Are your comments outdated? Towards automatically detecting code-comment consistency

In software development and maintenance, code comments can help developers understand source code, and improve communication among developers. However, developers sometimes neglect to update the corresponding comment when changing the code, resulting in outdated comments (i.e., inconsistent codes and comments). Outdated comments are dangerous and harmful and may mislead subsequent developers. More seriously, the outdated comments may lead to a fatal flaw sometime in the future. To automatically identify the outdated comments in source code, we proposed a learning-based method, called CoCC, to detect the consistency between code and comment. To efficiently identify outdated comments, we extract multiple features from both codes and comments before and after they change. Besides, we also consider the relation between code and comment in our model. Experiment results show that CoCC can effectively detect outdated comments with precision over 90%. In addition, we have identified the 15 most important factors that cause outdated comments, and verified the applicability of CoCC in different programming languages. We also used CoCC to find outdated comments in the latest commits of open source projects, which further proves the effectiveness of the proposed method

Microbial TLR Agonists and Humoral Immunopathogenesis in HIV Disease

Although T cells are the primary and most-studied targets of the Human Immunodeficiency Virus (HIV), B cells, especially memory B lymphocytes, are also chronically depleted in the course of HIV disease. Although the lack of CD4+ T cell help may explain these deficiencies, intrinsic defects in B lymphocytes appear to contribute to B cell depletion and reduced antibody (Ab) production in the setting of HIV, especially of some antigens eliciting T cell-independent responses. The gut mucosal barrier is disrupted in HIV disease, resulting in increased systemic exposure to microbial products such as Toll-Like Receptor (TLR) agonists. The association of enhanced systemic levels of TLR agonists and B cell dysfunction in HIV disease is not understood. This review discusses the potential role of microbial TLR agonists in the B cell depletion, enhanced autoantibody production and impaired responses to vaccination observed in HIV-infected hosts. Increased microbial translocation in HIV infection may drive B cells to produce autoantibodies and increase susceptibilities of B cells to apoptosis through activation-induced cell death. Determining the mechanisms of B cell perturbations in HIV disease will inform the design of novel strategies of improve immune responses to vaccines, reduce opportunistic infections and slow disease progression

Contrastive Counterfactual Learning for Causality-aware Interpretable Recommender Systems

There has been a recent surge in the study of generating recommendations within the framework of causal inference, with the recommendation being treated as a treatment. This approach enhances our understanding of how recommendations influence user behaviour and allows for identification of the factors that contribute to this impact. Many researchers in the field of causal inference for recommender systems have focused on using propensity scores, which can reduce bias but may also introduce additional variance. Other studies have proposed the use of unbiased data from randomized controlled trials, though this approach requires certain assumptions that may be difficult to satisfy in practice. In this paper, we first explore the causality-aware interpretation of recommendations and show that the underlying exposure mechanism can bias the maximum likelihood estimation (MLE) of observational feedback. Given that confounders may be inaccessible for measurement, we propose using contrastive SSL to reduce exposure bias, specifically through the use of inverse propensity scores and the expansion of the positive sample set. Based on theoretical findings, we introduce a new contrastive counterfactual learning method (CCL) that integrates three novel positive sampling strategies based on estimated exposure probability or random counterfactual samples. Through extensive experiments on two real-world datasets, we demonstrate that our CCL outperforms the state-of-the-art methods.Comment: conferenc

Mechanical overloading induces GPX4-regulated chondrocyte ferroptosis in osteoarthritis via Piezo1 channel facilitated calcium influx

Introductions: Excessive mechanical stress is closely associated with cell death in various conditions. Exposure of chondrocytes to excessive mechanical loading leads to a catabolic response as well as exaggerated cell death. Ferroptosis is a recently identified form of cell death during cell aging and degeneration. However, it's potential association with mechanical stress remains to be illustrated. Objectives: To identify whether excessive mechanical stress can cause ferroptosis. To explore the role of mechanical overloading in chondrocyte ferroptosis. Methods: Chondrocytes were collected from loading and unloading zones of cartilage in patients with osteoarthritis (OA), and the ferroptosis phenotype was analyzed through transmission electron microscope and microarray. Moreover, the relationship between ferroptosis and OA was analyzed by GPX4-conditional knockout (Col2a1-CreERT: GPX4flox/flox) mice OA model and chondrocytes cultured with high strain mechanical stress. Furthermore, the role of Piezo1 ion channel in chondrocyte ferroptosis and OA development was explored by using its inhibitor (GsMTx4) and agonist (Yoda1). Additionally, chondrocyte was cultured in calcium-free medium with mechanical stress, and ferroptosis phenotype was tested. Results: Human cartilage and mouse chondrocyte experiments revealed that mechanical overloading can induce GPX4-associated ferroptosis. Conditional knockout of GPX4 in cartilage aggravated experimental OA process, while additional treatment with ferroptosis suppressor protein (FSP-1) and coenzyme Q10 (CoQ10) abated OA development in GPX4-CKO mice. In mouse OA model and chondrocyte experiments, inhibition of Piezo1 channel activity increased GPX4 expression, attenuated ferroptosis phenotype and reduced the severity of osteoarthritis. Additionally, high strain mechanical stress induced ferroptosis damage in chondrocyte was largely abolished by blocking calcium influx through calcium-free medium. Conclusions: Our findings show that mechanical overloading induces ferroptosis through Piezo1 activation and subsequent calcium influx in chondrocytes, which might provide a potential target for OA treatment

Simulation study of BESIII with stitched CMOS pixel detector using ACTS

Reconstruction of tracks of charged particles with high precision is very crucial for HEP experiments to achieve their physics goals. As the tracking detector of BESIII experiment, the BESIII drift chamber has suffered from aging effects resulting in degraded tracking performance after operation for about 15 years. To preserve and enhance the tracking performance of BESIII, one of the proposals is to add one layer of thin CMOS pixel sensor in cylindrical shape based on the state-of-the-art stitching technology, between the beam pipe and the drift chamber. The improvement of tracking performance of BESIII with such an additional pixel detector compared to that with only the existing drift chamber is studied using the modern common tracking software ACTS, which provides a set of detector-agnostic and highly performant tracking algorithms that have demonstrated promising performance for a few high energy physics and nuclear physics experiments

Stemness Analysis Uncovers That The Peroxisome Proliferator-Activated Receptor Signaling Pathway Can Mediate Fatty Acid Homeostasis In Sorafenib-Resistant Hepatocellular Carcinoma Cells

Hepatocellular carcinoma (HCC) stem cells are regarded as an important part of individualized HCC treatment and sorafenib resistance. However, there is lacking systematic assessment of stem-like indices and associations with a response of sorafenib in HCC. Our study thus aimed to evaluate the status of tumor dedifferentiation for HCC and further identify the regulatory mechanisms under the condition of resistance to sorafenib. Datasets of HCC, including messenger RNAs (mRNAs) expression, somatic mutation, and clinical information were collected. The mRNA expression-based stemness index (mRNAsi), which can represent degrees of dedifferentiation of HCC samples, was calculated to predict drug response of sorafenib therapy and prognosis. Next, unsupervised cluster analysis was conducted to distinguish mRNAsi-based subgroups, and gene/geneset functional enrichment analysis was employed to identify key sorafenib resistance-related pathways. In addition, we analyzed and confirmed the regulation of key genes discovered in this study by combining other omics data. Finally, Luciferase reporter assays were performed to validate their regulation. Our study demonstrated that the stemness index obtained from transcriptomic is a promising biomarker to predict the response of sorafenib therapy and the prognosis in HCC. We revealed the peroxisome proliferator-activated receptor signaling pathway (the PPAR signaling pathway), related to fatty acid biosynthesis, that was a potential sorafenib resistance pathway that had not been reported before. By analyzing the core regulatory genes of the PPAR signaling pathway, we identified four candidate target genes, retinoid X receptor beta (RXRB), nuclear receptor subfamily 1 group H member 3 (NR1H3), cytochrome P450 family 8 subfamily B member 1 (CYP8B1) and stearoyl-CoA desaturase (SCD), as a signature to distinguish the response of sorafenib. We proposed and validated that the RXRB and NR1H3 could directly regulate NR1H3 and SCD, respectively. Our results suggest that the combined use of SCD inhibitors and sorafenib may be a promising therapeutic approach

Dickkopf Homolog 3 Induces Stem Cell Differentiation into Smooth Muscle Lineage via ATF6 Signalling

Smooth muscle cells (SMCs) are a key component of healthy and tissue engineered vessels and play a crucial role in vascular development and the pathogenic events of vascular remodeling i.e. restenosis. However, the cell source from which they can be isolated is limited. Embryonic stem (ES) cells that have the remarkable capability to differentiate into vascular SMCs in response to specific stimuli provide a useful model for studying SMC differentiation. Previous studies suggested that dickkopf homolog 3 (DKK3) has a role in human partially induced pluripotent stem cell to SMC differentiation. Here, we demonstrate that the expression of DKK3 is essential for the expression of SMC markers and myocardin at both the mRNA and protein levels during mouse ES cell differentiation into SMCs (ESC-SMC differentiation). Overexpression of DKK3 leads to further up-regulation of the aforementioned markers. Further investigation indicates that DKK3 added as a cytokine activates activating transcription factor 6 (ATF6), leading to the increased binding of ATF6 on the myocardin promoter and increased its expression. In addition, inhibition of extracellular signal-regulated kinases 1/2 (ERK1/2) promotes the expression of ATF6 and leads to further increase of myocardin transcription. Our findings offer a novel mechanism by which DKK3 regulates ESC-SMC differentiation by activating ATF6 and promoting myocardin expression

Examination Stress Results in Attentional Bias and Altered Neural Reactivity in Test-Anxious Individuals

Examination stress occurs so frequently in the lives of students. The neural mechanisms of attentional bias induced by examination stress in test-anxious individuals remain unclear. Accordingly, we investigated the attentional bias toward test-related threatening words in selected high and low test-anxious participants under the stress of final examinations by using an event-related potential (ERP) technique. A classic dot-probe paradigm was adopted with a test-related/test-unrelated threatening word and a neutral word pair as cues. Results showed attention bias and enhanced N200 amplitude toward test-related threat in high test-anxious individuals, whereas avoidance of test-related threat and decreased N200 amplitude were shown in low test-anxious individuals. Additionally, ERP data revealed the relatively enhanced LPP amplitude in low test-anxious participants compared with that in high test-anxious participants. No attentional bias toward test-unrelated threat was found. In conclusion, examination stress resulted in attentional bias and functional perturbations of a brain circuitry that reacted rapidly to test-related threat in high test-anxious individuals