Layer-wise Representation Fusion for Compositional Generalization

Despite successes across a broad range of applications, sequence-to-sequence models' construct of solutions are argued to be less compositional than human-like generalization. There is mounting evidence that one of the reasons hindering compositional generalization is representations of the encoder and decoder uppermost layer are entangled. In other words, the syntactic and semantic representations of sequences are twisted inappropriately. However, most previous studies mainly concentrate on enhancing token-level semantic information to alleviate the representations entanglement problem, rather than composing and using the syntactic and semantic representations of sequences appropriately as humans do. In addition, we explain why the entanglement problem exists from the perspective of recent studies about training deeper Transformer, mainly owing to the ``shallow'' residual connections and its simple, one-step operations, which fails to fuse previous layers' information effectively. Starting from this finding and inspired by humans' strategies, we propose \textsc{FuSion} (\textbf{Fu}sing \textbf{S}yntactic and Semant\textbf{i}c Representati\textbf{on}s), an extension to sequence-to-sequence models to learn to fuse previous layers' information back into the encoding and decoding process appropriately through introducing a \emph{fuse-attention module} at each encoder and decoder layer. \textsc{FuSion} achieves competitive and even \textbf{state-of-the-art} results on two realistic benchmarks, which empirically demonstrates the effectiveness of our proposal.Comment: work in progress. arXiv admin note: substantial text overlap with arXiv:2305.1216

Multicenter validation of the value of BASFI and BASDAI in Chinese ankylosing spondylitis and undifferentiated spondyloarthropathy patients

The objectives of this study were to evaluate the reliability of Bath ankylosing spondylitis functional index (BASFI) and Bath ankylosing spondylitis disease activity index (BASDAI) in Chinese ankylosing spondylitis (AS) and undifferentiated spondyloarthropathy (USpA) patients. 664 AS patients by the revised New York criteria for AS and 252 USpA patients by the European Spondyloarthropathy Study Group criteria were enrolled. BASDAI and BASFI questionnaires were translated into Chinese. Participants were required to fill in BASFI and BASDAI questionnaires again after 24 h. Moreover, BASDAI and BASFI were compared in AS patients receiving Enbrel or infliximab before and after treatment. For AS group, BASDAI ICC: 0.9502 (95% CI: 0.9330–0.9502, α = 0.9702), BASFI ICC: 0.9587 (95% CI: 0.9521–0.9645, α = 0.9789). For USpA group, BASDAI ICC: 0.9530 (95% CI: 0.9402–0.9632, α = 0.9760), BASFI ICC: 0.9900 (95% CI: 0.9871–0.9922, α = 0.9950). In the AS group, disease duration, occipital wall distance, modified Schober test, chest expansion, ESR, and CRP showed significant correlation with BASDAI and BASFI (all P < 0.01). In the USpA group, onset age, ESR, and CRP were significantly correlated with BASDAI (all P < 0.05), while modified Schober test, ESR, and CRP were significantly associated with BASFI (all P < 0.05). The change in BASDAI and BASFI via Enbrel or infliximab treatment showed a significant positive correlation (P < 0.01). The two instruments have good reliability and reference value regarding the evaluation of patient’s condition and anti-TNF-α treatment response

Antitumor activity and mechanisms of action of total glycosides from aerial part of Cimicifuga dahurica targeted against hepatoma

<p>Abstract</p> <p>Background</p> <p>Medicinal plant is a main source of cancer drug development. Some of the cycloartane triterpenoids isolated from the aerial part of <it>Cimicifuga dahurica </it>showed cytotoxicity in several cancer cell lines. It is of great interest to examine the antiproliferative activity and mechanisms of total triterpenoid glycosides of <it>C. dahurica </it>and therefore might eventually be useful in the prevention or treatment of Hepatoma.</p> <p>Methods</p> <p>The total glycosides from the aerial part (TGA) was extracted and its cytotoxicity was evaluated in HepG2 cells and primary cultured normal mouse hepatocytes by an MTT assay. Morphology observation, Annexin V-FITC/PI staining, cell cycle analysis and western blot were used to further elucidate the cytotoxic mechanism of TGA. Implanted mouse H₂₂hepatoma model was used to demonstrate the tumor growth inhibitory activity of TGA <it>in vivo</it>.</p> <p>Results</p> <p>The IC₅₀values of TGA in HepG2 and primary cultured normal mouse hepatocytes were 21 and 105 μg/ml, respectively. TGA induced G₀/G₁cell cycle arrest at lower concentration (25 μg/ml), and triggered G₂/M arrest and apoptosis at higher concentrations (50 and 100 μg/ml respectively). An increase in the ratio of Bax/Bcl-2 was implicated in TGA-induced apoptosis. In addition, TGA inhibited the growth of the implanted mouse H₂₂tumor in a dose-dependent manner.</p> <p>Conclusion</p> <p>TGA may potentially find use as a new therapy for the treatment of hepatoma.</p

Esketamine reduces ischemia-reperfusion injury of skeletal muscle of rats

Objective To investigate the role of low dose esketamine in pretreated limb ischemia-reperfusion injury. Methods The rats were divided into sham-operated group (Sham group), ischemia-reperfusion group (I/R group, 3 h of ischemia and 2 h of reperfusion), esketamine group (ESK group, ip, 5 mg/kg). The plasma concentrations of creatine kinase (CK) and lactate dehydrogenase (LDH) were measured. The wet/dry weight ratio of skeletal muscle was immediately detected. The gastrocnemius muscle was harvested and the level of malondialdehyde (MDA) and superoxide dismutase (SOD) was detected by colorimetric assay. The expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) were detected by Western blot and immunohistochemical staining. Results Compared with Sham group, the index of wet/dry weight ratio, MDA, CK, LDH, Nrf2 and HO-1 were all increased, but SOD was decreased in I/R group(P＜0.05). Compared with I/R group, the index of wet/dry weight ratio, MDA, CK and LDH were significantly lower, but SOD and Nrf2 and HO-1 were significantly higher in ESK group (P＜0.05). Conclusions ESK may increase Nrf2 in the nucleus, thereby increase the HO-1 protein as an antioxidant agent

Recurrence-Associated Multi-RNA Signature to Predict Disease-Free Survival for Ovarian Cancer Patients

Ovarian cancer (OvCa) is an intractable gynecological malignancy due to the high recurrence rate. Several molecular biomarkers have been previously screened for early identifying patients with a high recurrence risk and poor prognosis. However, all the known studies focused on a single type of RNAs, not integrating various types. This study was to construct a new multi-RNA-based model to predict the recurrence and prognosis for OvCa patients by using the messenger RNA (mRNA, including long noncoding RNA (lncRNA)) and microRNA (miRNA) sequencing data of The Cancer Genome Atlas database. After univariate Cox regression and least absolute shrinkage and selection operator analyses, a multi-RNA-based signature (2 miRNAs: hsa-miR-508, hsa-miR-506; 1 lncRNA: TM4SF1-AS1; 11 mRNAs: MAGI3, SLAMF7, GLI2, PDK1, ARID3A, PLEKHG4B, TNFAIP8L3, C1QTNF3, NDUFAF1, CH25H, TMEM129) was generated and used to establish a risk score model. The high- and low-risk patients classified by the median risk score exhibited significantly different recurrence risks (89% versus 61%, p<0.001) and survival time (the area under the receiver operating characteristic curve (AUC) = 0.901 for 5-year disease-free survival (DFS)). This risk model was independent of other clinical features and superior to pathologic staging for DFS prediction (AUC, 0.906 versus 0.524; C-index, 0.633 versus 0.510). Furthermore, some new interaction axes were revealed to explain the possible functions of these RNAs (competing endogenous RNA: TM4SF1-AS1-miR-186-STEAP2, LINC00536-miR-508-STEAP2, LINC00475-miR-506-TMEM129; coexpression: LINC00598-PLEKHG4B). In conclusion, this multi-RNA-based risk model may be clinically useful to stratify OvCa patients with different recurrence risks and survival outcomes and included RNAs may be potential therapeutic targets

Predicting potential medicinal plants with phylogenetic topology: Inspiration from the research of traditional Chinese medicine

Ethnopharmacological relevance: Plants are a dominant source of pharmacological drugs for the treatment and cure of different disorders and diseases. However, selecting the most biologically active plant species for further screening is still challenging. Phylogeny has strong explanatory powers and provides predictive perspectives that are not available in traditional plant classifications. China, which is endowed with a diverse set of therapeutic cures from Mother Nature, represents an ideal environment for the phylogenetic analysis of potential medicinal plants. Materials and methods: Herein, we prepared a database of 7,451 traditional Chinese medicinal (TCM) plants, including species with therapeutic effects grouped in 14 categories. To limit our exploration of novel therapeutic species, we plotted the medicinal effects on the phylogenetic tree of almost 30,000 species of China to find hot nodes of therapeutic effects. We used the net relatedness index (NRI) and the nearest taxon index (NTI) to identify clustering and overdispersion of the phylogenetic distribution of TCM plants. Results: The NRI and NTI analyses highlighted 3,392 hot node species with single therapeutic effects within 507 genera and 89 families on the phylogenetic tree and about 70% of the 14 medicinal categories clusters identified. The general pattern of the hot nodes on the phylogenetic tree indicates that basal angiosperms and basal eudicots radiated for therapeutic effects. Conclusions: Our study may provide a more targeted way to discover phylogeny-guided drugs in the early screening stage, which may lead to a higher discovery efficiency of new drugs with meaningful biological activities. Phylogenetic studies of plants that are richer in bioactive compounds can set the ground for the identification and discovery of alternative drugs

Establishment of a risk prediction model for prolonged mechanical ventilation after lung transplantation: a retrospective cohort study

Abstract Background Prolonged mechanical ventilation (PMV), mostly defined as mechanical ventilation > 72 h after lung transplantation with or without tracheostomy, is associated with increased mortality. Nevertheless, the predictive factors of PMV after lung transplant remain unclear. The present study aimed to develop a novel scoring system to identify PMV after lung transplantation. Methods A total of 141 patients who underwent lung transplantation were investigated in this study. The patients were divided into PMV and non-prolonged ventilation (NPMV) groups. Univariate and multivariate logistic regression analyses were performed to assess factors associated with PMV. A risk nomogram was then established based on the multivariate analysis, and model performance was further examined regarding its calibration, discrimination, and clinical usefulness. Results Eight factors were finally identified to be significantly associated with PMV by the multivariate analysis and therefore were included as risk factors in the nomogram as follows: the body mass index (BMI, P = 0.036); primary diagnosis as idiopathic pulmonary fibrosis (IPF, P = 0.038); pulmonary hypertension (PAH, P = 0.034); primary graft dysfunction grading (PGD, P = 0.011) at T0; cold ischemia time (CIT P = 0.012); and three ventilation parameters (peak inspiratory pressure [PIP, P < 0.001], dynamic compliance [Cdyn, P = 0.001], and P/F ratio [P = 0.015]) at T0. The nomogram exhibited superior discrimination ability with an area under the curve of 0.895. Furthermore, both calibration curve and decision-curve analysis indicated satisfactory performance. Conclusion A novel nomogram to predict individual risk of receiving PMV for patients after lung transplantation was established, which may guide preventative measures for tackling this adverse event. Graphic Abstrac