We have developed a one‐pot procedure for the preparation of N,N‐disubstituted (Z)‐4‐(halomethylidene)‐4H‐3,1‐benzothiazin‐2‐amines 3 from 2‐(2,2‐dihaloethenyl)phenyl isothiocyanates 1, easily ...accessible from known 2‐(2,2‐dihaloethenyl)benzenamines by a three‐step sequence, and secondary amines. Thus, the isothiocyanates 1 react with secondary amines to afford the corresponding thiourea derivatives, of which the treatment with NaH provides the desired products.
Porphyran (POR) from the red alga Porphyra yezoensis is a water soluble dietary fiber. In this study, we investigated the effect of dietary POR on glucose metabolism in KK-Ay mice (a model for type 2 ...diabetes). Mice were divided into 4 groups and fed a diet containing 5% cellulose (control), POR, POR Arg or POR K. After 3 wk of feeding, plasma insulin levels and the calculated homeostasis model assessment-insulin resistance (HOMA-IR) index were significantly lower in the POR group than in the control group. Compared with the control group, plasma adiponectin levels were significantly increased in the POR, POR Arg and POR K groups. These results suggest that dietary POR should improve glucose metabolism in diabetes via up-regulation of adiponectin levels. In addition, the amount of propionic acid in the cecum of the POR group was significantly higher than in the control group and the profile of bacterial flora was changed by dietary POR. In the cecum of the POR, POR Arg and POR K groups, Bacteroides was significantly increased and Clostridium coccoides was significantly decreased compared with in the control group. The effects of dietary POR on the hindgut environment might contribute to the improvement of glucose metabolism.
To manage refractory and invasive glioblastomas (GBM)s, photodynamic therapy (PDT) using talaporfin sodium (NPe6) (NPe6-PDT) was recently approved in clinical practice. However, the molecular ...machineries regulating resistance against NPe6-PDT in GBMs and mechanisms underlying the changes in GBM phenotypes following NPe6-PDT remain unknown. Herein, we established an in vitro NPe6-mediated PDT model using human GBM cell lines. NPe6-PDT induced GBM cell death in a NPe6 dose-dependent manner. However, this NPe6-PDT-induced GBM cell death was not completely blocked by the pan-caspase inhibitor, suggesting NPe6-PDT induces both caspase-dependent and -independent cell death. Moreover, treatment with poly (ADP-ribose) polymerase inhibitor blocked NPe6-PDT-triggered caspase-independent GBM cell death. Next, it was also revealed resistance to re-NPe6-PDT of GBM cells and GBM stem cells survived following NPe6-PDT (NPe6-PDT-R cells), as well as migration and invasion of NPe6-PDT-R cells were enhanced. Immunoblotting of NPe6-PDT-R cells to assess the behavior of the proteins that are known to be stress-induced revealed that only ERK1/2 activation exhibited the same trend as migration. Importantly, treatment with the MEK1/2 inhibitor trametinib reversed resistance against re-NPe6-PDT and suppressed the enhanced migration and invasion of NPe6-PDT-R cells. Overall, enhanced ERK1/2 activation is suggested as a key regulator of elevated malignant phenotypes of GBM cells surviving NPe6-PDT and is therefore considered as a potential therapeutic target against GBM.
This study addresses the challenging problem of efficient buffer allocation in production lines. Suitable locations for buffer allocation are determined to satisfy the desired throughput, while a ...suitable balance between solution quality and computation time is achieved. A throughput calculation approach that yields the state probability of production lines is adopted to evaluate the effectiveness of candidate buffer allocation solutions. To generate candidate buffer allocation solutions, an active probability index based on state probability is proposed to rapidly detect suitable locations of buffer allocations. A variable neighborhood search algorithm is used to maintain acceptable solution quality; an additional neighborhood structure is used in the case where no satisfactory solution is generated in the initial neighborhood structure. Extensive numerical experiments demonstrate the efficacy of the proposed approach. The proposed approach can facilitate agile design of production lines in industry by rapidly estimating production line topologies.
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Based on a study of the structure–activity relationship of methyl jasmonate (MeJA), an antibolting agrochemical was developed as a test case. Consequently, ent-MeJA was found to be a ...promising antibolting agent because the compound showed the bolting inhibition activity lacking leaf senescence inducing activity. During field experiments, applying ent-MeJA could prevent radish plants from bolting without inhibiting leaf and root growth. Therefore, ent-MeJA was considered a potential antibolting agrochemical for radishes.
Background: Reports on the prognostic significance of serum γ-glutamyltransferase (GGT) in men with metastatic castration-resistant prostate cancer (mCRPC) are limited. In addition, GGT expression ...status in cancer tissues has not been well characterized regardless of cancer types. Methods: This retrospective study included 107 consecutive men with mCRPC receiving docetaxel therapy. The primary endpoints were associations of serum GGT with overall survival (OS) and prostate-specific antigen (PSA) response. The secondary endpoint was an association of serum GGT with progression-free survival (PFS). Additionally, GGT expression status was immunohistochemically semi-quantified using tissue microarrays. Results: A total of 67 (63%) men died during follow-up periods (median 22.5 months for survivors). On multivariable analysis, high Log GGT was independently associated with adverse OS (HR 1.49, p = 0.006) as were low hemoglobin (HR 0.79, p = 0.002) and high PSA (HR 1.40, p < 0.001). In contrast, serum GGT was not significantly associated with PSA response or PFS. Moreover, incorporation of serum GGT into established prognostic models (i.e., Halabi and Smaletz models) increased their C-indices for predicting OS from 0.772 to 0.787 (p = 0.066) and from 0.777 to 0.785 (p = 0.118), respectively. Furthermore, there was a positive correlation between serum and tissue GGT levels (ρ = 0.53, p = 0.003). Conclusions: Serum GGT may be a prognostic biomarker in men with mCRPC receiving docetaxel therapy. GGT overexpression by prostate cancer cells appears to be responsible for the elevation of GGT in the serum.
Background
Esophageal thermal lesion (ETL) is a complication of radiofrequency ablation for atrial fibrillation (RFAF). To prospectively compare the incidence of ETL, we used two linear, five‐ and ...three‐sensor esophageal thermal monitoring catheters (ETMC5 and ETMC3). We also evaluated the predictors of ETL.
Methods
Patients receiving their first RFAF (n = 106) were randomized into two groups, ETMC5 (n = 52) and ETMC3 (n = 54). Ablation was followed by esophagogastroduodenoscopy within 3 days.
Results
Esophageal thermal lesion was detected in 7/106 (6.6%) patients (ETMC5: 3/52 5.8% vs. ETMC3: 4/54 7.4%; p = 1.0). The maximum temperature and number of measurements > 39.0°C did not differ between the groups (ETMC5: 40.5°C and 5.4 vs. ETMC3: 40.6°C and 4.9; p = .83 and p = .58, respectively). In ETMC5 group, the catheter had to be moved significantly less often (0.12 vs. 0.42; p = .0014) and fluoroscopy time was significantly shorter (79.2 min vs. 101.7 min; p = .0038) compared with ECMC3 group. The total number of ablations in ETMC5 group was significantly greater (50.2 vs. 37.7; p = .030) and ablation time was significantly longer (52.1 min vs. 40.1 min; p = .0039). Only body mass index (BMI) was significantly different between patients with and without ETL (21.4 ± 2.5 vs. 24.3 ± 3.4; p = .022).
Conclusions
The incidence of ETL was comparable between ETMC5 and ETMC3 groups; however, fluoroscopy time, total ablation time, and total number of ablations differed significantly. Lower BMI may increase the risk of developing ETL.
In 2013, the Ministry of Health, Labor, and Welfare (MHLW) in Japan announced a suspension of the governmental recommendation for routine HPV vaccinations. In 2020, MHLW started individual ...notifications of HPV vaccine to the targeted girls. In April 2022, the governmental recommendation was restarted, and catch-up vaccinations started. We evaluated the benefits and limitations of the MHLW’s new vaccination strategies by estimating the lifetime risk for cervical cancer for each birth FY under different scenarios to suggest a measure for the vaccine suspension generation. It was revealed that catch-up immunization coverage among the unvaccinated must reach as high as 90% in FY2022, when the program begins, in order to reduce the risk of the females already over the targeted ages to the same level or lower than that of women born in FY1994-1999 who had high HPV vaccination rates. For women whose vaccination coverage waned because of their birth FYs, strong recommendations for cervical cancer screening should be implemented.
Abstract
This study sought to optimise the swallowing computed tomography (SCT) scan protocol for use with the new wide-area detector-row CT (ADCT) scanner and to estimate patient dose in terms of ...the organ-absorbed dose and the effective dose. The conventional ADCT (ADCTViSION) and the new ADCT (ADCTGENESIS) scanner were compared using: (1) the organ-absorbed dose and the effective dose, with a phantom study, (2) the detailed organ-absorbed doses of the neck region, using a Monte Carlo simulation and (3) a relative visual quality analysis. The effective energy differed significantly between the ADCTViSION (50 keV) and the ADCTGENESIS (57 keV). The effective doses were 2.9 and 1.9 mSv, respectively. Compared with the ADCTViSION, the absorbed dose was reduced by 34% with the ADCTGENESIS. With the ADCTGENESIS, the tube current could be reduced from 40 to 30 mA. With the optimised scan protocol, a further 25% dose reduction can be achieved.
There is no gold standard indicator that is currently used to predict posthepatectomy liver failure (PHLF). A novel indicator of liver function, the LU15 index of .sup.99m Tc-galactosyl serum albumin ...(GSA) scintigraphy, refers to the liver uptake ratio over a 15-min interval. We aimed to evaluate the usefulness of the future liver remnant (FLR)-LU15 in predicting PHLF. The clinical data of 102 patients (70 males and 32 females; median age, 70 years) who underwent liver resection between January 2011 and August 2019 were analyzed. The FLR-LU15 was calculated by a fusion of simulated 3-dimensional images and .sup.99m Tc-GSA scintigraphy. PHLF was determined according to the definition of the International Study Group of Liver Surgery. The FLR-LU15 was an independent risk factor for PHLF greater than or equal to Grade B according to multivariate analysis, and its value correlated with the PHLF grade. The area under the receiver operating characteristic curve of the FLR-LU15 for PHLF greater than or equal to Grade B was 0.816 (95% confidence interval, 0.704-0.929), which was better than that of other indicators. When the cut-off value of FLR-LU15 was set at 16.7, the sensitivity was 86.7%, specificity was 74.7%, and odds ratio was 19.2 (95% confidence interval, 4.0-90.9), all of which were superior to other indicators. If the cut-off value was 13, the positive predictive value was 57.1%. The FLR-LU15 is a useful predictor of PHLF and may be more reliable than other predictors.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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