Metformin monotherapy downregulates diabetes-associated inflammatory status and impacts on mortality

Aging is the main risk factor for developing diabetes and other age-related diseases. One of the most common features of age-related comorbidities is the presence of low-grade chronic inflammation. This is also the case of metabolic syndrome and diabetes. At the subclinical level, a pro-inflammatory phenotype was shown to be associated with Type-2 diabetes mellitus (T2DM). This low to mid-grade inflammation is also present in elderly individuals and has been termed inflammaging. Whether inflammation is a component of aging or exclusively associated with age-related diseases in not entirely known. We used clinical data and biological readouts in a group of individuals stratified by age, diabetes status and comorbidities to investigate this aspect. While aging is the main predisposing factor for several diseases there is a concomitant increased level of pro-inflammatory cytokines. DM patients show an increased level of sTNFRll, sICAM-1, and TIMP-1 when compared to Healthy, Non-DM and Pre-DM individuals. These inflammatory molecules are also associated with insulin resistance and metabolic syndrome in Non-DM and pre-DM individuals. We also show that metformin monotherapy was associated with significantly lower levels of inflammatory molecules, like TNF, sTNFRI and sTNFRII, when compared to other monotherapies. Longitudinal follow up indicates a higher proportion of death occurs in individuals taking other monotherapies compared to metformin monotherapy. Together our finding shows that chronic inflammation is present in healthy elderly individuals and exacerbated with diabetes patients. Likewise, metformin could help target age-related chronic inflammation in general, and reduce the predisposition to comorbidities and mortality

Single antenna power measurements based direction finding

In this paper, the problem of estimating direction-ofarrival (DOA) of multiple uncorrelated sources from single antenna power measurements is addressed. Utilizing the fact that the antenna pattern is bandlimited and can be modeled as a finite sum of complex exponentials, we first show that the problem can be transformed into a frequency estimation problem. Then, we explain how the annihilating filter method can be used to solve for the DOA in the noiseless case. In the presence of noise, we propose to use Cadzow denoising that is formulated as an iterative algorithm derived fromexploiting the matrix rank and linear structure properties. Furthermore, we have also derived the Cramér–Rao Bound (CRB) and reviewed several alternative approaches that can be used as a comparison to the proposed approach. From the simulation and experimental results, we demonstrate that the proposed approach significantly outperforms other approaches. It is also evident from the Monte Carlo analysis that the proposed approach converges to the CRB.Accepted versio

A robust approach to optimum widely linear MVDR beamformer

In many array processing, the received signals are nonstationary, or in particular, noncircular. Widely linear minimum variance distortionless response (WL MVDR) beamformers can exploit the noncircularity of received signals and improve the performance of the conventional MVDR beamformer. However, in the optimum WL MVDR beamformer, the array steering vector (ASV) and the signal noncircularity coefficient should be known a priori for the signal of interest. This requirement puts strict limitation to the implementation of this beamformer. We therefore in this paper propose a robust approach to the optimal WL MVDR beamformer that can deal with the uncertainties in the ASV and noncircularity coefficient. Two variants of the proposed approach are developed based on the treatment of the uncertainties. By doing so, the requirement on the exact information is relaxed while the performance improvement can still be obtained. Simulation studies are also provided to illustrate the performance of the proposed approach

Harnessing novel strategies and cell types to overcome immune tolerance during adoptive cell therapy in cancer

Cell therapy encompasses an expanding spectrum of cell-based regimes for the treatment of human ailments, such as the use of immune cells, in particular T cells, for combating tumors and the modulation of inflammatory immune responses. In this review, we focus on cell therapy in the immuno-oncology space, which is largely driven by interests and demands from the clinics for better solutions to target various hard-to-treat cancers. We discuss recent advances in various types of cell therapies, including T cell receptor-T cells, chimeric antigen receptor (CAR)-T cells, tumor-infiltrating lymphocytes and natural killer cells. Particularly, the present review focuses on the strategies to improve therapeutic responses by either enhancing tumor recognition or the resilience of infused immune cells within tumor microenvironment. Finally, we discuss the potential of other innate or innate-like immune cell types currently being explored as promising CAR-cell alternatives that seek to address the limitations of conventional adoptive cell therapies.National Medical Research Council (NMRC)National Research Foundation (NRF)Published versionThis work was supported by the National Research Foundation of Singapore (NRF-CRP26-2021RS-0001), National Medical Research Council (NMRC/OFLCG/003/2018), Taishan Scholar Program of Shandong Province (To Jing Wu), Shandong Natural Science Foundation (ZR2022MH001), National Natural Science Foundation of China (No. 81703617) and Shandong Provincial Qianfoshan Hospital Culture Foundation (No. QYPY-RC2022NSFC1003). Schematic illustrations were created on Biorender

Going Global: Insights of Indonesian Policymakers on International Migration of Nurses

he Indonesian policymakers need to respond to the current challenges, particularly the excess of nurses and the increased demand for nurses in the global market. Objective: This study aimed to present the perception of policymakers and stakeholders on the management of overseas migration of Indonesian nurses. Methods: This study is a descriptive qualitative design where data were collected through structured interviews with key stakeholders representing the Indonesian government, namely the Ministry of Health (MOH), the Ministry of Labour (MOL), Ministry of Education (MOE) and the Indonesian Migrant Workers Protection Agency (BP2MI). The in-depth interviews involved participants who were responsible for managing Indonesian nurses’ migration. The qualitative data were analyzed thematically using a content analysis approach. Results: The issues involving nurses’ migration policy are quite complex and sectoral. Themes emerging from this study include the move towards global market orientation, addressing challenges on international nurse migration, strengthening coordination among stakeholders and making the most of opportunities. All the themes reflect that the country should work hard to achieve the balance between quantity and quality of nursing resources for the international market. Conclusion: As regulator and executor of Indonesian nurse migration, various government policies have responded to the low number of Indonesian nurses’ migration overseas, emphasizing the three cycles of migration: pre-migration, migration and post-migration.The preparation of resources, regulations and placements for Indonesian nurses abroad open the opportunity to the international nursing labour market. Hence, the policies need to be strengthened from upstream to downstream to make Indonesian nurses more competitive and adaptive in global market