Background and Aims The efficacy of palliative biliary drainage by using bilateral or unilateral self-expandable metal stents (SEMSs) for a malignant hilar biliary stricture (MHS) remains ...controversial. This prospective, randomized, multicenter study investigated whether bilateral drainage by using SEMSs is superior to unilateral drainage in patients with inoperable MHSs. Methods Patients with inoperable high-grade MHSs who underwent palliative endoscopic insertion of bilateral or unilateral SEMSs were enrolled. The main outcome measurements were the rate of primary reintervention for malfunction after successful placement of SEMSs, stent patency, technical and clinical success rates, adverse events, and survival duration. Results A total of 133 pathology-diagnosed patients were randomized to the bilateral group (n = 67) or the unilateral group (n = 66). The primary technical success rates were 95.5% (64/67) and 100% (66/66) in the bilateral and unilateral groups, respectively ( P = .244). The clinical success rates were 95.3% (61/64) and 84.9% (56/66), respectively ( P = .047). The primary reintervention rates based on the per-protocol analysis were 42.6% (26/61) in the bilateral group and 60.3% (38/63) in the unilateral group ( P = .049). The median cumulative stent patency duration was 252 days in the bilateral group and 139 days in the unilateral group. The risk of stent patency failure was significantly higher in the unilateral group (log-rank test; P < .01). In a multivariate Cox proportional hazard model to assess stent patency, bilateral SEMS placement was a favorable factor (adjusted hazard ratio 0.30, 95% confidence interval, 0.172-0.521; P < .001). Survival probability and late adverse events were not different between the 2 groups. Conclusions Unilateral and bilateral drainage strategies by using SEMSs had similar technical success rates, but bilateral drainage resulted in fewer reinterventions and more durable stent patency in patients with inoperable high-grade MHSs. (Clinical trial registration number: NCT02166970.)
A high‐performance novel photodetector is demonstrated, which consists of graphene and CH3 NH3PbI3 perovskite layers. The resulting hybrid photodetector exhibits a dramatically enhanced photo ...responsivity (180 A/W) and effective quantum efficiency (5× 104%) over a broad bandwidth within the UV and visible ranges.
A conformal tactile sensor based on MoS2 and graphene is demonstrated. The MoS2 tactile sensor exhibits excellent sensitivity, high uniformity, and good repeatability in terms of various strains. In ...addition, the outstanding flexibility enables the MoS2 strain tactile sensor to be realized conformally on a finger tip. The MoS2‐based tactile sensor can be utilized for wearable electronics, such as electronic skin.
Graphene provides outstanding properties that can be integrated into various flexible and stretchable electronic devices in a conventional, scalable fashion. The mechanical, electrical, and optical ...properties of graphene make it an attractive candidate for applications in electronics, energy‐harvesting devices, sensors, and other systems. Recent research progress on graphene‐based flexible and stretchable electronics is reviewed here. The production and fabrication methods used for target device applications are first briefly discussed. Then, the various types of flexible and stretchable electronic devices that are enabled by graphene are discussed, including logic devices, energy‐harvesting devices, sensors, and bioinspired devices. The results represent important steps in the development of graphene‐based electronics that could find applications in the area of flexible and stretchable electronics.
The outstanding properties of graphene enable a novel form of electronics in a conventional, scalable fashion. Recent progress in graphene‐based flexible and stretchable electronics is reviewed, from the production of the graphene to its applications, including logic gates, energy‐harvesting devices, sensors, and bioinspired devices.
Commercial anti-CD19 chimeric antigen receptor T-cell therapies (CART19) are efficacious against advanced B-cell non-Hodgkin lymphoma (NHL); however, most patients ultimately relapse. Several ...mechanisms contribute to this failure, including CD19-negative escape and CAR T dysfunction. All four commercial CART19 products utilize the FMC63 single-chain variable fragment (scFv) specific to a CD19 membrane-distal epitope and characterized by slow association (on) and dissociation (off) rates. We hypothesized that a novel anti-CD19 scFv that engages an alternative CD19 membrane-proximal epitope independent of FMC63 and that is characterized by faster on- and off-rates could mitigate CART19 failure and improve clinical efficacy.
We developed an autologous CART19 product with 4-1BB co-stimulation using a novel humanized chicken antibody (h1218). This antibody is specific to a membrane-proximal CD19 epitope and harbors faster on/off rates compared to FMC63. We tested h1218-CART19 in vitro and in vivo using FMC63-CART19-resistant models. We conducted a first-in-human multi-center phase I clinical trial to test AT101 (clinical-grade h1218-CART19) in patients with relapsed or refractory (r/r) NHL.
Preclinically, h1218- but not FMC63-CART19 were able to effectively eradicate lymphomas expressing CD19 point mutations (L174V and R163L) or co-expressing FMC63-CAR19 as found in patients relapsing after FMC63-CART19. Furthermore, h1218-CART19 exhibited enhanced killing of B-cell malignancies in vitro and in vivo compared with FMC63-CART19. Mechanistically, we found that h1218-CART19 had reduced activation-induced cell death (AICD) and enhanced expansion compared to FMC63-CART19 owing to faster on- and off-rates. Based on these preclinical results, we performed a phase I dose-escalation trial, testing three dose levels (DL) of AT101 (the GMP version of h1218) using a 3 + 3 design. In 12 treated patients (7 DLBCL, 3 FL, 1 MCL, and 1 MZL), AT101 showed a promising safety profile with 8.3% grade 3 CRS (n = 1) and 8.3% grade 4 ICANS (n = 1). In the whole cohort, the overall response rate was 91.7%, with a complete response rate of 75.0%, which improved to 100% in DL-2 and -3. AT101 expansion correlates with CR and B-cell aplasia.
We developed a novel, safe, and potent CART19 product that recognizes a membrane-proximal domain of CD19 with fast on- and off-rates and showed significant efficacy and promising safety in patients with relapsed B-cell NHL.
NCT05338931; Date: 2022-04-01.
Big data is expected to drive the new digital transformation of society, government, and business. The proportion of firms implementing and utilizing big data, however, is not high. There are many ...challenges and obstacles related to firm adoption of big data. The purpose of this study is to identify the factors influencing the adoption of big data among Korean firms using the technology-organization-environment (TOE) framework. The results of the analytic hierarchy process (AHP) and regression analysis from data collected from 50 experts and 226 companies, respectively, are as follows: the benefits from big data, technological capabilities, financial investment competence, and data quality and integration are perceived by the experts and the firms as the strongest determinants of adoption. Management support for big data, security and privacy, and government support and policy are also influential factors of firm big data adoption.
Single‐atom catalysts (SACs) have attracted growing attention because they maximize the number of active sites, with unpredictable catalytic activity. Despite numerous studies on SACs, there is ...little research on the support, which is essential to understanding SAC. Herein, we systematically investigated the influence of the support on the performance of the SAC by comparing with single‐atom Pt supported on carbon (Pt SA/C) and Pt nanoparticles supported on WO3−x (Pt NP/WO3−x). The results revealed that the support effect was maximized for atomically dispersed Pt supported on WO3−x (Pt SA/WO3−x). The Pt SA/WO3−x exhibited a higher degree of hydrogen spillover from Pt atoms to WO3−x at the interface, compared with Pt NP/WO3−x, which drastically enhanced Pt mass activity for hydrogen evolution (up to 10 times). This strategy provides a new framework for enhancing catalytic activity for HER, by reducing noble metal usage in the field of SACs.
The influence of the support on the performance of a single‐atom catalyst was investigated by comparing single‐atom Pt supported on carbon and Pt nanoparticles supported on WO3−x (Pt NP/WO3−x). The support effect is maximized for single‐atom Pt on WO3−x, which drastically enhances the Pt mass activity for the hydrogen evolution reaction compared with Pt NP/WO3−x and Pt/C.
In response to concerns about rapid climate change and air pollution, electric vehicles (EVs) have been diffusing rapidly in some countries since the early 2010s. Many researchers have investigated ...the value attributes affecting consumers' attitudes to and behaviors around EVs. Little effort has been made, however, to identify the interacting factors in the relationship between perceived value and adoption. To fill this research gap, we examine the moderating effects of environmental traits and government supports on adoption intention. Using survey data collected from 285 drivers in Korea, we identify the significant impacts of perceived value as a predictor of consumers' intention to adopt EVs. Operational economic benefit and charging risk are revealed as the main motivators of and barriers to EV diffusion, respectively. We also find that environmental concern and financial incentives significantly enhance the effects of perceived value on adoption intention. The implications of these findings for the success of EV market diffusion are discussed.
•We identified benefits and risks influencing the intention to adopt EVs in Korea.•We analyzed the moderating effects of environmental traits and government supports.•Operational economic benefit and charging risk were perceived as critical issues.•Environmental concern enhanced the relationship between value and adoption.•Financial incentives played a positive moderating role in EV adoption.
Empathy is crucial for our emotional experience and social interactions, and its abnormalities manifest in various psychiatric disorders. Observational fear is a useful behavioral paradigm for ...assessing affective empathy in rodents. However, specific genes that regulate observational fear remain unknown. Here we showed that 129S1/SvImJ mice carrying a unique missense variant in neurexin 3 (Nrxn3) exhibited a profound and selective enhancement in observational fear. Using the CRISPR/Cas9 system, the arginine-to-tryptophan (R498W) change in Nrxn3 was confirmed to be the causative variant. Selective deletion of Nrxn3 in somatostatin-expressing (SST+) interneurons in the anterior cingulate cortex (ACC) markedly increased observational fear and impaired inhibitory synaptic transmission from SST+ neurons. Concordantly, optogenetic manipulation revealed that SST+ neurons in the ACC bidirectionally controlled the degree of socially transmitted fear. Together, these results provide insights into the genetic basis of behavioral variability and the neurophysiological mechanism controlling empathy in mammalian brains.
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•The 129S1 mouse strain exhibits a selective enhancement in observational fear•A missense variant (R498W) in Nrxn3 causes elevation of observational fear•Selective deletion of Nrxn3 in SST+ neurons reduces GABA release in the ACC•SST+ inhibitory neurons in the ACC control the degree of socially transmitted fear
Keum et al. demonstrate that a protein variant in the Nrxn3 gene causes an enhancement in observational fear and that Nrxn3-dependent inhibitory synaptic functions in somatostatin-positive interneurons in the anterior cingulate cortex control the degree of empathy fear.
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