Graph Representation Learning Based on Specific Subgraphs for Biomedical Interaction Prediction.

Discovering the novel associations of biomedical entities is of great significance and can facilitate not only the identification of network biomarkers of disease but also the search for putative drug targets. Graph representation learning (GRL) has incredible potential to efficiently predict the interactions from biomedical networks by modeling the robust representation for each node. However, the current GRL-based methods learn the representation of nodes by aggregating the features of their neighbors with equal weights. Furthermore, they also fail to identify which features of higher-order neighbors are integrated into the representation of the central node. In this work, we propose a novel graph representation learning framework: a multi-order graph neural network based on reconstructed specific subgraphs (MGRS) for biomedical interaction prediction. In the MGRS, we apply the multi-order graph aggregation module (MOGA) to learn the wide-view representation by integrating the multi-hop neighbor features. Besides, we propose a subgraph selection module (SGSM) to reconstruct the specific subgraph with adaptive edge weights for each node. SGSM can clearly explore the dependency of the node representation on the neighbor features and learn the subgraph-based representation based on the reconstructed weighted subgraphs. Extensive experimental results on four public biomedical networks demonstrate that the MGRS performs better and is more robust than the latest baselines.

Development of an optimal short form of the GAD-7 scale with cross-cultural generalizability based on Riskslim.

Despite the relatively small number of items in the GAD-7, fewer items are increasingly sought to shorten testing time in large-scale mental health screenings. As a result, short forms based on the GAD-7, the GAD-2, and GAD-mini, have become popular. However, the GAD-2 and GAD-mini have reported lower diagnostic accuracy in some cultural contexts, implying that a validated short-form version of the GAD-7 may be lacking in large-scale cross-cultural anxiety screening. Based on this, to develop an optimal short form of the GAD-7 with cross-cultural stability, we utilized seven GAD-7 datasets from six different countries, totaling 47,484 participants. Five 2 to 6 item short forms of the GAD were constructed using the Riskslim machine learning algorithm. We evaluated the diagnostic accuracy of the GAD-7 short forms in the training and test sets based on the coefficient of determination(R2) and area under the curve(AUC) metrics, and the results showed that GAD-R2 performed poorly in some cultures, and all of the 3 to 6 item short forms of the GAD performed good in cross-cultural diagnostic rates, with the GAD-R6 showing the highest diagnostic accuracy in all cultures; GAD-R3 outperformed GAD-R2, GAD-2, and GAD-mini in all cultures; GAD-R3 had higher generalizability across cultures and special populations; Given that the GAD-R3 was shorter and nearly as accurate as the GAD-R6, we recommend the use of the GAD-R3 in clinical studies and epidemiologic investigations. And we recommend the optimal actual cutoff value of 15 for GAD-R3. Overall, we recommend GAD-R3 as the short-form version of GAD-7 in cross-cultural studies. However, the 2-item GAD scale is also optimal for the short-form version in clinical practice.

Protozoan-Derived Cytokine-Transgenic Macrophages Reverse Hepatic Fibrosis.

Macrophage therapy for liver fibrosis is on the cusp of meaningful clinical utility. Due to the heterogeneities of macrophages, it is urgent to develop safer macrophages with a more stable and defined phenotype for the treatment of liver fibrosis. Herein, a new macrophage-based immunotherapy using macrophages stably expressing a pivotal cytokine from Toxoplasma gondii, a parasite that infects ≈ 2 billion people is developed. It is found that Toxoplasma gondii macrophage migration inhibitory factor-transgenic macrophage (Mφtgmif) shows stable fibrinolysis and strong chemotactic capacity. Mφtgmif effectively ameliorates liver fibrosis and deactivates aHSCs by recruiting Ly6Chi macrophages via paracrine CCL2 and polarizing them into the restorative Ly6Clo macrophage through the secretion of CX3CL1. Remarkably, Mφtgmif exhibits even higher chemotactic potential, lower grade of inflammation, and better therapeutic effects than LPS/IFN-γ-treated macrophages, making macrophage-based immune therapy more efficient and safer. Mechanistically, TgMIF promotes CCL2 expression by activating the ERK/HMGB1/NF-κB pathway, and this event is associated with recruiting endogenous macrophages into the fibrosis liver. The findings do not merely identify viable immunotherapy for liver fibrosis but also suggest a therapeutic strategy based on the evolutionarily designed immunomodulator to treat human diseases by modifying the immune microenvironment.

A secondary jejunal malignant melanoma from nasal mucosal melanoma: Case report.

Melanomas most commonly localized in the skin can arise anywhere in the body, and approximately 5% of all melanomas appear in other sites of mucosal surfaces out of skin. Primary melanoma from nasal mucosa is quite rare. We present this case: a 46-year-old man had complained a pain in the left upper abdomen for 2 months when he was admitted to the Northern Jiangsu People's Hospital. The pain was paroxysmal and enhanced when eating. There was no nausea, vomiting, or anorexia. There had been no change in weight in previous months. This patient had a past history of surgery for nasal mucosal malignant melanoma 2 years ago. Abdominal enhanced computed tomography (CT) indicated that a mass originated from small bowel and occupied the left upper abdomen. The patient underwent a laparotomy during which a black lesion measuring about 5 cm × 5 cm × 4 cm was found at the jejunum and resected totally together with partial jejunum. The patient was eventually diagnosed as secondary jejunal malignant melanoma from nasal mucosal melanoma. For patients with a history of melanoma, gastrointestinal metastasis should be considered when patients develop gastrointestinal symptoms. In addition, we recommend positive anti-tumor therapy after surgery.

The feasibility of laparoscopic TSME preserving the left colic artery and superior rectal artery for upper rectal cancer.

BACKGROUND: Laparoscopic tumor-specific mesorectal excision (TSME) preserving the left colic artery and superior rectal artery is still a technically challenging procedure. We conducted this study to demonstrate the feasibility of this procedure for upper rectal cancer. METHODS: A total of 184 patients with upper rectal cancer were retrospectively analyzed in our cancer center between April 2010 and April 2017. These patients were treated with either laparoscopic TSME (n = 46) or laparoscopic total mesorectal excision (TME) (n = 138). In the TSME group, the left colonic artery and superior rectal artery were preserved while they were not in the TME group. RESULTS: The operation time in the TSME group was longer than that in the TME group (218.56 ± 35.85 min vs. 201.13 ± 42.65 min, P = 0.004). Furthermore, the number of resected lymph nodes in the TSME group was greater than that in the TME group (19.43 ± 9.46 vs. 18.03 ± 7.43, P = 0.024). The blood loss between the TSME and TME groups was not significant. No mortality occurred in either the TSME or TME groups. One patient in the TME group underwent conversion to laparotomy. The total postoperative complication rates in the TSME and TME groups were 8.7% and 17.4%, respectively. There was no difference in severe complications between the two groups (anastomotic leakage and stenosis). CONCLUSIONS: Laparoscopic TSME preserving the left colic artery and superior rectal artery can be safely conducted for upper rectal cancer.