ALT to qHBsAg ratio predicts long-term HBsAg seroclearance after entecavir cessation in Chinese patients with chronic hepatitis B.

BACKGROUND & AIMS: Factors predicting HBsAg seroclearance after treatment cessation, irrespective of nucleos(t)ide analogue (NA) resumption, have important clinical implications. We evaluated predictors of long-term HBsAg seroclearance after entecavir cessation. METHODS: This study followed-up Chinese patients with chronic hepatitis B from two previous studies of entecavir cessation. All patients were non-cirrhotic, HBeAg-negative, with undetectable HBV DNA (<20 IU/ml) at end-of-treatment (EOT). They were monitored closely for 48 weeks with regular HBV DNA, quantitative HBsAg (qHBsAg) and alanine aminotransferase (ALT) measurements. Entecavir was resumed at HBV DNA >2,000 IU/ml, irrespective of ALT levels. After the initial 48 weeks, patients were assessed every 6 months, regardless of entecavir resumption, to monitor for HBsAg seroclearance. RESULTS: A total of 194 patients (63.4% male, mean age 49.9 years, on entecavir for a median of 47.2 months) were recruited; 94 (48.5%) and 158 (81.4%) patients had EOT qHBsAg <100 IU/ml and <1,000 IU/ml, respectively; 151 (77.8%) patients were eventually resumed on entecavir. After follow-up for a median of 70.7 (51.0-118.2) months, 28 (14.4%) patients had HBsAg seroclearance. qHBsAg levels at weeks 36 and 48 after EOT independently predicted HBsAg seroclearance (both p <0.01), whereas qHBsAg from EOT to week 24 only trended towards statistical significance. The ratio of ALT/qHBsAg at all time points from EOT to week 48 independently predicted HBsAg seroclearance (hazard ratios ranging from 1.003-1.028, all p <0.01) with excellent diagnostic performance (area under the receiver-operating characteristic curve 0.799-0.933, negative predictive value >90% at different time points), regardless of whether entecavir was resumed. CONCLUSIONS: The ALT/qHBsAg ratio after entecavir cessation predicts HBsAg seroclearance, even in patients who were resumed on treatment. Its use may mitigate the risk of severe hepatitis flares in patients managed by observation without treatment resumption. IMPACT AND IMPLICATIONS: Current predictors of HBsAg seroclearance after finite nucleos(t)ide analogue (NA) therapy have suboptimal predictive value. We demonstrated that the ALT/qHBsAg ratio may be able to reflect the balance between host control and virological activity. The ALT/qHBsAg ratio at different time points from end-of-treatment till week 48 independently and accurately predicted HBsAg seroclearance in patients who have stopped entecavir. The ALT/qHBsAg ratio may be utilized by clinicians for patient selection and retreatment decisions in finite NA therapy.

The Landscape of Pediatric High-Grade Gliomas: The Virtues and Pitfalls of Pre-Clinical Models.

Pediatric high-grade gliomas (pHGG) are malignant and usually fatal central nervous system (CNS) WHO Grade 4 tumors. The majority of pHGG consist of diffuse midline gliomas (DMG), H3.3 or H3.1 K27 altered, or diffuse hemispheric gliomas (DHG) (H3.3 G34-mutant). Due to diffuse tumor infiltration of eloquent brain areas, especially for DMG, surgery has often been limited and chemotherapy has not been effective, leaving fractionated radiation to the involved field as the current standard of care. pHGG has only been classified as molecularly distinct from adult HGG since 2012 through Next-Generation sequencing approaches, which have shown pHGG to be epigenetically regulated and specific tumor sub-types to be representative of dysregulated differentiating cells. To translate discovery research into novel therapies, improved pre-clinical models that more adequately represent the tumor biology of pHGG are required. This review will summarize the molecular characteristics of different pHGG sub-types, with a specific focus on histone K27M mutations and the dysregulated gene expression profiles arising from these mutations. Current and emerging pre-clinical models for pHGG will be discussed, including commonly used patient-derived cell lines and in vivo modeling techniques, encompassing patient-derived xenograft murine models and genetically engineered mouse models (GEMMs). Lastly, emerging techniques to model CNS tumors within a human brain environment using brain organoids through co-culture will be explored. As models that more reliably represent pHGG continue to be developed, targetable biological and genetic vulnerabilities in the disease will be more rapidly identified, leading to better treatments and improved clinical outcomes.

Development of a multiple-biomarker approach using the green-lipped mussel Perna viridis for marine pollution monitoring: a case study in Victoria Harbour, Hong Kong.

Pollutants often exist as mixtures in environmental settings, creating a challenge in selecting the most effective combination of biomarkers for routine monitoring. This study was conducted seasonally in Victoria Harbour, Hong Kong, to compare the responses of nine biomarkers in the green-lipped mussel Perna viridis with respect to its tissue levels of persistent organic pollutants and heavy metals. Multivariate statistical techniques were utilised to determine the single best predictor and optimal subset of biomarkers in P. viridis for each of the four scenarios: representing overall biomarker responses in the dry season, and wet season, as well as correlating tissue levels of mixed pollutants in the dry season, and wet season. Our findings recommend lysosomal destabilisation, and the nucleic acid ratio of RNA to DNA, as the core biomarkers in P. viridis for marine pollution monitoring. The non-specificity of these biomarkers allows effective identification of pollution hotspots and guides further detailed assessment.

Bioaccumulation of pollutants in the green-lipped mussel Perna viridis: Assessing pollution abatement in Victoria Harbour and its adjacent aquaculture area, Hong Kong, and the minimal human health risks from mussel consumption.

The green-lipped mussel Perna viridis was utilised for pollution biomonitoring in Victoria Harbour and its adjacent aquaculture area in Hong Kong. P. viridis was collected from a reference site and redeployed at five study sites for five weeks during the dry and wet seasons of 2019. Our study found various polycyclic aromatic hydrocarbons (PAHs) and heavy metals in the mussel tissue, while polychlorinated biphenyls (PCBs) and organochlorine pesticides (OCPs) were not detected. P. viridis at the reference site generally displayed lower levels of pollutants. Comparing with previous research in the 1980s and 2000s, we observed substantial reduction in the tissue levels of PAHs, PCBs, OCPs and heavy metals in P. viridis. The human health risks associated with consuming these mussels were determined to be insignificant. Our findings imply that the Harbour Area Treatment Scheme has been effective in improving the water quality in Victoria Harbour and its adjacent aquaculture area.

3D documentation and classification of incense tree Aquilaria sinensis (Lour.) Spreng. wounds by photogrammetry and its potential conservation applications.

In recent years, illegal felling of and damage to the incense tree Aquilaria sinensis (Lour.) Spreng. have been reported in Hong Kong. Their native populations are under increasingly severe threat. Therefore, the development of a standard and efficient method to classify and document wounds on vulnerable trees is urgently needed for conservation purposes. In this study, photogrammetry was used to document wounds in A. sinensis through 3D modeling. A total of 752 wound records from 484 individual A. sinensis trees from Hong Kong were included to establish a new wound classification system. Our major findings include a novel standardized procedure for photogrammetric documentation and a wound classification system. The results of this study will facilitate A. sinensis conservation, by enhancing wound documentation and information transfer to law enforcement and education.

Esophageal Function and Reflux Evaluations in Lung Transplantation: A Nationwide Survey of UNOS-Accredited Transplant Centers in the United States.

INTRODUCTION: Gastroesophageal reflux disease has been associated with worse lung transplant outcomes. We aimed to assess local practices for esophageal function testing (EFT) across transplant centers. METHODS: This was a survey study of all United Network for Organ Sharing-accredited adult lung transplant centers regarding local EFT practice. RESULTS: Among 39/63 (60%) responded centers, 38.5% required any EFT (35.9% esophageal manometry, 15.4% pH monitoring, and 28.2% pH impedance), while another 28.2% may consider EFT based on symptoms. Five-year transplant volume was higher among centers requiring EFT (253 vs 159, P = 0.04). DISCUSSION: Only a minority of lung transplant centers routinely obtained EFT, supporting the need for guidelines for standardized reflux/esophageal assessment.

Adverse impacts of high-density microplastics on juvenile growth and behaviour of the endangered tri-spine horseshoe crab Tachypleus tridentatus.

The impacts of high-density microplastics, namely polyamine 6,6 (nylon), polymethyl methacrylate (PMMA) and polyethylene terephthalate (PET), on growth and behaviour of the endangered tri-spine horseshoe crab Tachypleus tridentatus were investigated for 100 days. Negative changes in wet weight and prosomal width of the juveniles were observed in all treatments of microplastics, but significant difference was only detected in prosomal width between control and PMMA. T. tridentatus became significantly less active upon exposure to nylon and PET. The extent of burrowing by T. tridentatus did not significantly differ among the treatments but was overall significantly reduced towards day 100. T. tridentatus exposed to PET significantly showed the lowest survival probability (30 %), compared to the other treatments (70-90 %). In conclusion, high-density microplastics compromised growth and behaviour of juvenile horseshoe crabs. Among the polymers that were tested, PET was considered more harmful and associated with higher mortality.

Silver-loaded mesoporous silica nanoparticles enhanced the mechanical and antimicrobial properties of 3D printed denture base resin.

The aim of this study is to develop a novel 3D printed denture base resin material modified with mesoporous silica nanocarrier loaded with silver (Ag/MSN) to enhance mechanical and antimicrobial properties. Acrylate resin-based was incorporated with various proportion of Ag/MSN (0.0-2.0 wt%). Specimens with different geometry were printed and characterized accordingly for the effect of modification on properties such as: mechanical and physical properties, chemical composition and degree of conversion, as well as biological response in term of biocompatibility and antimicrobial against oral fibroblast and candida biofilm (C. albicans), respectively. The consecutive addition of Ag/MSN improved significantly surface hardness and crack propagation resistance, while flexural strength remained similar to control; however, a negligible decrease was observed with higher concentrations ≥1 wt%. No significant difference was noticed with water sorption, while water solubility had a remarkable trend of reduction associated with filler content. The surface roughness significantly increased when concentration of Ag/MSN was ≥1.0 wt%. A significant reduction in C. albicans biofilm mass, as the inhibition proficiency was correlated with the proportion of the filler. With respect to the amount of Ag/MSN, the modification was compatible toward fibroblast cells. The sequential addition of Ag/MSN enhanced significantly the mechanical and antimicrobial properties of the 3D printed resin-based material without affecting adversely compatibility. The acrylic resin denture base material has susceptibility of microbial adhesion which limits its application. Silver loaded MSN showed a significant performance to enhance antimicrobial activity against C. albicans which is the main cause of denture stomatitis. The proposed invention is a promise technique for clinical application to provide an advanced prosthesis fabrication and serve as long-term drug delivery.

Genetic Regulation of Vertebrate Forebrain Development by Homeobox Genes.

Forebrain development in vertebrates is regulated by transcription factors encoded by homeobox, bHLH and forkhead gene families throughout the progressive and overlapping stages of neural induction and patterning, regional specification and generation of neurons and glia from central nervous system (CNS) progenitor cells. Moreover, cell fate decisions, differentiation and migration of these committed CNS progenitors are controlled by the gene regulatory networks that are regulated by various homeodomain-containing transcription factors, including but not limited to those of the Pax (paired), Nkx, Otx (orthodenticle), Gsx/Gsh (genetic screened), and Dlx (distal-less) homeobox gene families. This comprehensive review outlines the integral role of key homeobox transcription factors and their target genes on forebrain development, focused primarily on the telencephalon. Furthermore, links of these transcription factors to human diseases, such as neurodevelopmental disorders and brain tumors are provided.

Do Gut Microbes Taste?

Gut microbiota has emerged as a major metabolically active organ with critical functions in both health and disease. The trillions of microorganisms hosted by the gastrointestinal tract are involved in numerous physiological and metabolic processes including modulation of appetite and regulation of energy in the host spanning from periphery to the brain. Indeed, bacteria and their metabolic byproducts are working in concert with the host chemosensory signaling pathways to affect both short- and long-term ingestive behavior. Sensing of nutrients and taste by specialized G protein-coupled receptor cells is important in transmitting food-related signals, optimizing nutrition as well as in prevention and treatment of several diseases, notably obesity, diabetes and associated metabolic disorders. Further, bacteria metabolites interact with specialized receptors cells expressed by gut epithelium leading to taste and appetite response changes to nutrients. This review describes recent advances on the role of gut bacteria in taste perception and functions. It further discusses how intestinal dysbiosis characteristic of several pathological conditions may alter and modulate taste preference and food consumption via changes in taste receptor expression.

Impaired Proximal Esophageal Contractility Predicts Pharyngeal Reflux in Patients With Laryngopharyngeal Reflux Symptoms.

OBJECTIVES: The pathophysiology of laryngopharyngeal reflux (LPR) remains incompletely understood. Proximal esophageal motor dysfunction may impair bolus clearance, increasing the risk of pharyngeal refluxate exposure. We aimed to evaluate the association of proximal esophageal contractility with objective reflux metrics. METHODS: We evaluated adults with LPR symptoms undergoing high-resolution manometry (HRM) and combined hypopharyngeal-esophageal multichannel intraluminal impedance-pH testing at a tertiary center between March 2018 and August 2019. Routine parameters per Chicago classification were obtained on HRM. Proximal esophageal contractility was evaluated using proximal contractile integral (PCI), which quantifies contractile pressure >20 mm Hg for the region spanning the distal margin of the upper esophageal sphincter and transition zone. Univariate (Kendall correlation and Student t test) and multivariable (general linear regression and logistic regression) analyses were performed. RESULTS: We enrolled 138 patients (66.7% women, mean age 57.1 years) in this study. Lower PCI was associated with an elevated risk of increased pharyngeal reflux (adjusted odds ratio 0.83 per 100 mm Hg-s-cm change in PCI, 95% confidence interval: 0.69-0.98), with a trend toward increased bolus exposure time and total reflux events, after multivariable adjustment. The relationship between PCI and pharyngeal reflux was strongest among participants without a primary motility disorder on HRM (adjusted odds ratio 0.63, 95% confidence interval: 0.42-0.85, P interaction = 0.04). Among continuously expressed reflux parameters, lower PCI was significantly associated with more distal acid reflux events (ß = -0.0094, P = 0.03) and total reflux events (ß = -0.0172, P = 0.05), after adjusting for confounders. DISCUSSION: Reduced proximal esophageal contractility as assessed by decreased PCI on HRM independently predicted increased pharyngeal reflux in patients with LPR symptoms, particularly among those without a coexisting motility disorder.

Antibiotic-chemoattractants enhance neutrophil clearance of Staphylococcus aureus.

The pathogen Staphylococcus aureus can readily develop antibiotic resistance and evade the human immune system, which is associated with reduced levels of neutrophil recruitment. Here, we present a class of antibacterial peptides with potential to act both as antibiotics and as neutrophil chemoattractants. The compounds, which we term 'antibiotic-chemoattractants', consist of a formylated peptide (known to act as chemoattractant for neutrophil recruitment) that is covalently linked to the antibiotic vancomycin (known to bind to the bacterial cell wall). We use a combination of in vitro assays, cellular assays, infection-on-a-chip and in vivo mouse models to show that the compounds improve the recruitment, engulfment and killing of S. aureus by neutrophils. Furthermore, optimizing the formyl peptide sequence can enhance neutrophil activity through differential activation of formyl peptide receptors. Thus, we propose antibiotic-chemoattractants as an alternate approach for antibiotic development.

Applications of functionalized polyethylene terephthalate aerogels from plastic bottle waste.

Millions of tons of plastic are produced annually, but less than 10% are reported to be recycled. This work sets out to transform environmental plastic (polyethylene terephthalate - PET) waste into aerogels for high-value engineering applications, primarily to enhance the monetary incentive in recycling plastics. Coating techniques, using silicone ceramic (SCC) and (3-aminopropyl)triethoxysilane (APS, or APTES) solutions, are successfully devised to enhance the thermal stability and CO2 adsorption capability of rPET aerogel. The rPET/SCC aerogel exhibits improved thermal stability (up to 600 °C), enhanced thermal insulation (thermal conductivity Kavg = [31.8-34.9] mW/m·K), hydrophobic characteristics (up to 144.7° in contact angle) and enhanced rigidity (Young modulus Eavg = [4.5-124.8] kPa), while maintaining an ultra-low density (ρa = [14-62] g/cm3) and a high porosity (Φavg = [95.6-99.0]%). Moreover, the amine-functionalised rPET aerogel achieves a CO2 adsorption capacity of up to 0.44 mmol CO2/g, superior to several commercial physio-sorbents. These promising results obtained demonstrate that the rPET aerogel is a versatile material suitable for a wide variety of high-value engineering applications, including thermal insulation and direct CO2 capture applications.

Molecular epidemiology of coxsackievirus A6 circulating in Hong Kong reveals common neurological manifestations and emergence of novel recombinant groups.

BACKGROUND: Coxsackievirus A6 (CV-A6) represents the predominant enterovirus serotype in Hong Kong, but its epidemiology in our population was unknown. OBJECTIVES: To examine the clinical and molecular epidemiology of CV-A6 and detect emerging recombinant strains in Hong Kong. STUDY DESIGN: Nasopharyngeal aspirates (NPAs) from patients with febrile or respiratory illness were subject to RT-PCR for CV-A6 and sequencing of 5'-NCR and VP1. CV-A6-positive samples were further subject to 2C and 3D gene sequencing. Complete genome sequencing was performed on potential recombinant strains. RESULTS: Thirty-six (0.35%) NPAs were positive for CV-A6 by 5'-NCR RT-PCR and sequencing, 28 of which confirmed by partial VP1 gene sequencing. Among the 28 patients (mainly young children) with CV-A6 infection, hand-foot-and-mouth disease (HFMD) (43%), herpangina (18%) and tonsillitis (11%) were the most common diagnoses. Seven (25%) patients had neurological manifestations, including febrile seizures, encephalitis and meningitis. VP1 gene analysis showed that 24 CV-A6 strains circulating in Hong Kong belonged to genotype D5, while 4 strains belonged to D4. Further 2C and 3D gene analysis revealed eight potential recombinant strains. Genome sequencing of five selected strains confirmed four recombinant strains: HK459455/2013 belonging to recombination group RJ arisen from CV-A6/CV-A4, HK458288/2015 and HK446377/2015 representing novel group RL arisen from CV-A6/CV-A4, and HK462069/2015 representing novel group RM arisen from CV-A6/EV-A71. Recombination breakpoints located at 3D were identified in the latter three recombinant strains, with HK462069/2015 (from a child with encephalitis) having acquired 3D region from EV-A71. CONCLUSIONS: We identified novel recombinant CV-A6 strains in Hong Kong, with 3D being a common recombination site.