ASIAM-HGNN: Automatic Selection and Interpretable Aggregation of Meta-Path Instances for Heterogeneous Graph Neural Network

In heterogeneous information network (HIN)-based applications, the existing methods usually use Heterogeneous Graph Neural Networks (HGNN) to handle some complex tasks. However, these methods still have some shortcomings: 1) they manually pre-select some meta-paths and thus some important ones are missing, while the missing ones still contains the information and features of the node in the entire graph structure; and 2) they have no high interpretability since they do not consider the logical sequences in an HIN. In order to deal with them, we propose ASIAM-HGNN: a heterogeneous graph neural network combined with the automatic selection and interpretable aggregation of meta-path instances. Our model can automatically filter important meta paths for each node, while preserving the logical sequence between nodes, so as to solve the problems existing in other models. A group of experiments are conducted on real-world datasets, and the results demonstrate that the models learned by our method have a better performance in most of task scenarios

Synthetic lethality between TP53 and ENDOD1

The atypical nuclease ENDOD1 functions with cGAS-STING in innate immunity. Here we identify a previously uncharacterized ENDOD1 function in DNA repair. ENDOD1 is enriched in the nucleus following H2O2 treatment and ENDOD1−/− cells show increased PARP chromatin-association. Loss of ENDOD1 function is synthetic lethal with homologous recombination defects, with affected cells accumulating DNA double strand breaks. Remarkably, we also uncover an additional synthetic lethality between ENDOD1 and p53. ENDOD1 depletion in TP53 mutated tumour cells, or p53 depletion in ENDOD1−/− cells, results in rapid single stranded DNA accumulation and cell death. Because TP53 is mutated in ~50% of tumours, ENDOD1 has potential as a wide-spectrum target for synthetic lethal treatments. To support this we demonstrate that systemic knockdown of mouse EndoD1 is well tolerated and whole-animal siRNA against human ENDOD1 restrains TP53 mutated tumour progression in xenograft models. These data identify ENDOD1 as a potential cancer-specific target for SL drug discovery

A meaningful exploration of ofatumumab in refractory NMOSD: a case report

ObjectiveTo report the case of a patient with refractory neuromyelitis optica spectrum disorder (NMOSD), who, despite showing poor response or intolerance to multiple immunosuppressants, was successfully treated with Ofatumumab.Case presentationA 42-year-old female was diagnosed with NMOSD in the first episode of the disease. Despite treatment with intravenous methylprednisolone, immunoglobulin, rituximab and immunoadsorption, together with oral steroids, azathioprine, mycophenolate mofetil and tacrolimus, she underwent various adverse events, such as abnormal liver function, repeated infections, fever, rashes, hemorrhagic shock, etc., and experienced five relapses over the ensuing four years. Finally, clinicians decided to initiate Ofatumumab to control the disease. The patient received 9 doses of Ofatumumab over the next 10 months at customized intervals. Her symptoms were stable and there was no recurrence or any adverse events.ConclusionOfatumumab might serve as an effective and safe alternative for NMOSD patients who are resistant to other current immunotherapies

MicroRNAs Up-Regulated by CagA of Helicobacter pylori Induce Intestinal Metaplasia of Gastric Epithelial Cells

CagA of Helicobacter pylori is a bacterium-derived oncogenic protein closely associated with the development of gastric cancers. MicroRNAs (miRNAs) are a class of widespread non-coding RNAs, many of which are involved in cell growth, cell differentiation and tumorigenesis. The relationship between CagA protein and miRNAs is unclear. Using mammalian miRNA profile microarrays, we found that miRNA-584 and miRNA-1290 expression was up-regulated in CagA-transformed cells, miRNA-1290 was up-regulated in an Erk1/2-dependent manner, and miRNA-584 was activated by NF-κB. miRNA-584 sustained Erk1/2 activities through inhibition of PPP2a activities, and miRNA-1290 activated NF-κB by knockdown of NKRF. Foxa1 was revealed to be an important target of miRNA-584 and miRNA-1290. Knockdown of Foxa1 promoted the epithelial-mesenchymal transition significantly. Overexpression of miRNA-584 and miRNA-1290 induced intestinal metaplasia of gastric epithelial cells in knock-in mice. These results indicate that miRNA-584 and miRNA-1290 interfere with cell differentiation and remodel the tissues. Thus, the miRNA pathway is a new pathogenic mechanism of CagA

Deadline guaranteed packet scheduling for overloaded traffic in input-queued switches

Many applications need to solve the deadline guaranteed packet scheduling problem. However, it is a very difficult problem if three or more deadlines are present in a set of packets to be scheduled. The traditional approach to dealing with this problem is to use EDF (Earliest Deadline First) or similar methods. Recently, a non-EDF based algorithm was proposed that constantly produces a higher throughput than EDF-based algorithms by repeatedly finding an optimal scheduling for two classes. However, this new method requires the two classes be non-overloaded, which greatly restricts its applications. Since the overloaded situation is not avoidable from one iteration to the next in dealing with multiple classes, it is compelling to answer the open question: Can we find an optimal schedule for two overloaded classes efficiently? This paper first proves that this problem is NP-complete. Then, this paper proposes an optimal preprocessing algorithm that guarantees to drop a minimum number of packets from the two classes such that the remaining set is non-overloaded. This result directly improves on the new method

Relationship between PD-L1 expression and clinical characteristics in patients with breast invasive ductal carcinoma

To evaluate the expression of PD-L1 (programmed death 1 ligand 1, PD-L1) and its clinical significance in breast invasive ductal carcinoma