Search

Abstract Liver fibrosis is a pathological condition characterized by the abnormal proliferation of liver tissue, subsequently able to progress to cirrhosis or possibly hepatocellular carcinoma. The development of artificial intelligence and deep learning have begun to play a significant role in fibrosis detection. This study aimed to develop SMART AI‐PATHO, a fully automated assessment method combining quantification of histopathological architectural features, to analyze steatosis and fibrosis in nonalcoholic fatty liver disease (NAFLD) core biopsies and employ Metavir fibrosis staging as standard references and fat assessment grading measurement for comparison with the pathologist interpretations. There were 146 participants enrolled in our study. The correlation of Metavir scoring system interpretation between pathologists and SMART AI‐PATHO was significantly correlated (Agreement = 68%, Kappa = 0.59, p‐value

ABSTRACTIntroduction Inactivated vaccines were delivered to low- and middle-income countries during the early pandemics of COVID-19. Currently, more than 10 inactivated COVID-19 vaccines have been developed. Most inactivated vaccines contain an inactivated whole-cell index SARS-CoV-2 strain that is adjuvant. Whole virions inactivated with aluminum hydroxide vaccines were among the most commonly used. However, with the emerging of COVID-19 variants and waning of the immunity of two doses of after 3 months, WHO and many local governments have recommended the booster-dose program especially with heterologous platform vaccine.Area Covered This review was conducted through a literature search of the MEDLINE database to identify articles published from 2020 to 2023 covered the inactivated COVID-19 vaccines primary series with homologous and heterologous booster focusing on safety, immunogenicity, efficacy, and effectiveness.Expert opinion The inactivated vaccines, especially whole virion inactivated in aluminum hydroxide appeared to be safe and had good priming effects. Immune responses generated after one dose of heterologous boost were high and able to preventing severity of disease and symptomatic infection. A new approach to inactivated vaccine has been developed using inactivating recombinant vector virus-NDV-HXP-S vaccine.

The RV144 Thai phase III clinical trial’s canarypox–protein HIV vaccine regimen showed modest efficacy in reducing infection. We therefore sought to determine the effects of vaccine administration on innate cell activation and subsequent associations with vaccine-induced immune responses. RV306 was a randomized, double-blind clinical trial in HIV-uninfected Thai adults that tested delayed boosting following the RV144 regimen. PBMC collected from RV306 participants prior to and 3 days after the last boost were used to investigate innate immune cell activation. Our analysis showed an increase in CD38+ mucosal associated invariant T (MAIT) cells, CD38+ invariant natural killer T (iNKT) cells, CD38+ γδ T cells, CD38+, CD69+ and HLA-DR+ NK cells 3 days after vaccine administration. An increase in CD14-CD16+ non-classical monocytes and CD14+CD16+ intermediate monocytes accompanied by a decrease in CD14+CD16- classical monocytes was also associated with vaccine administration. Inclusion of ALVAC-HIV in the boost did not further increase MAIT, iNKT, γδ T, and NK cell activation or increase the proportion of non-classical monocytes. Additionally, NK cell activation 3 days after vaccination was positively associated with antibody titers of HIV Env-specific total IgG and IgG1. Vδ1 T cell activation 3 days after vaccine administration was associated with HIV Env-specific IgG3 titers. Finally, we observed trending associations between MAIT cell activation and Env-specific IgG3 titers and between NK cell activation and TH023 pseudovirus neutralization titers. Our study identifies a potential role for innate cells, specifically NK, MAIT, and γδ T cells, in promoting antibody responses following HIV-1 vaccine administration.

Objectives: The study aimed to compare the immunogenicity and safety of fractional (half) third doses of heterologous COVID-19 vaccines (AZD1222 or BNT162b2) to full doses after the two-dose CoronaVac and when boosting after three different extended intervals. Methods: At 60-

Background: International guidelines recommend dietary interventions as one of the most important treatments for patients with gastroesophageal reflux disease (GERD). Evidence to confirm the efficacy of these treatment modalities is lacking. The present study aims to evaluate the efficacy of dietary interventions on GERD-related outcomes evaluated in intervention studies on GERD patients. Methods: A systematic review and meta-analysis was performed according to PRISMA. The PubMed/MEDLINE, Web of Sciences, and Scopus databases were utilized for the literature search. Two independent researchers searched for relevant publications published up until June 2023. Intervention studies evaluating the efficacy of dietary interventions in patients with GERD were included. Results: A total of 577 articles were identified during the initial literature search. After reviewing, 21 studies with 16 different types of dietary interventions were included in the analysis. The interventions were divided into low-carbohydrate diets (3 studies), high-fat diets (2 studies), speed of eating studies (3 studies), low-FODMAP diets (2 studies), and other interventions (12 studies). A meta-analysis could be performed for low-carbohydrate diets and speed of eating interventions. Low-carbohydrate diets resulted in a significant reduction in esophageal acid exposure time (mean difference = −2.834%, 95% confidence interval (CI): −4.554 to −1.114), while a slow speed of eating did not lead to a lower percentage of reflux events compared to fast eating (risk ratio = 1.044, 95% CI: 0.543–2.004). Most other interventions showed positive effects in only a single study. Conclusion: Low-carbohydrate diets showed a significant improvement in GERD-related outcomes, while a slow eating speed did not result in a reduction in reflux events. The overall evidence regarding dietary interventions in GERD remains scarce. High-quality, long-term RCTs are still required to confirm the effects of dietary interventions in GERD patients.

Abstract Nonalcoholic fatty liver disease (NAFLD) is now the leading cause of liver disease, and its prevalence is expected to increase in the future due to the increasing prevalence of obesity and an increasing aging population. With increases in longevity, NAFLD has emerged as a growing public health concern worldwide. NAFLD is a multisystem disease that has a strong association with metabolic risk factors. The presence of NAFLD increases the risks of liver‐ and cardiovascular‐related mortality. Many studies have found age to be an additional risk factor for advanced fibrosis, which is associated with adverse outcomes. The identification of high‐risk older persons using noninvasive methods is a key step in community management. Limitations in the diagnostic performance of current assessment methods have been encountered. This review provides an update on the new terminology that has changed from NAFLD to metabolic‐associated fatty liver disease (MAFLD), and the epidemiology, clinical characteristics, noninvasive assessment, and prognosis of older persons with NAFLD.

As of November 2023, 140 World Health Organization (WHO) member states had introduced human papillomavirus (HPV) vaccination in their routine immunization schedules. Despite a continuously increasing demand from countries across all income groups, supply constraints, COVID-19 pandemic disruptions, and other factors have slowed the pace of introduction, particularly in low-resource settings. Using a population-based forecasting methodology and leveraging the WHO’s yearly vaccine supply data collection, we updated global demand and supply projections for the HPV vaccine for the period of 2022–2031. The analysis aimed at clarifying the magnitude of the challenges to bringing in equitable access to HPV vaccines, which can hinder the achievement of the Global Strategy for the Elimination of Cervical Cancer. The results of this analysis show that the risk of HPV shortages has significantly decreased, and global supply is now, under normal circumstances, sufficient to meet global demand. In the long term, HPV supply will be more than sufficient to meet the Global Strategy’s goal of 90% of girls fully vaccinated with the HPV vaccine by the age of 15 years. Nonetheless, paying attention to the formulation of policies and carefully managing demand and supply will be required to ensure the long-term sustainability of the HPV vaccine program.

Abstract Background Routine screening for HIV and other sexually transmitted infections (STIs) facilitates early diagnosis and treatment, thereby preventing morbidity and onward transmission. We estimated the prevalence of prior HIV/STI testing among men who have sex with men (MSM) and transgender women (TGW) in Bangkok, Thailand, and identified factors associated with prior testing. Methods Cross-sectional analyses were performed using data collected at enrollment into an HIV incidence cohort. From April to October 2017, MSM and TGW were enrolled if they were aged 18–35 years, reported anal intercourse with a male or TGW partner, and reported behavioral vulnerability to HIV. Participants answered questions about demographics, sexual behaviors, and lifetime HIV/STI testing history. Multivariable robust Poisson regression was used to estimate risk ratios (RRs) and 95% confidence intervals (CIs) for factors potentially associated with prior testing. Results Among 1,014 participants, 348 (34.3%) were TGW and the median age was 21.6 (interquartile range 20.0-24.8) years. Prior testing for HIV was reported by 421 (41.5%) and for other STIs by 268 (26.4%). HIV testing was more common among participants aged ≥ 22 years (RR 1.37 [95% CI 1.13–1.67]), with college education as compared to secondary or less (RR 1.37 [95% CI 1.08–1.72]), and who met male sexual partners online (RR 1.52 [95% CI 1.24–1.85]), but lower among participants attracted to both men and women as compared to men only (RR 0.64 [95% CI 0.51–0.81]) and who met male sexual partners in bars (RR 0.83 [95% CI 0.72–0.97]). Similar associations were observed with prior testing for other STIs, including increased testing among participants with college education (RR 1.52 [95% CI 1.11–2.09]) and who met male sexual partners online (RR 1.73 [95% CI 1.30–2.31]), but lower among participants attracted to both men and women (RR 0.70 [95% CI 0.51–0.96]) and who met male sexual partners in bars (RR 0.67 [95% CI 0.54–0.83]). Conclusions Despite behavioral vulnerability, prior testing for HIV and other STIs was uncommon. Online engagement strategies may be effectively reaching Thai MSM and TGW who meet sexual partners online, but new interventions are needed to encourage testing among younger, less educated, and bisexual MSM and TGW.

Immunogens and vaccination regimens can influence patterns of immune-epitope recognition, steering them towards or away from epitopes of potential viral vulnerability. HIV-1 envelope (Env)-specific antibodies targeting variable region 2 (V2) or 3 (V3) correlated with protection during the RV144 trial, however, it was suggested that the immunodominant V3 region might divert antibody responses away from other relevant sites. We mapped IgG responses against linear Env epitopes in five clinical HIV vaccine trials, revealing a specific pattern of Env targeting for each regimen. Notable V2 responses were only induced in trials administering CRF01_AE based immunogens, but targeting of V3 was seen in all trials, with the soluble, trimeric CN54gp140 protein eliciting robust V3 recognition. Strong V3 targeting was linked to greater overall response, increased number of total recognised antigenic regions, and where present, stronger V2 recognition. Hence, strong induction of V3-specific antibodies did not negatively impact the targeting of other linear epitopes in this study, suggesting that the induction of antibodies against V3 and other regions of potential viral vulnerability need not be necessarily mutually exclusive.

Being vigilant of the potential for an influenza pandemic, the Global Action Plan for Influenza Vaccines (GAP) promoted the establishment and maintenance of local vaccine manufacturing capacity. In accordance with this, the Thai government has developed its national strategic plan for influenza pandemic preparedness including the plan for manufacturing influenza vaccine in Thailand. With the support of WHO, the Thai Government Pharmaceutical Organization (GPO) as the developed local production capacity of influenza vaccines. The H1N1 live attenuated influenza vaccine (LAIV) and H5N2 LAIV produced by GPO have been proven to be safe and immunogenic through clinical trials, followed by Thai FDA licensure for pandemic use. The GPO-produced H5N2 LAIV has been proven to have priming effects on an inactivated subunit H5N1 booster vaccine. This Thai local manufacturer is now expanding its capacity to Inactivated Influenza Vaccine (IIV), aiming for sustainable influenza vaccine production for national coverage.

The RV144 clinical trial showed the partial efficacy of a vaccine regimen with an estimated vaccine efficacy (VE) of 31% for protecting low-risk Thai volunteers against acquisition of HIV-1. The impact of vaccine-induced immune responses can be investigated through sieve analysis of HIV-1 breakthrough infections (infected vaccine and placebo recipients). A V1/V2-targeted comparison of the genomes of HIV-1 breakthrough viruses identified two V2 amino acid sites that differed between the vaccine and placebo groups. Here we extended the V1/V2 analysis to the entire HIV-1 genome using an array of methods based on individual sites, k-mers and genes/proteins. We identified 56 amino acid sites or "signatures" and 119 k-mers that differed between the vaccine and placebo groups. Of those, 19 sites and 38 k-mers were located in the regions comprising the RV144 vaccine (Env-gp120, Gag, and Pro). The nine signature sites in Env-gp120 were significantly enriched for known antibody-associated sites (p = 0.0021). In particular, site 317 in the third variable loop (V3) overlapped with a hotspot of antibody recognition, and sites 369 and 424 were linked to CD4 binding site neutralization. The identified signature sites significantly covaried with other sites across the genome (mean = 32.1) more than did non-signature sites (mean = 0.9) (p < 0.0001), suggesting functional and/or structural relevance of the signature sites. Since signature sites were not preferentially restricted to the vaccine immunogens and because most of the associations were insignificant following correction for multiple testing, we predict that few of the genetic differences are strongly linked to the RV144 vaccine-induced immune pressure. In addition to presenting results of the first complete-genome analysis of the breakthrough infections in the RV144 trial, this work describes a set of statistical methods and tools applicable to analysis of breakthrough infection genomes in general vaccine efficacy trials for diverse pathogens.

The RV144 prime-boost regimen demonstrated efficacy against HIV acquisition while VAX003 and VAX004 did not. Although these trials differed by risk groups, immunization regimens, and immunogens, antibody responses may have contributed to the differences observed in vaccine efficacy. We assessed HIV-specific IgG, both total and subclass, and IgA binding to HIV envelope (Env): gp120 proteins and Cyclic V2 (CycV2) and CycV3 peptides and gp70 V1 V2 scaffolds in these 3 HIV vaccine trials. After two protein immunizations, IgG responses to 92TH023 gp120 (contained in ALVAC-HIV vaccine) were significantly higher in RV144 but responses to other Env were higher in the VAX trials lacking ALVAC-HIV. IgG responses declined significantly between vaccinations. All trials induced antibodies to gp70 V1 V2 but VAX004 responses to 92TH023 gp70 V1 V2 were weak. All CycV2 responses were undetectable in VAX004 while 92TH023 gp70 V1 V2 was detected in both RV144 and VAX003 but MN CycV2 was detected only in VAX003. Multiple protein vaccinations in VAX trials did not improve magnitude or durability of V1 V2 and CycV2 antibodies. Herpes simplex virus glycoprotein D (gD) peptide at the N terminus of AIDSVAX® B/E and B/B gp120 proteins induced antibodies in all trials, although significantly higher in VAX trials. gD peptide induced IgA, IgG1, IgG2, and IgG3 but not IgG4. Multiple protein vaccinations decreased IgG3 and increased IgG4 changing subclass contribution to total IgG. Although confounded by different modes of HIV transmission, higher Env-specific IgA and IgG4 binding antibodies induced in the VAX trials compared to RV144 raises the hypothesis that these differences may have contributed to different vaccine efficacy results. [ABSTRACT FROM AUTHOR]