Clear Cell Squamous Cell Carcinoma of the Maxillary Gingiva Associated with PIK3CA and HRAS Mutations: Report of a Case and Literature Review

The version of record of this article, first published in Head and Neck Pathology, is available online at Publisher’s website: https://doi.org/10.1007/s12105-023-01580-8.Background: Squamous cell carcinoma (SCC) is the most common oral malignancy, and somatic mutations in some driver genes have been implicated in SCC development. Clear cell SCC (CCSCC) is a rare histological variant of SCC, and various clear cell neoplasms must be considered in the differential diagnosis of CCSCC in the oral cavity. Based on a limited number of CCSCC cases reported in the oral cavity, CCSCC is considered an aggressive variant of SCC with a poor prognosis; however, its genetic characteristics remain unknown. Methods: A maxillary gingival tumor in an 89-year-old female was described and investigated using immunohistochemical staining, special staining, fluorescence in situ hybridization, and next-generation sequencing (NGS) with a custom panel of driver genes, including those associated with SCC and clear cell neoplasm development. Results: Histopathological examination revealed a proliferation of atypical epithelial cells with abundant clear cytoplasm and enlarged and centrally placed round nuclei. The tumor was exophytic with deep, penetrating proliferation. The atypical clear cells were continuous with the conventional SCC cells. Immunohistochemical analysis showed that the clear cells were positive for CK AE1/AE3 and CK5/6 and nuclear-positive for p63. In contrast, the clear cells were negative for αSMA, S100, HMB45, Melan-A, CD10, and p16. p53 immunoreactivity exhibited a wild-type expression pattern. Additionally, the clear cells were positive for periodic acid-Schiff (PAS) and negative for diastase-PAS, mucicarmine, and Alcian blue. Based on these results, the diagnosis of CCSCC was confirmed. Molecular analysis of the clear cells identified PIK3CA p.E542K (c.1624G>A) and HRAS p.G12A (c.35 G>C) somatic mutations classified as oncogenic. No pathogenic variants were identified in TP53, EWSR1, AKT1, PTEN, BRAF, KRAS, NRAS, RASA1, or MAML2. Conclusions: We report a case of CCSCC of the oral cavity with PIK3CA and HRAS mutations. The identification of PIK3CA and/or HRAS mutations is rare in SCC; however, both mutations are important potential targets for antitumor therapy. A detailed analysis of gene mutations in CCSCC may lead to a better understanding of its biological behavior and an improved prognosis, as well as a differential diagnosis from other clear cell neoplasms

Effects of Respiratory Muscle Stretch Gymnastics on Children\u27s Emotional Responses

Respiratory muscle stretch gymnastics (RMSG) are designed to decrease chest wall stiffness, reduce dyspnea at rest and improve the quality of life. The focus of this study was to determine whether a RMSG program affects the psychological state of healthy subjects. A previous study showed that there is a positive correlation between anxiety level and respiratory rate (RR). We hypothesize that RMSG will decrease the RR related to alterations in anxiety or other factors that are associated with the quality of life in healthy children. Forty-four primary school children living in Tokyo participated in the study and were randomly assigned to either gymnastics or control groups. Baseline assessment of both groups included completion of the Questionnaire for Measuring Health-Related Quality of Life in Children (Kid-KINDL) and the State-Trait Anxiety Inventories for Children (STAI-C). RRs were recorded initially and the children in the gymnastics group were instructed on how to perform RMSG. The RR was measured again and the participants completed the state anxiety scale. The gymnastics group was told to perform the gymnastics once a day for one week, whereupon post-testing using the testing protocol used for the baseline measurement was performed again on both groups. RR and anxiety level significantly decreased while Kid-KINDL increased after one week of RMSG in high trait anxiety subjects of the gymnastics group. We suggest that the decrease in RR after RMSG reduces anxiety levels in children, and contributes to an improvement in their Kid-KINDL score

Study on development policy for new cryogenic structural material for superconducting magnet of fusion reactor

A fusion DEMO will require large-scale cryogenic structure including TF coil cases. Because of huge electromagnetic forces, extra thick plates and/or wrought products will be supplied. Since the midsection of the huge block is weaker than the block surface region, the design yield stress must be determined taking account of this lower strength part. To search the manufacturing process to improve the midsection strength, the crystal refinement strengthening and the precipitation strengthening are considered together with the carbon and nitrogen solid solution strengthening. XM-19 was focused based on the variation of the yield stress and the fracture toughness, a 100 mm thick block and a 30 mm thick plate were trial produced, and strength and the fracture toughness at the midsection were evaluated. This study will present the experimental data and discuss the development policy for a new cryogenic structural material for a fusion reactor

Tryptophan and Kynurenine Enhances the Stemness and Osteogenic Differentiation of Bone Marrow-Derived Mesenchymal Stromal Cells In Vitro and In Vivo

Aging tissues present a progressive decline in homeostasis and regenerative capacities, which has been associated with degenerative changes in tissue-specific stem cells and stem cell niches. We hypothesized that amino acids could regulate the stem cell phenotype and differentiation ability of human bone marrow-derived mesenchymal stromal cells (hBMSCs). Thus, we performed a screening of 22 standard amino acids and found that D-tryptophan (10 mu M) increased the number of cells positive for the early stem cell marker SSEA-4, and the gene expression levels of OCT-4, NANOG, and SOX-2 in hBMSCs. Comparison between D- and L-tryptophan isomers showed that the latter presents a stronger effect in inducing the mRNA levels of Oct-4 and Nanog, and in increasing the osteogenic differentiation of hBMSCs. On the other hand, L-tryptophan suppressed adipogenesis. The migration and colony-forming ability of hBMSCs were also enhanced by L-tryptophan treatment. In vivo experiments delivering L-tryptophan (50 mg/kg/day) by intraperitoneal injections for three weeks confirmed that L-tryptophan significantly increased the percentage of cells positive for SSEA-4, mRNA levels of Nanog and Oct-4, and the migration and colony-forming ability of mouse BMSCs. L-kynurenine, a major metabolite of L-tryptophan, also induced similar effects of L-tryptophan in enhancing stemness and osteogenic differentiation of BMSCs in vitro and in vivo, possibly indicating the involvement of the kynurenine pathway as the downstream signaling of L-tryptophan. Finally, since BMSCs migrate to the wound healing site to promote bone healing, surgical defects of 1 mm in diameter were created in mouse femur to evaluate bone formation after two weeks of L-tryptophan or L-kynurenine injection. Both L-tryptophan and L-kynurenine accelerated bone healing compared to the PBS-injected control group. In summary, L-tryptophan enhanced the stemness and osteoblastic differentiation of BMSCs and may be used as an essential factor to maintain the stem cell properties and accelerate bone healing and/or prevent bone loss

Olfactory Response in Patients with Cerebral Palsy: Investigation of the Possible Use of Olfactory Testing to Evaluate Patients and Reduce Anxiety of Their Parents

Cerebral palsy (CP) is a developmental disorder associated with lifelong motor impairment and disability. Several studies have investigated the effects of CP on sensory responses, but there has been no research on olfactory function in CP. This study had two specific aims. First, by observing respiratory responses which serve as an index for the ability to detect and recognize odors, we aimed to estimate the patients\u27 ability to distinguish pleasant from unpleasant odors. These responses can also indicate the capacity for an emotional response to pleasant or unpleasant stimuli. Second, we aimed to investigate the psychological response in the parents as they observed the respiratory response in their children during the odor test. Parents were assessed with the Spielberger State-Trait Anxiety Inventory (STAI) to measure their state anxiety levels before and after they had observed their children being tested. In patients with CP, respiratory rate (RR) significantly decreased during pleasant odor stimuli (P < 0.05). There was a significant increase in RR during the presentation of the unpleasant odor (P < 0.05). All the CP patients showed respiratory changes in response to both pleasant and unpleasant smells, and we found that the parents\u27 anxiety levels decreased after the test. We intend to develop this olfactory test technique to contribute to the neurological rehabilitation for CP patients and to reduce anxiety of their parents

SERENADE II: An ALMA Multi-Band Dust-Continuum Analysis of 28 Galaxies at 5<z<85<z<8 and the Physical Origin of the Dust Temperature Evolution

We present an analysis of ALMA multi-band dust-continuum observations for 28 spectroscopically-confirmed bright Lyman-break galaxies at $5<z<8$. Our sample consists of 11 galaxies at $z\sim6$ newly observed in our ALMA program, which substantially increases the number of $5<z<8$ galaxies with both rest-frame 88 and 158 $\mu{\rm m}$ continuum observations, allowing us to simultaneously measure the IR luminosity and dust temperature for a statistical sample of $z\gtrsim5$ galaxies for the first time. We derive the relationship between the UV slope ($\beta_{\rm UV}$) and infrared excess (IRX) for the $z\sim6$ galaxies, and find a shallower IRX-$\beta_{\rm UV}$ relation compared to the previous results at $z\sim2$--4. Based on the IRX-$\beta_{\rm UV}$ relation consistent with our results and the $\beta_{\rm UV}$-$M_{\rm UV}$ relation including fainter galaxies in the literature, we find a limited contribution of the dust-obscured star formation to the total SFR density, $\sim30\%$ at $z\sim6$. Our measurements of the dust temperature at $z\sim6-7$, $T_{\rm dust}=40.9_{-9.1}^{+10.0}\,{\rm K}$ on average, supports a gentle increase of $T_{\rm dust}$ from $z=0$ to $z\sim6$--7. Using an analytic model with parameters consistent with recent {\it{JWST}} results, we discuss that the observed redshift evolution of the dust temperature can be reproduced by an $\sim0.6\,{\rm dex}$ increase in the gas depletion timescale and $\sim0.4\,{\rm dex}$ decrease of the metallicity. The variety of $T_{\rm dust}$ observed at high redshifts can also be naturally explained by scatters around the star-formation main sequence and average mass-metallicity relation, including an extremely high dust temperature of $T_{\rm dust}>80\,{\rm K}$ observed in a galaxy at $z=8.3$.Comment: Submitted to Ap

Photoinduced dynamics during electronic transfer from narrow to wide bandgap layers in one-dimensional heterostructured materials

Electron transfer is a fundamental energy conversion process widely present in synthetic, industrial, and natural systems. Understanding the electron transfer process is important to exploit the uniqueness of the low-dimensional van der Waals (vdW) heterostructures because interlayer electron transfer produces the function of this class of material. Here, we show the occurrence of an electron transfer process in one-dimensional layer-stacking of carbon nanotubes (CNTs) and boron nitride nanotubes (BNNTs). This observation makes use of femtosecond broadband optical spectroscopy, ultrafast time-resolved electron diffraction, and first-principles theoretical calculations. These results reveal that near-ultraviolet photoexcitation induces an electron transfer from the conduction bands of CNT to BNNT layers via electronic decay channels. This physical process subsequently generates radial phonons in the one-dimensional vdW heterostructure material. The gathered insights unveil the fundamentals physics of interfacial interactions in low dimensional vdW heterostructures and their photoinduced dynamics, pushing their limits for photoactive multifunctional applications

Organoids with cancer stem cell-like properties secrete exosomes and HSP90 in a 3D nanoenvironment

Ability to form cellular aggregations such as tumorspheres and spheroids have been used as a morphological marker of malignant cancer cells and in particular cancer stem cells (CSC). However, the common definition of the types of cellular aggregation formed by cancer cells has not been available. We examined morphologies of 67 cell lines cultured on three dimensional morphology enhancing NanoCulture Plates (NCP) and classified the types of cellular aggregates that form. Among the 67 cell lines, 49 cell lines formed spheres or spheroids, 8 cell lines formed grape-like aggregation (GLA), 8 cell lines formed other types of aggregation, and 3 cell lines formed monolayer sheets. Seven GLA-forming cell lines were derived from adenocarcinoma among the 8 lines. A neuroendocrine adenocarcinoma cell line PC-3 formed asymmetric GLA with ductal structures on the NCPs and rapidly growing asymmetric tumors that metastasized to lymph nodes in immunocompromised mice. In contrast, another adenocarcinoma cell line DU-145 formed spheroids in vitro and spheroid-like tumors in vivo that did not metastasize to lymph nodes until day 50 after transplantation. Culture in the 3D nanoenvironment and in a defined stem cell medium enabled the neuroendocrine adenocarcinoma cells to form slowly growing large organoids that expressed multiple stem cell markers, neuroendocrine markers, intercellular adhesion molecules, and oncogenes in vitro. In contrast, the more commonly used 2D serum-contained environment reduced intercellular adhesion and induced mesenchymal transition and promoted rapid growth of the cells. In addition, the 3D stemness nanoenvironment promoted secretion of HSP90 and EpCAM-exosomes, a marker of CSC phenotype, from the neuroendocrine organoids. These findings indicate that the NCP-based 3D environment enables cells to form stem cell tumoroids with multipotency and model more accurately the in vivo tumor status at the levels of morphology and gene expression