A novel reductive amino cyclization method and its application for the syntheses of pyrrolidine and piperidine nucleus

金沢大学大学院自然科学研究科生理活性物質科学金沢大学薬学

Investigation of the individual genetic evolution of SARS-CoV-2 in a small cluster during the rapid spread of the BF.5 lineage in Tokyo, Japan

There has been a decreasing trend in new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) cases and fatalities worldwide. The virus has been evolving, indicating the potential emergence of new variants and uncertainties. These challenges necessitate continued efforts in disease control and mitigation strategies. We investigated a small cluster of SARS-CoV-2 Omicron variant infections containing a common set of genomic mutations, which provided a valuable model for investigating the transmission mechanism of genetic alterations. We conducted a study at a medical center in Japan during the Omicron surge (sub-lineage BA.5), sequencing the entire SARS-CoV-2 genomes from infected individuals and evaluating the phylogenetic tree and haplotype network among the variants. We compared the mutations present in each strain within the BA.5 strain, TKYnat2317, which was first identified in Tokyo, Japan. From June 29th to July 4th 2022, nine healthcare workers (HCWs) tested positive for SARS-CoV-2 by real-time PCR. During the same period, five patients also tested positive by real-time PCR. Whole genome sequencing revealed that the infected patients belonged to either the isolated BA.2 or BA.5 sub-lineage, while the healthcare worker infections were classified as BF.5. The phylogenetic tree and haplotype network clearly showed the specificity and similarity of the HCW cluster. We identified 12 common mutations in the cluster, including I110V in nonstructural protein 4 (nsp4), A1020S in the Spike protein, and H47Y in ORF7a, compared to the BA.5 reference. Additionally, one case had the extra nucleotide-deletion mutation I27* in ORF10, and low frequencies of genetic alterations were also found in certain instances. The results of genome sequencing showed that the nine HCWs shared a set of genetic mutations, indicating transmission within the cluster. Minor mutations observed in five HCW individuals suggested the emergence of new virus variants. Five amino acid substitutions occurred in nsp3, which could potentially affect virus replication or immune escape. Intra-host evolution also generated additional mutations. The cluster exhibited a mild disease course, with individuals in this case, recovering without requiring any medical treatments. Further investigation is needed to understand the relationship between the genetic evolution of the virus and the symptoms

Comparison of the clinical performance and usefulness of five SARS-CoV-2 antibody tests

We examined the usefulness of five COVID-19 antibody detection tests using 114 serum samples at various time points from 34 Japanese COVID-19 patients. We examined Elecsys Anti-SARS-CoV-2 from Roche, and four immunochromatography tests from Hangzhou Laihe Biotech, Artron Laboratories, Chil, and Nadal. In the first week after onset, Elecsys had 40% positivity in Group S (severe cases) but was negative in Group M (mild-moderate cases). The immunochromatography kits showed 40–60% and 0–8% positivity in Groups S and M, respectively. In the second week, Elecsys showed 75% and 50% positivity, and the immunochromatography tests showed 5–80% and 50–75% positivity in Groups S and M, respectively. After the third week, Elecsys showed 100% positivity in both groups. The immunochromatography kits showed 100% positivity in Group S. In Group M, positivity decreased to 50% for Chil and 75–89% for Artron and Lyher. Elecsys and immunochromatography kits had 91–100% specificity. Elecsys had comparable chronological change of cut-off index values in the two groups from the second week to the sixth week. The current SARS-CoV-2 antibody detection tests do not provide meaningful interpretation of severity and infection status. Its use might be limited to short-term epidemiological studies

Occupational therapy using a robotic-assisted glove ameliorates finger dexterity and modulates functional connectivity in amyotrophic lateral sclerosis.

Introduction:Although rehabilitation is recommended for amyotrophic lateral sclerosis (ALS), improvement of functional decline has hardly been achieved. We investigated the effect of occupational therapy that uses a robotic-assisted glove (RAG) on hand dexterity and the functional connectivities found in the brain of ALS patients.Method:Ten patients diagnosed with ALS and admitted to the Shiga University of Medical Science (SUMS) Hospital from December 2018 to December 2021 participated in the study. These participants chose the hand side to wear RAG and exercised for two weeks. A sham movement was performed on the other side. We administered several functional assessments, including the Simple Test for Evaluating Hand Function (STEF), grip strength, pinch meter for grip strength, Canadian occupational performance measure (COPM), as well as nerve conduction study (NCS) before and after the exercise, and evaluated the results. We also analyzed six patients\u27 resting-state functional magnetic resonance imaging (rs-fMRI).Results:Two-week robotic rehabilitation improved the STEF, grip strength, and COPM scores when compared with those of the other side. However, no significant effect was observed in the pinch meter and the NCS results. The rs-fMRI data analysis revealed that the robotic rehabilitation augmented two functional connectivities between the left pallidum-right supplementary motor cortex and right insular cortex-right sensorimotor network among the patients, which had beneficial effects.Conclusion:The occupational therapy using RAG displayed improved hand dexterity. The enhanced functional connectivities around the sensorimotor network might be associated with the improvement in hand dexterity because of the RAG

An Experimental Multilingual Speech Translation System

In this paper, we describe an experimental speech translation system utilizing small, PC-based hardware with multi-modal user interface. Two major problems for people using an automatic speech translation device are speech recognition errors and language translation errors. In this paper we focus on developing techniques to overcome these problems. The techniques include a new language translation approach based on example sentences, simplified expression rules, and a multi-modal user interface which shows possible speech recognition candidates retrieved from the example sentences. Combination of the proposed techniques can provide accurate language translation performance even if the speech recognition result contains some errors. We propose to use keyword classes by looking at the dependency between keywords to detect the misrecognized keywords and to search the example expressions. Then, the suitable example expression is chosen using a touch panel or by pushing buttons. The language translation picks up the expression in the other language, which should always be grammatically correct. Simplified translated expressions are realized by speech-act based simplifying rules so that the system can avoid various redundant expressions. A simple comparison study showed that the proposed method outputs almost 2 to 10 times faster than a conventional translation device

A study on the transformation and succession of a historical environment a case study in Cakranegara, Indonesia

This study sought to clarify the transformation and succession of the historical environment of Cakranegara, a historical Indonesian city based on the following viewpoints: 1) transformation of building lots and their uses; 2) utilization of space on the streets; and 3) proposing appropriate indices to evaluate the historical environment of Cakranegara. The major findings were: 1) the transformation of the spatial structure of the city can be evaluated by analyzing the relationship between the change of building lots and their uses. The tendency of splitting or consolidating lots varies depending on land use type and location; however, almost half of the building lots have retained their original size; 2) the utilization of public space in Cakranegara can be analyzed and evaluated using seven categories of objects, three time scales, three types of ownership, and five categories of open space; 3) usage of Tagtagan, which is a space installed along both sides of a street, has transformed from a space for religious activities and planting trees to a space with multiple uses for daily living activities; and 4) public space is characterized by a dualistic spatial structure – space for commercial/transportation uses and space for residential uses – based on road hierarchies

Development and validation of a symptom scale specific for ascites accompanied with cirrhosis : The ASI-7

OBJECTIVES: Ascites markedly affects the quality of life of patients with cirrhosis; however, there is currently no scale to measure the symptoms of ascites. We developed a scale to measure ascites-specific symptoms according to psychometric procedures. METHODS: A team consisting of specialists developed constructs representing the symptoms of ascites and question item pool. The constructs were verified in a qualitative study involving a small number of patients. The item pool was improved through a pilot study, and a prototype of the scale was prepared. To establish the scale and assess its properties, a questionnaire survey was conducted on 175 patients with ascites accompanied with cirrhosis. RESULTS: On the basis of the results of factor analysis and item response theory–based analyses, seven items, covering a wide range of severities and diverse symptoms, were selected to comprise the final scale (Ascites Symptom Inventory-7; ASI-7). The ASI-7 had a unidimensional factorial structure and high reliability (Cronbach's α coefficient of 0.96). The scale score was correlated with the degree of ascites evaluated by physicians, Short Form-36 (SF-36) physical functioning (PF), and SF-36 vitality (VT; P<0.001 each), indicating the criterion validity. The responsiveness after treatment was demonstrated by the mean standardized response of 1.18. Moreover, responses in the scale score were correlated with those in the degree of ascites, body weight, SF-36 PF, and SF-36 VT, respectively (P<0.001 each). CONCLUSIONS: An ascites-specific symptom scale was developed and its reliability, validity, and responsiveness were demonstrated. This simple scale may be used for the evaluation of ascites treatment and monitoring of treatment responses in patients with ascites