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. Future research should pay more attention to the addition of novel promising predictors, external validation, and head-to-head comparisons of existing models.Assessment of patient-reported outcome measures (PROMs) in spinocerebellar ataxias (SCAs) could provide valuable insights into self-perceived health status. Although they are considered additional endpoints in future clinical trials, determinants and interactions of different PROMs in early disease stages remain largely unknown. The aims of the present study were to evaluate health-related quality of life, depressive symptoms, fatigue, and physical activity in mildly to moderately affected SCA3 patients and to examine interrelations between these PROMs and objective disease severity indices. Twenty SCA3 patients and twenty healthy controls of comparable age and sex completed the EQ-5D-5L, Patient Health Questionnaire-9, Profile of Mood States, and International Physical Activity Questionnaire. Disease severity was quantified by the Scale for the Assessment and Rating of Ataxia (SARA) and Inventory of Non-Ataxia Signs (INAS). Mildly to moderately affected SCA3 patients reported lower quality of life (p = 0.049h ataxia severity and extracerebellar involvement, and could therefore represent a useful marker of motor impairment in a home setting.We compared gender dysphoria (GD) patients and their same-sex siblings in terms of their 2D4D ratios, which may reflect prenatal exposure to androgen, one of the possible etiological mechanisms underlying GD. Sixty-eight GD patients (46 Female-to-Male [FtM]; 22 Male-to-Female [MtF]), 68 siblings (46 sisters of FtMs; 22 brothers of MtFs), and 118 heterosexual controls (62 female; 56 male) were included in the study. FtMs were gynephilic and MtFs were androphilic. We found that 2D4D ratios in the both right hand (p less then .001) and the left hand (p = .003) were lower in male controls than in female controls. Regarding right hands, FtM GD patients had lower 2D4D ratios than female controls (p less then .001) but their ratios did not differ from those of their sisters or male controls. STSinhibitor FtM GD patients had no significant difference in their left-hand 2D4D ratios compared to their sisters or female and male controls. While there was no significant difference in right hands between FtM's sisters and male controls, left-hand 2D4D ratios were significantly higher in FtM's sisters (p = .017). MtF GD patients had lower right-hand 2D4D ratios than female controls (p less then .001), but their right-hand ratios did not differ from those of their brothers and male controls. There was no significant difference in left-hand 2D4D ratios between MtF GD patients, and their brothers, or female and male controls. FtM GD patients showed significantly masculinized right-hand 2D4D ratios, while there was no evidence of feminization in MtF GD patients.
TwPDR1, a PDR transporter from Tripterygium wilfordii Hook.f., was proved to efflux triptolide and its stability could be enhanced by A
T mutation. Triptolide, an abietane-type diterpene in Tripterygium wilfordii Hook.f., possesses many pharmacological activities. However, triptolide is in short supply and very expensive because it is present at low amounts in natural plants and lack alternative production methods. Transporter engineering, which increases the extracellular secretion of secondary metabolites in in vitro culture systems, is an effective strategy in metabolic engineering but is rarely reported. In this study, TwPDR1, a pleiotropic drug resistance-type ATP binding cassette transporter, was identified as the best efflux pump candidate for diterpenoids through bioinformatics analysis. TwPDR1 was located in the plasma membrane, highly expressed in adventitious roots, and induced by methyl jasmonate. The triptolide efflux function of TwPDR1 was confirmed by transient expression in tobacco BY-2 celein stability. We identified the A1033 residue in TwPDR1 by sequence alignment and confirmed that A1033T mutation could increase the expression of TwPDR1 and result in the higher release ratio of triptolide (78.8%) of the mutants than that of control (60.1%). The identification and functional characterization of TwPDR1 will not only provide candidate gene material for the metabolic engineering of triptolide but also guide other transporter engineering researches in the future.
Body composition is associated with survival outcome in oncological patients, but it is not routinely calculated. Manual segmentation of subcutaneous adipose tissue (SAT) and muscle is time-consuming and therefore limited to a single CT slice. Our goal was to develop an artificial-intelligence (AI)-based method for automated quantification of three-dimensional SAT and muscle volumes from CT images.
Ethical approvals from Gothenburg and Lund Universities were obtained. Convolutional neural networks were trained to segment SAT and muscle using manual segmentations on CT images from a training group of 50 patients. The method was applied to a separate test group of 74 cancer patients, who had two CT studies each with a median interval between the studies of 3 days. Manual segmentations in a single CT slice were used for comparison. The accuracy was measured as overlap between the automated and manual segmentations.
The accuracy of the AI method was 0.96 for SAT and 0.94 for muscle. The average differences in volumes were significantly lower than the corresponding differences in areas in a single CT slice 1.8% versus 5.0% (p < 0.001) for SAT and 1.9% versus 3.9% (p < 0.001) for muscle. The 95% confidence intervals for predicted volumes in an individual subject from the corresponding single CT slice areas were in the order of ± 20%.
The AI-based tool for quantification of SAT and muscle volumes showed high accuracy and reproducibility and provided a body composition analysis that is more relevant than manual analysis of a single CT slice.
The AI-based tool for quantification of SAT and muscle volumes showed high accuracy and reproducibility and provided a body composition analysis that is more relevant than manual analysis of a single CT slice.
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