Cell-based ex vivo gene therapy in solid organs, especially the liver, has proven technically challenging. Here, we report a feasible strategy for the clinical application of hepatocyte therapy. We ...first generated high-quality autologous hepatocytes through the large-scale expansion of patient-derived hepatocytes. Moreover, the proliferating patient-derived hepatocytes, together with the AAV2.7m8 variant identified through screening, enabled CRISPR-Cas9-mediated targeted integration efficiently, achieving functional correction of pathogenic mutations in FAH or OTC. Importantly, these edited hepatocytes repopulated the injured mouse liver at high repopulation levels and underwent maturation, successfully treating mice with tyrosinemia following transplantation. Our study combines ex vivo large-scale cell expansion and gene editing in patient-derived transplantable hepatocytes, which holds potential for treating human liver diseases.
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•Human hepatocytes with genetic liver diseases are expanded in a large scale•AAV2.7m8 with HITI enables efficient, targeted integration in patient hepatocytes•Targeted integration corrects defective gene functions in patient-derived ProliHHs•Edited ProliHHs repopulate and undergo maturation following transplantation
Zhang et al. demonstrated an approach for hepatocyte transplantation by correcting pathogenic mutations in patient-derived hepatocytes through large-scale expansion in vitro and targeted integration. The edited hepatocytes repopulated and matured in injured mouse livers, effectively treating tyrosinemia. This strategy holds promise for the treatment of human liver diseases.
The radiation hardness of commercial 4H-SiC Schottky barrier diodes (STPSC1006D) has been investigated in this study. Primarily, intermittent irradiation at 0.5 Hz and continuous irradiation were ...analyzed and compared. Current–voltage (I–V), capacitance–voltage transform deep-level transient spectroscopy (FT-DLTS) were used to characterize the devices before and after irradiation. The devices show stability in their I–V characteristics upon irradiation. The free carrier concentration of the devices obtained from the C–V results decreased with the increasing of electron fluence. Additionally, new defects were observed after irradiation, which was the reason for the degradation in the electrical properties of the devices. The comparison of the devices irradiated intermittently and those irradiated continuous reveals that intermittent irradiation causes greater changes in electrical properties than continuous irradiation. These characteristics show the impact of STPSC1006D in space applications.
To investigate the psychometric properties, administration efficiency and implementational feasibility of a previously piloted voice recognition- based digital cognitive screener for dementia ...detection in a large-scale community of elderly participants.
Eligible participants completed the demographic, lifestyle investigations and the DCS. Domain-specific and global cognition was assessed by a comprehensive neuropsychological test battery. Diagnosis of mild cognitive impairment(MCI) and dementia was made based on the clinical dementia rating. Completion rate and administration time for the DCS were recorded. Correlation between the DCS and domain-specific and global cognitive performance were assessed. Receiver operating characteristic (ROC) analyses examined the discriminate validity of the DCS in detecting MCI and dementia. A cost-consequences analysis was conducted to compare the screening efficacy of DCS with two traditionally administered cognitive assessment tools, the Mini-Mental State Examination (MMSE) and the Montreal Cognitive Assessment (MoCA), was conducted.
Among a total of 11,186 participants, the completion rate of the DCS was 97·5% with a conduction time of 5·6–6·1 minutes, regardless of gender, age and education stratifications. DCS total score was significantly associated with domain-specific and global cognitive z-scores. Area under the curves (AUCs) of the DCS were 0·95 (0·92, 0·99) and 0·83 (0·79, 0·88) for dementia and MCI detection, respectively. There was no significant difference on the AUCs among different age- and education-stratified subgroups. Comparing with the MoCA and MMSE, DCS resulted in time savings of 35·4%–36·0% and 30·7%–31·2% for identifying dementia cases, as well as 22·6%–22·8% and 16·2%–16·4% for identifying MCI cases.
Our findings demonstrated that the DCS was an effective and efficient tool for case-finding of dementia and MCI in a Chinese community. The large-scale implementation of the DCS among older Chinese adults could be a practical cognitive screening strategy to improve the management of healthcare resources.
INTRODUCTION
We investigated the validity, feasibility, and effectiveness of a voice recognition‐based digital cognitive screener (DCS), for detecting dementia and mild cognitive impairment (MCI) in ...a large‐scale community of elderly participants.
METHODS
Eligible participants completed demographic, cognitive, functional assessments and the DCS. Neuropsychological tests were used to assess domain‐specific and global cognition, while the diagnosis of MCI and dementia relied on the Clinical Dementia Rating Scale.
RESULTS
Among the 11,186 participants, the DCS showed high completion rates (97.5%) and a short administration time (5.9 min) across gender, age, and education groups. The DCS demonstrated areas under the receiver operating characteristics curve (AUCs) of 0.95 and 0.83 for dementia and MCI detection, respectively, among 328 participants in the validation phase. Furthermore, the DCS resulted in time savings of 16.2% to 36.0% compared to the Mini‐Mental State Examination (MMSE) and Montral Cognitive Assessment (MoCA).
DISCUSSION
This study suggests that the DCS is an effective and efficient tool for dementia and MCI case‐finding in large‐scale cognitive screening.
Highlights
To our best knowledge, this is the first cognitive screening tool based on voice recognition and utilizing conversational AI that has been assessed in a large population of Chinese community‐dwelling elderly.
With the upgrading of a new multimodal understanding model, the DCS can accurately assess participants' responses, including different Chinese dialects, and provide automatic scores.
The DCS not only exhibited good discriminant ability in detecting dementia and MCI cases, it also demonstrated a high completion rate and efficient administration regardless of gender, age, and education differences.
The DCS is economically efficient, scalable, and had a better screening efficacy compared to the MMSE or MoCA, for wider implementation.
Background
To investigate the psychometric properties, administration efficiency and implementational feasibility of a previously piloted voice recognition‐based digital cognitive screener for ...dementia detection in a large‐scale community of elderly participants.
Method
Eligible participants completed the demographic, lifestyle investigations and the DCS. Domain‐specific and global cognition was assessed by a comprehensive neuropsychological test battery. Diagnosis of mild cognitive impairment(MCI) and dementia was made based on the clinical dementia rating. Completion rate and administration time for the DCS were recorded. Correlation between the DCS and domain‐specific and global cognitive performance were assessed. Receiver operating characteristic (ROC) analyses examined the discriminate validity of the DCS in detecting MCI and dementia. A cost‐consequences analysis was conducted to compare the screening efficacy of DCS with two traditionally administered cognitive assessment tools, the Mini‐Mental State Examination(MMSE) and the Montreal Cognitive Assessment (MoCA), was conducted.
Result
Among a total of 11,186 participants, the completion rate of the DCS was 97·5% with a conduction time of 5·6–6·1 minutes, regardless of gender, age and education stratifications. DCS total score was significantly associated with domain‐specific and global cognitive z‐scores. Area under the curves (AUCs) of the DCS were 0·95 (0·92, 0·99) and 0·83 (0·79, 0·88) for dementia and MCI detection, respectively. There was no significant difference on the AUCs among different age‐ and education‐stratified subgroups. Comparing with the MoCA and MMSE, DCS resulted in time savings of 35·4%–36·0% and 30·7%–31·2% for identifying dementia cases, as well as 22·6%–22·8% and 16·2%–16·4% for identifying MCI cases.
Conclusion
Our findings demonstrated that the DCS was an effective and efficient tool for case‐finding of dementia and MCI in a Chinese community. The large‐scale implementation of the DCS among older Chinese adults could be an practical cognitive screening strategy to improve the management of healthcare resources.
Melanosomes in nature have diverse morphologies, including spheres, rods, and platelets. By contrast, shapes of synthetic melanins have been almost entirely limited to spherical nanoparticles with ...few exceptions produced by complex templated synthetic methods. Here, we report a non‐templated method to access synthetic melanins with a variety of architectures including spheres, sheets, and platelets. Three 1,8‐dihydroxynaphthalene dimers (4‐4′, 2‐4′ and 2‐2′) were used as self‐assembling synthons. These dimers pack to form well‐defined structures of varying morphologies depending on the isomer. Specifically, distinctive ellipsoidal platelets can be obtained using 4‐4′ dimers. Solid‐state polymerization of the preorganized dimers generates polymeric synthetic melanins while maintaining the initial particle morphologies. This work provides a new route to anisotropic synthetic melanins, where the building blocks are preorganized into specific shapes, followed by solid‐state polymerization.
A new method to achieve synthetic melanin materials with various well‐defined architectures, ranging from spheres to anisotropic sheets and ellipsoidal platelets, is described. The specific shapes are obtained through pre‐organizing the building blocks of melanins, followed by solid‐state oxidative polymerization to render polymeric materials without changing the overall morphology.
