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Possible local influence of an extreme marine heatwave is investigated on unprecedentedly hot summer around northern Japan in 2023. Sea-surface temperatures (SSTs) and subsurface ocean temperatures around northern Japan were also unprecedentedly high in the summer. This was especially the case off the east coast of Japan, where cool Oyashio water was replaced with much warmer water due to a striking poleward meander of the Kuroshio Extension persistent from the spring. Particularly amplified near-surface air temperature anomalies and even stronger warm anomalies in the subsurface ocean suggest that the marine heatwave acted to sustain the atmospheric heatwave. Anomalous upward of latent and sensible heat fluxes from the warmed sea surface are indicative of local oceanic impact. The warm SST anomalies reduced the lower-tropospheric stratification to maintain unfavourable condition for low-level cloud formation, which in turn led to increased surface insolation for further SST warming as positive feedback. The increased moisture in the warmed lower troposphere contributed to the enhanced surface downward longwave radiation. This enhanced greenhouse effect acted not only as positive feedback on the warm SST anomalies that increased evaporation but also as a contributor for the extreme warmth over northern Japan landmass. [ABSTRACT FROM AUTHOR]

The accelerated approval (AA) program in the USA has succeeded in expediting the regulatory approval of new cancer drugs based on surrogate endpoint data. It is unclear whether the AA program promotes overall drug development, including verification of the clinical benefit, as the verification of drugs granted AA often takes long time. To determine the impact of the AA program on overall drug development, the time required for verification of clinical benefits was compared between anticancer drugs that initially received AA and those that received regular approval (RA). It was found that anticancer drugs that were approved under the AA program took longer time for verification, suggesting that the program may delay the start of a confirmatory study, and there may be room for speeding up the process. In addition, discordance was found in the pivotal study between the USA and the EU and the USA and Japan for obtaining the indication for which AA was granted in the USA and a delay in the start of the confirmatory study for the AA indication was considered to lead to a delay in approval in the EU and Japan. Early initiation of confirmatory studies for AA indications is recommended to reduce the time that patients receive drugs with unproven benefit in the USA, as well as to deliver innovative new drugs to patients earlier in the EU and Japan. [ABSTRACT FROM AUTHOR]

Bioluminescence generated by luciferase and luciferin has been extensively used in biological research. However, detecting signals from deep tissues in vivo poses a challenge to traditional methods. To overcome this, the Akaluc and AkaLumine bioluminescent systems were developed, resulting in improved signal detection. We evaluate the potential of Akaluc/AkaLumine in Drosophila melanogaster to establish a highly sensitive, non-invasive, and temporal detection method for gene expression. Our results show that oral administration of AkaLumine to flies expressing Akaluc provided a higher luminescence signal than Luc/D-luciferin, with no observed harmful effects on flies. The Akaluc/AkaLumine system allows for monitoring of dynamic temporal changes in gene expression. Additionally, using the Akaluc fusion gene allows for mRNA splicing monitoring. Our findings indicate that the Akaluc/AkaLumine system is a powerful bioluminescence tool for analyzing gene expression in deep tissues and small numbers of cells in Drosophila. In Drosophila melanogaster, the red-shifted bioluminescence system Akaluc/AkaLumine is useful for studying gene expression, cell numbers, and innate immunity levels in deep tissues without harming the individual. [ABSTRACT FROM AUTHOR]

Peripheral nerve injury causes long-term motor dysfunction. Ultrasound (US) therapy is expected to accelerate peripheral nerve regeneration. However, its optimal usage and effects on macrophage phenotypes during peripheral nerve regeneration remain unknown. In this study, we investigated the optimal duration of US therapy and its effects on macrophage phenotype. Twenty-seven rats with autologous sciatic nerve grafting were divided into three groups: two received US therapy (1 MHz frequency, intensity of 140 mW/cm2, 20% duty cycle, 5 min/day) for one (US1) or 4 weeks (US4), and one group received sham stimulation. Immunohistochemistry was performed 3 and 7 days after injury in another set of 12 rats. Eight weeks after the injury, the compound muscle action potential amplitude of the gastrocnemius in the US1 and US4 groups was significantly higher than that in the sham group. The toe-spreading test showed functional recovery, whereas the gait pattern during treadmill walking did not recover. There were no significant differences in motor function, histomorphometry, or muscle weight between groups. Immunohistochemistry showed that US therapy decreased the number of pro-inflammatory macrophages seven days after injury. Therefore, US therapy for both one or 4 weeks can similarly promote reinnervation and reduce proinflammatory macrophages in autograft model rats. [ABSTRACT FROM AUTHOR]

Homomorphic encryption (HE) method can be used to realize arithmetic operations on encrypted data. This method, however, is limited owing to its low efficiency in performing certain functions, especially those involving several multiplications. As a solution, this paper proposes a new HE-based secure computation scheme, termed as the HE for stochastic computing (HESC); this scheme can homomorphically evaluate both the stochastic addition and multiplication operations, without any bootstrapping. This HESC scheme is constructed based on additive/multiplicative HE, which only supports homomorphic addition/multiplication, and realizes the homomorphic evaluation of stochastic multiplication. The HESC employs the features of stochastic computing (SC) for homomorphic stochastic operations, where stochastic additions and multiplications are performed using random multiplexing and bit-parallel logic operations, respectively. This paper first presents a basic HESC scheme based on additive/multiplicative HE. It then presents an efficient HESC scheme that utilizes the parallelism of lattice-based cryptography (i.e., plaintext packing and vectorized homomorphic evaluation). A new stochastic addition operation is also introduced in this study, which can be used for the HESC instantiated by lattice-based cryptography. This new stochastic addition operation significantly improves the accuracy of the HESC, albeit with the trade-off of increased ciphertext size. Accordingly, this paper also proposes a technique that can reduce the size of ciphertexts, while maintaining the accuracy of the scheme. The basic performance of the HESC implemented with various HEs is demonstrated, along with its applications in polynomial functions and an oblivious inference with a neural network. Lastly, the results thus obtained indicate that the proposed scheme is more advantageous than the conventional schemes. This paper is concluded with some implications/research directions for HESC from perspectives of cryptography and HE implementations. [ABSTRACT FROM AUTHOR]

Hyperthermia using magnetic nanoparticles enables tumor-specific heating and can destroy tumor tissues. This approach works as in situ vaccination with tumor antigens released from dying tumor cells. However, in situ vaccination caused by magnetic hyperthermia is often insufficient to induce complete regression of poorly immunogenic tumors surrounded by an immunosuppressive microenvironment. In this study, we explored a novel strategy for immunotherapy using magnetic hyperthermia to regress poorly immunogenic melanoma. Magnetic hyperthermia induced tumor cell death in a B16-F10 melanoma mouse model. After hyperthermia treatment, we found elevated levels of HMGB1, which is known to be released from dying cells to promote inflammation, and the proinflammatory cytokine TNF-α was increased in serum of the mice. Systemic administration of glycyrrhizin, an HMGB1 inhibitor, reduced the levels of TNF-α in serum and successfully delayed the regrowth of tumors after magnetic hyperthermia. To achieve complete tumor regression, TLR9 activation by intratumor injection of CpG was combined with systemic administration of anti-PD-1 antibody and anti-CTLA-4 antibody. The combination therapy of magnetic hyperthermia at 46°C with the immunomodulators (glycyrrhizin+CpG+anti-PD-1+anti-CTLA-4) achieved complete tumor regression in 80% of growing 5-mm B16-F10 tumors. These findings have important implications for the development of novel cancer immunotherapy using magnetic hyperthermia for poorly immunogenic tumors. [ABSTRACT FROM AUTHOR]

Purpose: To investigate whether texture features from tumor and peritumoral areas based on sequence combinations can differentiate between low- and non-low-grade meningiomas. Methods: Consecutive patients diagnosed with meningioma by surgery (77 low-grade and 28 non-low-grade meningiomas) underwent preoperative magnetic resonance imaging including T1-weighted imaging (T1WI), T2-weighted imaging (T2WI), diffusion-weighted imaging (DWI), and contrast-enhanced T1WI (CE-T1WI). Manual segmentation of the tumor area was performed to extract texture features. Segmentation of the peritumoral area was performed for peritumoral high-signal intensity (PHSI) on T2WI. Principal component analysis was performed to fuse the texture features to principal components (PCs), and PCs of each sequence of the tumor and peritumoral areas were compared between low- and non-low-grade meningiomas. Only PCs with statistical significance were used for the model construction using a support vector machine algorithm. k-fold cross-validation with receiver operating characteristic curve analysis was used to evaluate diagnostic performance. Results: Two, one, and three PCs of T1WI, apparent diffusion coefficient (ADC), and CE-T1WI, respectively, for the tumor area, were significantly different between low- and non-low-grade meningiomas, while PCs of T2WI for the tumor area and PCs for the peritumoral area were not. No significant differences were observed in PHSI. Among models of sequence combination, the model with PCs of ADC and CE-T1WI for the tumor area showed the highest area under the curve (0.84). Conclusion: The model with PCs of ADC and CE-T1WI for the tumor area showed the highest diagnostic performance for differentiating between low- and non-low-grade meningiomas. Neither PHSI nor PCs in the peritumoral area showed added value. [ABSTRACT FROM AUTHOR]

Purpose: Intraoperative motor-evoked potential (MEP) monitoring is widely used in the neck clipping of cerebral aneurysms. Little is known regarding the usefulness of intraoperative MEP monitoring in endovascular aneurysm surgery. The purpose of this study was to validate the feasibility of intraoperative MEP monitoring during the coil embolization of anterior choroidal artery (AChA) aneurysms. Methods: Clinical and angiographic data of consecutive patients who underwent coil embolization for unruptured AChA aneurysms with or without intraoperative MEP monitoring between January 2014 and December 2018 at our institute were abstracted and analyzed retrospectively. Results: Twenty-three unruptured AChA aneurysms were treated. Eleven patients received MEP monitoring, and three of them experienced intraoperative reduction or disappearance of the MEP wave. Even during MEP changes, AChA filling showed no change in any of the three cases. Although one case with MEP monitoring encountered the disappearance of AChA filling, there was no change in MEP. This might be due to retrograde filling of the AChA from the anastomosis with the lateral posterior choroidal artery. AChA blood flow detected by angiography did not always reflect MEP status. When comparing the presence or absence of MEP monitoring, the volume embolization ratio of coiled aneurysms was significantly better in the MEP group. Conclusion: Intraoperative MEP monitoring during endovascular coiling for AChA aneurysms may be feasible. AChA blood flow detected by angiography does not always reflect MEP status. [ABSTRACT FROM AUTHOR]

Recently, trans-radial intervention has gained popularity as a common procedure to reduce hemorrhagic complications. However, the cuff-type hemostatic device (TR Band) previously used at our institution required 6 h to achieve hemostasis. Since July 2016, we have been using the VasoSTAT, a new hemostatic device that could achieve hemostasis in 4 h. In a verification study, we found that prolonged activated clotting time (ACT) was related to transient hemorrhage occurrence after the hemostatic procedure. Therefore, we designed a hemostatic protocol based on ACT and evaluated its efficacy. In this retrospective and observational study, 78 and 111 patients used the VasoSTAT and TR Band, respectively, from July 2015 to May 2017. In the VasoSTAT group, the ACTs were significantly lower in the hemostasis success (246 ± 46 s) than in the failure group patients (327 ± 59 s) (P < 0.01). Therefore, we applied the hemostatic protocol to 271 patients from May 2017 to March 2020. The hemostasis success rate was 96% in the post-protocol applied group patients, which was significantly higher than the 82% success rate in the pre-protocol applied group patients (P < 0.01). VasoSTAT resulted in adequate hemostasis in 4 h. Further, ACT was predictive of adequate hemostasis. [ABSTRACT FROM AUTHOR]

Purpose: There is no concrete evidence to support the association between the amount of subcutaneous fat area (SFA) in the central venous port-insertion site (precordium) and port-related complications. We aimed to investigate the relationship between SFA in the midclavicular line and postoperative infectious complications in patients undergoing port-insertion surgery. Methods: This was a single-institute and historical cohort study of 174 patients who underwent first central venous port implantation surgery for chemotherapy between January 2014 and December 2018. SFA in the midclavicular line was measured using preoperative computed tomography scans. The patients were divided into three groups according to SFA amount tertiles, and we investigated the association of SFA with infectious and all-cause complication events within 1 year. Results: Within a median follow-up of 306 days, the patients with intermediate SFA had significantly higher infection-free survival than those with low and high SFA (low vs. intermediate vs. high: 80.4% vs. 97.7% vs. 83.4%, respectively, p=0.034). In contrast, there was no significant difference in the overall complication-free survival among the groups (low vs. intermediate vs. high: 80.4% vs. 88.9% vs. 81.8%, respectively, p=0.29). Low SFA was independently associated with high risk of infectious complications (hazard ratio, 9.45; 95% confidence interval, 1.07–83.22, p=0.043). Conclusion: Low SFA in the midclavicular line was an independent risk factor for infectious complications in the chemotherapy setting. This practical indicator can be useful for optimizing patients' nutritional status and when considering other types of vascular access to support administration of intravenous chemotherapy. [ABSTRACT FROM AUTHOR]

Background: The association of long-term acute kidney injury (AKI) risk with angiotensin-converting enzyme (ACE) inhibitor use in neonates/infants is poorly understood. We examined this association to identify potential AKI risk factors. Methods: We retrospectively evaluated 119 children aged < 2 years (72 boys; median age, 5.0 months) who received ACE inhibitors for congenital heart disease for ≥ 6 months between January 2009 and June 2019. We monitored the occurrence of AKI, defined according to the Kidney Disease Improving Global Outcomes guidelines. Demographic and clinical data were extracted from medical records. Risk factors associated with AKI onset were identified by a Cox proportional hazards regression analysis of variables previously identified as risk factors of AKI and those significant in a univariate analysis. Results: Thirty-three of 119 patients (28%) developed AKI at a median follow-up of 1.3 years (interquartile range, 0.8–3.2 years). AKI incidence was 1257 events per 10,000 patient-years. Concomitant tolvaptan use (hazard ratio [HR], 3.81; 95% confidence interval [CI], 1.82–7.97; P < 0.01) and Down syndrome (HR, 3.22; 95% CI, 1.43–7.29; P < 0.01) were identified as independent risk factors of AKI onset. Conclusions: AKI was strongly associated with concomitant tolvaptan use and Down syndrome in our study population. Physicians should consider these factors when prescribing ACE inhibitors for neonates/infants. Low-dose ACE inhibitors slow CKD progression because of their antifibrotic properties. ACE inhibitors may be beneficial for patients with Down syndrome who have underlying CKD in a non-acute setting. Therefore, they should be administered to such patients with caution. [ABSTRACT FROM AUTHOR]

Hepatoma cells are a promising cell source for the construction of bioartificial liver (BAL) systems owing to their high proliferative capability. However, their low liver function compared with primary hepatocytes is a major problem. In a previous study, we established a genetically modified hepatoma cell line, Hepa/8F5, in which eight liver-enriched transcription factor (LETF) genes were transduced into mouse hepatoma Hepa1-6 cells using a drug-inducible transactivator system. These cells proliferate actively under normal culture conditions, meaning that large quantities can be prepared easily. When the overexpression of the LETFs is induced by the addition of an inducer drug, cell growth stops and cell morphology changes with concomitant high expression of liver functions. However, the liver functions largely depend on the presence of the inducer drug, which must be continuously added to maintain these enhanced functions. In the present study, we attempted to modify the method of induction of LETF overexpression in Hepa/8F5 cells to remove the requirement for continual drug addition. To this end, we constructed a system in which the artificial transactivator was transcribed and amplified under the control of a heat-shock protein promoter, and introduced the system into the genome of Hepa/8F5 cells. In our modified cell line, heat-triggered LETF expression was confirmed to induce high liver function. After drug-screening of transfected cells, we established a hepatoma cell line (Hepa/HS), which exhibited high, heat-inducible liver functions. The Hepa/HS cells may represent a new cell source for hepatic studies such as the construction of BAL systems. [ABSTRACT FROM AUTHOR]

This document is a correction notice for an article titled "Induction of functional tissue-engineered skeletal muscle constructs by defined electrical stimulation" published in Scientific Reports. The correction addresses an error in the Methods section of the article. Specifically, it corrects the mention of the equipment used to count the total number of nuclei in the tissue construct. The correct equipment is NucleoCounter® by ChemoMetec, not NucleoCassette™ and NuceloCounter by Chemometec. The authors of the article are Akira Ito, Yasunori Yamamoto, Masanori Sato, Kazushi Ikeda, Masahiro Yamamoto, Hideaki Fujita, Eiji Nagamori, Yoshinori Kawabe, and Masamichi Kamihira. [Extracted from the article]

Scale-up of production is needed for industrial applications and clinical translation of human induced pluripotent stem cells (hiPSCs). However, in cryopreservation of hiPSCs, successful rewarming of vitrified cells can only be achieved by convective warming of small volumes (generally 0.2 mL). Here, we present a scalable nano-warming technology for hiPSC cryopreservation employing inductive heating of magnetic nanoparticles under an alternating magnetic field. The conventional method by water bath heating at 37 °C resulted in a decrease of cell viability owing to devitrification caused by slow warming of samples with large volumes (≥ 20 mL). Nano-warming showed uniform and rapid rewarming of vitrified samples and improved viability of hiPSCs in the 20-mL system. In addition to single cells, hiPSC aggregates prepared using a bioreactor-based approach were successfully cryopreserved by the nano-warming technique. These results demonstrate that nano-warming is a promising methodology for cryopreservation in mass production of hiPSCs. [ABSTRACT FROM AUTHOR]

Background: Ulcerative colitis (UC) developing during chemotherapy is very rare. Here, we describe a case of acute onset during chemoradiotherapy for lung adenocarcinoma, requiring a total proctocolectomy. Case presentation: A 52-year-old man was admitted to the hospital for chemoradiotherapy of lung cancer. He had no obvious history of gastrointestinal diseases, and concurrent chemoradiotherapy was initiated. Thirteen days after 2 cycles of cisplatin and vinorelbine, he experienced persistent hematochezia. Findings of the colonoscopy revealed edematous thickening from the rectum to the transverse colon, suggesting UC, drug-induced colitis, or infectious colitis. Results from bacterial culture were negative for Clostridium difficile and methicillin-resistant Staphylococcus aureus (MRSA). Immunohistological staining for cytomegalovirus was also negative. Although he was clinically diagnosed with UC and treated with intravenous glucocorticoid, his symptoms gradually worsened and an abdominal X-ray revealed megacolon. Thirty-five days after conservative therapy, a total proctocolectomy with end permanent ileostomy was performed. Based on pathological findings and clinical course, he was diagnosed with UC. Conclusion: Although the pathogenesis of UC during chemotherapy has been unknown, chemotherapy could be one of the causes of UC in this case. UC should be included in the differential diagnosis in patients with progressive colitis during chemotherapy. [ABSTRACT FROM AUTHOR]

Cystic echinococcosis (CE), the parasitic disease caused by the larval stage of Echinococcus granulosus sensu lato (s.l.), is a global public health problem. In Mongolia, despite wide distribution of human CE, not enough information is available on the prevalence and molecular characterization of CE in livestock and its zoonotic linkage with human cases. We investigated the distribution of human CE cases and livestock population using statistical models to get insight into the zoonotic linkage. The incidence of human CE cases increased by a factor of 1.71 for one interquartile range increment in the density of the camel population. No significant association was observed with other livestock species. The samples collected from 96 camels and 15 goats in an endemic region showed a CE prevalence of 19.7% and 6.7%, respectively. All livestock CE were E. granulosus s.l. G6/G7 species of the E. granulosus s.l. complex. The genetic diversity was investigated using the haplotype network based on full cox1 gene analysis of the samples collected from livestock CE and nucleotide sequences previously reported from human CE and wild canids infection in Mongolia. Four haplotypes were identified within the livestock samples, two of which had not been previously reported. A common haplotype was identified among humans, camels, goats, and a wolf, all of which were within the same geographical area. A mixed infection of E. granulosus s.l. G6/G7 with different haplotypes in the intermediate host was identified. To the best of our knowledge, this is the most comprehensive description of the current epidemiological situation of CE in Mongolia with substantial evidence that camels might be the main intermediate host of E. granulosus s.l. G6/G7 in Mongolia. Moreover, our result presents the first report in the country to provide insight into the prevalence of E. granulosus s.l. G6/G7 in livestock. [ABSTRACT FROM AUTHOR]

Groundwater movement through the slope area of Mt. Fuji to the coastal area of Suruga Bay (central Japan) was investigated using spatially dense geochemical data, as a case study for elucidating the groundwater flow system in a stratovolcano adjacent to the coast. Spatial distributions of the hydrogen stable isotope ratio, vanadium concentration, and water temperature in the groundwater showed anomalies at the coastal area of Suruga Bay. The anomalies were characterized as depleted isotope ratio, high vanadium concentration, and low water temperature relative to surroundings. This can be explained as a regional deep groundwater flow from the slope of Mr. Fuji to the coastal area of Suruga Bay because groundwater recharged at higher elevation has a depleted isotope ratio caused by the altitude effect and high vanadium concentration as a result of dissolution from the basaltic aquifer. These characteristics also imply a hierarchical flow system, which is incorporated into a hydrogeological model of the coastal aquifer. [ABSTRACT FROM AUTHOR]

The effects of amino acids on calcium phosphate phase transformation were investigated by using attenuated total reflection (ATR)-infrared (IR) spectroscopy. A self-setting apatite cement, which consisted of tetracalcium phosphate and dicalcium phosphate, was transformed into hydroxyapatite (HAp) by kneading with a phosphoric acid solution. Phosphate buffer (0.2 M, pH 6.8) or aqueous solutions of 0.1 w/v% amino acids (alanine, asparagine, serine, and o-phospho-L-serine) were used as the kneading solutions. The kneaded samples were analyzed by ATR-IR spectroscopy. The amount of HAp produced was determined by the multivariate curve resolution alternative least-squares method based on the ATR-IR spectra. The phase transformations to HAp were fitted to several solid-state kinetic models. The results indicate that o-phospho-L-serine inhibits the crystal growth of HAp. A simulation model of HAp surface interaction was developed by using the molecular dynamics method. The total energy of the HAp surface with amino acids was sufficient to explain the o-phospho-L-serine inhibition model. The inhibition is attributed to the specific adsorption of o-phospho-L-serine on the surface of HAp seed crystals. [ABSTRACT FROM AUTHOR]

An amendment to this paper has been published and can be accessed via a link at the top of the paper. [ABSTRACT FROM AUTHOR]

Objectives: The progression level of extracapsular spread (ECS) for cervical lymph node metastasis of oral squamous cell carcinoma (OSCC) was previously divided into three types, and their relationships with the prognosis of patients were re-examined.Patients and methods: The Kaplan-Meier method was used to examine overall survival (OS) and relapse-free survival (RFS) curves. Prognosis factor for recurrence was analyzed with univariate and multivariate analysis.Results: ECS was detected in 216 cases of OSCC and analyzed. The 5-year overall survival and RFS rates of patients with type C, which was microscopically defined as tumor invasion to perinodal fat or muscle tissue, were significantly poor at 40.6 and 37.8%, respectively. The results of a univariate analysis suggested that the prognosis of ECS in OSCC patients is associated with its progression level, particularly type C. The 5-year RFS rate of type C with tumor budding was significantly poor at 31.5%. Type C with tumor budding correlated with local and regional recurrence as well as distant metastasis. In a multivariate analysis, tumor budding was identified as an independent prognostic factor.Conclusions: These results suggest that the progression level of ECS and tumor budding are useful prognostic factors in OSCC patients.Clinical relevance: This study indicated that the progression level and tumor budding of ECS for cervical lymph node metastasis were useful prognostic factors in OSCC patients. [ABSTRACT FROM AUTHOR]

Hepatoma cells are a candidate cell source for bio-artificial livers. However, they exhibit reduced liver functions compared with primary hepatocytes. In our previous study, genetically engineered mouse hepatoma cells were created by transduction with vectors mediating inducible overexpression of eight liver-enriched transcription factors. Upon the induction of the liver-enriched transcription factors transduced, the cells expressed both phenotypic and genotypic liver functions at high levels. In the present study, we performed three-dimensional culture of these cells using macroporous gelatin beads. When immobilized on the macroporous gelatin beads, these cells exhibited further enhancement in liver functionality, including increased albumin secretion, ammonia removal and cytochrome P450 activity. The levels of these functions were significantly enhanced compared to monolayer culture. The method is simple and scalable, and provides highly functional cells that can be used in basic and applied fields of hepatic research. [ABSTRACT FROM AUTHOR]

Chloroapatite (ClAp), which is more soluble than hydroxyapatite (HAp), was synthesized in order to improve the inert nature of HAp as implant material. Two mechanochemical synthetic methods were investigated. In one method, CaCl was added after the formation of amorphous calcium phosphate from CaHPO·2HO and CaO in a planetary ball mill; in the other method, CaCl, CaHPO·2HO, and CaO were mixed from the beginning in the mill. Thus, obtained products were evaluated by a powder X-ray diffractometry and an attenuated total reflection-infrared spectroscopy. The mechanochemical synthetic method is found to be useful for the synthesis of ClAp because of its simplicity in operation and equipment. The ClAp produced by the former method is contaminated with carbonate ion and its crystallinity is lower than that produced by the latter method. The carbonate ion also affects the behavior of ClAp in pure water and in a simulated body fluid. [ABSTRACT FROM AUTHOR]

We observed photoexcited carrier responses in solar cells excited by femtosecond laser pulses with spatial and temporal resolution using an optical pump-terahertz emission probe technique. We visualized the ultrafast local variation of the intensity of terahertz emission from a polycrystalline silicon solar cell using this technique and clearly observed the change in signals between a grain boundary and the inside of a grain in the solar cell. Further, the time evolution of the pump-probe signals of the polycrystalline and monocrystalline silicon solar cells was observed, and the relaxation times of photoexcited carriers in the emitter layers of crystalline silicon solar cells were estimated using this technique. The estimated relaxation time was consistent with the lifetime of the Auger recombination process that was dominant in heavily doped silicon used as an emitter layer for the silicon solar cells, which is difficult to obtain with photoluminescence method commonly used for the evaluation of solar cells. [ABSTRACT FROM AUTHOR]

The effect of hydroxypropyl cellulose (HPC) and hydroxypropyl methylcellulose (HPMC) on carbamazepine (CBZ) polymorphic transformation has been investigated by an attenuated total reflectance-infrared (ATR-IR) spectroscopy and chemoinformatics. CBZ anhydrate samples were each kneaded with 35.0 μL of pure water, aqueous solution of 0.005 w/ v% HPC, or that of 0.005 w/ v% HPMC. Each paste was put on a germanium glass of an ATR accessory and was covered with a sheet of Parafilm® at 20 ± 2 °C. Measured IR spectra were analyzed by a multivariate curve resolution-alternating least squares (MCR-ALS) and a two-dimensional correlation spectroscopic analysis. Source vectors of MCR-ALS were assigned to CBZ anhydrate and dihydrate. Concentration data of MCR-ALS were evaluated for the kinetics of CBZ polymorphic transformation. The combination of ATR-IR spectroscopy and MCR-ALS is concluded to be useful for the elucidation of rapid polymorphic transformation in suspension. The transformation rate is delayed by HPC and HPMC. [ABSTRACT FROM AUTHOR]

Purpose: Leg muscle activation profiles and muscle-tendon interaction were studied with eleven internationally high-level Kenyan and eleven national level Japanese distance runners. Methods: Ultrasonography and kinematics were applied together with surface electromyography (EMG) recordings of leg muscles when subjects ran on treadmill at 9.0 (SLOW) and 13.9 km h (MEDIUM). Results: At each speed, both groups presented similar contact and flight times. The kinematic and ultrasound analyses revealed that, in contrast to the Japanese runners, the Kenyans demonstrated during contact smaller stretching and shortening amplitudes ( p < 0.01) of the tendinous tissue of medial gastrocnemius (MG), but greater tendon contribution to the muscle-tendon unit shortening ( p < 0.05). The MG fascicles of the Kenyans were shorter not only at the resting standing position, but also during the contact phase at both running speeds ( p < 0.01). The EMG profiles of the Kenyans showed lower braking/preactivation ratio in both MG and tibialis anterior ( p < 0.05) muscles. They were also characterized by negative relationships between the Achilles tendon moment arm and the MG fascicle shortening during contact ( r = −0.54, p < 0.01). In contrast, the Japanese presented the classical stretch-shortening cycle muscle activation profile of relatively high MG EMG activity during the braking phase. Conclusion: These findings provide new suggestions that the Kenyans have unique structural characteristics which can result in the reduction of muscle and tendinous stretch-shortening loading together with smaller muscle activation during contact at submaximal running speed. [ABSTRACT FROM AUTHOR]

Renal hypouricemia type 1 is caused by mutations in the SLC22A12 gene, whereas type 2 is caused by defects in the SLC2A9 gene. Although both subtypes predispose to exercise-induced acute kidney injury (EIAKI), posterior reversible encephalopathy syndrome (PRES) occurring with this disorder is an uncommon phenomenon that has only been reported to date in a patient with renal hypouricemia type 2. We describe a 13-year-old boy with renal hypouricemia type 1 (serum uric acid, 0.9 mg/dL) with a homozygous W258X mutation in the SLC22A12 gene, presenting with EIAKI and PRES. On admission, his body weight was 61 kg (11 kg above the dry weight), and blood pressure was 153/88 mmHg. Cranial magnetic resonance imaging revealed high-intensity areas in the cortical and subcortical white matter of the occipital lobe. After admission, the patient responded well to a combination of hemodialysis and intravenous nicardipine. This is the first case of concurrent PRES and EIAKI in a patient with renal hypouricemia type 1. We suggest that PRES is not due to severe hypouricemia caused by SLC2A9 mutation but is a manifestation of severe EIAKI associated with renal hypouricemia. [ABSTRACT FROM AUTHOR]

It is often difficult to classify rare malignant pediatric mixed brain tumors composed of mesenchymal elements. A 6-year-old boy presented to our hospital with a left frontal massive tumor manifesting as complaints of rapidly progressive right hemiparesis and motor aphasia over 2 weeks. Computed tomography showed a left frontal mass with thick calcification. Magnetic resonance imaging revealed an enhanced lesion with perifocal edema and mass effect. Total removal of the tumor was performed. Histological examination of the resected tumor revealed an anaplastic malignant small round cell component with a bland-looking mesenchymal spindle cell component. The patient was treated with irradiation to the whole craniospinal axis and a boost to the tumor bed, followed by chemotherapy consisting of ifosfamide, cisplatin, and etoposide, resulting in good control without local recurrence or metastasis at 2 years. A combined malignant tumor composed of ectodermal and mesenchymal components is generally named malignant ectomesenchymoma (MEM). The more malignant part of MEM is the mesenchymal component in most cases. In the present case, the more malignant component was not the mesenchymal component, but the small round cells. [ABSTRACT FROM AUTHOR]

The efficacy of rituximab (RTX) as the sole therapy for preventing relapses of nephrotic syndrome (NS) is transient in most patients; therefore, the optimal therapy required for maintaining a successful response to a biological agent remains a challenge. We conducted a prospective study to compare the efficacy of cyclosporine (CsA) with that of mycophenolate mofetil (MMF) as maintenance therapy after a single infusion of RTX. Of 29 patients with persistent steroid-dependent NS despite the use of CsA and/or MMF, 13 without chronic nephrotoxicity continued CsA therapy, maintaining a 2-h post-dose CsA level of 400-500 ng/ml (CsA group). The remaining 16 were treated with MMF, maintaining a pre-dose level of 2-5 μg/ml of mycophenolic acid (MMF group). The median duration of CsA and MMF treatment was 18 and 19 months, respectively. Despite the mean number of relapses before RTX treatment being significantly lower in the MMF group than in the CsA group (2.3/year vs. 4.6/year, p < 0.01), treatment failure occurred more frequently in the MMF group (7/16) than in the CsA group (2/13). The rate of sustained remission was also significantly higher in the CsA group than in the MMF group ( p < 0.05). Conclusion: In patients with severe steroid-dependent NS, CsA appears to be more effective than MMF for maintaining remission after a single infusion of RTX. [ABSTRACT FROM AUTHOR]

Neospora caninum is an obligate intracellular protozoan parasite that causes severe neuromuscular diseases, repeated abortion, stillbirth, and congenital infection in livestock and companion animals. The development of an effective vaccine against neosporosis in cattle is an important issue due to the significant worldwide economic impact of this disease. We evaluated the immunogenicity of four bradyzoite antigens, NcBAG1 (first described in this study), NcBSR4, NcMAG1, and NcSAG4, using an acute infection mouse model to determine synergistic effects with the tachyzoite antigen as a candidate for vaccine production. Mice were inoculated with the recombinant vaccines (r-)NcBAG1, rNcBSR4, rNcMAG1, rNcSAG4, or phosphate-buffered saline (PBS) (adjuvant control group) in an oil-in-water emulsion with bitter gourd extract, a Th1 immune stimulator, or PBS alone as the infection control group. Mice inoculated with each vaccine developed antigen-specific IgG1 and IgG2a antibodies and isolated splenocytes from mice produced high levels of interferon-γ when infected with the N. caninum tachyzoite. The mice inoculated with rNcBAG1, rNcMAG1, or rNcSAG4 developed slight to moderate clinical symptoms but did not succumb to infection. In contrast, rNcBSR4 and both control groups developed severe disease and some mice required euthanasia. The parasitic burden in the brain tissues of vaccinated mice was assessed by N. caninum-specific real-time PCR at 5 weeks after infection. The parasite load in rNcBAG1-, rNcMAG1-, and rNcSAG4-inoculated mice was significantly lower than that in adjuvant and infection control mice. Therefore, these antigens may be useful for the production of a N. caninum-specific vaccination protocol. [ABSTRACT FROM AUTHOR]

Due to serious concerns on very late stent thrombosis (VLST), extended use of dual antiplatelet therapy (DAPT) beyond 1 year after DES implantation has become a common clinical practice despite apparent lack of evidence suggesting its efficacy in reducing VLST. The study population consisted of 12812 patients in the j-Cypher registry who were treated with at least one sirolimus-eluting stent (SES). We assessed the relation between duration of thienopyridine therapy and clinical outcomes with a landmark analysis at 1 year after SES implantation. Among 11713 patients without myocardial infarction (MI), stent thrombosis and stroke at 1 year who were eligible for the landmark analysis, 7414 patients (63 %) were maintained on thienopyridine at 1-year landmark point, while 4299 patients (37 %) had discontinued thienopyridine before 1-year landmark point. Patients in the on-thienopyridine group had more complex characteristics than patients in the off-thienopyridine group. Cumulative incidence of and the risk for definite VLST in the on-thienopyridine group relative to the off-thienopyridine group favored prolonged DAPT, but were not significant [0.9 and 1.2 %, P = 0.1, and adjusted HR (95 % CI): 0.71 (0.47-1.06), P = 0.11]. Cumulative incidence of and the risk for a composite of death, MI, or stroke in the on-thienopyridine group relative to the off-thienopyridine group were also not significant [15.3 and 14.3 %, P = 0.15, and adjusted HR (95 % CI): 0.99 (0.89-1.11), P = 0.89]. Prolonged use of thienopyridine beyond 1 year after SES implantation was not associated with significant decrease in the risks for VLST or for serious cardiovascular events including death, MI or stroke. [ABSTRACT FROM AUTHOR]

The Qinghai-Tibetan Plateau (QTP, in western China), which is the largest and highest plateau on Earth, is a highly epidemic region for Echinococcus spp. We collected 70 Echinococcus samples from humans, dogs, sheep, yaks, plateau pikas, and voles in eastern and southern Qinghai and genotyped them using the mitochondrial DNA marker cytochrome oxidase subunit I gene and maximum parsimony and Bayesian reconstruction methods. Based on the 792-bp sequence matrix, we recorded 124 variable sites, of which, 115 were parsimony-informative. Thirty-four haplotypes (H1-H34) were detected, of which H1-H15, H16-H17, and H18-H34 belonged to Echinococcus shiquicus, Echinococcus multilocularis, and Echinococcus granulosus, respectively. Within 26 human isolates, three were identified as E. multilocularis and 23 were E. granulosus. We also detected a dual infection case in a dog with E. multilocularis and E. granulosus. The intraspecific haplotype (Hd ± SD) and nucleotide (Nd ± SD) diversity of E. shiquicus (0.947 ± 0.021; 0.00441 ± 0.00062) was higher than that for E. granulosus (0.896 ± 0.038; 0.00221 ± 0.00031) and E. multilocularis (0.286 ± 0.196; 0.00036 ± 0.00025). Moreover, the haplotype network of E. shiquicus showed a radial feature rather than a divergent feature in a previous study, indicating this species in the QTP has also evolved with bottleneck effects. [ABSTRACT FROM AUTHOR]

We previously reported an accumulative site-specific gene integration system using Cre recombinase and mutated loxP sites, where a recombinase-mediated cassette exchange (RMCE) reaction is repeatable. This gene integration system was applied for antibody production using recombinant Chinese hamster ovary (CHO) cells. We introduced an exchange cassette flanked by wild-type and mutated loxP sites into the chromosome of CHO cells for the establishment of recipient founder cells. Then, the donor plasmids including an expression cassette for an antibody gene flanked by a compatible pair of loxP sites were prepared. The donor plasmid and a Cre expression vector were co-transfected into the founder CHO cells to give rise to RMCE in the CHO genome, resulting in site-specific integration of the antibody gene. The RMCE procedure was repeated to increase the copy numbers of the integrated gene. Southern blot and genomic PCR analyses for the established cells revealed that the transgenes were integrated into the target site. Antibody production determined by ELISA and western blotting was increased corresponding to the number of transgenes. These results indicate that the accumulative site-specific gene integration system could provide a useful tool for increasing the productivity of recombinant proteins. [ABSTRACT FROM AUTHOR]

The dysbindin-1 and neuregulin-1 (NRG-1) genes are related to schizophrenia. Expression studies in postmortem brains have revealed lower expression of dysbindin-1 and higher expression of NRG-1 in brain tissue from subjects with schizophrenia. In addition to the difficulty of sampling, the use of postmortem brain tissues is not ideal because these tissues are heterogeneous with respect to biochemical parameters, lifetime history of medications and physiological status at the time of death. In contrast, medication and environmental influences that could mask the genetic basis of differences in RNA expression are removed in immortalized lymphocytes by culturing. Only a few microarray analysis studies using immortalized lymphocytes in schizophrenia have been reported, and whether immortalized lymphocytes are an appropriate alternative to neuronal tissue remains controversial. In this study, we measured the mRNA expression levels of dysbindin-1, NRG-1 and two other genes (NPY1R and GNAO1) in immortalized lymphocytes from 45 patients with schizophrenia and 45 controls using real-time quantitative reverse transcriptase-PCR. No difference was observed between patients and controls with respect to the expression of dysbindin-1, NRG-1, NPY1R or GNAO1 gene. Our findings suggest that the gene expression profile of immortalized lymphocyte from schizophrenic patients is different from that in postmortem brain tissue at least with respect to the dysbindin-1 and NRG-1 genes. [ABSTRACT FROM AUTHOR]

We previously reported the production of human erythropoietin (hEpo) using genetically manipulated (GM) chickens. The recombinant hEpo was produced in the serum and egg white of the GM chickens, and the oligosaccharide chain structures of the serum-derived hEpo were more favorable than those of the egg white-derived hEpo. In the present study, a retroviral vector encoding an expression cassette for a fusion protein of hEpo and the Fc region of human immunoglobulin G (hEpo/Fc) was injected into developing chicken embryos, with the aim of recovering the serum-derived hEpo from egg yolk through the yolk accumulation mechanism of maternal antibodies. The GM chickens that hatched stably produced the hEpo/Fc fusion protein not only in their serum and egg white, but also in the egg yolk as expected. Lectin blot analyses revealed that significant amounts of the oligosaccharide chains of hEpo/Fc produced in the serum and eggs of GM chickens terminated with galactose, and that the oligosaccharide chains of the serum- and yolk-derived hEpo/ Fc incorporated sialic acid residues. Moreover, biological activity assessment using Epo-dependent cells revealed that the yolk-derived hEpo/Fc exhibited a comparable performance to the serum- and CHO-derived hEpo/Fc. These results indicate that transport of Fc fusion proteins from the blood circulation to the yolk in chickens represents an effective strategy for the production of pharmaceutical glycoproteins using transgenic chicken bioreactors. [ABSTRACT FROM AUTHOR]

Taste buds and the peripheral nerves innervating them are two important components of the peripheral gustatory system. They require appropriate connections for the taste system to function. Neurotrophic factors play crucial roles in the innervation of peripheral sensory organs and tissues. Both brain-derived neurotrophic factor (BDNF) null-mutated and neurotrophin-4 (NT-4) null-mutated mice exhibit peripheral gustatory deficits. BDNF and NT-4 bind to a common high affinity tyrosine kinase receptor, TrkB (NTRK-2), and a common p75 neurotrophin receptor (NGFR). We are currently using a transgenic mouse model to study peripheral taste system development and innervation in the absence of both TrkB ligands. We show that taste cell progenitors express taste cell markers during early stages of taste bud development in both BDNF−/−xNT-4−/− and wild-type mice. At early embryonic stages, taste bud progenitors express Troma-1, Shh, and Sox2 in all mice. At later stages, lack of innervation becomes a prominent feature in BDNF−/−xNT-4−/− mice leading to a decreasing number of fungiform papillae and morphologically degenerating taste cells. A total loss of vallate taste cells also occurs in postnatal transgenic mice. Our data indicate an initial independence but a later permissive and essential role for innervation in taste bud development and maintenance. [ABSTRACT FROM AUTHOR]

We describe the fabrication of three-dimensional tissue constructs using a magnetic force-based tissue engineering technique, in which cellular organization is controlled by magnetic force. Target cells were labeled with magnetite cationic liposomes (MCLs) so that the MCL-labeled cells could be manipulated by applying a magnetic field. Line patterning of human umbilical vein endothelial cells (HUVECs) labeled with MCLs was successfully created on monolayer cells or skin tissues using a magnetic concentrator device. Multilayered cell sheets were also inducible on a culture surface by accumulating MCL-labeled cells under a uniform magnetic force. Based on these results, we attempted to construct a complex multilayered myoblast C2C12 cell sheet. Here, patterned HUVECs were embedded by alternating the processes of magnetic accumulation of C2C12 cells for cell layer formation and magnetic patterning of HUVECs on the cell layers. This technique may be applicable for the fabrication of complex tissue architectures required in tissue engineering. [ABSTRACT FROM AUTHOR]