Search Results (5)

Steroidogenic factor 1 (SF-1) is a nuclear receptor that regulates steroidogenesis and reproductive development. NR5A1/SF-1 variants are associated with a broad spectrum of phenotypes across individuals with disorders of sex development (DSDs). Oligogenic inheritance has been suggested as an explanation. SF-1 interacts with numerous partners. Here, we investigated a constellation of gene variants identified in a 46,XY severely undervirilized individual carrying an ACMG-categorized ‘pathogenic’ NR5A1/SF-1 variant in comparison to the healthy carrier father. Candidate genes were revealed by whole exome sequencing, and pathogenicity was predicted by different in silico tools. We found variants in NR1H2 and INHA associated with steroidogenesis, sex development, and reproduction. The identified variants were tested in cell models. Novel SF-1 and NR1H2 binding sites in the AR and INHA gene promoters were found. Transactivation studies showed that wild-type NR5A1/SF-1 regulates INHA and AR gene expression, while the NR5A1/SF-1 variant had decreased transcriptional activity. NR1H2 was found to regulate AR gene transcription; however, the NR1H2 variant showed normal activity. This study expands the NR5A1/SF-1 network of interacting partners, while not solving the exact interplay of different variants that might be involved in revealing the observed DSD phenotype. It also illustrates that understanding complex genetics in DSDs is challenging. Full article

In Mexico, according to data from the General Directorate of Health Information (2018), there is an annual incidence of 689 newborns with Trisomy 21, well-known as Down Syndrome. Worldwide, this incidence is estimated between 1 in every 1000 newborns, approximately. That is why this work focuses on the detection and analysis of facial emotions in children with Down Syndrome in order to predict their emotions throughout a dolphin-assisted therapy. In this work, two databases are used: Exploratory Data Analysis, with a total of 20,214 images, and the Down’s Syndrome Dataset database, with 1445 images for training, validation, and testing of the neural network models. The construction of two architectures based on a Deep Convolutional Neural Network manages an efficiency of 79%, when these architectures are tested with a large reference image database. Then, the architecture that achieves better results is trained, validated, and tested in a small-image database with the facial emotions of children with Down Syndrome, obtaining an efficiency of 72%. However, this increases by 9% when the brain activity of the child is included in the training, resulting in an average precision of 81%. Using electroencephalogram (EEG) signals in a Convolutional Neural Network (CNN) along with the Down’s Syndrome Dataset (DSDS) has promising advantages in the field of brain–computer interfaces. EEG provides direct access to the electrical activity of the brain, allowing for real-time monitoring and analysis of cognitive states. Integrating EEG signals into a CNN architecture can enhance learning and decision-making capabilities. It is important to note that this work has the primary objective of addressing a doubly vulnerable population, as these children also have a disability. Full article

Background: Many classifications exist to select patients with “high-risk” head and neck cutaneous squamous cell carcinoma (HNCSCC). Objective: To compare the performance of the Brigham and Women’s Hospital (BWH) classification with the performance of the American Joint Committee on Cancer 8th Edition (AJCC8), the Union for International Cancer Control 8th Edition (UICC8), and the National Comprehensive Cancer Network (NCCN) classifications. Methods: In this single-center retrospective study, HNCSCC resected in a tertiary care center were classified as “low-risk” or “high-risk” tumors according to the four classifications. Rates of local recurrence (LR), lymph node recurrence (NR), and disease-specific death (DSD) were collected. The performance of each classification was then calculated in terms of homogeneity, monotonicity, and discrimination and compared. Results: Two hundred and seventeen HNCSCC from 160 patients, with a mean age of 80 years, were included. For predicting the risk of any poor outcome and risk of NR, the BWH classification had the best specificity and positive predictive value. However, its concordance index was not significantly higher than that of the AJCC8 and UICC8 classifications. The NCCN classification was the least discriminant. Conclusions and Relevance: This study suggests that the BWH classification is the most appropriate for predicting the risk of poor outcomes in patients with HNCSCC when compared with the NCCN, UICC8, and AJCC8 classifications. Full article

The observation of and research on raindrop size distribution (DSD) is important for mastering and understanding the mutual restriction relationship between cloud dynamics and cloud microphysics in a process of precipitation; it also plays an irreplaceable role in many fields, such as radar meteorology, weather modification, boundary layer land surface processes, aerosols, etc. Using more than 1.7 million minutes of raindrop data observed with 17 laser disdrometers at 17 stations in Anhui Province, China, from 7 August 2009 to 30 April 2020, a DSD training dataset was constructed. Furthermore, the data are fitted to a normalized Gamma function and used to obtain its three parameters, i.e., the normalized intercept N_w, the mass weighted average diameter D_m, and the shape factor μ. Based on the long short-term memory network (LSTM), a DSD Gamma distribution prediction network (DSDnet) was designed. In the process of modeling based on DSDnet, a self-defined loss function (SLF) was proposed in order to improve the DSD prediction by increasing the weight values in the poor fitting regions according to the common mean square error loss function (MLF). By means of the training dataset, a DSDnet-based model was trained to realize the prediction of N_w, D_m, and μ minute-to-minute over the course of 30 min, and then was evaluated by the test dataset according to three indicators, namely, mean relative error (MRE), mean absolute error (MAE), and correlation coefficient (CC). The CC of lgN_w, D_m, and μ can reach 0.93403, 0.90934, and 0.89741 for 12-min predictions, and 0.87559, 0.85261, and 0.84564 for 30-min predictions, respectively, which means that the DSD prediction accuracy within 30 min can basically reach the application level. Furthermore, the 12- and 30-min predictions of 3 precipitation processes were taken as examples to fully demonstrate the application effect of model. The prediction effects of N_w and D_m are better than that of μ, and the stratiform precipitation is better than the convective and convective-stratiform mixed cloud precipitation. Full article

Generally, the bioconversion of lignocellulolytics into a new biomolecule is carried out through two or more steps. The current study used one-step bioprocessing of date palm fronds (DPF) into citric acid as a natural product, using a pioneer strain of Trichodermaharzianum (PWN6) that has been selected from six tested isolates based on the highest organic acid (OA) productivity (195.41 µmol/g), with the lowest amount of the released glucose. Trichoderma sp. PWN6 was morphologically and molecularly identified, and the GenBank accession number was MW78912.1. Both definitive screening design (DSD) and artificial neural network (ANN) were applied, for the first time, for modeling the bioconversion process of DPF. Although both models are capable of making accurate predictions, the ANN model outperforms the DSD model in terms of OA production, as ANN is characterized by a higher value of R² (0.963) and validation R² (0.967), and lower values of the RMSE (13.44), MDA (11.06), and SSE (9749.5). Citric acid was the only identified OA as was confirmed by GC-MS and UPLC, with a total of 1.5%. In conclusion, DPF together with T. harzianum PWN6 is considered an excellent new combination for citric acid biosynthesis, after modeling with artificial intelligence procedure. Full article