Abstract
We present an interim analysis of a registered clinical study (NCT04800133) to establish immunobridging with various antibody and cellular immunity markers and to compare the immunogenicity ...and reactogenicity of 2-dose BNT162b2 and CoronaVac in healthy adolescents as primary objectives. One-dose BNT162b2, recommended in some localities for risk reduction of myocarditis, is also assessed. Antibodies and T cell immune responses are non-inferior or similar in adolescents receiving 2 doses of BNT162b2 (BB,
N
= 116) and CoronaVac (CC,
N
= 123) versus adults after 2 doses of the same vaccine (BB,
N
= 147; CC,
N
= 141) but not in adolescents after 1-dose BNT162b2 (B,
N
= 116). CC induces SARS-CoV-2 N and N C-terminal domain seropositivity in a higher proportion of adolescents than adults. Adverse reactions are mostly mild for both vaccines and more frequent for BNT162b2. We find higher S, neutralising, avidity and Fc receptor-binding antibody responses in adolescents receiving BB than CC, and a similar induction of strong S-specific T cells by the 2 vaccines, in addition to N- and M-specific T cells induced by CoronaVac but not BNT162b2, possibly implying differential durability and cross-variant protection by BNT162b2 and CoronaVac, the 2 most used SARS-CoV-2 vaccines worldwide. Our results support the use of both vaccines in adolescents.
While activation of BAX/BAK by BH3-only molecules (BH3s) is essential for mitochondrial apoptosis, the underlying mechanisms remain unsettled. Here we demonstrate that BAX undergoes stepwise ...structural reorganization leading to mitochondrial targeting and homo-oligomerization. The α1 helix of BAX keeps the α9 helix engaged in the dimerization pocket, rendering BAX as a monomer in cytosol. The activator BH3s, tBID/BIM/PUMA, attack and expose the α1 helix of BAX, resulting in secondary disengagement of the α9 helix and thereby mitochondrial insertion. Activator BH3s remain associated with the N-terminally exposed BAX through the BH1 domain to drive homo-oligomerization. BAK, an integral mitochondrial membrane protein, has bypassed the first activation step, explaining why its killing kinetics are faster than those of BAX. Furthermore, death signals initiated at ER induce BIM and PUMA to activate mitochondrial apoptosis. Accordingly, deficiency of Bim/Puma impedes ER stress-induced BAX/BAK activation and apoptosis. Our study provides mechanistic insights regarding the spatiotemporal execution of BAX/BAK-governed cell death.
A phase III trial was conducted to compare the safety and efficacy of erlotinib with that of gefitinib in advanced non-small cell lung cancer harbouring epidermal growth factor receptor mutations in ...exon 19 or 21.
Eligible patients were randomised to receive erlotinib (150 mg per day) or gefitinib (250 mg per day) orally until disease progression or unacceptable toxicity. We aimed to determine whether erlotinib is superior to gefitinib in efficacy. The primary end point was progression-free survival.
A total of 256 patients were randomised to receive erlotinib (N=128) or gefitinib (N=128). Median progression-free survival was not better with erlotinib than with gefitinib (13.0 vs 10.4 months, 95% confidence interval (CI) 0.62-1.05, P=0.108). The corresponding response rates and median overall survival were 56.3% vs 52.3% (P=0.530) and 22.9 vs 20.1 months (95% CI 0.63-1.13, P=0.250), respectively. There were no significant differences in grade 3/4 toxicities between the two arms (P=0.172).
The primary end point was not met. Erlotinib was not significantly superior to gefitinib in terms of efficacy in advanced non-small cell lung cancer with epidermal growth factor receptor mutations in exon 19 or 21, and the two treatments had similar toxicities.
Abstract Background Research on the clinicopathology and prognosis of gastric neuroendocrine carcinoma (GNEC) is rare, and a uniform standard for treatment has not been established. Therefore, we ...retrospectively analyzed the clinical data of 132 cases of GNEC to investigate the factors influencing prognosis. Methods A total of 132 patients diagnosed with GNEC at Fujian Medical University Union Hospital from January 2006 to December 2013 were enrolled. This study was performed to analyze the factors related to patient prognosis. Results In total, 58 men and 74 women whose ages ranged from 38 to 83 years old (62 ± 10) were enrolled. The 1- and 3-year survival rates for these patients were 83.9% and 47.6%, respectively. Of these patients, 100 underwent radical resection, 22 underwent palliative resection, and 10 received chemotherapy alone. The median survival times following radical resection, palliative resection and chemotherapy alone were 48, 20 and 12 months, respectively (P<0.01). Univariate and multivariate survival analyses of patients who underwent radical resection showed that tumor size, N stage, Ki-67 labeling index, mitotic index and the application of postoperative adjuvant chemotherapy were independent factors affecting patient prognosis. The correlation analysis of the Ki-67 labeling index and mitotic index with prognosis showed that patient survival decreased significantly when the Ki-67 labeling index increased (P<0.05). Conclusions Patients who underwent radical resection had the best prognosis among GNEC. For these patients, tumor size, N stage, Ki-67 labeling index, mitotic index and the application of postoperative adjuvant chemotherapy were the clinicopathological factors significantly associated with patient prognosis.
In current sampling approaches, there exists a divergence between the surveillance of arthropod‐borne and that of non‐arthropod‐borne viruses. It is commonly held that the collection of vector ...specimens applies only to arbovirus surveillance and that the surveillance of non‐arboviruses must rely on traditional methods that involve the sampling of blood, faeces or saliva, or other examinations. The vector‐based approach is a sampling method that has the ability to survey both arboviruses and non‐arboviruses by distinguishing engorged vector specimens from entire vector samples. Accordingly, five arboviruses and three non‐arboviruses were detected in a study using a vector‐based approach conducted during 2012–2015. Hence, this report provides the first description of the Taiwanese vector species for the bovine arboviruses detected. The present investigations demonstrate that the vector‐based approach applies not only to the surveillance of arboviruses, but also has potential as a possible tool for monitoring non‐arboviruses on livestock farms in the future.
Vector‐based sampling has potential for the simultaneous monitoring of arboviruses and non‐arboviruses on livestock farms.
The vector or potential vector species of five bovine arboviruses detected in Taiwan were identified for the first time.
Aino virus and Peaton virus were detected in Taiwan for the first time.
Employing Oliver's disconfirmation theory as a theoretical basis, we examined the relationships between school teachers' attitudes, expectations and satisfaction with collaborating with school ...counsellors. Also, structural equation modelling was used to determine the effects of counsellors' professional traits on teacher satisfaction. Stratified sampling yielded a sample of 395 homeroom teachers from 26 public schools in Taoyuan City, Taiwan, representing a 94.4% response rate. We found: (1) teachers were highly satisfied with their collaborations with school counsellors, (2) teachers' collaborative attitudes and expectations were significant predictors of their satisfaction, supporting Oliver's theory, and (3) counsellor's professional traits significantly affected teachers' collaborative attitudes, expectations, and satisfaction.
Abstract Most previous studies on facial asymmetry have not specifically differentiated mandible deviation from structural asymmetry of the mandible. The purpose of this study was to assess the ...symmetry of the mandible by examining its contour in a cohort of patients with significant facial asymmetry. Eleven cases of facial asymmetry with chin deviation ≥10 mm were enrolled. A voxel-paired median plane (optimal symmetry plane, OSP) and two landmark-based median planes were generated. The OSP was created by computing the best pairing of the bony voxels on the two sides. One side of the mandibular contour was mirrored onto the other side using the test plane. The contour differences were measured by distance and by area ratio. They were examined both in frontal and frontal downward inclined view. The contour symmetry of the mandible was that revealed by the plane that presented the best symmetry. The results showed that the OSP worked best in bisecting the contour into two symmetrical halves. Contour analysis showed relatively small discrepancies between the two sides. In conclusion, the mandibles retained an acceptable contour symmetry despite the presence of significant mandibular deviations. It is suggested that proper mandibular alignment be the primary objective in the correction of facial asymmetry.
A “hybrid photochromic” molecule with intertwined tetraazaporphyrin and bisthienylethene (BTE) chromophores is presented. The key photo‐process is the simultaneous cyclization of two BTE units ...(yielding the molecule shown in the Figure) with high quantum yield at RT, and with a strongly temperature‐dependent yield for the reverse reaction. The molecule is, thus, an ideal candidate for non‐ destructive readout optical memory devices.
Ni–P–carbon nanotube (CNT) composite coating and carbon nanotube/copper matrix composites were prepared by electroless plating and powder metallurgy techniques, respectively. The effects of CNTs on ...the tribological properties of these composites were evaluated. The results demonstrated that the Ni–P–CNT electroless composite coating exhibited higher wear resistance and lower friction coefficient than Ni–P–SiC and Ni–P–graphite composite coatings. After annealing at 673 K for 2 h, the wear resistance of the Ni–P–CNT composite coating was improved. Carbon nanotube/copper matrix composites revealed a lower wear rate and friction coefficient compared with pure copper, and their wear rates and friction coefficients showed a decreasing trend with increasing volume fraction of CNTs within the range from 0 to 12 vol.% due to the effects of the reinforcement and reduced friction of CNTs. The favorable effects of CNTs on the tribological properties are attributed to improved mechanical properties and unique topological structure of the hollow nanotubes.
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