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Introduction: The number of patients with chronic kidney disease is increasing worldwide; previous studies have suggested that advanced practice nurses, including nurse practitioners and clinical nurse specialists, with expert practice skills can provide high-quality care and solve complex healthcare problems. In general, nurse practitioners are generalist nurses who work as autonomous clinicians with whole personal care. Clinical nurse specialists, in contrast, are nurses with advanced nursing knowledge and skills for individuals or specific populations. Their roles are independent and different; however, similarities exist in their role in potentially improving healthcare outcomes. Although two previous studies described the role of nephrology nurse practitioners, they were systematic reviews, and their outcomes were limited. To clarify the overall aspect of advanced practice nurses' role, it is necessary to extract the studies illustrating advanced practice nurses' practices for patients with chronic kidney disease., Objective: This study aims to map the literature describing the role of advanced practice nurses in improving healthcare outcomes for patients with chronic kidney disease., Materials and Methods: This scoping review will be conducted using the Joanna Briggs Institute methodology for scoping review. Online databases will be searched across MEDLINE (PubMed), CINAHL (EBSCOhost), Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, and Web of Science. Only studies published in English will be included, and no date limit will be set. Chronic kidney disease, renal replacement therapy, and advanced practice nurses as keywords and related search terms will be used. Two independent reviewers will screen the title and abstract/full-text; in case of discrepancy, a third reviewer will make the final decision. The results will be extracted and presented following the review question concerning the study characteristics, patients' characteristics, condition of chronic kidney disease, and role of advanced practice nurses., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Nozu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

The relationship between the expression of microRNAs (miRNAs) in blood and a variety of diseases has been investigated. MiRNA-based liquid biopsy has attracted much attention, and cancer-specific miRNAs have been reported. However, the results of analyses of the expression of these miRNAs vary among studies. The reproduction of results regarding miRNA expression levels could be difficult if there are differences in the data acquisition process. Previous studies have shown that the anticoagulant type used during plasma preparation and sample storage conditions could contribute to differences in measured miRNA levels. Thus, the impact of these preanalytical conditions on comprehensive miRNA expression profiles was examined. First, the miRNA expression profiles of samples obtained from healthy volunteers were analyzed using next-generation sequencing. Based on an analysis of the library concentration, human genome identification rate, ratio of unique sequences and expression profiles, the optimal preanalytical conditions for obtaining highly reproducible miRNA expression profiles were established. The optimal preanalytical conditions were as follows: ethylenediaminetetraacetic acid (EDTA) as the anticoagulant, whole-blood storage at room temperature within 6 hours, and plasma storage at 4°C or -20°C within 30 days. Next, plasma samples were collected from 60 cancer patients (3 facilities × 20 patients/facility), and miRNA expression profiles were analyzed. There were no significant differences in measurements except in the expression of erythrocyte-derived hsa-miR-451a. However, the variation in hsa-miR-451a levels was smaller among facilities than among individuals. This finding suggests that samples obtained from the same facility could show significantly different degrees of hemolysis across individuals. We found that the standardization of anticoagulant use and storage conditions contributed to reducing the variation in sample quality across facilities. The findings from this study could be useful in developing protocols for collecting samples from multiple facilities for cancer screening tests., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2022 Suzuki et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Pneumonia is a common cause of illness and death of the elderly in Japan. Its prevalence is escalating globally with the aging of population. To describe the latest trends in pneumonia hospitalizations, especially aspiration pneumonia (AP) cases, we assessed the clinical records of pneumonia patients admitted to core acute care hospitals in Miyagi prefecture, Japan., Methods: A retrospective multi-institutional joint research was conducted for hospitalized pneumonia patients aged ≥20 years from January 2019 to December 2019. Clinical data of patients were collected from the medical records of eight acute care hospitals., Results: Out of the 1,800 patients included in this study, 79% of the hospitalized pneumonia patients were aged above 70 years. The most common age group was in the 80s. The ratio of AP to total pneumonia cases increased with age, and 692 out of 1,800 patients had AP. In univariate analysis, these patients had significantly older ages, lower body mass index (BMI), a lower ratio of normal diet intake and homestay before hospitalization, along with more AP recurrences and comorbidities. During hospitalization, AP patients had extended fasting periods, more swallowing assessments and interventions, longer hospitalization, and higher in-hospital mortality rate than non-AP patients. A total of 7% and 2% AP patients underwent video endoscopy and video fluorography respectively. In multivariate analysis, lower BMI, lower C-reactive protein, a lower ratio of homestay before hospitalization, a higher complication rate of cerebrovascular disease, dementia, and neuromuscular disease were noted as a characteristic of AP patients. Swallowing interventions were performed for 51% of the AP patients who had been hospitalized for more than two weeks. In univariate analysis, swallowing intervention improved in-hospital mortality. Lower AP recurrence before hospitalization and a lower ratio of homestay before hospitalization were indicated as characteristics of AP patients of the swallowing intervention group from multivariate analysis. Change in dietary pattern from normal to modified diet was observed more frequently in the swallowing intervention group., Conclusion: AP accounts for 38.4% of all pneumonia cases in acute care hospitals in Northern Japan. The use of swallowing evaluations and interventions, which may reduce the risk of dysphagia and may associate with lowering mortality in AP patients, is still not widespread., Competing Interests: The authors have declared that no competing interests exist.

ARHGAP36 is an atypical Rho GTPase-activating protein (GAP) family member that drives both spinal cord development and tumorigenesis, acting in part through an N-terminal motif that suppresses protein kinase A and activates Gli transcription factors. ARHGAP36 also contains isoform-specific N-terminal sequences, a central GAP-like module, and a unique C-terminal domain, and the functions of these regions remain unknown. Here we have mapped the ARHGAP36 structure-activity landscape using a deep sequencing-based mutagenesis screen and truncation mutant analyses. Using this approach, we have discovered several residues in the GAP homology domain that are essential for Gli activation and a role for the C-terminal domain in counteracting an N-terminal autoinhibitory motif that is present in certain ARHGAP36 isoforms. In addition, each of these sites modulates ARHGAP36 recruitment to the plasma membrane or primary cilium. Through comparative proteomics, we also have identified proteins that preferentially interact with active ARHGAP36, and we demonstrate that one binding partner, prolyl oligopeptidase-like protein, is a novel ARHGAP36 antagonist. Our work reveals multiple modes of ARHGAP36 regulation and establishes an experimental framework that can be applied towards other signaling proteins., Competing Interests: The authors have declared that no competing interests exist.

The Japanese Ministry of Health requires large-scale cooking facilities to use sodium hypochlorite aqueous solution (HYP) on food preparation tools, equipment, and facilities to prevent secondary contamination. This study aimed to compare the disinfecting effect of HYP and surfactant using adenosine triphosphate (ATP) swab testing on large-scale equipment and facilities that could not be disassembled and disinfected in hospital kitchen. From May 2018 to July 2018, ATP swab tests were performed on the following six locations in the Shizuoka Cancer Centre Dietary Department Kitchen: cooking counter, mobile cooking counter, refrigerator handle, conveyor belt, tap handle, and sink. Six relative light unit (RLU) measurements were taken from each location. The log10 values of the RLU measurements were evaluated by dividing the samples into two groups: the control group (surfactant followed by HYP swabbing) and the HYP group (HYP swabbing only). The results showed that the RLUs (log10 values) in both the groups improved after disinfection (p<0.05), except for the RLUs (log10 values) of the mobile cooking counter, tap handle, and sink in the control group after the HYP swab. The changes in the RLU (log10 value) did not differ between the two groups for all locations of the kitchen. Hence, HYP swabbing of large-scale equipment and facilities provides the same level of disinfection as surfactants and can be as beneficial., Competing Interests: NO authors have competing interests.

The purpose is to experimentally examine the effect of disclosing the risk probability of each unit in a production system on human behavior and the resulting system reliability. We used an economic experiment based on the theoretical model of Hausken (2002) to evaluate the effect of disclosing the relation between effort and unit reliability. We conducted first the non-disclosed-risk experiment and then the disclosed-risk experiment within subjects in both series and parallel systems. Our experimental results show that disclosing the relation between effort and unit reliability has two positive effects. First, subjects succeeded in improving the system reliability while cutting back on efforts to reduce the risk of their units when the risk probability was disclosed. In each system, the disclosed-risk condition achieves significantly higher system reliability on average than does the non-disclosed-risk condition, although the average level of effort is significantly lower under the disclosed-risk condition than under the non-disclosed-risk condition. Second, disclosing the risk probability simplified the subjects' decision-making process and reduced its cost because subjects made their decisions on the amount of effort to exert based only on the risk probability information without considering other factors, such as the number of accidents., Competing Interests: The authors have declared that no competing interests exist.

The aim of this study was to clarify the factors affecting anxiety among administrative officers working within the urgent protective action planning zone of a nuclear power station to establish an effective education program on radiation and its health effects to help reduce anxiety in residents. We included 1,181 officers who worked at local authorities within the urgent protective action planning zone of Sendai Nuclear Power Station in Kagoshima Prefecture, Japan. Logistic regression analysis revealed that female sex (odds ratio = 2.33), working more than 21 years as an administrative officer (odds ratio = 1.49), lack of participation in training on nuclear disasters (odds ratio = 1.42), and not knowing the three principles of radiation protection (odds ratio = 1.36) were independently associated with anxiety among administrative officers working within the urgent protective action planning zone. It is important to establish an effective education program on radiation and its health effects for administrative officers working within the urgent protective action planning zone to reduce anxiety in residents., Competing Interests: The authors have declared that no competing interests exist.

Seed shape is an important agronomic trait with continuous variation among genotypes. Therefore, the quantitative evaluation of this variation is highly important. Among geometric morphometrics methods, elliptic Fourier analysis and semi-landmark analysis are often used for the quantification of biological shape variations. Elliptic Fourier analysis is an approximation method to treat contours as a waveform. Semi-landmark analysis is a method of superimposed points in which the differences of multiple contour positions are minimized. However, no detailed comparison of these methods has been undertaken. Moreover, these shape descriptors vary when the scale and direction of the contour and the starting point of the contour trace change. Thus, these methods should be compared with respect to the standardization of the scale and direction of the contour and the starting point of the contour trace. In the present study, we evaluated seed shape variations in a sorghum (Sorghum bicolor Moench) germplasm collection to analyze the association between shape variations and genome-wide single-nucleotide polymorphisms by genomic prediction (GP) and genome-wide association studies (GWAS). In our analysis, we used all possible combinations of three shape description methods and eight standardization procedures for the scale and direction of the contour as well as the starting point of the contour trace; these combinations were compared in terms of GP accuracy and the GWAS results. We compared the shape description methods (elliptic Fourier descriptors and the coordinates of superposed pseudo-landmark points) and found that principal component analysis of their quantitative descriptors yielded similar results. Different scaling and direction standardization procedures caused differences in the principal component scores, average shape, and the results of GP and GWAS., Competing Interests: This research was supported by grant (JPMJCR12B5) from the JST/CREST. The first author, L.S., was supported by grant (17J05431) from the JSPS.EARTHNOTE Co. contributed to the preparation of materials. PRESTO provided support in the form of salaries for authors KN, but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

In response to the Fukushima Daiichi nuclear power plant disaster, the Nuclear Regulation Authority of Japan issued the new "Nuclear Emergency Response Guideline." However, there is a perception that scientific information about the health impact of radiation exposure has not been adequately shared among the local government staffs, including schoolteachers. We contacted schoolteachers at all 120 schools within the Urgent Protective Action Planning Zone of the Sendai Nuclear Power Plant, Kagoshima prefecture, in 2017. We invited them to take part in a written survey to clarify their concerns and risk perceptions regarding the effects of radiation exposure on health. Five hundred and fifty schoolteachers' replies were included in the analysis. The results revealed that 355 schoolteachers had concerns about the health effects of radiation exposure due to working within the Urgent Protective Action Planning Zone. A logistic regression analysis revealed that sex (OR = 2.26, 95% CI: 1.49-3.45, p < 0.001), age (OR = 3.39, 95% CI: 2.10-5.47, p < 0.001), reluctance to undergo a radiological examination at a hospital (OR = 1.91, 95% CI: 1.23-2.88, p = 0.004), place of work (OR = 2.18, 95% CI: 1.46-3.27, p < 0.001), and anxiety about having to address questions about radiation from students (OR = 4.66, 95% CI: 2.83-7.67, p < 0.001) were independently associated with schoolteachers' concerns about the health effects of radiation exposure due to working in the area around the nuclear power plant. Therefore, it is important to respond to these concerns in order to establish a meaningful education program for school children on radiation and its health effects., Competing Interests: The authors have declared that no competing interests exist.

Purpose: Pancreatic cancer is the 4th most common cause of cancer death in Japan and exhibits a 5-year overall survival rate of approximately 7%. The accurate diagnosis of pancreatic cancer is important for determining the optimal management strategy. Fludeoxyglucose-positron emission tomography (FDG PET) integrated with computed tomography (18F-FDG PET/CT) has emerged as a powerful imaging tool for detecting and evaluating various cancers, and it is used for staging, detecting local recurrence and distant metastasis, measuring therapeutic effects, and predicting prognosis in pancreatic cancer patients. Lately, FDG PET/CT-derived parameters, such as standardized uptake values (SUV), the metabolic tumor volume (MTV), and total lesion glycolysis (TLG), have been suggested as prognostic factors for various types of cancer, including pancreatic cancer. However, there is no consensus regarding the best parameters for evaluating patient prognosis, operability, etc. The purpose of this study was to examine the differences between operable and non-operable pancreatic cancer using FDG PET/CT-derived parameters, and to investigate whether volumetric parameters (TLG and the MTV) are superior to SUV-based parameters for predicting infiltration status/determining operability., Materials and Methods: We conducted a retrospective study of the cases of 48 patients with clinically proven pancreatic adenocarcinoma, who underwent FDG PET/CT imaging before treatment. In the operable group, the surgical specimens were subjected to histopathological examinations, and the cases were separated into those exhibiting less and greater infiltration. SUVmax, SUVpeak, the tumor background ratio (TBR), TLG, and the MTV were compared between these groups as well as between the operable and non-operable groups., Results: Venous infiltration showed significant associations with several metabolic parameters (SUVmax, SUVpeak, and the TBR). However, it did not display any significant associations with volumetric parameters, such as TLG or the MTV. None of the FDG PET/CT-derived parameters exhibited significant associations with lymphatic or neural infiltration. Significant differences in volumetric parameters, such as the MTV and TLG, were detected between the operable and non-operable subgroups., Conclusions: Metabolic 18F-FDG PET/CT-derived parameters, such as SUVmax, SUVpeak, and the TBR, are useful for predicting venous infiltration status in patients with operable pancreatic adenocarcinoma., Competing Interests: The authors have declared that no competing interests exist.

Chondroitin sulfate (CS) is a sulfated glycosaminoglycan (GAG) chain. In cartilage, CS plays important roles as the main component of the extracellular matrix (ECM), existing as side chains of the major cartilage proteoglycan, aggrecan. Six glycosyltransferases are known to coordinately synthesize the backbone structure of CS; however, their in vivo synthetic mechanism remains unknown. Previous studies have suggested that two glycosyltransferases, Csgalnact1 (t1) and Csgalnact2 (t2), are critical for initiation of CS synthesis in vitro. Indeed, t1 single knockout mice (t1 KO) exhibit slight dwarfism and a reduction in CS content in cartilage compared with wild-type (WT) mice. To reveal the synergetic roles of t1 and t2 in CS synthesis in vivo, we generated systemic single and double knockout (DKO) mice and cartilage-specific t1 and t2 double knockout (Col2-DKO) mice. DKO mice exhibited postnatal lethality, whereas t2 KO mice showed normal size and skeletal development. Col2-DKO mice survived to adulthood and showed severe dwarfism compared with t1 KO mice. Histological analysis of epiphyseal cartilage from Col2-DKO mice revealed disrupted endochondral ossification, characterized by drastic GAG reduction in the ECM. Moreover, DKO cartilage had reduced chondrocyte proliferation and an increased number of apoptotic chondrocytes compared with WT cartilage. Conversely, primary chondrocyte cultures from Col2-DKO knee cartilage had the same proliferation rate as WT chondrocytes and low GAG expression levels, indicating that the chondrocytes themselves had an intact proliferative ability. Quantitative RT-PCR analysis of E18.5 cartilage showed that the expression levels of Col2a1 and Ptch1 transcripts tended to decrease in DKO compared with those in WT mice. The CS content in DKO cartilage was decreased compared with that in t1 KO cartilage but was not completely absent. These results suggest that aberrant ECM caused by CS reduction disrupted endochondral ossification. Overall, we propose that both t1 and t2 are necessary for CS synthesis and normal chondrocyte differentiation but are not sufficient for all CS synthesis in cartilage.

Spaceflight entails various stressful environmental factors including microgravity. The effects of gravity changes have been studied extensively on skeletal, muscular, cardiovascular, immune and vestibular systems, but those on the nervous system are not well studied. The alteration of gravity in ground-based animal experiments is one of the approaches taken to address this issue. Here we investigated the effects of centrifugation-induced gravity changes on gene expression of brain-derived neurotrophic factor (BDNF) and serotonin receptors (5-HTRs) in the mouse brain. Exposure to 2g hypergravity for 14 days showed differential modulation of gene expression depending on regions of the brain. BDNF expression was decreased in the ventral hippocampus and hypothalamus, whereas increased in the cerebellum. 5-HT1BR expression was decreased in the cerebellum, whereas increased in the ventral hippocampus and caudate putamen. In contrast, hypergravity did not affect gene expression of 5-HT1AR, 5-HT2AR, 5-HT2CR, 5-HT4R and 5-HT7R. In addition to hypergravity, decelerating gravity change from 2g hypergravity to 1g normal gravity affected gene expression of BDNF, 5-HT1AR, 5-HT1BR, and 5-HT2AR in various regions of the brain. We also examined involvement of the vestibular organ in the effects of hypergravity. Surgical lesions of the inner ear's vestibular organ removed the effects induced by hypergravity on gene expression, which suggests that the effects of hypergravity are mediated through the vestibular organ. In summary, we showed that gravity changes induced differential modulation of gene expression of BDNF and 5-HTRs (5-HT1AR, 5-HT1BR and 5-HT2AR) in some brain regions. The modulation of gene expression may constitute molecular bases that underlie behavioral alteration induced by gravity changes.

Introduction: The endothelial function plays key roles in both promoting and protecting against atherosclerotic disease. Several methods, including peripheral arterial tonometry (PAT), have been reported to be useful for investigating endothelial dysfunction. Furthermore, the level of thrombomodulin (TM) is assumed to reflect the endothelial dysfunction. In the present study, we investigated endothelial dysfunction in patients with peripheral arterial disease (PAD) by measuring their TM levels, and evaluated the correlation between TM and various parameters., Materials and Methods: We measured the TM levels and performed PAT in 17 patients with PAD. We also recorded the patients' demographic information, including comorbidities, and investigated their hemodynamic status by measuring the ankle brachial pressure index (ABI). The PAT results were used to calculate the reactive hyperemia index (RHI), which reflected the patients' level of endothelial dysfunction., Results: The RHI and ABI values and the serum level of creatinine were found to be significantly correlated with the TM level (P = 0.040, 0.041 and 0.005, respectively). After setting an RHI value of 1.67 as the cut-off, the patients with RHI values of <1.67 were found to have significantly higher TM levels (median, 20.3 U/mL) than the patients with RHI values of ≥1.67 (median, 13.7 U/mL) (P = 0.023)., Conclusions: The degree of endothelial dysfunction, as calculated by the TM level, might influence the prognostic value of the RHI, which is determined by PAT. The measurement of the TM level and PAT might both be useful methods of measuring endothelial dysfunction in patients with PAD., Competing Interests: All authors have declared that no competing interests exist.

Signaling networks are made up of limited numbers of molecules and yet can code information that controls different cellular states through temporal patterns and a combination of signaling molecules. In this study, we used a data-driven modeling approach, the Laguerre filter with partial least square regression, to describe how temporal and combinatorial patterns of signaling molecules are decoded by their downstream targets. The Laguerre filter is a time series model used to represent a nonlinear system based on Volterra series expansion. Furthermore, with this approach, each component of the Volterra series expansion is expanded by Laguerre basis functions. We combined two approaches, application of a Laguerre filter and partial least squares (PLS) regression, and applied the combined approach to analysis of a signal transduction network. We applied the Laguerre filter with PLS regression to identify input and output (IO) relationships between MAP kinases and the products of immediate early genes (IEGs). We found that Laguerre filter with PLS regression performs better than Laguerre filter with ordinary regression for the reproduction of a time series of IEGs. Analysis of the nonlinear characteristics extracted using the Laguerre filter revealed a priming effect of ERK and CREB on c-FOS induction. Specifically, we found that the effects of a first pulse of ERK enhance the subsequent effects on c-FOS induction of treatment with a second pulse of ERK, a finding consistent with prior molecular biological knowledge. The variable importance of projections and output loadings in PLS regression predicted the upstream dependency of each IEG. Thus, a Laguerre filter with partial least square regression approach appears to be a powerful method to find the processing mechanism of temporal patterns and combination of signaling molecules by their downstream gene expression.

Gravity change affects many immunological systems. We investigated the effects of hypergravity (2G) on murine thymic cells. Exposure of mice to 2G for three days reduced the frequency of CD4+CD8+ thymocytes (DP) and mature medullary thymic epithelial cells (mTECs), accompanied by an increment of keratin-5 and keratin-8 double-positive (K5+K8+) TECs that reportedly contain TEC progenitors. Whereas the reduction of DP was recovered by a 14-day exposure to 2G, the reduction of mature mTECs and the increment of K5+K8+ TEC persisted. Interestingly, a surgical lesion of the inner ear's vestibular apparatus inhibited these hypergravity effects. Quantitative PCR analysis revealed that the gene expression of Aire and RANK that are critical for mTEC function and development were up-regulated by the 3-day exposure and subsequently down-regulated by the 14-day exposure to 2G. Unexpectedly, this dynamic change in mTEC gene expression was independent of the vestibular apparatus. Overall, data suggest that 2G causes a temporary reduction of DP and a persistent reduction of mature mTECs in a vestibular system-dependent manner, and also dysregulates mTEC gene expression without involving the vestibular system. These data might provide insight on the impact of gravity change on thymic functions during spaceflight and living.

Characteristics of peripheral arterial disease (PAD) are the occlusion or stenosis of multiple vessel sites caused mainly by atherosclerosis and chronic lower limb ischemia. To identify PAD susceptible loci, we conducted a genome-wide association study (GWAS) with 785 cases and 3,383 controls in a Japanese population using 431,666 single nucleotide polymorphisms (SNP). After staged analyses including a total of 3,164 cases and 20,134 controls, we identified 3 novel PAD susceptibility loci at IPO5/RAP2A, EDNRA and HDAC9 with genome wide significance (combined P = 6.8 x 10-14, 5.3 x 10-9 and 8.8 x 10-8, respectively). Fine-mapping at the IPO5/RAP2A locus revealed that rs9584669 conferred risk of PAD. Luciferase assay showed that the risk allele at this locus reduced expression levels of IPO5. To our knowledge, these are the first genetic risk factors for PAD.

After the Chernobyl Nuclear Power Plant accident, the residents living around the Chernobyl were revealed to have been internally exposed to 137Cs through the intake of contaminated local foods. To evaluate the current situation of internal 137Cs exposure and the relationship between the 137Cs soil contamination and internal exposure in residents, we investigated the 137Cs body burden in residents who were living in 10 selected cities from the northern part of the Zhitomir region, Ukraine, and collected soil samples from three family farms and wild forests of each city to measured 137Cs concentrations. The total number of study participants was 36,862, of which 68.9% of them were female. After 2010, the annual effective doses were less than 0.1 mSv in over 90% of the residents. The 137Cs body burden was significantly higher in autumn than other seasons (p < 0.001) and in residents living in more contaminated areas (p < 0.001). We also found a significant correlation between the proportion of residents in each city with an estimated annual exposure dose exceeding 0.1 mSv and 137Cs concentration of soil samples from family farms (r = 0.828, p = 0.003). In conclusion, more than 25 years after the Chernobyl accident, the internal exposure doses to residents living in contaminated areas of northern Ukraine is limited but still related to 137Cs soil contamination. Furthermore, the consumption of local foods is considered to be the cause of internal exposure.

To elucidate the pure impact of microgravity on small mammals despite uncontrolled factors that exist in the International Space Station, it is necessary to construct a 1 g environment in space. The Japan Aerospace Exploration Agency has developed a novel mouse habitat cage unit that can be installed in the Cell Biology Experiment Facility in the Kibo module of the International Space Station. The Cell Biology Experiment Facility has a short-arm centrifuge to produce artificial 1 g gravity in space for mouse experiments. However, the gravitational gradient formed inside the rearing cage is larger when the radius of gyration is shorter; this may have some impact on mice. Accordingly, biological responses to hypergravity induced by a short-arm centrifuge were examined and compared with those induced by a long-arm centrifuge. Hypergravity induced a significant Fos expression in the central nervous system, a suppression of body mass growth, an acute and transient reduction in food intake, and impaired vestibulomotor coordination. There was no difference in these responses between mice raised in a short-arm centrifuge and those in a long-arm centrifuge. These results demonstrate the feasibility of using a short-arm centrifuge for mouse experiments.

We conducted a survey among nurses who were working at the Fukushima Medical University Hospital at the time of the Fukushima Daiichi Nuclear Power Plant accident to clarify the factors associated with their intention to leave their jobs during the radiation emergency. We asked 345 nurses (17 men and 328 women) about their intention to leave their jobs after the accident. We also asked about relevant factors including the participants' demographic factors, living situation, working status, and knowledge of radiation health effects. We found that living with preschoolers (OR = 1.87, 95%CI: 1.02-3.44, p = 0.042), anxiety about life in Fukushima City after the accident (OR = 5.55, 95%CI: 1.18-26.13, p = 0.030), consideration of evacuation from Fukushima after the accident (OR = 2.42, 95%CI: 1.45-4.06, p = 0.001), consideration of the possible radiation health effects in children (OR = 1.90, 95%CI: 1.02-3.44, p = 0.042), and anxiety about relationships with colleagues in the hospital after the accident (OR = 3.23, p = 0.001) were independently associated with the nurses' intention to leave their jobs after the accident. On the other hand, the percentage of nurses with knowledge on radiation health effects was relatively low among those who had the intention to leave the job and among those who did not have the intention to leave the job after the accident, with no significant differences between the two groups. Our results suggest the need for an education program for nurses regarding radiation health effects.

To confirm the availability of individual dose evaluation for the return of residents after the accident at the Fukushima Dai-ichi Nuclear Power Plant (FNPP), we evaluated individual doses of radiation as measured by personal dosimeters in residents who temporarily stayed in Evacuation Order Areas in Kawauchi village, which is partially located within a 20 km radius of the FNPP. We also compared individual doses with the external radiation doses estimated from the ambient dose rates and with doses estimated from the concentrations of radionuclides in the soil around each individual's house. Individual doses were significantly correlated with the ambient doses in front of the entrances to the houses (r = 0.90, p<0.01), in the backyards (r = 0.41, p<0.01) and in the nearby fields (r = 0.80, p<0.01). The maximum cumulative ambient doses in the backyards and fields around the houses were 6.38 and 9.27 mSv/y, respectively. The maximum cumulative individual dose was 3.28 mSv/y, and the median and minimum doses were 1.35 and 0.71 mSv/y. The estimated external effective doses from concentrations of artificial radionuclides in soil samples ranged from 0.03 to 23.42 mSv/y. The individual doses were moderately correlated with external effective doses in the backyards (r = 0.38, p<0.01) and in the fields (r = 0.36, p<0.01); however, the individual doses were not significantly correlated with the external effective doses in front of the entrances (r = 0.01, p = 0.92). Our study confirmed that individual doses are low levels even in the evacuation order area in Kawauchi village, and external effective dose levels are certainly decreasing due to the decay of artificial radionuclides and the decontamination of contaminated soil. Long-term follow-up of individual doses as well as internal-exposure doses, environmental monitoring and reconstruction of infrastructure are needed so that residents may return to their hometowns after a nuclear disaster.

As a result of the accident at the Fukushima Daiichi Nuclear Power Plant (FNPP) on 11 March 2011, a huge amount of radionuclides, including radiocesium, was released and spread over a wide area of eastern Japan. Although three years have passed since the accident, residents around the FNPP are anxious about internal radiation exposure due to radiocesium. In this study, we screened internal radiation exposure doses in Iwaki city of Fukushima prefecture, using a whole-body counter. The first screening was conducted from October 2012 to February 2013, and the second screening was conducted from May to November 2013. Study participants were employees of ALPINE and their families who underwent examination. A total of 2,839 participants (1,366 men and 1,473 women, 1-86 years old) underwent the first screening, and 2,092 (1,022 men and 1,070 women, 1-86 years old) underwent the second screening. The results showed that 99% of subjects registered below 300 Bq per body in the first screening, and all subjects registered below 300 Bq per body in the second screening. The committed effective dose ranged from 0.01-0.06 mSv in the first screening and 0.01-0.02 mSv in the second screening. Long-term follow-up studies are needed to avoid unnecessary chronic internal exposure and to reduce anxiety among the residents by communicating radiation health risks.

Background: Mast cells (MCs) are multifaceted immune cells that are capable of recognizing and responding to various stimuli by releasing an array of cytokines. We aimed to use human cord blood-derived mast cells (hCBMCs) as a model to evaluate different conditions under which chemokines and growth factors are expressed and secreted as mediators upon stimulation with the alarmin interleukin-33 (IL-33). Methods: hCBMCs were stimulated with 10 ng/mL or 20 ng/mL of recombinant human IL-33 (rhIL-33) for 6 h (acute) or 24 h (chronic). The mRNA expression of chemokines and growth factors was analyzed using microarrays, and the mediators released in the supernatant were evaluated using a multiplex assay. Results: The mRNA expression levels of C-C chemokine ligands (CCL) CCL1, CCL5, granulocyte macrophage colony-stimulating factor (GM-CSF), and macrophage inflammatory protein (MIP)-4/CCL18 were upregulated under all conditions. In contrast, C-X-C motif chemokine ligand (CXCL) CXCL8 and CCL24 levels increased only under acute (6 h) and prolonged (24 h) conditions, respectively. Moreover, high levels of CXCL8, MIP-1α, and MIP-1β were secreted during acute inflammation, whereas the release of GM-CSF and CXCL9 proteins increased under all four conditions. Conclusions: This study highlights the sentinel role of MCs in mounting a specific immune response against a pathogenic-like stimulus in a timely and dose-dependent manner and is relevant for improving inflammatory treatment options. [ABSTRACT FROM AUTHOR]

A novel nickel-molybdenum carbide-graphite nanofiber composite is introduced as an electrocatalyst for ethanol electrooxidation. The proposed nanofibers have been prepared by calcinating electrospun nanofibers composed of nickel acetate tetrahydrate, molybdenum chloride, and polyvinyl alcohol. The calcination process was conducted at different temperatures (700, 850, and 1000°C) under a nitrogen gas atmosphere with a heating rate of 2.5 deg/min and a holding time of 5 h. Physicochemical characterizations have indicated that nickel acetate is entirely reduced to nickel metal during the sintering process, and molybdenum has bonded with carbon to produce molybdenum carbide. At the same time, the used polymer has been pyrolyzed to produce a carbon nanofiber matrix embedding formed inorganic nanoparticles. Electrochemical measurements concluded that molybdenum content and calcination temperature should be controlled to maximize the electrocatalytic activity of the proposed catalyst. Typically, the oxidation peak current density was 28.5, 28.8, 51.5, 128.3, 25.6, and 3 mA/cm2 for nanofibers prepared from an electrospun solution containing 0, 5, 10, 15, 25, and 35 wt% molybdenum carbide, respectively. Moreover, it was observed that increasing the calcination temperature distinctly improves the electrocatalytic activity. Kinetic studies have indicated that the reaction order is close to zero with a reaction temperature-dependent value. Moreover, it was detected that the electrooxidation reaction of ethanol over the proposed nanofiber composite follows the Arrhenius equation. The determined activation energy is 33 kJ/mol, which indicates good catalytic activity for the introduced nanofibers. Through the application of a set of visualization-based tools and the general linear model (GLM), the optimal conditions that generate the highest current density were identified. The computations unveiled that the optimal parameter settings are as follows: Mo content at 15 wt.%, methanol concentration of 1.55 M, and reaction temperature of 59°C. [ABSTRACT FROM AUTHOR]

Recent studies on the large Maf transcription factors have shown that Mafb and Mafa have respective and distinctive roles in β-cell development and maturation. However, whether this difference in roles is due to the timing of the gene expression (roughly, expression of Mafb before birth and of Mafa after birth) or to the specific function of each gene is unclear. Our aim was to examine the functional differences between these genes that are closely related to β cells by using an in vivo model of β-like cell generation. We monitored insulin gene transcription by measuring bioluminescence emitted from the liver of insulin promoter-luciferase transgenic (MIP-Luc-VU) mice. Adenoviral gene transfers of Pdx1/Neurod/Mafa (PDA) and Pdx1/Neurod/Mafb (PDB) combinations generated intense luminescence from the liver that lasted for more than 1 week and peaked at 3 days after transduction. The peak signal intensities of PDA and PDB were comparable. However, PDA but not PDB transfer resulted in significant bioluminescence on day 10, suggesting that Mafa has a more sustainable role in insulin gene activation than does Mafb. Both PDA and PDB transfers ameliorated the glucose levels in a streptozotocin (STZ)-induced diabetic model for up to 21 days and 7 days, respectively. Furthermore, PDA transfer induced several gene expressions necessary for glucose sensing and insulin secretion in the liver on day 9. However, a glucose tolerance test and liver perfusion experiment did not show glucose-stimulated insulin secretion from intrahepatic β-like cells. These results demonstrate that bioluminescence imaging in MIP-Luc-VU mice provides a noninvasive means of detecting β-like cells in the liver. They also show that Mafa has a markedly intense and sustained role in β-like cell production in comparison with Mafb.

Objective: This study investigated the relationship between aortic 18F-fluoro-2-deoxy-D-glucose (18F-FDG) uptake and clinical and laboratory findings related to atherosclerosis in a general population., Methods: 18F-FDG uptake in the ascending aorta was measured on the positron emission tomography/computed tomography (PET/CT) scans of 211 Japanese adults. The maximum target-to-background ratio (TBR) was compared with clinical and laboratory atherosclerosis findings., Results: By multivariate regression analysis adjusted for age and sex, TBR-ascending aorta (TBR-A) was significantly correlated with various clinical and laboratory parameters, such as body mass index, log visceral fat area, low-density lipoprotein cholesterol (LDL-C), log fasting immunoreactive insulin, log homeostasis model assessment of insulin resistance, log total adiponectin and log-leptin, in all subjects. Furthermore, by multivariate linear regression analysis adjusted for confounding factors, TBR-A was significantly correlated with LDL-C (β = 0.001, p = 0.03) and log-leptin (β = 0.336, p<0.01) in all subjects., Conclusion: TBR-A was significantly correlated with LDL-C and log-leptin independent from confounding factors. Our results suggest that aortic 18F-FDG uptake is a good marker of atherosclerosis, even in a general population.

Despite their abundance at gastrointestinal sites, little is known about the role of galectins in gut immune responses. We have therefore investigated the Citrobacter rodentium model of colonic infection and inflammation in Galectin-1 or Galectin-3 null mice. Gal-3 null mice showed a slight delay in colonisation after inoculation with C. rodentium and a slight delay in resolution of infection, associated with delayed T cell, macrophage and dendritic cell infiltration into the gut mucosa. However, Gal-1 null mice also demonstrated reduced T cell and macrophage responses to infection. Despite the reduced T cell and macrophage response in Gal-1 null mice, there was no effect on C. rodentium infection kinetics and pathology. Overall, Gal-1 and Gal-3 play only a minor role in immunity to a gut bacterial pathogen.

Cells use common signaling molecules for the selective control of downstream gene expression and cell-fate decisions. The relationship between signaling molecules and downstream gene expression and cellular phenotypes is a multiple-input and multiple-output (MIMO) system and is difficult to understand due to its complexity. For example, it has been reported that, in PC12 cells, different types of growth factors activate MAP kinases (MAPKs) including ERK, JNK, and p38, and CREB, for selective protein expression of immediate early genes (IEGs) such as c-FOS, c-JUN, EGR1, JUNB, and FOSB, leading to cell differentiation, proliferation and cell death; however, how multiple-inputs such as MAPKs and CREB regulate multiple-outputs such as expression of the IEGs and cellular phenotypes remains unclear. To address this issue, we employed a statistical method called partial least squares (PLS) regression, which involves a reduction of the dimensionality of the inputs and outputs into latent variables and a linear regression between these latent variables. We measured 1,200 data points for MAPKs and CREB as the inputs and 1,900 data points for IEGs and cellular phenotypes as the outputs, and we constructed the PLS model from these data. The PLS model highlighted the complexity of the MIMO system and growth factor-specific input-output relationships of cell-fate decisions in PC12 cells. Furthermore, to reduce the complexity, we applied a backward elimination method to the PLS regression, in which 60 input variables were reduced to 5 variables, including the phosphorylation of ERK at 10 min, CREB at 5 min and 60 min, AKT at 5 min and JNK at 30 min. The simple PLS model with only 5 input variables demonstrated a predictive ability comparable to that of the full PLS model. The 5 input variables effectively extracted the growth factor-specific simple relationships within the MIMO system in cell-fate decisions in PC12 cells.

Box C/D-type small nucleolar RNAs (snoRNAs) are functional RNAs responsible for mediating 2'-O-ribose methylation of ribosomal RNAs (rRNAs) within the nucleolus. In the past years, evidence for the involvement of human U50 snoRNA in tumorigenesis has been accumulating. We previously identified U50HG, a non-protein-coding gene that hosted a box C/D-type U50 snoRNA, in a chromosomal breakpoint in a human B-cell lymphoma. Mouse genome analysis revealed four mouse U50 (mU50) host-genes: three mU50HG-a gene variants that were clustered in the genome and an mU50HG-b gene that we supposed to be the U50HG ortholog. In this study, to investigate the physiological importance of mU50 snoRNA and its involvement in tumorigenesis, we eliminated mU50 snoRNA sequences from the mU50HG-b gene. The established mouse line (ΔmU50(HG-b)) showed a significant reduction of mU50 snoRNA expression without alteration of the host-gene length and exon-intron structure, and the corresponding target rRNA methylation in various organs was reduced. Lifelong phenotypic monitoring showed that the ΔmU50(HG-b) mice looked almost normal without accelerated tumorigenicity; however, a notable difference was the propensity for anomalies in the lymphoid organs. Transcriptome analysis showed that dozens of genes, including heat shock proteins, were differentially expressed in ΔmU50(HG-b) mouse lymphocytes. This unique model of a single snoRNA knockdown with intact host-gene expression revealed further new insights into the discrete transcriptional regulation of multiple mU50 host-genes and the complicated dynamics involved in organ-specific processing and maintenance of snoRNAs.

Sleep and circadian disruptions are commonly reported by patients with neurodegenerative diseases, suggesting these may be an endophenotype of the disorders. Several mouse models of Huntington's disease (HD) that recapitulate the disease progression and motor dysfunction of HD also exhibit sleep and circadian rhythm disruption. Of these, the strongest effects are observed in the transgenic models with multiple copies of mutant huntingtin gene. For developing treatments of the human disease, knock-in (KI) models offer advantages of genetic precision of the insertion and control of mutation copy number. Therefore, we assayed locomotor activity and immobility-defined sleep in a new model of HD with an expansion of the KI repeats (Q175). We found evidence for gene dose- and age-dependent circadian disruption in the behavior of the Q175 line. We did not see evidence for loss of cells or disruption of the molecular oscillator in the master pacemaker, the suprachiasmatic nucleus (SCN). The combination of the precise genetic targeting in the Q175 model and the observed sleep and circadian disruptions make it tractable to study the interaction of the underlying pathology of HD and the mechanisms by which the disruptions occur.

In diabetes research, bioluminescence imaging (BLI) has been applied in studies of β-cell impairment, development, and islet transplantation. To develop a mouse model that enables noninvasive imaging of β cells, we generated a bacterial artificial chromosome (BAC) transgenic mouse in which a mouse 200-kbp genomic fragment comprising the insulin I gene drives luciferase expression (Ins1-luc BAC transgenic mouse). BLI of mice was performed using the IVIS Spectrum system after intraperitoneal injection of luciferin, and the bioluminescence signal from the pancreatic region analyzed. When compared with MIP-Luc-VU mice [FVB/N-Tg(Ins1-luc)VUPwrs/J] expressing luciferase under the control of the 9.2-kbp mouse insulin I promoter (MIP), the bioluminescence emission from Ins1-luc BAC transgenic mice was enhanced approximately 4-fold. Streptozotocin-treated Ins1-luc BAC transgenic mice developed severe diabetes concomitant with a sharp decline in the BLI signal intensity in the pancreas. Conversely, mice fed a high-fat diet for 8 weeks showed an increase in the signal, reflecting a decrease or increase in the β-cell mass. Although the bioluminescence intensity of the islets correlated well with the number of isolated islets in vitro, the intensity obtained from a living mouse in vivo did not necessarily reflect an absolute quantification of the β-cell mass under pathological conditions. On the other hand, adenovirus-mediated gene transduction of β-cell-related transcription factors in Ins1-luc BAC transgenic mice generated luminescence from the hepatic region for more than 1 week. These results demonstrate that BLI in Ins1-luc BAC transgenic mice provides a noninvasive method of imaging islet β cells and extrapancreatic activity of the insulin gene in the liver under normal and pathological conditions.

This paper reports an experimental study of the formation of a mixed O(3)+ O(2)+ CO(2) hydrate and its frozen storage under atmospheric pressure, which aimed to establish a hydrate-based technology for preserving ozone (O(3)), a chemically unstable substance, for various industrial, medical and consumer uses. By improving the experimental technique that we recently devised for forming an O(3)+ O(2)+ CO(2) hydrate, we succeeded in significantly increasing the fraction of ozone contained in the hydrate. For a hydrate formed at a system pressure of 3.0 MPa, the mass fraction of ozone was initially about 0.9%; and even after a 20-day storage at -25°C and atmospheric pressure, it was still about 0.6%. These results support the prospect of establishing an economical, safe, and easy-to-handle ozone-preservation technology of practical use.

The relationship between xylophagous termites and the protists resident in their hindguts is a textbook example of symbiosis. The essential steps of lignocellulose degradation handled by these protists allow the host termites to thrive on a wood diet. There has never been a comprehensive analysis of lignocellulose degradation by protists, however, as it has proven difficult to establish these symbionts in pure culture. The trends in lignocellulose degradation during the evolution of the host lineage are also largely unknown. To clarify these points without any cultivation technique, we performed meta-expressed sequence tag (EST) analysis of cDNA libraries originating from symbiotic protistan communities in four termite species and a wood-feeding cockroach. Our results reveal the establishment of a degradation system with multiple enzymes at the ancestral stage of termite-protistan symbiosis, especially GHF5 and 7. According to our phylogenetic analyses, the enzymes comprising the protistan lignocellulose degradation system are coded not only by genes innate to the protists, but also genes acquired by the protists via lateral transfer from bacteria. This gives us a fresh perspective from which to understand the evolutionary dynamics of symbiosis.

The classification of Microbispora, a bacterial genus of significant ecological, agricultural, biotechnological, and clinical importance, has traditionally been carried out based on 16S rRNA gene sequences or phenotypic characteristics, which may lead to equivocal conclusions and it is not in line with the current standards. Moreover, some of the recent species descriptions have not been made using whole genome sequences (WGS), or when used, not all the species were included in the analyses. Consequently, some of the taxonomic conclusions drawn are equivocal, and therefore some currently accepted species should be synonymized. In this study, we revised the taxonomy of the genus Microbispora using digital DNA-DNA hybridization (dDDH) and average nucleotide identity (ANI) values, and by reconstructing phylogenetic relationships using whole genome sequences. Based on the clear phylogenomic separations and on the sequence divergence values, we propose to elevate Microbispora rosea subsp. rosea and Microbispora rosea subsp. aerata to the species level, and therefore to create Microbispora aerata sp. nov. with JCM 3076T (= DSM 43176T = ATCC 15448T = IFO 14624T = NBRC 14624T = VKM Ac-1507T) as the type strain. Hence, with this proposition, the correct name for Microbispora rosea subsp. rosea is M. rosea. Furthermore, we propose to reclassify M. camponoti as a subspecies within M. bryophytorum. Consequently, we propose the creation of the following two subspecies: Microbispora bryophytorum subsp. bryophytorum subsp. nov. with DSM 46710T (= CGMCC 4.7138T = NEAU TX2-2T) as the type strain, and Microbispora bryophytorum subsp. camponoti subsp. nov., comb. nov. with DSM 2C-HV3T (= DSM 100527T = CGMCC 4.7281T) as the type strain. In addition, we propose to reinstate M. amethystogenes as an independent species and not as a M. rosea synonym, and reclassify "M. cellulosiformans" as a subspecies within M. amethystogenes. Hence, we propose the creation of the following two subspecies: Microbispora amethystogenes subsp. amethystogenes subsp. nov. with NBRC 101907T (= DSM 43164T = JCM 3021T = NRRL B-2637T) as the type strain, and Microbispora amethystogenes subsp. cellulosiformans subsp. nov., comb. nov. with Gxj-6T (= DSM 109712T = CGMCC 4.7605T) as the type strain. Lastly, we propose M. fusca NEAU-HEGS1-5T and "M. tritici" MT50T as later homotypic synonyms of M. triticiradicis NEAU-HRDPA2-9T. [ABSTRACT FROM AUTHOR]

Analyzing tissue microstructure is essential for understanding complex biological systems in different species. Tissue functions largely depend on their intrinsic tissue architecture. Therefore, studying the three-dimensional (3D) microstructure of tissues, such as the liver, is particularly fascinating due to its conserved essential roles in metabolic processes and detoxification. Here, we present TiMiGNet, a novel deep learning approach for virtual 3D tissue microstructure reconstruction using Generative Adversarial Networks and fluorescence microscopy. TiMiGNet overcomes challenges such as poor antibody penetration and time-intensive procedures by generating accurate, high-resolution predictions of tissue components across large volumes without the need of paired images as input. We applied TiMiGNet to analyze tissue microstructure in mouse and human liver tissue. TiMiGNet shows high performance in predicting structures like bile canaliculi, sinusoids, and Kupffer cell shapes from actin meshwork images. Remarkably, using TiMiGNet we were able to computationally reconstruct tissue structures that cannot be directly imaged due experimental limitations in deep dense tissues, a significant advancement in deep tissue imaging. Our open-source virtual prediction tool facilitates accessible and efficient multi-species tissue microstructure analysis, accommodating researchers with varying expertise levels. Overall, our method represents a powerful approach for studying tissue microstructure, with far-reaching applications in diverse biological contexts and species. [ABSTRACT FROM AUTHOR]

The accurate early diagnosis of colorectal cancer significantly relies on the precise segmentation of polyps in medical images. Current convolution-based and transformer-based segmentation methods show promise but still struggle with the varied sizes and shapes of polyps and the often low contrast between polyps and their background. This research introduces an innovative approach to confronting the aforementioned challenges by proposing a Dual-Channel Hybrid Attention Network with Transformer (DHAFormer). Our proposed framework features a multi-scale channel fusion module, which excels at recognizing polyps across a spectrum of sizes and shapes. Additionally, the framework's dual-channel hybrid attention mechanism is innovatively conceived to reduce background interference and improve the foreground representation of polyp features by integrating local and global information. The DHAFormer demonstrates significant improvements in the task of polyp segmentation compared to currently established methodologies. [ABSTRACT FROM AUTHOR]

Highlighting minorities and crime survivors through public discourse is essential for their support and protection. However, advocating for minorities is challenging due to the fear of potential isolation from one's social circles. This reluctance contributes to the societal phenomenon known as the "spiral of silence," significantly impeding efforts to support socially vulnerable individuals. This study centers on a pivotal instance where the silence surrounding sexual abuse in the Japanese entertainment industry was disrupted, in which the late company president had allegedly abused idol trainees of the company for decades. Utilizing extensive data from news media and social media, the study probes the engagement dynamics of public attention to this scandal. Results indicate that users on social media provided earlier and greater coverage for this scandal compared to news media outlets. Furthermore, television demonstrated a significant delay in addressing this issue compared to other news media, such as tabloids, magazines, and online news. Regarding social media engagement, idol fans exhibited a more subdued response to the issue compared to the general public. Notably, fans more loyal to the company tended to be slower to mention the issue, with a higher likelihood of standing in defense of the perpetrators. Moreover, conflicting attitudes were observed within the fan communities, culminating in an observable "echo chamber" phenomenon. This paper presents a novel examination of the process of disruption of social silence and offers critical insights for aiding vulnerable individuals in environments dominated by an unacknowledged spiral of silence. This study is novel in that it suggests a reinterpretation of the "spiral of silence theory" in the age of social media, through a comprehensive analysis of relevant social media data and news media data. This contributes to the body of research that has analyzed the spiral of silence theory online. [ABSTRACT FROM AUTHOR]

Background: Anti-vascular endothelial growth factor (VEGF) monoclonal antibodies (mAbs) are widely used for tumor treatment, including metastatic colorectal cancer (mCRC). So far, there are no biomarkers that reliably predict resistance to anti-VEGF mAbs like bevacizumab. A biomarker-guided strategy for early and accurate assessment of resistance could avoid the use of non-effective treatment and improve patient outcomes. We hypothesized that repeated analysis of multiple cytokines and angiogenic growth factors (CAFs) before and during treatment using machine learning could provide an accurate and earlier, i.e., 100 days before conventional radiologic staging, prediction of resistance to first-line mCRC treatment with FOLFOX plus bevacizumab. Patients and methods: 15 German and Austrian centers prospectively recruited 50 mCRC patients receiving FOLFOX plus bevacizumab as first-line treatment. Plasma samples were collected every two weeks until radiologic progression (RECIST 1.1) as determined by CT scans performed every 2 months. 102 pre-selected CAFs were centrally analyzed using a cytokine multiplex assay (Luminex, Myriad RBM). Results: Using random forests, we developed a predictive machine learning model that discriminated between the situations of "no progress within 100 days before radiological progress" and "progress within 100 days before radiological progress". We could further identify a combination of ten out of the 102 CAF markers, which fulfilled this task with 78.2% accuracy, 71.8% sensitivity, and 82.5% specificity. Conclusions: We identified a CAF marker combination that indicates treatment resistance to FOLFOX plus bevacizumab in patients with mCRC within 100 days prior to radiologic progress. [ABSTRACT FROM AUTHOR]

The number of Americans with multiple jobs is increasing and multiple jobholders work more hours per week. However, the associations between multiple jobholding and hypertension are unknown. The aim of this study was to examine the associations of multiple jobholding with hypertension and determine whether weekly working hours moderated this association. Data from the 2015 National Health Interview Survey on adults (age ≥18 years) were used and included participants who self-identified as non-Hispanic Asian, non-Hispanic Black, Hispanic, or non-Hispanic White in the U.S. (n = 16,926), The associations of multiple jobholding with self-reported hypertension by sex were assessed using modified Poisson regressions. Both the number of working hours per week and race/ethnicity were assessed as moderators using multiplicative interaction terms. Multiple jobholding was not associated with hypertension among women. However, there was a significant three-way interaction such that multiple jobholding was associated with hypertension among non-Hispanic Black men who worked ≥55 hours per week (relative risk = 1.02, 95% confidence interval = 1.01–1.05). The results suggest that the associations between multiple jobholding, number of working hours, and hypertension should be examined at the intersection of race/ethnicity and sex. Future studies should further characterize multiple jobholding and hypertension among non-Hispanic Black men. [ABSTRACT FROM AUTHOR]

The expanding urbanization of coastal areas has led to increased ocean sprawl, which has had both physical and chemical adverse effects on marine and coastal ecosystems. To maintain the health and functionality of these ecosystems, it is imperative to develop effective solutions. One such solution involves the use of biodegradable polymers as bioactive coatings to enhance the bioreceptivity of marine and coastal infrastructures. Our study aimed to explore two main objectives: (1) investigate PHA-degrading bacteria on polymer-coated surfaces and in surrounding seawater, and (2) comparing biofilm colonization between surfaces with and without the polymer coating. We applied poly(3-hydroxybutyrate) [P(3HB)) coatings on concrete surfaces at concentrations of 1% and 6% w/v, with varying numbers of coating cycles (1, 3, and 6). Our findings revealed that the addition of P(3HB) indeed promoted accelerated biofilm growth on the coated surfaces, resulting in an occupied area approximately 50% to 100% larger than that observed in the negative control. This indicates a remarkable enhancement, with the biofilm expanding at a rate roughly 1.5 to 2 times faster than the untreated surfaces. We observed noteworthy distinctions in biofilm growth patterns based on varying concentration and number of coating cycles. Interestingly, treatments with low concentration and high coating cycles exhibited comparable biofilm enhancements to those with high concentrations and low coating cycles. Further investigation into the bacterial communities responsible for the degradation of P(3HB) coatings identified mostly common and widespread strains but found no relation between the concentration and coating cycles. Nevertheless, this microbial degradation process was found to be highly efficient, manifesting noticeable effects within a single month. While these initial findings are promising, it's essential to conduct tests under natural conditions to validate the applicability of this approach. Nonetheless, our study represents a novel and bio-based ecological engineering strategy for enhancing the bioreceptivity of marine and coastal structures. [ABSTRACT FROM AUTHOR]

The claustrum is an irregular and fine sheet of grey matter in the basolateral telencephalon present in almost all mammals. The claustrum has been the object of several studies using animal models and, more recently, in human beings using neuroimaging. One of the most extended cognitive processes attributed to the claustrum is the salience process, which is also related to the insular cortex. In the same way, studies with human subjects and functional magnetic resonance imaging have reported the coactivation of the claustrum/insular cortex in the integration of sensory signals. This coactivation has been reported in the left claustrum/insular cortex or in the right claustrum/insular cortex. The asymmetry has been reported in task studies and literature related to neurological disorders such as Alzheimer's disease and schizophrenia, relating the severity of delusions with the reduction in left claustral volume. We present a functional connectivity study of the claustrum. Resting-state functional and anatomical MRI data from 100 healthy subjects were analyzed; taken from the Human Connectome Project (HCP, NIH Blueprint: The Human Connectome Project), with 2x2x2 mm3 voxel resolution. We hypothesize that 1) the claustrum is a node involved in different brain networks, 2) the functional connectivity pattern of the claustrum is different from the insular cortex's pattern, and 3) the asymmetry is present in the claustrum's functional connectivity. Our findings include at least three brain networks related to the claustrum. We found functional connectivity between the claustrum, frontoparietal network, and the default mode network as a distinctive attribute. The functional connectivity between the right claustrum with the frontoparietal network and the dorsal attention network supports the hypothesis of claustral asymmetry. These findings provide functional evidence, suggesting that the claustrum is coupled with the frontoparietal network serving together to instantiate new task states by flexibly modulating and interacting with other control and processing networks. [ABSTRACT FROM AUTHOR]

Introduction: Biliary tract cancer (BTC) is a lethal disease with a bad overall survivability, partly arising from inadequate therapeutic alternatives, detection at a belated stage, and a resistance to common therapeutic approaches. Ferroptosis is a form of programmed cell death that depends on reactive oxygen species (ROS) and iron, causing excessive peroxidation of polyunsaturated fatty acids (PUFAs). Therefore, the objective of this investigation is, whether ferroptosis can be induced in BTC in vitro and whether this induction is dependent on specific molecular markers. Methods: The study conducted resazurin assay and IC25/50 calculation to explore the possible cytotoxic outcomes of different classes of ferroptosis-inducing substances (FINs) on a comprehensive in vitro model of 11 BTC cell lines. Combinatory treatments with different cell death inhibitors were performed to evaluate the magnitude of ferroptosis induction. To ascertain whether ferroptotic cell death occurred, liperfluo and iron assay kits were employed to evaluate lipid ROS and intracellular iron abundance. Potential biomarkers of ferroptosis sensitivity were then assessed via western blot analysis, a rtPCR panel and functional assay kits. Results: The study found that different FINs reduced cell viability in a cell line-dependent manner. In addition, we measured increased lipid ROS and intracellular Fe2+ levels upon exposure to FINs in BTC cells. Combining FINs with inhibitors of ferroptosis, necroptosis or apoptosis suggests the occurrence of ferroptotic events in BTC cell lines CCC-5, HuH-28 and KKU-055. Furthermore, we found that BTC cells display a heterogeneous profile regarding different molecular genes/markers of ferroptosis. Subsequent analysis revealed that sensitivity of BTC cells towards IKE and RSL3 positively correlated with CD71 and SLC7A11 protein expression. Conclusion: Our results demonstrate that induction of ferroptosis is a promising approach to inhibit BTC cell growth and that the sensitivity of BTC cells towards ferroptosis induction might be dependent on molecular markers such as CD71 and SLC7A11. [ABSTRACT FROM AUTHOR]

Photoreceptor cell death can cause progressive and irreversible visual impairments. Still, effective therapies on retinal neuroprotection are not available. Hypoxia-inducible factors (HIFs) are transcriptional factors which strongly regulate angiogenesis, erythropoiesis, intracellular metabolism, and programed cell death under a hypoxic or an abnormal metabolic oxidative stress condition. Therefore, we aimed to unravel that inhibition of HIFs could prevent disease progression in photoreceptor cell death, as recent studies showed that HIFs might be pathologic factors in retinal diseases. Adult male balb/cAJcl (8 weeks old; BALB/c) were used to investigate preventive effects of a novel HIF inhibitor halofuginone (HF) on a murine model of light-induced retinopathy. After intraperitoneal injections of phosphate-buffered saline (PBS) or HF (0.4 mg/kg in PBS) for 5 days, male BALB/c mice were subjected to a dark-adaption to being exposed to a white LED light source at an intensity of 3,000 lux for 1 hour in order to induce light-induced retinal damage. After extensive light exposure, retinal damage was evaluated using electroretinography (ERG), optical coherence tomography (OCT), and TUNEL assay. Light-induced retinal dysfunction was suppressed by HF administration. The amplitudes of scotopic a-wave and b-wave as well as that of photopic b-wave were preserved in the HF-administered retina. Outer retinal thinning after extensive light exposure was suppressed by HF administration. Based on the TUNEL assay, cell death in the outer retina was seen after light exposure. However, its cell death was not detected in the HF-administered retina. Halofuginone was found to exert preventive effects on light-induced outer retinal cell death. [ABSTRACT FROM AUTHOR]

Insulin secretion from pancreatic β-cells is integral in maintaining the delicate equilibrium of blood glucose levels. Calcium is known to be a key regulator and triggers the release of insulin. This sub-cellular process can be monitored and tracked through live-cell imaging and subsequent cell segmentation, registration, tracking, and analysis of the calcium level in each cell. Current methods of analysis typically require the manual outlining of β-cells, involve multiple software packages, and necessitate multiple researchers—all of which tend to introduce biases. Utilizing deep learning algorithms, we have therefore created a pipeline to automatically segment and track thousands of cells, which greatly reduces the time required to gather and analyze a large number of sub-cellular images and improve accuracy. Tracking cells over a time-series image stack also allows researchers to isolate specific calcium spiking patterns and spatially identify those of interest, creating an efficient and user-friendly analysis tool. Using our automated pipeline, a previous dataset used to evaluate changes in calcium spiking activity in β-cells post-electric field stimulation was reanalyzed. Changes in spiking activity were found to be underestimated previously with manual segmentation. Moreover, the machine learning pipeline provides a powerful and rapid computational approach to examine, for example, how calcium signaling is regulated by intracellular interactions. [ABSTRACT FROM AUTHOR]

Public comments are an important opinion for civic when the government establishes rules. However, recent AI can easily generate large quantities of disinformation, including fake public comments. We attempted to distinguish between human public comments and ChatGPT-generated public comments (including ChatGPT emulated that of humans) using Japanese stylometric analysis. Study 1 conducted multidimensional scaling (MDS) to compare 500 texts of five classes: Human public comments, GPT-3.5 and GPT-4 generated public comments only by presenting the titles of human public comments (i.e., zero-shot learning, GPTzero), GPT-3.5 and GPT-4 emulated by presenting sentences of human public comments and instructing to emulate that (i.e., one-shot learning, GPTone). The MDS results showed that the Japanese stylometric features of the public comments were completely different from those of the GPTzero-generated texts. Moreover, GPTone-generated public comments were closer to those of humans than those generated by GPTzero. In Study 2, the performance levels of the random forest (RF) classifier for distinguishing three classes (human, GPTzero, and GPTone texts). RF classifiers showed the best precision for the human public comments of approximately 90%, and the best precision for the fake public comments generated by GPT (GPTzero and GPTone) was 99.5% by focusing on integrated next writing style features: phrase patterns, parts-of-speech (POS) bigram and trigram, and function words. Therefore, the current study concluded that we could discriminate between GPT-generated fake public comments and those written by humans at the present time. [ABSTRACT FROM AUTHOR]

Candida albicans is a commensal yeast that has important impacts on host metabolism and immune function, and can establish life-threatening infections in immunocompromised individuals. Previously, C. albicans colonization has been shown to contribute to the progression and severity of alcoholic liver disease. However, relatively little is known about how C. albicans responds to changing environmental conditions in the GI tract of individuals with alcohol use disorder, namely repeated exposure to ethanol. In this study, we repeatedly exposed C. albicans to high concentrations (10% vol/vol) of ethanol—a concentration that can be observed in the upper GI tract of humans following consumption of alcohol. Following this repeated exposure protocol, ethanol small colony (Esc) variants of C. albicans isolated from these populations exhibited increased ethanol tolerance, altered transcriptional responses to ethanol, and cross-resistance/tolerance to the frontline antifungal fluconazole. These Esc strains exhibited chromosomal copy number variations and carried polymorphisms in genes previously associated with the acquisition of fluconazole resistance during human infection. This study identifies a selective pressure that can result in evolution of fluconazole tolerance and resistance without previous exposure to the drug. [ABSTRACT FROM AUTHOR]

COVID-19 has a range of complications, from no symptoms to severe pneumonia. It can also affect multiple organs including the nervous system. COVID-19 affects the brain, leading to neurological symptoms such as delirium. Delirium, a sudden change in consciousness, can increase the risk of death and prolong the hospital stay. However, research on delirium prediction in patients with COVID-19 is insufficient. This study aimed to identify new risk factors that could predict the onset of delirium in patients with COVID-19 using machine learning (ML) applied to nursing records. This retrospective cohort study used natural language processing and ML to develop a model for classifying the nursing records of patients with delirium. We extracted the features of each word from the model and grouped similar words. To evaluate the usefulness of word groups in predicting the occurrence of delirium in patients with COVID-19, we analyzed the temporal changes in the frequency of occurrence of these word groups before and after the onset of delirium. Moreover, the sensitivity, specificity, and odds ratios were calculated. We identified (1) elimination-related behaviors and conditions and (2) abnormal patient behavior and conditions as risk factors for delirium. Group 1 had the highest sensitivity (0.603), whereas group 2 had the highest specificity and odds ratio (0.938 and 6.903, respectively). These results suggest that these parameters may be useful in predicting delirium in these patients. The risk factors for COVID-19-associated delirium identified in this study were more specific but less sensitive than the ICDSC (Intensive Care Delirium Screening Checklist) and CAM-ICU (Confusion Assessment Method for the Intensive Care Unit). However, they are superior to the ICDSC and CAM-ICU because they can predict delirium without medical staff and at no cost. [ABSTRACT FROM AUTHOR]

This study explores the determinants of the export performance of Indonesia's low-, medium-, and high-technology manufacturing industries by focusing on the role of raw-material imports and technical efficiency. Micro firm-level data from 2010–2015 were utilized for the analysis in this study. The stochastic frontier analysis was employed to measure technical inefficiency and to determine its effect on export performance. Our findings indicate that in all categories of industry technical efficiency, raw materials imports, foreign direct investment (FDI), location, firm size, labour productivity, and concentration of industries were significant determinants of export performance. While high efficiency increases exports in low- and medium-technology firms, exports decrease in firms with high efficiency accompanied by high imports, FDI, size, and labour productivity. Furthermore, in high-technology industries, efficiency reduces exports and again increases them when mediated by a concentration of industries and location. The empirical strategy also supports the positive effect of imports on export performance in both industries, which also aligns with decreased exports in firms with high imports accompanied by high FDI, efficiency, labour productivity, the concentration of industries, and size. To this end, the study has implications for low-, medium-, and high-technology manufacturing that are mainly concerned with increasing exports. [ABSTRACT FROM AUTHOR]

The ironwood tree (Casuarina equisetifolia, family Casuarinaceae), an indigenous agroforestry species in Guam, has been threatened by ironwood tree decline (IWTD) since 2002. Formation of bacterial ooze by the wilt pathogen from the Ralstonia solanacearum species complex and wetwood bacteria (primarily Klebsiella species) has been linked to IWTD. In addition, termite infestation of trees was statistically associated with IWTD. Termites are known carriers of a diverse microbiome. Therefore, we hypothesized that termites could be vectors of bacteria linked to IWTD. To investigate the potential role of termites as pathogen vectors, we employed next-generation 16S rRNA gene sequencing to describe the bacteria diversity of Nasutitermes takasagoensis (Family Termitidae) workers collected from 42 ironwood trees of different disease stages in Guam in association with tree-, plot-, and location-related factors. Nasutitermes takasagoensis workers account for the majority of termite infestations of ironwood trees. The bacterial phyla composition of N. takasagoensis workers was typical for wood-feeding higher termites consisting mainly of Spirochaetes and Fibrobacteres. However, Ralstonia species were not detected and Klebsiella species were rare even in termites collected from trees infected with Ralstonia and wetwood bacteria. Feeding experiments suggested that termites prefer to consume wood with low pathogen content over wood with high pathogen load. Termites were able to ingest Ralstonia but Ralstonia could not establish itself in healthy termite bodies. We concluded that N. takasagoensis workers are not vectors for Ralstonia spp. or the bacterial endophytes associated with wetwood (Klebsiella, Pantoea, Enterobacter, Citrobacter, and Erwinia) that were previously observed in IWTD-infested trees. The bacterial diversity in termite samples was significantly influenced by various factors, including Tree Health, Site Management, Plot Average Decline Severity, Proportion of Dead Trees in the Plot, Proportion of Trees with Termite Damage in the Plot, Presence of Ralstonia, and Altitude. [ABSTRACT FROM AUTHOR]

Knowledge of the 10B microdistribution is of great relevance in BNCT studies. Since 10B concentration assesment through neutron autoradiography depends on the correct quantification of tracks in a nuclear track detector, image acquisition and processing conditions should be controlled and verified, in order to obtain accurate results to be applied in the frame of BNCT. With this aim, an image verification process was proposed, based on parameters extracted from the quantified nuclear tracks. Track characterization was performed by selecting a set of morphological and pixel-intensity uniformity parameters from the quantified objects (area, diameter, roundness, aspect ratio, heterogeneity and clumpiness). Their distributions were studied, leading to the observation of varying behaviours in images generated by different samples and acquisition conditions. The distributions corresponding to samples coming from the BNC reaction showed similar attributes in each analyzed parameter, proving to be robust to the experimental process, but sensitive to light and focus conditions. Considering those observations, a manual feature extraction was performed as a pre-processing step. A Support Vector Machine (SVM) and a fully dense Neural Network (NN) were optimized, trained, and tested. The final performance metrics were similar for both models: 93%-93% for the SVM, vs 94%-95% for the NN in accuracy and precision respectively. Based on the distribution of the predicted class probabilities, the latter had a better capacity to reject inadequate images, so the NN was selected to perform the image verification step prior to quantification. The trained NN was able to correctly classify the images regardless of their track density. The exhaustive characterization of the nuclear tracks provided new knowledge related to the autoradiographic images generation. The inclusion of machine learning in the analysis workflow proves to optimize the boron determination process and paves the way for further applications in the field of boron imaging. [ABSTRACT FROM AUTHOR]

Background: Endocytoscopy (EC) is a nuclei and micro-vessels visualization in real-time and can facilitate "optical biopsy" and "virtual histology" of colorectal lesions. This study aimed to investigate the significance of employing artificial intelligence (AI) in the field of endoscopy, specifically in diagnosing colorectal lesions. The research was conducted under the supervision of experienced professionals and trainees. Methods: EMBASE, PubMed, Cochrane Library, Web of Science, Chinese National Knowledge Infrastructure (CNKI) database, and other potential databases were surveyed for articles related to the EC with AI published before September 2023. RevMan (5.40), Stata (14.0), and R software (4.1.0) were used for statistical assessment. Studies that measured the accuracy of EC using AI for colorectal lesions were included. Two authors independently assessed the selected studies and their extracted data. This included information such as the country, literature, total study population, study design, characteristics of the fundamental study and control groups, sensitivity, number of samples, assay methodology, specificity, true positives or negatives, and false positives or negatives. The diagnostic accuracy of EC by AI was determined by a bivariate random-effects model, avoiding a high heterogeneity effect. The ANOVA model was employed to determine the more effective approach. Results: A total of 223 studies were reviewed; 8 articles were selected that included 2984 patients (4241 lesions) for systematic review and meta-analysis. AI assessed 4069 lesions; experts diagnosed 3165 and 5014 by trainees. AI demonstrated high accuracy, sensitivity, and specificity levels in detecting colorectal lesions, with values of 0.93 (95% CI: 0.90, 0.95) and 0.94 (95% CI: 0.73, 0.99). Expert diagnosis was 0.90 (95% CI: 0.85, 0.94), 0.87 (95% CI: 0.78, 0.93), and trainee diagnosis was 0.74 (95% CI: 0.67, 0.79), 0.72 (95% CI: 0.62, 0.80). With the EC by AI, the AUC from SROC was 0.95 (95% CI: 0.93, 0.97), therefore classified as excellent category, expert showed 0.95 (95% CI: 0.93, 0.97), and the trainee had 0.79 (95% CI: 0.75, 0.82). The superior index from the ANOVA model was 4.00 (1.15,5.00), 2.00 (1.15,5.00), and 0.20 (0.20,0.20), respectively. The examiners conducted meta-regression and subgroup analyses to evaluate the presence of heterogeneity. The findings of these investigations suggest that the utilization of NBI technology was correlated with variability in sensitivity and specificity. There was a lack of solid evidence indicating the presence of publishing bias. Conclusions: The present findings indicate that using AI in EC can potentially enhance the efficiency of diagnosing colorectal abnormalities. As a valuable instrument, it can enhance prognostic outcomes in ordinary EC procedures, exhibiting superior diagnostic accuracy compared to trainee-level endoscopists and demonstrating comparability to expert endoscopists. The research is subject to certain constraints, namely a limited number of clinical investigations and variations in the methodologies used for identification. Consequently, it is imperative to conduct comprehensive and extensive research to enhance the precision of diagnostic procedures. [ABSTRACT FROM AUTHOR]