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91.
《Vaccine》2020,38(50):7916-7927
Respiratory syncytial virus (RSV) is the major cause of acute lower respiratory illness in children of less than 5 years of age which usually results in hospitalization or even in death. Vaccine development is hampered in consequence of a failed vaccine trial with fatalities in the 1960s. Even though research has been more focused on the RSV fusion protein in its pre-fusion conformation, maternal vaccination with post-fusion protein (post F) was considered as a promising vaccine strategy for passive immunization of babies, because post F preserves very potent neutralizing epitopes. We extensively analyzed post F-binding B cell receptor (BCR) repertoires of three vaccinees who received a post F-subunit vaccine in the context of a first-in-human, Phase 1, randomized, observer-blind, placebo-controlled clinical trial (ClinicalTrials.gov Identifier: NCT02298179). In order to compare the vaccine-induced BCR repertoires with BCR repertoires induced by natural infection, we also analyzed pre F- and post F-binding BCRs isolated from a healthy blood donor with relatively high F-binding memory B cell (MBC) frequencies. Analysis of the vaccine-induced repertoires revealed that preferentially VH4-encoded BCRs were expanded in response to vaccination. Estimation of antigen-driven selection further demonstrated that expanded BCRs accumulated positively selected replacement mutations which substantiated the hypothesis that post F-vaccination induces diversification of VH4-encoded BCRs in germinal centers. Comparison of the vaccine-induced BCR repertoires with clonally related pre and post F-binding BCRs of the healthy blood donor suggested that the vaccine expanded pre/post F cross-reactive MBCs. Interestingly, several vaccine-induced BCRs shared stereotypic VDJ gene junctions with known neutralizing Abs. Once expressed for functional characterization, the selected monoclonal Abs demonstrated the predicted neutralization activities in plaque reduction neutralization assays indicating that the post F-vaccine induced expansion of neutralizing BCRs. 相似文献
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背景与目的以免疫检查点抑制剂(immune checkpoint inhibitors, ICIs)为代表的免疫治疗越来越广泛地应用于肺癌治疗。然而,对于程序性死亡受体配体1(programmed cell death-ligand 1, PD-L1)高表达,即肿瘤比例评分(tumor proportion score, TPS)≥50%的晚期非小细胞肺癌(non-small cell lung cancer, NSCLC)患者,采用单纯免疫治疗还是免疫联合化疗在临床上仍存争议。本研究旨在评估PD-L1高表达的晚期NSCLC患者接受单纯免疫治疗与免疫联合化疗的疗效。方法本研究回顾性分析了49例PD-L1高表达晚期NSCLC患者的临床资料。PD-L1表达采用22C3抗体行免疫组化染色,按TPS判读PD-L1表达水平。比较不同临床特征分组患者的客观缓解率(objective response rate,ORR)和无进展生存时间(progression free survival, PFS)。结果免疫单药与免疫联合化疗组的ORR分别为47.1%(8/17)和43.8%(14/32),差异无统计学意义(P=0.825)。免疫单药与免疫联合化疗组的中位PFS分别为8.0个月和6.8个月,差异无统计学意义(P=0.502)。并对本组PD-L1高表达患者免疫治疗的预测因素进行了分析,结果显示,一线免疫治疗ORR(12/19, 63.2%)显著优于二线及以上免疫治疗(10/30, 33.3%),差异有统计学意义(P=0.041),二者间PFS无差异。年龄、性别、吸烟史、功能状态评分(performance status, PS)、病理类型、肿瘤大小、肿瘤淋巴结转移(tumor node metastasis, TNM)分期与ORR和PFS不相关。结论PD-L1高表达的晚期NSCLC患者接受免疫单药和免疫联合化疗的疗效相近。PD-L1高表达患者一线免疫治疗的ORR更佳。对此类人群的最佳治疗方案有待于前瞻性临床研究进一步探索。 相似文献
94.
《Clinical neurophysiology》2021,132(12):3104-3115
ObjectiveWe aimed to establish an objective neurophysiological test protocol that can be used to assess the somatosensory nervous system.MethodsIn order to assess most fiber subtypes of the somatosensory nervous system, repetitive stimuli of seven different modalities (touch, vibration, pinprick, cold, contact heat, laser, and warmth) were synchronized with the electroencephalogram (EEG) and applied on the cheek and dorsum of the hand and dorsum of the foot in 21 healthy subjects and three polyneuropathy (PNP) patients. Latencies and amplitudes of the modalities were assessed and compared. Patients received quantitative sensory testing (QST) as reference.ResultsWe found reproducible evoked potentials recordings for touch, vibration, pinprick, contact-heat, and laser stimuli. The recording of warm-evoked potentials was challenging in young healthy subjects and not applicable in patients. Latencies were shortest within Aβ-fiber-mediated signals and longest within C-fibers. The test protocol detected function loss within the Aβ-fiber and Aδ-fiber-range in PNP patients. This function loss corresponded with QST findings.ConclusionIn this pilot study, we developed a neurophysiological test protocol that can specifically assess most of the somatosensory modalities. Despite technical challenges, initial patient data appear promising regarding a possible future clinical application.SignificanceEstablished and custom-made stimulators were combined to assess different fiber subtypes of the somatosensory nervous system using modality-specific evoked potentials. 相似文献
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Prabhakaran Dhanasekaran Swaminathan Rajavarman Sivasuriyanarayanan Vinod Selvaganesh Santoshkumar Dattatray Bhat 《Materials》2021,14(9)
Nanocrystalline platinum with different morphologies is synthesized via electrochemical deposition technique. The nucleation mechanism and its structural effect over the electrodeposited Pt on carbon electrodes have been systematically studied. Powder X-ray diffraction, X-ray photoelectron spectroscopy, and field-emission scanning electron microscopy are employed to study nucleation, oxidation states, and Pt structure growth on a carbon electrode. This study reports significant development of Pt metal nanoparticles with different morphologies such as a sphere, flower, core-flower, and rod-like structure directly fabricated on carbon electrode while tuning the deposition parameters such as current density, time, temperature, pH during the deposition process. The proposed electrochemical route represents a superior fabrication procedure for large-scale electrode fabrication compared to a conventional method for preparing membrane electrode assemblies for fuel cell stacks. 相似文献