NaNa and MiGu: Semantic Data Augmentation Techniques to Enhance Protein Classification in Graph Neural Networks

Protein classification tasks are essential in drug discovery. Real-world protein structures are dynamic, which will determine the properties of proteins. However, the existing machine learning methods, like ProNet (Wang et al., 2022a), only access limited conformational characteristics and protein side-chain features, leading to impractical protein structure and inaccuracy of protein classes in their predictions. In this paper, we propose novel semantic data augmentation methods, Novel Augmentation of New Node Attributes (NaNa), and Molecular Interactions and Geometric Upgrading (MiGu) to incorporate backbone chemical and side-chain biophysical information into protein classification tasks and a co-embedding residual learning framework. Specifically, we leverage molecular biophysical, secondary structure, chemical bonds, and ionic features of proteins to facilitate protein classification tasks. Furthermore, our semantic augmentation methods and the co-embedding residual learning framework can improve the performance of GIN (Xu et al., 2019) on EC and Fold datasets (Bairoch, 2000; Andreeva et al., 2007) by 16.41% and 11.33% respectively. Our code is available at https://github.com/r08b46009/Code_for_MIGU_NANA/tree/main

Pelvic skeletal metastasis of hepatocellular carcinoma with sarcomatous change: a case report

Sarcomatoid hepatocellular carcinoma (HCC) is a very rare histologic variant of HCC. The characteristic of skeletal metastatic sarcomatoid hepatocellular carcinoma has never been reported. We reported a patient with sarcomatoid hepatocellular carcinoma pelvic metastasis who presented with huge pelvic metastasis that had relatively small osteolytic lesion centrally located accompanied by huge bipeduncular invasive expansile lesions into surrounding soft tissue. The lesion showed almost non-isotope uptake in 99mTc-methylene diphosphonate bone scintigraphy study. He underwent radiotherapy and tumor excision but the tumor rapidly recurred. In addition, serum α-fetoprotein level was never elevated beyond normal limit (< 20 ng/mL) through the whole course of treatment. We considered sarcomatoid hepatocellular carcinoma bone metastasis a highly aggressive lesion with unusual metastatic pattern. Surgical treatment with adequate safe margin in such a huge tumor with hypervascularity and extensive invasion in the pelvis was difficult; and radiotherapy maybe refractory regarding the sarcomatous nature. Therefore, debulking operation with local symptoms control may provide a better quality of life. And the clinical course suggests sarcomatoid hepatocellular carcinoma is derived from the transition of an ordinary hepatocellular carcinoma

Hirsutella sinensis mycelium attenuates bleomycin-induced pulmonary inflammation and fibrosis in vivo

Hirsutella sinensis mycelium (HSM), the anamorph of Cordyceps sinensis, is a traditional Chinese medicine that has been shown to possess various pharmacological properties. We previously reported that this fungus suppresses interleukin-1β and IL-18 secretion by inhibiting both canonical and non-canonical inflammasomes in human macrophages. However, whether HSM may be used to prevent lung fibrosis and the mechanism underlying this activity remain unclear. Our results show that pretreatment with HSM inhibits TGF-β1–induced expression of fibronectin and α-SMA in lung fibroblasts. HSM also restores superoxide dismutase expression in TGF-β1–treated lung fibroblasts and inhibits reactive oxygen species production in lung epithelial cells. Furthermore, HSM pretreatment markedly reduces bleomycin–induced lung injury and fibrosis in mice. Accordingly, HSM reduces inflammatory cell accumulation in bronchoalveolar lavage fluid and proinflammatory cytokines levels in lung tissues. The HSM extract also significantly reduces TGF-β1 in lung tissues, and this effect is accompanied by decreased collagen 3α1 and α-SMA levels. Moreover, HSM reduces expression of the NLRP3 inflammasome and P2X7R in lung tissues, whereas it enhances expression of superoxide dismutase. These findings suggest that HSM may be used for the treatment of pulmonary inflammation and fibrosis

Influenza Pandemics: Past, Present and Future

Influenza A virus is well known for its capability for genetic changes either through antigen drift or antigen shift. Antigen shift is derived from reassortment of gene segments between viruses, and may result in an antigenically novel virus that is capable of causing a worldwide pandemic. As we trace backwards through the history of influenza pandemics, a repeating pattern can be observed, namely, a limited wave in the first year followed by global spread in the following year. In the 20th century alone, there were three overwhelming pandemics, in 1918, 1957 and 1968, caused by H1N1 (Spanish flu), H2N2 (Asian flu) and H3N2 (Hong Kong flu), respectively. In 1957 and 1968, excess mortality was noted in infants, the elderly and persons with chronic diseases, similar to what occurred during interpandemic periods. In 1918, there was one distinct peak of excess death in young adults aged between 20 and 40 years old; leukopenia and hemorrhage were prominent features. Acute pulmonary edema and hemorrhagic pneumonia contributed to rapidly lethal outcome in young adults. Autopsies disclosed multiple-organ involvement, including pericarditis, myocarditis, hepatitis and splenomegaly. These findings are, in part, consistent with clinical manifestations of human infection with avian influenza A H5N1 virus, in which reactive hemophagocytic syndrome was a characteristic pathologic finding that accounted for pancytopenia, abnormal liver function and multiple organ failure. All the elements of an impending pandemic are in place. Unless effective measures are implemented, we will likely observe a pandemic in the coming seasons. Host immune response plays a crucial role in disease caused by newly emerged influenza virus, such as the 1918 pandemic strain and the recent avian H5N1 strain. Sustained activation of lymphocytes and macrophages after infection results in massive cytokine response, thus leading to severe systemic inflammation. Further investigations into how the virus interacts with the host's immune system will be helpful in guiding future therapeutic strategies in facing influenza pandemics

The Functional Haplotypes of CHRM3 Modulate mRNA Expression and Associate with Bladder Cancer among a Chinese Han Population in Kaohsiung City

Bladder cancer is one of the major cancer types and both environmental factors and genetic background play important roles in its pathology. Kaohsiung is a high industrialized city in Taiwan, and here we focused on this region to evaluate the genetic effects on bladder cancer. Muscarinic acetylcholine receptor M3 (CHRM3) was reported as a key receptor in different cancer types. CHRM3 is located at 1q42-43 which was reported to associate with bladder cancer. Our study attempted to delineate whether genetic variants of CHRM3 contribute to bladder cancer in Chinese Han population in south Taiwan. Five selected SNPs (rs2165870, rs10802789, rs685550, rs7520974, and rs3738435) were genotyped for 30 bladder cancer patients and 60 control individuals and genetic association studies were performed. Five haplotypes (GTTAT, ATTGT, GCTAC, ACTAC, and ACCAC) were found significantly associated with low CHRM3 mRNA level and contributed to increased susceptibility of bladder cancer in Kaohsiung city after rigid 10000 consecutive permutation tests. To our knowledge, this is the first genetic association study that reveals the genetic contribution of CHRM3 gene in bladder cancer etiology

Effect of patient decision aids on choice between sugammadex and neostigmine in surgeries under general anesthesia: a multicenter randomized controlled trial

Background Shared decision making using patient decision aids (PtDAs) was established over a decade ago, but few studies have evaluated its efficacy in Asian countries. We therefore evaluated the application of PtDAs in a decision conflict between two muscle relaxant reversal agents, neostigmine and sugammadex, and sequentially analyzed the regional differences and operating room turnover rates. Methods This multicenter, outcome-assessor-blind, randomized controlled trial included 3,132 surgical patients from two medical centers admitted between March 2020 and August 2020. The patients were randomly divided into the classical and PtDA groups for pre-anesthesia consultations. Their clinicodemographic characteristics were analyzed to identify variables influencing the choice of reversal agent. On the day of the pre-anesthesia consultation, the patients completed the four SURE scale (sure of myself, understand information, risk-benefit ratio, encouragement) screening items. The operating turnover rates were also evaluated using anesthesia records. Results Compared with the classical group, the PtDA group felt more confident about receiving sufficient medical information (P < 0.001), felt better informed about the advantages and disadvantages of the medications (P < 0.001), exhibited a superior understanding of the benefits and risks of their options (P < 0.001), and felt surer about their choice (P < 0.001). Moreover, the PtDA group had a significantly greater tendency to choose sugammadex over neostigmine (P < 0.001). Conclusions PtDA interventions in pre-anesthesia consultations provided surgical patients with clear knowledge and better support. PtDAs should be made available in other medical fields to enhance shared clinical decision-making