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INTRODUCTION: In recent years, the influence of artificial intelligence technology on clinical trials has been steadily increasing. It has brought about significant improvements in the efficiency and cost reduction of clinical trials. The objective of this scoping review is to systematically map, describe and summarise the current utilisation of artificial intelligence in recruitment and retention process of clinical trials that has been reported in research. Additionally, the review aims to identify benefits and drawbacks, as well as barriers and facilitators associated with the application of artificial intelligence in optimising recruitment and retention in clinical trials. The findings of this review will provide insights and recommendations for future development of artificial intelligence in the context of clinical trials. METHODS AND ANALYSIS: The review of relevant literature will follow the methodological framework for scoping studies provided by the Joanna Briggs Institute. A comprehensive electronic search will be conducted using the search strategy developed by the authors. Leading medical and computer science databases such as PubMed, Embase, Scopus, IEEE Xplore and Web of Science Core Collection will be searched. The search will encompass analytical observational studies, descriptive observational studies, experimental and quasi-experimental studies published in all languages, without any time limitations, which use artificial intelligence tools in the recruitment and retention process of clinical trials. The review team will screen the identified studies and import them into a dedicated electronic library specifically created for this review. Data extraction will be performed using a data charting table. ETHICS AND DISSEMINATION: Secondary data will be attained in this scoping review; therefore, no ethical approval is required. The results of the final review will be published in a peer-reviewed journal. It is expected that results will inform future artificial intelligence and clinical trials research.
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Inteligencia Artificial , Ensayos Clínicos como Asunto , Selección de Paciente , Humanos , Proyectos de InvestigaciónRESUMEN
BACKGROUND: Although the number of cancer clinical drug trials is increasing rapidly in China, issues concerning informed consent in this research context are understudied. By performing a narrative literature review, we aim to describe the current situation and identify the most salient challenges affecting informed consent in cancer clinical drug trials among adult patients in China since 2000. METHODS: We searched Web of Science (WOS), PubMed, Scopus, EMBASE, the Cochrane Library databases, China National Knowledge Infrastructure (CNKI), China Biomedical Literature Database on Disc (CBMdisc), Chinese Scientific Journals Fulltext Database (CQVIP), and WANFANG Data to identify relevant publications since 2000. Data were extracted by three reviewers on six items pertaining to study type, theme, and challenges. RESULTS: We identified 37 unique manuscripts, from which 19 full texts were obtained and six were included in the review. All six studies were published in Chinese journals, and the publication years of the majority (five out of six) of the studies were 2015 or later. The authors of the six studies were all from clinical departments or ethical review committees at five hospitals in China. All of the included publications were descriptive studies. Publications reported challenges related to the following aspects of informed consent: information disclosure, patient understanding, voluntariness, authorization, and procedural steps. CONCLUSION: Based on our analysis of publications over the past two decades, there are currently frequent challenges related to various aspects of informed consent in cancer clinical drug trials in China. Furthermore, only a limited number of high-quality research studies on informed consent in cancer clinical drug trials in China are available to date. Efforts toward improvement of informed consent practice, in the form of guidelines or further regulations in China, should draw on both experience from other countries and high-quality local evidence.
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Consentimiento Informado , Neoplasias , Adulto , Humanos , Revelación , Narración , Manejo de Datos , Neoplasias/tratamiento farmacológicoRESUMEN
Zaire ebolavirus (EBOV) causes a severe hemorrhagic fever in humans and non-human primates with high morbidity and mortality. EBOV infection is dependent on its structural glycoprotein (GP), but high levels of GP expression also trigger cell rounding, detachment, and downregulation of many surface molecules that is thought to contribute to its high pathogenicity. Thus, EBOV has evolved an RNA editing mechanism to reduce its GP expression and increase its fitness. We now report that the GP expression is also suppressed at the protein level in cells by protein disulfide isomerases (PDIs). Although PDIs promote oxidative protein folding by catalyzing correct disulfide formation in the endoplasmic reticulum (ER), PDIA3/ERp57 adversely triggered the GP misfolding by targeting GP cysteine residues and activated the unfolded protein response (UPR). Abnormally folded GP was targeted by ER-associated protein degradation (ERAD) machinery and, unexpectedly, was degraded via the macroautophagy/autophagy-lysosomal pathway, but not the proteasomal pathway. PDIA3 also decreased the GP expression from other ebolavirus species but increased the GP expression from Marburg virus (MARV), which is consistent with the observation that MARV-GP does not cause cell rounding and detachment, and MARV does not regulate its GP expression via RNA editing during infection. Furthermore, five other PDIs also had a similar inhibitory activity to EBOV-GP. Thus, PDIs negatively regulate ebolavirus glycoprotein expression, which balances the viral life cycle by maximizing their infection but minimizing their cellular effect. We suggest that ebolaviruses hijack the host protein folding and ERAD machinery to increase their fitness via reticulophagy during infection.Abbreviations: 3-MA: 3-methyladenine; 4-PBA: 4-phenylbutyrate; ACTB: ß-actin; ATF: activating transcription factor; ATG: autophagy-related; BafA1: bafilomycin A1; BDBV: Bundibugyo ebolavirus; CALR: calreticulin; CANX: calnexin; CHX: cycloheximide; CMA: chaperone-mediated autophagy; ConA: concanamycin A; CRISPR: clusters of regularly interspaced short palindromic repeats; Cas9: CRISPR-associated protein 9; dsRNA: double-stranded RNA; EBOV: Zaire ebolavirus; EDEM: ER degradation enhancing alpha-mannosidase like protein; EIF2AK3/PERK: eukaryotic translation initiation factor 2 alpha kinase 3; Env: envelope glycoprotein; ER: endoplasmic reticulum; ERAD: ER-associated protein degradation; ERN1/IRE1: endoplasmic reticulum to nucleus signaling 1; GP: glycoprotein; HA: hemagglutinin; HDAC6: histone deacetylase 6; HMM: high-molecular-mass; HIV-1: human immunodeficiency virus type 1; HSPA5/BiP: heat shock protein family A (Hsp70) member 5; IAV: influenza A virus; IP: immunoprecipitation; KIF: kifenesine; Lac: lactacystin; LAMP: lysosomal associated membrane protein; MAN1B1/ERManI: mannosidase alpha class 1B member 1; MAP1LC3/LC3: microtubule associated protein 1 light chain 3; MARV: Marburg virus; MLD: mucin-like domain; NHK/SERPINA1: alpha1-antitrypsin variant null (Hong Kong); NTZ: nitazoxanide; PDI: protein disulfide isomerase; RAVV: Ravn virus; RESTV: Reston ebolavirus; SARS-CoV: severe acute respiratory syndrome coronavirus; SBOV: Sudan ebolavirus; sGP: soluble GP; SQSTM1/p62: sequestosome 1; ssGP: small soluble GP; TAFV: Taï Forest ebolavirus; TIZ: tizoxanide; TGN: thapsigargin; TLD: TXN (thioredoxin)-like domain; Ub: ubiquitin; UPR: unfolded protein response; VLP: virus-like particle; VSV: vesicular stomatitis virus; WB: Western blotting; WT: wild-type; XBP1: X-box binding protein 1.
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Autofagia , Ebolavirus , Actinas/metabolismo , Animales , Proteína 9 Asociada a CRISPR/genética , Proteína 9 Asociada a CRISPR/metabolismo , Proteína 9 Asociada a CRISPR/farmacología , Calnexina/metabolismo , Calreticulina/genética , Calreticulina/metabolismo , Calreticulina/farmacología , Cicloheximida , Cisteína/metabolismo , Disulfuros , Retículo Endoplásmico/metabolismo , Glicoproteínas/metabolismo , Proteínas de Choque Térmico/metabolismo , Hemaglutininas/metabolismo , Hemaglutininas/farmacología , Histona Desacetilasa 6/genética , Péptidos y Proteínas de Señalización Intercelular , Proteínas de Membrana de los Lisosomas/metabolismo , Lisosomas/metabolismo , Proteínas Asociadas a Microtúbulos/metabolismo , Mucinas/genética , Mucinas/metabolismo , Mucinas/farmacología , Factor 2 Procariótico de Iniciación/genética , Factor 2 Procariótico de Iniciación/metabolismo , Factor 2 Procariótico de Iniciación/farmacología , Proteína Disulfuro Isomerasas/genética , Proteína Disulfuro Isomerasas/metabolismo , ARN Bicatenario/metabolismo , ARN Bicatenario/farmacología , Proteína Sequestosoma-1/metabolismo , Tapsigargina/metabolismo , Tapsigargina/farmacología , Tiorredoxinas/genética , Tiorredoxinas/metabolismo , Tiorredoxinas/farmacología , Ubiquitinas/metabolismo , Proteína 1 de Unión a la X-Box/metabolismo , alfa-Manosidasa/genética , alfa-Manosidasa/metabolismo , alfa-Manosidasa/farmacologíaRESUMEN
To diminish the greenhouse effect by reducing CO2 emission into the air based on a capture and sequestration method through hydrates, the thermodynamic and kinetic effects of additives on CO2 hydrate formation under 1.5 MPa in the presence of 5, 6, 8, 10, and 20 wt % RNS-A (reactive SiO2 containing amino groups) were studied, and the stirrer speed was set to 800 rpm. This paper calculated the gas consumption and explained the possible mechanisms of RNS-A on CO2 hydrates. The results showed that RNS-A was a kinetic additive instead of a thermodynamic one. It was found that 5-10 wt % RNS-A all shortened the induction time of hydrates, but only 5 and 6 wt % RNS-A increased the gas consumption of CO2 hydrates. Although we observed the shortest induction time at a 10 wt % RNS-A system, the lowest gas consumption indicated its weak CO2 capture and storage ability. In addition, when the concentration was 6 wt %, RNS-A had the highest gas consumption and its reaction time was relatively short. Considering the induction time and gas consumption, 6 wt % RNS-A was the optimal RNS-A concentration for CO2 capture and sequestration, which was the most suitable for practical applications.
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Cyanobacterial blooms caused by Microcystis have become a menace to public health and water quality in the global freshwater ecosystem. Alkaline phosphatases (APases) produced by microorganisms play an important role in the mineralization of dissolved organic phosphorus (DOP) into orthophosphate (Pi) to promote cyanobacterial blooms. However, the response of extracellular and intracellular alkaline phosphatase activity (APA) of Microcystis to different DOP sources is poorly understood. In this study, we compared the growth of M. aeruginosa on two DOP substrates (ß-glycerol-phosphate (ß-GP) and lecithin (LEC)) and monitored the changes of P fractions and the extra- and intracellular APA under different P sources and concentrations. M. aeruginosa can utilize both ß-GP and LEC to sustain its growth, and the bioavailability of LEC was greater than ß-GP. For the ß-GP treatment, there was no significant difference in the algal growth at different concentrations (P > 0.05), while the algal growth in the LEC treatment groups was significantly affected by concentrations (P < 0.05). The results showed that intracellular APA of M. aeruginosa could be detected in all DOP treatment groups and generally higher than extracellular APA. In addition, the intracellular APA per cell increased first and then decreased in all DOP treatment groups. Compared with the ß-GP treatment, M. aeruginosa in the LEC groups could secret more extracellular APA.
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Cianobacterias , Microcystis , Fosfatasa Alcalina , Ecosistema , FósforoRESUMEN
The bacterial phoD gene encodes alkaline phosphatase plays an important role in the release of bioavailable inorganic phosphorus (P) from organic P in environmental systems. However, phoD gene diversity in suspended particles in shallow freshwater lakes is poorly understood. In this study, we explored the potential relationship between environmental factors and phoD phosphatase gene in suspended particles in different ecosystem types (lake zones) in Lake Taihu, a large shallow eutrophic lake in China. Quantitative PCR and high-throughput sequencing were used to analyze phoD gene abundance and the phoD-harboring bacterial community composition. Our results indicate that the distribution of phoD gene abundance in suspended particles had a high spatiotemporal heterogeneity. The phoD gene abundance in each lake zone decreased significantly from June to September. The dominant phoD-harboring phylum in all samples was Actinobacteria, followed by Proteobacteria, Cyanobacteria and Gemmatimonadetes. The first predominant phoD-harboring genera varied among samples, but most of them belonged to phylum Actinobacteria. Driven by different environmental factors, the phoD-harboring bacterial community structure varied with sampling month and ecosystem type. Nitrate and ammonia nitrogen were the main environmental drivers of phoD-harboring bacterial community in suspended particles in the river mouth zone, while water pH and dissolved oxygen were important factors for the algae-dominated, macrophyte-dominated and central lake zones.
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Fosfatasa Alcalina , Lagos , China , Ecosistema , Fósforo/análisisRESUMEN
The purpose of this study was to express the matrix protein of rabies virus in baculovirus expression system and prepare its polyclonal antibody. Using the total RNA of RABV strain BD06 as a template, RT-PCR technique was utilized to amplify the sequence of M gene, which were then inserted into shuttle vector pFastbac I to construct the recombinant vector pFastbac I-M. After identification using the double restriction endonuclease cleavage method, the recombinant vector pFastbac I-M were transformed into the competent E. coli DH10 Bac to construct the recombinant expression vector Bacmid-M, which were transfected into Sf9 cells mediated by lipofectamine 2000 to obtain the recombinant baculovirus AcMNPV-M. The mice anti-His monoclonal antibody, rabbit anti-RV positive serum and canine anti-RV positive serum were used in Western Blot assays to identify the expression and reactogenicity of the recombinant. The recombinant M protein were purified under denaturing conditions using the nickel iron affinity chromatography column, then used to immunize the New Zealand White rabbit to prepare its polyclonal antibody. Western Blot assay and FAVN assay were used to validate the polyclonal antibody. Our results showed that the M protein of RABV were successfully expressed in baculovirus expression system,of which molecular weight was of about 25kD;the recombinant M protein has a good reactogenicity and immunogenicity; the rabbit polyclonal antibody prepared by purification of M protein could react with the M protein of RABV strain BD06,SRV 9,CVS-24,ERA,PV2061 and aG. Undoubtedly, the successfully preparation of both recombinant M protein and its polyclonal antibody support a material foundation for further study on the properties of M protein of RABV.
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Anticuerpos Antivirales/inmunología , Virus de la Rabia/inmunología , Proteínas de la Matriz Viral/inmunología , Proteínas de la Matriz Viral/aislamiento & purificación , Animales , Anticuerpos Antivirales/análisis , Especificidad de Anticuerpos , Baculoviridae/genética , Baculoviridae/metabolismo , Western Blotting , Expresión Génica , Vectores Genéticos/genética , Vectores Genéticos/metabolismo , Conejos , Virus de la Rabia/genética , Células Sf9 , Proteínas de la Matriz Viral/genéticaRESUMEN
Rapid and efficient inactivation of a target gene in Escherichia coli chromosomes is required to investigate metabolic engineering. In the present study, a multiple gene inactivation approach was demonstrated in four strains of enterotoxigenic E. coli (ETEC), which are the predominant pathogenic bacteria causing piglet diarrhea, mediated by λ Red and Xer recombination. The chromosomal genes, luxS and pfs were inactivated using the multiple gene inactivation approach in the wildtype strains of E. coli, K88, K99, 987P and F41. This indicated that dif sites may be reused to inactivate multiple chromosomal genes when no antibioticresistant selectable markers remain. Following inactivation of luxS and pfs, the ability of ETEC to produce the quorum sensing signal, and induce autoinducer 2 activity and biofilm formation were significantly reduced. Furthermore, the multiple gene inactivation approach also exhibits a high recombination efficiency and follows a simple process.