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Background: Postoperative rotator cuff retear after arthroscopic rotator cuff repair (ARCR) is still a major problem. Various risk factors such as age, gender, and tear size have been reported. Recently, magnetic resonance imaging-based stump classification was reported as an index of rotator cuff fragility. Although stump type 3 is reported to have a high retear rate, there are few reports on the risk of postoperative retear based on this classification. Machine learning (ML), an artificial intelligence technique, allows for more flexible predictive models than conventional statistical methods and has been applied to predict clinical outcomes. In this study, we used ML to predict postoperative retear risk after ARCR., Methods: The retrospective case-control study included 353 patients who underwent surgical treatment for complete rotator cuff tear using the suture-bridge technique. Patients who initially presented with retears and traumatic tears were excluded. In study participants, after the initial tear repair, rotator cuff retears were diagnosed by magnetic resonance imaging; Sugaya classification types IV and V were defined as re-tears. Age, gender, stump classification, tear size, Goutallier classification, presence of diabetes, and hyperlipidemia were used for ML parameters to predict the risk of retear. Using Python's Scikit-learn as an ML library, five different AI models (logistic regression, random forest, AdaBoost, CatBoost, LightGBM) were trained on the existing data, and the prediction models were applied to the test dataset. The performance of these ML models was measured by the area under the receiver operating characteristic curve. Additionally, key features affecting retear were evaluated., Results: The area under the receiver operating characteristic curve for logistic regression was 0.78, random forest 0.82, AdaBoost 0.78, CatBoost 0.83, and LightGBM 0.87, respectively for each model. LightGBM showed the highest score. The important factors for model prediction were age, stump classification, and tear size., Conclusions: The ML classifier model predicted retears after ARCR with high accuracy, and the AI model showed that the most important characteristics affecting retears were age and imaging findings, including stump classification. This model may be able to predict postoperative rotator cuff retears based on clinical features., (Copyright © 2023 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Elsevier Inc. All rights reserved.)

B7-H4 (VTCN1), a member of the B7 family, is overexpressed in several types of cancer. Here we investigated the pattern of expression of B7-H4 in salivary gland carcinomas (SGC) and assessed its potential as a prognostic marker and therapeutic target. Immunohistochemistry (IHC) analyses were performed in a cohort of 340 patient tumors, composed of 124 adenoid cystic carcinomas (ACC), 107 salivary duct carcinomas (SDC), 64 acinic cell carcinomas, 36 mucoepidermoid carcinomas (MEC), 9 secretory carcinomas (SC), as well as 20 normal salivary glands (controls). B7-H4 expression was scored and categorized into negative (<5% expression of any intensity), low (5%-70% expression of any intensity or >70% with weak intensity), or high (>70% moderate or strong diffuse intensity). The associations between B7-H4 expression and clinicopathologic characteristics, as well as overall survival, were assessed. Among all tumors, B7-H4 expression was more prevalent in ACC (94%) compared with those of SC (67%), MEC (44%), SDC (32%), and acinic cell carcinomas (0%). Normal salivary gland tissue did not express B7-H4. High expression of B7-H4 was found exclusively in ACC (27%), SDC (11%), and MEC (8%). In SDC, B7-H4 expression was associated with female gender (P = .002) and lack of androgen receptor expression (P = .012). In ACC, B7-H4 expression was significantly associated with solid histology (P < .0001) and minor salivary gland primary (P = .02). High B7-H4 expression was associated with a poorer prognosis in ACC, regardless of clinical stage and histologic subtype. B7-H4 expression was not prognostic in the non-ACC SGC evaluated. Our comparative study revealed distinct patterns of B7-H4 expression according to SGC histology, which has potential therapeutic implications. B7-H4 expression was particularly high in solid ACC and was an independent prognostic marker in this disease but not in the other SGC assessed., (Copyright © 2023 United States & Canadian Academy of Pathology. Published by Elsevier Inc. All rights reserved.)

Background: Retear after arthroscopic rotator cuff repair (ARCR) remains a complication of important concern. Few reports have evaluated retear timing and its associated patient characteristics in large cohorts. This study aimed to investigate retear timing and patient characteristics and factors associated with this parameter., Methods: Of the 638 consecutive shoulders that underwent ARCR from August 2009 to November 2019, shoulders with retear complication within 1 year of surgery were included. Retears were defined as type IV or V of the Sugaya's classification, and magnetic resonance imaging was performed at 6 weeks, 3 months, 6 months, and 1 year after surgery. The distribution of patients with retears at the timing of retears was investigated. In addition, patients with retears were classified into the following two groups: early group with retears occurring at 6 weeks and 3 months postoperatively or late group with retears occurring between 6 months and 1 year postoperatively. Associated factors such as sex, age, tear size, pre and postoperative range of motion, surgical technique, and clinical outcome between the two groups were investigated., Results: The 41 shoulders with retears were divided into four groups: 1) within 6 weeks after surgery (n = 9, 22.0%), 2) 6 weeks-to 3 months after surgery (n = 19, 46.3%), 3) 3-6 months after surgery (n = 11, 26.8%), and 4) 6 months-1 year after surgery (n = 2, 4.9%). In addition, there were significantly larger retear sizes in the Sugaya's classification in the early group compared to the late group (P = .013), while there were significantly more males in the late group compared to the early group (P = .030)., Conclusion: The highest retear rate after ARCR was observed from 6 weeks to 3 months after surgery, with equivalent rates within 6 weeks and from 3 months to 6 months after surgery., (Copyright © 2023. Published by Elsevier Inc.)

Objectives: We aimed to determine if achieving a 10-m walk target within the first week of stroke onset correlates with independent outdoor walking at discharge and discharge to home for patients with stroke., Materials and Methods: This study included 226 patients transferred to the subacute rehabilitation hospital (SRH) between January 2018 and March 2021. Data obtained from hospital records included age, sex, stroke type, lesion side, body mass index, presence of acute treatment, length of days from onset to physical therapy intervention, National Institutes of Health Stroke Scale, length of hospital stay, Functional Independence Measure score, and the ability to complete the 10 m walk target within the first week of stroke onset. The primary outcomes were independent outdoor walking ability and discharge destination from the SRH. A logistic regression analysis was performed to determine if the 10 m walking ability correlated with the outdoor walking ability and discharge destination., Results: Compared with the inability to walk 10 m, walking 10 m independently walking within the first week of stroke onset correlated with the ability to walk independently outdoors at discharge (odds ratio [OR]: 4.38, p = 0.003) and being discharged home (OR: 4.52, p = 0.002), whereas, walking 10 m with assistance was associated with being discharged home (OR: 3.09, p = 0.043)., Conclusions: The ability to walk 10 m within the first week of stroke onset may be a helpful marker for prognosis., Competing Interests: Declaration of Competing Interest None to declare., (Copyright © 2023 Elsevier Inc. All rights reserved.)

In ELISA, blocking reagents and stabilizers are important to improve the sensitivity and/or quantitative nature of the measurement system. Usually, biological substances such as bovine serum albumin and casein are used, but they still have problems such as lot-to-lot differences and biohazard. Here, we describe the methods using a chemically synthesized polymer, BIOLIPIDURE®, as a new blocking agent and stabilizer that can solve these problems., (© 2023. The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: The aim of this study was to examine risk factors of respiratory complications at the diagnosis and establish an algorithm of clinical management in children and adolescents with mediastinal tumors., Methods: We retrospectively collected clinical information of all children and adolescents who presented with mediastinal tumors at Saitama Children's Medical Center from 1999 to 2019, including age, sex, pathological diagnosis, eight major clinical symptoms (cough, dyspnea, hypoxia, orthopnea, chest pain, wheeze, superior vena cava syndrome, and stridor), chest computed tomography (CT) findings (tumor location, mediastinal mass ratio, pleural fluid, pericardial effusion, and compression of trachea and bronchi), types of diagnostic procedure and anesthesia, respiratory complications (severe hypoxia, difficult ventilation, respiratory failure, and cardiopulmonary arrest), and clinical outcome. Subsequently, we calculated the risk score for predicting respiratory complications by combining clinical and radiological findings., Results: Of the 57 patients, 7 (12%) developed respiratory complications. Cough, dyspnea, hypoxia, and orthopnea were significantly more common in patients with complications (p = 0.02, p = 0.02, p < 0.01, p = 0.03, respectively). The reduction of percentage of tracheal cross-sectional area (%TCA) and compression of the carina in chest CT were also significantly more common in patients with complications (p < 0.01 and <0.01, respectively). We calculated the risk score of respiratory complications by combining cough, wheeze, stridor, orthopnea, dyspnea, hypoxia, %TCA < 0.5, and compression of the carina. A risk score ≥ 7 showed high predictive accuracy for complications (sensitivity: 100%, specificity: 97.7%, positive likelihood ratio: 43.0)., Conclusion: The risk score combining clinical symptoms with radiological findings is a promising predictive tool for respiratory complications in children with mediastinal tumors., (© 2022 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Aim: To study the effect of Ninjin'yoeito (NYT) on postpartum anemia and on the development of postpartum depression (PPD)., Methods: In this prospective, single-center, open-label, quasi-randomized controlled trial, patients with anemia 1-2 days postdelivery were randomized to receive either NYT or an oral iron preparation for 4 weeks. The primary endpoint was the hemoglobin (Hb) level. Secondary endpoints were fatigue (assessed by the numerical rating scale [NRS]) and prevalence of postpartum depressive symptoms, as defined by an Edinburgh postnatal depression scale (EPDS) score ≥9. Hb levels and fatigue were measured before, and 4 weeks after, treatment and the EPDS was measured 4 weeks posttreatment., Results: Of 1066 participants (NYT group: 532, iron group: 534) 1061 (NYT group: 529, iron group: 532) underwent full analysis. The Hb level increased significantly in both groups (p < 0.001), and there were no significant differences between the groups in terms of the change in Hb levels (NYT: 2.4 ± 0.8 g/dL vs. iron: 2.5 ± 0.7 g/dL, p = 0.098). Fatigue decreased significantly in the NYT group (p < 0.001) but did not change in the iron group, and the difference was significant (p < 0.001). There was a significant difference between the two groups in terms of the prevalence of postpartum depressive symptoms (NYT: 5.7% vs. iron: 9.4%, odds ratio [OR] = 0.58, 95% confidence interval [CI] = 0.36-0.93)., Conclusion: The results suggest that NYT improves postpartum anemia and fatigue, and may be able to prevent the development of PPD., (© 2022 Japan Society of Obstetrics and Gynecology.)

The hole-carrier transport of organic semiconductors is widely known to occur via intermolecular orbital overlaps of the highest occupied molecular orbitals (HOMO), though the effect of other occupied molecular orbitals on charge transport is rarely investigated. In this work, we first demonstrate evidence of a mixed-orbital charge transport concept in the high-performance N-shaped decyl-dinaphtho[2,3- d :2',3'- d ']benzo[1,2- b :4,5- b ']dithiophene (C 10 -DNBDT-NW), where electronic couplings of the second HOMO (SHOMO) and third HOMO (THOMO) also contribute to the charge transport. We then present the molecular design of an N-shaped bis(naphtho[2',3':4,5]thieno)[2,3- b :2',3'- e ]pyrazine (BNTP) π-electron system to induce more pronounced mixed-orbital charge transport by incorporating the pyrazine moiety. An effective synthetic strategy for the pyrazine-fused extended π-electron system is developed. With substituent engineering, the favorable two-dimensional herringbone assembly can be obtained with BNTP, and the decylphenyl-substituted BNTP (C 10 Ph-BNTP) demonstrates large electronic couplings involving the HOMO, SHOMO, and THOMO in the herringbone assembly. C 10 Ph-BNTP further shows enhanced mixed-orbital charge transport when the electronic couplings of all three occupied molecular orbitals are taken into consideration, which results in a high hole mobility up to 9.6 cm 2 V -1 s -1 in single-crystal thin-film organic field-effect transistors. The present study provides insights into the contribution of HOMO, SHOMO, and THOMO to the mixed-orbital charge transport of organic semiconductors.

Oligosaccharyltransferase (OST) catalyzes oligosaccharide transfer to the Asn residue in the N-glycosylation sequon, Asn-X-Ser/Thr, where Pro is strictly excluded at position X. Considering the unique structural properties of proline, this exclusion may not be surprising, but the structural basis for the rejection of Pro residues should be explained explicitly. Here we determined the crystal structure of an archaeal OST in a complex with a sequon-containing peptide and dolichol-phosphate to a 2.7 Å resolution. The sequon part in the peptide forms two inter-chain hydrogen bonds with a conserved amino acid motif, TIXE. We confirmed the essential role of the TIXE motif and the adjacent regions by extensive alanine-scanning of the external loop 5. A Ramachandran plot revealed that the ring structure of the Pro side chain is incompatible with the ϕ backbone dihedral angle around -150° in the rigid sequon-TIXE structure. The present structure clearly provides the structural basis for the exclusion of Pro residues from the N-glycosylation sequon., (© 2021. The Author(s).)

The interface of organic semiconductor films is of particular importance with respect to various electrochemical devices such as transistors and solar cells. In this study, we developed a new spectroscopic system, namely electrochemical attenuated total reflectance ultraviolet (EC-ATR-UV) spectroscopy, which can access the interfacial area. Ionic liquid-gated organic field-effect transistors (IL-gated OFETs) were successfully fabricated on the ATR prism. Spectral changes of the organic semiconductor were then investigated in relation to the gate voltage application and IL species, and the magnitude of spectral changes was found to correlate positively with the drain current. Additionally, the Stark shifts of not only the organic semiconductor, but also of the IL on the organic semiconductor films were detected. This new method can be applied to other electrochemical devices such as organic thin film solar cells, in which the interfacial region is crucial to their functioning., (© 2021. The Author(s).)

Operational stability, such as long-term ambient durability and bias stress stability, is one of the most significant parameters in organic thin-film transistors (OTFTs). The understanding of such stabilities has been mainly devoted to energy levels of frontier orbitals, thin-film morphologies, and device configuration involving gate dielectrics and electrodes, whereas the roles of molecular and aggregated structural features in device stability are seldom discussed. In this Letter, we report a remarkable enhancement of operational stability, especially bias stress, of n-channel single-crystal OTFTs derived from a replacement of phenyl with perfluorophenyl groups in the side chain. Because of the several-molecule-thick single-crystal nature employed for the OTFTs, the crystal-surface properties are thought to be critical, where the surface structure composed of perfluorophenyl moieties could suppress interactions between environmental species and field-induced carriers owing to increased hydrophobicity and steric protection of π-conjugated units.

Phosphatidic acid plays an important role in plant immune responses against phytopathogenic bacteria in Nicotiana benthamiana . Here we focused on phosphoinositide dependent protein kinases (PDKs) as a candidate required for phosphatidic acid signaling. Based on Arabidopsis PDK sequences, we identified four putative PDK orthologs in N. benthamiana genome. To address the role of PDKs in plant defense responses, we created all four NbPDKs -silenced plants by virus-induced gene silencing. the NbPDKs -silenced plants showed a moderately reduced growth phenotype. Induction of hypersensitive cell death was compromised in the NbPDKs -silenced plants challenged with Ralstonia solanacearum . The hypersensitive cell death induced by bacterial effectors was also reduced in the NbPDKs -silenced plants. the NbPDKs -silenced plants showed decreased production of salicylic acid, jasmonic acid and jasmonoyl-L-isoleucine, as well as hydrogen peroxide after inoculation with R. solanacearum . These results suggest that NbPDKs might have an important role in the regulation of the hypersensitive cell death via plant hormone signaling and oxidative burst., (© 2020 Japanese Society for Plant Biotechnology.)

Toward the development of high-performance organic semiconductors (OSCs), carrier mobility is the most important requirement for next-generation OSC-based electronics. The strategy is that OSCs consisting of a highly extended π-electron core exhibit two-dimensional (2D) aggregated structures to offer effective charge transport. However, such OSCs, in general, show poor solubility in common organic solvents, resulting in limited solution processability. This is a critical trade-off between the development of OSCs with simultaneous high carrier mobility and suitable solubility. To address this issue, herein, five-membered ring-fused selenium-bridged V-shaped binaphthalene with decyl substituents (C 10 -DNS-VW) is developed and synthesized by an efficient method. C 10 -DNS-VW exhibits significantly high solubility for solution processes. Notably, C 10 -DNS-VW forms a one-dimensional π-stacked packing motif (1D motif) and a 2D herringbone (HB) packing motif (2D motif), depending on the crystal growth condition. On the other hand, the fabrication of thin films by means of both solution process and vacuum deposition techniques forms only the 2D HB motif. External stress tests such as heating and exposure to solvent vapor indicated that 1D and 2D motifs could be synergistically induced by the total balance of intermolecular interactions. Finally, the single-crystalline films of C 10 -DNS-VW by solution process exhibit carrier mobility up to 11 cm 2 V -1 s -1 with suitable transistor stability under ambient conditions for more than two months, indicating that C 10 -DNS-VW is one of the most promising candidates for breaking the trade-off in the field of solution-processed technologies.

Thin film transistors (TFTs) are indispensable building blocks in any electronic device and play vital roles in switching, processing, and transmitting electronic information. TFT fabrication processes inherently require the sequential deposition of metal, semiconductor, and dielectric layers and so on, which makes it difficult to achieve reliable production of highly integrated devices. The integration issues are more apparent in organic TFTs (OTFTs), particularly for solution-processed organic semiconductors due to limits on which underlayers are compatible with the printing technologies. We demonstrate a ground-breaking methodology to integrate an active, semiconducting layer of OTFTs. In this method, a solution-processed, semiconducting membrane composed of few-molecular-layer-thick single-crystal organic semiconductors is exfoliated by water as a self-standing ultrathin membrane on the water surface and then transferred directly to any given underlayer. The ultrathin, semiconducting membrane preserves its original single crystallinity, resulting in excellent electronic properties with a high mobility up to 12 [Formula: see text] The ability to achieve transfer of wafer-scale single crystals with almost no deterioration of electrical properties means the present method is scalable. The demonstrations in this study show that the present transfer method can revolutionize printed electronics and constitute a key step forward in TFT fabrication processes., Competing Interests: The authors declare no competing interest., (Copyright © 2020 the Author(s). Published by PNAS.)

Background: In patients with epidermal growth factor receptor (EGFR)-mutated advanced non-small-cell lung cancer (NSCLC), epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) treatment has shown a good response. Subsequent treatments jeopardize the ability to determine the effect of first-line chemotherapy on overall survival (OS). Therefore, using patient-level data, we aimed to study the associations of progression-free survival (PFS) and post-progression survival (PPS) with OS after first-line EGFR-TKI treatment in patients with EGFR-mutated NSCLC., Methods: Between November 2006 and December 2016, we analyzed 92 patients with EGFR-mutated NSCLC treated with first-line EGFR-TKI. The correlations of PFS and PPS with OS were analyzed for each patient., Results: Spearman's rank correlation and linear regression analyzes showed that PPS correlated highly with OS (r = 0.85, P < 0.05, R 2 = 0.75), whereas PFS correlated weakly with OS (r = 0.76, P < 0.05, R 2 = 0.50). The best responses after first-line and second-line treatments were significantly associated with PPS., Conclusions: PPS has a higher impact on OS than PFS in patients with EGFR-mutated NSCLC treated with first-line EGFR-TKIs. These outcomes suggest that the OS in this patient group may be affected by treatments following first-line chemotherapy; however, this remains to be verified in prospective trials., (© 2019 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.)

Building on significant developments in materials science and printing technologies, organic semiconductors (OSCs) promise an ideal platform for the production of printed electronic circuits. However, whether their unique solution-processing capability can facilitate the reliable mass manufacture of integrated circuits with reasonable areal coverage, and to what extent mass production of solution-processed electronic devices would allow substantial reductions in manufacturing costs, remain controversial. In the present study, we successfully manufactured a 4-inch (c.a. 100 mm) organic single-crystalline wafer via a simple, one-shot printing technique, on which 1,600 organic transistors were integrated and characterized. Owing to their single-crystalline nature, we were able to verify remarkably high reliability and reproducibility, with mobilities up to 10 cm 2 V -1 s -1 , a near-zero turn-on voltage, and excellent on-off ratio of approximately 10 7 . This work provides a critical milestone in printed electronics, enabling industry-level manufacturing of OSC devices concomitantly with lowered manufacturing costs.

In this article, the chiroptical responses of Au9 clusters protected by chiral/achiral mixed bidentate phosphine ligands are reported. The mixed phosphine we use is (S)-BINAP/Xantphos in the molar ratio of 1/0 (= pure (S)-BINAP), 3/1, 1/1, or 0/1 (= pure Xantphos), where BINAP and Xantphos represent 2,2'-bis(diphenylphosphino)-1,1'-binaphthyl and 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene, respectively. Electronic absorption spectra of the clusters are similar between the samples with different molar diphosphine ratios, but the chiroptical activity or g-factor decreases nonlinearly with an increase in the fraction of Xantphos. Quantum chemical calculations and geometrical quantifications based on the Hausdorff chirality measure (HCM) for model Au9 cluster species suggest that (i) two types of metal core structures with pseudo-P- and M-chirality are found, and their appropriate contributions would cancel out the chiroptical response in the low-energy region; (ii) the origin of optical activity in pure (S)-BINAP-protected Au9 clusters can mainly be attributed to the metal core chirality, whereas that of other mixed-ligand protected clusters would be due to the chiral ligand arrangement. This work demonstrates that the modulation of chiroptical activity in Au9 clusters by chiral/achiral mixed-diphosphine ligation is controlled by the difference in the degree of chirality existing in the cluster core and/or the ligand array.

Background Monoallelic mutations of GHR have been described in idiopathic short stature (ISS), although the significance of these remain unclear. We report a case of ISS with novel monoallelic S219L mutation of GHR and discuss the possible significance of monoallelic GHR mutation in ISS. Case presentation The proband, a 13.9-year-old Japanese boy, had severe short stature (-3.8 standard deviation [SD]). Serum insulin-like growth factor (IGF)-I level and growth hormone (GH) secretion was normal. His parents were nonconsanguineous and had normal stature. Genetic analyses revealed a novel monoallelic missense variation in exon 7 of GHR (S219L). The proband's mother had the same variation. S219L might be the novel mutation judging from there being no registration of it as a single-nucleotide polymorphism (SNP) in any database, evolutional conservation of Ser219, in silico analyses, and computational molecular visualization analysis. Furthermore, a review of the literature showed that the median height of missense mutation carriers of GHR was relatively low. Conclusions We propose the possibility that monoallelic mutation of GHR increases the susceptibility to short stature.

Scdachitin is a polymethoxyflavone (5,7,4'-trihydroxy-6,8,3-trimethoxyflavone) that is found in the peel of Citrus sudachi . We examined the effect of sudachitin on immune response in ovalbumin-immunized BALB/c mice. Treatment with sudachitin increased ovalbumin-specific IL-4 and IL-10 productions. In addition, mice that received sudachitin showed higher levels of ovalbumin-specific IgE, IgG1 and IgG l production than did control mice. The antibody response to the thymus-independent antigen 2,4,6-trinitrophenyl Ficoll was not different in the control and sudachitin groups, suggesting that sudachitin does not directly stimulate antibody production. An in vitro study showed that treatment of sudachitin enhanced the ability of antigen presentation in bone marrow-derived dendritic cells. Furthermore, CD11c + cells that had been treated with sudachitin showed increased expression of co-stimulatory molecules. The results indicate that sudachitin regulates immune function both in vivo and in vitro ., Competing Interests: No potential conflicts of interest were disclosed.

We examined the effect of nobiletin (5,6,7,8,3',4'-hexamethoxyflavone) on immune response in ovalbumin (OVA)-immunized mice. Treatment with nobiletin increased OVA-specific IL-4 and IL-10 production. In addition, mice that received nobiletin showed higher levels of OVA-specific IgE, IgG and IgG1 production than did control mice. The antibody response to the thymus-independent antigen 2,4,6-trinitrophenyl-Ficoll was not different in the control and nobiletin groups, suggesting that nobiletin does not directly stimulate antibody production. An in vitro study showed that treatment with nobiletin enhanced the ability of antigen presentation of bone marrow-derived dendritic cells. The in vivo and in vitro results indicate that nobiletin regulates immune function.

Here we propose a new protocol for whole-mount bone staining, which allows the rapid preparation of highly cleared and nondestructive specimens. It only takes 3 days to complete whole procedure for small vertebrates, such as medaka, zebrafish, and Xenopus frogs. In this procedure, we used a newly developed fixative containing formalin, Triton X-100, and potassium hydroxide, which allows the fixation, decolorization, and transparentization of specimens at the same time. A bone staining solution containing alizarin red S with ethylene glycol and a clearing solution containing Tween 20 and potassium hydroxide also contributed the specificity and swiftness of this new system. As expected, although details of the skeletal system could be observed in specimens with high transparency, it was noteworthy that high-resolution fluorescence images acquired using zoom microscopes clearly delineated the shape of each bone. This new procedure would be expected to be widely used as a standard procedure for bone staining in the testing the developmental toxicity of chemicals and in the screening test of knockout or mutant animals.

Two-dimensional (2D) layered semiconductors are a novel class of functional materials that are an ideal platform for electronic applications, where the whole electronic states are directly modified by external stimuli adjacent to their electronic channels. Scale-up of the areal coverage while maintaining homogeneous single crystals has been the relevant challenge. We demonstrate that wafer-size single crystals composed of an organic semiconductor bimolecular layer with an excellent mobility of 10 cm 2 V -1 s -1 can be successfully formed via a simple one-shot solution process. The well-controlled process to achieve organic single crystals composed of minimum molecular units realizes unprecedented low contact resistance and results in high-speed transistor operation of 20 MHz, which is twice as high as the common frequency used in near-field wireless communication. The capability of the solution process for scale-up coverage of high-mobility organic semiconductors opens up the way for novel 2D nanomaterials to realize products with large-scale integrated circuits on film-based devices.

Supply of safe fresh water is currently one of the most important global issues. Membranes technologies are essential to treat water efficiently with low costs and energy consumption. Here, the development of self-organized nanostructured water treatment membranes based on ionic liquid crystals composed of ammonium, imidazolium, and pyridinium moieties is reported. Membranes with preserved 1D or 3D self-organized sub-nanopores are obtained by photopolymerization of ionic columnar or bicontinuous cubic liquid crystals. These membranes show salt rejection ability, ion selectivity, and excellent water permeability. The relationships between the structures and the transport properties of water molecules and ionic solutes in the sub-nanopores in the membranes are examined by molecular dynamics simulations. The results suggest that the volume of vacant space in the nanochannel greatly affects the water and ion permeability.

Although mutations in ACAN, FGFR3, NPR2, and SHOX typically lead to skeletal dysplasia, and mutations in GHRHR, GH1, GHR, STAT5B, IGF1, IGFALS, and IGF1R usually underlie hormonal defects of the growth hormone (GH)-insulin-like growth factor 1 (IGF1) axis, such mutations have also been identified in patients with idiopathic short stature (ISS). Of these, SHOX abnormalities are known to account for a certain percentage of ISS cases, whereas the frequency of mutations in the other 10 genes in ISS cohorts remains unknown. Here, we performed next-generation sequencing-based mutation screening of the 10 genes in 86 unrelated Japanese ISS patients without SHOX abnormalities. We searched for rare protein-altering variants. The functional significance of the identified variants was assessed by in silico analyses. Consequently, we identified 18 heterozygous rare variants in 19 patients, including four probable damaging variants in ACAN, six pathogenicity-unknown variants in FGFR3, GHRHR, GHR, and IGFALS, and eight possible benign variants. Pathogenic variants in NPR2, GH1, and IGF1 were absent from our cohort. Unlike previously reported patients with ACAN mutations, our four patients with ACAN variants manifested non-specific short stature with age-appropriate or mildly delayed bone ages, and had parents of normal stature. These results indicate that ACAN mutations can underlie ISS without characteristic skeletal features, and that such mutations are possibly associated with de novo occurrence or low penetrance. In addition, our data imply that mutations in FGFR3, NPR2, and GH-IGF1 axis genes play only limited roles in the etiology of ISS.

Citrus Sudachi is the special local product of Tokushima Prefecture, and over 98% of Sudachi consumed in Japan every year is produced in Tokushima Prefecture. In this study, we evaluated the function of sudachi peel extract (SPE) using an animal model of obesity. C57BL/6 mice were fed a high-fat diet containing 1% SPE powder. Treatment with SPE significantly decreased body weight compared to that of mice fed a high-fat diet. A significant difference in body weight was observed between the control and SPE groups from 7 weeks after the start of the experiment, the significant difference continued until the end of the 14-week experiment. Reduction of blood glucose levels following insulin administration in SPE-treated mice was grater than that in control mice. Determination of mRNA expression in adipose tissue showed that the expression level of TNF-α in the SPE group was significantly decreased compared to that on the control group. These results suggest that SPE potentially has the ability to attenuate body weight gain. J. Med. Invest. 64: 20-23, February, 2017.

Pseudohypoaldosteronism type II (PHA II) is a renal tubular disease that causes hyperkalemia, hypertension, and metabolic acidosis. Mutations in four genes ( WNK4 , WNK1 , KLHL3 , and CUL3 ) are known to cause PHA II. We report a patient with PHA II carrying a KLHL3 mutation, who also had congenital hypopituitarism. The patient, a 3-yr-old boy, experienced loss of consciousness at age 10 mo. He exhibited growth failure, hypertension, hyperkalemia, and metabolic acidosis. We diagnosed him as having PHA II because he had low plasma renin activity with normal plasma aldosterone level and a low transtubular potassium gradient. Further investigations revealed defective secretion of GH and gonadotropins and anterior pituitary gland hypoplasia. Genetic analyses revealed a previously known heterozygous KLHL3 mutation (p.Leu387Pro), but no mutation was detected in 27 genes associated with congenital hypopituitarism. He was treated with sodium restriction and recombinant human GH, which normalized growth velocity. This is the first report of a molecularly confirmed patient with PHA II complicated by congenital hypopituitarism. We speculate that both GH deficiency and metabolic acidosis contributed to growth failure. Endocrinological investigations will help to individualize the treatment of patients with PHA II presenting with growth failure.

In this article, we report a novel technique of high-frequency electron paramagnetic resonance (HFEPR) using a microcantilever. In this method, a sample is mounted on a cantilever, and the field-gradient force associated with EPR absorption is detected as a cantilever bending. By using a micrometer-sized cantilever, this technique can be applied to a very tiny sample on the order of μg. In addition, the use of a piezoresistive cantilever makes the experimental setup easy and compact. In this study, we applied this technique to multi-frequency HFEPR measurements of metal-containing porphyrin compounds, which are an important composing element of metal-containing proteins and coenzymes such as hemoglobin and cyanocobalamin., (Copyright © 2016. Published by Elsevier Inc.)

The possibility to change the molecular assembled structures of organic and organometallic materials through mechanical stimulation is emerging as a general and powerful concept for the design of functional materials. In particular, the photophysical properties such as photoluminescence color, quantum yield, and emission lifetime of organic and organometallic fluorophores can significantly depend on the molecular packing, enabling the development of molecular materials with mechanoresponsive luminescence characteristics. Indeed, an increasing number of studies have shown in recent years that mechanical force can be utilized to change the molecular arrangement, and thereby the optical response, of luminescent molecular assemblies of π-conjugated organic or organometallic molecules. Here, the development of such mechanoresponsive luminescent (MRL) molecular assemblies consisting of organic or organometallic molecules is reviewed and emerging trends in this research field are summarized. After a brief introduction of mechanoresponsive luminescence observed in molecular assemblies, the concept of "luminescent molecular domino" is introduced, before molecular materials that show turn-on/off of photoluminescence in response to mechanical stimulation are reviewed. Mechanically stimulated multicolor changes and water-soluble MRL materials are also highlighted and approaches that combine the concept of MRL molecular assemblies with other materials types are presented in the last part of this progress report., (© 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Objective: Vanishing white matter disease (VWM) is a chronic, progressive leukoencephalopathy associated with episodes of rapid deterioration following minor stress events such as head traumas or infectious disorders. The white matter of the patients with VWM exhibits characteristic radiological findings., Method: The genes encoding all five subunits of eukaryotic translation initiation factor 2B (EIF2B) were analyzed in patients, who were tentatively diagnosed with VWM, by Sanger sequencing., Results: Seven mutations were identified in the genes encoding the subunits 1, 2, 4, and 5 of EIF2B. Among them, one mutation (p.V83E) in the subunit 2 (EIF2B2) was recurrently identified in three alleles, indicating the most common mutation in Japanese patients with VWM. Two patients were homozygous, and the other four patients were compound heterozygous., Conclusion: All patients showed white matter abnormalities with various degrees. One patient showed manifestations of end-stage VWM disease. Some patients showed late onset and slow progression associated with brain magnetic resonance imaging displaying T2 high intensity only in the deep white matter. There was clinical heterogeneity among patients with VWM., (Copyright © 2015 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.)

We report herein on 29 patients with advanced oropharyngeal and tongue squamous-cell carcinoma who underwent a total glossolaryngectomy at the Cancer Institute Hospital of the JFCR between July 2005 and June 2013. In this study, we tried to evaluate associations between several variables of the primary tumor and prognosis in these 29 patients. The cause-specific 5-year survival rate with the Kaplan-Meier method was 45% in all patients. Tumor recurrence occurred in 15 patients. Four patients had recurrence in the primary site, 11 patients in neck lymph nodes or in the lungs or bone. The multivariate analysis revealed that the number of neck lymph node metastases, age and alcohol drinking were poor prognostic markers for patients undergoing a total glossolaryngectomy. Cause-specific survival was compared between patients with salvage surgery and initial surgery using Kaplan-Meier survival curves with log-rank tests. There was no significant association with survival (log-rank test: p = 0.13). The overall local control rate was 69% in all patients. Regarding salvage surgery, 9 of 16 patients had no recurrence in the primary site or neck lymph nodes. The limitations of this study include the small number of patients especially regarding the prognosis study and may have included a selection bias regarding undergoing a total glossolaryngectomy.