Out-of-Distributed Semantic Pruning for Robust Semi-Supervised Learning

Recent advances in robust semi-supervised learning (SSL) typically filter out-of-distribution (OOD) information at the sample level. We argue that an overlooked problem of robust SSL is its corrupted information on semantic level, practically limiting the development of the field. In this paper, we take an initial step to explore and propose a unified framework termed OOD Semantic Pruning (OSP), which aims at pruning OOD semantics out from in-distribution (ID) features. Specifically, (i) we propose an aliasing OOD matching module to pair each ID sample with an OOD sample with semantic overlap. (ii) We design a soft orthogonality regularization, which first transforms each ID feature by suppressing its semantic component that is collinear with paired OOD sample. It then forces the predictions before and after soft orthogonality decomposition to be consistent. Being practically simple, our method shows a strong performance in OOD detection and ID classification on challenging benchmarks. In particular, OSP surpasses the previous state-of-the-art by 13.7% on accuracy for ID classification and 5.9% on AUROC for OOD detection on TinyImageNet dataset. The source codes are publicly available at https://github.com/rain305f/OSP.Comment: Accpected by CVPR 202

Genome level analysis of rice mRNA 3′-end processing signals and alternative polyadenylation

The position of a poly(A) site of eukaryotic mRNA is determined by sequence signals in pre-mRNA and a group of polyadenylation factors. To reveal rice poly(A) signals at a genome level, we constructed a dataset of 55 742 authenticated poly(A) sites and characterized the poly(A) signals. This resulted in identifying the typical tripartite cis-elements, including FUE, NUE and CE, as previously observed in Arabidopsis. The average size of the 3′-UTR was 289 nucleotides. When mapped to the genome, however, 15% of these poly(A) sites were found to be located in the currently annotated intergenic regions. Moreover, an extensive alternative polyadenylation profile was evident where 50% of the genes analyzed had more than one unique poly(A) site (excluding microheterogeneity sites), and 13% had four or more poly(A) sites. About 4% of the analyzed genes possessed alternative poly(A) sites at their introns, 5′-UTRs, or protein coding regions. The authenticity of these alternative poly(A) sites was partially confirmed using MPSS data. Analysis of nucleotide profile and signal patterns indicated that there may be a different set of poly(A) signals for those poly(A) sites found in the coding regions. Based on the features of rice poly(A) signals, an updated algorithm termed PASS-Rice was designed to predict poly(A) sites

Effects of a neurokinin-1 receptor antagonist in the acute phase after thoracic spinal cord injury in a rat model

Objective: Disruption of the blood-spinal cord barrier (BSCB) with subsequent edema formation and further neuroinflammation contributes to aggravation of spinal cord injury (SCI). We aimed to observe the effect of antagonizing the binding of the neuropeptide Substance-P (SP) to its neurokinin-1 (NK1) receptor in a rodent SCI model. Methods: Female Wistar rats were subjected to a T9 laminectomy with or without (Sham) a T9 clip-contusion/compression SCI, followed by the implantation of an osmotic pump for the continuous, seven-day-long infusion of a NK1 receptor antagonist (NRA) or saline (vehicle) into the intrathecal space. The animals were assessed via MRI, and behavioral tests were performed during the experiment. 7 days after SCI, wet & dry weight and immunohistological analyses were conducted. Results: Substance-P inhibition via NRA showed limited effects on reducing edema. However, the invasion of T-lymphocytes and the number of apoptotic cells were significantly reduced with the NRA treatment. Moreover, a trend of reduced fibrinogen leakage, endothelial and microglial activation, CS-GAG deposition, and astrogliosis was found. Nevertheless, only insignificant general locomotion recovery could be observed in the BBB open field score and the Gridwalk test. In contrast, the CatWalk gait analysis showed an early onset of recovery in several parameters. Conclusion: Intrathecal administration of NRA might reinforce the integrity of the BSCB in the acute phase after SCI, potentially attenuating aspects of neurogenic inflammation, reducing edema formation, and improving functional recovery

Case report: Fatal Legionella infection diagnosed via by metagenomic next-generation sequencing in a patient with chronic myeloid leukemia

Legionella is an aerobic, gram-negative, intracellular pathogen and is an important cause of community-acquired pneumonia. Legionella pneumophila is the most common causative agent of Legionella pneumonia. Clinical diagnosis of Legionella pneumonia is challenging due to the lack of specific clinical manifestations and the low positive rates of conventional pathogen detection methods. In this study, we report a case of a patient with chronic myeloid leukemia who developed rigors and high fever after chemotherapy and immunotherapy. Chest computed tomography revealed consolidation in the left lower lobe of the lung and ground-glass opacities in both lower lobes. Multiple blood cultures showed Escherichia coli, Staphylococcus aureus, Bacillus licheniformis, and positive results in the β-D-glucan test (G test). The patient was treated with various sensitive antimicrobial agents, including meropenem plus fluconazole, meropenem plus carpofungin, and vancomycin. Unfortunately, the patient’s condition gradually worsened and eventually resulted in death. On the following day of death, metagenomic next-generation sequencing (mNGS) of 1whole blood revealed L. pneumophila pneumonia with concurrent bloodstream infection (blood mNGS reads 114,302). These findings suggest that when conventional empirical antimicrobial therapy proves ineffective for critically ill patients with pneumonia, the possibility of combined Legionella infection must be considered, and mNGS can provide a diagnostic tool in such cases

Transplantation of Neural Precursor Cells Attenuates Chronic Immune Environment in Cervical Spinal Cord Injury

Inflammation after traumatic spinal cord injury (SCI) is non-resolving and thus still present in chronic injury stages. It plays a key role in the pathophysiology of SCI and has been associated with further neurodegeneration and development of neuropathic pain. Neural precursor cells (NPCs) have been shown to reduce the acute and sub-acute inflammatory response after SCI. In the present study, we examined effects of NPC transplantation on the immune environment in chronic stages of SCI. SCI was induced in rats by clip-compression of the cervical spinal cord at the level C6-C7. NPCs were transplanted 10 days post-injury. The functional outcome was assessed weekly for 8 weeks using the Basso, Beattie, and Bresnahan scale, the CatWalk system, and the grid walk test. Afterwards, the rats were sacrificed, and spinal cord sections were examined for M1/M2 macrophages, T lymphocytes, astrogliosis, and apoptosis using immunofluorescence staining. Rats treated with NPCs had compared to the control group significantly fewer pro-inflammatory M1 macrophages and reduced immunodensity for inducible nitric oxide synthase (iNOS), their marker enzyme. Anti-inflammatory M2 macrophages were rarely present 8 weeks after the SCI. In this model, the sub-acute transplantation of NPCs did not support survival and proliferation of M2 macrophages. Post-traumatic apoptosis, however, was significantly reduced in the NPC group, which might be explained by the altered microenvironment following NPC transplantation. Corresponding to these findings, reactive astrogliosis was significantly reduced in NPC-transplanted animals. Furthermore, we could observe a trend toward smaller cavity sizes and functional improvement following NPC transplantation. Our data suggest that transplantation of NPCs following SCI might attenuate inflammation even in chronic injury stages. This might prevent further neurodegeneration and could also set a stage for improved neuroregeneration after SCI

HMGB1 promotes ductular reaction and tumorigenesis in autophagy-deficient livers

Autophagy is important for liver homeostasis, and the deficiency leads to injury, inflammation, ductular reaction (DR), fibrosis, and tumorigenesis. It is not clear how these events are mechanistically linked to autophagy deficiency. Here, we reveal the role of high-mobility group box 1 (HMGB1) in two of these processes. First, HMGB1 was required for DR, which represents the expansion of hepatic progenitor cells (HPCs) implicated in liver repair and regeneration. DR caused by hepatotoxic diets (3,5-diethoxycarbonyl-1,4-dihydrocollidine [DDC] or choline-deficient, ethionine-supplemented [CDE]) also depended on HMGB1, indicating that HMGB1 may be generally required for DR in various injury scenarios. Second, HMGB1 promoted tumor progression in autophagy-deficient livers. Receptor for advanced glycation end product (RAGE), a receptor for HMGB1, was required in the same two processes and could mediate the proliferative effects of HMBG1 in isolated HPCs. HMGB1 was released from autophagy-deficient hepatocytes independently of cellular injury but depended on NRF2 and the inflammasome, which was activated by NRF2. Pharmacological or genetic activation of NRF2 alone, without disabling autophagy or causing injury, was sufficient to cause inflammasome-dependent HMGB1 release. In conclusion, HMGB1 release is a critical mechanism in hepatic pathogenesis under autophagy-deficient conditions and leads to HPC expansion as well as tumor progression

Predictive modeling of plant messenger RNA polyadenylation sites

BACKGROUND: One of the essential processing events during pre-mRNA maturation is the post-transcriptional addition of a polyadenine [poly(A)] tail. The 3'-end poly(A) track protects mRNA from unregulated degradation, and indicates the integrity of mRNA through recognition by mRNA export and translation machinery. The position of a poly(A) site is predetermined by signals in the pre-mRNA sequence that are recognized by a complex of polyadenylation factors. These signals are generally tri-part sequence patterns around the cleavage site that serves as the future poly(A) site. In plants, there is little sequence conservation among these signal elements, which makes it difficult to develop an accurate algorithm to predict the poly(A) site of a given gene. We attempted to solve this problem. RESULTS: Based on our current working model and the profile of nucleotide sequence distribution of the poly(A) signals and around poly(A) sites in Arabidopsis, we have devised a Generalized Hidden Markov Model based algorithm to predict potential poly(A) sites. The high specificity and sensitivity of the algorithm were demonstrated by testing several datasets, and at the best combinations, both reach 97%. The accuracy of the program, called poly(A) site sleuth or PASS, has been demonstrated by the prediction of many validated poly(A) sites. PASS also predicted the changes of poly(A) site efficiency in poly(A) signal mutants that were constructed and characterized by traditional genetic experiments. The efficacy of PASS was demonstrated by predicting poly(A) sites within long genomic sequences. CONCLUSION: Based on the features of plant poly(A) signals, a computational model was built to effectively predict the poly(A) sites in Arabidopsis genes. The algorithm will be useful in gene annotation because a poly(A) site signifies the end of the transcript. This algorithm can also be used to predict alternative poly(A) sites in known genes, and will be useful in the design of transgenes for crop genetic engineering by predicting and eliminating undesirable poly(A) sites

Comparison of Three Risk Prediction Models for Carotid Atherosclerosis in Steelworkers

BackgroundAs a leading cause of ischemic cerebrovascular disease, carotid atherosclerosis (CAS) lowers the productivity of steelworkers. An increasing number of scholars have used machine learning to identify readily available factors to predict the risk of diseases. But there is still a lack of research on risk prediction models for CAS.ObjectiveTo compare the performance of support vector machine (SVM) -, BP neural network (BPNN) - and random forest (RF) -based models in predicting the risk of CAS in steelworkers.Methods4 568 steelworkers who underwent physical examination and health monitoring in Tangshan Hongci Hospital from March to June 2017 were selected for a survey using the Health Assessment Checklist developed by us for understanding their information about demographic characteristics (sex, age, BMI, education level, marital status) , personal behavior and lifestyle (smoking and drinking) , medical history (hypertension, diabetes, family history of CAS) , occupation history (current work in shifts, working under high temperature or in noisy environments) . Levels of serum cholesterol, triglyceride, homocysteine and uric acid were also collected. Variables for building SVM-, BPNN- and RF-based models for predicting the risk of CAS were determined using unconditioned multivariate Logistic regression analysis and literature review.ResultsIn predicting the risk of CAS in participants in the training set, the accuracy, sensitivity and specificity were 83.81%, 80.10%, 87.32%, respectively, for the SVM-based model, 79.27%, 66.19%, 91.62%, respectively, for the BPNN-based model, and 86.60%, 73.62%, and 98.90%, respectively, for the RF-based model. And the AUC for SVM-, BPNN- and RF-based models was 0.84, 0.79 and 0.86, respectively. The SVM-based model had the highest sensitivity, while the RF-based model had the highest accuracy and specificity (P<0.05) . In predicting the risk of CAS in participants in the test set, the accuracy, sensitivity and specificity were 85.70%, 81.63%, 90.29%, respectively, for the SVM-based model, 75.46%, 64.65%, 87.66%, respectively, for the BPNN-based model, and 73.37%, 60.00%, and 88.45%, respectively, for the RF-based model. And the AUC for SVM-, BPNN- and RF-based models was 0.86, 0.76, and 0.74, respectively. The SVM-based model had the greatest accuracy, sensitivity and AUC. The sensitivity, accuracy and AUC of the SVM-based model were significantly different from those of the BPNN- or RF-based model in predicting the CAS risk (P<0.05) .ConclusionThe SVM-based model may be better than other two models in predicting the risk of CAS in steelworkers

Supplementation of hyaluronic acid injections with vitamin D improve knee function by attenuating synovial fluid oxidative stress in osteoarthritis patients with vitamin D insufficiency

ObjectivesThere is still controversy about the effect of vitamin D supplementation on osteoarthritis (OA). The purpose of this study was to investigate the effects of vitamin D supplementation with Hyaluronic acid (HA) injection on OA.MethodsWe investigated serum vitamin D levels and oxidative stress (OS) in synovial fluid from patients with OA who underwent total knee arthroplasty (grade IV, n = 24) and HA injection (grade II and III, n = 40). The effects of HA injection with or without oral vitamin D supplementation on synovial fluid OS and knee pain and function were then further investigated. Finally, patients underwent HA injection were divided into two groups according to vitamin D levels (vitamin D < or > 30 ng/ml), and the efficacy of the two groups were compared.ResultsThe results showed that the levels of glutathione peroxidase (GSH-PX) (P < 0.05) in the synovial fluid were lower in patients with stage IV OA than that in patients with stage II-III OA, while the levels of malondialdehyde (MDA) (P < 0.05) and lactate dehydrogenase (LDH) (P < 0.01) were significantly higher. Moreover, we found that age, BMI and vitamin D levels were significantly associated with the levels of oxidants and/or antioxidants in synovial fluid, and that vitamin D was significantly negatively correlated with BMI (R = −0.3527, p = 0.0043). Supplementation of HA injections with vitamin D significantly reduced the OS status in synovial fluid, attenuated knee pain and improved knee function in OA patients with vitamin D insufficiency.ConclusionWe conclude that maintenance of vitamin D sufficiency may be beneficial for the treatment of OA by improving OS in synovial fluid