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.
An active matrix‐type stretchable display is realized by overlay‐aligned transfer of inorganic light‐emitting diode (LED) and single‐crystal Si thin film transistor (TFT) with roll processes. The ...roll‐based transfer enables integration of heterogeneous thin film devices on a rubber substrate while preserving excellent electrical and optical properties of these devices, comparable to their bulk properties. The electron mobility of the integrated Si‐TFT is over 700 cm2 V−1 s−1, and this is attributed to the good interface between the Si channel and the thermally grown SiO2 insulator. The light emission properties of the LED are of wafer quality. The resulting display stably operates under tensile strains up to 40%, over 200 cycles, demonstrating the potential of stretchable displays based on inorganic materials.
All‐inorganic‐based stretchable active matrix display is demonstrated by integration of inorganic light‐emitting diode and single‐crystal Si thin film transistor. Overlay‐aligned roll transfer technique provides good integration of two devices on rubber substrate with outstanding electrical and optical properties. Furthermore, a serpentine‐shaped interconnector allows the effective strain division for stable operation of display over 40% applied strain.
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.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Skin‐mountable devices that can directly measure various biosignals and external stimuli and communicate the information to the users have been actively studied owing to increasing demand for ...wearable electronics and newer healthcare systems. Research on skin‐mountable devices is mainly focused on those materials and mechanical design aspects that satisfy the device fabrication requirements on unusual substrates like skin and also for achieving good sensing capabilities and stable device operation in high‐strain conditions. 2D materials that are atomically thin and possess unique electrical and optical properties offer several important features that can address the challenging needs in wearable, skin‐mountable electronic devices. Herein, recent research progress on skin‐mountable devices based on 2D materials that exhibit a variety of device functions including information input and output and in vitro and in vivo healthcare and diagnosis is reviewed. The challenges, potential solutions, and perspectives on trends for future work are also discussed.
The unique electrical, mechanical, and optical properties of 2D materials provide a promising route to skin‐mountable electronics, which is necessary for the development of various applications, such as human–machine interfaces and healthcare systems. The recent research progress of skin‐mountable electronics based on 2D materials is reviewed and the challenges and opportunities pertaining to this field are discussed.
Although flakes of two-dimensional (2D) heterostructures at the micrometer scale can be formed with adhesive-tape exfoliation methods, isolation of 2D flakes into monolayers is extremely time ...consuming because it is a trial-and-error process. Controlling the number of 2D layers through direct growth also presents difficulty because of the high nucleation barrier on 2D materials. We demonstrate a layer-resolved 2D material splitting technique that permits high-throughput production of multiple monolayers of wafer-scale (5-centimeter diameter) 2D materials by splitting single stacks of thick 2D materials grown on a single wafer. Wafer-scale uniformity of hexagonal boron nitride, tungsten disulfide, tungsten diselenide, molybdenum disulfide, and molybdenum diselenide monolayers was verified by photoluminescence response and by substantial retention of electronic conductivity. We fabricated wafer-scale van der Waals heterostructures, including field-effect transistors, with single-atom thickness resolution.
Tactile sensor technology has been researched extensively in response to the increasing demand for robotic and wearable healthcare systems. Studies on tactile sensory systems have primarily focused ...on achieving two goals: (1) developing technologies with high sensing abilities that mimic the biological functions and characteristics of the sensory systems of human skin and (2) satisfying the requirements of wearable device applications by fabricating mechanically flexible devices with low-power data analysis and processing abilities. In this Perspective, we present recent advances in artificial tactile sensory systems, which are based on biomimetic technologies that exhibit functional features of biological systems including mechanoreceptors and human skin sensory neurons for human–machine interfaces. We also discuss the opportunities, current challenges, potential solutions, and future investigative directions pertaining to this field.
High levels of microsatellite instability (MSI‐H) occurs in about 15% of sporadic colorectal cancer (CRC) and is an important predictive marker for response to immune checkpoint inhibitors. To test ...the feasibility of a deep learning (DL)‐based classifier as a screening tool for MSI status, we built a fully automated DL‐based MSI classifier using pathology whole‐slide images (WSIs) of CRCs. On small image patches of The Cancer Genome Atlas (TCGA) CRC WSI dataset, tissue/non‐tissue, normal/tumor and MSS/MSI‐H classifiers were applied sequentially for the fully automated prediction of the MSI status. The classifiers were also tested on an independent cohort. Furthermore, to test how the expansion of the training data affects the performance of the DL‐based classifier, additional classifier trained on both TCGA and external datasets was tested. The areas under the receiver operating characteristic curves were 0.892 and 0.972 for the TCGA and external datasets, respectively, by a classifier trained on both datasets. The performance of the DL‐based classifier was much better than that of previously reported histomorphology‐based methods. We speculated that about 40% of CRC slides could be screened for MSI status without molecular testing by the DL‐based classifier. These results demonstrated that the DL‐based method has potential as a screening tool to discriminate molecular alteration in tissue slides.
What's new?
Microsatellite instability (MSI) levels are an important predictive biomarker for response to immune checkpoint inhibitors in colorectal cancer. To test the feasibility of a deep learning (DL)‐based classifier as a screening tool for MSI status, here the authors built a fully‐automated DL‐based MSI classifier using pathology whole‐slide images of hematoxylin and eosin‐stained tissue slides of colorectal cancer. By automatically removing artefacts and selecting tumour patches with high tumour probability, the DL‐based system could screen out a considerable number of tissue slides for their MSI status, demonstrating its potential as a screening tool for molecular alterations in tissue slides.
Efficient and highly functional three-dimensional systems that are ubiquitous in biology suggest that similar design architectures could be useful in electronic and optoelectronic technologies, ...extending their levels of functionality beyond those achievable with traditional, planar two-dimensional platforms. Complex three-dimensional structures inspired by origami, kirigami have promise as routes for two-dimensional to three-dimensional transformation, but current examples lack the necessary combination of functional materials, mechanics designs, system-level architectures, and integration capabilities for practical devices with unique operational features. Here, we show that two-dimensional semiconductor/semi-metal materials can play critical roles in this context, through demonstrations of complex, mechanically assembled three-dimensional systems for light-imaging capabilities that can encompass measurements of the direction, intensity and angular divergence properties of incident light. Specifically, the mechanics of graphene and MoS
, together with strategically configured supporting polymer films, can yield arrays of photodetectors in distinct, engineered three-dimensional geometries, including octagonal prisms, octagonal prismoids, and hemispherical domes.
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.
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