Mobile Messenger rating, sharing and engagement in global social commerce

The use of the Short Message Service (SMS), available on mobile phones and other devices, for exchanging text messages is gradually diminishing. SMS has been replaced by Smart Phone Apps offering free messaging services; example include Whatsapp, Kakao, WeChat and Viber. The use of these platforms is constantly evolving; they are now used for advertising, group chatting, the sharing of information, and e-commerce communication. This paper provides a review of the currently available Mobile Messenger Applications, comparing their abilities, function and features. In particular the paper focuses on the engaging of these Apps in Global Social Commerce. In addition, the engagement of users towards sharing, commenting and rating the products and services were also discussed

AN EVALUATION OF THE POOLED LOLLI-METHOD RT-qPCR TESTING FOR COVID-19 SURVEILLANCE IN SINGAPORE

Background: Following the success of the Lolli-Method or Lolli-Test as a surveillance method in Germany, the Ministry of Health, Singapore investigated the feasibility of deploying the method as a rostered routine testing in vulnerable individuals such as children, nursing homes and frontline workers; and evaluated the sensitivity and ideal pooling ratio of the Lolli-Method.  Methods: The study was conducted in two phases – the first phase was to assess the operational feasibility of the Lolli-Method. It was held in conjunction with air sampling at a childcare centre with children ages 2 to 6 years old across 40 days. The second phase was to evaluate the sensitivity of the Lolli-Method with different pooling ratios and was conducted in collaboration with the National Centre for Infectious Diseases (NCID) where each pool was spiked with one Lolli swab from a COVID-positive patient. All patients enrolled in this study have their viral load cycle threshold (CT) levels assessed prior to admission via a mid-turbinate oropharyngeal (MTOP) polymerase chain reaction (PCR) swab.  Results: The sensitivity of the pooled Lolli-Test was similar to antigen rapid tests with 100% sensitivity (3/3) in a pooling ratio of 20:1 for patients with viral loads of cycle threshold (CT) levels below 20. For individuals with lower viral loads, the sensitivity of the Lolli-Test was 66.7% (2/3) in a pooling ratio of 20:1 and 100% (2/2) in a smaller pooling ratio of 15:1. The operational feasibility of the Lolli-Test was assessed to be high amongst study participants although students were noted to require some additional assistance from teachers.  Conclusion: The Lolli-Test is an effective surveillance method with adequate sensitivity to detect a COVID-19 infected individual in a pool of up to 20 albeit largely dependent on the viral load. Furthermore, the Lolli-Test also provides a less invasive alternative sample collection method for individuals who cannot tolerate or have contraindications for the regular nasal or oropharyngeal swabs such as young children. More studies should be done to assess the Lolli-Test’s true limit of detection and to evaluate the use of the Lolli-Method in infants and for other respiratory diseases such as influenza

Human fetal dendritic cells promote prenatal T-cell immune suppression through arginase-2.

During gestation the developing human fetus is exposed to a diverse range of potentially immune-stimulatory molecules including semi-allogeneic antigens from maternal cells, substances from ingested amniotic fluid, food antigens, and microbes. Yet the capacity of the fetal immune system, including antigen-presenting cells, to detect and respond to such stimuli remains unclear. In particular, dendritic cells, which are crucial for effective immunity and tolerance, remain poorly characterized in the developing fetus. Here we show that subsets of antigen-presenting cells can be identified in fetal tissues and are related to adult populations of antigen-presenting cells. Similar to adult dendritic cells, fetal dendritic cells migrate to lymph nodes and respond to toll-like receptor ligation; however, they differ markedly in their response to allogeneic antigens, strongly promoting regulatory T-cell induction and inhibiting T-cell tumour-necrosis factor-α production through arginase-2 activity. Our results reveal a previously unappreciated role of dendritic cells within the developing fetus and indicate that they mediate homeostatic immune-suppressive responses during gestation

Association analyses of East Asian individuals and trans-ancestry analyses with European individuals reveal new loci associated with cholesterol and triglyceride levels

Large-scale meta-analyses of genome-wide association studies (GWAS) have identified >175 loci associated with fasting cholesterol levels, including total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and triglycerides (TG). With differences in linkage disequilibrium (LD) structure and allele frequencies between ancestry groups, studies in additional large samples may detect new associations. We conducted staged GWAS meta-analyses in up to 69,414 East Asian individuals from 24 studies with participants from Japan, the Philippines, Korea, China, Singapore, and Taiwan. These meta-analyses identified (P < 5 × 10-8) three novel loci associated with HDL-C near CD163-APOBEC1 (P = 7.4 × 10-9), NCOA2 (P = 1.6 × 10-8), and NID2-PTGDR (P = 4.2 × 10-8), and one novel locus associated with TG near WDR11-FGFR2 (P = 2.7 × 10-10). Conditional analyses identified a second signal near CD163-APOBEC1. We then combined results from the East Asian meta-analysis with association results from up to 187,365 European individuals from the Global Lipids Genetics Consortium in a trans-ancestry meta-analysis. This analysis identified (log10Bayes Factor ≥6.1) eight additional novel lipid loci. Among the twelve total loci identified, the index variants at eight loci have demonstrated at least nominal significance with other metabolic traits in prior studies, and two loci exhibited coincident eQTLs (P < 1 × 10-5) in subcutaneous adipose tissue for BPTF and PDGFC. Taken together, these analyses identified multiple novel lipid loci, providing new potential therapeutic targets

Multiancestry Genome-Wide Association Study of Lipid Levels Incorporating Gene-Alcohol Interactions

A person's lipid profile is influenced by genetic variants and alcohol consumption, but the contribution of interactions between these exposures has not been studied. We therefore incorporated gene-alcohol interactions into a multiancestry genome-wide association study of levels of high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and triglycerides. We included 45 studies in stage 1 (genome-wide discovery) and 66 studies in stage 2 (focused follow-up), for a total of 394,584 individuals from 5 ancestry groups. Analyses covered the period July 2014-November 2017. Genetic main effects and interaction effects were jointly assessed by means of a 2-degrees-of-freedom (df) test, and a 1-df test was used to assess the interaction effects alone. Variants at 495 loci were at least suggestively associated (P <1 x 10(-6)) with lipid levels in stage 1 and were evaluated in stage 2, followed by combined analyses of stage 1 and stage 2. In the combined analysis of stages 1 and 2, a total of 147 independent loci were associated with lipid levels at P <5 x 10(-8) using 2-df tests, of which 18 were novel. No genome-wide-significant associations were found testing the interaction effect alone. The novel loci included several genes (proprotein convertase subtilisin/kexin type 5 (PCSK5), vascular endothelial growth factor B (VEGFB), and apolipoprotein B mRNA editing enzyme, catalytic polypeptide 1 (APOBEC1) complementation factor (A1CF)) that have a putative role in lipid metabolism on the basis of existing evidence from cellular and experimental models.Peer reviewe

Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples

Funder: NCI U24CA211006Abstract: The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) curated consensus somatic mutation calls using whole exome sequencing (WES) and whole genome sequencing (WGS), respectively. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2,658 cancers across 38 tumour types, we compare WES and WGS side-by-side from 746 TCGA samples, finding that ~80% of mutations overlap in covered exonic regions. We estimate that low variant allele fraction (VAF < 15%) and clonal heterogeneity contribute up to 68% of private WGS mutations and 71% of private WES mutations. We observe that ~30% of private WGS mutations trace to mutations identified by a single variant caller in WES consensus efforts. WGS captures both ~50% more variation in exonic regions and un-observed mutations in loci with variable GC-content. Together, our analysis highlights technological divergences between two reproducible somatic variant detection efforts

Scar prevention through topical delivery of gelatin-tyramine-siSPARC nanoplex loaded in dissolvable hyaluronic acid microneedle patch across skin barrier

Currently, there is no effective method to prevent the formation of hypertrophic scars and keloids, which can cause severe physical and psychological burdens to patients. Secreted protein acidic and cysteine-rich (SPARC) is involved in wound fibrosis by modulating fibroblast functions, causing excessive collagen deposition during wound healing. Thus, the reduction in SPARC gene expression after wounding can contribute to the downstream reduction in collagen production at the wound site and prevent scar formation. In this study, a dissolvable and biocompatible hyaluronic acid (HA) microneedle patch loaded with nanoplexes containing tyramine-modified gelatin and siRNA for SPARC (siSPARC/Gtn-Tyr) was investigated for topical scar prevention. Tyramine-modified gelatin (Gtn-Tyr) provides electrostatic protection and enhances cell internalization for siSPARC. In vitro studies using human dermal fibroblasts showed that both siSPARC/Gtn-Tyr nanoplexes and siSPARC/Gtn-Tyr-loaded microneedle patches can significantly reduce SPARC gene expression (P < 0.05) and do not cause discernable cytotoxic effects. Further studies using a mouse wound model demonstrate that the siSPARC/Gtn-Tyr-loaded microneedle patch can reduce collagen production during wound healing without triggering an immune response. When Gtn-Tyr-siSPARC is administered transdermally at the wound site, effective collagen reduction is achieved through silencing of the matricellular SPARC protein, thus promising the reduction of scar formation. Overall, the siSPARC/Gtn-Tyr loaded microneedle patch can potentially provide an effective transdermal anti-fibrotic treatment.Ministry of Education (MOE)Ministry of Health (MOH)National Medical Research Council (NMRC)The authors gratefully acknowledge the support by Singapore Ministry of Education under its NTUitive Gap Fund grant scheme (NGF-2019-07-004) and Singapore Ministry of Health’s National Medical Research Council under its Clinician Scientist Award (CSAINV20nov-0003)

A 9.87 nW 1 kS/s 8.7 ENOB SAR ADC for implantable epileptic seizure detection microsystems

This paper presents an ultra low-power SAR ADC in 0.18 μm CMOS technology for epileptic seizure detection applications. The ADC is powered by a single supply voltage of both analog and digital circuits to avoid using the level-shifters. A latched comparator is used to quickly generate the comparison results while consuming no DC current. Split-cap architecture with an attenuation cap is used to minimize area and to further reduce the power consumption. A smaller-than-unit capacitor is used at the end of the least significant bit array to mitigate the negative impact of the parasitic components on the linearity of the capacitors array. As a result, both DNL/INL and SNDR of the ADC is improved. Our post-layout simulation shows that at 1 V supply, 1 kS/s the proposed SAR archives 8.7 ENOB while consuming only 9.87 nW. This yields an FOM of 23.7 fJ/conversion-step. Its leakage power consumption is 1.46 nW

Ex vivo-expanded but not in vitro-induced human regulatory T cells are candidates for cell therapy in autoimmune diseases thanks to stable demethylation of the FOXP3 regulatory T cell-specific demethylated region

Regulatory T cell (Treg) therapy is a promising approach for transplant rejection and severe autoimmunity. Unfortunately, clinically meaningful Treg numbers can be obtained only upon in vitro culture. Functional stability of human expanded (e)Tregs and induced (i)Tregs has not been thoroughly addressed for all proposed protocols, hindering clinical translation. We undertook a systematic comparison of eTregs and iTregs to recommend the most suitable for clinical implementation, and then tested their effectiveness and feasibility in rheumatoid arthritis (RA). Regardless of the treatment, iTregs acquired suppressive function and FOXP3 expression, but lost them upon secondary restimulation in the absence of differentiation factors, which mimics in vivo reactivation. In contrast, eTregs expanded in the presence of rapamycin (rapa) retained their regulatory properties and FOXP3 demethylation upon restimulation with no stabilizing agent. FOXP3 demethylation predicted Treg functional stability upon secondary TCR engagement. Rapa eTregs suppressed conventional T cell proliferation via both surface (CTLA-4) and secreted (IL-10, TGF-β, and IL-35) mediators, similarly to ex vivo Tregs. Importantly, Treg expansion with rapa from RA patients produced functionally stable Tregs with yields comparable to healthy donors. Moreover, rapa eTregs from RA patients were resistant to suppression reversal by the proinflammatory cytokine TNF-α, and were more efficient in suppressing synovial conventional T cell proliferation compared with their ex vivo counterparts, suggesting that rapa improves both Treg function and stability. In conclusion, our data indicate Treg expansion with rapa as the protocol of choice for clinical application in rheumatological settings, with assessment of FOXP3 demethylation as a necessary quality control step

A 160 nW 25 kS/s 9-bit SAR ADC for neural signal recording applications

This paper presents a 9-bit 25 kS/s SAR ADC in 0.18 μm CMOS technology for neural signal recording applications. The ADC is powered by a single supply voltage of 1V to comply with other digital processing units on the same chip. The proposed ADC has one common-mode DC input of 0.5V thus offering a full-range sampling with only one pair of PMOS input transistors in the latched comparator. A versatile digital interface block is implemented to translate external control signals to internally useful Sample-and-Hold (S/H) commands, allowing a flexible S/H duration to match with the driving strength of the input buffer. To realize an ultra low-power performance, all digital blocks and the comparator are carefully optimized. At the same time, split-cap architecture with an attenuation cap is used to minimize area and to further reduce the power consumption. Our simulation shows that the proposed SAR archives 8.5 ENOB while consuming only 160 nW