Transl Clin Pharmacol
December 2024
An 18-month-old boy presented with septic arthritis and osteomyelitis caused by Hypervirulent Klebsiella pneumoniae harboring cardinal virulence genes. The condition necessitated several surgical interventions, and a prolonged course of antibiotic therapy to effectively manage the severe infection and prevent complications, highlighting the challenges posed by Hypervirulent Klebsiella pneumoniae in pediatric cases.
View Article and Find Full Text PDFBackground: Error-corrected next-generation sequencing (ecNGS) technologies have enabled the direct evaluation of genome-wide mutations after exposure to mutagens. Previously, we reported an ecNGS methodology, Hawk-Seq™, and demonstrated its utility in evaluating mutagenicity. The evaluation of technical transferability is essential to further evaluate the reliability of ecNGS-based assays.
View Article and Find Full Text PDFThis study aimed to clarify changes in antimicrobial prescribing trends in pediatric clinics before and after the chronic shortage of amoxicillin and amoxicillin-clavulanic acid from 2023 in Japan. Amoxicillin and amoxicillin-clavulanic acid have been in chronic short supply since May 24, 2023 due to increased demand. It is unclear whether this situation has changed the type of oral antimicrobials prescribed by clinics.
View Article and Find Full Text PDFFamilial adenomatous polyposis (FAP) is a heritable disease that increases the risk of colorectal cancer (CRC) development because of heterozygous mutations in APC. Little is known about the microenvironment of FAP. Here, single-cell RNA sequencing was performed on matched normal tissues, adenomas, and carcinomas from four patients with FAP.
View Article and Find Full Text PDFBackground: Beckwith-Wiedemann syndrome (BWS) is a genomic imprinting disorder caused by diverse genetic and/or epigenetic disorders of chromosome 11p15.5. BWS presents with a variety of clinical features, including overgrowth and an increased risk of embryonal tumors.
View Article and Find Full Text PDFBackground: Acute bacterial arthritis (ABA) is a serious, pediatric infection that can result in motor comorbidities. Normally, a joint fluid white blood cell (WBC) count of 50,000 or more cells/mm 3 is used to make a presumptive diagnosis of ABA. This study evaluated the utility of the joint fluid WBC count for diagnosing pediatric ABA confirmed by a positive culture result.
View Article and Find Full Text PDFCertain proteins assemble into diverse complex states, each having a distinct and unique function in the cell. Target of rapamycin (Tor) complex 1 (TORC1) plays a central role in signalling pathways that allow cells to respond to the environment, including nutritional status signalling. TORC1 is widely recognised for its association with various diseases.
View Article and Find Full Text PDFVacancy-ordered 12H-type hexagonal perovskites BaRuNaXO (X = P, V) with a (') stacking sequence of [BaO], [BaO], and [BaO] layers, where and represent a cubic and hexagonal stacking sequence, were previously reported by Quarez et al. in 2003. They also synthesized BaTaNaVO, but structural refinement was absent.
View Article and Find Full Text PDFBackground: Gastric cancer (GC) is characterized by an immunosuppressive and treatment-resistant tumor immune microenvironment (TIME). Here, we investigated the roles of different immunosuppressive cell types in the development of the GC TIME.
Methods: Single-cell RNA sequencing (scRNA-seq) and multiplex immunostaining of samples from untreated or immune checkpoint inhibitor (ICI)-resistant GC patients were used to examine the correlation between certain immunosuppressive cells and the prognosis of GC patients.
Background: Comprehensive genomic profiling (CGP) has become generally accepted practice in cancer care since CGP has become reimbursed by national healthcare insurance in Japan in 2019. However, its usefulness for cancer patients is insufficient for several reasons.
Methods: In an observational clinical study of FoundationOne CDx, potential biomarkers were explored and the cause of testing failure was investigated.
The stress response is one of the most fundamental cellular processes. Although the molecular mechanisms underlying responses to a single stressor have been extensively studied, cellular responses to multiple stresses remain largely unknown. Here, we characterized fission yeast cellular responses to a novel stress inducer, non-thermal atmospheric-pressure plasma.
View Article and Find Full Text PDFThe fission yeast Schizosaccharomyces pombe ecl family genes respond to various starvation signals and induce appropriate intracellular responses, including the extension of chronological lifespan and induction of sexual differentiation. Herein, we propose that the colonization of hemocoel 1 (COH1) protein of Metarhizium robertsii, an insect-pathogenic fungus, is a functional homolog of S. pombe Ecl1 family proteins.
View Article and Find Full Text PDFSpinal muscular atrophy (SMA) is an autosomal recessive neuromuscular disorder caused by the deletion or mutation of the survival motor neuron 1 (SMN1) gene. The establishment of effective newborn screening (NBS) for SMA is important for early diagnosis so that treatment can be administered in the pre-symptomatic or early disease stages. Polymerase chain reaction (PCR)-based genetic testing with dried blood spots has been used in NBS to detect the homozygous deletion of exon 7 in SMN1, however, this methodology is not able to detect newborn infants with heterozygous deletions and/or point mutations in SMN1.
View Article and Find Full Text PDFAlthough the percentage of multi-regional clinical trials (MRCTs) submitted for drug approval in Japan increased significantly since the 2007 publication of the regulatory guideline, "Basic principles on global clinical trials", strategic collaborations between Asian countries will be important to promote MRCTs in accordance with the ICH E17 guideline published in 2017. In this study, characteristics of MRCTs reviewed for drug approval in Japan, especially those with participation by South-East Asia and East Asia, were investigated to explore opportunities for collaborations on global drug development in Asia. More than 90% of reviewed trials were conducted as global MRCTs.
View Article and Find Full Text PDFIn the fission yeast Schizosaccharomyces pombe, the duration of survival in the stationary phase, termed the chronological lifespan (CLS), is affected by various environmental factors and the corresponding gene activities. The ecl family genes were identified in the genomic region encoding non-coding RNA as positive regulators of CLS in S. pombe, and subsequently shown to encode relatively short proteins.
View Article and Find Full Text PDFThe steric zipper is a common hydrophobic packing structure of peptide side chains that forms between two adjacent β-sheet layers in amyloid and related fibrils. Although previous studies have revealed that peptide fragments derived from native protein sequences exhibit steric zipper structures, their de novo designs have rarely been studied. Herein, steric zipper structures were artificially constructed in the crystalline state by metal-induced folding and assembly of tetrapeptide fragments Boc-3pa-X-3pa-X-OMe (3pa: β-(3-pyridyl)-l-alanine; X and X: hydrophobic amino acids).
View Article and Find Full Text PDFTo ensure high-reliability communication in healthcare networks, this paper presents a smart gateway system that includes an angle-of-arrival (AOA) estimation and a beam steering function for a small circular antenna array. To form a beam toward healthcare sensors, the proposed antenna estimates the direction of the sensors utilizing the radio-frequency-based interferometric monopulse technique. The fabricated antenna was assessed based on the measurements of complex directivity and the over-the-air (OTA) testing in Rice propagation environments using a two-dimensional fading emulator.
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