Kramersmidt2167
hat a numerically relevant subset of CRCs carrying heterozygous ATM mutations may benefit from the combination treatment with low doses of niraparib and irinotecan, suggesting a new potential approach in the treatment of ATM-mutated CRC, that deserves to be prospectively validated in clinical trials.
Organ transplantations cause discrepancy in results from cell-free DNA (cfDNA) testing, but scientific literature is scarce.
A 33-year old gravida underwent cfDNA testing, which showed high levels of Y chromosome (ChrY) in the maternal bloodstream. The ChrY pattern was comparable to an adult male reference. As a result, cfDNA testing was only informative for autosomes. Routine 20-week ultrasound scan showed no structural alterations and the presence of female external genitalia. Post-clinical research revealed that the patient received a bone marrow transplant from a male donor several years before. Fluorescence in situ hybridization showed that 100% of nuclei analysed from the patient's lymphocytes presented a ChrY.
This case demonstrates ChrY can be used as a marker to avoid sex discrepancies in certain patients with organ transplants.
This case demonstrates ChrY can be used as a marker to avoid sex discrepancies in certain patients with organ transplants.
To evaluate the genetic effects of sex hormone traits on the development of mental traits in middle-aged adults.
The SNPs associated with sex hormone traits were derived from a two-stage genome-wide association study (GWAS). Four sex hormone traits were selected in the current study, including sex hormone-binding globulin (SHBG), testosterone, bioavailable testosterone and estradiol. The polygenic risk score (PRS) of sex hormone traits were calculated from individual-level genotype data of the United Kingdom (UK) Biobank cohort. We then used logistic and linear regression models to assess the associations between individual PRS of sex hormone traits and the frequency of alcohol consumption, anxiety, intelligence and so on. LAQ824 Finally, gene-environment-wide interaction study (GEWIS) was performed to detect novel candidate genes interacting with the sex hormone traits on the development of fluid intelligence and the frequency of smoking and alcohol consumption by PLINK2.0.
We observed positive association between SHBG and the frequency of alcohol consumption (b = 0.0101, p = 3.84 × 10
) in middle-aged males and females. In addition, estradiol was positively associated with the frequency of alcohol consumption (b = 0.0128, p = 1.96 × 10
) in middle-aged males. Moreover, bioavailable testosterone was associated with the fluid intelligence (b = -0.0136, p = 5.74 × 10
) in middle-aged females. Finally, GEWIS identified one significant loci, Tenascin R (TNR) (rs34633780, p = 3.45 × 10
) interacting with total testosterone for fluid intelligence.
Our study results support the genetic effects of sex hormone traits on the development of intelligence and the frequency of alcohol consumption in middle-aged adults in UK.
Our study results support the genetic effects of sex hormone traits on the development of intelligence and the frequency of alcohol consumption in middle-aged adults in UK.
Insomnia as one of the dominant diseases of traditional Chinese medicine (TCM) has been extensively studied in recent years. To explore the novel approaches of research on TCM diagnosis and treatment, this paper presents a strategy for the research of insomnia based on machine learning.
First of all, 654 insomnia cases have been collected from an experienced doctor of TCM as sample data. Secondly, in the light of the characteristics of TCM diagnosis and treatment, the contents of research samples have been divided into four parts the basic information, the four diagnostic methods, the treatment based on syndrome differentiation and the main prescription. And then, these four parts have been analyzed by three analysis methods, including frequency analysis, association rules and hierarchical cluster analysis. Finally, a comprehensive study of the whole four parts has been conducted by random forest.
Researches of the above four parts revealed some essential connections. Simultaneously, based on the algorithm model established by the random forest, the accuracy of predicting the main prescription by the combinations of the four diagnostic methods and the treatment based on syndrome differentiation was 0.85. Furthermore, having been extracted features through applying the random forest, the syndrome differentiation of five zang-organs was proven to be the most significant parameter of the TCM diagnosis and treatment.
The results indicate that the machine learning methods are worthy of being adopted to study the dominant diseases of TCM for exploring the crucial rules of the diagnosis and treatment.
The results indicate that the machine learning methods are worthy of being adopted to study the dominant diseases of TCM for exploring the crucial rules of the diagnosis and treatment.Adaptations to the gold standard randomised controlled trial (RCT) have been introduced to decrease trial costs and avoid high sample sizes. To facilitate development of precision medicine algorithms that aim to optimise treatment allocation for individual patients, we propose a new RCT adaptation termed the nested-precision RCT (npRCT). The npRCT combines a traditional RCT (intervention A versus B) with a precision RCT (stratified versus randomised allocation to A or B). This combination allows online development of a precision algorithm, thus providing an integrated platform for algorithm development and its testing. Moreover, as both the traditional and the precision RCT include participants randomised to interventions of interest, data from these participants can be jointly analysed to determine the comparative effectiveness of intervention A versus B, thus increasing statistical power. We quantify savings of the npRCT compared to two independent RCTs by highlighting sample size requirements for different target effect sizes and by introducing an open-source power calculation app. We describe important practical considerations such as blinding issues and potential biases that need to be considered when designing an npRCT. We also highlight limitations and research contexts that are less suited for an npRCT. In conclusion, we introduce the npRCT as a novel precision medicine trial design strategy which may provide one opportunity to efficiently combine traditional and precision RCTs.
