The shift to redefine nonalcoholic fatty liver disease (NAFLD) as metabolic associated fatty liver disease (MAFLD) can profoundly affect patient care, health care professionals, and progress within ...the field. To date, there remains no consensus on the characterization of NAFLD vs MAFLD. Thus, this study sought to compare the differences between the natural history of NAFLD and MAFLD.
Medline and Embase databases were searched to include articles on prevalence, risk factors, or outcomes of patients with MAFLD or NAFLD. Meta-analysis of proportions was conducted using the generalized linear mix model. Risk factors and outcomes were evaluated in conventional pairwise meta-analysis.
Twenty-two articles involving 379,801 patients were included. Pooled prevalence of MAFLD was 39.22% (95% confidence interval CI, 30.96%-48.15%) with the highest prevalence in Europe and Asia, followed by North America. The current MAFLD Definition only accounted for 81.59% (95% CI, 66.51%-90.82%) of NAFLD diagnoses. Patients had increased odds of being diagnosed with MAFLD compared with NAFLD (odds ratio, 1.37; 95% CI, 1.16-1.63; P < .001). Imaging modality resulted in a significantly higher odds of being diagnosed with MAFLD compared with NAFLD, but not biopsy. MAFLD was significantly associated with males, higher body mass index, hypertension, diabetes, lipids, transaminitis, and greater fibrosis scores compared with NAFLD.
There were stark differences in the prevalence and risk factors between MAFLD and NAFLD. However, in the use of the MAFLD Definition, a greater emphasis on the management of concomitant metabolic diseases and a collaborative effort is required to explore the complex pathophysiologic mechanisms underlying the disease.
Background: The newly identified coronavirus known as 2019-nCoV has posed a serious global health threat. According to the latest report (18-February-2020), it has infected more than 72,000 people ...globally and led to deaths of more than 1,016 people in China.
Methods: The 2019 novel coronavirus proteome was aligned to a curated database of viral immunogenic peptides. The immunogenicity of detected peptides and their binding potential to HLA alleles was predicted by immunogenicity predictive models and NetMHCpan 4.0.
Results: We report
in silico identification of a comprehensive list of immunogenic peptides that can be used as potential targets for 2019 novel coronavirus (2019-nCoV) vaccine development. First, we found 28 nCoV peptides identical to Severe acute respiratory syndrome-related coronavirus (SARS CoV) that have previously been characterized immunogenic by T cell assays. Second, we identified 48 nCoV peptides having a high degree of similarity with immunogenic peptides deposited in The Immune Epitope Database (IEDB). Lastly, we conducted a
de novo search of 2019-nCoV 9-mer peptides that i) bind to common HLA alleles in Chinese and European population and ii) have T Cell Receptor (TCR) recognition potential by positional weight matrices and a recently developed immunogenicity algorithm, iPred, and identified in total 63 peptides with a high immunogenicity potential.
Conclusions: Given the limited time and resources to develop vaccine and treatments for 2019-nCoV, our work provides a shortlist of candidates for experimental validation and thus can accelerate development pipeline.
Adaptive immune recognition is mediated by specific interactions between heterodimeric T cell receptors (TCRs) and their cognate peptide-MHC (pMHC) ligands, and the methods to accurately predict ...TCR:pMHC interaction would have profound clinical, therapeutic and pharmaceutical applications. Herein, we review recent developments in predicting cross-reactivity and antigen specificity of TCR recognition. We discuss current experimental and computational approaches to investigate cross-reactivity and antigen-specificity of TCRs and highlight how integrating kinetic, biophysical and structural features may offer valuable insights in modeling immunogenicity. We further underscore the close inter-relationship of these two interconnected notions and the need to investigate each in the light of the other for a better understanding of T cell responsiveness for the effective clinical applications.
In this work we present a study into the usage of crosslinker growth of Reversible addition-fragmentation chain-transfer polymerization (RAFT)-based Living Polymer Networks (LPNs) for the purpose of ...mechanical strengthening. Previous work with LPNs has thoroughly covered growth with monomers for various goals, and has touched on using a small amount of crosslinker during growth to retain mechanical strength after growth. Herein, we demonstrate growth with both purely crosslinker and purely monomer for the sake of comparison. We also show this across both symmetries of RAFT agent to see how their different growth behaviors affect the results. The asymmetric RAFT underwent a mesh-filling process during growth which resulted in both crosslinker and monomer strengthening the parent network to a similar degree. However, with the symmetric RAFT agent we saw that the crosslinker and monomer growth caused opposite effects due to their impact on the average crosslinking density; while monomer growth lowered it, growth with crosslinker increased it and strengthened the gel accordingly.
Background: The newly identified coronavirus known as 2019-nCoV has posed a serious global health threat. According to the latest report (18-February-2020), it has infected more than 72,000 people ...globally and led to deaths of more than 1,016 people in China.
Methods: The 2019 novel coronavirus proteome was aligned to a curated database of viral immunogenic peptides. The immunogenicity of detected peptides and their binding potential to HLA alleles was predicted by immunogenicity predictive models and NetMHCpan 4.0.
Results: We report
in silico identification of a comprehensive list of immunogenic peptides that can be used as potential targets for 2019 novel coronavirus (2019-nCoV) vaccine development. First, we found 28 nCoV peptides identical to Severe acute respiratory syndrome-related coronavirus (SARS CoV) that have previously been characterized immunogenic by T cell assays. Second, we identified 48 nCoV peptides having a high degree of similarity with immunogenic peptides deposited in The Immune Epitope Database (IEDB). Lastly, we conducted a
de novo search of 2019-nCoV 9-mer peptides that i) bind to common HLA alleles in Chinese and European population and ii) have T Cell Receptor (TCR) recognition potential by positional weight matrices and a recently developed immunogenicity algorithm, iPred, and identified in total 63 peptides with a high immunogenicity potential.
Conclusions: Given the limited time and resources to develop vaccine and treatments for 2019-nCoV, our work provides a shortlist of candidates for experimental validation and thus can accelerate development pipeline.
While individuals infected with coronavirus disease 2019 (COVID-19) manifested a broad range in susceptibility and severity to the disease, the pre-existing immune memory to related pathogens ...cross-reactive against SARS-CoV-2 can influence the disease outcome in COVID-19. Here, we investigated the potential extent of T cell cross-reactivity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that can be conferred by other coronaviruses and influenza virus, and generated an
map of public and private CD8+ T cell epitopes between coronaviruses. We observed 794 predicted SARS-CoV-2 epitopes of which 52% were private and 48% were public. Ninety-nine percent of the public epitopes were shared with SARS-CoV and 5.4% were shared with either one of four common coronaviruses, 229E, HKU1, NL63, and OC43. Moreover, to assess the potential risk of self-reactivity and/or diminished T cell response for peptides identical or highly similar to the host, we identified predicted epitopes with high sequence similarity with human proteome. Lastly, we compared predicted epitopes from coronaviruses with epitopes from influenza virus deposited in IEDB, and found only a small number of peptides with limited potential for cross-reactivity between the two virus families. We believe our comprehensive
profile of private and public epitopes across coronaviruses would facilitate design of vaccines, and provide insights into the presence of pre-existing coronavirus-specific memory CD8+ T cells that may influence immune responses against SARS-CoV-2.
To test the hypothesis that smooth muscle cell (SMC) TGF-β (transforming growth factor beta) signaling contributes to maintenance of aortic structure and function beyond the early postnatal period.
...We deleted the TBR2 (type 2 TGF-β receptor) in SMC of 11-month-old mice (genotype
-CreER
, termed TBR2
) and compared their ascending aorta structure and vasomotor function to controls (
-CreER
, termed TBR2
).
We confirmed loss of aortic SMC TBR2 by immunoblotting. Four weeks after SMC TBR2 loss, TBR2
mice did not have aortic rupture, ulceration, dissection, dilation, or evidence of medial hemorrhage. However, aortic medial area of TBR2
mice was increased by 27% (0.14±0.01 versus 0.11±0.01 mm
;
=0.01) and medial thickness was increased by 23% (40±1.9 versus 33±1.3 μm;
=0.004) compared with littermate controls. Wire myography performed on ascending aortic rings showed hypercontractility of TBR2
aortas to phenylephrine (E
, 15.9±1.2 versus 10.8±0.7 mN;
=0.0003) and reduced relaxation and sensitivity to acetylcholine (E
, 64±14% versus 96±2%;
=0.001; -logEC
, 6.9±0.1 versus 7.7±0.1;
=0.0001). Neither maximal relaxation nor sensitivity to sodium nitroprusside differed (E
, 102±0.3% versus 101±0.3%; -logEC
, 8.0±0.04 versus 7.9±0.08;
>0.4 for both).
Loss of TGF-β signaling in aortic SMC of 1-year-old mice does not cause early severe aortopathy or death; however, it causes mild structural and substantial physiological abnormalities. SMC TGF-β signaling plays an important role in maintaining aortic homeostasis in older mice. This role should be considered in the design of clinical studies that aim to prevent aortopathy by blocking SMC TGF-β signaling.
The conditions and extent of cross‐protective immunity between severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) and common‐cold human coronaviruses (HCoVs) remain open despite several ...reports of pre‐existing T cell immunity to SARS‐CoV‐2 in individuals without prior exposure. Using a pool of functionally evaluated SARS‐CoV‐2 peptides, we report a map of 126 immunogenic peptides with high similarity to 285 MHC‐presented peptides from at least one HCoV. Employing this map of SARS‐CoV‐2‐non‐homologous and homologous immunogenic peptides, we observe several immunogenic peptides with high similarity to human proteins, some of which have been reported to have elevated expression in severe COVID‐19 patients. After combining our map with SARS‐CoV‐2‐specific TCR repertoire data from COVID‐19 patients and healthy controls, we show that public repertoires for the majority of convalescent patients are dominated by TCRs cognate to non‐homologous SARS‐CoV‐2 peptides. We find that for a subset of patients, >50% of their public SARS‐CoV‐2‐specific repertoires consist of TCRs cognate to homologous SARS‐CoV‐2‐HCoV peptides. Further analysis suggests that this skewed distribution of TCRs cognate to homologous or non‐homologous peptides in COVID‐19 patients is likely to be HLA‐dependent. Finally, we provide 10 SARS‐CoV‐2 peptides with known cognate TCRs that are conserved across multiple coronaviruses and are predicted to be recognized by a high proportion of the global population. These findings may have important implications for COVID‐19 heterogeneity, vaccine‐induced immune responses, and robustness of immunity to SARS‐CoV‐2 and its variants.
We identified 126 SARS‐CoV‐2 T cell targets that exhibit cross‐reactive potential with HCoV predicted peptide‐MHC. We found a subset of COVID‐19 patients whose SARS‐CoV‐2‐specific public TCRs are primarily directed toward these targets with cross‐reactive potential. For these patients, we found distinct HLA profiles. It is plausible that such patients may exhibit more robust protection against SARS‐CoV‐2 and its variants. Ten of the identified SARS‐CoV‐2‐HCoV peptides are highly conserved across multiple coronaviruses and are predicted to invoke T cell responses in high proportions of the global population, which is an encouraging insight in the search for pan‐coronavirus T cell targets.
Large artificial coral reef communities, such as those thriving on sunken shipwrecks, tend to mirror those of nearby natural coral reefs and their long-term dynamics may help future reef resilience ...to environmental change. We examined the community structure of the world-renown "SS Thistlegorm" wreck in the northern Red Sea from 2007 through 2014, analyzing data collected during the recreational citizen science Red Sea monitoring project "Scuba Tourism for the Environment". Volunteer divers collected data on 6 different diving parameters which included the date of the dive, maximum depth, average depth, temperature, dive time, hour of dive, and gave an abundance estimation of sighted taxa from a list of 72 target taxa. Although yearly variations in community structure were significant, there was no clear temporal trend, and 71 of all 72 target taxa were sighted throughout the 8 years. The 5 main taxa driving variations among year clusters in taxa presence/absence (Soft Tree Coral-Dendronephthya spp., Giant Moray-Gymnothorax javanicus, Squirrel Fish-Sargocentron spp., Humpback Batfish-Platax spp., and Caranxes-Carangidae) and taxa abundance (Soft Tree Coral, Giant Moray, Red Sea Clownfish-Amphiprion bicinctus, Napoleon Wrasse-Cheilinus undulatus, and Caranxes) data were determined. The "SS Thistlegorm" provides a compelling example of how artificial coral reefs can sustain a well-established community structure similar to those of their natural counterparts.
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