Here, we present a method for concentrating radiocesium in seawater using ammonium molybdophosphate-polyacrylonitrile (AMP-PAN) resin using custom-made sample-loading equipment. It was designed to ...reduce analytical time and labor with eight peristaltic pumps connected in parallel with eight columns, each packed with AMP-PAN. Eighty liters of seawater containing radiocesium were concentrated to 0.01 L in 6 h with the proposed method and Cs recovery was > 85%. The minimum detectable activity was 0.2 mBq L
–1
at 160,000-s measurement with a high-purity germanium detector.
Extranodal NK/T-cell lymphoma is an aggressive lymphoma that is strongly associated with Epstein-Barr virus infection. Although some extranodal NK/T-cell lymphoma patients have shown responses to ...immune checkpoint blockade, biomarkers for predicting extranodal NK/T-cell lymphoma patient response to immunotherapy have not yet been defined. To understand the tumor immune microenvironment, we analyzed the expression of 579 immune-related genes and characterized the immune cells using immunohistochemistries and in situ hybridization for EBER. Based on comprehensive analyses, we developed an immune subtyping model that classifies extranodal NK/T-cell lymphoma patients into four tumor immune microenvironment subgroups using three immunohistochemical markers (FoxP3, PD-L1, and CD68). The four tumor immune microenvironment subgroups were named immune tolerance, immune evasion-A, immune evasion-B, and immune silenced. The immune tolerance group was characterized by high-Treg counts and was frequently observed in early stage, and nasal extranodal NK/T-cell lymphoma. The immune evasion group showed high cytotoxic T-cell counts and high PD-L1 expression but low Treg counts. In the immune-silenced group, almost all immune responses were exhausted, most patients were at an advanced stage, and had the poorest disease prognosis among the tumor immune microenvironment subgroups. In some patients (n = 3), a shift in the tumor immune microenvironment subgroup classification was observed in sequential biopsies. The response rate to pembrolizumab, an anti-PD-1 antibody, was 100% (1/1) in the immune tolerance group, 60% (3/5) in the immune evasion group, and 0% (0/5) in the immune-silenced group. We classified extranodal NK/T-cell lymphoma into four tumor immune microenvironment subgroups using a new classification system. In conclusion, we propose that the tumor immune microenvironment of extranodal NK/T-cell lymphoma may change during disease progression and may serve as a useful biomarker for immunotherapy.
The era of climate change strongly requires higher efficiency of energies, such as light, water, nutrients, etc., during crop production. Rice is the world's greatest water-consuming plant, and, ...thus, water-saving practices such as alternative wetting and drying (AWD) are widely recommended worldwide. However the AWD still has concerns such as lower tillering, shallow rooting, and an unexpected water deficit. The AWD is a possibility to not only save water consumption but also utilize various nitrogen forms from the soil. The current study tried to investigate the transcriptional expression of genes in relation to the acquisition-transportation-assimilation process of nitrogen using qRT-PCR at the tillering and heading stages and to profile tissue-specific primary metabolites. We employed two water supply systems, continuous flooding (CF) and alternative wetting and drying (AWD), during rice growth (seeding to heading). The AWD system is effective at acquiring soil nitrate; however, nitrogen assimilation was predominant in the root during the shift from the vegetative to the reproductive stage. In addition, as a result of the greater amino acids in the shoot, the AWD was likely to rearrange amino acid pools to produce proteins in accordance with phase transition. Accordingly, it is suggested that the AWD 1) actively acquired nitrate from soil and 2) resulted in an abundance of amino acid pools, which are considered a rearrangement under limited N availability. Based on the current study, further steps are necessary to evaluate form-dependent N metabolism and root development under the AWD condition and a possible practice in the rice production system.
Homologous recombination deficiency (HRD) stands as a clinical indicator for discerning responsive outcomes to platinum-based chemotherapy and poly ADP-ribose polymerase (PARP) inhibitors. One of the ...conventional approaches to HRD prognostication has generally centered on identifying deleterious mutations within the BRCA1/2 genes, along with quantifying the genomic scars, such as Genomic Instability Score (GIS) estimation with scarHRD. However, the scarHRD method has limitations in scenarios involving tumors bereft of corresponding germline data. Although several RNA-seq-based HRD prediction algorithms have been developed, they mainly support cohort-wise classification, thereby yielding HRD status without furnishing an analogous quantitative metric akin to scarHRD. This study introduces the expHRD method, which operates as a novel transcriptome-based framework tailored to n-of-1-style HRD scoring. The prediction model has been established using the elastic net regression method in the Cancer Genome Atlas (TCGA) pan-cancer training set. The bootstrap technique derived the HRD geneset for applying the expHRD calculation. The expHRD demonstrated a notable correlation with scarHRD and superior performance in predicting HRD-high samples. We also performed intra- and extra-cohort evaluations for clinical feasibility in the TCGA-OV and the Genomic Data Commons (GDC) ovarian cancer cohort, respectively. The innovative web service designed for ease of use is poised to extend the realms of HRD prediction across diverse malignancies, with ovarian cancer standing as an emblematic example. Our novel approach leverages the transcriptome data, enabling the prediction of HRD status with remarkable precision. This innovative method addresses the challenges associated with limited available data, opening new avenues for utilizing transcriptomics to inform clinical decisions.
Background:The ratio of the early transmitral flow velocity to early diastolic velocity of the mitral annulus (E/e′) is an echocardiographic index of mean left ventricular (LV) filling pressure. We ...investigated the association between the preoperative E/e′ ratio and postoperative acute kidney injury (AKI) during off-pump coronary artery bypass surgery (OPCAB).Methods and Results:We reviewed 585 patients who underwent OPCAB and with preserved LV ejection fraction determined by preoperative echocardiography. AKI was determined by the Kidney Disease Improving Global Outcomes (KDIGO) criteria. Multivariable logistic regression analysis was performed. E/e′ was also analyzed as 3 categories (E/e′ <8, 8≤E/e′≤15, and E/e′ >15) and as a continuous variable. A propensity score analysis was used to match the patients with E/e′ >15 and E/e′ ≤15. A preoperative E/e′ >15 was an independent predictor for AKI (odds ratio 3.01, 95% confidence interval 1.40–6.17). E/e′ >15 was also an independent predictor for AKI when E/e′ was analyzed with 3 categories or as a continuous variable. In the matched sample, the incidence of AKI and 1-year mortality was significantly higher in patients with E/e′ >15.Conclusions:Among patients undergoing OPCAB with preserved LV systolic function, a preoperative E/e′ ratio >15 was an independent predictor of postoperative AKI. Measurement of the preoperative E/e′ ratio may help to assess the risk of postoperative AKI.
Although a support vector machine (SVM) is one of the most frequently used classifiers in the field of intelligent transportation systems and shows competitive performances in various problems, it ...has the disadvantage of requiring relatively large computations in the testing phase. To make up for this weakness, diverse methods have been researched to reduce the number of support vectors determining the computations in the testing phase. This paper is intended to help engineers using the SVM to easily apply support vector number reduction to their own particular problems by providing a state-of-the-art survey and quantitatively comparing three implementations belonging to postpruning, which exploits the result of a standard SVM. In particular, this paper confirms that the support vector number of a pedestrian classifier using a histogram-of-oriented-gradient-based feature and a radial-basis-function-kernel-based SVM can be reduced by more than 99.5% without any accuracy degradation using iterative preimage addition, which can be downloaded from the Internet.
To achieve endemic phases, repeated vaccinations are necessary. However, individuals may grapple with whether to get vaccinated due to potential side effects. When an individual is already immune due ...to previous infections or vaccinations, the perceived risk from vaccination is often less than the risk of infection. Yet, repeated rounds of vaccination can lead to avoidance, impeding the establishment of endemic phases. We explore this phenomenon using an individual-based Monte Carlo simulation, validating our findings with game theory. The Nash equilibrium encapsulates individuals' non-cooperative behavior, while the system's optimal value represents the societal benefits of altruistic cooperation. We define the difference between these as the price of anarchy. Our simulations reveal that the price of anarchy must fall below a threshold of 12.47 for endemic phases to be achieved in a steady state. This suggests that for a basic reproduction number of 10, a consistent vaccination rate greater than 89% is required. These findings offer new insights into vaccination-related decision-making and can inform effective strategies to tackle infectious diseases.
Hunner-type interstitial cystitis (HIC) is a chronic inflammatory condition of the bladder. However, it remains unclear whether there is a causal relationship between the presence of Hunner lesions ...and seemingly normal-appearing areas in the bladder (non-Hunner lesions). This study aimed to investigate the fundamental aspects of HIC by examining potential genetic differences between Hunner and non-Hunner lesions and elucidate their role as potential markers in the progression and suppression of the disease.
This cross-sectional study enrolled patients with HIC (
= 10) who underwent supratrigonal cystectomy along with augmentation cystoplasty. Full-thickness bladder tissue was collected from Hunner and non-Hunner lesions in the same patient. Normal bladder tissue biopsies were also obtained as controls. Whole transcriptome analysis was performed to analyze the gene expression patterns and immune cell populations.
The mucosal layers of patients exhibited similar pathway dysregulation across Hunner and non-Hunner lesions, with immunerelated pathways being prominently affected. In the mucosal layer, genes related to anti-inflammatory and immune suppression were downregulated in Hunner lesions compared to non-Hunner lesions. Moreover, in Hunner lesions, genes related to macrophage differentiation and polarization, such as
,
,
, and
, were downregulated. The cell fraction of M2 macrophages was found to decrease in Hunner lesions. Immunohistochemical staining revealed an elevated fraction of M1 macrophages and a reduced fraction of M2 macrophages in Hunner lesions compared to those in non-Hunner lesions. In the muscular layer, transcriptomic evidence of muscle thickness was observed in both Hunner and non-Hunner lesions; however, the difference was not significant.
Hunner lesions showed a reduced expression of anti-inflammatory and immunosuppressive factors compared to non-Hunner lesions, along with alterations in immune cell populations. This study suggests the possibility that macrophage polarization is related to the progression from non-Hunner lesions to Hunner lesions, suggesting its relevance to the characteristics of autoimmune diseases.
Vegetarianism is on the rise worldwide and its importance is being emphasized in various ways, such as in its sustainability, environmental, food system, and ethical aspects. The purpose of the study ...is to identify motivations behind food choices and dietarian identity, to investigate the perceptions about plant-based foods, and to identify differences between vegetarians and omnivores. We conducted an online survey of 245 vegetarians and 246 omnivores. There was a significant difference between vegetarians and omnivores. In food choice motivations, vegetarians scored higher in the factors of 'ethical concern', 'health', and 'convenience and price', while omnivores responded higher in 'sensory appeal' and 'weight control' factors. In the dietarian identity, vegetarians scored higher in the 'complex motivation' and 'strictness' factors, while on the other hand omnivores scored higher in 'out-group regard' and 'public regard' factors. Although the reasons can be different, we confirmed that both vegetarians and omnivores are positive toward plant-based foods. Our results suggest that different strategies will be needed to promote plant-based food consumption to vegetarians and to omnivores.
BackgroundTargeting the DNA damage repair (DDR) pathways is an attractive strategy for boosting cancer immunotherapy. Ceralasertib (AZD6738) is an oral kinase inhibitor of ataxia telangiectasia and ...Rad3 related protein, which is a master regulator of DDR. We conducted a phase II trial of ceralasertib plus durvalumab in patients with previously treated advanced gastric cancer (AGC) to demonstrate the safety, tolerability, and clinical activity of the combination.MethodsThis phase II, open-label, single-center, non-randomized study was designed to evaluate the efficacy and safety of ceralasertib in combination with durvalumab in patients with AGC. The study drug regimen was ceralasertib (240 mg two times a day) days 15–28 in a 28-day cycle in combination with durvalumab (1500 mg) at day 1 every 4 weeks. The primary end point was overall response rate (ORR) by Response Evaluation Criteria in Solid Tumors (V.1.1). Exploratory biomarker analysis was performed using fresh tumor biopsies in all enrolled patients.ResultsAmong 31 patients, the ORR, disease control rate, median progression-free survival (PFS), and overall survival were 22.6% (95% CI 9.6% to 41.1%), 58.1% (95% CI 39.1% to 75.5%), 3.0 (95% CI 2.1 to 3.9) months, and 6.7 (95% CI 3.8 to 9.6) months, respectively. Common adverse events were manageable with dose modification. A subgroup of patients with a loss of ataxia telangiectasia mutated (ATM) expression and/or high proportion of mutational signature attributable to homologous repair deficiency (sig. HRD) demonstrated a significantly longer PFS than those with intact ATM and low sig. HRD (5.60 vs 1.65 months; HR 0.13, 95% CI 0.045 to 0.39; long-rank p<0.001). During the study treatment, upregulation of the innate immune response by cytosolic DNA, activation of intratumoral lymphocytes, and expansion of circulating tumor-reactive CD8 +T cell clones were identified in responders. Enrichment of the tumor vasculature signature was associated with treatment resistance.ConclusionsCeralasertib plus durvalumab has promising antitumor activity, with durable responses in patients with refractory AGC. Thus, a biomarker-driven trial is required.Trial registrationNCT03780608.
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