Summary
Background
Chronic hepatitis B (CHB) cannot be completely eradicated due to the presence of covalently closed circular DNA (cccDNA) in the nuclei of infected hepatocytes. While quantification ...of intrahepatic cccDNA requires liver biopsies, serological markers can be non‐invasive alternatives to reflect intrahepatic viral replicative activity. Recently, hepatitis B core‐related antigen (HBcrAg) has been advocated as a novel serum marker for disease monitoring and prognostication of CHB.
Aim
To examine the virological aspect and clinical application of HBcrAg with respect to the natural history and treatment of CHB.
Methods
We reviewed all papers published in the PubMed journal list and s from major international meetings that included the keyword “HBcrAg” or “hepatitis B core‐related antigen” until March 2017. Selected studies were compared and summarised on the basis of existing theories, as well as the authors’ experience.
Results
HBcrAg exhibited good correlation with intrahepatic (ih) cccDNA, ih total hepatitis B virus (HBV) DNA, serum HBV DNA and to a lesser extent HBV surface antigen (HBsAg). In situations where serum HBV DNA levels become undetectable or HBsAg loss is achieved, HBcrAg can still be detectable. This marker is helpful in differentiation of HBeAg‐negative chronic hepatitis from HBeAg‐negative chronic infection, predicting spontaneous or treatment‐induced HBeAg seroconversion, sustained response to nucleos(t)ide analogue (NA), risk of HBV reactivation in occult HBV infection under immunosuppressive therapies, and risk of hepatocellular carcinoma (HCC) development as well as post‐operative HCC recurrence.
Conclusions
HBcrAg is a potential surrogate marker of cccDNA. It may soon become a useful marker for disease monitoring, predicting treatment response and disease outcome of chronic hepatitis B.
Linked Content
This article is linked to Wang et al and Mak and Yuen papers. To view these articles visit https://doi.org/10.1111/apt.14673 and https://doi.org/10.1111/apt.14684.
Complex motor commands for human locomotion are generated through the combination of motor modules representable as muscle synergies. Recent data have argued that muscle synergies are inborn or ...determined early in life, but development of the neuro-musculoskeletal system and acquisition of new skills may demand fine-tuning or reshaping of the early synergies. We seek to understand how locomotor synergies change during development and training by studying the synergies for running in preschoolers and diverse adults from sedentary subjects to elite marathoners, totaling 63 subjects assessed over 100 sessions. During development, synergies are fractionated into units with fewer muscles. As adults train to run, specific synergies coalesce to become merged synergies. Presences of specific synergy-merging patterns correlate with enhanced or reduced running efficiency. Fractionation and merging of muscle synergies may be a mechanism for modifying early motor modules (Nature) to accommodate the changing limb biomechanics and influences from sensorimotor training (Nurture).
Summary
Background
A meta‐analysis on the risk of hepatocellular carcinoma (HCC) among hepatitis B virus (HBV) genotypes is warranted as the current data are conflicting.
Aim
To investigate the ...relative risk of HCC among the four major HBV genotypes (A–D).
Methods
A meta‐analysis was performed based on literature search from electronic databases and bibliography between 1950 and 2012. All s with keywords ‘hepatitis B’, ‘hepatocellular carcinoma’ and ‘genotype’ were screened. Studies were included if they reported HBV genotype as an exposure and HCC as an outcome.
Results
Nine hundred and eighty‐eight s were found through literature search, among them 43 studies were eligible for this meta‐analysis. A total of 14 545 patients with an average age of 43 years were included; 71% were male patients and 17% had cirrhosis. In 33 studies, HCC was found in 1541/6060 (25%) genotype C vs. 550/4417 (12%) genotype B HBV‐infected patients odds ratio (OR) = 2.05, 95% confidence interval (CI) = 1.52–2.76, P < 0.001. No difference in the risk of HCC was found among genotype A (71/517, 14%) vs. genotype D (170/1506, 11%) HBV‐infected patients in 14 studies (OR = 0.94, 95% CI = 0.67–1.32). In 10 studies, the risk of HCC was also found higher among genotype C (498/1659, 30%) than genotype A&D (103/1403, 7%) HBV‐infected patients (OR = 2.34, 95% CI = 1.63–3.34, P < 0.001). Subgenotype Ce and Cs HBV‐infected patients had similar risk on HCC (OR = 1.13, 95% CI = 0.76–1.67, P = 0.54). On funnel plot analysis, there was no significant publication bias in all comparisons.
Conclusion
Genotype C hepatitis B virus is associated with a higher risk of hepatocellular carcinoma than other major hepatitis B virus genotypes.
Short-chain fatty acids (SCFAs), especially acetate, propionate and butyrate, are the end products from the intestinal microbial fermentation of dietary fibers and resistant starch. It has been well ...documented that plasma and colonic SCFAs are associated with metabolic syndromes. Recently, the involvement of SCFAs in energy homeostasis regulation has been extensively studied. The importance of SCFAs on energy metabolism has highlighted the potential of modulating SCFAs as a nutritional target to prevent and counteract metabolism disorders and its associated diseases such as obesity and type 2 diabetes. Here, we summarize the current knowledge about the biological properties of SCFAs with their impact on the energy homeostasis.
The central nervous system (CNS) may produce coordinated motor outputs via the combination of motor modules representable as muscle synergies. Identification of muscle synergies has hitherto relied ...on applying factorization algorithms to multimuscle electromyographic data (EMGs) recorded during motor behaviors. Recent studies have attempted to validate the neural basis of the muscle synergies identified by independently retrieving the muscle synergies through CNS manipulations and analytic techniques such as spike-triggered averaging of EMGs. Experimental data have demonstrated the pivotal role of the spinal premotor interneurons in the synergies' organization and the presence of motor cortical loci whose stimulations offer access to the synergies, but whether the motor cortex is also involved in organizing the synergies has remained unsettled. We argue that one difficulty inherent in current approaches to probing the synergies' neural basis is that the EMG generative model based on linear combination of synergies and the decomposition algorithms used for synergy identification are not grounded on enough prior knowledge from neurophysiology. Progress may be facilitated by constraining or updating the model and algorithms with knowledge derived directly from CNS manipulations or recordings. An investigative framework based on evaluating the relevance of neurophysiologically constrained models of muscle synergies to natural motor behaviors will allow a more sophisticated understanding of motor modularity, which will help the community move forward from the current debate on the neural versus nonneural origin of muscle synergies.
COVID-19 abatement strategies have risks and uncertainties which could lead to repeating waves of infection. We show-as proof of concept grounded on rigorous mathematical evidence-that periodic, ...high-frequency alternation of into, and out-of, lockdown effectively mitigates second-wave effects, while allowing continued, albeit reduced, economic activity. Periodicity confers (i) predictability, which is essential for economic sustainability, and (ii) robustness, since lockdown periods are not activated by uncertain measurements over short time scales. In turn-while not eliminating the virus-this fast switching policy is sustainable over time, and it mitigates the infection until a vaccine or treatment becomes available, while alleviating the social costs associated with long lockdowns. Typically, the policy might be in the form of 1-day of work followed by 6-days of lockdown every week (or perhaps 2 days working, 5 days off) and it can be modified at a slow-rate based on measurements filtered over longer time scales. Our results highlight the potential efficacy of high frequency switching interventions in post lockdown mitigation. All code is available on Github at https://github.com/V4p1d/FPSP_Covid19. A software tool has also been developed so that interested parties can explore the proof-of-concept system.
Summary
The potential interaction between chronic hepatitis B (CHB) and nonalcoholic fatty liver disease (NAFLD), two of the most prevalent liver diseases worldwide, has not been well defined. We ...performed liver stiffness (LS) and controlled attenuation parameter (CAP) measurements using transient elastography in 1202 CHB patients. Of these, 601 steatotic patients were matched with nonsteatotic controls in a 1:1 ratio by age, gender, nucleoside analogue treatment status, and treatment duration. Severe fibrosis was defined according to EASL‐ALEH criteria, and steatosis was defined as CAP ≥222 dB m−1. Anthropometric measurements and metabolic‐related parameters were recorded. The mean age of the 1202 patients (51.4% male) was 51.8 years. 696 patients (57.9%) were on nucleoside analogues for a median duration of 76.2 months. Among treatment‐naïve patients, median serum HBV DNA was lower in steatotic individuals than in controls (3.0 vs 3.4 log IU mL−1, P < .05), with this inverse relationship remaining significant in multivariate analysis (odds ratio 0.859, 95% CI 0.743‐0.994, P < .05). With increased steatosis severity, there was a stepwise decrease in median HBV DNA levels (3.1 and 2.6 log IU mL−1 in no steatosis and severe steatosis, respectively, P = .032). Steatosis was associated with a higher median LS (5.4 kPa vs 5.0 kPa, P < .001). Severe steatosis, when compared to mild/moderate steatosis, was associated with an increased percentage of severe fibrosis (23.2% and 12.6%, respectively, P = .005). We conclude that severe steatosis was associated with increased fibrosis in CHB patients. Increasing steatosis was independently associated with lower serum HBV DNA levels, suggesting its potential negative effects on viral replication.
As evidence becomes increasingly important in educational policy, it is essential to understand how research design might contribute to reported effect sizes in experiments evaluating educational ...programs. A total of 645 studies from 12 recent reviews of evaluations of preschool, reading, mathematics, and science programs were studied. Effect sizes were roughly twice as large for published articles, small-scale trials, and experimenter-made measures, compared to unpublished documents, large-scale studies, and independent measures, respectively. Effect sizes were significantly higher in quasiexperiments than in randomized experiments. Excluding tutoring studies, there were no significant differences in effect sizes between elementary and middle/high studies. Regression analyses found that effects of all factors maintained after controlling for all other factors. Explanations for the effects of methodological features on effect sizes are discussed, as are implications for evidence-based policy.
Forced degradation studies have become integral to the development of recombinant monoclonal antibody therapeutics by serving a variety of objectives from early stage manufacturability evaluation to ...supporting comparability assessments both pre- and post- marketing approval. This review summarizes the regulatory guidance scattered throughout different documents to highlight the expectations from various agencies such as the Food and Drug Administration and European Medicines Agency. The various purposes for forced degradation studies, commonly used conditions and the major degradation pathways under each condition are also discussed.
A
bstract
In this paper, we construct explicit Type IIA uplifts of
D
= 5 minimal gauged supergravity by T-dualising known Type IIB uplifts on
N
5
=
S
5
,
T
1
,
1
and
Y
p,q
along their SU(2) ...isometries. When the
D
= 5 gauge field is set to zero, our uplifts recover precisely the known non-Abelian T-duals of the
AdS
5
× N
5
solutions. As an application, we obtain new supersymmetric
AdS
3
×
Σ
× M
5
solutions in Type IIA, where
Σ
=
WCP
n
−
n
+
1
is a weighted projective space. Existing holographic results of T-dualised AdS solutions suggest that our solutions capture features of
d
= 2 SCFTs with
N
= (0
,
2) supersymmetry.
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