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Background: Reluctance of people to receive recommended vaccines is a growing concern, as distribution of vaccines is considered critical to ending the COVID-19 pandemic. There is little information regarding pregnant women’s views toward coronavirus vaccination in Japan. Therefore, we investigated the vaccination rate and reasons for vaccination and vaccine hesitancy among pregnant women in Japan.Methods: We conducted a cross-sectional study involving 1,791 pregnant women using data from the Japan “COVID-19 and Society” Internet Survey, conducted from July to August 2021, and valid response from 1,621 respondents were analyzed. We defined participants with vaccine hesitancy as those who identified with the statement “I do not want to be vaccinated” or “I want to ‘wait and see’ before getting vaccinated.” Multivariate Poisson regression analysis was used to investigate the factors contributing to vaccine hesitancy.Results: The prevalence of vaccination and vaccine hesitancy among pregnant women was 13.4% (n = 217) and 50.9% (n = 825), respectively. The main reasons for hesitancy were concerns about adverse reactions and negative effects on the fetus and breastfeeding. Vaccine hesitancy was significantly associated with the lack of trust in the government (adjusted prevalence ratio, 1.26; 95% confidence interval, 1.03–1.54). Other factors, such as age, educational attainment, and state of emergency declaration, were not associated with vaccine hesitancy.Conclusions: COVID-19 vaccination is not widespread among pregnant women in Japan, although many vaccines have been shown to be safe in pregnancy. Accurate information dissemination and boosting trust in the government may be important to address vaccine hesitancy among pregnant women.

The regulation of gene expression is a promising therapeutic approach for many intractable diseases. However, its use in clinical applications requires the efficient delivery of nucleic acids to target tissues, which is a major challenge. Recently, various delivery systems employing physical energy, such as ultrasound, magnetic force, electric force, and light, have been developed. Ultrasound-mediated delivery has particularly attracted interest due to its safety and low costs. Its delivery effects are also enhanced when combined with microbubbles or nanobubbles that entrap an ultrasound contrast gas. Furthermore, ultrasound-mediated nucleic acid delivery could be performed only in ultrasound exposed areas. In this review, we summarize the ultrasound-mediated nucleic acid systemic delivery system, using microbubbles or nanobubbles, and discuss its possibilities as a therapeutic tool.

Endophytic actinomycetes associated with plant roots are a relatively untapped source of potential new bioactive compounds. This is becoming increasingly important, as the returns from discovery research on soil-dwelling microbes, have been continuously diminishing. We have isolated more than 1000 strains of actinomycetes from plant roots in our search for novel bioactive compounds, identified and assayed their bioactive metabolites, as well as investigated their biosynthetic genes for generating secondary metabolites. This has resulted in the discovery of several interesting compounds. Creation of plant root clone libraries enabled us to confirm that we had, indeed, isolated endophytes. In this paper, we introduce our approach to this promising line of research, incorporating data from other publications, and illustrate the potential that endophytic actinomycetes offer as a new source of novel lead compounds.

We aimed to determine whether acute disseminated encephalomyelitis (ADEM) diagnosis in children is delayed, and if so, to identify the clinical risk factors of delayed diagnosis. Standardised data were collected from children with ADEM from 2003 to 2020. Overall diagnostic delay (time between symptom onset and ADEM diagnosis), physicians’ delay (between the first medical visit and ADEM diagnosis), and patients’ delay (between symptom onset and the first medical visit) were analysed. Thirty ADEM patients were identified, including 16 (54%) with neurological deficits at discharge. Overall, physicians’, and patients’ delays were 9 (interquartile range [IQR] 6–20.5), 5.5 (IQR 3–14), and 4 (IQR 2–8) days, respectively. Overall delay was significantly associated with physicians’ delay, but not with patients’ delay. There were 61 misdiagnoses among 25 (83%) patients, while 5 (17%) were diagnosed correctly at the first visit. The misdiagnoses of common respiratory and gastrointestinal infection and aseptic meningitis were associated with overall and/or physicians’ delay. Later onset of specific neurological features suggestive of ADEM was associated with all three diagnostic delays. A unique diagnostic odyssey exists in ADEM. Several clinical risk factors were associated with the diagnostic delay.

We present a study to evaluate the feasibility and clinical utility of amplicon‐based Oncomine Pan‐Cancer cell‐free assay to detect circulating tumor DNA (ctDNA) in patients with early or advanced breast cancer. In this study, 109 early and metastatic breast cancer patients were recruited before the initiation of treatment. ctDNA mutation profiles were assessed through unique molecular tagging (UMT) and ultradeep next generation sequencing (NGS). For patients with mutations, DNA from corresponding white blood cells (WBC) was sequenced to exclude variants of clonal‐hematopoietic (CH) origin. UMT targeted sequencing from plasma of 109 patients achieved a median total coverage of 55 498X and a median molecular coverage of 4187X. Among 53 ctDNA positive samples, 38% were mutation positive by WBC sequencing, indicating potentially false‐positive results contributed by CH origin. Prevalence of CH‐related mutations was associated with age (P = 7.51 × 10−4). After exclusion of CH mutations, ctDNA detection rates were 37% for local or locally advanced breast cancer (stage I‐III) and 81% for metastatic or recurrent breast cancer. The ctDNA detection rate correlated with disease stage (P = 2.60 × 10−4), nodal spread (P = 6.49 × 10−3) and the status of distant metastases (P = 5.00 × 10−4). ctDNA variants were detected mostly in TP53, PIK3CA and AKT1 genes, with variants showing therapeutic relevance. This pilot study endorses the use of targeted NGS for non‐invasive molecular profiling of breast cancer. Paired sequencing of plasma ctDNA and WBC should be implemented to improve accurate interpretation of liquid biopsy. We present a study to evaluate the feasibility and clinical utility of amplicon‐based liquid biopsy assay to detect circulating tumor DNA (ctDNA) in patients with early or advanced breast cancer. After excluding CH mutations, the ctDNA detection rate correlated with disease stage, nodal spread and the status of distant metastases. Paired sequencing of plasma ctDNA and WBC should be implemented to improve accurate interpretation of liquid biopsy.

The genus Kitasatospora was proposed in 1982. Although Kitasatospora strains resemble Streptomyces strains in morphology, they are clearly different in cell-wall composition, as they contain both LL- and meso -diaminopimelic acid. Aerial and submerged spores contain LL−, while vegetative and submerged mycelia contain mainly meso - in their cell walls. Currently, 23 species have been validly proposed. Members of the genus Kitasatospora form a tight cluster and represent a legitimate genus distinct from Streptomyces on the basis of phylogenetic analysis of 16S rRNA gene sequences. A variety of biologically active compounds have been found from Kitasatospora strains and structures of these compounds are extremely diverse. Genome sequences of 15 strains published so far are about 7–9 Mb in size and contain many genes governing secondary metabolites.

The authors have provided a corrected version here. thumbnail Download: * PPT PowerPoint slide * PNG larger image * TIFF original image Fig 1. The positions of fraction numbers on SDS–PAGE analysis correspond to the time on the UV absorption curve.

Purpose This study investigated the clinical impact of pretreatment neutrophil-to-lymphocyte ratio (NLR) on survival in patients with oligometastatic breast cancer. Patients and methods We collected data from 397 patients who underwent primary breast surgery from 2004 to 2015 and developed recurrence during the follow-up. We reviewed the images and clinical information and defined OMD according to the European Society for Medical Oncology advanced breast cancer guidelines. The NLR was calculated using pretreatment data of primary breast cancer. The cutoff value of the NLR was determined by receiver operating characteristic curve with Youden Index. Results Among 397 patients, 131 had OMD at recurrence. The low-NLR group included patients of significantly older age at primary cancer than those in the high-NLR group. A low NLR indicated a better overall survival ( p  = 0.023) after adjusting for relevant factors, including estrogen receptor status, surgical resection of metastatic disease, metastatic organ number, disease-free interval, and liver metastasis than did the high-NLR group. We developed prognostic models for OMD using six independent prognostic factors, including the NLR. The number of factors was associated with overall survival; patients with all six favorable factors showed a good overall survival of 90.9% at 8 years and those with four or more factors showed 70.4%. Conclusions The NLR was an independent prognostic factor for overall survival in OMD. The number of favorable prognostic factors was associated with overall survival. A prognostic model, including the NLR, will help identify patients with a favorable prognosis.

Background The intratumor heterogeneity (ITH) of cancer cells plays an important role in breast cancer resistance and recurrence. To develop better therapeutic strategies, it is necessary to understand the molecular mechanisms underlying ITH and their functional significance. Patient-derived organoids (PDOs) have recently been utilized in cancer research. They can also be used to study ITH as cancer cell diversity is thought to be maintained within the organoid line. However, no reports investigated intratumor transcriptomic heterogeneity in organoids derived from patients with breast cancer. This study aimed to investigate transcriptomic ITH in breast cancer PDOs. Methods We established PDO lines from ten patients with breast cancer and performed single-cell transcriptomic analysis. First, we clustered cancer cells for each PDO using the Seurat package. Then, we defined and compared the cluster-specific gene signature (ClustGS) corresponding to each cell cluster in each PDO. Results Cancer cells were clustered into 3–6 cell populations with distinct cellular states in each PDO line. We identified 38 clusters with ClustGS in 10 PDO lines and used Jaccard similarity index to compare the similarity of these signatures. We found that 29 signatures could be categorized into 7 shared meta-ClustGSs, such as those related to the cell cycle or epithelial–mesenchymal transition, and 9 signatures were unique to single PDO lines. These unique cell populations appeared to represent the characteristics of the original tumors derived from patients. Conclusions We confirmed the existence of transcriptomic ITH in breast cancer PDOs. Some cellular states were commonly observed in multiple PDOs, whereas others were specific to single PDO lines. The combination of these shared and unique cellular states formed the ITH of each PDO.

Although lipoproteins are conventionally separated into a few classes using density gradient centrifugation, there may be a much higher number of physical classes that differ in origin or phase. Comprehensive knowledge of the classes of lipoproteins is rather limited, which hinders both the study of their functions and the identification of the primary causes of related diseases. This study aims to determine the number of classes of lipoproteins that can be practically distinguishable and identify the differences between them. We separated rat serum samples by gel filtration. The elution was continuously monitored for triglyceride (TG), cholesterol, and protein, and fractionated for further SDS-PAGE and immunological detection of apoprotein A-I (ApoA1) and apoprotein B (ApoB). The elution patterns were analyzed using a parsimonious method, i.e., the estimation of the least number of classes. Ten classes were recognized that contained different amounts of TG and cholesterol, as well as a unique protein content. Each of the classes contained much more protein than that observed previously, especially in low-density lipoproteins (LDL) classes. In particular, two major antiproteases formed complexes with specific classes of LDL; because these classes exclusively carry cholesterol and antiproteases, they may lead to the progression of atheroma by supplying materials that enlarge fatty streaks and protecting thrombi from enzymatic digestion. The separated classes may have specific biological functions. The attribution of protein species to certain classes will help understand the functions. A distinction among lipoprotein classes may provide important information in the field of vascular pathology.