Variation in presepsin and thrombomodulin levels for predicting COVID-19 mortality.

Coronavirus disease (COVID-19) has caused extensive mortality globally; therefore, biomarkers predicting the severity and prognosis of COVID-19 are essential. This study aimed to evaluate the application of presepsin (P-SEP) and thrombomodulin (TM), which are biomarkers of sepsis and endothelial dysfunction, respectively, in the prognosis of COVID-19. Serum P-SEP and TM levels from COVID-19 patients (n = 183) were measured. Disease severity was classified as mild, moderate I, moderate II, or severe based on hemoglobin oxygen saturation and the history of intensive care unit transfer or use of ventilation at admission. Patients in the severe group were further divided into survivors and non-survivors. P-SEP and TM levels were significantly higher in the severe group than those in the mild group, even after adjusting for creatinine values. In addition, TM levels were significantly higher in non-survivors than in survivors. Changes in the P-SEP levels at two time points with an interval of 4.1 ± 2.2 days were significantly different between the survivors and non-survivors. In conclusion, TM and continuous P-SEP measurements may be useful for predicting mortality in patients with COVID-19. Moreover, our data indicate that P-SEP and TM values after creatinine adjustment could be independent predictive markers, apart from renal function.

A Case of a Congenital Cholesteatoma Without Growth for a Long Term.

Congenital cholesteatoma is typically an expanding cystic mass of keratinizing squamous epithelium located medial to the intact tympanic membrane in patients with no prior history of perforation, otorrhea and ear. It is generally thought to be a progressive disease and is usually surgically removed upon detection as the first-choice treatment. As such, it is rare to be observed for a long term without progression. Here we report a rare case of congenital cholesteatoma that remained in an undetectable size and did not deteriorate mild hearing loss for 12 years. A seven years old boy was referred to us with right hearing impairment. Pure-tone audiometry found conductive hearing loss with an air-bone gap of 25 dB and a high-resolution computed tomography (CT) scan found the eroded long process of incus but did not detect any soft tissue density indicating congenital cholesteatoma. He initially did not wish to undergo surgery. His hearing level and image finding remained virtually unchanged during the next 12 years of the follow-up period. Twelve years later, endoscopic ear surgery was performed, which revealed a very small cholesteatoma mass, an eroded long process of the incus and ossicular chain discontinuities. We suspect that the cholesteatoma was originally larger, partially eroded the incus, then regressed to a very small size, and remained small for at least 12 years under our observation.

Effect of Subthalamic Deep Brain Stimulation on Upper Limb Dexterity in Patients with Parkinson Disease.

OBJECTIVE: The efficacy of deep brain stimulation (DBS) of the subthalamic nucleus (STN) on dexterity remains controversial despite its recognition as an effective strategy for Parkinson disease. The present study investigated the efficacy of STN-DBS for ameliorating bradykinesia and dexterity compared with dopaminergic medications. METHODS: Part III of the Unified Parkinson's Disease Rating Scale was used for the evaluation of bradykinesia, whereas the Purdue Pegboard Test and the Box and Block test were selected for dexterity. RESULTS: Our findings indicate that bradykinesia is significantly improved with both DBS and dopaminergic medication, whereas dexterity is improved only with DBS. Dopaminergic medication did not show a satisfactory efficacy on dexterity, and there was little synergistic effect of dopaminergic medication and STN-DBS for improving dexterity associated with Parkinson disease. CONCLUSIONS: Our results suggest that DBS is potentially more effective than dopaminergic medications for improving dexterity. The disparities in efficacy for bradykinesia and dexterity between DBS and dopaminergic medication hint at the potential mechanisms of STN-DBS. We speculate that DBS follows at least 2 different mechanisms for improving parkinsonian symptoms: 1) the dopaminergic system, primarily for the improvement of bradykinesia and 2) the nondopaminergic system, for the improvement of dexterity. This hypothesis requires further verification and investigation.

Effects of MERTK Inhibitors UNC569 and UNC1062 on the Growth of Acute Myeloid Leukaemia Cells.

BACKGROUND: MER proto-oncogene tyrosine kinase (MERTK) is a receptor tyrosine kinase that affects cancer cell proliferation. This study evaluated the effects of the synthetic MERTK inhibitors UNC569 and UNC1062 on in vitro growth of acute myeloid leukaemia (AML) cells. MATERIALS AND METHODS: Four AML cell lines expressing MERTK were treated with UNC569 and UNC1062 and analyzed for cell proliferation, immunoblotting, and gene expression. The effects of MERTK knockdown were also evaluated. RESULTS: Treatment with the inhibitors suppressed cell growth and induced apoptosis in all cell lines. OCI/AML5 and TMD7 cells, in which MERTK was constitutively phosphorylated by autocrine mechanisms, were highly susceptible to these inhibitors. The treatment reduced the phosphorylation of MERTK and its down-stream signalling molecules, v-akt murine thymoma viral oncogene homolog 1 (AKT) and extracellular signal-regulated kinase (ERK). Similar effects were observed after MERTK knockdown. The inhibitors and the knockdown caused similar changes in mRNA expression. CONCLUSION: These MERTK inhibitors are potential molecular-targeted drugs for treating AML expressing constitutively phosphorylated MERTK.

Convolutional neural network based on SMILES representation of compounds for detecting chemical motif.

BACKGROUND: Previous studies have suggested deep learning to be a highly effective approach for screening lead compounds for new drugs. Several deep learning models have been developed by addressing the use of various kinds of fingerprints and graph convolution architectures. However, these methods are either advantageous or disadvantageous depending on whether they (1) can distinguish structural differences including chirality of compounds, and (2) can automatically discover effective features. RESULTS: We developed another deep learning model for compound classification. In this method, we constructed a distributed representation of compounds based on the SMILES notation, which linearly represents a compound structure, and applied the SMILES-based representation to a convolutional neural network (CNN). The use of SMILES allows us to process all types of compounds while incorporating a broad range of structure information, and representation learning by CNN automatically acquires a low-dimensional representation of input features. In a benchmark experiment using the TOX 21 dataset, our method outperformed conventional fingerprint methods, and performed comparably against the winning model of the TOX 21 Challenge. Multivariate analysis confirmed that the chemical space consisting of the features learned by SMILES-based representation learning adequately expressed a richer feature space that enabled the accurate discrimination of compounds. Using motif detection with the learned filters, not only important known structures (motifs) such as protein-binding sites but also structures of unknown functional groups were detected. CONCLUSIONS: The source code of our SMILES-based convolutional neural network software in the deep learning framework Chainer is available at http://www.dna.bio.keio.ac.jp/smiles/ , and the dataset used for performance evaluation in this work is available at the same URL.

Genome sequence and analysis of the Japanese morning glory Ipomoea nil.

Ipomoea is the largest genus in the family Convolvulaceae. Ipomoea nil (Japanese morning glory) has been utilized as a model plant to study the genetic basis of floricultural traits, with over 1,500 mutant lines. In the present study, we have utilized second- and third-generation-sequencing platforms, and have reported a draft genome of I. nil with a scaffold N50 of 2.88 Mb (contig N50 of 1.87 Mb), covering 98% of the 750 Mb genome. Scaffolds covering 91.42% of the assembly are anchored to 15 pseudo-chromosomes. The draft genome has enabled the identification and cataloguing of the Tpn1 family transposons, known as the major mutagen of I. nil, and analysing the dwarf gene, CONTRACTED, located on the genetic map published in 1956. Comparative genomics has suggested that a whole genome duplication in Convolvulaceae, distinct from the recent Solanaceae event, has occurred after the divergence of the two sister families.

Reduced expression of SET7/9, a histone mono-methyltransferase, is associated with gastric cancer progression.

SET7/9, a histone methyltransferase, has two distinct functions for lysine methylation. SET7/9 methylates non-histone proteins, such as p53, and participates in their posttranslational modifications. Although SET7/9 transcriptionally activate the genes via H3K4 mono-methylation, its target genes are poorly understood. To clarify whether or not SET7/9 is related to carcinogenesis, we studied alterations of SET7/9 in gastric cancers (GCs). Among the 376 primary GCs, 129 cases (34.3%) showed loss or weak expression of SET7/9 protein compared to matched non-cancerous tissues by immunohistochemistry. Reduced SET7/9 expression was significantly correlated with clinical aggressiveness and worse prognosis. Knockdown of SET7/9 in GC cells markedly increased cell proliferation, migration and invasion. Expression of SREK1IP1, PGC and CCDC28B were inhibited in GC cells with SET7/9 knockdown, while matrix metalloproteinase genes (MMP1, MMP7 and MMP9) were activated. SET7/9 bound and mono-methylated H3K4 at the region of the approximately 4-6 kb upstream from the SREK1IP1 transcriptional start site and the promoters of PGC and CDC28B. Cell proliferation, migration and invasion, and expression of three MMPs were increased in GC cells with SREK1IP knockdown, which were similar to those of SET7/9 knockdown. These data suggest that SET7/9 has tumor suppressor functions, and loss of SET7/9 may contribute to gastric cancer progression.

Terahertz balanced self-heterodyne spectrometer with SNR-limited phase-measurement sensitivity.

Photonics-based frequency-domain terahertz (THz) wave measurement systems have received significant attention in both scientific and industrial fields due to their high-frequency resolution. Highly sensitive phase-measurement systems have been desired in the chemical, material, and biomedical sciences to facilitate microanalysis of materials. Here, we demonstrate a balanced self-heterodyne technique that, for the first time, simultaneously offers wide frequency tunability of more than 2.5 THz and high phase sensitivity, which is limited only by the signal-to-noise ratio (SNR) of the amplitude measurement. Using free-running lasers for THz wave generation and detection, the experimentally achieved minimum detectable optical path length change was 400±50 nm at 2 THz for a SNR of 37.7 ± 0.7 dB, even though the theoretically expected SNR-limited value was 310 ± 20 nm. The phase measurement sensitivity of our system is almost one order of magnitude better than that of the conventional systems in which limitations arise from phase instabilities in the optical components and/or laser linewidth.

Active three-way catalysis of rhodium particles with a low oxidation state maintained under an oxidative atmosphere on a La-containing ZrO2 support.

Rhodium on a La-containing ZrO2 support effectively eliminated NOx from a synthetic auto exhaust gas under fluctuating oxygen conditions. Rhodium particles maintained a low oxidation state on the ZrO2-La2O3 mixed oxide even after treatment with 5% O2 at 773 K, highlighting the significant effect of the La addition.

[Clinical features of accessory parotid gland tumors].

Accessory parotid gland tumors are relatively rare; hence, adequately detailed clinical analyses of these tumors are difficult to perform at a single institution. In this report, we describe the findings for 65 patients [29 men, 36 women; median age, 51 (9-81) years] with accessory parotid gland tumors, consisting of 4 cases documented by us and 61 cases previously reported by other Japanese authors. Approximately 50% of the patients were treated in an otolaryngology department, while the remaining patients were treated in plastic surgery, oral surgery, or dermatology departments. In 4 patients, the results of preoperative fine-needle aspiration cytology indicated that the tumor was benign; however, the postoperative histopathology results revealed malignant tumors. The frequencies of malignant and benign tumors were 44.6% (n = 29) and 55.4% (n = 36), respectively. Mucoepidermoid carcinoma and pleomorphic adenoma were the most frequent types of malignant and benign accessory parotid gland tumors, respectively. Among the various surgical methods that were used, such as direct cheek and intraoral incisions, a standard parotidectomy incision was the most preferred treatment approach for these tumors. Recently, an endoscopic approach has also been found to yield satisfactory results. An optimal approach should be selected after evaluating the advantages and disadvantages of these methods. No definite guidelines are available regarding the choice of elective neck dissection and postoperative radiation therapy for malignant accessory parotid gland tumors. Although tumor resection (plus elective neck dissection) and postoperative radiation therapy have been frequently performed for various kinds of malignant accessory parotid gland tumors to date, additional studies are needed regarding the criteria for selecting elective neck dissection and postoperative radiation therapy. Since the malignancy rate for accessory parotid gland tumors is higher than that for parotid gland tumors, the possibility of malignancy (especially mucoepidermoid carcinoma and carcinoma ex pleomorphic adenoma) should be considered when resecting accessory parotid gland tumors, even if the results of preoperative fine-needle aspiration cytology indicate that the tumor is benign.