Understanding tumor attachments and management of feeding arteries are very important factors to achieve safe resection of skull base meningioma. We examined the distributions and frequencies of feeding arteries in skull base meningioma by cerebral angiography, and also assessed relationships to tumor attachment for skull base meningioma. We enrolled patients with skull base meningioma who underwent MRI and cerebral digital subtraction angiography (DSA), from September 2015 to October 2022. Subjects comprised 115 patients (32 males, 83 females; mean age, 52.7 years) with 117 meningiomas showing tumor attachments around the “cavernous sinus to upper part of the clivus” (Area 1), “lower part of the clivus to foramen magnum” (Area 2), and “tentorium around the petrous bone” (Area 3). We examined feeding arteries based on cerebral angiography and counted the number of related feeding arteries. Particularly frequent arteries, such as the dorsal meningeal artery (DMA), ascending pharyngeal artery (APA), tentorial artery (TA), and petrosal branch (PB) of the middle meningeal artery (MMA) were analyzed for associations of tumor attachment to Areas 1–3. DMA, APA, TA, and PB are very frequent feeding arteries among skull base meningiomas. In some cases, the artery of the foramen rotundum, posterior ethmoidal artery, recurrent meningeal artery, posterior meningeal artery, etc., supply blood to the skull base meningioma. Meningiomas with DMA as a feeding artery correlated strongly with tumor attachment to Area 1 (p<0.001). Meningiomas with APA correlated strongly with tumor attachment to Area 2 (p<0.001). Meningiomas with TA correlated strongly with tumor attachment to Area 3 (p<0.001). PB correlated with Area 3 (p<0.05). Visualization of these arteries suggests tumor attachments to the correlated areas. An accurate anatomical understanding of tumor attachment and feeding arteries is essential to determine appropriate surgical strategies for skull base meningioma. Pre-operative DSA can provide further understanding of the feeding arteries and attachments of skull base meningioma.

A protocol was designed for plasmid curing using a novel counter-selectable marker, named pylSZK-pylT, in Escherichia coli. The pylSZK-pylT marker consists of the archaeal pyrrolysyl-tRNA synthetase (PylRS) and its cognate tRNA (tRNApyl) with modification, and incorporates an unnatural amino acid (Uaa), Nε-benzyloxycarbonyl-l-lysine (ZK), at a sense codon in ribosomally synthesized proteins, resulting in bacterial growth inhibition or killing. Plasmid curing is performed by exerting toxicity on pylSZK-pylT located on the target plasmid, and selecting only proliferative bacteria. All tested bacteria obtained using this protocol had lost the target plasmid (64/64), suggesting that plasmid curing was successful. Next, we attempted to exchange plasmids with the identical replication origin and an antibiotic resistance gene without plasmid curing using a modified protocol, assuming substitution of plasmids complementing genomic essential genes. All randomly selected bacteria after screening had only the substitute plasmid and no target plasmid (25/25), suggesting that plasmid exchange was also accomplished. Counter-selectable markers based on PylRS-tRNApyl, such as pylSZK-pylT, may be scalable in application due to their independence from the host genotype, applicability to a wide range of species, and high tunability due to the freedom of choice of target codons and Uaa’s to be incorporated.

This paper is our attempt on the basis of physical theory to bring more clarification on the question ``What is life?'' formulated in the well-known book of Schr\"odinger in 1944. According to Schr\"odinger, the main distinguishing feature of biosystem's functioning is the ability to preserve its order structure or, in the mathematical terms, to prevent increasing of entropy. Since any biosystem is fundamentally open, it is natural to use open system's theory. However, Schr\"odinger's analysis shows that the classical theory is not able to adequately describe the order-stability in a biosystem. Schr\"odinger should also appeal to the ambiguous notion of negative entropy. We suggest to apply the quantum theory. As is well-known, behaviour of the quantum von Neumann entropy crucially differs from behaviour of the classical entropy. We consider a complex biosystem $S$ composed of many subsystems, say proteins, or cells, or neural networks in the brain, i.e., $S=(S_i).$ We study the following problem: if the composed system $S$ can preserve the ``global order'' in the situation of increase of local disorder and if $S$ can preserve its entropy while some of $S_i$ increase their entropies We show that within quantum information theory the answer is positive. The significant role plays entanglement of the subsystems states. In the absence of entanglement, increasing of local disorder generates disorder increasing in the compound system $S$ (as in the classical regime).

We designed a novel growth controller regulated by feeding of an unnatural amino acid, Nε-benzyloxycarbonyl-L-lysine (ZK), using a specific incorporation system at a sense codon. This system is constructed by a pair of modified pyrrolisyl-tRNA synthetase (PylRS) and its cognate tRNA (tRNApyl). Although ZK is non-toxic for normal organisms, the growth of Escherichia coli carrying the ZK incorporation system was inhibited in a ZK concentration-dependent manner without causing rapid bacterial death, presumably due to generation of non-functional or toxic proteins. The extent of growth inhibition strongly depended on the anticodon sequence of the tRNApyl gene. Taking advantage of the low selectivity of PylRS for tRNApyl anticodons, we experimentally determined the most effective anticodon sequence among all 64 nucleotide sequences in the anticodon region of tRNApyl gene. The results suggest that the ZK-regulated growth controller is a simple, target-specific, environmental noise-resistant and titratable system. This technique may be applicable to a wide variety of organisms because the growth inhibitory effects are caused by “informational disturbance”, in which the highly conserved system for transmission of information from DNA to proteins is perturbed.

Nitroxyl radical catalysts oxidize alcohols under an applied electric potential. It is possible to quantify the alcohol concentration from the resulting oxidation current. In this work, we evaluated the catalytic activity of nitroxyl radicals (or their corresponding hydroxylamines), including 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO) as representative nitroxyl radicals, acetoamido-TEMPO, which shows higher oxidation potential than TEMPO owing to the acetoamido group, AZADO, Nor-AZADO, and NNO as less-hindered bicyclic nitroxyl radicals, and NHPI as an N,N-diacyl-type hydroxylamine, in acetonitrile solution. TEMPO, AZADO and NNO were also evaluated for their ability to oxidize alcohols in organic solvents, and their reactivity was compared with the electrochemical response. The most active NNO was used for electrochemical detection of cyclosporin A, a drug with a hydroxyl group.

For condensed systems, the incorporation of quantum chemical solvent effects into molecular dynamics simulations has been a major concern. To this end, quantum mechanical/molecular mechanical (QM/MM) techniques are popular and powerful options to treat gigantic systems. However, they cannot be directly applied because of temporal and spatial discontinuity problems. To overcome these problems, in a previous study, we proposed a corrective QM/MM method, size-consistent multipartitioning (SCMP) QM/MM, and successfully demonstrated that, using SCMP, it is possible to perform stable molecular dynamics simulations by effectively taking into account solvent quantum chemical effects. The SCMP method is characterized by two original features: size-consistency of a QM region among all QM/MM partitioning and partitioning update. However, in our previous study, the performance was not fully elicited compared to the theoretical upper bound, and the optimal partitioning update protocol and parameters were not fully verified. To elicit the potential performance, in the present study, we simplified the theoretical framework and modified the partitioning protocol.

Ground-level ozone (O3) increases in the northeastern part of Eurasia, where larch species are dominant trees and have been planted intensively. The Japanese larch (Larix kaempferi; hereafter larch) is classified as the tree species most of its sensitive to O3 based on data from long-shoot needles of seedlings. This criterion should be reconsidered based on O3 uptake, which is strongly depended on stomatal conductance (Gs) of adult trees through the difference in relevant needle traits. Because Gs is closely correlated with photosynthetic activity, we measured the in situ seasonal and yearly change in photosynthetic function, needle mass per area (LMA) and nitrogen (N) content of both short- and long-shoot needles of the canopy of larch trees over successive 3 years. No difference was observed in the in light saturated photosynthetic rate at ambient CO2 (Psat) between needles of hetero types of shoot in the latter part of the growing season, but clear differences were found within a specific year, indicating that seasonal changes in climatic factors determine Psat in the long term. The Psat-N relations differed significantly between the needle types. However, Psat at saturated CO2 (Pmax)-N was quite similar, implying that the CO2 diffusion difference between short- and long-shoots is responsible for the differing Psat -N. In conclusion, seasonal and yearly variations in photosynthetic capacity are mainly determined mainly by climatic variations, whereas shoot type determined the traits of photosynthetic N utilization as well as Gs regulation.

To monitor the detail information in the sea and on the seafloor, sensors are generally installed on Autonomous Underwater Vehicle (AUV). AUV cannot accurately grasp the absolute position and needs to communicate with the sea-surface vehicle. However, the sea-surface vehicle cannot perform observation operations at high speed and with high efficiency due to low mobility and high human and financial costs. From this perspective, Unmanned Aerial Vehicle (UAV) has possibilities as the next-generation platform. In this study, we conducted a demonstration experiment to use UAV as a sea-surface base for AUV’s underwater communication. We additionally verified the capability of UAV, which can land on and separate from the sea surface, as a drifting buoy to monitor underwater data. Experiment results and obtained data suggest that UAV is suitable for a research operation near the coastal region in terms of position keeping ability, performance against sway, and operation speed as a communication base. To carry out more complicated work (transportation of AUV, etc.) with UAV, new research and development such as weight reduction of AUV will be required.

SDG target 12.3 calls for halving food waste at retail, food service, and household by 2030. The food waste index for this purpose includes parts attached to food that are usually removed intentionally ("unavoidable food waste") and allows counting the conversion to animal feed and utilisation as biomaterial as means of reduction. In Japan, the "Food Waste Recycling Law" which has been in effect since 2001, promotes the recycling of food waste generated from businesses, designating feed conversion as top priority. On the other hand, based on the more recent "Food Loss Reduction Promotion Act" of 2019, the government is currently promoting the reduction of avoidable food waste, as to meet the SDG target. Based on statistical sources and interviews with Ministry officers, this paper explains the history and achievements of Japan's 23-year policy based on the Food Recycling Law, as well as the tension between the two legislations.

Cardiovascular diseases remain the leading cause of mortality worldwide. Although new therapies are actively being developed and used for cardiovascular pathologies, these attempts have not significantly decreased mortality rates. Regenerative medicine has made enormous progress and set promising approaches over the past half-century. However, since autologous (donor-derived) vascular grafts are lacking, an alternative prosthesis must be constructed for cardiovascular disease patients. In vascular tissue manufacturing and regenerative medicine, scientists seek to improve this significant clinical challenge using bio-fabrication techniques combining additive manufacturing, biomaterials science, and advanced cellular biology. In the last few decades, many improvements and changes in various approaches have helped develop bioengineered concepts that reflect native blood vessels’ structure and function. However, numerous challenges must be overcome to clinically translate the next generation of tissue-engineered vascular transplants. This review provides update on the cell sources, scaffold essential for cardiovascular tissue engineering, and tissue engineering approaches as prospective options for curative therapy for blood vessel disease.

The Glasgow Declaration called for scientifically based measurements of CO2 emissions in the tourism industry to achieve the goals of the Paris Agreement. Despite the economic and employment downturn caused by COVID-19, there are limited cases of environmental assessments related to tourism. This study estimates the carbon footprint of the tourism industry in major G20 countries before and after COVID-19. Understanding the characteristics of inbound tourism and domestic tourism is important as they impact different markets. GHG emissions from tourism mainly stem from transportation, but the type of travel and country differences also make souvenirs, accommodation, and food and beverages significant emission factors. The pandemic has greatly impacted the tourism industry. In 2020, GHG emissions from both domestic and inbound tourism significantly decreased, affecting the number of tourists. In some countries, measures against COVID-19 influenced these figures, and although signs of recovery were observed in 2021, the reduction rates varied by country. These emission reductions should be the goals pursued by the tourism industry in the post-COVID-19 era, requiring efforts to achieve sustainable tourism.

Coronary artery lesions (CALs) after Kawasaki disease present complex coronary hemodynamics. We investigated the relationship between coronary fractional flow reserve (FFR), myocardial blood flow reserve (MFR), and myocardial blood flow volume fraction (MBF), and their clinical usefulness in CALs after Kawasaki disease. Nineteen patients (18 male, 1 female) who underwent cardiac catheterization and 13N-ammonia positron emission tomography, with 24 coronary artery branches, were included. Five branches had inconsistent FFR and MFR values, two had normal FFR but abnormal MFR, and three had abnormal FFR and normal MFR. The abnormal MFR group had significantly higher MBF at rest than the normal group (0.86±0.13 vs. 1.08±0.09, p=0.001). The abnormal FFR group had significantly lower MBF at adenosine loading than the normal group (2.23±0.23 vs. 1.88±0.29, p=0.021). The three branches with abnormal FFR only had stenotic lesions, but the MFR may have been normal because blood was supplied by collateral vessels. Combining FFR, MFR, and MBF will enable a more accurate assessment of peripheral coronary circulation and stenotic lesions in CALs and help determine treatment strategy and timing of intervention.

Coronavirus disease 2019 (COVID-19) caused by novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has reached a global epidemic across the world after first reported in Wuhan, China’s Hubei province in December 2019. The pandemic is also associated with acute respiratory distress syndrome (ARDS) characterized by excess inflammation, progressive arterial hypoxemia and dyspnea. Mesenchymal stem/ stromal cells (MSCs) have been investigated as treatment for ARDS due to immunomodulatory property. Exosomes derived from MSCs play an important role in paracrine signaling of MSCs, thereby contributed to immunomodulation of the immune microenvironment. Exosomes are emerged as potential alternative to MSC cell therapy with superiority of safety. In this review, we will introduce MSC-derived exosomes and briefly discuss current progress on MSCs and exosomes in ARDS, which may have clinical implications in pathogenesis and treatment of COVID-19.

Solidification microstructure is formed under high cooling rates and temperature gradients in powder-based additive manufacturing. In this study, a non-equilibrium multi-phase field method (MPFM), which was based on a finite interface dissipation model proposed by Steinbach et. al., coupled with a CALPHAD database was developed for a multicomponent Ni alloy. A qua-si-equilibrium MPFM was also developed for comparison. Two-dimensional equiaxed micro-structural evolution for the Ni (Bal.)–Al–Co–Cr–Mo–Ta–Ti–W–C alloy was performed at various cooling rates. The temperature–γ fraction profiles obtained under 10^5 K/s using non- and qua-si-equilibrium MPFMs were in good agreement with each other. Over 10^6 K/s, the differences between non- and quasi-equilibrium methods grew as the cooling rate increased. The non-equilibrium solidification was strengthened over a cooling rate of 10^6 K/s. Colum-nar-solidification microstructural evolution was performed under cooling rates from 5×10^5 K/s to 1×10^7 K/s at various temperature gradient values under the constant interface velocity (0.1 m/s). The results showed that as the cooling rate increased, the cell space decreased in both methods, and the non-equilibrium MPFM agreed well with experimental measurements. Our results show that the non-equilibrium MPFM can simulate solidification microstructure in powder bed fusion additive manufacturing.

Retinoid X receptor (RXR) antagonists are not only useful as chemical tools for biological research, but also are candidate drugs for treatment of various diseases, including diabetes and allergy, although no RXR antagonist has yet been approved for clinical use. In this review, we describe currently available RXR antagonists, their structural classification, and their evaluation, focusing on the latest research.

The core pathological event in Parkinson’s disease (PD) is the specific dying of dopamine (DA) neurons of the substantia nigra pars compacta (SNc). Why SNc DA neurons are especially vulnerable and why idiopathic PD has only been found in humans is still puzzling. The two main underlying factors of SNc DA neuron vulnerability appear related to high DA production, namely (i) the toxic effects of cytoplasmic DA metabolism and (ii) continuous cytosolic Ca2+ oscillations in the absence of the Ca2+-buffer protein calbindin. Both factors cause oxidative stress by producing highly reactive quinones and increasing intra-mitochondrial Ca2+ concentrations, respectively. High DA expression in human SNc DA neuron cell bodies is suggested by the abundant presence of the DA-derived pigment neuromelanin, which is not found in such abundance in other species and has been associated with toxicity at higher levels. The oxidative stress created by their DA production system, despite that the SN does not use unusually high amounts of energy, explains why SNc DA neurons are sensitive to various genetic and environmental factors that create mitochondrial damage and thereby promote PD. Aging increases multiple of the risk factors for PD, and, to a large extent, PD is accelerated aging. To prevent PD neurodegeneration, possible approaches that are discussed here are (1) reducing cytoplasmic DA accumulation, (2) blocking cytoplasmic Ca2+ oscillations, and (3) providing bioenergetic support.

Background The purpose of this study was to clarify the relationship structure of quality of life (QOL) in survivors of breast cancer, including difficulty in daily life and negative experience as health-related indicators. Methods Participants were survivors of breast cancer for more than 2 years after primary breast cancer surgery and belonged to self-help groups. The assessment used FACT-B (QOL), HADS (anxiety and depression), SOC (sense of coherence), WHODAS 2.0 (difficulties in daily life), and CAOD (negative experiences). Bayesian structural equation modeling (BSEM) was performed to analyze the hypothesized model. If the causal model was significant, multiplication of the path coefficient from anxiety and depression to QOL, and from SOC to anxiety and depression, was considered a direct effect on QOL, and from SOC to difficulty in daily life, from difficulty in daily life to negative experiences, and from negative experiences to anxiety and depression were considered indirect effects on QOL. Results Goodness of fit of the model in the BSEM was satisfactory. The direct effect was 0.274, and indirect effect was 0.163. Conclusions These direct and indirect approaches to difficulties in daily life are very significant because they can provide a basis for development of support strategies to increase QOL.

Cells form a bipolar spindle during mitosis to ensure accurate chromosome segregation. Proper spindle architecture is established by a set of kinesin motors and microtubule-associated proteins. In most eukaryotes, kinesin-5 motors are essential for this process, and genetic or chemical inhibition of their activity leads to the emergence of monopolar spindles and cell death. However, these deficiencies can be rescued by simultaneous inactivation of kinesin-14 motors, as they counteract kinesin-5. We conducted detailed genetic analyses in fission yeast to understand the mechanisms driving spindle assembly in the absence of kinesin-5. Here we show that deletion of the nrp1 gene, which encodes a putative RNA-binding protein with unknown function, can rescue temperature sensitivity caused by cut7-22, a fission yeast kinesin-5 mutant. Interestingly, kinesin-14/Klp2 levels on the spindles in the cut7 mutants were significantly reduced by the nrp1 deletion, although the total levels of Klp2 and the stability of spindle microtubules remained unaffected. Moreover, RNA-binding motifs of Nrp1 are essential for its cytoplasmic localization and function. We have also found that a portion of Nrp1 is spatially and functionally sequestered by chaperone-based protein aggregates upon mild heat stress and limits cell division at high temperatures. We propose that Nrp1 might be involved in post-transcriptional regulation through its RNA-binding ability to promote the loading of Klp2 on the spindle microtubules.

Target 12.3 of the United Nations Sustainable Development Goals (SDGs) calls for halving per capita global food waste at the retail and consumer levels, by 2030. The Food Waste Index is suggested as a methodology for grasping the situation. This paper focuses on the consumer level (household food waste). We argue that in order for generating useful information for devising and implementing effective measures for reducing food waste, it should be measured at Level 3 of the Food Waste Index, based on sorting analysis of generated waste, making a distinction between avoidable and non-avoidable food waste. Furthermore, a breakdown by sub-categories that reflect the flow of food in the household could help identify target behaviours. We have developed a categorisation scheme that is internationally agreeable and adoptable, and 1) generates useful information for policy-making and for tackling with reduction of food waste, 2) makes clear the concept of avoidable food waste, and 3) is practical and does not overcomplicate the work of grasping the situation of food wastage. Results of workshops regarding this scheme suggest that the scheme satisfies the criteria. This scheme has been applied to a few sorting analyses of household food waste in Japan, and their results are compared.

Garnet-type Ta-doped Li7La3Zr2O12 (LLZO) ceramic solid electrolytes with Ga2O3 additive were synthesized via a conventional solid-state reaction process. When the amounts of Ga2O3 additive were below 2 mol %, the sintered sample has a dense structure composed of grains with the averaged size of 5 to 10 μm, while 3 mol % or more Ga2O3 addition causes the significant increase in grain size above several 10 to 100 μm, due to the sintering with large amount of liquid Li-Ga-O phase at high temperature. The highest total (bulk + grain-boundary) ionic conductivity of 1.1 mS cm1 at room temperature was obtained in the sample with 5 mol % Ga2O3 addition. However, in galvanostatic testing of the symmetric cell with Li metal electrodes, this sample was shorted by Li dendrite growth into solid electrolyte at current density below 0.2 mA cm2. The tolerance for Li dendrite growth is maximized in sample sintered with 2 mol % Ga2O3 addition, which was shorted at 0.8 mA cm2 in the symmetric cell. Since the interfacial resistance between Li metal and solid electrolyte was nearly identical among the all samples, the difference in tolerance for Li dendrite growth is mainly attributed to the difference in microstructure of sintered samples depending on the amounts of Ga2O3.

Background. Epidemiological and clinical studies demonstrated that excessive salt intake causes severe hypertension and exacerbated organ derangement such as chronic kidney disease (CKD). In this study, we focused on evaluating histological and gene-expression findings in the kidney using stroke-prone spontaneously hypertensive rats (SHRSP) with high-salt intake and thromboxane A2/ prostaglandin H2 receptor (TPR) blocker ONO-8809. Methods. SHRSP aged 6 weeks were divided into three groups eating normal chow containing 0.4% NaCl, 2.0%NaCl, or 2.0%NaCl +ONO-8809 (0.6mg/kg p.o. daily). Histological analyses with immunohistochemistry and a gene-expression assay with a DNA kidney microarray were performed after 8 weeks. Results. The following changes were observed with high-salt intake. Glomerular sclerotic changes were remarkably observed in the juxtaglomerular cortex areas. ED1, MCP-1, nitrotyrosine, and HIF-1α staining areas were increased in the glomeruli and interstitial portion. Tbxa2r which encodes TPR, Prcp, and Car7 were significantly underexpressed in the kidney. The plasma 8-isoprostane level was significantly elevated, and was attenuated with ONO-8809 treatment. Conclusion. TXA2 and oxidative stresses exaggerated renal dysfunction in salt-loading SHRSP, and ONO-8809 as a TPR blocker suppressed these changes. Therefore, ONO-8809 is a candidate drug to prevent CKD for hypertensive patients associated with high-salt intake.

The importance of the contribution from tourism to climate change was pointed out by the International Tourism Organization (UNWTO). By combining process-based Life Cycle Assessment (LCA) and Input-output analysis, several researches have tried to evaluate the impacts of the tourism industry as well as its products and services. Indeed, the tourism sector has a wide range of industries including travel and tour, transportation, accommodation, food and beverage, amusement, souvenirs etc. However, the existing cases did not show a breakdown of the impact on climate change. In this paper, the carbon footprint (CFP) of the Japanese tourism industry was calculated based on tourist consumption, using the Japanese Input-output table and the Japanese tourism industry. It was shown that the total emissions were approximately 136 million t-CO2 per year. The contribution ratio of each stage is as follows: Transport 56.3%, Souvenirs 23.2%, Petrol (direct emissions) 16.9%, Accommodation 9.8%, Food and Beverage 7.5%, Activities 3.0%. Then, in the breakdown, the impact is high in the following order Air transport 24.7%, Petrol (direct emissions) 16.9%,Accommodation 9.8%, Food and Beverage 7.5%, Petrol 6.1%, Textile products 5.3%, Food items 4.9%, Confectionery 4.8%, Rail transport 3.9%, Cosmetics 1.9%, Footwear 1.8%, etc. In addition to transportation, this research also highlighted especially the contribution from souvenirs, accommodation, food and beverages.

Kaposi’s sarcoma-associated herpesvirus (KSHV), also known as human herpesvirus-8, is the causative agent of Kaposi’s sarcoma, Castleman’s disease, and primary effusion lymphoma. Although the functions of the viral thymidine kinases (vTK) of herpes simplex virus-1/2 and varicella zoster virus are well understood, that of KSHV ORF21 (an ortholog of vTK) is largely unknown. Here, we investigated the role of ORF21 in lytic replication and infection by generating two ORF21-mutated KSHV BAC clones: ORF21-kinase activity deficient-KSHV (21KD) and stop codon-induced ORF21-deleted-KSHV (21del). The results showed that both ORF21-mutations did not affect viral genome replication, lytic genes transcription, or the production of viral genome-encapsidated particles. ORF21 molecule-dependent function, other than the kinase function of ORF21, was involved in the infectivity of progeny virus. ORF21 was expressed at 36 h after induction of lytic replication, and endogenously expressed ORF21 was localized in the whole cytoplasm and decreased on the cell surface area. Moreover, the effects of ORF21 expression on signaling pathways and proliferation were analyzed. The results showed that ORF21 upregulated the MEK phosphorylation and anchorage-independent cell growth. These findings indicate that ORF21 plays key roles in both infection and oncogenesis of KSHV through the manipulation of cellular function.

Acai (Euterpe oleracea Mart. Palmae, Arecaceae) is a palm plant native to the Brazilian Amazon. It contains many nutrients, such as polyphenols, iron, vitamin E, and unsaturated fatty acids, so in recent years, many of the antioxidant and anti-inflammatory effects of acai have been reported. However, the effects of acai on hematopoiesis have not been investigated yet. In the present study, we administered acai extract to mice and evaluated its hematopoietic effects. Acai treatment significantly increased the erythrocytes, hemoglobin, and hematocrit contents compared to controls for four days. We then examined the hematopoietic-related markers following a single injection. Acai administration significantly increased the levels of the hematopoietic-related hormone erythropoietin in blood compared to controls and also significantly upregulated the gene expression of Epo in the kidney. Furthermore, in the mice treated with acai extract, the kidneys were positively stained with the hypoxic probe pimonidazole in comparison to the controls. These results demonstrated that acai increases the number of blood cells through an increased erythropoietin expression via hypoxic action in the kidney. Acai can be expected to improve motility through hematopoiesis.

Acute coronary syndrome (ACS) is a life-threatening condition that requires a prompt diagnosis and therapeutic intervention. Although serum troponin T and creatinine kinase-MB (CK-MB) are established biomarkers for ACS, it may take several hours to reach diagnostic values for ACS. In this study, we attempted to explore novel biomarkers for ACS with higher sensitivity than that of troponin T and CK-MB. The metabolomic profiles of 18 patients with ACS upon hospital arrival and those of the age-matched control (HC) group consisted of 24 healthy volunteers were analyzed using liquid chromatography-time-of-flight mass spectrometry. Volcano plots showed 24 metabolites whose concentrations differed significantly between the ACS and HC groups. Using these data, we developed a multiple logistic regression model for the ACS diagnosis, in which lysine, isocitrate, and tryptophan were selected as minimum-independent metabolites. The area under the receiver operating characteristic curve value for discriminating ACS from HC was 1.00 (95% confidence interval [CI]: 1.00-1.00). In contrast, those for troponin T and CK-MB were 0.917 (95% confidence interval [CI]: 0.812-1.00) and 0.988 (95% CI: 0.966-1.00), respectively. This study showed the potential of combining three plasma metabolites to discriminate ACS from HC with a higher sensitivity than that of troponin T and CK-MB.

Nanostructured transition metal nitrides (TMNs) have been considered a promising substitute for precious metal catalysts toward ORR due to their multi-electron orbitals, metallic properties, and low cost. To design TMNs catalysts with high catalytic activity toward ORR, the intrinsic features of the influencing factor on the catalytic activity toward ORR of nanostructured TMNs need to be investigated. In the paper, titanium nitride (TiN), zirconium nitride (ZrN), and hafnium nitride (HfN) nanoparticles (NPs) are high-efficiency and one-step synthesized by the direct current arc plasma. TiN, ZrN, and HfN NPs with an oxidation layer are applied as the catalysts of hybrid sodium-air batteries (HSABs). The effect of composition and structure attributes of TMNs on ORR catalysis is defined as follows. (ⅰ) Composition effect. With the increase of the oxygen content, the catalytic ORR capability of TMNs decreases progressively due to the reduction of oxygen adsorption capacity; (ⅱ) Structure effect. The redistribution of the density of states (DOS) of ZrN indicates higher ORR activity than TiN and HfN. HSABs with ZrN exhibit an excellent cyclic stability up to 137 cycles (about 140 h), an outstanding rate performance, and a specific capacity of 2817 mAh·g−1 at 1.0 mA·cm−2.

Immunoglobulin G (IgG) adopts a modular multidomain structure that mediates antigen recognition and effector functions, such as complement-dependent cytotoxicity. IgG molecules are self-assembled into a hexameric ring on antigen-containing membranes, recruiting the complement component, C1q. To provide deeper insights into the initial step of the complement pathway, we report a high-speed atomic force microscopy study for quantitative visualization of the interaction between IgG and the C1 complex composed of C1q, C1r, and C1s. Results showed that C1q in the C1 complex is restricted regarding internal motion and has a stronger binding affinity for on-membrane IgG assemblages than C1q alone, presumably because of smaller conformational entropy loss upon binding. Furthermore, we visualized a 1:1 stoichiometric interaction between C1/C1q and an IgG variant that lacks the entire CH1 domain in the absence of antigen. In addition to the canonical C1q-binding site on Fc, their interactions are mediated through a secondary site on the CL domain that is cryptic in the presence of the CH1 domain. Our findings offer clues for novel-modality therapeutic antibodies.

Insufficient oral ridge tissue presents a challenge in the treatment of dental implants. One method to enhance alveolar crest dimensions is guided bone regeneration (GBR); however, existing membranes have certain limitations. To address this issue, we aimed to compare the effectiveness of a resorbable bilayer membrane composed of poly(l-lactic acid) and poly(-caprolactone) （PLACL）with that of a collagen membrane（COL） in a rat GBR model. The rat calvaria was used as an experimental model by placing a plastic cylinder. Forty male Fisher rats underwent surgery, and micro-computed tomography and histomorphometric analyses were performed to assess bone regeneration. The results showed that bone regeneration was similar across all the groups. However, after 24 weeks, the PLACL membrane demonstrated significant resilience, occasional partial degradation, and intermittent air bubble formation. This extended preservation of the barrier effect has great potential to facilitate optimal bone regeneration. In conclusion, this study shows that the PLACL membrane is a promising alternative to GBR. By providing a durable barrier and supporting bone regeneration over an extended period, this resorbable bilayer membrane may address the limitations of the current membranes. Further studies and clinical trials are warranted to validate the efficacy and safety of this drug in humans.

The Seven Country study showed that traditional Japanese diet and Mediterranean diets are protective against cardiovascular diseases (CVDs). Japanese diet is considered the healthiest because it provides highest longevity and health to Japanese. DASH diet and Mediterranean style diets are also considered the healthy diets, although, it is possible that Indo-Mediterranean style diet may provide better protective effects among patients with CVDs, compared to other diets. The concept of Indo-Mediterranean type of diets was developed, after examining its role in the prevention of CVDs in India, the value of which was confirmed by a landmark study from France; The Lyon Heart Study. These workers found that eating alpha-linolenic acid rich Mediterranean style diet can cause significant decline in CVDs and all-cause mortality. Later on in 2018, PREDIMED Study from Spain also reported that a modified Mediterranean style diet can cause significant decline in CVDs, type 2 diabetes mellitus (T2DM) and cancer. The Indo-Mediterranean diet may be superior to DASH diet and Mediterranean diet because it contains millets, porridge, beans and spices; turmeric, cumin, fenugreek and coriander which may have better anti-inflammatory and cardio-protective effects. These foods are rich sources of nutrients; flavonoids, calcium and iron as well as proteins which are useful in the prevention of under as well as over-nutrition and related diseases. It is known that DASH diet and Mediterranean style diets have similar influence on CVDs. However, Indo-Mediterranean style diet, may be as good as Japanese diet, due to improved food diversity and high content of antioxidants in the diets.

The contactless coalescence of a droplet is of paramount importance for physical and industrial applications. This paper describes a coalescence method in mid-air via acoustic levitation using an ultrasonic phased array system. Acoustic levitation using ultrasonic phased arrays provides promising lab-on-a-drop applications, such as transportation, coalescence, mixing, separation, evaporation, and extraction in a continuous operation. The mechanism of droplet coalescence in mid-air may be better understood by experimentally and numerically exploring the droplet dynamics immediately before the coalescence. In this study, water droplets were experimentally levitated, transported, and coalesced by controlling acoustic fields. We observed that the edge of droplets deformed and attracted each other immediately before the coalescence. Through image processing, the radii of curvature of the droplets were quantified and the pressure difference between the inside and outside the droplet was simulated to obtain the pressure and velocity information on the droplet surface. The results revealed that the sound pressure acting on the droplet clearly decreased before the impact of the droplets. This pressure on the droplets was quantitatively analyzed from the experimental data. Our experimental and numerical results provide deeper physical insights into contactless droplet manipulation for futuristic lab-on-a-drop applications.

A tabletop system can facilitate multi-user collaboration in a variety of settings including small meetings, group work, and education and training exercises. The ability of identifying the users touching the table and their positions can promote collaborative work among participants, so methods have been studied that involve the attaching of sensors to the table or chairs or to the users themselves. An effective method of recognizing user actions without placing a burden on the user would be some type of visual process, so the development of a method that processes multi-touch gestures by visual means is desired. This paper describes the development of a multi-touch tabletop system using infrared image recognition for user position identification and presents the results of touch-gesture recognition experiments and a system usability evaluation. Using an FTIR touch panel and infrared light, this system picks up the shadow area of the user’s hand by infrared camera in relation to user touch operations and estimates user position by image recognition. The multi-touch gestures prepared for this system include an operation to change the direction of an object to face the user and a copy operation in which two users generate duplicates of an object. The average recognition rate of the change-direction gesture and copy gesture were found to be 96% and 85%, respectively. In addition, the system usability evaluation revealed that prior learning was easy and that system operations could be easily performed.

Aedes aegypti is inherently susceptible to arboviruses. The geographical expansion of this vector host species has led to the persistence of Dengue, Zika and Chikungunya human infections. These viruses take advantage of the mosquito’s cell to create an environment conducive for their growth. Arboviral infection triggers transcriptomic and protein dysregulation in Ae. aegypti and in effect, host antiviral mechanisms are compromised. Currently, there are no existing vaccines able to protect human hosts from these infections and thus, vector control strategies such as Wolbachia mass release program is regarded as a viable option. Considerable evidence demonstrates how the presence of Wolbachia interferes with arboviruses by decreasing cellular components vital for the pathogen and strengthening antiviral host responses. However, variation in the magnitude of Wolbachia’s viral inhibition that is neither due to strain nor density has been observed. Furthermore, the cellular mechanisms involved in the endosymbiont’s pathogen-blocking differs among hosts. This prompts the need to explore the cellular interactions between Ae. aegypti-arboviruses-Wolbachia and how these interactions overall affect the mosquito’s cell. Understanding what happens at the cellular and molecular level will provide evidence on the sustainability of Wolbachia vector control.

High-grade gliomas present a significant challenge in neuro-oncology because of their aggressive nature and resistance to current therapies. Boron neutron capture therapy (BNCT) is a potential treatment method; however, the boron carrier compounds used — such as 4-borono-L-phenylalanine (L-BPA) — have limitations. This study evaluated the use of boron-conjugated 4-iodophenylbutanamide (BC-IP), a novel boron compound in BNCT, for the treatment of glioma. Using in vitro drug exposure experiments and in vivo studies, we compared BC-IP and BPA, with a focus on boron uptake and retention characteristics. The results showed that although BC-IP had a lower boron uptake than BPA, it exhibited superior retention. Furthermore, despite lower boron accumulation in tumors, BC-IP showed significant survival improvement in glioma-bearing rats compared to controls. These results suggest that BC-IP, with its unique properties, may be an alternative boron carrier for BNCT. Further research is required to optimize this potential treatment modality, which could significantly contribute to advancing the treatment of high-grade gliomas.

Parkinson’s disease (PD) is an aging-related and the second most common neurodegenerative disease after Alzheimer’s disease. The main symptoms of PD are movement disorders accompanied with deficiency of neurotransmitter dopamine (DA) in the striatum due to cell death of the nigro-striatal DA neurons. Two main histopathological hallmarks exist in PD: cytosolic inclusion bodies termed Lewy bodies that mainly consist of α-synuclein protein, the oligomers of which produced by misfolding are regarded to be neurotoxic, causing DA cell death; and black pigments termed neuromelanin (NM) that are contained in DA neurons and markedly decrease in PD. Synthesis of human NM is regarded to be similar to that of melanin in melanocytes; Melanin synthesis in skin is via DOPAquinone (DQ) by tyrosinase, whereas NM synthesis in DA neurons is via DAquinone (DAQ) by tyrosine hydroxylase (TH) and aromatic L-amino acid decarboxylase (AADC). DA in cytoplasm is highly reactive and is assumed to be oxidized spontaneously or by an unidentified tyrosinase to DAQ and then synthesized to NM. Intracellular NM accumulation above a specific threshold was reported to be associated to DA neuron death and PD phenotypes. This review reports recent progress in biosynthesis and pathophysiology of NM in PD.

Multichannel EEGs were obtained from healthy participants in the eyes-closed no-task condition (where the alpha component is typically abolished). EEG dynamics in the two conditions were quantified with two related binary Lempel-Ziv measures of the first principal component and with three measures of integrated information including the more recently proposed integrated synergy. Both integrated information and integrated synergy with model order p=1 had greater values in the eyes closed condition. If the model order of integrated synergy was determined with the Bayesian Information Criterion, this pattern was reversed, and in common with other measures, integrated synergy was greater in the eyes open condition. Eyes open versus eyes closed separation was quantified by calculation of the between-condition effect size. Lempel-Ziv complexity of the first principal component showed greater separation than the measures of integrated information. The performance of the integrated information measures investigated here when distinguishing between indisputably different physiological states encourages caution when advocating for their use as measures of consciousness.

In this paper, a novel pendulum-type accelerometer based on hetero-core fiber optics has been proposed for structural health monitoring targeting large-scale civil infrastructures. Vibration measurement is a non-destructive method for diagnosing the failure of structures by assessing natural frequencies and other vibration patterns. The hetero-core fiber optic sensor utilized in the proposed accelerometer can serve as a displacement sensor with robustness to temperature changes in addition to immunity to electromagnetic interference and chemical corrosions. Thus the hetero-core sensor inside the accelerometer measures applied acceleration by detecting the rotation of an internal pendulum. A series of experiments showed that the hetero-core fiber sensor linearly responded to the rotation angle of the pendulum ranging within ±5°, and furthermore the proposed accelerometer could reproduce the waveform of input vibration in a frequency band of several Hz order.

The power-generation capacity of grid-connected photovoltaic (PV) power systems is increasing. As output power forecasting is required by electricity market participants and utility operators for the stable operation of power systems, several methods have been proposed using physical and statistical approaches for various time ranges. A short-term (30 min ahead) forecasting method has been previously proposed by our laboratory for geographically distributed PV systems using motion estimation. This study focuses on an important parameter for estimating the proposed motion and optimizing the parameter. This parameter is important because it is associated with the smoothness of the vector field, which is the result of motion estimation and influences the forecasting accuracy. In the periods with drastic power output changes, the evaluation was conducted on 101 PV systems located within a circle of 15-km radius in the Kanto region of Japan. The results indicate that the absolute mean error of the proposed method with the optimized parameter is 10.3%, whereas that of the persistent prediction method is 23.7%. Therefore, the proposed method is effective in forecasting for periods when PV output changes drastically in a short time.

After screening nearly 1000 synthetic peptides, a synthetic peptide termed JAL-AK22 (KYEGHWYPEKPYKGSGFRCIHI) derived from the BoxA domain in Tob1 protein was found to activate both unfolded and folded proMMP-7. In addition, JAL-AK22 showed auto-proteolytic activity. Interestingly, the smaller derivative of JAL-AK22 termed JAL-TA9 (YKGSGFRMI) also possessed auto-proteolytic activity and cleaved 2 fragment peptides (MMP18-33 and MMP18-40) derived from the prodomain of proMMP-7 under physiological conditions. These proteolytic activities were inhibited by AEBSF, a serine protease inhibitor. Our results demonstrate that a small synthetic peptide consisting of only 9 amino acids has serine protease-like activity and activates proMMP-7 by cleaving the prodomain region. We thus propose calling small peptides possessing with protease-like activity Catalytides (catalytic peptides). We expect that our findings will stimulate the development of novel Catalytides and related applications.

AIM Non-alcoholic　fatty liver disease (NAFLD) is the most common cause of chronic liver disease. Pemafibrate, a selective peroxisome proliferator-activated receptor α modulator (SPPARMα), has been reported to ameliorate liver function among patients with dyslipidemia. However, there are not many reports of the clinical effects of the pemafibrate. This study aims to summarize the experience of using pemafibrate and analyze the effects on liver function in patients with dyslipidemia. METHODS One hundred twelve cases of hyperlipidemia receiving pemafibrate 0.2 mg/day were retrospectively enrolled in this study. Age, gender, BMI, complications, concomitant medications, serum parameters (TG, HDL-C, LDL-C, AST, ALT, γGTP, ALP, platelets, M2BPGi, Cre, eGFR, HbA1c, blood glucose level at any time) were investigated and evaluated. RESULTS Pemafibrate administration significantly improved serum TG and HDL-C, but not in LDL-C. Serum AST, ALT, γGTP, and ALP were also significantly improved. The fib-4 index, a liver fibrosis score, did not change significantly, but M2-BPGi, an index of fibrosis, decreased significantly. No correlation was observed between each lipid parameter and ALT, and ALT decreased independently of the lipid parameters. Conclusions As we expected, pemafibrate demonstrated a lipid-improving effect without adversely affecting hepatic and renal functions. An unexpected finding was the decrease in ALT that was independent of lipid parameters.

Children's screen time may affect their growth and development. However, different aspects of children and their parents that affect children's screen time has not been investigated in the Japanese context. This study aimed to explore the relationship between relevant factors affecting children's screen time based on their sleep, difficulties, and parental control, among Japanese elementary and junior high school students. A cross-sectional survey was conducted among parents in Japan. Data on screen time duration, parent-child background, strengths and difficulties, sleep variables, and parental control types were collected from 225 households. Path analysis revealed that high Strengths and Difficulties Questionnaire (SDQ) scores (β = 0.167, p = 0.007), sleep duration (β = -0.282, p < 0.001), and parental control (β = -0.205, p < 0.001) were significantly related to children's screen time. Additionally, late parental bedtime negatively correlated with children's sleep duration (β = -0.326, p < 0.001). The findings suggest that children's difficulties, sleep duration, and parental control are associated with children's screen time. This study, together with previous research, provides comprehensive insights to design interventions to decrease screen time in children in the Japanese context.

Heme proteins serve diverse and pivotal biological functions. Therefore, clarifying the mechanisms of these diverse functions of heme is a crucial scientific topic. Distortion of heme porphyrin is one of the key factors regulating the chemical properties of heme. Here, we constructed convolutional neural network models for predicting heme distortion from the tertiary structure of the heme-binding pocket to examine their correlation. For saddling, ruffling, doming, and waving distortions, the experimental structure and predicted values were closely correlated. Furthermore, we assessed the correlation between the cavity shape and molecular structure of heme and demonstrated that hemes in protein pockets with similar structures exhibit near-identical structures, indicating the regulation of heme distortion through the protein environment. These findings indicate that the tertiary structure of the heme-binding pocket regulates the distortion of heme porphyrin, thereby controlling the chemical properties of heme relevant to the protein function; this implies a structure–function correlation in heme proteins.

Quality-of-life (QOL) is important for cancer patients with poor prognosis. However, QOL survey is difficult using patients. We created cancer scenarios and investigated QOL utility values among the general public using vignette-based methods. On the other hand, some scenarios may have been difficult for the general public to image and understand. Therefore, we conducted a QOL survey among physicians. This survey was conducted by interviewing physicians adminis-tering chemotherapy to patients for recurrent/metastatic pancreatic cancer. Responses were eval-uated using Composite Time Trade-Off (cTTO) and Visual Analog Scale (VAS) for 11 pancreatic cancer status scenarios to be evaluated (survey scenarios). Survey scenarios consisted of health state, type and Grade of adverse events. Health status was classified into two categories: Stable disease (SD) and Progressive disease (PD). Twenty responders answered in this survey, however two responses were excluded because of inconsistent responses. The stable disease had the highest QOL value for both assessment method. Whereas progression disease (PD) had the lowest QOL value. The physicians scored higher QOL values on VAS and cTTO than the general public in all survey scenarios. The QOL values obtained by physicians were consistent with the degree of sta-tus in any assessment scenarios.

Coronavirus disease 2019 (COVID-19) affected not only individuals but also families. The purpose of this study was to clarify the temporal changes in the impact of the COVID-19 pandemic on entire families with older adults susceptible to infection living on small islands in Japan over the duration of the pandemic. Family ethnographic research was conducted from 2021 to 2023, using the Concentric Sphere Family Environment Theory as the theoretical framework. Formal interviews were conducted with 20 families. In addition, data from informal interviews, participant observation and other sources were compiled into field notes. All data on the impact on the entire family were extracted and content analysis was conducted. Five categories and a total of 85 subcategories were extracted. The results show that COVID-19 exerted not only negative but also positive impacts on the entire family, and their temporal changes are clarified. The impact on families is believed to have been influenced by the family external environment, such as increases and decreases of infection cases or events that occurred outside the family. The knowledge acquired from these studies will help healthcare professionals in providing appropriate family support.

Impact load was applied to hardened cement paste (HCP) specimens using a gas gun to investigate microscopic changes in the specimens and develop a better response model of concrete subjected to impact load. Plasma emission was observed at the moment of impact at 420 m/s and the colour of the portion near the impact point turned brighter. This brighter portion was analysed, and it was observed that the pore structure was coarser compared to the other portion; however, the results of thermogravimetry and X-ray diffraction analysis were similar. A possible reason is that the generated heat was instantaneous and the rate of the temperature increase in the HCP decreased due to evaporation of water in the HCP. These results indicate that during impact at a few hundred m/s, porosity increase due to heat effect is more dominant than porosity decrease due to mechanical compaction.

Kaposi’s sarcoma-associated herpesvirus (KSHV) is the etiologic agent of Kaposi’s sarcoma, primary effusion lymphoma (PEL) and multicentric Castleman’s disease. During KSHV lytic infection, lytic-related genes, categorized as immediate-early, early, and late genes, are expressed in a temporal manner. The transcription of late genes requires the virus-specific pre-initiation complex (vPIC), which consists of viral transcription factors. However, the characterization of the protein-protein interactions of the vPIC factors has not been completely elucidated. KSHV ORF18 is one of the vPIC factors, and its interaction with other viral factors has not been sufficiently revealed. Here, we analyzed the interaction between ORF18 and another vPIC factor, ORF30, in living cells using the bimolecular fluorescence complementation (BiFC) assay. We identified four amino-acid residues (Leu29, Gln36, His41 and Trp170) on ORF18 that were responsible for its interaction with ORF30. The artificial intelligence (AI) system AlphaFold2 predicted that identified four residues are exposed to the surface of ORF18 and located in proximity to each other in the surface of ORF18. Thus, AI-predicted model supports the importance of four residues for binding of ORF18 to ORF30. Our results indicated that wet experiments in combination with AI may enhance the structural characterization of vPIC protein-protein interactions.

With the rapid increase in diabetes worldwide, the number of patients with diabetic kidney disease (DKD), a complication of diabetes mellitus, is also on the rise. DKD is a major cause of chronic kidney disease progressing to end-stage renal failure; however, current medical treatments for DKD do not achieve satisfactory outcomes. Molecular hydrogen (H2) is an antioxidant that selectively reduces hydroxyl radicals, a reactive oxygen species with a very potent oxidative capacity. H2 was recently shown to exert not only antioxidant, but also anti-inflammatory, cell lethality-regulating, and signal transduction-regulating effects, and is now being applied clinically. Many factors contribute to the onset and progression of DKD, with mitochondrial dysfunction, oxidative stress, and inflammation being strongly implicated. Recent preclinical and clinical trials reported that substances with antioxidant properties may slow the progression of DKD. Therefore, we conducted a literature review on animal models and human clinical trials in which H2 showed efficacy against various renal diseases. This literature review and our previous findings collectively suggest that H2 exerts therapeutic effects in patients with DKD by improving mitochondrial function. Future large-scale clinical studies are needed to confirm these findings.

The relationship between city size, coastal land use and air temperature rise with distance from coast during summer day is analyzed using the meso-scale Weather Research & Forecasting (WRF) model in five coastal cities in Japan with different sizes and coastal land use (Tokyo, Osaka, Nagoya, Hiroshima and Sendai) and inland cities in Germany (Berlin, Essen and Karlsruhe). Air temperature increased as distance from the coast increased, reached its maximum, and then decreased slightly. In Nagoya and Sendai, the number of urban land use in coastal areas is less than the other three cities, where air temperature is a little lower. As a result, air temperature difference between coastal and inland urban area is small and the curve of air temperature rise is smaller than those in Tokyo and Osaka. In Sendai, air temperature in the inland urban area is the same as in the other cities, but air temperature in the coastal urban area is a little lower than the other cities, due to about one degree lower sea surface temperature influenced by the latitude. In three German cities, the urban boundary layer may not develop sufficiently because the fetch distance is not enough.

Daytime napping offers benefits for motor memory learning and is used as habitual countermeasure to improve daytime functioning. A single napping is shown to ameliorate motor memory learning, although the effect of consecutive napping on motor memory consolidation remains unclear. This study aimed to explore the effect of daytime napping over multiple days on motor memory learning. Twenty university students were divided into the napping group and no-nap (awake) group. Napping group performed motor adaption tasks before and after napping for three consecutive days, whereas no-nap group performed the task on the similar time schedule as the napping group. In addition, a subsequent retest was conducted one week after the end of the intervention. The speed to complete the task of the napping group was significantly shorter than that of the awake group in the retention test. No significant difference was confirmed for trajectory length to complete the task. Thus, consecutive napping may facilitate motor learning and motor memory consolidation in the long term.

INTRODUCTION AND OBJECTIVES: Osteoporosis is a common consequence of androgen deprivation therapy (ADT) for prostate cancer. Up to 20% of men on ADT have suffered from fracture within 5 years. The WHO Fracture Risk Assessment Tool (FRAX) has been utilized to predict the 10-year probability of major osteoporotic and hip fracture. However, no large studies assessing the utility of FRAX with versus without dual-energy X-ray absorptiometry (DEXA) in prostate cancer patients have been performed. We validated the usefulness of FRAX combined with DEXA in men with prostate cancer. METHODS: FRAX was done in a total of 1,220 prostate cancer patients including those who underwent brachytherapy (n=547), radical prostatectomy (n=200), external beam radiation therapy (n=264), hormonal therapy only (n=187), and definitive treatment along with hormonal therapy (n=645) in Yokohama City University Hospital. Of these, 109 patients received DEXA. RESULTS: In men without receiving DEXA, the median (mean ± SD) risks for major osteoporotic and hip fracture were 8.5% (9.3 ± 4.8) and 3.2% (4.2 ± 3.9), respectively. One hundred sixteen (9.5%) and 634 (52.0%) of these patients had the major osteoporotic risk of more than 15% and hip fracture risk of more than 3%, respectively. In contrast, in men with DEXA, the median (mean ± SD) risks for major osteoporotic and hip fracture were 5.3% (5.4 ± 2.1) and 0.85% (1.3 ± 1.2), respectively. Two (0.2%) and 4 (8.0%) of these patients had the major osteoporotic risk of more than 15% and hip fracture risk of more than 3%, respectively [Table1]. In the same cohort who received DEXA, the risks for major osteoporotic (p < 0.001) and hip (p < 0.001) fracture were significantly lower in men with DEXA than in those without DEXA. CONCLUSIONS: Our results suggest that FRAX combined with DEXA might prevent unnecessary osteoporosis medication in prostate cancer patients.

The digital era has significantly amplified the volume of online reviews, presenting both opportunities and challenges in harnessing insights from consumer feedback. Aspect-Based Sentiment Analysis (ABSA) has emerged as a crucial tool for distilling sentiments from these reviews, providing valuable data for enhancing product and service quality. This study introduces an advanced hybrid model, AdvSentiNet, which integrates adversarial training into the state-of-the-art framework to elevate the precision of sentiment detection at the aspect level. By employing an adversarial network, where a generative model competes against a classifier by crafting highly realistic synthetic samples, we aim to bolster the model's resilience against varied data samples. This innovative approach, unexplored in its entirety within the realm of ABSA, demonstrated remarkable performance improvements on benchmark datasets. For instance, accuracy on the SemEval 2015 dataset escalated from 81.7% to 82.5%, and for the SemEval 2016 dataset, it surged from 84.4% to 87.3%.

Structure–function relationships in proteins have been one of the crucial scientific topics. Heme proteins have diverse and pivotal biological functions. Therefore, clarifying their structure–function correlation is significant to understand their functional mechanism and is informative for various fields of science. In this study, we constructed convolutional neural network models for predicting protein functions from the tertiary structures of heme-binding sites (active sites) of heme proteins to examine the structure–function correlation. As a result, we succeeded in the classification of oxygen-binding protein (OB), oxidoreductase (OR), proteins with both functions (OB–OR), and electron transport protein (ET) with high accuracy. Although the misclassification rate for OR and ET was high, the rates between OB and ET and between OB and OR were almost zero, indicating that the prediction model works well between protein groups with very different functions. However, predicting the function of proteins modified with amino acid mutation(s) remains a challenge. Our findings indicate a structure–function correlation in the active site of heme proteins. This study is expected to be applied to the prediction of more detailed protein functions such as catalytic reactions.

DNA origami has emerged in recent years as a powerful technique for designing and building 2D and 3D nanostructures. While the breadth of structures that have been produced is impressive, one of the remaining challenges, especially for DNA origami structures intended to carry out useful biomedical tasks in vivo, is to endow them with the ability to detect and respond to molecules of interest. Target molecules may be disease indicators or cell surface receptors, and the responses may include conformational changes leading to release of therapeutically relevant cargo. Nucleic acid aptamers are ideally suited to this task and are beginning to be used in DNA origami designs. In this review we consider examples of uses of DNA aptamers in DNA origami structures and summarise what is currently understood regarding aptamer-origami integration. We review three major roles for aptamers in such applications: protein immobilisation, triggering of structural transformation, and cell targeting. Finally, we consider future perspectives for DNA aptamer integration with DNA origami.

Contrast-enhanced ultrasonography (CEUS) is useful for evaluation of the hemodynamics of hepatic tumors and surrounding he-patic parenchyma in real time. CEUS with intravenous contrast administration is well established for evaluation of hepatocellular carcinoma (HCC). On the other hand, intra-arterial (transcatheter) CEUS (IAUS) is an emerging technique that allows more selective evaluation of the arterial supply to the tumor. IAUS was performed by administration of Sonazoid® through the microcatheter and imaging of the area of the target lesion with a dedicated, contrast-specific technique. Sonazoid® (0.5 ml diluted with 49.5 ml of distilled water) was used as the contrast medium in IAUS. The diluted Sonazoid® was introduced into the feeding artery by in-termittent injection of 0.3-1.0 ml through a microcatheter placed in the artery and flushing with saline at the same flow rate. We report the three cases in which IAUS was useful in transarterial chemoembolization (TACE) for HCC. Two cases were performed TACE for hepatic metastasis. In any cases, plain computed tomography (CT) after TACE showed accumulation of Lipiodol® only in the metastases. One case was suspected having HCC rupture and urgent abdominal angiography was performed. IAUS was performed frequently to reduce the amount of iodinated contrast agent as much as possible because of renal failure. Concomitant use of IAUS enabled reduction of the amount of contrast agent.

Ultrasound has become widely used as a mean to measure the rectus femoris muscle in the acute and chronic phase of critical illness. Despite its noninvasiveness and accessibility, its accuracy highly depends on the skills of the technician. However, few ultrasound phantoms for the confirmation of its accuracy or to improve technical skills exist. In this study, we created a novel phantom model and used it for investigating the accuracy of measurements and for training. Study 1 investigated how various conditions affect ultrasound measurements such as thickness, cross-sectional area, and echogenicity. Study 2 investigated if the phantom can be used for training of various health care providers in vitro and vivo. Study 1 showed that thickness, cross-sectional area, and echogenicity were affected by probe compression strength, probe angle, phantom compression, and varying equipment. Study 2 in vitro showed that using the phantom for training improved the accuracy of the measurements taken within phantom, and Study 2 in vivo showed the phantom training had a short-term effect on improving the measurement accuracy in a human volunteer. The new ultrasound phantom model revealed that various conditions affected ultrasound measurements, and phantom training improved the measurement accuracy.

Mesenchymal stem cells (MSCs) have the tumor-homing capacity, and therefore MSCs are considered to be a promising drug delivery carrier for cancer therapy. To maintain the viability and activity of MSCs, anti-cancer drugs are preferably modified on the surface of MSCs, rather than directly introduced into MSCs. In this study, we attempted to construct surface-modified MSCs with liposomes as a drug carrier by using magnetic anionic liposome/atelocollagen complexes we previously developed. We observed that large-sized magnetic anionic liposome/atelocollagen complexes were abundantly associated with MSCs via electrostatic interactions under a magnetic field, and its cellular internalization was lower than that of the small-sized complexes. Moreover, the complexes with higher atelocollagen concentration showed lower cellular internalization than the complexes with lower atelocollagen concentration. Based on these results, we succeeded in the efficient surface modification of MSCs with liposome by using large-sized magnetic anionic liposomes complexed with high concentration of atelocollagen. The constructed liposome-modified MSCs showed comparable proliferation rate and differentiation potential to unmodified MSCs. Furthermore, liposome-modified MSCs efficiently adhered to vascular endothelial cells and migrated toward the conditioned medium from cancer cells in vitro. These findings suggest that liposome-modified MSCs could serve as an efficient cell-based drug carrier for tumor targeted delivery.

Utilization of wasted heat instead of fuel combustion is effective to reduce primary energy consumption for mitigating global warming problem. Because wasted heat sources are not necessarily located close to areas of heat demand, one of the difficulties is that wasted heat has to be transferred from heat source side to heat demand side, which may require heat transportation over long distance. From this point we proposed and have examined new idea of heat transportation using ammonia-water as the working fluid which system is named Solution Transportation Absorption chiller, in short STA. Our previous studies of STA were mainly the experimental investigation with STA facility which cooling power was 25RT (90kW). As a result, the COP of STA was found almost same value 0.65 with the conventional absorption chiller without depending on the transportation distances. The simulation using AspenHYSYS also examined with same experimental condition. The experimental data showed good agreement with the simulation calculation. In this study, we examined the large-scale cooling power STA on simulation. The examination cooling powers were from 90 kW(25RT) to 3517 kW(1000RT). All cooling power achieved around COP 0.64 including pump power consumptions. In addition, we performed the dynamic simulation. As the results, there was no effect of pipeline size on the cooling capacities and mass flow rates. Furthermore, the stability time of the cooling capacities and mass flow rates were almost same regardless of the pipeline size and cooling capacity. In other words, STA may be achieved the same COP even though having various complex conditions compared with the conventional absorption chiller.

Food allergies are common worldwide and have become a major public health concern; more than 220 million people are estimated to suffer from food allergies worldwide. On the other hand, polyphenols, phenolic substances found in plants, have attracted attention for their health-promoting functions, including their anti-allergic effects. In this study, we examined the potential inhibitory effects of 80% ethanol extracts from 22 different vegetables on the degranulation process in RBL-2H3 cells. Our aim was to identify vegetables that could prevent and treat type I allergic diseases. We found strong inhibition of degranulation by the extracts of perilla and chives. Furthermore, we verified the respective efficacy via animal experiments, which revealed that the anaphylactic symptoms caused by ovalbumin (OVA) load were alleviated in OVA allergy model mice that ingested vegetable extracts of perilla and chives. These phenomena were suggested to be caused by induction of suppression in the expression of subunits that constitute the high-affinity IgE receptor, particularly the α-chain of FcεR I. Notably, the anti-allergic effects of vegetables that can be consumed daily are expected to result in the discovery of new anti-immediate allergenic drugs based on the components of these vegetables.

We investigated humoral immune responses in 222 unvaccinated Japanese people after recovery from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in 2021. Anti-spike protein IgG antibody levels and neutralizing antibody titers were measured in serum samples obtained within 20–180 days after diagnosis. The geometric mean of antibody titers was 1555 ELU/mL (95% confidence interval [CI] = 1257-1923), and the neutralizing activities (50% inhibitory dilution) was 253 (95% CI = 204-313). The antibody titer and neutralizing activity both increased with increasing disease severity, and both values were approximately 4-fold higher for hospitalized patients than for non-hospitalized patients. However, these differences were smaller in older patients. The humoral immune response, which increased with increasing disease severity, gradually decreased over time after SARS-CoV-2 infection. Most patients with mild or moderate symptoms sustained neutralizing activity for up to 180 days after the infection, the decay of the neutralizing activity in the patients with asymptomatic was rather faster than other groups. 11.7% (26/222) of patients had very low neutralizing activity, and half of these were in the age of 20s. Our study results show the importance of measuring the neutralizing activity to confirm the immune status and also estimate the timing of vaccine.

We evaluated the change in water dispersibility of lactic acid bacteria (LAB, Enterococcus faecalis KH2) upon powderization and its influence on their efficacy. When cultured LAB are washed, heat-killed, and powdered, adhesion between LAB occurs and they form aggregation (non-treated LAB, n-LAB). However, a dispersed LAB (d-LAB) powder with less aggregates can be prepared by treating them with a high-pressure homogenizer and adding an excipient during powdering. n-LAB or d-LAB was administered to mice and the Peyer's patches in the small intestine were observed. n-LAB administration showed a high amount of aggregated LAB drifting in the intestinal mucosa, whereas d-LAB reached the Peyer's patches and was taken up into the Peyer's patches. Evaluation in a mouse influenza virus infection model showed that d-LAB was more effective than n-LAB in influenza yield of bronchoalveolar lavage fluids (BALFs) on day 3 post-infection, neutralizing antibody titers of sera and influenza virus-specific IgA in the feces on day 14 post-infection. Thus, the physical properties of LAB affect their efficacy; controlling their water dispersibility can improve their effectiveness.

This paper deals with the possibility for construction of the database on friction coefficient on the actual roads from the viewpoint of traffic safety. A measurement algorithm is determined in order to construct road friction measuring device. Next, the tires used for measurement are selected and the characteristics are measured using bench tire characteristic tester, and the measuring device is designed and constructed based on the characteristics. Finally, using this device, the measurement results of the road friction characteristics for two types of road surfaces are shown.

Background; Programmed death-1 (PD-1) and PD-1 ligand 1 (PD-L1) are target molecules for immunotherapy in non-small cell lung cancer. PD-L1 is expressed not only in cancer cells, but also on macrophages, and has been suggested to contribute to macrophage-mediated immune suppression. Methods; Clinical significance of PD-L1 expression on macrophages in human lung adenocarcinoma was examined. The mechanisms of PD-L1 overexpression on macrophages were investigated by means of cell culture studies. Results; High PD-L1 expression on macrophages was correlated with the presence of EGFR mutation, a lower cancer grade, and a shorter cancer-specific overall survival. In an in vitro study using lung cancer cell lines and human monocyte-derived macrophages, the conditioned medium from cancer cells was found to up-regulate PD-L1 expression on macrophages via STAT3 activation, and a cytokine array revealed that granulocyte-macrophage colony-stimulating factor (GM-CSF) was a candidate factor that induced PD-L1 expression. Culture studies using recombinant GM-CSF, neutralizing antibody, and inhibitors indicated that PD-L1 overexpression was induced via STAT3 activation by GM-CSF derived from cancer cells. Conclusions; PD-L1 overexpression on macrophages via the GM-CSF/STAT3 pathway was suggested to promote cancer progression in lung adenocarcinoma. Cancer cell-derived GM-CSF might be a promising target for anti-cancer therapy.

Ethyl loflazepate (EL) is a benzodiazepine derivative that has been reported to activate the gustatory cortex. Our department routinely uses EL as a first-line treatment for idiopathic and psychogenic taste disorders, although little has been reported in the literature with respect to patient outcomes, so we conducted a retrospective study examining its safety and efficacy. Between 2008 and 2020, 49 patients (14 males and 35 females; mean age, 62.1 years) were diagnosed with taste disorders and received EL as their only treatment for &gt;14 days. Severity of taste disorder was evaluated using the paper disc method by Sakai et al [7], and treatment efficacy was evaluated using the Visual Analogue Scale, wherein patients gave subjective ratings for their symptoms (reductions by &gt;50% after administration of EL for 4 weeks were defined as mprovements). Results showed that the improvement rates for patients with idiopathic and psychogenic taste disorders were 55% and 70%, respectively. Additionally, the majority (78%) improved within 2 weeks, and side effects were mild (seven cases of sleepiness and one case of dizziness). We conclude that EL is an appropriate first-line medication for patients with idiopathic and psychogenic taste disorders.

Purinergic receptors (P2X) are ATP-gated ion channels with an elusive role in the CNS. While the P2X2 and P2X4 subtypes are widely expressed in most neurons (i.e. at the edge of the postsynaptic densities of excitatory synapses), the direct contribution of P2X to synaptic transmission is uncertain. Several P2X have been shown to participate in receptor cross-talk: an interaction where one receptor (e.g. P2X2) influences the activity of another (e.g. GABA or AMPA receptors.) In this study, we tested for interactions between P2X2 or P2X4 and N-methyl-D-aspartate receptors (NMDARs). Using two-electrode voltage-clamp electrophysiology experiments in X. laevis oocytes, we demonstrate that both P2X2 and P2X4 interact with NMDARs in an inhibitory manner. When investigating the molecular domains responsible for this phenomenon, we found that the P2X2 c-terminus (CT) could interfere with P2X2 and P2X4 interactions with NMDARs. We also report that 11 distal CT residues on the P2X4 facilitate the P2X4-NMDAR interaction, and that a peptide consisting of these P2X4 CT residues (11C) can disrupt the interaction between NMDARs and P2X2 or P2X4. Collectively, these results provide new evidence for the modulatory nature of P2X2 and P2X4, suggesting they might play a more nuanced role in the CNS.

This research program investigated the effects of layer thickness (50 and 100 microns) on the microstructure and mechanical properties of electron beam powder bed fusion (EBPBF) additive manufacturing of Inconel 625 alloy. The as-built 50 and 100 micron layer thickness components were also heat treated at temperatures above 1100 oC, which produced a recrystallized grain structure containing annealing twins in the 50 micron layer thickness components, and a duplex grain structure consisting of islands of very small equiaxed grains dispersed in a recrystallized, large-grain structure containing annealing twins. The heat treated component microstructures and mechanical properties were compared with the as-built components in both the build direction (vertical) and perpendicular (horizontal) to the build direction. Vickers microindentation hardness (HV) values for the vertical and horizontal geometries averaged 227 and 220 for the as-built 50 and 100 micron layer components, and 185 and 282 for the corresponding heat treated components. The yield stress values were 387 MPa and 365 MPa for the as-built layer horizontal and vertical 50 micron layer geometries, and 330 MPa and 340 MPa for the as-built 100 micron layer components. For the heat treated 50 micron components, the yield stress values were 340 and 321 MPa for the horizontal and vertical geometries, and 581 and 489 MPa for the 100 micron layer components, respectively. The elongation for the 100 micron layer as-built horizontal components was 28% in contrast to 65% for the corresponding 100 micron heat treated layer components, an increase of 132% for the duplex grain structure. However, the coarse grains containing annealing twins and the equiaxed small grain islands in the duplex structure for the heat treated components contained continuous carbides in the grain boundaries, and this may indicate sensitization and a reduction in corrosion resistance. These findings point to the potential mechanical property advantage for heat treatment of Inconel 625 alloy 100 micron layer thickness components fabricated by EBPBF.

Aim: The aim of this study was to estimate the number of nurses who independently care for pa-tients with severe respiratory failure receiving mechanical ventilation (MV) or veno-venous ex-tracorporeal membrane oxygenation (VV-ECMO). Additionally, the study analyzed the actual role of nurses in the treatment of patients with MV and VV-ECMO. Methods: We conducted a cross-sectional study using postal surveys. The study included 725 Japanese intensive care units (ICUs). Descriptive statistics were conducted. Results: Among the 725 ICUs, we obtained 302 re-sponses (41.7%) and analyzed 282 responses. The median number of nurses per bed was 3.25. The median proportion of nurses who independently cared for patients with MV was 60% [IQR: 42.3-77.3]. The median proportion of nurses who independently cared for patients with VV-ECMO was 46.9 (35.7-63.3%) in the ICU experiencing VV-ECMO use. Concerning task-sharing, 33.8% of ICUs and nurses did not facilitate weaning from MV. Nurses always ti-trated sedatives in 44.5% of ICUs. Conclusion: Nurse staffing might be inadequate in all ICUs, es-pecially for severe respiratory failure. The proportion of competent nurses for caring for severe respiratory failure in ICUs should be considered when determining the work force of nurses.

With increasing interest in understanding contribution of secondary organic aerosol (SOA) to particulate air pollution in urban areas, an exploratory study was carried out to determine levels of carbonaceous aerosols and polycyclic aromatic hydrocarbons (PAHs) in the City of Kuala Lumpur, Malaysia. PM2.5 samples were collected using a high-volume sampler for 24 h in several areas in Kuala Lumpur during the north-easterly monsoon from January to March 2019. Samples were analysed for water soluble organic carbon (WSOC), organic carbon (OC), elemental carbon (EC) and secondary organic carbon (SOC) in PM2.5 was estimated. Particle-bound PAHs were analysed using gas chromatography-flame ionization detector (GC-FID). Average concentrations of WSOC, OC and EC were 2.7 ± 2.2 (range of 0.63-9.1) µg/m3, 6.9 ± 4.9 (3.1-24.1) µg/m3 and 3.7 ± 1.6 (1.3-6.8) µg/m3, respectively, with estimated average SOC of 2.3 µg/m3, contributing 34% to total OC. The average of total PAHs was 1.8 ± 2.7 ng/m3. Source identification methods revealed natural gas and biomass burning, and urban traffic combustion as dominant sources of PAHs in Kuala Lumpur. To understand human health risk posed by PAHs, a deterministic screening health risk assessment was also conducted for several age groups including infant, toddler, children, adolescent and adult. The total concentration of BaPeq is 3.8 ng/m3, with the average of 0.29 (range of 0.001-1.6) ng/m3. Carcinogenic and non-carcinogenic risk of PAH species were well below the acceptable levels recommended by the USEPA. Future work is needed using long-term monitoring data to understand the origin of PAH contributing to SOA formation and to apply source-risk apportionment to know better the potential risk factors posed by the various sources in urban areas in Kuala Lumpur.

In this study, the friction factor of turbulent pipe flow for dried rice malt extract solutions is reduced experimentally to that of a Newtonian fluid. The friction factor is measured for four types of solutions at different culture times and concentrations. The results indicate that the experimental data points of the test solutions diverge from the maximum drag reduction asymptote at and above Re√f ≅ 200 and align parallel to those of Newtonian fluids. This drag reduction phenomenon differs from that of artificial high molecular polymer solutions. It is classified as a Type B drag reduction phenomenon of biopolymer solutions and fine solid particle suspensions. The order of drag reduction corresponds approximately to that of 5–50 ppm xanthan-gum solutions reported previously. Furthermore, the velocity profile in a turbulent pipe flow was predicted using a semi-theoretical equation, in which the friction factors were determined using the difference between the experimental results of the tested solutions and Newtonian fluids. The results indicate a more considerable thickening of the viscous sublayer in the turbulent pipe flow of the test solutions than that of Newtonian fluids.

The Kanchenjunga Conservation Area (KCA) is a high mountain protected area in eastern Nepal undergoing socio-economic and environmental changes that are unprecedented in the region’s history. In the following paper, we discuss recent changes involving new road construction, climate change, adventure tourism, and the wildlife/forest cover/medicinal plant sectors. Our assessments are based on the collective results of past and recent field research, remote sensing analysis, oral histories, and literature reviews. While similar changes are occurring in mountain protected areas (MPA) throughout Nepal, it is suggested that the KCA differs from other regions in that it still retains the option of conducting detailed feasibility, environmental, and impact assessments prior to the implementation of major change-associated projects, particularly the construction of roads. In turn, the KCA might avoid many of the environmental, social, and economic problems experienced elsewhere in Nepal, while enhancing its status, income-generating capacities, and sustainability as a global destination for adventure, nature, and cultural tourism.

Purpose: To examine the effectiveness of patterned laser trabeculoplasty (PSLT) as an additional treatment for patients of open-angle glaucoma (OAG) receiving maximized ocular hypotensive medications (OHM). Methods: Forty eyes of 33 patients (average age 72.7±10.7 years) who had not previously undergone open glaucoma surgery or laser trabeculoplasty and were treated with maximized OHM between June 2018 and March 2022 were included. A 360-degree PSLT was conducted and postoperative intraocular pressure (IOP) and survival curves at 1, 3, 6, 9, and 12 months were evaluated. Results: According to the Kaplan-Meier survival analysis, the average survival time was 8.1 months with death defined as postoperative IOP reduction of less than 10% or requiring additional treatment. The average survival time was 4.9 months with death defined as postoperative IOP reduction of less than 20% or requiring additional treatment. In the 31 eyes which received no additional treatment after PSLT, the mean preoperative IOP was 18.5±3.9 mmHg, which reduced to 15.3±4.1 mmHg (p=1.62 x 10-6)), 15.5±3.4 mmHg (p=1.51 x 10-5), 15.7±4.0 mmHg (p=1.75 x 10-5), 14.7±4.38 (p=2.89 x 10-6), and 15.0±4.0 mmHg (p=5.74 x 10-9) at 1, 3, 6, 9 and 12 months after PSLT, respectively. The IOP reduction rate one year after PSLT was 18.7%. Thirteen of the 31 eyes (42%) achieved a 20% reduction in IOP compared to the baseline. Conclusion: Adjunctive treatment with PSLT in OAG patients receiving maximized OHM may be effective over 12-months of follow-up.

Abstract: Background and Objectives: Holter-based late potentials (LPs) are useful for predicting lethal arrhythmias in organic cardiac diseases. Although Holter-based LPs exhibit diurnal varia-tion, no studies have evaluated the optimal timing of LP measurement over 24 h for predicting lethal arrhythmia that leads to sudden cardiac death. Thus, this study aimed to validate the most effective timing for Holter-based LP testing and to explore factors influencing diurnal variability of LP parameters. Materials and Methods: We retrospectively analyzed 126 patients with post-myocardial infarction (MI) status and 60 control participants who underwent high-resolution Holter electrocardiography. Among the 126 post-MI patients, 23 developed sustained ventricular tachycardia (VT) (the MI-VT group), while 103 did not (the MI-non-VT group) during the obser-vation period. Holter-based LPs were measured at 0:00, 4:00, 8:00, 12:00, 16:00, and 20:00, and heart rate variability analysis was simultaneously performed to investigate factors influencing diurnal variability of LP parameters. Results: Holter-based LP parameters showed diurnal variation with significant deterioration at night and improvement during the day. Assessment at the time with the longest duration of low-amplitude signals <40 μV in the filtered QRS complex terminus (LAS40) gave the highest receiver operating characteristics curve (area under the curve, 0.659) and the highest odds ratio (3.75; 95% confidence interval, 1.45–9.71; p=0.006) for predicting VT. In the multiple regression analysis, heart rate and noise were significant factors affecting LP parameters in the MI-VT and control groups. In the non-VT group, LP parameters were significantly influenced by noise and parasympathetic heart rate variability parameters such as logPNN50. Conclusions: For Holter-based LP measurements, test accuracy was higher when LP was measured at the time of the highest or worst value of LAS40. Changes in autonomic nervous system activity, including heart rate and noise levels, were factors influencing diurnal variability.

Chemotherapy for lung cancer has made remarkable progress, and its selection has been subdivided by genetic analysis. Although response evaluation criteria in solid tumors (RECIST) is a simple and highly objective evaluation method, it has been pointed out that it has the disadvantage of not being able to accurately evaluate the therapeutic effect of molecularly targeted drugs and immune checkpoint inhibitors. The purpose of this study is to determine whether quantitative evaluation of DWIBS is useful in determining the effectiveness of treatment for lung cancer. There were 31 patients with lung cancer and 56 patterns were obtained. First, the determination of treatment effect (PD, SD, PR) based on RECIST was performed on CT. Second, tDV and ADC (median) were measured using BD score from DWI images taken at the same time, and the rate of change was calculated. Then, we compared and examined the correlation between RECIST and the rate of change in tDV. There were correlations between RECIST and the rate of change in tDV in PD and PR cases respectively. Compared RECIST on CT, DWIBS using BD score would be more accurate for response evaluation of treatment. There was a tendency that tDV decreased with increasing ADC values, but some of the cases had a dissociated response with increasing ADC values and increasing tDV. Thus, since the color display of ADC values allows us to infer their contents, it would be useful for the evaluation of cases such as dissociated response and pseudoprogression, which are suspected to be atypical responses that are difficult to evaluate with RECIST and other methods.

Over a century ago, low-dose-rate (LDR) brachytherapy was introduced to treat prostate cancer (PCa). Since then, it has been widely applied worldwide, including in East Asia. LDR brachythera-py has been performed in 88 institutes in Japan. Beneficial clinical outcomes of LDR brachytherapy for intermediate-to-high-risk PCa have been demonstrated in large clinical trials. These clinical outcomes were achieved through advances in methods, such as urological precise needle puncture and seed placement, and the quantitative decision-making regarding radiological parameters by radiation oncologists. Combined use of LDR brachytherapy with other therapeutical modalities, such as external beam radiation and androgen deprivation therapy, for clinical risk classification of PCa has led to better anticancer treatment efficacy. In this study, we summarized basic LDR brachytherapy findings that should remain unchanged and be passed down in urology depart-ments. We also discussed the applications of LDR brachytherapy for PCa in various clinical settings, including focal and salvage therapies. In addition, we highlighted technologies associated with brachytherapy that are under development.

Tertiary lymphoid structures (TLSs) have become the focus of antitumor immunity. However, the prognostic significance of TLSs in epithelial ovarian cancer (EOC) treated with primary debulking surgery (PDS) or interval debulking surgery (IDS) remains unelucidated. This retrospective study examined the prognostic value of TLSs in tumor tissues obtained during PDS and IDS. Pathological specimens were collected from patients with EOC who underwent PDS or IDS between 2017 and 2020 at the National Cancer Center Hospital East. The correlation of tumor-infiltrating lymphocyte frequency, TLS presence, and PD-L1 expression with progression-free survival (PFS) and overall survival (OS) and the correlation between TLS and PD-L1 expression were analyzed. Overall, 25 specimens (15 from PDS and 10 from IDS) were analyzed. The presence of TLS was associated with a significantly longer OS in patients who underwent PDS but not in patients who underwent IDS. No correlation was identified between TLS and PFS in patients with PDS or with IDS. However, TLS was positively correlated with PD-L1 positivity. The prognostic impact of TLS, specifically in pre-chemotherapy specimens, and a positive correlation between TLS and PD-L1 indicate the potential of TLS as a meaningful biomarker for understanding antitumor immunity and developing immunotherapy for EOC.

Background Community infections of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have increased rapidly since the emergence of the Omicron strain. During the eighth and ninth pandemic waves—when movement restrictions in the community were eased—the all-case registration system was changed, and the actual status of infection became uncertain. Methods We conducted regular rapid antigen tests (R-RAT) once or twice a week to examine the actual state of coronavirus disease (COVID-19) diagnosis among healthcare employees. Results Overall, 320 (1.42/day) and 299 (1.76/day) employees were infected in the eighth and ninth pandemic waves. During both periods, 59/263 doctors (22.4%), 335/806 nurses (41.6%), 92/194 administrative employees (47.4%), and 129/218 clinical laboratory technicians (59.2%) were infected. In the eighth wave, 56 of 195 employees were infected through close contact; in the ninth wave, 26 of 62 employees were infected. No significant difference was observed in the number of vaccinations between infected and non-infected employees. The positivity rate of R-RAT was 0.41% and 0.45% in the eighth and ninth waves. R-RAT detected infection in 212 and 229 employees during the eighth and ninth waves, respectively; the ratio of R-RAT-detected positive employees to those who reported infection was significantly higher during the ninth wave (odds ratio: 1.67, 95% confidence interval: 1.17–2.37, p

Two novel members of the subfamily Betarhabdovirinae, family Rhabdoviridae, were identified in Brazil. Overall, their genomes have the typical organization 3’-N-P-P3-M-G-L-5’ observed in mono-segmented plant-infecting rhabdoviruses. In aristolochia-associated cytorhabdovirus (AaCV), found in the liana aristolochia (Aristolochia gibertii Hook), an additional short orphan ORF encoding a transmembrane helix was detected between P3 and M. AaCV genome and deduced encoded proteins share the highest identity values, consistently < 60%, with their counterparts of yerba mate chlorosis-associated virus (Cytorhabdovirus flaviyerbamate). The second virus, false jalap virus (FaJV), was detected in the herbaceous plant false jalap (Mirabilis jalapa L.) and represents together with tomato betanucleorhabdovirus 2, originally found in tomato plants in Slovenia, a tentative new species of the genus Betanucleorhabdovirus. FaJV particles accumulate in the peri-nuclear space, and electron-lucent viroplasms were observed in the nuclei of the infected cells. Notably, distinct from typical rhabdoviruses, most virions of AaCV were observed to be non-enclosed within membrane-bounded cavities. Instead, they were frequently seen in close association with surfaces of mitochondria or peroxisomes. Unlike FaJV, AaCV was successfully graft-transmitted to healthy plants of three species of the genus Aristolochia, while mechanical and seed transmission proved unsuccessful for both viruses. Data suggest that these viruses belong to two new tentative species within the subfamily Betarhabdovirinae.

Background: High coronary thrombus burden has been associated with unfavorable outcomes in patients with ST-segment elevation myocardial infarction (STEMI), the optimal management of which has not yet to be established. Methods: We evaluated the safety and efficacy of adjunctive catheter-directed thrombolysis (CDT) during primary percutaneous coronary intervention (PCI) in patients with STEMI and high thrombus burden. Results: Among the 1,849 consecutive patients with STEMI, 263 had high thrombus burden. Moreover, 41 patients received intracoronary infusion of tissue plasminogen activator during primary PCI (CDT group), whereas 222 did not receive (non-CDT group). No significant differences in bleeding complications and in-hospital and long-term mortalities were observed (9.8% vs. 7.2%, p=0.53; 7.3% vs. 2.3%, p=0.11; and 12.6% vs. 17.5%, p=0.84, CDT vs. non-CDT). In patients who underwent antecedent aspiration thrombectomy during PCI (75.6%; CDT group and 87.4%; non-CDT group), thrombolysis in myocardial infarction grade 2 or 3 flow rate after thrombectomy was significantly lower in the CDT group than in the non-CDT group (32.2% vs. 61.0%, p&lt;0.01). However, the final rates improved considerably without significant difference (90.3% vs. 97.4%, p=0.14). Conclusions: For STEMI patients with high thrombus burden, adjunctive CDT is safe and effective for improving coronary flow. CDT resulted in favorable coronary flow even after unsatisfactory aspiration thrombectomy.

Since the 1970s, the usefulness of nailfold capillaroscopy (NFC) in the diagnosis of rheumatological disorders such as systemic sclerosis has been well known, and further studies also showed that NFC can detect non-rheumatic diseases such as diabetes, glaucoma, dermatitis, Alzheimer disease, and so on. In the past decade, the morphological changes in the nailfold capillary have been also reported in the unhealthy lifestyle habits such as smoking, inappropriate diets, sleep shortage, and even psychological stress which presents slow blood flow. Therefore, study in the relationships between the morphology of nailfold capillaries and lifestyle habits has high potential to understand the unhealthy state, or even predict the pre-disease condition. So, simple, inexpensive, and non-invasive methods such as NFC are constantly needed for routine health checkups. Thus, we undertook a systematic search in PubMed database, and summarized the studies reporting the assessment of morphological NFC in order to undertake a comprehensive review on the usefulness of NFC not only in clinical diagnosis, but also in unhealthy dietary lifestyle improvements. Here in this review paper, we finally summarized the dietary and lifestyle health promotion strategy judging from NFC- and the other relating-measurement from the viewpoint of healthy microvascular blood flow and endothelial function.

A smartphone plummeted from a stratospheric height of 36 km (~119,000 feet), providing a complete record of its rapid descent and abrupt deceleration when it hit the ground. The smartphone was configured to collect internal sensor data at high rates. We discuss the state-of-the-art of smartphone environmental and sensing capabilities at the closing of year 2020 and present a flexible mobile sensor data model. The associated open-source application programing interface (API) and python software development kit (SDK) used in this work is transportable to any hardware platform and operating system.

Pv11, an insect cell line established from the midge Polypedilum vanderplanki, is capable of ametabolic desiccation tolerance, so-called anhydrobiosis. We previously discovered that heat shock factor 1 (HSF1) contributes to the acquisition of desiccation tolerance by Pv11 cells, but the mechanistic details have yet to be elucidated. Here, by analyzing the gene expression profiles of newly established HSF1-knockout and -rescue cell lines, we show that HSF1 has a genome-wide effect on gene regulation in Pv11. HSF1-knockout cells exhibit a reduced desiccation survival rate, but this is completely restored in HSF1-rescue cells. By comparing mRNA profiles of the two cell lines, we reveal that HSF1 induces anhydrobiosis-related genes, especially genes encoding late embryogenesis abundant proteins and thioredoxins, but represses a group of genes involved in basal cellular processes, thus promoting an ametabolic state in the cell. In addition, HSF1 binding motifs are enriched in the promoters of anhydrobiosis-related genes and we demonstrate binding of HSF1 to these promoters by ChIP-qPCR. Thus, HSF1 directly regulates the transcription of anhydrobiosis-related genes and consequently plays a pivotal role in the induction of anhydrobiotic ability in Pv11 cells.

The giant anteater (Myrmecophaga tridactyla) is a vulnerable specie from Central and South America and is considered extinct in Belize, Guatemala, El Salvador, and Uruguay. Therefore, studies describing the reproductive characteristics of this species are pivotal for its conservation. Thus, this study aimed to provide a morphological description of their female reproductive tissues. We collected tissue samples from six female giant anteaters, and performed gross, morphological, and histochemical analyses. Five adult and one young subjects were enrolled in the study. In the ovary, classifications were made according to the follicle and oocyte sizes: primordial, primary, secondary, early antral, or antral. Typical follicles with a single oocyte surrounded by a simple or stratified layer of cubic epithelium, atretic follicles, corpora lutea, corpora albicans, and ovarian cysts were also observed. No ovarian lesions were observed. By contrast, endometritis, metritis, mucometra, and endometrial cysts were identified in the uterus. Uterine alterations in these subjects were frequent and could affect reproduction.

Nanoparticles have been used as a novel drug delivery system. Drug-incorporated nanoparticles for local delivery might optimize the efficacy and minimize the side effects of drugs. The efficacy and safety of intratracheal administration of prostacyclin analog (beraprost)-incorporated nanoparticles and imatinib, a PDGF-receptor tyrosine kinase inhibitor, -incorporated nanoparticles in Sugen-hypoxia-normoxia or monocrotaline rat models of PAH and in human PAH-pulmonary arterial smooth muscle cells have been reported. The use of inhaled drug-incorporated nanoparticles might be a novel approach for treatment of PAH.

Multimodal therapy including surgery, radiation treatment and temozolomide (TMZ) is performed on glioblastoma (GBM). However, the prognosis is still poor and there is an urgent need to develop effective treatments to improve survival. Molecular biological analysis was conducted to exam-ine the signal activation patterns at GBM specimens and remains an open problem. Advanced macrolides, such as azithromycin, reduce the phosphorylation of p70 ribosomal protein S6 kinase (p70S6K), a downstream mammalian target of rapamycin (mTOR) effector, and suppress the proliferation of T-cells. We focused on its unique profile and screened for the antitumor activity of approved macrolide antibiotics. Clindamycin (CLD) reduced the viability of GBM cells in vitro. We assessed the effects of the candidate macrolide on the mTOR pathway through Western blotting. CLD attenuated p70S6K phosphorylation in a dose dependent manner. These effects of on GBM cells were enhanced by co-treatment with TMZ. Furthermore, CLD inhibited the expression of O6-methylguanine-DNA methyltransferase (MGMT) protein in cultured cells. In the mouse xenograft model, CLD and TMZ co-administration significantly suppressed the tumor growth and markedly decreased the number of Ki-67 (clone MIB-1) positive cells within the tumor. These results suggest that CLD suppresses GBM cell growth by the inhibiting mTOR signaling. Moreover, CLD and TMZ showed promising synergistic antitumor activity.

Objectives: This study aimed to determine the relationship between objective chewing ability and nutritional status of Japanese community-dwelling elders. Design: Cross sectional study. Participants: In total, 509 community-dwelling elders living in the Tokyo metropolitan area participated in a comprehensive survey occurring in October 2013. Measurements: Basic characteristics referred to sex, age, and body mass index. Undernutrition was examined through serum albumin levels. Chewing ability was examined through a color-changeable xylitol gum. By evaluating color changes in the chewing gum. Nutritional intake was examined through the semi-quantitative Food Frequency Questionnaire. Results: In the poor chewing ability group, all nutrient intake levels were significantly low, except for carbohydrates and all food groups intake levels were significantly low, except for cereals, confectionery, sugars, seasonings, and spices. Additionally, after adjusting for covariates, chewing ability showed a significant association with undernutrition. Conclusion: We concluded that chewing ability was closely associated with nutrient and different food groups intake as well as undernutrition among Japanese community-dwelling elders. Thus, in order to ensure a comprehensive nutritional management, nutritionists and dentists should collaborate when treating the same patients.

We previously reported a novel secondary progressive multiple sclerosis (SPMS) model, progressive experimental autoimmune encephalomyelitis (pEAE), in oligodendroglia-specific Cx47-inducible conditional knockout (Cx47 icKO) mice. Based on our prior study showing the efficacy of iguratimod (IGU), an anti-rheumatic drug, for acute EAE treatment, we aimed to elucidate the effect of IGU on the SPMS animal model. We induced pEAE by immunizing Cx47 icKO mice with myelin oligodendrocyte glycoprotein peptide 35–55. IGU was orally administered from 17 to 50 days postimmunization. We also prepared primary mixed glial cell culture and measured cytokine levels in the culture supernatant after stimulation with designated cytokines (IL-1α, C1q, TNF-α) and lipopolysaccharide. A migration assay was performed to evaluate the effect of IGU on the migration ability of T cells toward mixed glial cell cultures. IGU treatment ameliorated the clinical signs of pEAE, decreased the demyelinated area, and attenuated glial inflammation on immunohistochemical analysis. Additionally, IGU decreased the intrathecal IL-6 level and infiltrating Th17 cells. The migration assay revealed reduced Th17 cell migration and IL-6 levels in the culture supernatant after IGU treatment. Collectively, IGU successfully mitigated the clinical signs of pEAE by suppressing Th17 migration through inhibition of IL-6 production by proinflammatory-activated glial cells.

The phenomenon of decreased serum uric acid (UA) levels in patients with Parkinson’s disease (PD) and its relationship with purine metabolic pathways remain unclear. We compared inosine, hy-poxanthine, xanthine, and UA levels in serum and cerebrospinal fluid (CSF) of PD patients with those of controls, and investigated the effect of changes in the purine metabolic system on UA levels in PD. Overall, 134 samples (serum, 45 PD patients and 30 controls; CSF, 39 PD patients and 20 controls), were analyzed using liquid chromatography-tandem mass spectrometry. A general linear model (GLM) was used to investigate relationships among purine metabolites. Compared to controls, PD patients had significantly lower UA levels in the serum and CSF, and serum and CSF UA levels were significantly correlated. Additionally, in PD, decreased serum hypoxanthine levels were observed with decreased CSF inosine and hypoxanthine levels, suggesting the involvement of the purine recycling system. GLM analysis indicated that the reduced UA levels in PD were mainly due to sources other than the purine metabolic system, such as exercise, nutritional indices, muscle volume, or adipose tissue. Our results highlight the impairment of purine recycling pathways in PD, as evidenced by the decreased serum hypoxanthine and CSF inosine.

Pachychoroid neovasculopathy (PNV) is a pachychoroid-spectrum disease. As blood circulation throughout the choroid may be involved in PNV pathogenesis, analysis using ultra-wide-field (UWF) fundus imaging is crucial. We evaluated choroidal thickness after half-fluence photodynamic therapy (PDT) combined with intravitreal aflibercept injection for PNV using UWF swept-source optical coherence tomography. Seventeen eyes with PNV that underwent half-fluence PDT with adjuvant single intravitreal aflibercept injection were analyzed. To compare choroidal thicknesses in the central and peripheral choroids, we set subfields <3, <9, and 9–18 mm from the fovea. The <9- and 9–18-mm subfields were divided into four quadrants. Choroidal thickness in each subfield decreased significantly after half-fluence PDT (P<0.001); this reduction was more pronounced in the central area. We also investigated the relationship between the dominant side of the deep choroidal veins that harbor choroidal vein efflux from the macula. When choroidal thickness in the supratemporal and infratemporal 9x9-mm subfields were evaluated, the ratio of choroidal thickness reduction was not significantly different between the dominant and non-dominant sides. The dominant side was not associated with the extent of choroidal thickness reduction in PNV. In conclusion, half-fluence PDT caused thinning of the entire choroid, especially in the central area, in PNV.

Lipopolysaccharides are a type of polysaccharide mainly present in the bacterial outer membrane of Gram-negative bacteria. Recent studies have revealed that lipopolysaccharides contribute to the immune response of the host by functioning as a cancer antigen. We retrospectively recruited 198 patients with gastric cancer who underwent surgery. The presence of lipopolysaccharides was determined using immunohistochemical staining, with the intensity score indicating positivity. The relationship between lipopolysaccharides and CD8, PD-L1, TGFBI (a representative downstream gene of TGF-β signaling), E-cadherin, and claudin-4 (epithelial–mesenchymal transition markers) was also investigated. Thereafter, we identified 20 patients with advanced gastric cancer receiving nivolumab and investigated the relationship between lipopolysaccharides and nivolumab sensitivity. After staining for lipopolysaccharides in the nucleus of cancer cells, 150 negative (75.8%) and 48 positive cases (24.2%) were found. The lipopolysaccharide-positive group showed increased cancer stromal TGFBI expression (p &lt; 0.0001) and PD-L1 expression in cancer cells (p = 0.0029). Lipopolysaccharide positivity was significantly correlated with decreased E-cadherin expression (p = 0.0055) and claudin-4 expression (p = 0.029); however, no significant correlation was found between lipopolysaccharide expression and overall survival rate (p = 0.71). Among cases receiving nivolumab, the lipopolysaccharide-negative and -positive groups had a disease control rate of 66.7% and 11.8%, respectively (p = 0.049). Lipopolysaccharide positivity was associated with TGF-β signaling and epithelial–mesenchymal transition and was considered to promote therapeutic resistance to nivolumab.

Modified FOLFIRINOX is effective for advanced pancreatic cancer but frequently causes severe neutropenia. The present study was designed to investigate the influence of severe neutropenia on clinical outcomes in advanced pancreatic cancer patients receiving modified FOLFIRINOX. Fifty-one advanced pancreatic cancer patients who received modified FOLFIRINOX during January 2014 and May 2018 were subjects of the present study. Adverse events, including neutropenia, were graded according to the Common Terminology Criteria for Adverse Events, version 4.0. Median overall survival (OS) was determined as the primary endpoint, while median time to treatment failure (TTF), overall response rate (ORR), and the incidence of other adverse events were measured as secondary endpoints. Severe neutropenia (grade≥3) occurred in 39 patients (76.4%), in which high level of total bilirubin (>0.6mg/dL) was a significant risk as assessed by a multivariate logistic regression analysis. Median duration of OS was significantly longer in patients with severe neutropenia than in those without it (15.2 months versus 7.2 months, P=0.032). Moreover, there was a significant correlation between OS and the grade of neutropenia (R=0.306, P=0.029). ORR tended to be higher, though not significantly, in patients with severe neutropenia. In contrast, the incidence rates of other adverse events were not different between the two groups. Severe neutropenia is an independent predictor of prognosis in advanced pancreatic cancer patients received modified FOLFIRNOX therapy.

We conducted a retrospective evaluation of the clinical outcomes and prognostic factors in patients with non-metastatic castration-resistant prostate cancer (nmCRPC) treated with first-line androgen receptor signaling inhibitors (ARSI) in real-world clinical practice in Japan. Between 2012 and 2023, a total of 127 consecutive patients with nmCRPC received ARSI treatment. Overall survival (OS), metastatic-free survival (MFS), and prostate-specific antigen progression–free survival (PSA-PFS) from ARSI initiation were assessed using Kaplan–Meier methodology. Clinical factors associated with OS in nmCRPC were analyzed using the Cox proportional hazards model. Among the patients, 72, 26, 12, and 17 received enzalutamide (ENZ), abiraterone (ABI), apalutamide (APA), and darolutamide (DARO) as first-line therapy. The median OS and MFS for all patients were 79.0 and 42.0 months, respectively. Median PSA-PFS was 27.0, 20.0, 10.0, and 14.0 months for patients treated with ENZ, ABI, APA, and DARO, respectively (p = 0.33). Multivariate analysis revealed that a baseline PSA level ≥3.67 ng/ml at ARSI initiation was significantly associated with poorer OS (p = 0.002). ARSI demonstrated favorable efficacy in nmCRPC patients. There were no significant differences in clinical outcomes among different types of ARSI therapy for nmCRP. Elevated baseline PSA at ARSI initiation was significantly associated with poorer OS.

The pathology of idiopathic intracranial hypertension (IIH), a disease characterized by papillary edema and increased intracranial pressure (IICP), is not yet understood; this disease significantly affects quality of life due to symptoms, including vision loss, headache, and pulsatile tinnitus. By contrast, superficial siderosis (SS), a disorder in which hemosiderin is deposited on the surface of the cerebral cortex and cerebellum, potentially causes cerebellar ataxia or hearing loss. So far, no cases of IIH with infratentorial and supratentorial cortical SS have been reported. Herein, we report a case of a 31-year-old woman with obesity who developed this condition. The patient suddenly developed headache and dizziness, had difficulty walking, and subsequently became aware of diplopia. Fundus examination revealed bilateral optic nerve congestive papillae and right eye abducens disturbance. Head magnetic resonance imaging (MRI) showed prominent SS on the cerebellar surface and cerebral cortex. Lumbar puncture revealed IICP of 32 cmH2O, consistent with the diagnostic criteria for IIH, and treatment with oral acetazolamide was started; subsequently, the intracranial pressure decreased to 20 cmH2O. Her abduction disorder disappeared, and the swelling of the optic papilla improved. She was now able return to her life as a teacher without any sequelae. SS is caused by persistent slight hemorrhage into the subarachnoid space. In this case, both infratentorial and supratentorial cortical superficial SS was observed. Although cases of IIH complicated by SS are rare, it should be kept in mind that a causal relationship between IIH and SS was inferred from our case. Our findings also suggest that cerebrospinal fluid dynamic analysis using MRI is effective in diagnosing IIH and in determining the efficacy of treatment.

Solar flares are broadly classified as impulsive or gradual. Ions accelerated in a gradual flare are thought to be accelerated through a shock acceleration mechanism, but the particle acceleration process in an impulsive flare is still largely unexplored. To understand the acceleration process, it is necessary to measure the high-energy gamma-rays and neutrons produced by the impulsive flare. Under such circumstances, on November 7, 2004, a huge X2.0 flare occurred on the solar surface, where ions were accelerated to energies greater than 10 GeV. The accelerated primary protons collided with the solar atmosphere and produced line gamma-rays and neutrons. These particles were received as neutrons and line gamma-rays, respectively. Neutrons of a few GeV, on the other hand, decay to produce secondary protons while traveling 0.06 au in the solar-terrestrial space. These secondary protons arrived at the magnetopause. Although the flux of secondary protons is very low, the effect of collecting secondary protons arriving in a wide region of the magnetosphere (the Funnel or Horn effect) has resulted in significant signals being received by the solar neutron telescope at Mt. Sierra Negra (4,600 m). This information suggests that ions on the solar surface are accelerated to over 10 GeV with an impulsive flare.

A potential association between hematopoietic stem cell status in the bone marrow and the surrounding bone tissue has been hypothesized, and some studies have investigated the link between blood count and bone mineral density (BMD), although their exact relationship remains controversial. Moreover, biological factors linking the two are largely unknown. In our present study, we found no clear association between platelet count and BMD in the female group, with aging having a very strong effect on BMD. On the other hand, a significant negative correlation was found between platelet count and BMD in the male group. As a potential mechanism, we examined whether megakaryocytes, the source of platelet production, secrete cytokines that regulate BMD, namely OPG, M-CSF, and RANKL. We detected the production of these cytokines by megakaryocytes deriving from bone marrow mononuclear cells and found that RANKL was negatively correlated with BMD. This finding suggests that RANKL production by megakaryocytes may mediate the negative correlation between platelet count and BMD. To our knowledge, this is the first report to analyze bone marrow cells as a mechanism for the association between blood count and BMD. Our study may provide new insights into the development and potential treatment of osteoporosis.

Congenital malformations are functional and structural alterations in embryonic or foetal development resulting from a variety of factors including maternal health status. This study aimed to investigate the association between maternal birth weight (MBW) and the prevalence of congenital malformations in the offspring using data from a nationwide birth cohort study in Japan including 103,060 pregnancies. A binary logistic regression model with adjustment for various covariates revealed that MBW of &lt;2,500 g (low MBW) was associated with increased risk of congenital heart disease (adjusted odds ratio: 1.388, [95% confidence interval: 1.075–1.792]), angioma (1.491 [1.079–2.059]), and inguinal hernia (1.746, [1.189–2.565]), while MBW of ≥4,000 g (high MBW) with congenital anomalies of the urinary tract (2.194, [1.261–3.819]), and arrhythmia (1.775, [1.157–2.725]), compared with those with MBW of 3,000-3,499 g. Low MBW was associated with cleft lip and/or palate (1.473, [1.052–2.064]), congenital heart disease (1.615, [1.119–2.332]), genital organs(1.648, [1.130–2.405]), hypospadias (1.804, [1.130–2.881]), and inguinal hernia (1.484, [1.189–1.851]) in male infants and CAKUT (1.619, [1.154–2.273]) in female infants, whereas high MBW was associated with congenital heart disease(1.745, [1.058–2.877]) and CAKUT (2.470, [1.350–4.517]) in male infants. The present study is the first to demonstrate a link between MBW and congenital malformations in Japanese children. While these results must be interpreted with caution, MBW should be considered a major predictor of congenital malformation risk.

Insulin resistance is the most important underlying cause of obesity and type 2 Diabetes (T2DM), and insulin sensitizing treatments have proved effective in preventing diabetes and inducing weight loss. Obesity and T2DM are also associated with increased inflammation. Mangosteen is a tropical tree, whose fruits, widely known for their antioxidant properties, have been recently suggested having a possible further role in the treatment of obesity and T2DM. The objective of this pilot study has been to evaluate safety, compliance and efficacy of mangosteen on insulin resistance, weight management, and inflammatory status in obese female patients with insulin resistance. 22 patients were randomized 1:1 to behavioral therapy alone or behavioral therapy and mangosteen and 20 completed the 26-week study. The mangosteen group reported a significant improvement in insulin sensitivity (HOmeostatic Model Assessment-Insulin Resistance, HOMA-IR -53.22% vs -15.23%, p=.0037), and a trend decrease in inflammation markers serum levels, together with trend greater weight loss and trend increased HDL levels. No side effect attributable to treatment was reported. Given the positive preliminary results we report and the excellent safety profile, we suggest a possible role of mangosteen in the treatment of obesity, insulin resistance and inflammation.

Reactive oxygen species (ROS) play a pivotal role in cellular function, and their overproduction contributes to oxidative stress, fatigue, aging, and diseases. To counteract these effects, incorpo-rating antioxidant-rich nutrients is recommended. Functional waters, including electrolyzed hydrogen water (EHW), are gaining attention for potential antioxidant effects through daily in-take. This study employs aquaphotomics and near-infrared spectroscopy (NIRS) to elucidate the molecular mechanisms behind the antioxidant activity of EHW. Previous investigation reported a 100% loss in antioxidant functionality through autoclaving, and a 40% decrease with hydrogen gas removal, prompting the current investigation into the mechanisms of antioxidant effects and especially the role of water molecular structure in it. Aquaphotomics analysis of near infrared (NIR) spectral data revealed that the primary characteristic of EHW associated with anti-radical function is presence of water solvation shells. Autoclaving and degassing led to loss of these water molecular species and a significant increase in free water molecules. The study suggests that water shells (solvation shells) in EHW play a crucial role in neutralizing ROS, although the specific ions or nanoparticles responsible for creating these shells remain unidentified. This concept aligns well with existing proposals of the crucial role of water solvation shells in ROS neutralization.

Abstract: Long noncoding RNAs (lncRNAs) are deregulated in human cancers and are associated with disease progression. Plasmacytoma Variant Translocation 1 (PVT1), an lncRNA, is located adjacent to MYC, linked to multiple myeloma (MM). PVT1 is expressed in MM and is associated with carcinogenesis, however, its role and regulation machinery remain uncertain. We examined PVT1/MYC expression through real time PCR in plasma cells purified from 59 MGUS and 140 MM patients. MM cell lines KMS11, KMS12PE, OPM2, and RPMI8226 were treated with JQ1, a MYC superenhancer inhibitor, or MYC inhibitor 10058-F4. The expression levels of PVT1 and MYC were significantly higher in MM than in MGUS (p &lt; 0.0001), and showed positive correlation with disease progression (r = 0.394, p &lt; 0.0001). JQ1 inhibited cell proliferation and decreased the expression levels of MYC and PVT1. However, 10054-F4 did not alter the expression level of PVT1. The positive correlation between MYC and PVT1 in patients, synchronous downregulation of MYC and PVT1 by JQ1, and no effect of MYC inhibitor on PVT1 expression suggest that the expression of these two genes is coregulated by a superenhancer. Cooperative effects between these two genes may contribute to MM pathogenesis and progression.

Coronavirus disease 2019 (COVID-19) has affected medical practice. More than 7,000,000 patients died worldwide after being infected with COVID-19; however, no specific laboratory markers have yet been established to predict death related to this disease. In contrast, electrocardiographic changes owing to COVID-19 include QT prolongation and ST-T changes; however, there have been no studies on ambulatory electrocardiographic markers of COVID-19. We encountered three patients diagnosed as having COVID-19 who did not have a prior history of significant structural heart diseases. All had abnormalities in ambulatory echocardiogram parameters detected by high-resolution 24-h electrocardiogram monitoring: positive late potentials (LPs) and T-wave alternans (TWA), abnormal heart rate variability (HRV), and heart rate turbulence (HRT). Case 1 involved a 78-year-old woman with a history of chronic kidney disease, Case 2 a 76-year-old man with hypertension and diabetes, and Case 3 a 67-year-old man with renal cancer, lung cancer, and diabetes. None of them had a prior history of significant structural heart disease. Although no significant consistent increases in clinical markers were observed, all three patients died, mainly because of respiratory failure with mild heart failure. LP, TWA, HRV, and HRT were all positive in three cases with no significant structural cardiac disease at the initial phase of admission. There is a possibility that LP, TWA, HRV, and HRT have the potential to be risk stratifiers of COVID-19 pneumonia in the early phase of admission. Further accumulation of data regarding ambulatory electrocardiographic markers in patients with COVID-19 is needed.

Patients with neuromuscular diseases usually have progressive neuromuscular scoliosis (NMS), requiring invasive surgery. Some patients present with severe scoliosis at the time of consultation and are difficult to treat. Posterior spinal fusion (PSF) surgery combined with anterior release and pre or intraoperative traction would be effective for severe spinal deformity, but invasive. This study aimed to evaluate the outcomes of PSF only surgery for patients with severe NMS with Cobb angle &gt;100 °. Thirty NMS patients (13 boys and 17 girls; mean age 13.8 years) who underwent PSF only surgery for scoliosis with Cobb angle &gt;100 ° were included. We reviewed the lower instrumented vertebra (LIV), duration of surgery, blood loss, perioperative complications, preoperative clinical findings, and radiographic findings including Cobb angle and pelvic obliquity (PO) in the sitting position pre and postoperatively. The correction rate and correction loss of the Cobb angle and PO were also calculated. The mean duration of surgery was 338 min, intraoperative blood loss was 1,440 mL, preoperative %VC was 34.1%, FEV1.0 (%) was 91.5%, and EF was 66.1%. There were eight cases of perioperative complications. The Cobb angle and PO correction rates were 48.5% and 42.0%, respectively. We divided the patients into two groups: the L5 group, in which the LIV was L5, and the pelvis group, in which the LIV was the pelvis. The duration of surgery and PO correction rate in the pelvis group was significantly higher than that of the L5 group. Patients with severe NMS demonstrated severe preoperative restrictive ventilatory impairments. PSF only surgery for severe NMS showed satisfactory outcomes, although highly invasive. Instrumentation and fusion to the pelvis for severe scoliosis in patients with NMS showed good PO correction and low correction loss of Cobb angle and PO, but a longer duration of surgery.

Strigolactones (SLs), a group of plant hormones, induce germination of root-parasitic plants and inhibit shoot branching in many plants. Shoot branching is an important trait that affects the number and quality of flowers and fruits. Root-parasitic plants such as Phelipanche spp. infect tomato roots and cause economic damage in Europe and North Africa. Thus, resistant tomato cultivars are needed. In this study, we found carotenoid cleavage dioxygenase 8-defective mutants of Micro-Tom tomato (slccd8) by the “targeting induced local lesions in genomes” (TILLING) method. The mutants showed excess branching, which was suppressed by exogenously applied SL. Grafting shoot scions of the slccd8 mutants onto wild-type (WT) rootstocks restored normal branching in the scions. The levels of endogenous orobanchol and solanacol in WT were enough detectable, whereas that in the slccd8 mutants were below the detection limit of quantification analysis. Accordingly, root exudates of the slccd8 mutants hardly stimulated seed germination of root parasitic plants. In addition, SL deficiency did not critically affect the fruit traits of Micro-Tom. Using a rhizotron system, we also found that Phelipanche aegyptiaca infection was lower in the slccd8 mutants than in wild-type Micro-Tom because of the low germination. We propose that the slccd8 mutants might be useful as new tomato lines resistant to P. aegyptiaca.

With the rapid development of gene therapy technology in recent years, its abuse as a method of sports doping in athletic has become a concern. However, there is still room for improvement in gene doping testing methods, and a robust animal model needs to be developed. Therefore, the purposes of this study were to establish a model of gene doping using recombinant adeno-associated virus vector-9 including the human erythropoietin gene (rAAV9-hEPO), and to establish a relevant testing method. First, it was attempted to establish the model using rAAV9-hEPO on mice. The results showed a significant increase in erythrocyte volume accompanied by an increase in spleen weight, confirming the validity of the model. Next, we attempted to detect proof of gene doping by targeting DNA and RNA. Direct proof of gene doping was detected using a TaqMan-qPCR assay with certain primers/probes. In addition, some indirect proof was identified in RNAs through the combination of a TB Green qPCR assay with RNA sequencing. Taken together, these results could provide the foundation for an effective test for gene doping in human athletes in the future.