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Managing safety and supply-chain risks associated with lithium-ion batteries (LIBs) is an urgent task for sustainable development. Aqueous proton batteries are attractive alternatives to LIBs because using water and protons addresses these two risks. However, most host materials undergo large volume changes upon H + intercalation, which induces intraparticle cracking to accelerates parasitic reactions. Herein, we report that Mo 3 Nb 2 O 14 bronze exhibits reversible H + intercalation (200 mAh g -1 ) with a Coulombic efficiency of 99.7 % owing to near-zero volume change and solid-solution-type phase transition. Combination of experimental and theoretical analyses clarifies that rotation and shrinkage of open tunnels, which consist of flexible corner-sharing Mo/NbO n polyhedra, relieve local structural distortions upon H + intercalation to suppress intraparticle cracking. The prototype full cell of an aqueous proton battery with a Mo 3 Nb 2 O 14 anode operates stably over 1000 charge/discharge cycles. This study reveals the importance of implementing distortion-relieving voids in host materials to reduce volume change upon charge/discharge., (© 2024 Wiley-VCH GmbH.)

Background: There is an increasing interest in cross-linguistic influences of the second language (L2) on the first (L1), but its communicative impact remains to be elucidated. This study investigates how L2 learners' L1 pronunciation is perceived as foreign-accented and (in) comprehensible as a function of their L2 learning experience and proficiency levels., Methods: Read speech of 154 L1 Japanese learners of L2 English in the J-AESOP corpus was examined, where approximately one-third of them had lived in English-speaking countries and the rest had never lived outside of Japan. Their L1 speech was rated by another group of native Japanese listeners for accentedness and comprehensibility (from October 25, 2022 to August 20, 2023), while their L2 speech was previously rated by native American English listeners for nativelikeness or proficiency. The speakers' vowel acoustics were also examined., Results: More proficient L2 speakers were perceived as more foreign-accented in their L1, but only if they had lived overseas; their length of residence abroad predicted the degree of perceived accentedness. In contrast, more proficient L2 speakers were consistently perceived as more comprehensible in the L1, regardless of prior overseas experience. Acoustic analyses indicated that perceived accentedness is associated with a clockwise chain shift of all vowel categories in the vowel space. It was also revealed that the dispersion, rather than compactness, of vowel production contributed to perceived comprehensibility, although the degree of L1 vowel dispersion did not predict L2 proficiency., Conclusions: The overall results suggest two main conclusions. First, perceptible L1 foreign accent likely results from L1 disuse rather than L2 interference, thereby L1 pronunciation differs from native norms at a system-wide rather than category-specific level. Second, L2 learning has a positive influence on perceived L1 comprehensibility, rather than individuals with clearer and more comprehensible L1 speech being inherently better L2 learners., Competing Interests: No competing interests were disclosed., (Copyright: © 2024 Yazawa K et al.)

Controlling the rotation of carbon-carbon bonds, which is ubiquitous in organic molecules, to create functionality has been a subject of interest for a long time. In this context, it would be interesting to explore whether cooperative and collective rotation could occur if dipolar molecular rotors were aligned close together while leaving adequate space for rotation. However, it is difficult to realize such structures as bulk molecular assemblies, since molecules generally tend to assemble into the closest packing structure to maximize intermolecular forces. To tackle this question, we examined an approach using a supramolecular scaffold composed of a tripodal triptycene, which has been demonstrated to strongly promote the assembly of various molecular and polymer units into regular "2D hexagonal packing + 1D layer" structures. We found that a molecule (1) consisting of a dipolar 1,2-difluorobenzene rotor sandwiched by two 10-ethynyl-1,8,13-tridodecyloxy triptycenes, successfully self-assembles into the desired structure, where the dipolar rotor units align two-dimensionally at a close interval of approximately 0.8 nm while having a degree of freedom for rotational motion. Here we describe the self-assembly behavior of 1 in comparison with the general trend in molecular self-assembly, as well as the motility of the two-dimensionally aligned molecular rotors investigated using solid-state 19 F-MAS NMR spectroscopy., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

The domestic silkworm, Bombyx mori , has been widely used in silk production for centuries. It is also used as a bioreactor by the textile and pharmaceutical industries to mass produce recombinant bioactive proteins containing silk-based materials. Furthermore, silkworms are well-known as a source of food and have also been orally administered to prevent and treat several human disorders. In this study, we aimed to investigate the inherent bio-physicochemical properties of edible silkworms to accurately evaluate their clinical and nutritional potential. We prepared raw powder from whole larvae of silkworm. The yield rate of the powder derived from dried larvae was almost 100% (98.1-99.1% in replicates). As "percentage yield" translates to "Budomari" in Japanese, this raw powder was named "B100rw." We further prepared B100dn that was denatured through autoclaving. Thereafter, we examined whether B100rw sustained the original bio-physicochemical properties by comparing it with B100dn. There was no significant difference in nutritional content between B100rw and B100dn. B100rw contained proteins derived from silkworm larvae and mulberry leaves, whereas the proteins of B100dn were mostly degraded. On measuring the enzymatic activity of both powders using trehalase as an indicator enzyme, B100rw was found to maintain trehalase activity. B100rw also maintained a random coil conformation, similar to that of liquid silk. This suggested that B100rw sustained the unique bio-physicochemical properties of living larvae. These findings may facilitate the development of novel food products or orally administered vaccines., Competing Interests: HU was employed by the Morus Inc. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Hashimoto, Yamazaki, Uehara, Yamazaki, Kobayashi, Yokoyama, Yazawa and Shiomi.)

Wurtzite-type ferroelectrics have drawn increasing attention due to the promise of better performance and integration than traditional oxide ferroelectrics with semiconductors such as Si, SiC, and III-V compounds. However, wurtzite-type ferroelectrics generally require enormous electric fields, approaching breakdown, to reverse their polarization. The underlying switching mechanism(s), especially for multinary compounds and alloys, remains elusive. Here, we examine the switching behaviors in Al 1- x Sc x N alloys and wurtzite-type multinary candidate compounds we recently computationally identified. We find that switching in these tetrahedrally coordinated materials proceeds via a variety of nonpolar intermediate structures and that switching barriers are dominated by the more-electronegative cations. For Al 1- x Sc x N alloys, we find that the switching pathway changes from a collective mechanism to a lower-barrier mechanism enabled by inversion of individual tetrahedra with increased Sc composition. Our findings provide insights for future engineering and realization of wurtzite-type materials and open a door to understanding domain motion.

The use of nucleic acid-derived fibers has not been developed in contrast to the traditional use of polysaccharide- and protein-based fibers in daily life. Salmon, Oncorhynchus keta, is an abundant fishery resource, and its milt contains a huge amount of DNA. Most of the milt is discarded because it degrades easily and is unsuitable for food consumption. DNA-based fibers are expected to possess functionality and mechanical strength because DNA is a polyanion with a high molecular weight. Here, using DNA extracted from the salmon milt, we produced nucleotide-based fibers. A solution spinning system was applied using ethanol as a coagulant. Adding the salt to the dope solution reduced the solubility of DNA, which was essential for the successful spinning of DNA-based fibers. The obtained fibers became insoluble in water by ultraviolet (UV) exposure. Fibril-like structures were detected on the fracture surface, and humidity influenced the conformational structure. This study focuses on the bulk-scale production of biodegradable DNA-based fibers. Therefore, it can be used not only for clothing and filters but also as a functional material to remove harmful pollutants released into the ocean, such as heavy metal ions and aromatic derivatives., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Isomerism in covalent organic frameworks (COFs) has scarcely been known. Here, for the first time we show 3D COFs with three framework isomers or polymorphs constructed from the same building blocks. All isomers were obtained as large (>10 μm) crystals; although their crystal shapes were distinctly different, they showed identical FT-IR and solid-state NMR spectra. Our structural analyses revealed unprecedented triple isomerism in 3D COFs (noninterpenetrated dia , qtz , and 3-fold interpenetrated dia-c3 nets). Furthermore, this Communication reports the first known COF with qtz topology for which the structure determination was based on Rietveld analysis. We achieved triple framework isomerism by reticulating a tetrahedral building block with a flexible junction and a linear building block with PEO side chains and by varying solution compositions. Our energy calculations, along with the discovery of interisomer transition, revealed that the isomer with qtz topology was a kinetic isomer. Thus, this simple yet little-explored concept of reticulating only flexible building blocks is an effective pathway to significantly broaden the diversity of 3D COFs, which have been proposed for a myriad of applications.

Heated tobacco products (HTPs) have emerged as novel alternatives to conventional cigarettes (CCs), marketed by the tobacco industry as having a reduced potential for harm. Nevertheless, a significant dearth of information remains regarding the long-term effects of HTPs on the central nervous system (CNS). Here, we sought to shed light on the repercussions of prolonged exposure to HTPs on the CNS, employing a mouse model mimicking prodromal Alzheimer's disease (AD). Our study entailed subjecting App knock-in mice to 16 weeks of HTP exposure, administered 5 days per week, with serum cotinine concentration serving as confirmation of HTP exposure within this model. Histological analysis, aimed at assessing amyloid pathology, unveiled a minimal impact attributable to HTPs. However, exploration of differentially expressed genes in the cerebral cortex, using unadjusted p values, indicated an association between HTP exposure and non-inflammatory pathways, specifically linked to neurohypophyseal and neuropeptide hormone activity within the CNS. Of note, similar results have already been observed after exposure to CCs in vivo. Our study not only contributes insights into the potential non-inflammatory effects of HTPs within the context of AD pathogenesis but also underscores the significance of continued research to comprehend the full scope of their impact on the CNS., (© 2024. The Author(s).)

Apolipoprotein E4 (APOE4), the strongest risk factor for late-onset Alzheimer's disease (AD), has been revealed to cause greater accumulation of extracellular amyloid β (Aβ) aggregates than does APOE3 in traditional transgenic mouse models of AD. However, concerns that the overexpression paradigm might have affected the phenotype remain. Amyloid precursor protein (APP)-knock-in (KI) mice, incorporating APP mutations associated with AD development, offer an alternative approach for overproducing pathogenic Aβ without needing overexpression of APP. Here, we present the results of comprehensive analyses of pathological and biochemical traits in the brains of APP-KI mice harboring APP-associated familial AD mutations (APP NL - G-F /NL - G-F mice) crossed with human APOE-KI mice. Immunohistochemical and biochemical analyses revealed the APOE genotype-dependent increase in Aβ pathology and glial activation, which was evident within 8 months in the mouse model. These results suggested that this mouse model may be valuable for investigating APOE pathobiology within a reasonable experimental time frame. Thus, this model can be considered in investigating the interaction between APOE and Aβ in vivo, which may not be addressed appropriately by using other transgenic mouse models., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Takashi Kurashige reports financial support was provided by Takeda Science Foundation., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Speech perception patterns are strongly influenced by one's native phonology. It is generally accepted that native English listeners rely primarily on spectral cues when perceiving vowels, making limited use of duration cues because English lacks phonemic vowel length. However, the literature on vowel perception by English listeners shows a marked bias toward American English, with the phonological diversity among different varieties of English largely overlooked. The current study investigates the perception of Japanese vowel length contrasts by native listeners of Australian English, which is reported to use length to distinguish vowels unlike most other varieties of English. Twenty monolingual Australian English listeners participated in a forced-choice experiment, where they categorized Japanese long and short vowels as most similar to their native vowel categories. The results showed a general tendency for Japanese long and short vowels (e.g., /ii, i/) to be categorized as Australian English long and short vowels (e.g., /i:, ɪ/ as in "heed," "hid"), respectively, which contrasts with American English listeners' categorization of all Japanese vowels as tense regardless of length (e.g., /ii, i/ as both "heed") as reported previously. Moreover, this duration-based categorization was found not only for Australian English categories that contrast in duration alone (e.g., /ɐ:, ɐ/ as in "hard," "hud") but also for those that contrast in both duration and spectra (e.g., /o:, ɔ/ as in "hoard," "hod"), despite their spectral mismatch from the corresponding Japanese vowels (e.g., /aa, a/ and /oo, o/). The results, therefore, suggest that duration cues play a prominent role across all vowel categories-even nonnative-for Australian English listeners. The finding supports a feature-based framework of speech perception, where phonological features like length are shared across multiple categories, rather than the segment-based framework that is currently dominant, which regards acoustic cues like duration as being tied to a specific native segmental category. Implications for second and foreign language learning are discussed., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Yazawa, Whang and Escudero.)

Ferroelectric polarization switching is one common example of a process that occurs via nucleation and growth, and understanding switching kinetics is crucial for applications such as ferroelectric memory. Here we describe and interpret anomalous switching dynamics in the wurtzite-structured nitride thin film ferroelectrics Al 0.7 Sc 0.3 N and Al 0.94 B 0.06 N using a general model that can be directly applied to other abrupt transitions that proceed via nucleation and growth. When substantial growth and impingement occur while nucleation rate is increasing, such as in these wurtzite-structured ferroelectrics under high electric fields, abrupt polarization reversal leads to very large Avrami coefficients ( e.g. , n = 11), inspiring an extension of the KAI (Kolmogorov-Avrami-Ishibashi) model. We apply this extended model to two related but distinct scenarios that crossover between (typical) behavior described by sequential nucleation and growth and a more abrupt transition arising from significant growth prior to peak nucleation rate. This work therefore provides a more complete description of general nucleation and growth kinetics applicable to any system while specifically addressing the anomalously abrupt polarization reversal behavior in new wurtzite-structured ferroelectrics.

Alzheimer's disease (AD) is a neurodegenerative disease that is accompanied by memory decline and cognitive dysfunction. Aggregated amyloid β formation and accumulation may be one of the underlying mechanisms of the pathophysiology of AD. Therefore, compounds that can inhibit amyloid β aggregation may be useful for treatment. Based on this hypothesis, we screened plant compounds used in Kampo medicine for chemical chaperone activity and identified that alkannin had this property. Further analysis indicated that alkannin could inhibit amyloid β aggregation. Importantly, we also found that alkannin inhibited amyloid β aggregation after aggregates had already formed. Through the analysis of circular dichroism spectra, alkannin was found to inhibit β -sheet structure formation, which is an aggregation-prone toxic structure. Furthermore, alkannin attenuated amyloid β -induced neuronal cell death in PC12 cells, ameliorated amyloid β aggregation in the AD model of Caenorhabditis elegans ( C. elegans ), and inhibited chemotaxis observed in AD C. elegans , suggesting that alkannin could potentially inhibit neurodegeneration in vivo. Overall, these results suggest that alkannin may have novel pharmacological properties for inhibiting amyloid β aggregation and neuronal cell death in AD. SIGNIFICANCE STATEMENT: Aggregated amyloid β formation and accumulation is one of the underlying mechanisms of the pathophysiology of Alzheimer's disease. We found that alkannin had chemical chaperone activity, which can inhibit β-sheet structure formation of amyloid β and its aggregation, neuronal cell death, and Alzheimer's disease phenotype in C. elegans. Overall, alkannin may have novel pharmacological properties for inhibiting amyloid β aggregation and neuronal cell death in Alzheimer's disease., (Copyright © 2023 by The American Society for Pharmacology and Experimental Therapeutics.)

Wild silkworm silk fibers have garnered attention owing to their softness, natural color, lightweight, and excellent mechanical properties. Because most wild silkworm cocoons obtained are pierced or dirty after the eclosion process, it is difficult to reel the long filament from the pierced cocoons to use as textile materials. Therefore, damaged wild silkworm cocoons are typically removed during the industrial process. Artificial silk spinning has been developed to transform domesticated silkworm silk solutions into regenerated silk fibers. However, regenerated fibers derived from wild silkworm silk have not been reported. Here, we produced regenerated silk fibers using a dry-wet spinning method using a dope solution derived from wild silkworm silk cocoon wastes. These regenerated silk fibers have thick and uniform diameters, unlike native silk fibers, contributing to their usefulness for sterilization and handling in medical applications. Moreover, they exhibited the same level of mechanical strength as their native counterparts. The molecular orientation and crystallinity of the regenerated silk fibers were adjustable by the drawing process, enabling the realization of their various tensile properties. This study promotes the utilization of unused protein resources to produce mechanically stable and tough silk-based fibers.

Mitochondrial respiratory chain disorders (MRCD) constitute a highly heterogeneous group both with regard to clinical manifestations and underlying genetic/biochemical defects. Management of urological complications such as vesicoureteral reflux (VUR) has not been discussed in cases with MRCD. We report a pediatric case of MRCD with recurrent urinary tract infections (UTI) due to primary and secondary VUR.A 6-month-old boy with multiple malformations and a history of aspiration pneumonia was referred to our department for febrile UTI (fUTI). Voiding cystourethrography showed high-grade left VUR and a normal bladder. As a spontaneous resolution of VUR was not observed, he underwent left ureteral reimplantation concomitant with left orchidopexy at the age of 1 year and 7 months. Although he had fUTI immediately after surgery, no recurrence of the UTI occurred after discharge. At the age of 3 years, he had septic shock and cardiac arrest caused by aspiration pneumonia, as well as, encephalopathy following cardiopulmonary resuscitation. At this event, the diagnosis of MRCD was achieved by liver biopsy. Since the age of 4 years, he has had repeated fUTI. VCUG confirmed the bladder deformity and right VUR. He underwent vesico-cutaneostomy at the age of 6 years. The postoperative course was uneventful. No recurrence of UTI was observed at the one-year follow-up.

Abnormally high serum homocysteine levels have been associated with several disorders, including obesity, cardiovascular diseases or neurological diseases. Leptin is an anti-obesity protein and its action is mainly mediated by the activation of its Ob-R receptor in neuronal cells. The inability of leptin to induce activation of its specific signaling pathways, especially under endoplasmic reticulum stress, leads to the leptin resistance observed in obesity. The present study examined the effect of homocysteine on leptin signaling in SH-SY5Y neuroblastoma cells expressing the leptin receptor Ob-Rb. Phosphorylation of the signal transducer and activator of transcription (STAT3) and leptin-induced STAT3 transcriptional activity were significantly inhibited by homocysteine treatment. These effects may be specific to homocysteine and to the leptin pathway, as other homocysteine-related compounds, namely methionine and cysteine, have weak effect on leptin-induced inhibition of STAT3 phosphorylation, and homocysteine has no impact on IL-6-induced activation of STAT3. The direct effect of homocysteine on leptin-induced Ob-R activation, analyzed by Ob-R BRET biosensor to monitor Ob-R oligomerization and conformational change, suggested that homocysteine treatment does not affect early events of leptin-induced Ob-R activation. Instead, we found that, unlike methionine or cysteine, homocysteine increases the expression of the endoplasmic reticulum (ER) stress response gene, a homocysteine-sensitive ER resident protein. These results suggest that homocysteine may induce neuronal resistance to leptin by suppressing STAT3 phosphorylation downstream of the leptin receptor via ER stress., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2022 Preninka et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

A high-speed and high-power current measurement instrument is described for measuring rapid switching of ferroelectric samples with large spontaneous polarization and coercive field. Instrument capabilities (±200 V, 200 mA, and 200 ns order response) are validated with a LiTaO 3 single crystal whose switching kinetics are well known. The new instrument described here enables measurements that are not possible using existing commercial measurement systems, including the observation of ferroelectric switching in large coercive field and large spontaneous polarization Al 0.7 Sc 0.3 N thin films.

A preschool child with refractory peritoneal dialysis-related exit-site infection (ESI)/peritonitis caused by Mycobacterium abscessus (M. abscessus) received multidrug antibacterial therapy for 6 months and then successfully underwent living-donor kidney transplantation. The patient was a 2.7-year-old boy and the primary disease was bilateral hypo/dysplastic kidneys. Peritoneal dialysis (PD) was initiated at the age of 4 months. Purulent drainage from the PD catheter exit site was observed, and pus and PD effluent cultures were negative. Since living kidney transplantation was scheduled for 2 months later, the PD catheter was replaced. Due to dialysate leakage from the exit site, the new PD catheter was removed and hemodialysis was initiated. M. abscessus subsequently grew from the PD effluent and abscesses that formed at the exit site continued to present bacteria even after catheter removal; therefore, additional debridement was performed. He received combination treatment with antibiotics, amikacin, clarithromycin, imipenem/cilastatin sodium, and tigecycline, for 6 months. After a 4-month observation period without antibiotics, the patient underwent living-donor kidney transplantation. The post-transplantation course was uneventful without the recurrence of infection for 2 years. Although PD-related ESI/peritonitis caused by M. abscessus was intractable, PD catheter removal, multiple debridement, and 6-month antibiotic combination therapy led to improvements. Follow-up observations for 4 months after the cessation of antibacterial treatment confirmed no recurrence of M. abscessus infection, which allowed kidney transplantation. The establishment of an appropriate treatment strategy and observation period for M. abscessus infection ahead of kidney transplantation requires further case accumulation., (© 2022. The Author(s) under exclusive licence to The Japan Society of Nephrology.)

Spider silks are among the toughest known materials and thus provide models for renewable, biodegradable, and sustainable biopolymers. However, the entirety of their diversity still remains elusive, and silks that exceed the performance limits of industrial fibers are constantly being found. We obtained transcriptome assemblies from 1098 species of spiders to comprehensively catalog silk gene sequences and measured the mechanical, thermal, structural, and hydration properties of the dragline silks of 446 species. The combination of these silk protein genotype-phenotype data revealed essential contributions of multicomponent structures with major ampullate spidroin 1 to 3 paralogs in high-performance dragline silks and numerous amino acid motifs contributing to each of the measured properties. We hope that our global sampling, comprehensive testing, integrated analysis, and open data will provide a solid starting point for future biomaterial designs.

Silk-based materials have garnered attention for use as medical supplies due to their mechanical toughness and low cytotoxicity. Silkworm silk has been applied as surgical sutures for decades. In contrast, the utilization of spider silk is limited mainly because of its scarcity. Although the biomimicry of spider silk has been developed using recombinant protein expression systems with the use of genetic engineering, the product often results in lower molecular weight and a lack of the N- or C-terminal regions. The incomplete sequence of the spider silk-like protein prevents the objective evaluation of the native spider silk as a medical application and retards the development of spider silk-inspired materials. Here, we reeled the native spider silk directly from live spiders and investigated the cell adhesion behavior based on three kinds of surface topography of spider silk-based substrates, namely, fibers, films, and non-woven fabrics. The cell adhesion behavior was largely influenced by the surface micro/nanostructure rather than the wettability of the surface. This study will contribute to promote the utilization of spider silk in the medical field as a candidate for promising bio-based fibers in the context of sustainable development goals.

Currently, there is a lack of nonvolatile memory (NVM) technology that can operate continuously at temperatures > 200 °C. While ferroelectric NVM has previously demonstrated long polarization retention and >1013 read/write cycles at room temperature, the largest hurdle comes at higher temperatures for conventional perovskite ferroelectrics. Here, we demonstrate how AlScN can enable high-temperature (>200 °C) nonvolatile memory. The c-axis textured thin films were prepared via reactive radiofrequency magnetron sputtering onto a highly textured Pt (111) surface. Photolithographically defined Pt top electrodes completed the capacitor stack, which was tested in a high temperature vacuum probe station up to 400 °C. Polarization−electric field hysteresis loops between 23 and 400 °C reveal minimal changes in the remanent polarization values, while the coercive field decreased from 4.3 MV/cm to 2.6 MV/cm. Even at 400 °C, the polarization retention exhibited negligible loss for up to 1000 s, demonstrating promise for potential nonvolatile memory capable of high−temperature operation. Fatigue behavior also showed a moderate dependence on operating temperature, but the mechanisms of degradation require additional study.

A 60-year-old woman was not accompanied by any symptom. She had a gallstone which was identified 20 years prior. Ultrasonography performed by a local doctor revealed that the gallbladder was filled with small stones, and the patient was referred to our department for further examination and treatment for gallbladder stone. Tumor markers are elevated. Contrast- enhanced CT revealed gallbladder stones and thickening in the gallbladder body. PET-CT showed abnormal accumulation of FDG-PET with SUVmax 3.6 in the body of the gallbladder. With a diagnosis of gallbladder cancer, extended cholecystectomy and gallbladder bed resection with regional lymph node dissection were performed. The tumor was diagnosed histologically as small cell type neuroendocrine carcinoma of the gallbladder(pT2a[SS], pN0, pStage ⅡA; Japanese society of hepato-biliary-pancreatic surgery, the 7th edition). The postoperative course was uneventful. This patient has been followed up for 8 years without obvious signs of recurrence. R0 resection and lack of lymph node metastasis can allow long- term survival.

MSE-type zeolites synthesized by different organic structure-directing agents (OSDAs), UZM-35 and MCM-68, were prepared. The location of Brønsted acid sites derived from the framework Al atoms and acidic properties were investigated based on 27 Al MQMAS NMR and in situ IR techniques combined with the evaluation of the catalytic activity. We have successfully found a significant difference in the location of Brønsted acid sites in the MSE-type framework; 61 and 33% of acid sites were located at the 12-ring channel for MCM-68 and UZM-35, respectively. The differences in the location of the acid sites yielded their unique catalytic activities for the hydrocarbon cracking reactions, indicating that a well-chosen type of OSDAs for the synthesis is one of the possibilities for controlling the distribution of the framework Al atoms in the MSE-type framework.

Background/aim: We previously observed higher prevalence of high-grade pancreatic intraepithelial neoplasia (PanIN) in LSL-Kras G12D/+ ; Pdx1 Cre/+ (KC-Crmp4 wild ) mice than LSL-Kras G12D/+ ; Pdx1 Cre/+ ; Crmp4 -/- (KC-Crmp4 -/- ) mice. This study investigated the relationship between collapsin response mediator protein 4 (CRMP4) and immune cell infiltration in pancreatic cancer., Materials and Methods: PanIN was induced by intraperitoneal injection of caerulein into KC-Crmp4 wild and KC-Crmp4 -/- mice, and immune cells in PanIN lesions were compared. Subcutaneous tumors were created by injecting Pan02 cells, and tumor diameter was compared between Crmp4 wild and Crmp4 -/- mice every 7 days. Peritumoral immune cells were examined immunohisto chemically., Results: High-grade PanIN in KC mice showed statistically significantly high expression of CD163 (p=0.031) and CD11b (p=0.027). Following subcutaneous injection of Pan02 cells, tumor diameter was greater in Crmp4 wild mice than Crmp4 -/- mice. Crmp4 wild mice exhibited higher CD163 and CD11b expression than Crmp4 -/- mice in tumors (p<0.001)., Conclusion: CRMP4 might promote pancreatic cancer by up-regulating M2 macrophages and myeloid-derived suppressor cells., (Copyright © 2022 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Wild silkworms survive in environmental habitats in which temperature and humidity vary based on the weather. In contrast, domesticated silkworms live in mild environments where temperature and humidity are generally maintained at constant levels. Previous studies showed that the mechanical strengths and molecular orientation of the silk fibers reeled from domesticated silkworms are significantly influenced by the reeling speed. Here, we investigated the effects of reeling speed on the mechanical properties of eri silk fibers produced by wild silkworms, Samia cynthia ricini, which belong to the family of Saturniidae. We found that the structural, morphological and mechanical features of eri silk fibers are maintained irrespective of the reeling speed, in contrast to those of domesticated silkworm silk fibers. The obtained results are useful not only for understanding the biological basis underlying the natural formation of silk fibers but also for contributing to the design of artificial spinning systems for producing synthetic silk fibers., Competing Interests: Competing interests The authors declare no competing or financial interests., (© 2022. Published by The Company of Biologists Ltd.)

The fabrication of novel oxide glass is a challenging topic in glass science. Alumina (Al 2 O 3 ) glass cannot be fabricated by a conventional melt-quenching method, since Al 2 O 3 is not a glass former. We found that amorphous Al 2 O 3 synthesized by the electrochemical anodization of aluminum metal shows a glass transition. The neutron diffraction pattern of the glass exhibits an extremely sharp diffraction peak owing to the significantly dense packing of oxygen atoms. Structural modeling based on X-ray/neutron diffraction and NMR data suggests that the average Al-O coordination number is 4.66 and confirms the formation of OAl 3 triclusters associated with the large contribution of edge-sharing Al-O polyhedra. The formation of edge-sharing AlO 5 and AlO 6 polyhedra is completely outside of the corner-sharing tetrahedra motif in Zachariasen's conventional glass formation concept. We show that the electrochemical anodization method leads to a new path for fabricating novel single-component oxide glasses., (© 2022. The Author(s).)

(Objective) The etiology of acute epididymitis in children remains poorly understood. Several studies have demonstrated that urine tests are negative in the majority of children with acute epididymitis, and the condition is self-limiting. The need for radiological evaluation of the urinary tract in children with acute epididymitis is still debatable. The aim of this study was to describe clinical and imaging findings in children with acute epididymitis. (Methods) We identified 47 children with acute epididymitis at our institute between 2017 and 2021.We retrospectively reviewed their clinical features and radiological and laboratory data. All children underwent ultrasonography of the kidney and urinary tract. (Results) Median patient age was 9 years (range, 6 months-16 years) and 60% of the cases occurred between the ages of 7 and 12 years. Thirteen children (28%) had a past history of genitourinary malformations. The common malformations were hypospadias in eight children and bladder dysfunction in three. Ultrasound revealed no new urinary tract abnormalities in the remaining 34 children. Urinalysis were performed in 27 children, nine of whom (33%) had pyuria. Urine culture was positive in two children. Of the nine children with genitourinary malformations, eight had pyuria. All 18 children without genitourinary malformations had a negative urinalysis except for one patient (p< 0.0001). (Conclusions) Acute epididymitis is a common cause of acute scrotum in pediatric patients. In this study, one-third of acute epididymitis cases presented pyuria, and about 30% had a past history of genitourinary malformations. The presence of pyuria was associated with a past history of genitourinary malformations. For children with no previous genitourinary malformations, routine use of ultrasound for the detection of urinary tract abnormalities is questionable due to the low yield.

Pancytopenia associated with vitamin B 12 and folic acid deficiency has been reported in patients who have undergone total gastrectomy. Therefore, myelosuppression due to chemotherapy following total gastrectomy is considered to be more serious. We encountered three cases of severe thrombocytopenia in patients who received chemotherapy after total gastrectomy. The lowest platelet levels in these patients were 1.7 × 10 4 /mm 3 , 2.3 × 10 4 /mm 3 , and 0.9 × 10 4 /mm 3 , respectively. None of the patients presented with vitamin B 12 deficiency, and one patient presented with folic acid deficiency. The association between serum vitamin levels and chemotherapy-related adverse events is controversial. Since folic acid has a shorter half-life (6 hours) and cannot accumulate in the body, unlike vitamin B 12 that is stored for a long time in the liver, folic acid deficiency is suspected to be associated with thrombocytopenia induced by post-total gastrectomy chemotherapy. However, serum folic acid levels fluctuate depending on the timing of evaluation and require a few days to evaluate. In conclusion, patients who undergo chemotherapy after total gastrectomy should be monitored for severe thrombocytopenia but serum vitamin B 12 levels are not necessarily clinically important. By measuring serum folic acid levels at appropriate times, folic acid deficiency may prove to be a reference for predicting severe thrombocytopenia.

Dysphonia has been reported with anti-angiogenic chemotherapy agents. Dysphonia in patients with cancer receiving chemotherapy tends to be overlooked in clinical practice since it is non-life-threatening. However, it reduces quality of life. Although inhibition of vascular endothelial growth factor receptor is the reported mechanism of dysphonia, it has not been elucidated. We report 6 cases of patients with dysphonia suspected to be due to panitumumab and nivolumab that have not been reported previously. Peripheral edema, a factor in dysphonia, can be seen with aflibercept, bevacizumab, panitumumab, and nivolumab. Therefore, chemotherapy drugs with peripheral edema may be related to dysphonia.

Aim: We identified chemical components that exhibited antitumor activity against oral squamous cell carcinoma (OSCC) cells and examined their effective concentrations and additive and/or synergistic effects in combinational usage on the proliferation, apoptosis and cell cycle of OSCC cells., Materials and Methods: Using high-performance liquid chromatography, nuclear magnetic resonance spectroscopy and electrospray ionization-mass spectrometry, we identified the main chemical components of the methanol extracts from Paeonia lutea. We investigated the pharmaceutical effects of those components on the proliferation, apoptosis, and cell cycle of an OSCC cell line, SAS, using the tetrazolium salt 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) and caspase assays, as well as flow cytometry cell cycle analysis. We also examined the effects of those components on the mitogen-activated protein kinase signal transduction pathway by western blotting. Finally, the effects on normal human epidermal keratinocyte cells were also examined in similar experiments., Results: Three chemicals have been identified in P. lutea leaves using high performance liquid chromatography: gallic acid methyl ester (GAME), pentagalloyl glucose (PGG) and paeoniflorin (PF). Both GAME and PGG significantly suppressed cell proliferation, and their combined effects were synergistic, while the effect of PF was minimal. However, those chemicals did not induce apoptosis. Cell cycle and western blotting analysis showed that the suppressive effects on cell proliferation resulted from G2 arrest and the suppression of phosphorylation of Akt/PKB. No effect was identified on normal human epidermal keratinocyte cells., Conclusion: These results indicate that GAME and PGG are the main chemical components of P. lutea leaves that have potential anti-cancer therapeutic effects., (Copyright © 2021 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background: Clinical evidence of thiamine-related neuropsychiatric symptoms, including the initial stage, is limited because serum thiamine levels tend to be evaluated only for patients who develop severe neuropsychiatric symptoms suspected to be related to severe thiamine deficiency. This study aimed to evaluate the relationship between thiamine decline and neuropsychiatric symptoms, including initial symptoms, and the effect of chemotherapy on serum thiamine levels in gastrointestinal and hematological cancer patients receiving chemotherapy., Method: We retrospectively identified 87 patients who were diagnosed with gastrointestinal and hematological cancers at our hospital. We evaluated the risk factors associated with neuropsychiatric symptoms, including initial symptoms (neuropsychiatric symptoms), the relationship between the presence of neuropsychiatric symptoms and serum thiamine levels, and changes in serum thiamine levels after chemotherapy., Results: Logistic regression analysis identified thiamine decline as a significant factor associated with neuropsychiatric symptoms (p < 0.001, odds ratio = 0.040, 95% confidence interval [CI]: 0.010-0.163). The Mann-Whitney U test showed that patients with neuropsychiatric symptoms had significantly lower serum thiamine levels (19.5 ± 5.4 ng/mL, n = 39) than patients without neuropsychiatric symptoms (31.9 ± 14.2 ng/mL, n = 48) (p = 0.001). In hematological cancer patients, serum thiamine levels gradually declined after chemotherapy, with the lowest levels at 5-8 weeks (23.5 ± 7.6 ng/mL, P = 0.035 vs. 0 weeks, Wilcoxon rank sum test)., Conclusion: Our study showed that a decrease in serum thiamine levels can be a risk factor for neuropsychiatric symptoms, and chemotherapy can lead to a decrease in serum thiamine levels., (Copyright © 2021 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Li 7 P 3 S 11 glass ceramics have high conductivities competitive with liquid electrolytes, making them good candidates as solid-state electrolytes for all-solid-state lithium-ion batteries. However, the metastable nature and performance of Li 7 P 3 S 11 glass ceramics remain mysterious. Herein, modified Li 7 P 3 S 11 glass ceramics with compositions of 70Li 2 S-30P 2 S 5 were prepared via two-step mechanical milling and thermal annealing. Li 7 P 3 S 11 glass ceramics synthesized using the conventional method (mechanical milling and thermal annealing) were again ball-milled to obtain amorphous 70Li 2 S-30P 2 S 5 with a peculiar glass structure. Further thermal annealing was carried out to crystallize the glass. The obtained crystalline phase was analogous to the original Li 7 P 3 S 11 phase, but the conductivity was enhanced by a factor of 1.7. Based on 31 P solid-state nuclear magnetic resonance (NMR) spectroscopy, the Li 7 P 3 S 11 phase contained an additional PS 4 3- unit. A rational deconvolution procedure for the 31 P solid-state NMR spectra based on crystalline Li 7 P 3 S 11 was developed and applied to the samples. The analysis can resolve the additional crystalline PS 4 3- unit in the Li 7 P 3 S 11 structure. Based on two-dimensional double-quantum 31 P NMR spectroscopy, the additional PS 4 3- unit is located adjacent to the P 2 S 7 4- unit, suggesting that P 2 S 7 4- is divided into two PS 4 3- units in the Li 7 P 3 S 11 phase. The flip motion of Li + was also investigated based on the 7 Li spin-lattice relaxation time. The independent activation energy of spin-lattice relaxation with respect to temperature in the Li 7 P 3 S 11 phase was attributed to a conduction path between the two PS 4 3- units. The findings provide a synthetic route that can be used to develop metastable solid-state electrolytes.

Axial chirality was induced by circularly polarized light to covalent organic frameworks as well as hyperbranched polymers composed of bezene-1,3,5-triyl core units and oligo(benzene-1,4-diyl) as linker units where variation in induction efficiency was rationally interpreted in terms of internal rotation dynamics studied through CPMAS 13C NMR experiments including CODEX measurements.

Introduction: Primary benign adenomas of the appendix occur rarely. According to appendectomy and autopsy reports, benign adenomas of the appendix are sporadically reported, accounting for ~0.02-0.08% cases., Presentation of Case: We report the case of a 58-year-old woman with a segmental polyp protruding into the appendiceal orifice. The polyp was spotted during lower gastrointestinal endoscopy; however, treatment was postponed at the patient's request. During a confirmatory lower gastrointestinal endoscopy for treatment, the polyp was no longer found protruding from the appendiceal orifice and had disappeared. An appendicectomy was performed for diagnostic and therapeutic purposes. Pathological examination showed a low-degree atypical tubular adenoma with no malignant findings., Discussion: Despite the risk of perforation, surgical resection remains the gold standard for treating appendiceal adenoma. Resection can be performed endoscopically if the stem and base of the adenoma can be identified. In the present case, laparoscopy was a good indication from the safety standpoint, and it was radically curative. Furthermore, upon performing an appendectomy, the patient was informed of the risks of cancer-related complications or the need for additional resection., Conclusion: This suggestive case proves that appendiceal tumors can disappear endoscopically depending on the timing of examination and treatment., (Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Objectives: FOLFOX is a standard chemotherapy regimen used to treat colorectal cancer. Adverse events associated with FOLFOX treatment include peripheral neuropathy and myelosuppression. This report discusses the case of a 64-year-old man with rectal cancer who developed hyperammonemia and impaired consciousness following initiation of mFOLFOX6 as a postoperative adjuvant therapy., Methods: This case study reports on the clinical disease progression of the aforementioned patient., Results: Following preoperative chemoradiotherapy, the patient underwent low anterior resection for rectal cancer. mFOLFOX6 was then initiated as postoperative adjuvant therapy. During the 5 th cycle of mFOLFOX6 treatment, the patient presented with impaired consciousness and upper extremity convulsions. Blood testing revealed marked hyperammonemia (349 µg/dL (normal range: 12 - 66 µg/dL)). Imaging did not reveal any intracranial lesions that could cause impaired consciousness. The patient recovered within a day after rehydration and BCAA substitution., Conclusion: Although impaired consciousness is a rare adverse reaction of FOLFOX, it has a major psychological impact on the patient and his/her family. Hyperammonemia should therefore be considered a potential cause of impaired consciousness during FOLFOX therapy and should be appropriately diagnosed and treated.

Genomic analysis revealed that the vaccine seed lot of Mycobacterium bovis bacillus Calmette-Guérin (BCG) Tokyo 172 contains two subclones (types I and II), but their phenotypic differences have not been elucidated. In this study, we compared the susceptibility of bacilli types I and II to oxidative stress in vitro and within host cells. Notably, the subclones displayed similar superoxide dismutase activity; however, foam height in the catalase test and lysate catalase/peroxidase activity were higher for type I bacilli than for type II bacilli. Additionally, type I bacilli were less susceptible to hydrogen peroxide (H 2 O 2 ) than type II bacilli. After exposure to H 2 O 2 , antioxidative stress response genes katG , ahpC , sodA , and trxA were more strongly induced in type I bacilli than in type II bacilli. Further, we investigated cell survival in macrophages. Fewer type II bacilli were recovered than type I bacilli. However, in the presence of apocynin, a specific inhibitor of NADPH oxidase, type II recovery was greater than that of type I. The production of interleukin 1β (IL-1β), IL-12 p40, and tumor necrosis factor alpha (TNF-α) was higher in type I bacillus-infected macrophages than in type II bacillus-infected macrophages. The proportions of type I and type II bacilli in vaccine lots over 3 years (100 lots) were 97.6% ± 1.5% and 2.4% ± 1.5%, respectively. The study results illustrated that type I bacilli are more resistant to oxidative stress than type II bacilli. Overall, these findings provide important information in terms of the quality control and safety of BCG Tokyo 172 vaccine. IMPORTANCE This study revealed the difference of in vivo and in vitro antioxidative stress properties of BCG Tokyo 172 types I and II as one of the bacteriological characteristics. In particular, the bacilli exhibited differences in catalase/peroxidase activity, which could explain their different protective effects against infection. The differences correlated with survival in the host cell and the production of proinflammatory cytokines to protect against infection by Mycobacterium tuberculosis The proportion of bacilli types I and II in all commercial lots of BCG Tokyo 172 over 3 years (100 lots) was constant. The findings also highlighted the importance of analyzing their content for quality control during vaccine production., (Copyright © 2021 Taniguchi et al.)

(1) Background: Lactococcus lactis strain Plasma (LC-Plasma) is a unique strain which directly activates plasmacytoid dendritic cells, resulting in the prevention against broad spectrum of viral infection. Additionally, we found that LC-Plasma intake stimulated skin immunity and prevents Staphylococcus aureus epicutaneous infection. The aim of this study was to investigate the effect of LC-Plasma dietary supplementation on skin microbiome, gene expression in the skin, and skin conditions in healthy subjects. (2) Method: A randomized, double-blind, placebo-controlled, parallel-group trial was conducted. Seventy healthy volunteers were enrolled and assigned into two groups receiving either placebo or LC-Plasma capsules (approximately 1 × 10 11 cells/day) for 8 weeks. The skin microbiome was analyzed by NGS and qPCR. Gene expression was analyzed by qPCR and skin conditions were diagnosed by dermatologists before and after intervention. (3) Result: LC-Plasma supplementation prevented the decrease of Staphylococcus epidermidis and Staphylococcus pasteuri and overgrowth of Propionibacterium acnes . In addition, LC-Plasma supplementation suggested to increase the expression of antimicrobial peptide genes but not tight junction genes. Furthermore, the clinical scores of skin conditions were ameliorated by LC-Plasma supplementation. (4) Conclusions: Our findings provided the insights that the dietary supplementation of LC-Plasma might have stabilizing effects on seasonal change of skin microbiome and skin conditions in healthy subjects.

Purpose: Most patients with Crohn's disease (CD) experience surgical recurrence. In this era of novel therapies, we conducted this study to clarify which treatments effectively decrease the risk of surgical recurrence in patients with CD., Methods: The subjects of this retrospective study were 37 patients with CD. We created cumulative surgery rate curves and performed univariate and multivariate analyses., Results: Univariate analysis revealed that patients who consumed an elemental diet (ED; ≥ 900 kcal/day), anti-tumor necrosis factor-alpha, and thiopurines had a significantly better prognosis than those who did not (p = 0.011, p = 0.025, and p = 0.0080, respectively). Multivariate analysis revealed that ED therapy and thiopurines were independent significant factors for controlling surgical recurrence (p = 0.046 and p = 0.032, respectively). Additional analyses showed that the most promising ED therapeutic dose was ≥ 1200 kcal/day, while an ED therapeutic dose of ≥ 900 kcal/day was acceptable., Conclusions: Although univariate analyses revealed that all three treatment strategies had significant effects on surgical recurrence in patients with CD, multivariate analysis revealed that only ED therapy was significantly associated with surgical recurrence rates. Thus, ED therapy plays an important role in the management of CD, even in the era of biological therapies.

Web-building spiders secrete dragline silk fibers to sustain their body and use them as frameworks during web construction. They spin dragline silk fibers at various spinning speed and humidity conditions depending on their natural habitat. Here, we investigated the effect of spinning speed and humidity on the structural and mechanical properties of dragline silk fibers from web-building spider Trichonephila clavata obtained by the forcibly spinning method. We found that the crystal and morphological structures did not rely on the spinning speed and humidity. Furthermore, the mechanical strength and extensibility of the dragline silk fibers were maintained, demonstrating that dragline silk fibers ensure robustness irrespective of the spinning speed and humidity. The results obtained in the present study are helpful not only to understand the biological basis of the silk fiber formation of spiders but also contribute to consider the spinning conditions for the process of creating synthetic silk fibers., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Lithium- and manganese-rich layered oxides (LMRs) are promising positive electrode materials for next-generation rechargeable lithium-ion batteries. Herein, the structural evolution of Li 1.2 Ni 0.2 Mn 0.6 O 2 during the initial charge-discharge cycle was examined using synchrotron-radiation X-ray diffraction, X-ray absorption spectroscopy, and nuclear magnetic resonance spectroscopy to elucidate the unique delithiation behavior. The pristine material contained a composite layered structure composed of Ni-free and Ni-doped Li 2 MnO 3 and LiMO 2 (M = Ni, Mn) nanoscale domains, and Li ions were sequentially and inhomogeneously extracted from the composite structure. Delithiation from the LiMO 2 domain was observed in the potential slope region associated with the Ni 2+ /Ni 4+ redox couple. Li ions were then extracted from the Li 2 MnO 3 domain during the potential plateau and remained mostly in the Ni-doped Li 2 MnO 3 domain at 4.8 V. In addition, structural transformation into a spinel-like phase was partly observed, which is associated with oxygen loss and cation migration within the Li 2 MnO 3 domain. During Li intercalation, cation remigration and mixing resulted in a domainless layered structure with a chemical composition similar to that of LiNi 0.25 Mn 0.75 O 2 . After the structural activation, the Li ions were reversibly extracted from the newly formed domainless structure.

Non-uniform self-heating and temperature hotspots are major concerns compromising the performance and reliability of submicron electronic and optoelectronic devices. At deep submicron scales where effects such as contact-related artifacts and diffraction limits accurate measurements of temperature hotspots, non-contact thermal characterization can be extremely valuable. In this work, we use a Bayesian optimization framework with generalized Gaussian Markov random field (GGMRF) prior model to obtain accurate full-field temperature distribution of self-heated metal interconnects from their thermoreflectance thermal images (TRI) with spatial resolution 2.5 times below Rayleigh limit for 530nm illumination. Finite element simulations along with TRI experimental data were used to characterize the point spread function of the optical imaging system. In addition, unlike iterative reconstruction algorithms that use ad hoc regularization parameters in their prior models to obtain the best quality image, we used numerical experiments and finite element modeling to estimate the regularization parameter for solving a real experimental inverse problem.

Objective: To describe the gonadal features of patients with 45,X/46,XY mosaicism, and to evaluate the prevalence of gonadal tumor in different phenotypes., Materials and Methods: The medical records of consecutive patients with 45,X/46,XY karyotype or its variants who had undergone gonadal biopsy or gonadectomy at a single institute between 1996 and 2017 were retrospectively reviewed., Results: Of 34 patients with 45,X/46,XY mosaicism, a unilateral dysgenetic testis and a contralateral streak gonad was detected in 20 patients (59%), bilateral streak gonads in 9 (26%), and bilateral dysgenetic testes in 5 (15%). A gonad composed of both streak and dysgenetic testicular portions was observed in 7 gonads of 6 patients. All streak gonads were removed, and bilateral gonadectomy was performed in 15 patients raised as girls. Pathologic examination revealed gonadal tumors in 6 of the 34 (18%) patients, including a gonadoblastoma in 7 gonads among 5 patients and an association of dysgerminoma with gonadoblastoma in 1 gonad. All 6 patients who developed gonadal tumor had female genitalia. Postoperative course was uneventful except 1 boy. A seminoma was developed in his soritaly scrotal testis at the age of 16 years., Conclusion: The prevalence of gonadal tumor in patients with 45,X/46,XY mosaicism may vary according to the phenotype, and high in patients with female phenotype. Considering the increased risk of gonadal tumors in such patients, early investigation and individual management, including prophylactic gonadectomy, are recommended. In male patients, a close follow-up of the preserved testes is mandatory until adulthood., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Pancreatic intraepithelial neoplasia (PanIN), the most common premalignant lesion of the pancreas, is a histologically well-defined precursor to invasive pancreatic ductal adenocarcinoma (PDAC). However, the molecular mechanisms underlying the progression of PanINs have not been fully elucidated. Previously, we demonstrated that the expression of collapsin response mediator protein 4 (CRMP4) in PDAC was associated with poor prognosis. The expression of CRMP4 was also augmented in a pancreatitis mouse model. However, the role of CRMP4 in the progression of PanIN lesions remains uncertain. In the present study, we examined the relationship between CRMP4 expression and progression of PanIN lesions using genetically engineered mouse models. PanIN lesions were induced by peritoneal injection of the cholecystokinin analog caerulein in LSL-KRAS G12D ; Pdx1-Cre (KC-Crmp4 wild-type, WT) mice and LSL-KRAS G12D ; Pdx1-Cre; Crmp4 -/- (KC-Crmp4 knockout, KO) mice. We analyzed pancreatic tissue sections from these mice and evaluated PanIN grade by hematoxylin and eosin staining. CRMP4 expression was examined and the cellular components assessed by immunohistochemistry using antibodies against CRMP4, CD3, and α-smooth muscle actin (SMA). The incidence of high-grade PanIN in KC-Crmp4 WT mice was higher than that in KC-Crmp4 KO animals. CRMP4 was expressed not only in epithelial cells but also in αSMA-positive cells in stromal areas of PanIN lesions. The CRMP4 expression in stromal areas correlated with PanIN grade in WT mice. These results suggested that the expression of CRMP4 in stromal cells may underlie the incidence or progression of PanIN., Competing Interests: Conflict of Interest None., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Objectives: The aim of this retrospective study was to search for risk factors for neurological adverse events in gastrointestinal cancer patients receiving chemotherapy and analyze the relationship between thiamine serum levels and neurological adverse events., Materials and Methods: This is a single-center retrospective observational study. We enrolled patients who were diagnosed with gastrointestinal cancer at our hospital, for whom we measured the thiamine serum levels. We then performed a multivariate analysis (logistic regression) to identify risk factors for the neurological symptoms in our cohort. We then divided the patients into two groups, with and without neurological symptoms, based on their electronic medical records. By using the Mann-Whitney U-test, we performed a comparative analysis of the thiamine serum levels between the two groups. We also used descriptive statistics to examine the presence/absence of neurological symptoms or other potentially related clinical features in patients with decreased thiamine serum levels., Results: The logistic regression analysis detected the decrease in thiamine serum levels as a statistically significant risk factor for neurological symptoms. The analysis of the relationship between the presence/absence of neurological symptoms and thiamine serum levels showed that the thiamine serum levels were significantly lower in the group presenting neurological symptoms. Descriptive statistics showed that all the patients with decreased thiamine serum levels had either cognitive decline, attention decline, or depression symptoms, and most of them were receiving the 5-fluorouracil anticancer drug and showing decreased serum albumin levels. We also observed a slight decrease in serum sodium, vitamin B12, and folate levels., Conclusion: When neurological symptoms occur in patients receiving chemotherapy for gastrointestinal cancer, the measurement of thiamine serum levels may become a standard reference for treatment indication.