Metabolic reprogramming is a hallmark of cancer. However, systematic characterizations of metabolites in triple-negative breast cancer (TNBC) are still lacking. Our study profiled the polar ...metabolome and lipidome in 330 TNBC samples and 149 paired normal breast tissues to construct a large metabolomic atlas of TNBC. Combining with previously established transcriptomic and genomic data of the same cohort, we conducted a comprehensive analysis linking TNBC metabolome to genomics. Our study classified TNBCs into three distinct metabolomic subgroups: C1, characterized by the enrichment of ceramides and fatty acids; C2, featured with the upregulation of metabolites related to oxidation reaction and glycosyl transfer; and C3, having the lowest level of metabolic dysregulation. Based on this newly developed metabolomic dataset, we refined previous TNBC transcriptomic subtypes and identified some crucial subtype-specific metabolites as potential therapeutic targets. The transcriptomic luminal androgen receptor (LAR) subtype overlapped with metabolomic C1 subtype. Experiments on patient-derived organoid and xenograft models indicate that targeting sphingosine-1-phosphate (S1P), an intermediate of the ceramide pathway, is a promising therapy for LAR tumors. Moreover, the transcriptomic basal-like immune-suppressed (BLIS) subtype contained two prognostic metabolomic subgroups (C2 and C3), which could be distinguished through machine-learning methods. We show that N-acetyl-aspartyl-glutamate is a crucial tumor-promoting metabolite and potential therapeutic target for high-risk BLIS tumors. Together, our study reveals the clinical significance of TNBC metabolomics, which can not only optimize the transcriptomic subtyping system, but also suggest novel therapeutic targets. This metabolomic dataset can serve as a useful public resource to promote precision treatment of TNBC.
I demonstrate that skill and scale are mismatched among actively managed equity mutual funds. Many mutual fund investors confuse the effects of fund exposures to common systematic factors with ...managerial skill when allocating capital among funds. Active mutual funds with positive factor-related past returns thus accumulate assets to the point that they significantly underperform. I also show that the negative aggregate benchmark-adjusted performance of active equity mutual funds is driven mainly by these oversized funds.
The tumor microenvironment is highly complex, and immune escape is currently considered an important hallmark of cancer, largely contributing to tumor progression and metastasis. Named for their ...capability of killing target cells autonomously, natural killer (NK) cells serve as the main effector cells toward cancer in innate immunity and are highly heterogeneous in the microenvironment. Most current treatment options harnessing the tumor microenvironment focus on T cell-immunity, either by promoting activating signals or suppressing inhibitory ones. The limited success achieved by T cell immunotherapy highlights the importance of developing new-generation immunotherapeutics, for example utilizing previously ignored NK cells. Although tumors also evolve to resist NK cell-induced cytotoxicity, cytokine supplement, blockade of suppressive molecules and genetic engineering of NK cells may overcome such resistance with great promise in both solid and hematological malignancies. In this review, we summarized the fundamental characteristics and recent advances of NK cells within tumor immunometabolic microenvironment, and discussed potential application and limitations of emerging NK cell-based therapeutic strategies in the era of presicion medicine.
Critical studies on internationalisation of higher education (IHE) have addressed the uneven global geopolitics of knowledge production as reinforced and reproduced through policy making and ...mechanism of professional organisations. Yet it remains unknown about the dynamics of epistemic exchanges in between agents at multiple dimensions of IHE, particularly in Asian contexts. Adopting a critical epistemological perspective Chen, K.-H. 2010. Asia as Method: Toward Deimperialization. Durham, NC: Duke University Press, the present study examines international and Chinese students' epistemic practices in mixed English-Medium-Instruction (EMI) Master's degree programmes in a top-ranked comprehensive university in Shanghai, China. The in-depth student/instructor interviews and ethnographic classroom observation converge to reveal that the EMI curriculum constructs an implicit hegemonic hierarchy among students based on their pre-enrolment possessions of linguistic capital of English and cultural capital concerning Americanised academic norms and discipline-specific knowledge. Given the implicit hegemony, it is also argued that students have developed varied degrees of epistemic awareness and resorted to strategies of inter-referencing and cultural syncretism in order to negotiate diverse epistemic frames of reference with regards (1) English as an academic lingua franca, (2) the epistemic domination of the Global North, and (3) reimagining China and modernity. Practical and conceptual implications on IHE are proposed based on the analysis.
Background and Aims
There is growing evidence that single‐stranded, circular RNA (circRNA) plays a key role in the development of certain cancers, including hepatocellular carcinoma (HCC). It is less ...clear, however, what role circRNA plays in HCC metastasis.
Approach and Results
In this study, through circRNA sequencing, we identified a circRNA: circASAP1 (a circRNA derived from exons 2 and 3 of the ASAP1 gene, hsa_circ_0085616), which is associated with pulmonary metastasis after curative resection in patients with HCC. CircASAP1 was overexpressed in HCC cell lines with high metastatic potential and in metastatic HCCs. In vitro, circASAP1 promoted cell proliferation, colony formation, migration, and invasion, and in vivo, it enhanced tumor growth and pulmonary metastasis. Mechanism studies showed that circASAP1 acts as a competing endogenous RNA for microRNA 326 (miR‐326) and microRNA 532‐5p (miR‐532‐5p), both of which are tumor suppressors in HCC. We found that mitogen‐activated protein kinase (MAPK) 1 and colony stimulating factor (CSF)‐1 were direct common targets for microRNA 326 (miR‐326) and microRNA 532‐5p (miR‐532‐5p), which were regulated by circASAP1. CircASAP1 promotes HCC cell proliferation and invasion by regulating miR‐326/miR‐532‐5p‐MAPK1 signaling and, furthermore, mediates tumor‐associated macrophage infiltration by regulating the miR‐326/miR‐532‐5p‐CSF‐1 pathway. Clinical HCC samples exhibited a positive correlation between circASAP1 expression and levels of CSF‐1, MAPK1, and CD68+ tumor‐associated macrophages, all of which were predictive of patient outcomes.
Conclusion
We identified circASAP1 as a key regulator of HCC metastasis that acts on miR‐326/miR‐532‐5p‐MAPK1/CSF‐1 signaling and serves as a prognostic predictor in patients with HCC.
Empathy promotes positive physician-patient communication and is associated with improved patient satisfaction, treatment adherence and clinical outcomes. It has been suggested that personality ...traits should be taken into consideration in programs designed to enhance empathy in medical education due to the association found between personality and empathy among medical students. However, the associations between empathy and big five personality traits in medical education are still underrepresented in the existing literature and relevant studies have not been conducted among medical students in China, where tensions in the physician-patient relationship have been reported as outstanding problems in the context of China's current medical reform. Thus, the main objective of this study was to examine the associations between empathy and big five personality traits among Chinese medical students.
A cross-sectional study was conducted in a medical university in Northeast China in June 2016. Self-reported questionnaires including the Interpersonal Reactivity Index (IRI) and Big Five Inventory (BFI) and demographic characteristics were distributed. A total of 530 clinical medical students became our final subjects. Hierarchical regression analysis was performed to explore the effects of big five personality traits on empathy.
Results of this study showed that big five personality traits accounted for 19.4%, 18.1%, 30.2% of the variance in three dimensions of empathy, namely, perspective taking, empathic concern and personal distress, respectively. Specifically, agreeableness had a strong positive association with empathic concern (β = 0.477, P<0.01), and a moderate association with perspective taking (β = 0.349, P<0.01). Neuroticism was strongly associated with personal distress (β = 0.526, P<0.01) and modestly associated with perspective taking (β = 0.149, P<0.01). Openness to experience had modest associations with perspective taking (β = 0.150, P<0.01) and personal distress (β = -0.160, P<0.01). Conscientiousness had a modest association with perspective taking (β = 0.173, P<0.01).
This study revealed that big five personality traits were important predictors of self-reported measures of both cognitive and affective empathy among Chinese medical students. Therefore, individualized intervention strategies based on personality traits could be integrated into programs to enhance empathy in medical education.
Funding Value Adjustments ANDERSEN, LEIF; DUFFIE, DARRELL; SONG, YANG
The Journal of finance (New York),
02/2019, Letnik:
74, Številka:
1
Journal Article
Recenzirano
In this paper, we demonstrate that the funding value adjustments (FVAs) of major dealers are debt overhang costs to their shareholders. To maximize shareholder value, dealer quotations therefore ...adjust for FVAs. Our case studies include interest-rate swap FVAs and violations of covered interest parity. Contrary to current valuation practice, FVAs are not themselves components of the market values of the positions being financed. Current dealer practice does, however, align incentives between trading desks and shareholders. We also establish a pecking order for preferred asset financing strategies and provide a new interpretation of the standard debit value adjustment.
Renal cell carcinoma (RCC) is the most common form of kidney cancer, with a high recurrence rate and metastasis capacity. Circular RNAs (circRNAs) have been suggested to act as the critical regulator ...in several diseases. This study is designed to investigate the role of circCSNK1G3 on RCC progression. We observed a highly expression of circCSNK1G3 in RCC tissues compared with normal tissues. The aberrantly circCSNK1G3 promoted the tumour growth and metastasis in RCC. In the subsequent mechanism investigation, we discovered that the tumour‐promoting effects of circCSNK1G3 were, at least partly, achieved by up‐regulating miR‐181b. Increased miR‐181b inhibits several tumour suppressor gene, including CYLD, LATS2, NDRG2 and TIMP3. Furthermore, the decreased TIMP3 leads to the enhanced epithelial to mesenchymal transition (EMT) process, thus promoting the cancer metastasis. In conclusion, we identified the oncogenic role of circCSNK1G3 in RCC progression and demonstrated the regulatory role of circCSNK1G3 induced miR‐181b expression, which leads to TIMP3‐mediated EMT process, thus resulting in tumour growth and metastasis in RCC. This study reveals the promise of circCSNK1G3 to be developed as a potential diagnostic and prognostic biomarker in the clinic. And the roles of circCSNK1G3 in cancer research deserve further investigation.
Federated learning has emerged as an advanced privacy-preserving learning technique for mobile edge computing, where the model is trained in a decentralized manner by the clients, preventing the ...server from directly accessing those private data from the clients. This learning mechanism significantly challenges the attack from the server side. Although the state-of-the-art attacking techniques that incorporated the advance of Generative adversarial networks (GANs) could construct class representatives of the global data distribution among all clients, it is still challenging to distinguishably attack a specific client (i.e., user-level privacy leakage), which is a stronger privacy threat to precisely recover the private data from a specific client. To analyze the privacy leakage of federated learning, this paper gives the first attempt to explore user-level privacy leakage by the attack from a malicious server. We propose a framework incorporating GAN with a multi-task discriminator, called multi-task GAN - Auxiliary Identification (mGAN-AI), which simultaneously discriminates category, reality, and client identity of input samples. The novel discrimination on client identity enables the generator to recover user specified private data. Unlike existing works interfering the federated learning process, the proposed method works "invisibly" on the server side. Furthermore, considering the anonymization strategy for mitigating mGAN-AI, we propose a beforehand linkability attack which re-identifies the anonymized updates by associating the client representatives. A novel siamese network fusing the identification and verification models is developed for measuring the similarity of representatives. The experimental results demonstrate the effectiveness of the proposed approaches and the superior to the state-of-the-art.
Liquid-liquid phase separation (LLPS) is a crucial biological process that governs biomolecular condensation, assembly, and functionality within phase-separated aqueous environments. This phenomenon ...serves as a source of inspiration for the creation of artificial designs in both structured and functional biomaterials, presenting novel strategies for manipulating the structures of functional protein aggregates in a wide range of biomedical applications. This mini review summarizes my past research endeavors, offering a panoramic overview of LLPS-inspired biomaterials utilized in the design of structured materials, the development of cell mimetics, and the advancement of intelligent biomaterials.
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