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  • 1
    In: Nature Communications, Springer Science and Business Media LLC, Vol. 14, No. 1 ( 2023-02-24)
    Abstract: SARS-CoV-2 Omicron variants feature highly mutated spike proteins with extraordinary abilities in evading antibodies isolated earlier in the pandemic. Investigation of memory B cells from patients primarily with breakthrough infections with the Delta variant enables isolation of a number of neutralizing antibodies cross-reactive to heterologous variants of concern (VOCs) including Omicron variants (BA.1-BA.4). Structural studies identify altered complementarity determining region (CDR) amino acids and highly unusual heavy chain CDR2 insertions respectively in two representative cross-neutralizing antibodies—YB9-258 and YB13-292. These features are putatively introduced by somatic hypermutation and they are heavily involved in epitope recognition to broaden neutralization breadth. Previously, insertions/deletions were rarely reported for antiviral antibodies except for those induced by HIV-1 chronic infections. These data provide molecular mechanisms for cross-neutralization of heterologous SARS-CoV-2 variants by antibodies isolated from Delta variant infected patients with implications for future vaccination strategy.
    Type of Medium: Online Resource
    ISSN: 2041-1723
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2023
    detail.hit.zdb_id: 2553671-0
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  • 2
    In: Nature Communications, Springer Science and Business Media LLC, Vol. 10, No. 1 ( 2019-06-17)
    Abstract: The effectiveness of most cancer targeted therapies is short-lived. Tumors often develop resistance that might be overcome with drug combinations. However, the number of possible combinations is vast, necessitating data-driven approaches to find optimal patient-specific treatments. Here we report AstraZeneca’s large drug combination dataset, consisting of 11,576 experiments from 910 combinations across 85 molecularly characterized cancer cell lines, and results of a DREAM Challenge to evaluate computational strategies for predicting synergistic drug pairs and biomarkers. 160 teams participated to provide a comprehensive methodological development and benchmarking. Winning methods incorporate prior knowledge of drug-target interactions. Synergy is predicted with an accuracy matching biological replicates for 〉 60% of combinations. However, 20% of drug combinations are poorly predicted by all methods. Genomic rationale for synergy predictions are identified, including ADAM17 inhibitor antagonism when combined with PIK3CB/D inhibition contrasting to synergy when combined with other PI3K-pathway inhibitors in PIK3CA mutant cells.
    Type of Medium: Online Resource
    ISSN: 2041-1723
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2019
    detail.hit.zdb_id: 2553671-0
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  • 3
    Online Resource
    Online Resource
    Springer Science and Business Media LLC ; 2021
    In:  Rock Mechanics and Rock Engineering Vol. 54, No. 8 ( 2021-08), p. 3873-3889
    In: Rock Mechanics and Rock Engineering, Springer Science and Business Media LLC, Vol. 54, No. 8 ( 2021-08), p. 3873-3889
    Type of Medium: Online Resource
    ISSN: 0723-2632 , 1434-453X
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2021
    detail.hit.zdb_id: 1476578-0
    SSG: 16,13
    SSG: 19,1
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  • 4
    In: Advanced Materials, Wiley, Vol. 34, No. 10 ( 2022-03)
    Abstract: In recent years, significant evolutions have been made in applying nanotechnologies for prophylactic and therapeutic cancer vaccine design. However, the clinical translation of nanovaccines is still limited owing to their complicated compositions and difficulties in the spatiotemporal coordination of antigen‐presenting cell activation and antigen cross‐presentation. Herein, a minimalist binary nanovaccine (BiVax) is designed that integrates innate stimulating activity into the carrier to elicit robust antitumor immunity. The authors started by making a series of azole molecules end‐capped polyethylenimine (PEI‐M), and were surprised to find that over 60% of the PEI‐M polymers have innate stimulating activity via activation of the stimulator of interferon genes pathway. PEI‐4BImi, a PEI‐M obtained from a series of polymers, elicits robust antitumor immune responses when used as a subcutaneously injected nanovaccine by simply mixing with ovalbumin antigens, and this BiVax system performs much better than the traditional ternary vaccine system, as well as, commercialized aluminum‐containing adjuvants. This system also enables the fast preparation of personalized BiVax by compositing PEI‐4BImi with autologous tumor cell membrane protein antigens, and a 60% postoperative cure rate is observed when combined with immune checkpoint inhibitors.
    Type of Medium: Online Resource
    ISSN: 0935-9648 , 1521-4095
    URL: Issue
    RVK:
    Language: English
    Publisher: Wiley
    Publication Date: 2022
    detail.hit.zdb_id: 1474949-X
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  • 5
    In: Advanced Materials, Wiley, Vol. 33, No. 7 ( 2021-02)
    Abstract: Using nanotechnology for improving the immunotherapy efficiency represents a major research interest in recent years. However, there are paradoxes and obstacles in using a single nanoparticle to fulfill all the requirements in the complicated immune activation processes. Herein, a supramolecular assembled programmable immune activation nanomedicine (PIAN) for sequentially finishing multiple steps after intravenous injection and eliciting robust antitumor immunity in situ is reported. The programmable nanomedicine is constructed by supramolecular assembly via host–guest interactions between poly‐[( N ‐2‐hydroxyethyl)‐aspartamide]‐Pt(IV)/β‐cyclodextrin (PPCD), CpG/polyamidoamine‐thioketal‐adamantane (CpG/PAMAM‐TK‐Ad), and methoxy poly(ethylene glycol)‐thioketal‐adamantane (mPEG‐TK‐Ad). After intravenous injection and accumulation at the tumor site, the high level of reactive oxygen species in the tumor microenvironment promotes PIAN dissociation and the release of PPCD (mediating tumor cell killing and antigen release) and CpG/PAMAM (mediating antigen capturing and transferring to the tumor‐draining lymph nodes). This results in antigen‐presenting cell activation, antigen presentation, and robust antitumor immune responses. In combination with anti‐PD‐L1 antibody, the PIAN cures 40% of mice in a colorectal cancer model. This PIAN provides a new framework for designing programmable nanomedicine as in situ cancer vaccine for cancer immunotherapy.
    Type of Medium: Online Resource
    ISSN: 0935-9648 , 1521-4095
    URL: Issue
    RVK:
    Language: English
    Publisher: Wiley
    Publication Date: 2021
    detail.hit.zdb_id: 1474949-X
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  • 6
    In: Journal of NeuroInterventional Surgery, BMJ
    Abstract: Flow diverters have revolutionized the treatment of intracranial aneurysms. However, the delayed complications associated with flow diverter use are unknown. Objective To evaluate the incidence, severity, clinical outcomes, risk factors, and dynamic changes associated with in-stent stenosis (ISS) after treatment with a Pipeline embolization device (PED). Methods Patients who underwent PED treatment between 2015 and 2020 were enrolled. The angiographic, clinical, and follow-up data of 459 patients were independently reviewed by four neuroradiologists to identify ISS. Binary logistic regression was conducted to determine ISS risk factors, and an ISS–time curve was established to demonstrate dynamic changes in ISS after PED implantation. Results Of the 459 treated patients, 69 (15.0%) developed ISS. At follow-up, nine patients (2.0%) with ISS demonstrated reversal, while 18 (3.9%) developed parental artery occlusion. A total of 380 patients (82.8%) achieved complete aneurysm occlusion (O’Kelly–Marotta grade D). Patients with posterior-circulation aneurysm (OR=2.895, 95% CI (1.732 to 4.838; P 〈 0.001) or balloon angioplasty (OR=1.992, 95% CI 1.162 to 3.414; P=0.037) were more likely to develop ISS. Patients aged 〉 54 years (OR=0.464, 95% CI 0.274 to 0.785; P=0.006) or with a body mass index of 〉 28 kg/m 2 (OR=0.427, 95% CI 0.184 to 0.991; P=0.026) had a lower ISS risk. Intimal hyperplasia initiated by PED placement peaked within 1 year after the procedure, rarely progressed after 12 months, and tended to reverse within 24 months. Conclusions ISS is a common, benign, and self-limiting complication of PED implantation in the Chinese population.
    Type of Medium: Online Resource
    ISSN: 1759-8478 , 1759-8486
    Language: English
    Publisher: BMJ
    Publication Date: 2023
    detail.hit.zdb_id: 2506028-4
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  • 7
    Online Resource
    Online Resource
    Frontiers Media SA ; 2022
    In:  Frontiers in Neurology Vol. 13 ( 2022-9-6)
    In: Frontiers in Neurology, Frontiers Media SA, Vol. 13 ( 2022-9-6)
    Abstract: The Pipeline embolization device (PED) is a flow diverter used to treat intracranial aneurysms. In-stent stenosis (ISS) is a common complication of PED placement that can affect long-term outcome. This study aimed to establish a feasible, effective, and reliable model to predict ISS using machine learning methodology. Methods We retrospectively examined clinical, laboratory, and imaging data obtained from 435 patients with intracranial aneurysms who underwent PED placement in our center. Aneurysm morphological measurements were manually measured on pre- and posttreatment imaging studies by three experienced neurointerventionalists. ISS was defined as stenosis rate & gt;50% within the PED. We compared the performance of five machine learning algorithms (elastic net (ENT), support vector machine, Xgboost, Gaussian Naïve Bayes, and random forest) in predicting ISS. Shapley additive explanation was applied to provide an explanation for the predictions. Results A total of 69 ISS cases (15.2%) were identified. Six predictors of ISS (age, obesity, balloon angioplasty, internal carotid artery location, neck ratio, and coefficient of variation of red cell volume distribution width) were identified. The ENT model had the best predictive performance with a mean area under the receiver operating characteristic curve of 0.709 (95% confidence interval [CI], 0.697–0.721), mean sensitivity of 77.9% (95% CI, 75.1–80.6%), and mean specificity of 63.4% (95% CI, 60.8–65.9%) in Monte Carlo cross-validation. Shapley additive explanation analysis showed that internal carotid artery location was the most important predictor of ISS. Conclusion Our machine learning model can predict ISS after PED placement for treatment of intracranial aneurysms and has the potential to improve patient outcomes.
    Type of Medium: Online Resource
    ISSN: 1664-2295
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2564214-5
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  • 8
    Online Resource
    Online Resource
    American Chemical Society (ACS) ; 2018
    In:  ACS Macro Letters Vol. 7, No. 10 ( 2018-10-16), p. 1174-1179
    In: ACS Macro Letters, American Chemical Society (ACS), Vol. 7, No. 10 ( 2018-10-16), p. 1174-1179
    Type of Medium: Online Resource
    ISSN: 2161-1653 , 2161-1653
    Language: English
    Publisher: American Chemical Society (ACS)
    Publication Date: 2018
    detail.hit.zdb_id: 2644375-2
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  • 9
    Online Resource
    Online Resource
    Springer Science and Business Media LLC ; 2021
    In:  Scientific Reports Vol. 11, No. 1 ( 2021-03-25)
    In: Scientific Reports, Springer Science and Business Media LLC, Vol. 11, No. 1 ( 2021-03-25)
    Abstract: Laparoendoscopic single-site surgery (LESS) further minimizes the invasiveness of traditional laparoscopic surgery. However, the "chopstick" effect caused by the parallel arrangement of the instruments in the umbilicus is considered an obstacle indelicate operations. The purpose of this study was to introduce a new technique characterized by a double fulcrum formed by instruments, named the "chopstick" technique, which facilitates the expedient accomplishment of complicated surgeries such as LESS radical hysterectomy (LESS-RH). Seventy-three patients who underwent LESS-RH using the "chopstick" technique were retrospectively analyzed. The procedure was performed successfully in 72 patients. The median operative duration was 225 min, and the median intraoperative blood loss was 200 ml. Among the operations in the first 20 patients, intraoperative vascular injuries and bladder injury occurred in two patients and were repaired by LESS. Patients responded positively regarding minimal postoperative pain control. The score of satisfaction with the cosmetic outcome expressed by the patients was eight at discharge and nine 30 days later. In conclusion, this study presents the feasibility of accomplishing complicated procedures, such as radical hysterectomy, by LESS using the “chopstick” technique. This approach provides more options for both selected patients and surgeons.
    Type of Medium: Online Resource
    ISSN: 2045-2322
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2021
    detail.hit.zdb_id: 2615211-3
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  • 10
    Online Resource
    Online Resource
    Hindawi Limited ; 2022
    In:  Computational Intelligence and Neuroscience Vol. 2022 ( 2022-8-21), p. 1-10
    In: Computational Intelligence and Neuroscience, Hindawi Limited, Vol. 2022 ( 2022-8-21), p. 1-10
    Abstract: The improvement of small target detection and obscuration handling is the key problem to be solved in the object detection task. In the field operation of chemical plant, due to the occlusion of construction workers and the long distance of surveillance shooting, it often leads to the phenomenon of missed detection. Most of the existing work uses multiple feature fusion strategies to extract different levels of features and then aggregate them into global features, which does not utilize local features and makes it difficult to improve the performance of small target detection. To address this issue, this paper introduces Point Transformer, a transformer encoder, as the core backbone of the object detection framework that first uses a priori information of human skeletal points to obtain local features and then uses both self-attention and cross-attention mechanisms to reconstruct the local features corresponding to each key point. In addition, since the target to be detected is highly correlated with the position of human skeletal points, to further boost Point Transformer’s performance, a learnable positional encoding method is proposed by us to highlight the position characteristics of each skeletal point. The proposed model is evaluated on the dataset of field operation in a chemical plant. The results are significantly better than the classical algorithms. It also outperforms state-of-the-art by 12 percent of map points in the small target detection task.
    Type of Medium: Online Resource
    ISSN: 1687-5273 , 1687-5265
    Language: English
    Publisher: Hindawi Limited
    Publication Date: 2022
    detail.hit.zdb_id: 2388208-6
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