INSIGHT INTO THE BIOENERGETICS OF CLEAR CELL RENAL CELL CARCINOMA (CCRCC)

Master'sMASTER OF SCIENC

On the Robustness, Generalization, and Forgetting of Shape-Texture Debiased Continual Learning

Tremendous progress has been made in continual learning to maintain good performance on old tasks when learning new tasks by tackling the catastrophic forgetting problem of neural networks. This paper advances continual learning by further considering its out-of-distribution robustness, in response to the vulnerability of continually trained models to distribution shifts (e.g., due to data corruptions and domain shifts) in inference. To this end, we propose shape-texture debiased continual learning. The key idea is to learn generalizable and robust representations for each task with shape-texture debiased training. In order to transform standard continual learning to shape-texture debiased continual learning, we propose shape-texture debiased data generation and online shape-texture debiased self-distillation. Experiments on six datasets demonstrate the benefits of our approach in improving generalization and robustness, as well as reducing forgetting. Our analysis on the flatness of the loss landscape explains the advantages. Moreover, our approach can be easily combined with new advanced architectures such as vision transformer, and applied to more challenging scenarios such as exemplar-free continual learning

Keyword-Aware Relative Spatio-Temporal Graph Networks for Video Question Answering

The main challenge in video question answering (VideoQA) is to capture and understand the complex spatial and temporal relations between objects based on given questions. Existing graph-based methods for VideoQA usually ignore keywords in questions and employ a simple graph to aggregate features without considering relative relations between objects, which may lead to inferior performance. In this paper, we propose a Keyword-aware Relative Spatio-Temporal (KRST) graph network for VideoQA. First, to make question features aware of keywords, we employ an attention mechanism to assign high weights to keywords during question encoding. The keyword-aware question features are then used to guide video graph construction. Second, because relations are relative, we integrate the relative relation modeling to better capture the spatio-temporal dynamics among object nodes. Moreover, we disentangle the spatio-temporal reasoning into an object-level spatial graph and a frame-level temporal graph, which reduces the impact of spatial and temporal relation reasoning on each other. Extensive experiments on the TGIF-QA, MSVD-QA and MSRVTT-QA datasets demonstrate the superiority of our KRST over multiple state-of-the-art methods.Comment: under revie

PTEN/Akt Signaling Controls Mitochondrial Respiratory Capacity through 4E-BP1

10.1371/journal.pone.0045806PLoS ONE79

Health-related quality of life of patients with inflammatory bowel disease in Singapore

Background/Aims Inflammatory bowel disease (IBD) is associated with considerable impairment of patients’ health-related quality of life (HRQoL). Knowledge of factors that significantly affect IBD patients’ HRQoL can contribute to better patient care. However, the HRQoL of IBD patients in non-Western countries are limited. Hence, we assessed the HRQoL of Singaporean IBD patients and identified its determinants. Methods A prospective, cross-sectional study was conducted at Singapore General Hospital outpatient IBD Centre. The HRQoL of IBD patients was assessed using the short IBD questionnaire (SIBDQ), Short Form-36 physical and mental component summary (SF-36 PCS/MCS) and EuroQol 5-dimensions 3-levels (EQ-5D-3L) and visual analogue scale (VAS). Independent samples t-test was used to compare HRQoL between Crohn’s disease (CD) and ulcerative colitis (UC). Determinants of HRQoL were identified through multiple linear regression. Results A total of 195 IBD patients (103 UC, 92 CD) with a mean disease duration of 11.2 years were included. There was no significant difference in HRQoL between patients with UC and CD. Factors that significantly worsened HRQoL were presence of active disease (b=−6.293 [SIBDQ], −9.409 [PCS], −9.743 [MCS], −7.254 [VAS]), corticosteroids use (b=−7.392 [SIBDQ], −10.390 [PCS], −8.827 [MCS]), poor medication adherence (b=−4.049 [SIBDQ], −1.320 [MCS], −8.961 [VAS]), presence of extraintestinal manifestations (b=−13.381 [PCS]), comorbidities (b=−4.531 [PCS]), non-employment (b=−9.738 [MCS], −0.104 [EQ-5D-3L]) and public housing (b=−8.070 [PCS], −9.207 [VAS]). Conclusions The HRQoL is impaired in this Asian cohort of IBD. The magnitude of HRQoL impairment was similar in UC and CD. Clinical characteristics were better determinants of patients’ HRQoL than socio-demographic factors. Recognizing the factors that impact patients’ HRQoL would improve the holistic management of IBD patients

Injectable liposomal docosahexaenoic acid alleviates atherosclerosis progression and enhances plaque stability

Atherosclerosis is a chronic inflammatory vascular disease that is characterized by the accumulation of lipids and immune cells in plaques built up inside artery walls. Docosahexaenoic acid (DHA, 22:6n-3), an omega-3 polyunsaturated fatty acid (PUFA), which exerts anti-inflammatory and antioxidant properties, has long been purported to be of therapeutic benefit to atherosclerosis patients. However, large clinical trials have yielded inconsistent data, likely due to variations in the formulation, dosage, and bioavailability of DHA following oral intake. To fully exploit its potential therapeutic effects, we have developed an injectable liposomal DHA formulation intended for intravenous administration as a plaque-targeted nanomedicine. The liposomal formulation protects DHA against chemical degradation and increases its local concentration within atherosclerotic lesions. Mechanistically, DHA liposomes are readily phagocytosed by activated macrophages, exert potent anti-inflammatory and antioxidant effects, and inhibit foam cell formation. Upon intravenous administration, DHA liposomes accumulate preferentially in atherosclerotic lesional macrophages and promote polarization of macrophages towards an anti-inflammatory M2 phenotype, resulting in attenuation of atherosclerosis progression in both ApoE−/− and Ldlr−/− experimental models. Plaque composition analysis demonstrates that liposomal DHA inhibits macrophage infiltration, reduces lipid deposition, and increases collagen content, thus improving the stability of atherosclerotic plaques against rupture. Matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) further reveals that DHA liposomes can partly restore the complex lipid profile of the plaques to that of early-stage plaques. In conclusion, DHA liposomes offer a promising approach for applying DHA to stabilize atherosclerotic plaques and attenuate atherosclerosis progression, thereby preventing atherosclerosis-related cardiovascular events

A three-dimensional atlas of human dermal leukocytes, lymphatics, and blood vessels.

Dendritic cells (DCs), macrophages (Mφ), and T cells are major components of the skin immune system, but their interstitial spatial organization is poorly characterized. Using four-channel whole-mount immunofluorescence staining of the human dermis, we demonstrated the three-dimensional distribution of CD31(+) blood capillaries, LYVE-1(+) lymphatics, discrete populations of CD11c(+) myeloid DCs, FXIIIa(+) Mφ, and lymphocytes. We showed phenotypic and morphological differences in situ between DCs and Mφ. DCs formed the first dermal cellular layer (0-20 μm beneath the dermoepidermal junction), Mφ were located deeper (40-60 μm), and CD3(+) lymphocytes were observed throughout (0-60 μm). Below this level, DCs, T cells, and the majority of Mφ formed stable perivascular sheaths. Whole-mount imaging revealed the true extent of dermal leukocytes previously underestimated from cross-section views. The total area of apical dermis (0-30 μm) contained approximately 10-fold more myeloid DCs than the entire blood volume of an average individual. Surprisingly, <1% of dermal DCs occupied lymphatics in freshly isolated skin. Dermal DCs rapidly accumulated within lymphatics, but Mφ remained fixed in skin explants cultured ex vivo. The leukocyte architecture observed in normal skin was distorted in inflammation and disease. These studies illustrate the micro-anatomy of dermal leukocytes and provide further insights into their functional organization

DC mobilization from the skin requires docking to immobilized CCL21 on lymphatic endothelium and intralymphatic crawling

Dermal DC mobilization requires docking to CCL21 on lymphatic endotheliu

ROLE OF LYMPHATIC VESSELS IN CHOLESTEROL CLEARANCE AND THE INVOLVEMENT OF HIGH DENSITY LIPOPROTEINS IN REGULATING LYMPHATIC FUNCTION

Ph.DDOCTOR OF PHILOSOPHY (SOM