factor for both worse total SDQ (OR = 2.6; 95%CI 1.2–5.5; p = 0.009) and emotional SDQ scores (OR = 4.6; 95%CI 2.2–9.7; p < 0.001). Comparisons between ARD patients with and without current prednisone use showed higher median scores of peer problems in the first group [3 (0–10) vs. 2 (0–7), p = 0.049], whereas similar median and frequencies between JIA, JSLE, and JDM (p > 0.05). Conclusions: Approximately one third of JIA, JSLE, and JDM patients presented abnormal total and emotional scores of SDQ during COVID-19 quarantine. Sleep problems were the main factor associated with emotional difficulties in these ARD adolescents. The knowledge of mental health issues rates in adolescents with ARD supports the development of prevention strategies, like sleep hygiene counseling, as well as the references of the affected patients to specialized mental health services, as necessary. Key Points • One third of ARD patients presented mental health issues during COVID-19 quarantine • Sleep problems were associated with emotional difficulties. • It is necessary to warn pediatric rheumatologists about the importance of sleep hygiene counseling. [ABSTRACT FROM AUTHOR]