REVIEW | doi:10.20944/preprints201904.0007.v1
Subject: Life Sciences, Immunology Keywords: dendritic cells; Th2 immunity; genetic factors; environmental factors; Th2 disorders; therapeutic approaches
Online: 1 April 2019 (10:14:44 CEST)
Dendritic cells (DCs) are the professional antigen-presenting cells that recognize and present antigens to naïve T cells to induce antigen-specific adaptive immunity. Among the T-cell subsets, T helper type 2 (Th2) cells produce the humoral immune responses required for protection against helminthic disease by activating B cells. DCs induce a Th2 immune response at a certain immune environment. Basophil, eosinophil, mast cells, and type 2 innate lymphoid cells also induce Th2 immunity. However, in the case of DCs, controversy remains regarding which subsets of DCs induce Th2 immunity, which genes in DCs are directly or indirectly involved in inducing Th2 immunity, and the detailed mechanisms underlying induction, regulation, or maintenance of the DC-mediated Th2 immunity against allergic environments and parasite infection. A recent study has shown that a genetic defect in DCs causes an enhanced Th2 immunity leading to a severe atopic dermatitis. We summarize the Th2 immune-inducing DC subsets, the genetic and environmental factors which involved in DC-mediated Th2 immunity, and current therapeutic approaches for Th2-mediated immune disorders. This review is to provide an improved understanding of DC-mediated Th2 immunity and Th1/Th2 immune balancing, leading to control over their adverse consequences.
ARTICLE | doi:10.20944/preprints201801.0125.v1
Subject: Mathematics & Computer Science, Probability And Statistics Keywords: multi-criteria decision analysis (MCDA); online broker; misspecification of criteria; structural uncertainty; unsupervised machine learning; factor analysis, quality of service (QoS)
Online: 15 January 2018 (11:29:56 CET)
Multi-criteria decision analysis (MCDA), one of the prevalent branches of operations research, aims to design mathematical and computational tools for selecting the best alternative among several choices with respect to specific criteria. In the cloud, MCDA based online brokers uses customer specified criteria to rank different service providers. However, subjected to limited domain knowledge, the customer may exclude relevant or include irrelevant criterion, which could result in suboptimal ranking of service providers. To deal with such misspecification, this research proposes a model, which uses notion of factor analysis from the domain of unsupervised machine learning. The model is evaluated using two quality-of-service (QoS) based datasets. The first dataset i.e., feedback from customers, was compiled using leading review websites such as Cloud Hosting Reviews, Best Cloud Computing Providers, and Cloud Storage Reviews and Ratings. The second dataset i.e., feedback from servers, was generated from cloud brokerage architecture that was emulated using high performance computing (HPC) cluster at University of Luxembourg (HPC @ Uni.lu). The simulation runs in a stable cloud environment i.e. when uncertainty is low, shows that online broker (equipped with the proposed model) produces optimized ranking of service providers as compared to other brokers. This is due the fact that proposed model assigns priorities to criteria objectively (using machine learning) rather than using priorities based on subjective judgments of the customer. This research will benefit potential cloud customers that view insufficient domain knowledge as a limiting factor for acquisition of web services in the cloud.
REVIEW | doi:10.20944/preprints202105.0193.v1
Subject: Life Sciences, Immunology Keywords: Epitranscriptomics, acute myeloid leukemia, microRNA, CISH, Immunotherapeutics.
Online: 10 May 2021 (13:53:12 CEST)
Epigenetic alterations have contributed greatly to human carcinogenesis. Conventional epigenetic studies have been predominantly focused on DNA methylation, histone modifications and chromatin remodelling. However, recently, RNA modification (m6A-methylation) also termed ‘epitranscriptomics’ has emerged as a new layer of epigenetic regulation due to its diverse role in various biological processes. In this review, we have summarized the therapeutic potential of m6A-modifiers in controlling haematological disorders especially acute myeloid leukemia (AML). It is a type of blood cancer affecting specific subsets of blood-forming hematopoietic stem/progenitor cells (HSPCs) which proliferate rapidly and acquire self-renewable capacities with impaired terminal cell-differentiation and apoptosis leading to abnormal accumulation of white blood cells, and thus an alternative therapeutic approach is required urgently. Here, we have described how RNA m6A-modification machineries EEE (Editor/writer: Mettl3, Mettl14; Eraser/remover: FTO, ALKBH5 and Effector/reader: YTHDF-1/2) could be reformed into potential druggable candidate or as RNA modifying drug (RMD) to treat leukemia. Moreover, we have shed-light on the role of microRNA and suppressor of cytokine signalling (SOCS/CISH) in increasing anti-tumor immunity towards leukemia. We anticipate, our investigation will provide a fundamental knowledge in nurturing the potential of RNA modifiers in discovering novel therapeutics or immunotherapeutic procedures.
REVIEW | doi:10.20944/preprints202103.0720.v1
Subject: Engineering, Automotive Engineering Keywords: microneedle; microneedle array, interstitial fluid; bio sensing, wearable system; ISF sampling
Online: 30 March 2021 (09:55:02 CEST)
Dermal interstitial fluid (ISF) is a novel source of biomarkers that can be considered as an alternative to blood sampling for disease diagnosis and treatment. Nevertheless, in vivo extraction and analysis of ISF are challenging. On the other hand, microneedle (MN) technology can address most of the challenges associated with dermal ISF extraction and is well-suited for long-term, continuous ISF monitoring as well as in situ detection. In this review, we first briefly summarise the different dermal ISF collection methods and compare them with MN methods. Next, we elaborate on the design considerations and biocompatibility of MNs. Subsequently, the fabrication technologies of various MNs used for dermal ISF extraction, including solid MNs, hollow MNs, porous MNs and hydrogel MNs, are thoroughly explained. In addition, different sensing mechanisms of ISF detection will be discussed in detail. Subsequently, we identify the challenges and propose the possible solutions associated with ISF extraction. A detailed investigation is provided for the transport and sampling mechanism of ISF in vivo. Also, the current in vitro skin model integrated with the MN arrays will be discussed. Finally, future directions to develop a point-of-care (POC) device to sample ISF are proposed.
ARTICLE | doi:10.20944/preprints202107.0640.v1
Subject: Engineering, Automotive Engineering Keywords: SARS-COV-2; Loop-mediated isothermal amplification; Portable device.
Online: 28 July 2021 (17:49:56 CEST)
This paper reports the design, development, and testing of a novel, yet simple and low-cost portable device for the rapid detection of SARS-CoV-2. The device performs loop mediated isothermal amplification (LAMP) and provides visually distinguishable images of the fluorescence emitted from the samples. The device utilises an aluminium block embedded with a cartridge heater for isothermal heating of the sample and a single-board computer and camera for fluorescence detection. The device demonstrates promising results within 20 minutes using clinically relevant starting concentrations of the synthetic template. Time-to-signal data for this device are considerably lower compared to standard qPCR machine (~10-20 minutes vs >38 minutes) for 1×105 starting template copy number. The device in its fully optimized and characterized state can potentially be used as simple to operate, rapid, sensitive, and inexpensive platform for population screening as well as point-of-need SARS-CoV-2 detection and patient management.
ARTICLE | doi:10.20944/preprints202107.0181.v1
Subject: Chemistry, Analytical Chemistry Keywords: SARS-CoV-2 detection; Immunofluorescence; Paper-based diagnostic device
Online: 7 July 2021 (13:18:33 CEST)
We report on an immunofluorescent paper-based assay for the detection of severe acute respiratory symptom coronavirus 2 (SARS-CoV-2) humanized antibody. The paper-based device was fabricated by using lamination technique for easy and optimized handling. Our approach utilises a two-step strategy that involves (i) initial coating of the paper-electrode with recombinant SARS-CoV-2 nucleocapsid antigen to capture the target SARS-CoV-2 specific antibodies, and (ii) subsequent detection of SARS-CoV-2 antibodies using fluorophore-conjugated IgG antibody. The fluorescence readout was observed with fluorescence microscopy. The images were processed and quantified using a MATLAB program. The assay can selectively detect SARS-CoV-2 humanized antibodies spiked in PBS and healthy human serum samples with the relative standard deviation of approximately 6.4% (for n = 3). It has broad dynamic ranges (1 ng to 50 ng/µL in PBS and 5 to 100 ng/µL in human serum samples) for SARS-CoV-2 humanized antibodies with the detection limits of 2 ng/µL (0.025 IU/mL) and 10 ng/µL (0.125 IU/mL) in PBS and human serum samples, respectively. We believe that our assay has the potential to be used as a simple, rapid, and inexpensive paper-based diagnostic device with a portable fluorescent reader to provide point-of-care diagnosis. This assay can be used for rapid examination of a large batch of samples toward clinical screening of SARS-CoV-2 specific antibodies as a confirmed infected active case or to evaluate the immune response to a SARS-CoV-2 vaccine.
REVIEW | doi:10.20944/preprints202108.0112.v1
Subject: Life Sciences, Immunology Keywords: Epitranscriptomics, Immune checkpoint blockage (ICB) therapy, anti-PD-1/PD-L1 drug resistance, Personalized medicine, CISH, microRNAs
Online: 4 August 2021 (13:02:22 CEST)
Cellular immunotherapy has recently emerged as a fourth pillar in cancer treatment co-joining surgery, chemotherapy and radiotherapy. Where, the discovery of immune checkpoint blockage or inhibition (ICB/ICI), anti-PD-1/PD-L1 and anti-CTLA4-based, therapy has revolutionized the class of cancer treatment at a different level. However, still some cancer patient escape this immune surveillance mechanism and become resistant to ICB-therapy. Therefore, a more advanced or an alternative treatment is required instantly. Despite the functional importance of epitranscriptomics in diverse clinico-biological practices, its role in improving the efficacy of ICB therapeutics has been limited. Consequently, our study encapsulates the evidences, as a possible strategy, to improve the efficacy of ICB-therapy by co-targeting molecular checkpoints especially N6A-modification machineries which could be reformed into RNA modifying drugs (RMD). Here, we have explained the mechanism of individual RNA-modifiers (editor/writer, eraser/remover and effector/reader) in overcoming the issues associated with high-dose antibody toxicities and drug-resistance. Moreover, we have shed light on the importance of suppressor of cytokine signalling (SOCS/CISH) and microRNAs in improving the efficacy of ICB-therapy, with brief insight on the current monoclonal antibodies undergoing clinical trials or already approved against several solid tumor and metastatic cancers. We anticipate our investigation will encourage researchers and clinicians to further strengthen the efficacy of ICB-therapeutics by considering the importance of epitranscriptomics as a personalized medicine.
ARTICLE | doi:10.20944/preprints202107.0195.v1
Subject: Chemistry, Analytical Chemistry Keywords: Loop-mediated isothermal amplification; AXL over expression; core-shell beads assay
Online: 8 July 2021 (10:57:31 CEST)
The upregulated expression of thyrosine kinase AXL has been reported in several hematologic and solid human tumors including gastric, breast, colorectal, prostate, and ovarian cancers. Thus, AXL can potentially serve as a diagnostic and prognostic biomarker for various cancers. This paper reports the first-ever use of loop-mediated isothermal amplification (LAMP) of the AXL gene as a diagnostic method for ovarian cancer. We demonstrated simple instrumentation toward a point-of-care device to perform LAMP. This paper also reports the first-ever use of core-shell beads as a microreactor to perform LAMP as an attempt to promote environmentally friendly laboratory practices.