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Retroperitoneal leiomyosarcoma (RPLMS) is rare and usually presents as a large abdominal mass with poor clinical symptoms. Radiological findings of an RPLMS arising in the pelvis of a woman resemble those of adnexal tumors. Herein, we present a case of RPLMS mimicking an adnexal tumor which was differentiated from having an ovarian origin as the right ovarian vein was passing through the tumor but there was no direct vascular connection with the tumor. Therefore, it is important to identify the ovarian vein to distinguish between these tumors.

Cardiac angiosarcoma is a malignant tumor derived from vascular endothelium with a dismal prognosis. The imaging findings of cardiac angiosarcoma are nonspecific and endomyocardial and pericardial biopsies have insufficient accuracy. For these reasons, the diagnosis is sometimes difficult. Primary and metastatic tumors tend to bleed easily, causing hemoptysis and neurological symptoms. Brain metastases are not often known to be fatal when they cause hemorrhage. We report a 27-year-old man diagnosed with right atrium angiosarcoma, with metastases in the lung, brain, and bone. The patient had only respiratory symptoms at the first visit and did not show any symptoms derived from brain metastases yet died after 27 days due to hemorrhage from brain metastases. If brain metastasis from angiosarcoma is suspected based on imaging findings, urgent radiotherapy should be considered before histological examination for a definitive diagnosis.

Objective: Although cervical conization is considered a standard treatment for cervical intraepithelial neoplasia (CIN) 2/3, laser ablation can compensate for the disadvantages of the former. CO2, semiconductor, and holmium yttrium-aluminum-garnet (Ho:YAG) lasers are applied in ablation, but no previous studies have shown the effectiveness of any of these techniques. Here, we retrospectively analyzed the application of the Ho:YAG laser in our hospital to verify its efficacy, and discussed the methods for optimal recurrence detection. Methods: We evaluated the recurrence rates of the pathological condition in patients who underwent laser ablation with a Ho:YAG laser for CIN2/3 at our institution from June 2012 to November 2021. We defined the recurrence as histologically confirmed CIN2 or more advanced stage. Age, preoperative diagnosis, human papillomavirus (HPV) genotype, and postoperative high-risk HPV status were recorded to establish their association with recurrence rates. Results: We performed surgery in 607 patients and the 2-year recurrence rate after interventions was 5.6%. Five patients were diagnosed with invasive cancer at the time of recurrence. Older age significantly correlated with higher risk of recurrence, but preoperative CIN grade and preoperative HPV 16/18 status did not significantly affect it. The postoperative high-risk HPV test was 100% sensitive for detecting recurrence. Conclusions: Laser ablation with the Ho:YAG laser yields promising results. Together with postinterventional management, high-risk HPV test after laser ablation should be conducted after diagnostic conization.This study received the approval from the Ethics Committee of the NHO Tokyo Medical Center (Ethics Committee approval number: R22-067).

Abstract Due to the ecological importance of mutualism between reef-building corals and symbiotic algae (Family Symbiodiniaceae), various transcriptomic studies on coral-algal symbiosis have been performed; however, molecular mechanisms, especially genes essential to initiate and maintain these symbioses remain unknown. We investigated transcriptomic responses of Acropora tenuis to inoculation with the native algal symbiont, Symbiodinium microadriaticum, during early life stages, and identified possible symbiosis-related genes. Genes involved in immune regulation, protection against oxidative stress, and metabolic interactions between partners are particularly important for symbiosis during Acropora early life stages. In addition, molecular phylogenetic analysis revealed that some possible symbiosis-related genes originated by gene duplication in the Acropora lineage, suggesting that gene duplication may have been the driving force to establish stable mutualism in Acropora, and that symbiotic molecular mechanisms may vary among coral lineages.

To obtain the design and development guidelines for a cryo-capture system that combines an amine absorption method with a novel cryo-sublimation pump for recovering CO2 from flue gas using the cryogenic heat (−162 °C) of liquefied natural gas (LNG), we investigated the cooling, depressurization, and regeneration characteristics of CO2 through numerical analysis. We developed an unsteady lumped constant numerical model consisting of a regeneration tower, sublimation tank, and connecting passage. The numerical analysis investigated the effects of the partial pressure of CO2 in the inlet gas in the absorption tower, the CO2 regeneration rate in the regeneration tower, and the cooling wall area of the sublimation tank, on the temporal changes of various quantities in the process. The following findings were obtained as design and development guidelines: the interface area of CO2 regeneration tower SR should be a necessary and sufficient area where the integrated amount of dry ice production [Formula: see text] and the dry ice production efficiency η are as high as possible to make it compact and low-cost. At the same time, the area of the cooling wall SC is determined such that the sublimation and solidification capacity of CO2 is balanced with the CO2 regeneration capacity.

The cerebral arterial network covering the brain cortex has multiscale anastomosis structures with sparse intermediate anastomoses (O[102] μm in diameter) and dense pial networks (O[101] μm in diameter). Recent studies indicate that collateral blood supply by cerebral arterial anastomoses has an essential role in the prognosis of acute ischemic stroke caused by large vessel occlusion. However, the physiological importance of these multiscale morphological properties-and especially of intermediate anastomoses-is poorly understood because of innate structural complexities. In this study, a computational model of multiscale anastomoses in whole-brain-scale cerebral arterial networks was developed and used to evaluate collateral blood supply by anastomoses during middle cerebral artery occlusion. Morphologically validated cerebral arterial networks were constructed by combining medical imaging data and mathematical modeling. Sparse intermediate anastomoses were assigned between adjacent main arterial branches; the pial arterial network was modeled as a dense network structure. Blood flow distributions in the arterial network during middle cerebral artery occlusion simulations were computed. Collateral blood supply by intermediate anastomoses increased sharply with increasing numbers of anastomoses and provided one-order-higher flow recoveries to the occluded region (15%-30%) compared with simulations using a pial network only, even with a small number of intermediate anastomoses (≤10). These findings demonstrate the importance of sparse intermediate anastomoses, which are generally considered redundant structures in cerebral infarction, and provide insights into the physiological significance of the multiscale properties of arterial anastomoses.

Background Aminoglycoside antibiotics are used for treating certain acute infections. However, these drugs cause ototoxicity by inducing inner ear hair cell death. Aims/Objectives We investigated the protective effect of a nanoemulsion of the carotenoid astaxanthin on mammalian inner ear hair cells against neomycin-induced ototoxicity. Material and Methods Dose-response relationship, quantification of hair cell loss, and reactive oxygen species production were assayed in response to neomycin with and without astaxanthin in cultured utricles of CBA/N mice. In addition, auditory brain response (ABR) and hair cell loss after exposure to the nanoformulation and loud noise were examined in vivo in guinea pigs. Results Astaxanthin suppressed neomycin-induced reduction of hair cells by reducing the production of hydroxy radicals. Furthermore, hair cell loss in the second rotation of the cochlea was significantly lower in the astaxanthin group than in the noise-only group. Conclusions and Significance The blood-labyrinth barrier limits the successful delivery of drugs for inner ear complications. However, in the nanoemulsion form, astaxanthin can penetrate the round window (fenestra ovale) membrane, enabling topical administration. Thus, astaxanthin nanoemulsion could be useful in treating ototoxicity in individuals with inner ear complications.

Summary: The giant clam Tridacna crocea thrives in poorly nourished coral reef water by forming a holobiont with zooxanthellae and utilizing photosynthetic products of the symbiont. However, detailed metabolic crosstalk between clams and symbionts is elusive. Here, we discovered that the nonphosphorous microalgal betaine lipid DGCC (diacylglycerylcarboxy-hydroxymethylcholine) and its deacylated derivative GCC are present in all tissues and organs, including algae-free sperm and eggs, and are metabolized. Colocalization of DGCC and PC (phosphatidylcholine) evidenced by MS imaging suggested that DGCC functions as a PC substitute. The high content of GCC in digestive diverticula (DD) suggests that the algal DGCC was digested in DD for further utilization. Lipidomics analysis showing the organ-specific distribution pattern of DGCC species suggests active utilization of DGCC as membrane lipids in the clam. Thus, the utilization of zooxanthellal DGCC in animal cells is a unique evolutionary outcome in phosphorous-deficient coral reef waters.

Within microeukaryotes, genetic variation and functional variation sometimes accumulate more quickly than morphological differences. To understand the evolutionary history and ecology of such lineages, it is key to examine diversity at multiple levels of organization. In the dinoflagellate family Symbiodiniaceae, which can form endosymbioses with cnidarians (e.g., corals, octocorals, sea anemones, jellyfish), other marine invertebrates (e.g., sponges, molluscs, flatworms), and protists (e.g., foraminifera), molecular data have been used extensively over the past three decades to describe phenotypes and to make evolutionary and ecological inferences. Despite advances in Symbiodiniaceae genomics, a lack of consensus among researchers with respect to interpreting genetic data has slowed progress in the field and acted as a barrier to reconciling observations. Here, we identify key challenges regarding the assessment and interpretation of Symbiodiniaceae genetic diversity across three levels: species, populations, and communities. We summarize areas of agreement and highlight techniques and approaches that are broadly accepted. In areas where debate remains, we identify unresolved issues and discuss technologies and approaches that can help to fill knowledge gaps related to genetic and phenotypic diversity. We also discuss ways to stimulate progress, in particular by fostering a more inclusive and collaborative research community. We hope that this perspective will inspire and accelerate coral reef science by serving as a resource to those designing experiments, publishing research, and applying for funding related to Symbiodiniaceae and their symbiotic partnerships.

Microorganisms possess taxes, which are the behavioral response to stimuli. The interaction between taxis and fluid dynamic instability leads to a macroscopic flow called bioconvection. In this study, we demonstrated that an isolated, single, three-dimensional bioconvection cell can exist within Euglena suspension. The isolated convection cell was named a “bioconvection spot.” To reveal the formation of this bioconvection spot in a cylindrical container, position-control experiments were designed in a non-uniform light environment. Upon exposure of Euglena suspensions to varying light conditions with white and red regions, Euglena was determined to aggregate into the red (darker) region. This was attributed to its phototactic response of Euglena, causing its movement toward a darker environment and away from a strong light. Thus, the bioconvection spot was created by manipulating the local cell density of the suspension and the light environments. Using our experimental setup, we observed the structure of the spot and established that it radiated pulses of local cell densities of Euglena.

Abstract Background Scleractinian corals of the genus Montipora (Anthozoa, Cnidaria) possess some unusual biological traits, such as vertical transmission of algal symbionts; however, the genetic bases for those traits remain unknown. We performed extensive comparative genomic analyses among members of the family Acroporidae (Montipora, Acropora, and Astreopora) to explore genomic novelties that might explain unique biological traits of Montipora using improved genome assemblies and gene predictions for M. cactus, M. efflorescens and Astreopora myriophthalma. Results We obtained genomic data for the three species of comparable high quality to other published coral genomes. Comparative genomic analyses revealed that the gene families restricted to Montipora are significantly more numerous than those of Acropora and Astreopora, but their functions are largely unknown. The number of gene families specifically expanded in Montipora was much lower than the number specifically expanded in Acropora. In addition, we found that evolutionary rates of the Montipora-specific gene families were significantly higher than other gene families shared with Acropora and/or Astreopora. Of 40 gene families under positive selection (Ka/Ks ratio > 1) in Montipora, 30 were specifically detected in Montipora-specific gene families. Comparative transcriptomic analysis of early life stages of Montipora, which possesses maternally inherited symbionts, and Acropora, which lacks them, revealed that most gene families continuously expressed in Montipora, but not expressed in Acropora do not have orthologs in Acropora. Among the 30 Montipora-specific gene families under positive selection, 27 are expressed in early life stages. Conclusions Lineage-specific gene families were important to establish the genus Montipora, particularly genes expressed throughout early life stages, which under positive selection, gave rise to biological traits unique to Montipora. Our findings highlight evolutionarily acquired genomic bases that may support symbiosis in these stony corals and provide novel insights into mechanisms of coral-algal symbiosis, the physiological foundation of coral reefs.

Microorganisms respond to environmental conditions and often spontaneously form highly ordered convection patterns. This mechanism has been well-studied from the viewpoint of self-organization. However, environmental conditions in nature are usually dynamic. Naturally, biological systems respond to temporal changes in environmental condition. To elucidate the response mechanisms in such a dynamic environment, we observed the bioconvection pattern of Euglena under periodical changes in illumination. It is known that Euglena shows localized bioconvection patterns under constant homogeneous illumination from the bottom. Periodical changes in light intensity induced two different types of spatiotemporal patterns: alternation of formation and decomposition over a long period and complicated transition of pattern over a short period. Our observations suggest that pattern formation in a periodically changing environment is of fundamental importance to the behavior of biological systems.

The cell motion of Euglena gracilis in homogeneous and heterogeneous light environments was analyzed. Homogeneous and heterogeneous environments were prepared, with only a red color or with a red circle surrounded by brighter white regions, respectively. In a heterogeneous environment, the cells move into the red circle. Swimming orbits at 1/25 s intervals for 120 s were analyzed. The speed distribution of the 1 s-averaged cell orbits in a homogeneous environment was different from that in a heterogeneous environment, where the faster swimming fraction was enhanced. The relationship between speed and curvature radius was analyzed using a joint histogram. Histograms for short timescale motion, constructed by 1 s-averaged orbits, suggest that the cell swimming curves are not biased, while those for long timescale motion, constructed by 10 s-averaged orbits, suggest that the cell swimming curves are biased in the clockwise direction. Furthermore, the curvature radius determines the speed, which does not seem to depend on the light environment. The mean squared displacement in a heterogeneous environment is larger than that in a homogeneous environment on a 1 s timescale. These results will be the basis for constructing a model for the long-time behavior of photomovement for light differences.

There is little evidence concerning the need to treat gestational diabetes (GDM) in the same way as pregestational diabetes. We evaluated the efficacy of the simple insulin injection (SII) regimen for achieving the target glucose goal without increasing adverse perinatal outcomes in singleton pregnant women with GDM. All subjects underwent self-monitoring of blood glucose (SMBG), and insulin therapy was indicated according to the SMBG profile. Insulin was initially started with the SII regimen, in which one daily injection of NPH insulin before breakfast was used, and another NPH injection was added at bedtime, if necessary. We used the target glucose as the SII>the diet group. The rate of achieving target glucose levels before delivery in the SII group at fasting, postprandial

Abstract Although numerous dinoflagellate species (Family Symbiodiniaceae) are present in coral reef environments, Acropora corals tend to select a single species, Symbiodinium microadriaticum, in early life stages, even though this species is rarely found in mature colonies. In order to identify molecular mechanisms involved in initial contact with native symbionts, we analyzed transcriptomic responses of Acropora tenuis larvae at 1, 3, 6, 12, and 24 h after their first contact with S. microadriaticum, as well as with non-native symbionts, including the non-symbiotic S. natans and the occasional symbiont, S. tridacnidorum. Some gene expression changes were detected in larvae inoculated with non-native symbionts at 1 h post-inoculation, but those returned to baseline levels afterward. In contrast, when larvae were exposed to native symbionts, we found that the number of differentially expressed genes gradually increased in relation to inoculation time. As a specific response to native symbionts, upregulation of pattern recognition receptor-like and transporter genes, and suppression of cellular function genes related to immunity and apoptosis, were exclusively observed. These findings indicate that coral larvae recognize differences between symbionts, and when the appropriate symbionts infect, they coordinate gene expression to establish stable mutualism.

Abstract Background Both fragile X-associated tremor/ataxia syndrome (FXTAS) and late-onset neuronal intranuclear inclusion disease (NIID) show CGG/GGC trinucleotide repeat expansions. Differentiating these diseases are difficult because of the similarity in their clinical and radiological features. It is unclear that skin biopsy can distinguish NIID from FXTAS. We performed a skin biopsy in an FXTAS case with cognitive dysfunction and peripheral neuropathy without tremor, which was initially suspected to be NIID. Case presentation The patient underwent neurological assessment and examinations, including laboratory tests, electrophysiologic test, imaging, skin biopsy, and genetic test. A brain MRI showed hyperintensity lesions along the corticomedullary junction on diffusion-weighted imaging (DWI) in addition to middle cerebellar peduncle sign (MCP sign). We suspected NIID from the clinical picture and the radiological findings, and performed a skin biopsy. The skin biopsy specimen showed ubiquitin- and p62-positive intranuclear inclusions, suggesting NIID. However, a genetic analysis for NIID using repeat-primed polymerase chain reaction (RP-PCR) revealed no expansion detected in the Notch 2 N-terminal like C (NOTCH2NLC) gene. We then performed genetic analysis for FXTAS using RP-PCR, which revealed a repeat CGG/GGC expansion in the FMRP translational regulator 1 (FMR1) gene. The number of repeats was 83. We finally diagnosed the patient with FXTAS rather than NIID. Conclusions For the differential diagnosis of FXTAS and NIID, a skin biopsy alone is insufficient; instead, genetic analysis, is essential. Further investigations in additional cases based on genetic analysis are needed to elucidate the clinical and pathological differences between FXTAS and NIID.

Phase-contrast magnetic resonance imaging (PC-MRI) allows us to acquire biofluid flow velocity maps, whereas MRI data is restricted by spatiotemporal resolution limitations and contains theoretically inevitable errors. Although various approaches to estimating actual velocity from MR velocity maps using the mass and momentum conservation laws have been proposed, practically reasonable methodologies are still not well established. This study investigates a practical strategy for estimating physically consistent velocities from MR velocity maps based on variational optimal boundary control through examples of the 2D steady Stokes flow as an incompressible viscous fluid. We defined a minimization problem of the sum of squared residuals between MR and the estimated velocity at all pixels (voxels) considering the image data structure with respect to the Dirichlet boundary velocity condition subject to flow governing equations based on variational formulations. This optimization problem is treated as an unconstrained optimization problem by deriving the Lagrange functional, including the cost function, regularization term, and constraint conditions. The optimality condition is computed using the adjoint variable method in a finite element manner. The boundary velocity profile is iteratively updated by the optimality condition using gradient-based optimization until convergence. Numerical examples for 2D Poiseuille flow with noise-free and noisy reference data demonstrated good convergencies of the cost function minimization. The estimated flow velocities were in excellent agreement with reference data. Finally, we demonstrated the viability of the velocity estimation using the actual MR velocity of the cerebrospinal fluid flow. The proposed approach with further considerations specialized for the MRI may be feasible in providing physically consistent velocity profiles in a versatile target of the biofluid flow.

BackgroundEarly intervention and prevention of psychiatric comorbidities of children with autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD) are urgent issues. However, the differences in the diagnoses of ASD and ADHD and psychiatric comorbidities associated with age, long-term healthcare utilization trajectories, and its associated diagnostic features have not been fully elucidated in Japan.MethodWe conducted a retrospective observational study using the medical records. Member hospitals of three major consortiums of hospitals providing child and adolescent psychiatric services in Japan were recruited for the study. Children who accessed the psychiatry services of the participating hospitals in April 2015 were followed up for 5 years, and data on their clinical diagnoses, consultation numbers, and hospitalizations were collected. Non-hierarchical clustering was performed using two 10-timepoint longitudinal variables: consultation numbers and hospitalization. Among the major clusters, the differences in the prevalence of ASD, ADHD, comorbid intellectual disability, neurotic disorders, and other psychiatric disorders were assessed.ResultsA total of 44 facilities participated in the study (59.5%), and 1,003 participants were enrolled. Among them, 591 diagnosed with ASD and/or ADHD (58.9%) and 589 without missing data were assessed. The mean age was 10.1 years, and 363 (70.9%) were boys. Compared with the pre-schoolers, the school-aged children and adolescents had fewer ASD, more ADHD, and fewer comorbid intellectual disability diagnoses, as well as more diagnoses of other psychiatric disorders. A total of 309 participants (54.7%) continued consultation for 2 years, and 207 (35.1%) continued for 5 years. Clustering analysis identified three, two, and three major clusters among pre-schoolers, school-aged children, and adolescents, respectively. The largest cluster was characterized by early termination of the consultation and accounted for 55.4, 70.6, and 73.4% of pre-schoolers, school-aged children, and adolescents, respectively. Among the school-aged children, the diagnosis of ADHD was associated with a cluster that required longer periods of consultations. Among the adolescents, comorbid psychiatric disorders other than intellectual disability and neurotic disorders were associated with clusters that required hospitalization.ConclusionContinuous healthcare needs were common and psychiatric comorbidities were associated with complex trajectory among adolescents. The promotion of early intervention and prevention of comorbidities are important.

Abstract Background Recent studies have suggested that fetal sex influences maternal glucose and insulin metabolism during pregnancy. We examined whether fetal sex is associated with maternal insulin resistance and the β-cell function during mid-pregnancy. Methods This retrospective study included singleton pregnant women who underwent a 75-g oral glucose tolerance test (OGTT) at 24–34 weeks of gestation due to positive diabetic screening. In addition to plasma glucose (PG), we measured plasma insulin during the OGTT to obtain surrogate indices associated with insulin resistance (IR), including homeostasis assessment model (HOMA) -IR and insulin sensitivity index (IsOGTT), and β-cell function, including insulinogenic index (II), HOMA-β, and area under the curve of insulin response. We compared these indices between women carrying male fetuses to those carrying female fetuses. Results The study population included 617 women (mean age, 32.4 ± 4.9 years) with a mean pre-pregnancy body mass index (BMI) of 22.6±4.5. They underwent the 75g-OGTT at 29.0 ± 2.5 weeks. Two hundred fifty-eight (42%) women were diagnosed with gestational diabetes (GDM). There was no significant difference in maternal age, pre-pregnancy BMI, gestational age at OGTT, PG at OGTT, or the prevalence of GDM between women with a male fetus (n=338) (male group) and those with a female fetus (n=279) (female group). Regarding the indices of IR, IR was significantly higher and insulin sensitivity was lower in the female group than in the male group (HOMA-IR: 7.0 [5-9.6] vs. 6.2 [4.6-8.8], p< 0.05; IsOGTT: 5.86 [4.29-7.83] vs. 6.29 [4.59-8.84], p< 0.01) (median [quartile range]). These differences remained significant after adjustment for maternal age, pre-pregnancy BMI, gestational age and fasting PG at OGTT, and the diagnosis of GDM. In contrast, the β-cell function did not differ between the two groups. Conclusion Maternal IR during mid-pregnancy was significantly higher in women carrying a female fetus than in those with a male fetus. The sex of the fetus may affect maternal insulin sensitivity during mid-pregnancy.

Background and Aim Esophageal endoscopic submucosal dissection (ESD) is often technically difficult due to intraoperative body movements. The level of sedation can be increased to suppress body movements, but this may not be successful in all cases. Using local analgesics for submucosal injection during ESD may aid in conscious sedation. This study evaluated the feasibility of the lidocaine injection method (LIM) during esophageal ESD. Methods Twenty‐nine patients with superficial esophageal cancer were enrolled in this study at Osaka Saiseikai Nakatsu Hospital, and 1% lidocaine + 0.4% hyaluronate sodium was injected into the submucosa underneath the lesion during esophageal ESD. The main outcome was body movements that disturbed the procedure. Results Most patients were male (90%), with a median age of 70 years (interquartile range [IQR]: 66–75 years old), and the median lesion size was 17 mm (IQR: 12–21 mm). The median injection volume of lidocaine was 70 mg (IQR: 55–79 mg). All lesions were successfully removed en bloc. In all cases, there were no body movements that disturbed the procedure. Regarding adverse events of sedation, five patients (17%) had hypotension, four patients (14%) had bradycardia, and seven patients (24%) had hypoxemia during ESD. Convulsions or arrhythmia as adverse events associated with lidocaine were not observed. Conclusions Esophageal ESD with LIM did not cause body movements that disturbed the procedure. LIM may help create a stable conscious sedation method for esophageal ESD.

Species delimitation of closely related corals is often challenging due to high intraspecies morphological variation and phenotypic plasticity with a lack of characteristic features and scarcity of relevant molecular markers. Goniopora spp. are one such coralline group, and the species status of Goniopora lobata and Goniopora djiboutiensis, an Indian and Pacific Ocean hermatypic coral species complex, has been questioned on the basis of previous molecular and morphological analyses. To further examine the species boundaries between G. lobata and G. djiboutiensis in Japan, specimens collected from areas spanning from Ryukyu Island to temperate Japanese regions were morphologically identified based on traditional morphological descriptions. Then, the genetic structure of the G. lobata and G. djiboutiensis species complex was examined using six newly developed microsatellite markers. The majority of the collected specimens had intermediate morphologies, and a STRUCTURE analysis using the LOCPRIOR model based on typical G. lobata and G. djiboutiensis morphology indicated that there were no genetic differences between these morphologies. On the other hand, STRUCTURE analysis based on oceanographic regions revealed that there was a genetic break between the temperate and subtropical regions. This weak genetic break corresponded with the Kuroshio-associated barrier, which prevents larval transport between subtropical and temperate regions. This study confirms that the current morphological identification criteria for G. lobata and G. djiboutiensis do not match the existing genetic boundaries and thus the two should be regarded as a species complex. This study also highlighted the robustness of using a multi-locus population genetic approach, including a geographic context, to confirm the species boundaries of closely related species.

Abstract Background High serum calcium levels should be avoided in patients on hemodialysis (HD) because they can induce cardiovascular diseases and worsen the patient’s prognosis. In contrast, low serum calcium levels worsen the prognosis of patients with cerebral hemorrhage in the general population. So far, whether serum calcium levels in patients on HD are associated with cerebral hemorrhage remains unknown. This study aimed to reveal the association between serum calcium and cerebral hemorrhage in patients on HD, including in-hospital death, volume of hematoma, and onset of cerebral hemorrhage. Methods This cross-sectional case-control study included 99 patients on HD with cerebral hemorrhage at a single center between July 1, 2007 and December 31, 2017. Controls included 339 patients on HD at a single HD center between July 1, 2011 and June 30, 2012. Data on serum calcium level, patient demographics, and comorbid conditions were collected, and associations between cerebral hemorrhage and subsequent death were evaluated by multivariate logistic regression analysis. Further, the association of these backgrounds and hematoma volume was evaluated by multiple regression analysis. Results Of the 99 patients, 32 (32%) died from cerebral hemorrhage. The corrected serum calcium level (odds ratio [OR], 2.49; 95% confidence interval [CI], 1.43–4.35; P

One possibility to reduce the climate impact of aviation is the avoidance of climate-sensitive regions, which is synonymous with climate-optimised flight planning. Those regions can be identified by algorithmic Climate Change Functions (aCCFs) for nitrogen oxides (NOx), water vapour (H2O) as well as contrail cirrus, which provide a measure of climate effects associated with corresponding emissions. In this study, we evaluate the effectiveness of reducing the aviation-induced climate impact via ozone (O3) formation (resulting from NOx emissions), when solely using O3 aCCFs for the aircraft trajectory optimisation strategy. The effectiveness of such a strategy and the associated potential mitigation of climate effects is explored by using the chemistry–climate model EMAC (ECHAM5/MESSy) with various submodels. A summer and winter day, characterised by a large spatial variability of the O3 aCCFs, are selected. A one-day air traffic simulation is performed in the European airspace on those selected days to obtain both cost-optimised and climate-optimised aircraft trajectories, which more specifically minimised a NOx-induced climate effect of O3 (O3 aCCFs). The air traffic is laterally and vertically re-routed separately to enable an evaluation of the influences of the horizontal and vertical pattern of O3 aCCFs. The resulting aviation NOx emissions are then released in an atmospheric chemistry–climate simulation to simulate the contribution of these NOx emissions to atmospheric O3 and the resulting O3 change. Within this study, we use O3-RF as a proxy for climate impact. The results confirm that the climate-optimised flights lead to lower O3-RF compared to the cost-optimised flights, although the aCCFs cannot reproduce all aspects of the significant impact of the synoptic situation on the transport of emitted NOx. Overall, the climate impact is higher for the selected summer day than for the selected winter day. Lateral re-routing shows a greater potential to reduce climate impact compared to vertical re-routing for the chosen flight altitude. We find that while applying the O3 aCCFs in trajectory optimisation can reduce the climate impact, there are certain discrepancies in the prediction of O3 impact from aviation NOx emissions, as seen for the summer day. Although the O3 aCCFs concept is a rough simplification in estimating the climate impact of a local NOx emission, it enables a reasonable first estimate. Further research is required to better describe the O3 aCCFs allowing an improved estimate in the Average Temperature Response (ATR) of O3 from aviation NOx emissions. A general improvement in the scientific understanding of non-CO2 aviation effects could make climate-optimised flight planning practically feasible.

A 39-year-old man with type 1 diabetes, who had a 4-year history of Graves' disease being treated with propylthiouracil (PTU), had developed sudden hearing loss. However, he showed no other clinical manifestations. Intratympanic administration with dexamethasone had failed, and his hearing had deteriorated. Magnetic resonance imaging showed the contrast effect on T1-weighted image in both cochleae, and the serum immunological analysis showed the high titers for anti-neutrophil cytoplasmic antibodies (ANCA). Therefore, his sudden hearing loss was presumed to be initial presentation of ANCA-associated vasculitis owing to PTU. His hearing was rapidly restored by a PTU withdrawal while no use of immunosuppressive agents, and he confirmed his hearing improvement in ordinary conversation. The patient's clinical course suggests that bilateral sensorineural hearing loss that occurs during treating hyperthyroidism could be initial presentation of ANCA-associated vasculitis, and discontinuing anti-thyroid drugs should be considered before treating with glucocorticoids.

Most corals acquire symbiodiniacean symbionts from the surrounding environment to initiate symbiosis. The cell densities of Symbiodiniaceae in the environment are usually low, and mechanisms may exist by which new coral generations attract suitable endosymbionts. Phototaxis of suitable symbiodiniacean cells toward green fluorescence in corals has been proposed as one such mechanism. In the present study, we observed the phototaxis action wavelength of various strains of Symbiodiniaceae and the fluorescence spectra of aposymbiotic Acropora tenuis larvae at the time of endosymbiont uptake. The phototaxis patterns varied among the Symbiodiniaceae species and "native" endosymbionts-commonly found in Acropora juveniles present in natural environments; that is, Symbiodinium microadriaticum was attracted to blue light rather than to green light. Another native endosymbiont, Durusdinium trenchii, showed no phototaxis specific to any wavelength. Although the larvae exhibited green and broad orange fluorescence under blue-violet excitation light, the maximum green fluorescence peak did not coincide with that of the phototaxis action spectrum of S. microadriaticum. Rather, around the peak wavelength of larval green fluorescence, this native endosymbiont showed slightly negative phototaxis, suggesting that the green fluorescence of A. tenuis larvae may not play a role in the initial attraction of native endosymbionts. Conversely, broad blue larval fluorescence under UV-A excitation covered the maximum phototaxis action wavelength of S. microadriaticum. We also conducted infection tests using native endosymbionts and aposymbiotic larvae under red LED light that does not excite visible larval fluorescence. Almost all larvae failed to acquire S. microadriaticum cells, whereas D. trenchii cells were acquired by larvae even under red illumination. Thus, attraction mechanisms other than visible fluorescence might exist, at least in the case of D. trenchii. Our results suggest that further investigation and discussion, not limited to green fluorescence, would be required to elucidate the initial attraction mechanisms.

Objective: With increased screening, more patients with precancerous or early cervical cancer are now being identified. Age at pregnancy, and thus number of patients requiring fertility preservation, have also increased, resulting in more diagnostic and therapeutic cervical conization (conization) procedures. We here investigated the pathological and clinical characteristics of patients undergoing conization, with a focus on age. The objectives of our study were to identify the risk factors potentially involved in cervical intraepithelial neoplasia (CIN) recurrence or persistence, additional treatment after conization, the effects of conization on pregnancy, and the actual status of conization in Japan. Study design: A “Subcommittee for Investigation of Cervical Conization” within the Gynecologic Oncology Committee in the Japan Society of Obstetrics and Gynecology investigated pathological and clinical characteristics of conization at 205 institutions in Japan. We analyzed pathological and clinical characteristics according to age ≤50 and >50 years. Results: Patients aged 20–40 years accounted for 12904 (87%) of the 14,832 study patients (median: 37 years, range: 16–88 years). However, 1838 (12.4%) were aged >50 years. The commonest post-operative diagnosis was CIN grade 3 in all age groups. Rates of invasive cancer, post-operative detection of more advanced lesions, positive surgical margins, additional treatment, and recurrence were significantly higher in patients aged ≥50 years than those aged

The strong growth rate of the aviation industry in recent years has created significant challenges in terms of environmental impact. Air traffic contributes to climate change through the emission of carbon dioxide (CO2) and other non-CO2 effects, and the associated climate impact is expected to soar further. The mitigation of CO2 contributions to the net climate impact can be achieved using novel propulsion, jet fuels, and continuous improvements of aircraft efficiency, whose solutions lack in immediacy. On the other hand, the climate impact associated with non-CO2 emissions, being responsible for two-thirds of aviation radiative forcing, varies highly with geographic location, altitude, and time of the emission. Consequently, these effects can be reduced by planning proper climate-aware trajectories. To investigate these possibilities, this paper presents a survey on operational strategies proposed in the literature to mitigate aviation’s climate impact. These approaches are classified based on their methodology, climate metrics, reliability, and applicability. Drawing upon this analysis, future lines of research on this topic are delineated.

Delayed physical growth is a common complication of pediatric obstructive sleep apnea syndrome (OSAS). Adenotonsillectomy (AT) is the first-line treatment for pediatric OSAS. Only a few studies have performed time-course BMI evaluation in pediatric OSAS patients post-operatively. Thus, we aimed to evaluate the time-course changes in pediatric OSAS patients after AT. Thirty-three children with OSAS who underwent AT were included and divided into two groups on the basis of their BMI z-scores (delayed physical growth group, n = 15; non-delayed physical growth group, n = 18). Clinical records of height and weight were collected before AT and at 6, 12, 24, and 36 months after AT. Changes in the mean BMI z-scores of the two groups were assessed up to 36 months. The mean BMI z-score was significantly increased in the delayed physical growth group at 6 months after AT. In contrast, the increase in mean BMI z-score was not observed in the non-delayed physical growth group. Growth improvement was noted in pediatric OSAS patients with delayed physical growth after AT. Our results suggest that AT is a promising therapy for improving the physical growth of pediatric OSAS patients with such problems.

[This corrects the article DOI: 10.1371/journal.pone.0224111.].

Because more than 80% of species of gamete-spawning corals, including most Acroporidae species, do not inherit Symbiodiniaceae from their parents, they must acquire symbiont cells from sources in their environment. To determine whether photosynthetically competent Symbiodiniaceae expelled as fecal pellets from giant clams are capable of colonizing corals, we conducted laboratory experiments in which planula larvae of Acropora tenuis were inoculated with the cells in fecal pellets obtained from Tridacna crocea. T. crocea fecal pellets were administered once a day, and three days later, cells of Symbiodiniaceae from the fecal pellets had been taken up by the coral larvae. T. crocea fecal pellets were not supplied from the 4th day until the 8th day, and the cell densities in the larvae increased until the 8th day, which indicated the successful colonization by Symbiodiniaceae. The control group exhibited the highest mean percentage of larvae (100%) that were successfully colonized by culture strains of Symbiodiniaceae, and larvae inoculated with fecal pellets reached a colonization percentage of 66.7 ~ 96.7% on the 8th day. The highest colonization rate was achieved with the fecal pellets containing cells with high photosynthetic competency (Fv/Fm). Interestingly, the genetic composition of Symbiodiniaceae in the larvae retrieved on the 8th day differed from that in the fecal pellets and showed exclusive domination of the genus Symbiodinium. A minor but significant population of the genus Cladocopium in the fecal pellets was not inherited by the larvae. These experiments provided the first demonstration that the Symbiodiniaceae from tridacnine clams provided via fecal pellets can colonize and even proliferate in coral larvae.

Abstract Background Although the onset of gestational diabetes (GDM) is known to be a significant risk factor for the future development of type 2 diabetes, this risk specifically in women with GDM diagnosed by the International Association of Diabetes and Pregnancy Study Group (IADPSG) criteria has not yet been thoroughly investigated. This study was performed to investigate the risk factors associated with the development of postpartum diabetes in Japanese women with a history of GDM, and the effects of the differences in the previous Japanese criteria and the IADPSG criteria. Methods This retrospective cohort study included Japanese women with GDM who underwent at least one postpartum oral glucose tolerance test (OGTT) between 2003 and 2014. Cases with overt diabetes in pregnancy were excluded. We investigated the risk factors including maternal baseline and pregnancy characteristics associated with the development of postpartum diabetes. Results Among 354 women diagnosed with GDM during the study period, 306 (86%) (116/136 [85.3%] and 190/218 [87.2%] under the previous criteria and the IADPSG criteria, respectively) who underwent at least 1 follow-up OGTT were included in the study. Thirty-two women (10.1%) developed diabetes within a median follow-up period of 57 weeks (range, 6–292 weeks). Eleven (9.5%) and 21 (11.1%) were diagnosed as GDM during pregnancy based on the previous Japanese criteria and the IADPSG criteria, respectively, which did not significantly differ between those criteria. A multivariate logistic regression analysis revealed that HbA1c and 2-h plasma glucose (PG) at the time of the diagnostic OGTT during pregnancy were independent predictors of the development of diabetes after adjusting for confounders. The adjusted relative risk of HbA1c ≥5.6% for the development of diabetes was 4.67 (95% confidence interval, 1.53-16.73), while that of 2-h PG ≥183 mg/dl was 7.02 (2.51-20.72). Conclusions A modest elevation of the HbA1c and 2-h PG values at the time of the diagnosis of GDM during pregnancy are independent predictors of the development of diabetes during the postpartum period in Japanese women with a history of GDM. The diagnostic criteria did not affect the incidence of postpartum diabetes.

The continuous separation and filtration of particles immersed in fluid flows are important interests in various applications. Although the inertial focusing of particles suspended in a duct flow is promising in microfluidics, predicting the focusing positions depending on the parameters, such as the shape of the duct cross-section and the Reynolds number (Re) has not been achieved owing to the diversity of the inertial-focusing phenomena. In this study, we aimed to elucidate the variation of the inertial focusing depending on Re in rectangular duct flows. We performed a numerical simulation of the lift force exerted on a spherical particle flowing in a rectangular duct and determined the lift-force map within the duct cross-section over a wide range of Re. We estimated the particle trajectories based on the lift map and Stokes drag, and identified the particle-focusing points appeared in the cross-section. For an aspect ratio of the duct cross-section of 2, we found that the blockage ratio changes transition structure of particle focusing. For blockage ratios smaller than 0.3, particles focus near the centres of the long sides of the cross-section at low Re and near the centres of both the long and short sides at relatively higher Re. This transition is expressed as a subcritical pitchfork bifurcation. For blockage ratio larger than 0.3, another focusing pattern appears between these two focusing regimes, where particles are focused on the centres of the long sides and at intermediate positions near the corners. Thus, there are three regimes; the transition between adjacent regimes at lower Re is found to be expressed as a saddle-node bifurcation and the other transition as a supercritical pitchfork bifurcation.

An amendment to this paper has been published and can be accessed via the original article.

Human red blood cells (RBCs) are subjected to high viscous shear stress, especially during microcirculation, resulting in stable deformed shapes such as parachute or slipper shape. Those unique deformed RBC shapes, accompanied with axial or nonaxial migration, cannot be fully described according to traditional knowledge about lateral movement of deformable spherical particles. Although several experimental and numerical studies have investigated RBC behavior in microchannels with similar diameters as RBCs, the detailed mechanical characteristics of RBC lateral movement—in particular, regarding the relationship between stable deformed shapes, equilibrium radial RBC position, and membrane load—has not yet been fully described. Thus, we numerically investigated the behavior of single RBCs with radii of 4 μm in a circular microchannel with diameters of 15 μm. Flow was assumed to be almost inertialess. The problem was characterized by the capillary number, which is the ratio between fluid viscous force and membrane elastic force. The power (or energy dissipation) associated with membrane deformations was introduced to quantify the state of membrane loads. Simulations were performed with different capillary numbers, viscosity ratios of the internal to external fluids of RBCs, and initial RBC centroid positions. Our numerical results demonstrated that axial or nonaxial migration of RBC depended on the stable deformed RBC shapes, and the equilibrium radial position of the RBC centroid correlated well with energy expenditure associated with membrane deformations.

Orthosilicic acid is essential to many natural and synthetic materials but notoriously difficult to isolate, limiting its use in materials synthesis. Here, the authors successfully synthesize and stabilize orthosilicic acid and its oligomers, making available a new family of building blocks for silicon oxide-based materials.

Abstract Background Although breastfeeding is expected to reduce the incidence of diabetes in women with gestational diabetes, the effect has not been clearly confirmed. We examined whether or not high-intensity breastfeeding reduces the incidence of abnormal glucose tolerance and investigated the effect of high-intensity breastfeeding on insulin resistance during the first year postpartum in Japanese women with current gestational diabetes. Methods In this retrospective study, we included women with gestational diabetes who underwent postpartum 75 g oral glucose tolerance test during the first year (12-14 months) postpartum from 2009 to 2011 at a single tertiary perinatal care center in Japan. High-intensity breastfeeding was defined as the condition in which infants were fed by breastfeeding alone or 80% or more of the volume. We investigated the effect of high-intensity breastfeeding on the prevalence of postpartum abnormal glucose tolerance and the postpartum homeostasis model of assessment of insulin resistance (HOMA-IR), after controlling for confounders, including prepregnancy obesity and weight changes during pregnancy and postpartum. Results Among 88 women with gestational diabetes, 46 (52%) had abnormal glucose tolerance during the postpartum period. High-intensity breastfeeding women (n = 70) were significantly less likely to have abnormal glucose tolerance than non-high-intensity breastfeeding women (n = 18) (46% vs. 78%, p = 0.015). High-intensity breastfeeding was also associated with a lower HOMA-IR at 12-14 months postpartum than non-high-intensity breastfeeding (1.41 ± 1.02 vs. 2.28 ± 1.05, p = 0.035). Those associations remained significant after controlling for confounders. At least six months of high-intensity breastfeeding had a significant effect on lowering both the abnormal glucose tolerance prevalence and HOMA-IR compared with non-high-intensity breastfeeding. Conclusions In Japanese women with gestational diabetes, high-intensity breastfeeding ≥6 months had a protective effect against the development of abnormal glucose tolerance during the first year postpartum through improving insulin resistance, independent of obesity and postpartum weight change.

Tendons and ligaments are dense fibrous bands of connective tissue that integrate musculoskeletal components in vertebrates. Tendons connect skeletal muscles to the bone and function as mechanical force transmitters, whereas ligaments bind adjacent bones together to stabilize joints and restrict unwanted joint movement. Fibroblasts residing in tendons and ligaments are called tenocytes and ligamentocytes, respectively. Tenomodulin (Tnmd) is a type II transmembrane glycoprotein that is expressed at high levels in tenocytes and ligamentocytes, and is also present in periodontal ligament cells and tendon stem/progenitor cells. Tnmd is related to chondromodulin-1 (Chm1), a cartilage-derived angiogenesis inhibitor, and both Tnmd and Chm1 are expressed in the CD31− avascular mesenchyme. The conserved C-terminal hydrophobic domain of these proteins, which is characterized by the eight Cys residues to form four disulfide bonds, may have an anti-angiogenic function. This review highlights the molecular characterization and function of Tnmd, a specific marker of tendons and ligaments.

Unlike most bivalve shellfishes, giant clams (tridacnines) harbor symbiotic microalgae (zooxanthellae) in their fleshy bodies. Zooxanthellae are not maternally inherited by tridacnine offspring, hence, the larvae must acquire zooxanthellae from external sources, although such algal populations or sources in the environment are currently unknown. It is well known that giant clams expel fecal pellets that contain viable zooxanthellae cells, but whether these cells are infectious or just an expelled overpopulation from the giant clams has not been investigated. In this study, we observed the ultrastructural and photosynthetic competencies of zooxanthellae in the fecal pellets of Tridacna crocea and further tested the ability of these cells to infect T. squamosa juveniles. The ultrastructure of the zooxanthellae cells showed that the cells were intact and had not undergone digestion. Additionally, these zooxanthellae cells showed a maximum quantum yield of photosystem II (Fv/Fm) as high as those retained in the mantle of the giant clam. Under the assumption that feces might provide symbionts to the larvae of other giant clams, fecal pellets from Tridacna squamosa and T. crocea were given to artificially hatched 1-day-old T. squamosa larvae. On the 9th day, 15-34% of the larvae provided with the fecal pellets took up zooxanthellae in their stomach, and on the 14th day, zooxanthellae cells reached the larval margin, indicating the establishment of symbiosis. The rate reaching this stage was highest, ca. 5.3%, in the larvae given whole (nonhomogenized) pellets from T. crocea. The composition of zooxanthellae genera contained in the larvae were similar to those in the fecal pellets, although the abundance ratios were significantly different. This study is the first to demonstrate the potential of giant clam fecal pellets as symbiont vectors to giant clam larvae. These results also demonstrate the possibility that fecal pellets are a source of zooxanthellae in coral reefs.

Subepithelial deposits are observed in rare adult IgA nephropathy (IgAN) cases and are a key diagnostic finding in IgA-dominant infection-related glomerulonephritis (IgA-IRGN). Sometimes, it is difficult to distinguish IgA-IRGN from IgAN without a precise clinical history. We hypothesized that some IgA-IRGN cases might be diagnosed as IgAN with subepithelial deposits (IgAN-SD) and aimed to clarify the significance of subepithelial deposits in patients diagnosed with IgAN. We examined 464 patients diagnosed with IgAN at Nagasaki University Hospital and affiliated hospitals between 1996 and 2013. The differences in clinicopathological findings between IgAN-SD and IgAN with no subepithelial deposits (IgAN-NSD) were investigated. In addition to clinical data and typical IgAN pathological features, we analyzed complement levels, immunoglobulin localization, light chain staining patterns, and intramembranous deposits. There were 214 men and 250 women with a mean age of 38.8 ± 18.3 years. Subepithelial deposition was observed in 51 patients (11%). Compared to patients with IgAN-NSD, those with IgAN-SD had significantly lower mean serum protein (6.4 g/dL vs. 6.7 g/dL; p = 0.02), albumin (3.7 g/dL vs. 3.9 g/dL; p = 0.02), and complement (C3) (94 mg/dL vs. 103 mg/dL; p = 0.02) levels. Diffuse mesangial hypercellularity (M) (65% vs. 45%; p

The effect of statin on hemodialysis patients is controversial. Although previous large-scale studies did not clarify its effect in this population, recent studies suggest that statins could be useful in reducing the risk of cardiovascular events and all-cause mortality in specific groups of patients undergoing hemodialysis. The aforementioned large-scale studies included a small percentage of Asians, and few studies have investigated the effects of statins in Asians undergoing hemodialysis. Thus, we investigated the benefits of statins in patients undergoing maintenance hemodialysis at a single center in Japan. We obtained demographic, clinical, and hemodialysis data of all patients who underwent maintenance hemodialysis at the Nagasaki Renal Center between July 2011 and June 2012. Patients were followed-up until June 2018. We studied 339 patients, of which 51 (15.0%) were prescribed pitavastatin. The mean observation period was 4.1±2.3 years, 43% were women, and the median hemodialysis vintage at baseline was 4.7 years. During the follow-up, 198 patients (58%) died, of which 22 (43%) were prescribed pitavastatin and 176 (61%) were not prescribed any statins. After propensity score matching based on age, sex, dialysis vintage, dialysis time, diabetes mellitus, ischemic heart disease, dry weight, left ventricular ejection fraction, and serum albumin, an intergroup comparison between those who received statins and those who did not (44 patients in each group) showed significant differences in survival rate based on the log-rank test (P

Many corals establish symbiosis with Symbiodiniaceae cells from surrounding environments, but very few Symbiodiniaceae cells exist in the water column. Given that the N-acetyl-d-glucosamine-binding lectin ActL attracts Symbiodiniaceae cells, we hypothesized that corals must attract Symbiodiniaceae cells using ActL to acquire them. Anti-ActL antibody inhibited acquisition of Symbiodiniaceae cells, and rearing seawater for juvenile Acropora tenuis contained ActL, suggesting that juvenile A. tenuis discharge ActL to attract these cells. Among eight Symbiodiniaceae cultured strains, ActL attracted NBRC102920 (Symbiodinium tridacnidorum) most strongly followed by CS-161 (Symbiodinium tridacnidorum), CCMP2556 (Durusdinium trenchii), and CCMP1633 (Breviolum sp.); however, it did not attract GTP-A6-Sy (Symbiodinium natans), CCMP421 (Effrenium voratum), FKM0207 (Fugacium sp.), and CS-156 (Fugacium sp.). Juvenile polyps of A. tenuis acquired limited Symbiodiniaceae cell strains, and the number of acquired Symbiodiniaceae cells in a polyp also differed from each other. The number of Symbiodiniaceae cells acquired by juvenile polyps of A. tenuis was correlated with the ActL chemotactic activity. Thus, ActL could be used to attract select Symbiodiniaceae cells and help Symbiodiniaceae cell acquisition in juvenile polyps of A. tenuis, facilitating establishment of symbiosis between A. tenuis and Symbiodiniaceae cells.

The aerodynamic formation flight, which is also known as aircraft wake-surfing for efficiency (AWSE), enables aircraft to harvest the energy inherent in another aircraft’s wake vortex. As the thrust of the trailing aircraft can be reduced during cruise flight, the resulting benefit can be traded for longer flight time, larger range, less fuel consumption, or cost savings accordingly. Furthermore, as the amount and location of the emissions caused by the formation are subject to change and saturation effects in the cumulated wake of the formation can occur, AWSE can favorably affect the climate impact of the corresponding flights. In order to quantify these effects, we present an interdisciplinary approach combining the fields of aerodynamics, aircraft operations and atmospheric physics. The approach comprises an integrated model chain to assess the climate impact for a given air traffic scenario based on flight plan data, aerodynamic interactions between the formation members, detailed trajectory calculations as well as on an adapted climate model accounting for the saturation effects resulting from the proximity of the emissions of the formation members. Based on this approach, we derived representative AWSE scenarios for the world’s major airports by analyzing and assessing flight plans. The resulting formations were recalculated by a trajectory calculation tool and emission inventories for the scenarios were created. Based on these inventories, we quantitatively estimated the climate impact using the average temperature response (ATR) as climate metric, calculated as an average global near surface temperature change over a time horizon of 50 years. It is shown, that AWSE as a new operational procedure has a significant mitigation potential on climate impact. For a global formation flight scenario, we estimated the average relative change of climate response to range between 22% and 24% while the relative fuel saving effects sum up to 5–6%.

Climate-optimized routing is an operational measure to effectively reduce the climate impact of aviation with a slight increase in aircraft operating costs. This study examined variations in the flight characteristics among five aircraft routing strategies and discusses several characteristics of those routing strategies concerning typical weather conditions over the North Atlantic. The daily variability in the North Atlantic weather patterns was analyzed by using the European Center Hamburg general circulation model (ECHAM) and the Modular Earth Submodel System (MESSy) Atmospheric Chemistry (EMAC) model in the specified dynamics mode from December 2008 to August 2018. All days of the ten complete winters and summers in the simulations were classified into five weather types for winter and into three types for summer. The obtained frequency for each of the weather types was in good agreement with the literature data; and then representative days for each weather type were selected. Moreover, a total of 103 North Atlantic flights of an Airbus A330 aircraft were simulated with five aircraft routing strategies for each representative day by using the EMAC model with the air traffic simulation submodel AirTraf. For every weather type, climate-optimized routing shows the lowest climate impact, at which a trade-off exists between the operating costs and the climate impact. Cost-optimized routing lies between the time- and fuel-optimized routings and achieves the lowest operating costs by taking the best compromise between flight time and fuel use. The aircraft routing for contrail avoidance shows the second lowest climate impact; however, this routing causes extra operating costs. Our methodology could be extended to statistical analysis based on long-term simulations to clarify the relationship between the aircraft routing characteristics and weather conditions.

An operational measure that is inspired by migrant birds aiming toward the mitigation of aviation climate impact is to fly in aerodynamic formation. When this operational measure is adapted to commercial aircraft it saves fuel and is, therefore, expected to reduce the climate impact of aviation. Besides the total emission amount, this mitigation option also changes the location of emissions, impacting the non-CO2 climate effects arising from NOx and H2O emissions and contrails. Here, we assess these non-CO2 climate impacts with a climate response model to assure a benefit for climate not only due to CO2 emission reductions, but also due to reduced non-CO2 effects. Therefore, the climate response model AirClim is used, which includes CO2 effects and also the impact of water vapor and contrail induced cloudiness as well as the impact of nitrogen dioxide emissions on the ozone and methane concentration. For this purpose, AirClim has been adopted to account for saturation effects occurring for formation flight. The results of the case studies show that the implementation of formation flights in the 50 most popular airports for the year 2017 display an average decrease of fuel consumption by 5%. The climate impact, in terms of average near surface temperature change, is estimated to be reduced in average by 24%, with values of individual formations between 13% and 33%.

Frequent, high-density coral monitoring is essential to understand coral reef ecosystems. For this purpose, we developed a novel method for simultaneous monitoring of Acropora corals and their symbiont, Symbiodinium, from environmental DNA (eDNA) in seawater using next generation sequencing technology (NGS). We performed a tank experiment with running seawater using 19 Acropora species. Complete mitochondrial genomes of all the Acropora species were assembled to create a database and major types of their Symbiodinium symbionts were identified. Then eDNA was isolated by filtering inlet and outlet seawater from the tanks. Acropora and Symbiodinium DNA were amplified by PCR and sequenced. We detected all of the tested Acropora types from eDNA samples. Proportions and numbers of DNA sequences were both positively correlated with masses of corals in the tanks. In this trial, we detected DNA sequences from as little as 0.04 kg of Acropora colony, suggesting that existence of at least one adult Acropora colony (~30 cm diameter = 1 kg) per m2 at depths < 10 m could be detected using eDNA in the field. In addition, we detected major types of Symbiodinium within host corals from seawater, suggesting that it should be possible to detect major coral symbiont types if Acropora corals exist nearby, and possible free-living state Symbiodinium cells from eDNA in seawater. eDNA abundance of Symbiodinium types did not correlate well with frequencies of major Symbiodinium types in the corals, suggesting that quantification of Symbiodinium is difficult at this stage. Although this is the initial attempt to detect coral and Symbiodinium simultaneously from eDNA in seawater, this method may allow us to perform high-frequency, high-density coral reef monitoring of both corals and their symbionts in the near future.

Background: Cardiac resynchronization therapy is an effective device therapy for heart failure patients with conduction block. However, a problem with this invasive technique is the nearly 30% of non-responders. A number of studies have reported a functional line of block of cardiac excitation propagation in responders. However, this can only be detected using non-contact endocardial mapping. Further, although the line of block is considered a sign of responders to therapy, the mechanism remains unclear.Methods: Herein, we created two patient-specific heart models with conduction block and simulated the propagation of excitation based on a cellmodel of electrophysiology. In one model with a relatively narrow QRS width (176 ms), we modeled the Purkinje network using a thin endocardial layer with rapid conduction. To reproduce a wider QRS complex (200 ms) in the second model, we eliminated the Purkinje network, and we simulated the endocardial mapping by solving the inverse problem according to the actual mapping system.Results: We successfully observed the line of block using non-contact mapping in the model without the rapid propagation of excitation through the Purkinje network, although the excitation in the wall propagated smoothly. This model of slow conduction also reproduced the characteristic properties of the line of block, including dense isochronal lines and fractionated local electrocardiograms. Further, simulation of ventricular pacing from the lateral wall shifted the location of the line of block. By contrast, in the model with the Purkinje network, propagation of excitation in the endocardial map faithfully followed the actual propagation in the wall, without showing the line of block. Finally, switching the mode of propagation between the two models completely reversed these findings.Conclusions: Our simulation data suggest that the absence of rapid propagation of excitation through the Purkinje network is the major cause of the functional line of block recorded by non-contact endocardial mapping. The line of block can be used to identify responders as these patients loose rapid propagation through the Purkinje network.

A diverse antibody repertoire is primarily generated by the rearrangement of V, D, and J genes and subsequent somatic hypermutation (SHM). Class-switch recombination (CSR) produces various isotypes and subclasses with different functional properties. Although antibody isotypes and subclasses are considered to be produced by both direct and sequential CSR, it is still not fully understood how SHMs accumulate during the process in which antibody subclasses are generated. Here, we developed a new next-generation sequencing (NGS)-based antibody repertoire analysis capable of identifying all antibody isotype and subclass genes and used it to examine the peripheral blood mononuclear cells of 12 healthy individuals. Using a total of 5,480,040 sequences, we compared percentage frequency of variable (V), junctional (J) sequence, and a combination of V and J, diversity, length, and amino acid compositions of CDR3, SHM, and shared clones in the IgM, IgD, IgG3, IgG1, IgG2, IgG4, IgA1, IgE, and IgA2 genes. The usage and diversity were similar among the immunoglobulin (Ig) subclasses. Clonally related sequences sharing identical V, D, J, and CDR3 amino acid sequences were frequently found within multiple Ig subclasses, especially between IgG1 and IgG2 or IgA1 and IgA2. SHM occurred most frequently in IgG4, while IgG3 genes were the least mutated among all IgG subclasses. The shared clones had almost the same SHM levels among Ig subclasses, while subclass-specific clones had different levels of SHM dependent on the genomic location. Given the sequential CSR, these results suggest that CSR occurs sequentially over multiple subclasses in the order corresponding to the genomic location of IGHCs, but CSR is likely to occur more quickly than SHMs accumulate within Ig genes under physiological conditions. NGS-based antibody repertoire analysis should provide critical information on how various antibodies are generated in the immune system.

Giant clams (tridacnine shellfishes) are large bivalves that inhabit tropical and subtropical waters and harbor the symbiotic microalgae zooxanthellae, which consist of diverse phylotypes (clades). Each clade exhibits unique physiological characteristics, and the cladal composition may influence the host's survival and its ability to tolerate environmental changes. Using quantitative PCR (qPCR) assays, we investigated the zooxanthellal genetic clades in Tridacna crocea (n = 93) and Tridacna squamosa (n = 93). These two clam species were artificially bred and maintained for an extended time period under an equivalent environment in an outdoor pond. Results showed that T. crocea had a simpler cladal composition and with an apparent dominance of clade A, whereas multiple clades were present in T. squamosa. The zooxanthellae clade A is known to occur in other zooxanthellae-bearing animals that inhabit shallow waters, which is consistent to the shallow water habitat preference of T. crocea. Interestingly, in larger individuals of T. squamosa, the main zooxanthellal clade was C rather than A. The mechanism underlying the dominance of clade C in the larger T. squamosa has not yet been clarified. However, the additional photosynthates supplied by clade C may be preferable for growing clams, as is observed in corals. The cladal composition of giant clams has previously been reported to be primarily controlled by environmental factors. However, our experiments subjected different clam species to the same environmental conditions, and our results suggested that species-intrinsic and/or growth-related processes may also influence the cladal composition.

Objective. To demonstrate whether or not the routine use of prophylactic oxytocin (RUPO) reduces the blood loss and incidence of postpartum hemorrhaging (PPH). Methods. We used a prospective cohort and a historical control in a tertiary perinatal care center in Japan. In the prospective cohort, we introduced RUPO in April 2012 by infusing 10 units of oxytocin per 500 mL of normal saline into a venous line after anterior shoulder delivery (RUPO group). In the historical control, oxytocin was administered via a case-selective approach (historical control group). We included completed singleton vaginal deliveries and compared the volume of blood loss and the incidence of PPH between the groups. Results. We found a significantly lower volume of blood loss (520±327 versus 641±375 mL, p

Diterpenoid alkaloids are isolated from plants of the genera Aconitum, Delphinium, and Garrya (Ranunculaceae) and classified according to their chemical structures as C18-, C19- or C20-diterpenoid alkaloids. The extreme toxicity of certain compounds, e.g., aconitine, has prompted a thorough investigation of how structural features affect their bioactivities. Therefore, natural diterpenoid alkaloids and semi-synthetic alkaloid derivatives were evaluated for cytotoxic effects against human tumor cells [A549 (lung carcinoma), DU145 (prostate carcinoma), MDA-MB-231 (triple-negative breast cancer), MCF-7 (estrogen receptor-positive, HER2-negative breast cancer), KB (identical to cervical carcinoma HeLa derived AV-3 cell line), and multidrug-resistant (MDR) subline KB-VIN]. Among the tested alkaloids, C19-diterpenoid (e.g., lipojesaconitine, delcosine and delpheline derivatives) and C20-diterpenoid (e.g., kobusine and pseudokobusine derivatives) alkaloids exhibited significant cytotoxic activity and, thus, provide promising new leads for further development as antitumor agents. Notably, several diterpenoid alkaloids were more potent against MDR subline KB-VIN cells than the parental drug-sensitive KB cells.