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1.
Mikrochim Acta ; 187(7): 410, 2020 Jun 29.
Artículo en Inglés | MEDLINE | ID: mdl-32601916

RESUMEN

Bimetallic Ag-Pt nanoparticles decorated on the surface of reduced graphene oxide (Ag-Pt/rGO) were designed and selected as a nanozyme for the assay of hydrogen peroxide. The nanocomposites were prepared through a one-pot reduction of potassium chloroplatinate, silver nitrate, and graphene oxide under ultraviolet irradiation without using any extra chemical reducing agents or surfactants. The successful formation of Ag-Pt/rGO nanocomposites was confirmed by transmission electron microscopy, energy disperse spectroscopy mapping, X-ray photoelectron spectroscopy, and X-ray diffraction analysis. Significantly, Ag-Pt/rGO nanocomposites possessed excellent peroxidase-like activity toward the catalytic oxidation of 3,3',5,5'-tetramethylbenzidine to form a blue product in the presence of hydrogen peroxide. Steady-state kinetics studies suggested that Ag-Pt/rGO nanocomposites had high affinity to hydrogen peroxide. Based on these properties, a convenient and sensitive method for the colorimetric determination of hydrogen peroxide was developed. Under optimal conditions, the absorbance at 652 nm increases linearly in the 10-100 µM and 100 µM-1 mM ranges of hydrogen peroxide concentration, and the detection limit is 0.9 µM (S/N = 3). The method was successfully applied to the determination of hydrogen peroxide in real water samples. Graphical abstract Ag-Pt/rGO nanocomposites were prepared by a one-pot UV irradiation method and used as a novel nanozyme for colorimetric determination of H2O2.

2.
Phys Med Biol ; 2020 Jun 26.
Artículo en Inglés | MEDLINE | ID: mdl-32590382

RESUMEN

Motion compensation can eliminate the inconsistency of respiratory and cardiac phases during image acquisitions for precise vascular reconstruction in the clinical diagnosis of vascular disease from X-ray angiographic image sequences. In X-ray-based vascular interventional therapy, motion modeling can simulate the process of organ deformation driven by motion signals to display a dynamic organ on angiograms without contrast agent injection. Automatic respiratory signal estimation from X-ray angiographic image sequences is essential for motion compensation and modeling. The effects of respiratory motion, cardiac impulse, and tremor on the structures in the chest and abdomen bring difficulty in extracting accurate respiratory signals individually. In this study, an end-to-end deep learning framework based on motion-flow-guided recurrent network is proposed to address the aforementioned problem. The proposed method utilizes a convolutional neural network to learn the spatial feature of every single frame, and a recurrent neural network to learn the temporal feature of the entire sequence. The combination of the two networks can effectively analyze the image sequence to realize respiratory signal estimation. In addition, the motion-flow between consecutive frames is introduced to provide a dynamic constraint of spatial features, which enables the recurrent network to learn better temporal features from the dynamic spatial features than the static spatial features. We demonstrate the advantages of our approach on the designed datasets, which contain coronary and hepatic angiographic sequences with diaphragm structure, and coronary angiographic sequences without diaphragm structure. Our method improved over the state-of-the-art manifold learning-based methods by 85.7%, 81.5% and 75.3% in respiratory signal accuracy metric on these datasets. The results demonstrate that the proposed method can effectively estimate respiratory signals from multiple motion patterns.

3.
J Biotechnol ; 320: 57-65, 2020 Jun 19.
Artículo en Inglés | MEDLINE | ID: mdl-32569793

RESUMEN

Keratinase is capable of distinctive degradation of keratin, which provides an eco-friendly approach for keratin waste management towards sustainable development. In this study, the recombinant keratinase (KERBP) from Brevibacillus parabrevis was successfully expressed in Escherichia coli. The purified KERBP had the specific activity of 6005.3 U/mg. It showed remarkable tolerance to various surfactants and also no collagenolytic activity. However, the moderate thermal stability limited its further application. Thus, protein engineering was further adopted to improve its stability. The variants of T218S, S236C and N181D were constructed by site-directed mutagenesis and combinatorial mutagenesis. Compared with the wild type, the t1/2 at 60 °C for the variants T218S, S236C and N181D were 3.05-, 1.18- and 1-fold increase, respectively. Moreover, the double variants N181D-T218S and N181D-S236C significantly improved thermostability with 5.1 and 2.9 °C increase of T50, and prolonging t1/2 at 60 °C with 4.09 and 1.54-fold, respectively. And the catalytic efficiency of the T218S and N181D-T218S variants was also significantly improved. Furthermore, the keratinase displayed favorable ability to dehair wool from skin within 7 h, which showed potential in leather dehairing. Our work contributes to a further insight into the thermostability of keratinase and offers a promising alternative for industrial leather application.

4.
Sensors (Basel) ; 20(12)2020 Jun 18.
Artículo en Inglés | MEDLINE | ID: mdl-32570857

RESUMEN

With continuous development in the scales of cities, the role of the metro in urban transportation is becoming more and more important. When running at a high speed, the safety of the train in the tunnel is significantly affected by any foreign objects. To address this problem, we propose a foreign object intrusion detection method based on WiFi technology, which uses radio frequency (RF) signals to sense environmental changes and is suitable for lightless tunnel environments. Firstly, based on extensive experiments, the abnormal phase offset between the RF chains of the WiFi network card and its offset law was observed. Based on this observation, a fast phase calibration method is proposed. This method only needs the azimuth information between the transmitter and the receiver to calibrate the the phase offset rapidly through the compensation of the channel state information (CSI) data. The time complexity of the algorithm is lower than the existing algorithm. Secondly, a method combining the MUSIC algorithm and static clutter suppression is proposed. This method utilizes the incoherence of the dynamic reflection signal to improve the efficiency of foreign object detection and localization in the tunnel with a strong multipath effect. Finally, experiments were conducted using Intel 5300 NIC in the indoor environment that was close to the tunnel environment. The performance of the detection probability and localization accuracy of the proposed method is tested.

5.
Sci Rep ; 10(1): 10032, 2020 Jun 22.
Artículo en Inglés | MEDLINE | ID: mdl-32572100

RESUMEN

Cardiopulmonary resuscitation (CPR) training and its quality are critical in improving the survival rate of cardiac arrest. This randomized controlled study investigated the efficacy of a newly developed CPR training program for the public in a Taiwanese setting. A total of 832 adults were randomized to either a traditional or blended (18-minute e-learning plus 30-minute hands-on) compression-only CPR training program. The primary outcome was compression depth. Secondary outcomes included CPR knowledge test, practical test, quality of CPR performance, and skill retention. The mean compression depth was 5.21 cm and 5.24 cm in the blended and traditional groups, respectively. The mean difference in compression depth between groups was -0.04 (95% confidence interval -0.13 to infinity), demonstrating that the blended CPR training program was non-inferior to the traditional CPR training program in compression depth after initial training. Secondary outcome results were comparable between groups. Although the mean compression depth and rate were guideline-compliant, only half of the compressions were delivered with adequate depth and rate in both groups. CPR knowledge and skill retained similarly in both groups at 6 and 12 months after training. The blended CPR training program was non-inferior to the traditional CPR training program. However, there is still room for improvement in optimizing initial skill performance as well as skill retention. Clinical Trial Registration: NCT03586752; www.clinicaltrial.gov.

6.
Acta Pharmacol Sin ; 2020 Jun 17.
Artículo en Inglés | MEDLINE | ID: mdl-32555446

RESUMEN

Since the outbreak of novel coronavirus pneumonia (COVID-19) in December 2019, more than 2,500,000 people worldwide have been diagnosed with SARS-CoV-2 as of April 22. In response to this epidemic, China has issued seven trial versions of diagnosis and treatment protocol for COVID-19. According to the information that we have collected so far, this article provides an overview of potential therapeutic drugs and compounds with much attention, including favipiravir and hydroxychloroquine, as well as traditional Chinese medicine, which have been reported with good clinical treatment effects. Moreover, with further understanding of SARS-CoV-2 virus, new drugs targeting specific SARS-CoV-2 viral components arise and investigations on these novel anti-SARS-CoV-2 agents are also reviewed.

7.
Mol Cancer ; 19(1): 111, 2020 Jun 27.
Artículo en Inglés | MEDLINE | ID: mdl-32593305

RESUMEN

An amendment to this paper has been published and can be accessed via the original article.

8.
Sci Prog ; 103(3): 36850420932067, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32597711

RESUMEN

The surrounding rock may become unstable or even fall down and the initial support may crack and be destroyed when the construction method of the underground excavation tunnel is not properly selected in the turn line of metro. . A section of the Santunbei turn line of Urumqi Metro Line 1# was taken as the engineering background. The proposed construction method was analyzed by numerical simulation. Numerical analysis shows that the final surface settlement caused by the proposed construction method is 3.0 mm and the horizontal convergence is 3.2 mm. It also turns out that the proposed construction method causes less deformation, and the method can be applied to the construction of the small interval tunnel in the Santunbei turn line of metro. The rationality of the method and numerical model was further verified by comparison between the monitored data of surface settlement, horizontal convergence and vault sinking, and numerical simulation results. Finally, the deformation and stress of the six construction methods were compared. The deformation and stress caused by the six construction methods are almost the same. It indicates that the construction spacing between the left and right tunnels does not affect the safety of tunnel construction. Therefore, the appropriate construction spacing could be selected according to the resource configuration, instead of deformation and stress.

9.
Bioorg Chem ; 101: 103993, 2020 Jun 02.
Artículo en Inglés | MEDLINE | ID: mdl-32544737

RESUMEN

Eleven new cembrane diterpenes, namely, sarcoehrenins A-J (1-9, 11) and (2S,11S,12S)-isosarcophytoxide (10), along with six known compounds, gibberosene B (12), (13S)-cembra-1,3,7,11-tetraen-13-ol (13), (+)-sarcophtol (14), cembrene-C (15), (1R,4R,2E,7E,11E)-cembra-2,7,11-trien-4-ol (16) and (1S,4R,2E,7E,11E)-cembratrien-4-ol (17) were isolated from the soft coral Sarcophyton ehrenbergi collected from Weizhou Island, Beibu Gulf, South China Sea. The structures of these compounds were elucidated by a combination of detailed spectroscopic analyses, chemical methods, and comparison with reported data. The absolute configuration of compound 2 was established by the modified Mosher's method in association with TDDFT ECD calculation, while the absolute configuration of compound 3 was assigned by TDDFT ECD approach. In in vitro bioassays, compounds 13 and 17 showed potent TNF-α inhibitory activities being similar to that of positive control dexamethasone. A preliminary structural-activity relationship was also described.

10.
Ying Yong Sheng Tai Xue Bao ; 31(4): 1106-1112, 2020 Apr.
Artículo en Chino | MEDLINE | ID: mdl-32530184

RESUMEN

Solanum rostratum is a severely invasive alien plant species in China. Using four S. rostratum populations and non-invasive congener S. americanum, we conducted a common garden experiment to compare their breeding systems. No significant difference in average seed set between the two species under open pollination and supplementary pollination conditions. However, under the bagged self-pollination condition, S. rostratum had significantly lower average seed set (29.5%) than S. americanum (47.0%). No fertile seeds were detected in the emasculation treatments for both species, suggesting no autonomous apomixis in them. S. rostratum had a lower average autofertility index (0.38) than S. americanum (0.64). S. rostratum had higher average pollen limitation index (0.29) and average pollinator's contribution index (0.49) than S. americanum (0.08 and 0.31, respectively). S. rostratum was found in 12 provinces of China and in 3835 locations globally, which were lower than S. americanum with 18 Chinese provinces and 10897 locations globally. The invasive alien S. rostratum had lower self-compatibility than the non-invasive alien S. americanum. Thus, the invasiveness of those two species was not significantly correlated with their self-compatibility, but positively correlated with their distribution range.


Asunto(s)
Solanum , Cruzamiento , China , Flores , Especies Introducidas , Polinización , Reproducción , Semillas
11.
Nanotechnology ; 2020 Jun 18.
Artículo en Inglés | MEDLINE | ID: mdl-32554878

RESUMEN

In order to learn the active components and their functional mechanism during the plant-mediated synthesis of gold nanoparticles (GNPs), 16 kinds of plants were randomly selected as research objects, and statistical analysis was used to obtain more universal and systematic results. Polyphenols are proved to have the most prominent effect in both reductive and protective capability among all components. The relationship between polyphenols concentration and the protective and reductive capability was further studied in detail. Pyrogallic acid was used as a substitute for polyphenols to elucidate the functional mechanism. The concentration of polyphenols was found to be a critical factor for the preparation of GNPs, and the synergistic competition between phenolic hydroxyl and carbonyl groups caused by the oxidation of polyphenols could affect the particle size and morphology of GNPs. This work can provide excellent guidance for the controllable synthesis of GNPs via the plant-mediated method.

12.
J Am Heart Assoc ; 9(11): e015544, 2020 Jun 02.
Artículo en Inglés | MEDLINE | ID: mdl-32458720

RESUMEN

Background Should all out-of-hospital cardiac arrest (OHCA) patients be directly transported to cardiac arrest centers (CACs) remains under debate. Our study evaluated the impacts of different transport time and destination hospital on the outcomes of OHCA patients. Methods and Results Data were collected from 6655 OHCA patients recorded in the regional prospective OHCA registry database of Taoyuan City, Taiwan, between January 2012 and December 2016. Patients were matched on propensity score, which left 5156 patients, 2578 each in the CAC and non-CAC groups. Transport time was dichotomized into <8 and ≥8 minutes. The relations between the transport time to CACs and good neurological outcome at discharge and survival to discharge were investigated. Of the 5156 patients, 4215 (81.7%) presented with nonshockable rhythms and 941 (18.3%) presented with shockable rhythms. Regardless of transport time, transportation to a CAC increased the likelihoods of survival to discharge (<8 minutes: adjusted odds ratio [aOR], 1.95; 95% CI, 1.11-3.41; ≥8 minutes: aOR, 1.92; 95% CI, 1.25-2.94) and good neurological outcome at discharge (<8 minutes: aOR, 2.70; 95% CI, 1.40-5.22; ≥8 minutes: aOR, 2.20; 95% CI, 1.29-3.75) in OHCA patients with shockable rhythms but not in patients with nonshockable rhythms. Conclusions OHCA patients with shockable rhythms transported to CACs demonstrated higher probabilities of survival to discharge and a good neurological outcome at discharge. Direct ambulance delivery to CACs should thus be considered, particularly when OHCA patients present with shockable rhythms.

13.
Int Immunopharmacol ; 84: 106556, 2020 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-32416450

RESUMEN

ß-Caryophyllene (BCP) is a bicyclic sesquiterpene compound that has anti-diabetic activity. However, the effect of BCP on diabetic nephropathy (DN) remains unclear. Here, we aimed to evaluate the potential role of BCP in high glucose (HG)-induced glomerular mesangial cells (MCs). MCs were maintained under HG condition to simulate DN in vitro. Our results showed that BCP inhibited HG-induced cell proliferation, ROS production and NADPH oxidase (NOX) 2/4 expression. BCP exhibited anti-inflammatory activity with decreased levels of TNF-α, IL-1ß, IL-6 in HG-induced MCs. Moreover, BCP treatment suppressed the HG-induced secretion of fibronectin (FN) and collagen IV (Col IV) in MCs. Furthermore, BCP suppressed the NF-κB activation and enhanced the Nrf2 activation in HG-induced MCs. However, inhibition of Nrf2 attenuated the protective effects of BCP on HG-induced MCs, while inhibition of NF-κB enhanced the nephro-protective effects of BCP on MCs. In conclusion, these findings demonstrated that BCP executed protective effects on HG-induced MCs via regulating NF-κB and Nrf2 signaling pathways.

14.
J Environ Manage ; 266: 110609, 2020 Jul 15.
Artículo en Inglés | MEDLINE | ID: mdl-32392144

RESUMEN

In the past decade, the application of biochar in agricultural soils has attracted wide attention. However, few studies have carefully explored the effects of biochar modification on plant leaf nutrients and the physiological process of plant leaves. To provide a better growing environment for crops and explore the best regulation mode of biochar in the farmland soil environment in the typical black loam area of Heilongjiang Province, through field experiments, we selected soybeans as the test crop and applied biochar in the soil. The agronomic characteristics and soil conditions of soybean plants were monitored by stage. The effects of different application methods and biochar gradients on the water and heat changes in soil tillage layers during different growth stages of crops were discussed, and the subtle differences of agronomic characteristics in different growth stages of crops were compared. The results showed that all kinds of biochar application modes could not change the general trend of water and heat change in soil tillage layer affected by environmental factors, and the effect of biochar application on soil liquid moisture content at 20 cm soil layer was not obvious. Biochar application can increase plant height and reduce stem diameter, but the effect is non-linear. The leaf nitrogen content (Leaf N-content) and leaf chlorophyll relative content (SPAD) were vertically distributed in the canopy, but they did not change significantly with the change of biochar application rate and mode. The application of biochar in autumn may bring crops into maturity earlier. Under the biochar application rate of 9 kg m-2, the mixed application in spring and autumn can bring the best biochar application effect.


Asunto(s)
Suelo , Soja , Carbón Orgánico , Estaciones del Año , Temperatura
15.
ACS Appl Mater Interfaces ; 12(20): 23474-23483, 2020 May 20.
Artículo en Inglés | MEDLINE | ID: mdl-32352755

RESUMEN

Triboelectric nanogenerators (TENGs) with high transparency and stretchability are desired for invisible and adaptable energy harvesting and sensing. Hydrogel-based TENGs (H-TENG) have shown promising attributes toward flexible and transparent devices. However, the effect of hydrogel property on the triboelectric performance of H-TENG is rarely investigated. Herein, dual-network hydrogels composed of dual-cross-linked poly(vinyl alcohol) (PVA) and sodium alginate (SA) were synthesized and used as ionic electrodes in H-TENGs. The elasticity of the hydrogel was controlled by varying the concentration of SA, and the distinct influence of hydrogel viscoelastic property on H-TENG performance was verified for the first time. By tuning the conductivity and viscoelasticity of PVA/SA hydrogel, the optimum H-TENG exhibited high transparency (over 90%) and stretchability (over 250%) and peak output voltage and current of 203.4 V and 17.6 µA, respectively. A specially designed polydimethylsiloxane (PDMS) bag effectively prevents hydrogel dehydration and maintains a stable output in continuous operation. The H-TENG achieved a power density of 0.98 W/m2 on a 4.7 MΩ external resistor. The H-TENG could easily light 240 green and blue LEDs simultaneously and demonstrated capability to power small electronics, such as a digital timer and pedometer. This study provides insights into the influence of hydrogel property on H-TENG performance and gives guidance for designing and fabricating highly stretchable and transparent TENGs.

16.
Enzyme Microb Technol ; 137: 109550, 2020 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-32423677

RESUMEN

Keratinases are promising alternatives over ordinary proteases in several industrial applications due to their unique properties compared with their counterparts in the protease categories. However, their large-scale industrial application is limited by the low expression and poor fermentation efficiency of keratinase. Here, we demonstrate that the expression level of keratinase can be improved by constructing a more efficient enzyme expression system hereby enables the highest production titer as regarding recombinant keratinase production to date. Specially, ten promoters were evaluated and the aprE promoter exhibits a significant promotion of keratinase (kerBv) titer from 165 U/mL to 2605 U/mL in Bacillus subtilis. The batch fermentation mode resulted in a maximum keratinase activity of 7176 U/mL at 36 h in a 5-L fermenter. Furthermore, the extracellular keratinase activity attained up to 16,860 U/mL via fed-batch fermentation within 30 h. The combination of keratinase with l-cysteine brings about 66.4 % degree of degradation of feather. Our work provides a new insight into the development of efficient keratinase fermentation processes with B. subtilis cell factory.

17.
Int Braz J Urol ; 462020 Apr 10.
Artículo en Inglés | MEDLINE | ID: mdl-32459454

RESUMEN

PURPOSE: To evaluate the efficacy of adjunctive medical expulsive therapy (MET) with tamsulosin for the promotion of stone fragments clearance for repeated extracorporeal shock wave lithotripsy (ESWL). MATERIALS AND METHODS: This meta-analysis was conducted by systematic search for randomized controlled trial (RCT) studies in PubMed/Medline, Scopus, Cochrane Library, Web of Science databases in January 2020, which compared tamsulosin with either placebo or non-placebo control for repeated ESWL. The primary endpoint was stone-free rate (SFR), the second endpoints were stone clearance time and complications. The quality assessment of included studies was performed by using the Cochrane System and Jadad score. RESULTS: 7 RCTs were included in this meta-analysis. Tamsulosin provided higher SFR (for stones larger than 1cm, OR: 5.56, p=0.0003), except for patients with stones less than 1cm. For patients with renal stones (OR: 2.97, p=0.0005) or upper ureteral stones (OR: 3.10, p=0.004), tamsulosin can also provide a higher SFR. In addition, tamsulosin provided a shorter stone clearance time (WMD: -9.40, p=0.03) and lower pain intensity (WMD=-17.01, p< 0.0001) and incidences of steinstrasse (OR: 0.37, p=0.0002). CONCLUSION: Adjunctive MET with tamsulosin is effective in patients with specific stone size or location that received repeated ESWL. However, no well-designed RCT that used computed tomography for the detection and assessment of residual stone fragments was found. More studies with high quality and the comparison between tamsulosin and secondary ESWL are needed in the future. Available at. https://www.intbrazjurol.com.br/pdf/aop/2020-0093RW.pdf.

18.
Pract Radiat Oncol ; 2020 May 24.
Artículo en Inglés | MEDLINE | ID: mdl-32461036

RESUMEN

Radiation therapy for mesothelioma remains challenging, as normal tissue toxicity limits the amount of radiation that can be safely delivered to the pleural surfaces, especially radiation dose to the contralateral lung. The physical properties of proton therapy result in better sparing of normal tissues when treating the pleura, both in the post-pneumonectomy setting and the lung-intact setting. Compared to photon radiation, there are dramatic reductions in dose to the contralateral lung, heart, liver, kidneys, and stomach. However, the tissue heterogeneity in the thorax, organ motion, and potential for changing anatomy during the treatment course all present challenges to optimal irradiation with protons. The clinical data underlying proton therapy in mesothelioma are reviewed here, including indications, advantages, and limitations. The Particle Therapy Co-operative Group (PTCOG) Thoracic Subcommittee task group provides specific guidelines for the use of proton therapy for mesothelioma. This consensus report can be used to guide clinical practice, insurance approval, and future research.

19.
Arch Virol ; 2020 May 28.
Artículo en Inglés | MEDLINE | ID: mdl-32462286

RESUMEN

Enterovirus D68 (EV-D68) infection may cause severe respiratory system manifestations in pediatric populations. Because of the lack of an effective preventive vaccine or specific therapeutic drug for this infection, the development of EV-D68-specific vaccines and antibodies has become increasingly important. In this study, we prepared an experimental EV-D68 vaccine inactivated by formaldehyde and found that the serum of rhesus macaques immunized with the inactivated EV-D68 vaccine exhibited potent neutralizing activity against EV-D68 virus in vitro. Subsequently, the antibody-mediated immune response of B cells elicited by the inactivated vaccine was evaluated in a rhesus monkey model. The binding activity, in vitro neutralization activity, and sequence properties of 28 paired antibodies from the rhesus macaques' EV-D68-specific single memory B cells were analyzed, and the EV-D68 VP1-specific antibody group was found to be the main constituent in vivo. Intriguingly, we also found a synergistic effect among the E15, E18 and E20 monoclonal antibodies from the rhesus macaques. Furthermore, we demonstrated the protective efficacy of maternal antibodies in suckling C57BL/6 mice. This study provides valuable information for the future development of EV-D68 vaccines.

20.
J Biopharm Stat ; 30(3): 508-520, 2020 May 03.
Artículo en Inglés | MEDLINE | ID: mdl-32370640

RESUMEN

In this paper, a propensity score-integrated composite likelihood (PSCL) approach is developed for cases in which the control arm of a two-arm randomized controlled trial (RCT) (treated vs control) is augmented with patients from real-world data (RWD) containing both clinical outcomes and covariates at the patient-level. RWD patients who were treated with the same therapy as the control arm of the RCT are considered for the augmentation. The PSCL approach first estimates the propensity score for every patient as the probability of the patient being in the RCT rather than the RWD, and then stratifies all patients into strata based on the estimated propensity scores. Within each propensity score stratum, a composite likelihood function is specified and utilized to down-weight the information contributed by the RWD source. Estimates of the stratum-specific parameters are obtained by maximizing the composite likelihood function. These stratum-specific estimates are then combined to obtain an overall population-level estimate of the parameter of interest. The performance of the proposed approach is evaluated via a simulation study. A hypothetical two-arm RCT and a hypothetical RWD source are used to illustrate the implementation of the proposed approach.

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