Conformalized matrix completion

Matrix completion aims to estimate missing entries in a data matrix, using the assumption of a low-complexity structure (e.g., low rank) so that imputation is possible. While many effective estimation algorithms exist in the literature, uncertainty quantification for this problem has proved to be challenging, and existing methods are extremely sensitive to model misspecification. In this work, we propose a distribution-free method for predictive inference in the matrix completion problem. Our method adapts the framework of conformal prediction, which provides confidence intervals with guaranteed distribution-free validity in the setting of regression, to the problem of matrix completion. Our resulting method, conformalized matrix completion (cmc), offers provable predictive coverage regardless of the accuracy of the low-rank model. Empirical results on simulated and real data demonstrate that cmc is robust to model misspecification while matching the performance of existing model-based methods when the model is correct.Comment: accepted to 37th Conference on Neural Information Processing Systems (NeurIPS 2023

Conformalized survival analysis with adaptive cutoffs

This paper introduces a method that constructs valid and efficient lower predictive bounds (LPBs) for survival times with censored data. Traditional methods for survival analysis often assume a parametric model for the distribution of survival time as a function of the measured covariates, or assume that this conditional distribution is captured well with a non-parametric method such as random forests; however, these methods may lead to undercoverage if their assumptions are not satisfied. In this paper, we build on recent work by Cand\`es et al. (2021), which offers a more assumption-lean approach to the problem. Their approach first subsets the data to discard any data points with early censoring times and then uses a reweighting technique (namely, weighted conformal inference (Tibshirani et al., 2019)) to correct for the distribution shift introduced by this subsetting procedure. For our new method, instead of constraining to a fixed threshold for the censoring time when subsetting the data, we allow for a covariate-dependent and data-adaptive subsetting step, which is better able to capture the heterogeneity of the censoring mechanism. As a result, our method can lead to LPBs that are less conservative and give more accurate information. We show that in the Type I right-censoring setting, if either of the censoring mechanism or the conditional quantile of survival time is well estimated, our proposed procedure achieves approximately exact marginal coverage, where in the latter case we additionally have approximate conditional coverage. We evaluate the validity and efficiency of our proposed algorithm in numerical experiments, illustrating its advantage when compared with other competing methods. Finally, our method is applied to a real dataset to generate LPBs for users' active times on a mobile app.Comment: 21 pages, 6 figures, and 1 tabl

Cinchonine Prevents High-Fat-Diet-Induced Obesity through Downregulation of Adipogenesis and Adipose Inflammation

Cinchonine (C19H22N2O) is a natural compound of Cinchona bark. Although cinchonine's antiplatelet effect has been reported in the previous study, antiobesity effect of cinchonine has never been studied. The main objective of this study was to investigate whether cinchonine reduces high-fat-diet- (HFD-) induced adipogenesis and inflammation in the epididymal fat tissues of mice and to explore the underlying mechanisms involved in these reductions. HFD-fed mice treated with 0.05% dietary cinchonine for 10 weeks had reduced body weight gain (−38%), visceral fat-pad weights (−26%), and plasma levels of triglyceride, free fatty acids, total cholesterol, and glucose compared with mice fed with the HFD. Moreover, cinchonine significantly reversed HFD-induced downregulations of WNT10b and galanin-mediated signaling molecules and key adipogenic genes in the epididymal adipose tissues of mice. Cinchonine also attenuated the HFD-induced upregulation of proinflammatory cytokines by inhibiting toll-like-receptor-2- (TLR2-) and TLR4-mediated signaling cascades in the adipose tissue of mice. Our findings suggest that dietary cinchonine with its effects on adipogenesis and inflammation may have a potential benefit in preventing obesity

Macrophage inflammatory protein-related protein-2, a novel CC chemokine, can regulate preadipocyte migration and adipocyte differentiation

AbstractAdipocytes not only store energy, but also secrete biologically active molecules called adipocytokines, which play a pivotal role in adipocyte-related pathological processes such as diabetes and cardiovascular disease. Recent studies have shown that preadipocyte/adipocyte expresses chemokines (e.g. monocyte chemoattractant protein-1, macrophage inflammatory protein-1 alpha) which alter adipocyte function, indicating the involvement of chemokines in adipocyte-related pathologies. The current study investigated the potential of macrophage inflammatory protein-related protein-2 (MRP-2), a novel CC chemokine, to modulate preadipocyte trafficking and adipocyte differentiation. MRP-2 and its receptors were highly expressed in preadipocytes and differentiated adipocytes as well as in the mouse fat pad. Chemotaxis assays revealed that MRP-2 was a specific chemotactic regulator in preadipocyte migration. The levels of MRP-2 expression in adipose tissue were enhanced in obese mice compared to lean mice. MRP-2 secretion by preadipocytes was suppressed during differentiation. MRP-2 suppressed the expression of adipocyte differentiation markers such as adipocyte fatty acid-binding protein and glycerol-3 phosphate dehydrogenase. Taken together, our data suggest that MRP-2 plays a role in the regulation of preadipocyte migration and adipocyte differentiation during adipose tissue development. MRP-2 may be another adipocytokine, which can be involved in the adipocyte-related pathological process

Capsaicin, a spicy component of hot peppers, modulates adipokine gene expression and protein release from obese-mouse adipose tissues and isolated adipocytes, and suppresses the inflammatory responses of adipose tissue macrophages

AbstractAdipokines are involved in the obesity-induced chronic inflammatory response that plays a crucial role in the development of obesity-related pathologies such as type II diabetes and atherosclerosis. We here demonstrate that capsaicin, a naturally occurring phytochemical, can suppress obesity-induced inflammation by modulating adipokine release from and macrophage behavior in obese mice adipose tissues. Capsaicin inhibited the expressions of IL-6 and MCP-1 mRNAs and protein release from the adipose tissues and adipocytes of obese mice, whereas it enhanced the expression of the adiponectin gene and protein. The action of capsaicin is associated with NF-κB inactivation and/or PPARγ activation. Moreover, capsaicin suppressed not only macrophage migration induced by the adipose tissue-conditioned medium, but also macrophage activation to release proinflammatory mediators. Capsaicin may be a useful phytochemical for attenuating obesity-induced inflammation and obesity-related complications

Functional Food Targeting the Regulation of Obesity-Induced Inflammatory Responses and Pathologies

Obesity is associated with a low-grade systemic chronic inflammatory state, characterized by the abnormal production of pro- and anti-inflammatory adipocytokines. It has been found that immune cells such as macrophages can infiltrate adipose tissue and are responsible for the majority of inflammatory cytokine production. Obesity-induced inflammation is considered a potential mechanism linking obesity to its related pathologies, such as insulin resistance, cardiovascular diseases, type-2 diabetes, and some immune disorders. Therefore, targeting obesity-related inflammatory components may be a useful strategy to prevent or ameliorate the development of such obesity-related diseases. It has been shown that several food components can modulate inflammatory responses in adipose tissue via various mechanisms, some of which are dependent on peroxisome proliferator-activated receptor γ (PPARγ), whereas others are independent on PPARγ, by attenuating signals of nuclear factor-κB (NF-κB) and/or c-Jun amino-terminal kinase (JNK). In this review, we introduce the beneficial effects of anti-inflammatory phytochemicals that can help prevent obesity-induced inflammatory responses and pathologies

A bibliometric analysis of research progress on pharmacovigilance and cancer from 2002 to 2021

The complexity of cancer itself and treatment makes pharmacovigilance critical in oncology. Despite rapid progress on pharmacovigilance and cancer research in the past two decades, there has been no bibliometric analysis in this field. Therefore, based on the Web of Science database, we used CiteSpace, VOS-viewer and R-bibliometrix to analyze and visualize publications, and described the development trend and research hot spots in this field. 502 publications were included. The development of pharmacovigilance and cancer research has continued to grow. The USA has the largest number of publications and citations, followed by France and UK. Vanderbilt University and Sorbonne University are the institutions that contribute the most papers, and 5 of the top 10 high-yield institutions are from France. Salem JE and Lebrun-Vignes B of Sorbonne University have published the most papers, and they have a strong cooperative relationship. Salem JE has the highest H index. Drug Safety has the largest number of publications in the field of pharmacovigilance and cancer, with a high impact factor (IF). In recent years, immune checkpoint inhibitors (ICIs) have been identified as a hot topic and will continue to be maintained. This paper can help researchers get familiar with the current situation and trend of pharmacovigilance and cancer research, and provide valuable reference for the selection of future research directions

Chemokine Lkn-1/CCL15 enhances matrix metalloproteinase-9 release from human macrophages and macrophage-derived foam cells

Atherosclerosis is characterized by a chronic inflammatory disease, and chemokines play an important role in both initiation and progression of atherosclerosis development. Leukotactin-1 (Lkn-1/CCL15), a new member of the human CC chemokine family, is a potent chemoattractant for leukocytes. Our previous study has demonstrated that Lkn-1/CCL15 plays a role in the initiation of atherosclerosis, however, little is currently known whether Lkn-1/CCL15 is associated with the progression of atherosclerosis. Matrix metalloproteinases (MMPs) in human coronary atherosclerotic lesions play a crucial role in the progression of atherosclerosis by altering the vulnerability of plaque rupture. In the present study, we examined whether Lkn-1/CCL15 modulates MMP-9 release, which is a prevalent form expressed by activated macrophages and foam cells. Human THP-1 monocytic cells and/or human peripheral blood monocytes (PBMC) were treated with phorbol myristate acetate to induce their differentiation into macrophages. Foam cells were prepared by the treatment of THP-1 macrophages with human oxidized LDL. The macrophages and foam cells were treated with Lkn-1/CCL15, and the levels of MMP-9 release were measured by Gelatin Zymography. Lkn-1/CCL15 significantly enhanced the levels of MMP-9 protein secretion from THP-1 monocytic cells-derived macrophages, human PBMC-derived macrophages, as well as macrophage-derived foam cell in a dose dependent manner. Our data suggest that the action of Lkn-1/CCL15 on macrophages and foam cells to release MMP-9 may contribute to plaque destabilization in the progression of atherosclerosis