Bacterial biofilms are usually assumed to originate from individual cells deposited on a surface. However, many biofilm-forming bacteria tend to aggregate in the planktonic phase so that it is ...possible that many natural and infectious biofilms originate wholly or partially from pre-formed cell aggregates. Here, we use agent-based computer simulations to investigate the role of pre-formed aggregates in biofilm development. Focusing on the initial shape the aggregate forms on the surface, we find that the degree of spreading of an aggregate on a surface can play an important role in determining its eventual fate during biofilm development. Specifically, initially spread aggregates perform better when competition with surrounding unaggregated bacterial cells is low, while initially rounded aggregates perform better when competition with surrounding unaggregated cells is high. These contrasting outcomes are governed by a trade-off between aggregate surface area and height. Our results provide new insight into biofilm formation and development, and reveal new factors that may be at play in the social evolution of biofilm communities.
Chinese artichoke tuber (Stachys sieboldii Miq.) is used as an herbal medicine as well as edible food. This study examined the effect of the Chinese artichoke extracts on the nuclear factor erythroid ...2-related factor 2 (Nrf2)–antioxidant response element (ARE) pathway that induces the expression of antioxidant enzymes to explore its novel characteristics. Hot water extracts exhibited relatively high ARE activity. ARE activity was observed in two fractions when the hot water extracts were separated in the presence of trifluoroacetic acid using HPLC. Conversely, the highly active fraction disappeared when the hot water extracts were separated in the absence of trifluoroacetic acid. These results indicate that acidic degradation produces active ingredients. The structural analysis of the two active fractions identified harpagide, which is an iridoid glucoside, and harpagogenin. In vitro experiments revealed that harpagide was converted into harpagogenin under acidic conditions and that harpagogenin, but not harpagide, had potent ARE activity. Therefore, this study identified harpagogenin, which is an acid hydrolysate of harpagide, as an ARE activator and suggests that Nrf2–ARE pathway activation by Chinese artichoke contributes to the antioxidative effect.
Synthetic FLAIR images are of lower quality than conventional FLAIR images. Here, we aimed to improve the synthetic FLAIR image quality using deep learning with pixel-by-pixel translation through ...conditional generative adversarial network training.
Forty patients with MS were prospectively included and scanned (3T) to acquire synthetic MR imaging and conventional FLAIR images. Synthetic FLAIR images were created with the SyMRI software. Acquired data were divided into 30 training and 10 test datasets. A conditional generative adversarial network was trained to generate improved FLAIR images from raw synthetic MR imaging data using conventional FLAIR images as targets. The peak signal-to-noise ratio, normalized root mean square error, and the Dice index of MS lesion maps were calculated for synthetic and deep learning FLAIR images against conventional FLAIR images, respectively. Lesion conspicuity and the existence of artifacts were visually assessed.
The peak signal-to-noise ratio and normalized root mean square error were significantly higher and lower, respectively, in generated-versus-synthetic FLAIR images in aggregate intracranial tissues and all tissue segments (all
< .001). The Dice index of lesion maps and visual lesion conspicuity were comparable between generated and synthetic FLAIR images (
= 1 and .59, respectively). Generated FLAIR images showed fewer granular artifacts (
= .003) and swelling artifacts (in all cases) than synthetic FLAIR images.
Using deep learning, we improved the synthetic FLAIR image quality by generating FLAIR images that have contrast closer to that of conventional FLAIR images and fewer granular and swelling artifacts, while preserving the lesion contrast.
Portal vein complications (PVCs) after adult living donor liver transplantation (LDLT) are potentially lethal. We categorized PVCs by the time of onset (early versus late, <1 month versus ≥1 month, ...respectively) and deformity patterns (portal vein stenosis PVS, portal vein thrombosis PVT, and portal vein occlusion PVO) to establish optimal treatment strategies. Overall, 35/322 (10.9%) recipients developed PVCs between 2000 and 2019. Pretransplant PVT (odds ratio OR, 15.20; 95% confidence interval CI, 3.70‐62.40; P < 0.001) was the only independent risk factor for PVS. In contrast, male sex (OR, 5.57; 95% CI, 1.71‐18.20; P = 0.004), pretransplant PVT (OR, 4.79; 95% CI, 1.64‐14.00; P = 0.004), and splenectomy (OR, 3.24; 95% CI, 1.23‐8.57; P = 0.018) were independent risk factors for PVT. PVS was successfully treated with interventional radiology regardless of its time of onset. On the other hand, late PVT and PVO had significantly lower treatment success rates (2/15, 13%) compared with those that occurred in the early period (10/11, 91%) despite aggressive intervention (P < 0.001). Deformity patterns had a significant impact on the 5‐year cumulative incidence of graft loss as a result of PVC (PVO + Yerdel grades 2‐4 PVT group n = 16, 41% versus PVS + Yerdel grade 1 PVT group n = 19, 0%; P = 0.02). In conclusion, late grades 2 to 4 PVT and PVO are refractory to treatment and associated with poor prognoses, whereas PVS has a good prognosis regardless of time of onset. A tailored approach according to the time of onset and deformity patterns of PVC is essential.
Hepatoblastoma (HB) is the most common malignant liver tumor in children. Although the development of treatment strategies with advances in chemotherapy has greatly improved the prognosis of HB, ...surgical resection and liver transplantation still play a vital role in the treatment of HB. In recent years, technological innovations have led to the development of new surgical approaches for HB. In this review, we describe the latest research on the surgical management of HB, including new imaging technologies, minimally invasive approaches, and the application of associating liver partition portal vein ligation for staged hepatectomy. We also discuss the current role of liver transplantation, use of ante‐situm or ex‐situ liver resection with auto‐transplantation, and management of metastatic HB.
Hepatoblastoma is the most common malignant liver tumor in children. In this review, we describe the latest technologies and techniques for the surgical management of hepatoblastoma, including new imaging technologies, minimally invasive approaches, and the application of associating liver partition portal vein ligation for staged hepatectomy. We also discuss the current role of liver transplantation, liver transplant‐related surgical techniques, and management of metastatic hepatoblastoma.
The benchmark dose (BMD) approach is updated to create an international harmonizing process following rapid theoretical sophistication. We calculated the lower limit of BMD confidence interval (BMDL) ...for carcinogenicity based on 193 tumorigenicity bioassay data published in 50 pesticide risk assessment reports by the Food Safety Commission of Japan (FSCJ) to validate the appropriateness and necessity for the refinement of the FSCJ-established BMD guidance. Three well-known BMD software, PROAST, BMDS, and BBMD were used to compare their BMDLs with no-observed-adverse-effect levels (NOAELs) for carcinogenicity. Recently implemented methodologies such as model averaging or Bayesian inference were also used. Our results indicate that the BMD approach provides a point of departure similar to the NOAEL approach if the data used exhibit a clear dose-response relationship. In some cases, particularly in software with a frequentist approach, the calculation failed to provide BMDL or provided considerably lower BMDLs than NOAELs. However, most of the datasets that resulted in failed calculations or extremely low BMDLs exhibited unclear dose-response relationships, i.e., non-monotonous and sporadic responses. The expert review on the shape of the dose-response plot would help better apply the BMD approach. Furthermore, we observed that Bayesian approaches provided fewer failed or extreme BMD calculations than the frequentist approaches.
•Different software to compare BMDL with NOAEL.•Validated the appropriateness and necessity of refinement of the BMD guidance.•193 datasets were used from carcinogenicity studies of 50 pesticides in rat or mice.
Purpose
Image contrast differs between conventional multislice turbo spin echo (conventional TSE) and multiband turbo spin echo (SMS-TSE). Difference in time interval between excitations for adjacent ...slices (SETI) might cause this difference. This study aimed to evaluate the influence of SETI on MT effect for conventional TSE and compare conventional TSE with SMS-TSE in this respect.
Materials and methods
Three different agar concentration phantoms were scanned with conventional TSE by adjusting SETI and TR. Signal change for different SETI was evaluated using Pearson’s correlation analysis. SMS-TSE was acquired by changing TR similarly. Three human volunteers were scanned with similar settings to evaluate reproducibility of the phantom results in human brain.
Results
In conventional TSE, shorter SETI induced larger signal reduction. Longer TR and higher agar concentration emphasized this characteristic. Significant linear correlation (
P
< 0.05) was found in the major cases. The SMS-TSE signal intensity in each TR and phantom was smaller than the assumable levels in conventional TSE when the slices were simultaneously excited. Similar characteristic was observed in human brain.
Conclusion
Shorter SETI results in larger MT effect in conventional TSE. The contrast change in SMS-TSE was larger than the supposable level from simultaneous excitation, which needs consideration in clinics.
Aims/Introduction
To evaluate the efficacy and safety of once‐weekly (q.w.) extended‐release exenatide after switching from twice‐daily (b.i.d.) exenatide in patients with type 2 diabetes.
Materials ...and Methods
This was an investigator‐initiated, prospective, single‐arm, multicenter study. Individuals with type 2 diabetes who had been treated with exenatide b.i.d. for at least 3 months were enrolled and switched to exenatide q.w. for 24 weeks. The primary end‐point was change in HbA1c at week 24 to test the glucose‐lowering effect of exenatide q.w. versus exenatide b.i.d.
Results
A total of 58 Japanese individuals with type 2 diabetes completed the study. Glycated hemoglobin was reduced by 0.2% at week 24 (7.2 ± 1.2% vs 7.0 ± 1.2% 56 ± 13 vs 53 ± 13 mmol/mol, 95% confidence interval −0.4 to −0.03%, P < 0.005 for non‐inferiority, P = 0.01 for superiority). Fasting plasma glucose was reduced by 12 mg/dL at week 24 (154 ± 46 vs 142 ± 46 mg/dL, P = 0.02). β‐Cell function assessed by homeostasis model assessment of β‐cell function and C‐peptide index was significantly improved at week 24. The incidence of self‐reported hypoglycemia was reduced, and treatment satisfaction assessed by the Diabetes Treatment Satisfaction Questionnaire and Diabetes Medication Satisfaction Questionnaire was improved at week 24, with no change in body weight. There was no serious adverse event related to the study drug.
Conclusions
Switching from exenatide b.i.d. to exenatide q.w. resulted in a reduction in glycated hemoglobin, fasting plasma glucose and the incidence of hypoglycemia, and improvement in β‐cell function and treatment satisfaction in patients with type 2 diabetes. These findings will be useful for selecting optimal treatment in individuals with type 2 diabetes.
In the present study, we report the efficacy and safety of once‐weekly extended‐release exenatide after switching from twice‐daily exenatide in Japanese patients with type 2 diabetes.
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