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To commission and implement an Autoencoder based Classification-Regression (ACLR) model for VMAT patient-specific quality assurance (PSQA) in a multi-institution scenario.

1835 VMAT plans from seven institutions were collected for the ACLR model commissioning and multi-institutional validation. We established three scenarios to validate the gamma passing rates (GPRs) prediction and classification accuracy with the ACLR model for different delivery equipment, QA devices, and treatment planning systems (TPS). The prediction performance of the ACLR model was evaluated using mean absolute error (MAE) and root mean square error (RMSE). The classification performance was evaluated using sensitivity and specificity. An independent end-to-end test (E2E) and routine QA of the ACLR model were performed to validate the clinical use of the model.

For multi-institution validations, the MAEs were 1.30-2.80% and 2.42-4.60% at 3%/3mm and 3%/2mm, respectively, and RMSEs were 1.55-2.98% and 2.83-4.95% at 3%/3mm and 3%/2mm, respectively, with different delivery equipment, QA devices, and TPS, while the sensitivity was 90% and specificity was 70.1% at 3%/2mm. For the E2E, the deviations between the predicted and measured results were within 3%, and the model passed the consistency check for clinical implementation. The predicted results of the model were the same in daily QA, while the deviations between the repeated monthly measured GPRs were all within 2%.

The performance of the ACLR model in multi-institution scenarios was validated on a large scale. Routine QA of the ACLR model was established and the model could be used for VMAT PSQA clinically.

The performance of the ACLR model in multi-institution scenarios was validated on a large scale. Veliparib Routine QA of the ACLR model was established and the model could be used for VMAT PSQA clinically.Autism spectrum disorder (ASD) is a neurodevelopmental disorder with a strong genetic component. Recently developed genomic technologies, including microarray and next-generation sequencing (NGS), have enabled researchers to genetic analyses aimed at identifying genetic variations associated with ASD and to elucidate the genetic architecture of the disorder. Large-scale microarray, exome sequencing analyses, and robust statistical methods have resulted in successful gene discovery and identification of high-confidence ASD genes from among de novo and inherited variants. Efforts have been made to understand the genetic architecture of ASD using whole-genome sequencing and genome-wide association studies aimed at identifying noncoding mutations and common variants associated with ASD. In addition, the development of systems biology approaches has resulted in the integration of genetic findings with functional genomic datasets, thereby providing a unique insight into the functional convergence of ASD risk genes and their neurobiology. In this review, we summarize the latest findings of ASD genetic studies involving large cohorts and discuss their implications in ASD neurobiology and in clinical practice.In our previous study, it showed that P-3F, a podophyllotoxin derivative, causes the increased level of p53 expression by enhancing p53 stability, resulting from blockage of the Mdm2-p53 feedback loop via nucleolus-to-nucleoplasm translocation of Rps27a in human cervical cancer HeLa cell line. However, the mechanism of regulating Rps27a localization remains to be studied. In the current study, it has been demonstrated that the level of protein interacting with carboxyl terminus 1 (PICT1), originally identified as a tumor suppressor, was decreased in a concentration-dependent manner in response to P-3F, leading to inhibition of human cervical cancer cell lines proliferation. Also remarkably, reduction of serine phosphorylation of STMN1 at position 16 induced by P-3F was required in the downregulation of PICT1, in which p53 activity was likely to be directly involved. Note as well that, PICT1 also played an important role in p53 stability enhancement by inhibiting Mdm2-mediated p53 ubiquitination due to Rps27a translocation from the nucleolus to the nucleoplasm to interact with Mdm2 following treatment with P-3F. Collectively, these findings indicated that P-3F, a microtubule polymerization inhibitor, promotes the decreased level of PICT1 expression, which is critical for regulating the Rps27a-Mdm2-p53 pathway against cervical cancer.Myrmicinosporidium durumHölldobler (1933) is a widely distributed fungal endoparasite of ants. However, little is known about its biology, ecology, or evolutionary history. Our study investigated the phylogenetics of this entomopathogenic fungus using a molecular approach. Samples of M. durum were obtained from infected Solenopsis fugax workers collected in Warsaw (Poland). Analyses of rDNA markers revealed that M. durum belongs to a phylum of primarily aquatic fungi, Blastocladiomycota. It is currently the only species from this group known to parasitise hymenopterans. Our findings have clarified this fungus' taxonomy and suggest future directions for research into its biology, ecology, and infection dynamics.Cardiotoxicity is a major side effect of the chemotherapeutic drug doxorubicin (Dox), which is further exacerbated when it is combined with trastuzumab, a standard care approach for Human Epidermal growth factor Receptor-type 2 (HER2) positive cancer patients. However, the molecular mechanisms of the underlying cardiotoxicity of this combination are still mostly elusive. Increased oxidative stress, impaired energetic substrate uses and topoisomerase IIB inhibition are among the biological processes proposed to explain Dox-induced cardiomyocyte dysfunction. Since cardiomyocytes express HER2, trastuzumab can also damage these cells by interfering with neuroregulin-1 signaling and mitogen-activated protein kinase (MAPK), phosphoinositide 3-kinase (PI3K)/Akt and focal adhesion kinase (FAK)-dependent pathways. Nevertheless, Dox and trastuzumab target other cardiac cell types, such as endothelial cells, fibroblasts, cardiac progenitor cells and leukocytes, which can contribute to the clinical cardiotoxicity observed.