Abstract
Background
The high cost and insufficient supply of human papillomavirus (HPV) vaccines have slowed the pace of controlling cervical cancer. A phase III clinical trial was conducted to ...evaluate the efficacy, safety, and immunogenicity of a novel Escherichia coli-produced bivalent HPV-16/18 vaccine.
Methods
A multicenter, randomized, double-blind trial started on November 22, 2012 in China. In total, 7372 eligible women aged 18–45 years were age-stratified and randomly assigned to receive three doses of the test or control (hepatitis E) vaccine at months 0, 1, and 6. Co-primary endpoints included high-grade genital lesions and persistent infection (over 6 months) associated with HPV-16/18. The primary analysis was performed on a per-protocol susceptible population of individuals who were negative for relevant HPV type-specific neutralizing antibodies (at day 0) and DNA (at day 0 through month 7) and who received three doses of the vaccine. This report presents data from a prespecified interim analysis used for regulatory submission.
Results
In the per-protocol cohort, the efficacies against high-grade genital lesions and persistent infection were 100.0% (95% confidence interval = 55.6% to 100.0%, 0 of 3306 in the vaccine group vs 10 of 3296 in the control group) and 97.8% (95% confidence interval = 87.1% to 99.9%, 1 of 3240 vs 45 of 3246), respectively. The side effects were mild. No vaccine-related serious adverse events were noted. Robust antibody responses for both types were induced and persisted for at least 42 months.
Conclusions
The E coli-produced HPV-16/18 vaccine is well tolerated and highly efficacious against HPV-16/18–associated high-grade genital lesions and persistent infection in women.
Aims and objectives
To explore nurses' views regarding implementing advance care planning for older people.
Background
Advance care planning is recommended as a way for older people to discuss their ...future care with family members and health professionals. Nurses play key roles in the process of advance care planning, including ensuring that patients are informed of their rights and that decisions are known to, and respected by, the health care team. Thus, understanding of nurses' experiences and perspectives regarding implementing advance care planning for older people is a significant topic for review.
Design
Qualitative meta‐synthesis.
Methods
Four databases including CINAHL plus, Medline EBSCOhost, EMBASE, and PsycINFO were searched, and 1844 articles were initially screened. Finally, 18 articles were critically appraised and a thematic synthesis was undertaken.
Results
Four themes were identified regarding implementation of advance care planning: perceived disadvantages and advantages of advance directives; nurses' responsibility and roles; facilitators and barriers; and nurses' needs and recommendations. Nurses felt that advance directives provided more advantages than disadvantages. Nurses generally believed that they were well positioned to engage in advance care planning conversations. Nurses perceived barriers relating to older people, families, environment, time, culture, cost, language and knowledge of health care teams with regard to advance care planning. In nurses' needs, education and support were highlighted.
Conclusions
This study provides useful knowledge for implementing advance care planning through illustrating nurses' experiences and perspectives. The results showed that nurses were more concerned about barriers in relation to working environment, teamwork, time and knowledge of health care team members than older people's characteristics, when implementing advance care planning.
Relevance to clinical practice
The findings provide nurses and administrators with information to develop related policies and education. Additionally, the appointment of nurses to formal roles related to advance care planning is appropriate and warranted.
Background and Aims
Autoimmune hepatitis (AIH) is a rare and chronic autoimmune liver disease. While genetic factors are believed to play a crucial role in the etiopathogenesis of AIH, our ...understanding of these genetic risk factors is still limited. In this study, we aimed to identify susceptibility loci to further understand the pathogenesis of this disease.
Approach and Results
We conducted a case–control association study of 1,622 Chinese patients with AIH type 1 and 10,466 population controls from two independent cohorts. A meta‐analysis was performed to ascertain variants associated with AIH type 1. A single‐nucleotide polymorphism within the human leukocyte antigen (HLA) region showed the strongest association with AIH (rs6932730: OR = 2.32; p = 9.21 × 10−73). The meta‐analysis also identified two non‐HLA loci significantly associated with AIH: CD28/CTLA4/ICOS on 2q33.3 (rs72929257: OR = 1.31; p = 2.92 × 10−9) and SYNPR on 3p14.2 (rs6809477: OR = 1.25; p = 5.48 × 10−9). In silico annotation, reporter gene assays, and CRISPR activation experiments identified a distal enhancer at 2q33.3 that regulated expression of CTLA4. In addition, variants near STAT1/STAT4 (rs11889341: OR = 1.24; p = 1.34 × 10−7), LINC00392 (rs9564997: OR = 0.81; p = 2.53 × 10−7), IRF8 (rs11117432: OR = 0.72; p = 6.10 × 10−6), and LILRA4/LILRA5 (rs11084330: OR = 0.65; p = 5.19 × 10−6) had suggestive association signals with AIH.
Conclusions
Our study identifies two novel loci (CD28/CTLA4/ICOS and SYNPR) exceeding genome‐wide significance and suggests four loci as potential risk factors. These findings highlight the importance of costimulatory signaling and neuro‐immune interaction in the pathogenesis of AIH.
The cases of stomach cancer (SC) incidence are increasing per year and the SC burden has remained very high in some countries. We aimed to evaluate the global geographical variation in SC incidence ...and temporal trends from 1978 to 2007, with an emphasis on the effect of birth cohort. Joinpoint regression and age-period-cohort model were applied. From 2003 to 2007, male rate were 1.5- to 3-fold higher than female in all countries. Rates were highest in Eastern Asian and South American countries. Except for Uganda, all countries showed favorable trends. Pronounced cohort-specific increases in risk for recent birth cohorts were seen in Brazil, Colombia, Iceland, New Zealand, Norway, Uganda and US white people for males and in Australia, Brazil, Colombia, Costa Rica, Czech Republic, Ecuador, Iceland, India, Malta, New Zealand, Norway, Switzerland, United Kingdom, Uganda, US black and white people for females. The cohort-specific ratio for male significantly decreased in Japan, Malta and Spain for cohorts born since 1950 and in Austria, China, Croatia, Ecuador, Russia, Switzerland and Thailand for cohorts born since 1960 and for female in Japan for cohorts born since 1950 and in Canada, China, Croatia, Latvia, Russia and Thailand for cohorts born since 1960. Disparities in incidence and carcinogenic risk persist worldwide. The favorable trends may be due to changes in environmental exposure and lifestyle, including decreased Helicobacter pylori prevalence, increased intake of fresh fruits and vegetables, the availability of refrigeration and decreased intake of salted and preserved food and smoking prevalence.
The development of highly active, universal, and stable inexpensive electrocatalysts/cocatalysts for hydrogen evolution reaction (HER) by morphology and structure modulations remains a great ...challenge. Herein, a simple self-template strategy was developed to synthesize hollow Co-based bimetallic sulfide (M x Co3–x S4, M = Zn, Ni, and Cu) polyhedra with superior HER activity and stability. Homogenous bimetallic metal–organic frameworks are transformed to hollow bimetallic sulfides by solvothermal sulfidation and thermal annealing. Electrochemical measurements and density functional theory computations show that the combination of hollow structure and homoincorporation of a second metal significantly enhances the HER activity of Co3S4. Specifically, the homogeneous doping in Co3S4 lattice optimizes the Gibbs free energy for H* adsorption and improves the electrical conductivity. Impressively, hollow Zn0.30Co2.70S4 exhibits electrocatalytic HER activity better than most of the reported nobel-metal-free electrocatalysts over a wide pH range, with overpotentials of 80, 90, and 85 mV at 10 mA cm–2 and 129, 144, and 136 mV at 100 mA cm–2 in 0.5 M H2SO4, 0.1 M phosphate buffer, and 1 M KOH, respectively. It also exhibits photocatalytic HER activity comparable to that of Pt cocatalyst when working with organic photosensitizer (Eosin Y) or semiconductors (TiO2 and C3N4). Furthermore, this catalyst shows excellent stability in the electrochemical and photocatalytic reactions. The strategy developed here, i.e., homogeneous doping and self-templated hollow structure, provides a way to synthesize transition metal sulfides for catalysis and energy conversion.
Ordered mesoporous metal–organic frameworks (mesoMOFs) were constructed with a uniform pore size up to about 10 nm and thick microporous walls, opening up the possibility for the mass diffusion of ...large‐size molecules through crystalline MOFs. The synergistic effects based on triblock copolymer templates and the Hofmeister salting‐in anions promote the nucleation of stable MOFs in aqueous phase and the in situ crystallization of MOFs around templates, rendering the generation of a microcrystal with periodically arranged large mesopores. The improved mass transfer benefiting from large‐pore channels, together with robust microporous crystalline structure, endows them as an ideal nanoreactor for the highly efficient digestion of various biogenic proteins. This strategy could set a guideline for the rational design of new ordered large‐pore mesoMOFs with a variety of compositions and functionalities and pave a way for their potential applications with biomacromolecules.
Ordered mesoMOF microcrystals with a uniform mesopore size of up to 10 nm and thick microporous crystallized walls were constructed through a salt‐mediated template strategy. The structure‐directing effect of triblock copolymers and the Hofmeister effect of salting‐in ions promoted stable nucleation and in situ growth of crystallized MOF walls around surfactant micelles in the aqueous phase.
This Escherichia coli-produced bivalent HPV 16 and 18 vaccine was well tolerated and effective against HPV 16 and 18 associated high-grade genital lesions and persistent infection in interim analysis ...of this phase 3 trial. We now report data on long-term efficacy and safety after 66 months of follow-up.
This phase 3, double-blind, randomised, controlled trial was done in five study sites in China. Eligible participants were women aged 18–45 years, with intact cervix and 1–4 lifetime sexual partners. Women who were pregnant or breastfeeding, had chronic disease or immunodeficiency, or had HPV vaccination history were excluded. Women were stratified by age (18–26 and 27–45 years) and randomly (1:1) allocated by software (block randomisation with 12 codes to a block) to receive three doses of the E coli-produced HPV 16 and 18 vaccine or hepatitis E vaccine (control) and followed-up for 66 months. The primary outcomes were high-grade genital lesions and persistent infection (longer than 6 months) associated with HPV 16 or 18 in the per-protocol susceptible population. This trial was registered with ClinicalTrials.gov, NCT01735006.
Between Nov 22, 2012, and April 1, 2013, 8827 women were assessed for eligibility. 1455 women were excluded, and 7372 women were enrolled and randomly assigned to receive the HPV vaccine (n=3689) or control (n=3683). Vaccine efficacy was 100·0% (95% CI 67·2–100·0) against high-grade genital lesions (0 0% of 3310 participants in the vaccine group and 13 0·4% of 3302 participants in the control group) and 97·3% (89·9–99·7) against persistent infection (2 0·1% of 3262 participants in the vaccine group and 73 2·2% of 3271 participants in the control group) in the per-protocol population. Serious adverse events occurred at a similar rate between vaccine (267 7·2% of 3691 participants) and control groups (290 7·9% of 3681); none were considered related to vaccination.
The E coli-produced HPV 16 and 18 vaccine was well tolerated and highly efficacious against HPV 16 and 18 associated high-grade genital lesions and persistent infection and would supplement the global HPV vaccine availability and accessibility for cervical cancer prevention.
National Natural Science Foundation of China, National Key R&D Program of China, Fujian Provincial Project, Fundamental Funds for the Central Universities, Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences, and Xiamen Innovax.
2D transition metal carbides and/or nitrides (MXenes), by virtue of high electrical conductivity, abundant surface functional groups and excellent dispersion in various solvents, are attracting ...increasing attention and showing competitive performance in energy storage and conversion applications. However, like other 2D materials, MXene nanosheets incline to stack together via van der Waals interactions, which lead to limited number of active sites, sluggish ionic kinetics, and finally ordinary performance of MXene materials/devices. Constructing 2D MXene nanosheets into 3D architectures has been proven to be an effective strategy to reduce restacking, thus providing larger specific surface area, higher porosity, and shorter ion and mass transport distance over normal 1D and 2D structures. In this review, the commonly used strategies for manufacturing 3D MXene architectures (3D MXenes and 3D MXene‐based composites) are summarized, such as template, assembly, 3D printing, and other methods. Special attention is also given to the structure–property relationships of 3D MXene architectures and their applications in electrochemical energy storage and conversion, including supercapacitors, rechargeable batteries, and electrocatalysis. Finally, the authors propose a brief perspective on future opportunities and challenges for 3D MXene architectures/devices.
3D MXene architectures, by virtue of their high surface area, outstanding electrical conductivity, rich ion transport channels, abundant functional groups, and high reactivity, show great potential for electrochemical energy storage and conversion. This review summarizes the commonly used strategies for the construction of 3D MXene architectures, and their applications in supercapacitors, rechargeable batteries, and electrocatalysis.
Cytokine release syndrome (CRS) is a major cause of the multi-organ injury and fatal outcome induced by SARS-CoV-2 infection in severe COVID-19 patients. Metabolism can modulate the immune responses ...against infectious diseases, yet our understanding remains limited on how host metabolism correlates with inflammatory responses and affects cytokine release in COVID-19 patients. Here we perform both metabolomics and cytokine/chemokine profiling on serum samples from healthy controls, mild and severe COVID-19 patients, and delineate their global metabolic and immune response landscape. Correlation analyses show tight associations between metabolites and proinflammatory cytokines/chemokines, such as IL-6, M-CSF, IL-1α, IL-1β, and imply a potential regulatory crosstalk between arginine, tryptophan, purine metabolism and hyperinflammation. Importantly, we also demonstrate that targeting metabolism markedly modulates the proinflammatory cytokines release by peripheral blood mononuclear cells isolated from SARS-CoV-2-infected rhesus macaques ex vivo, hinting that exploiting metabolic alterations may be a potential strategy for treating fatal CRS in COVID-19.
This protocol is intended to provide chemists and physicists with a tool for predicting the charge carrier mobilities of π-stacked systems such as organic semiconductors and the DNA double helix. An ...experimentally determined crystal structure is required as a starting point. The simulation involves the following operations: (i) searching the crystal structure; (ii) selecting molecular monomers and dimers from the crystal structure; (iii) using density function theory (DFT) calculations to determine electronic coupling for dimers; (iv) using DFT calculations to determine self-reorganization energy of monomers; and (v) using a numerical calculation to determine the charge carrier mobility. For a single crystal structure consisting of medium-sized molecules, this protocol can be completed in ∼4 h. We have selected two case studies (a rubrene crystal and a DNA segment) as examples of how this procedure can be used.
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