Evaluation of the Safety Profile of the ASFV Vaccine Candidate ASFV-G-ΔI177L

African swine fever (ASF) is the cause of a recent pandemic that is posing a threat to much of the world swine production. The etiological agent, ASF virus (ASFV), infects domestic and wild swine, producing a variety of clinical presentations depending on the virus strain and the genetic background of the pigs infected. No commercial vaccine is currently available, although recombinant live attenuated vaccine candidates have been shown to be efficacious. In addition to determining efficacy, it is paramount to evaluate the safety profile of a live attenuated vaccine. The presence of residual virulence and the possibility of reversion to virulence are two of the concerns that must be evaluated in the development of live attenuated vaccines. Here we evaluate the safety profile of an efficacious live attenuated vaccine candidate, ASFV-G-ΔI177L. Results from safety studies showed that ASFV-G-ΔI177L remains genetically stable and phenotypically attenuated during a five-passage reversion to virulence study in domestic swine. In addition, large-scale experiments to detect virus shedding and transmission confirmed that even under varying conditions, ASFV-G-ΔI177L is a safe live attenuated vaccine.     

Mre11 inhibition by oncolytic adenovirus associates with autophagy and underlies synergy with ionizing radiation

New treatment approaches are needed for hormone refractory prostate cancer. Oncolytic adenoviruses are promising anti‐cancer agents, and their efficacy can be improved by combining with conventional therapies such as ionizing radiation. The aim of this study was to determine the timing of oncolytic adenovirus treatment with regard to radiation and study the mechanisms of synergy in combination treatment. Prostate cancer cells were infected with oncolytic adenoviruses, irradiated and synergy mechanisms were assessed. In vivo models of combination treatment were tested. Radiation and oncolytic viruses were synergistic when viral infection was scheduled 24 hr after irradiation. Combination of oncolytic adenovirus with radiotherapy significantly increased antitumor efficacy in vivo compared to either agent alone. Microarray analysis showed dysregulated pathways including cell cycle, mTOR and antigen processing pathways. Functional analysis showed that adenoviral infection was accompanied with degradation of proteins involved in DNA break repair. Mre11 was degraded for subsequent inactivation of Chk2‐Thr68 in combination treated cells, while γH2AX‐Ser139 was elevated implicating the persistence of DNA double strand breaks. Increased autophagocytosis was seen in combination treated cells. Combination treatment did not increase apoptosis or virus replication. The results provide evidence of the antitumor efficacy of combining oncolytic adenoviruses with irradiation as a therapeutic strategy for the treatment of prostate cancer. Further, these findings propose a molecular mechanism that may be important in radiation induced cell death, autophagy and viral cytopathic effect. © 2009 UICC     

High electrochemical performance of ink solution based on manganese cobalt sulfide/reduced graphene oxide nano-composites for supercapacitor electrode materials

Large scale supercapacitor electrodes were prepared by 3D-printing directly on a graphite paper substrate from ink solution containing manganese cobalt sulfide/reduced graphene oxide (MCS/rGO) nanocomposites. The MCS/rGO composite solution was synthesized through the dispersion of MCS NPs and rGO in dimethylformamide (DMF) solvent at room temperature. Their morphology and composition were investigated by scanning electron microscopy (SEM), transmission electron microscopy (TEM), and energy dispersive X-ray diffraction (EDS). The role of rGO on decreasing charge transfer resistance and enhancing ion exchange was discussed. The MCS/rGO electrode exhibits an excellent specific capacitance of 3812.5 F g⁻¹ at 2 A g⁻¹ and it maintains 1780.8 F g⁻¹ at a high current density of 50 A g⁻¹. The cycling stability of the electrodes reveals capacitance retention of over 92% after 22 000 cycles at 50 A g⁻¹.

Large scale supercapacitor electrodes were prepared by 3D-printing directly on a graphite paper substrate from ink solution containing manganese cobalt sulfide/reduced graphene oxide (MCS/rGO) nanocomposites.     

SARS-CoV-2 Infection in a Hippopotamus,Hanoi, Vietnam

While investigating the death of a hippopotamus at a zoo in Hanoi, Vietnam, we isolated SARS-CoV-2 and sequenced the RNA-dependent RNA polymerase gene from different organs. Phylogenetic analysis showed that the SARS-CoV-2 strain was closely related to 3 human SARS-CoV-2 strains in Vietnam.     

Pembrolizumab in Asian patients with microsatellite‐instability‐high/mismatch‐repair‐deficient colorectal cancer

The phase 3 KEYNOTE‐177 study evaluated pembrolizumab versus chemotherapy with or without bevacizumab or cetuximab in patients with newly diagnosed, microsatellite‐instability‐high (MSI‐H)/mismatch‐repair‐deficient (dMMR) metastatic colorectal cancer (mCRC). Primary endpoints were progression‐free survival (PFS) per RECIST v1.1 by blinded independent central review (BICR) and overall survival (OS). Secondary endpoints were overall response rate (ORR) per RECIST v1.1 by BICR and safety. Here, we report results from the post hoc analysis of patients who were enrolled in Asia from the final analysis (FA) of KEYNOTE‐177. A total of 48 patients from Japan, Korea, Singapore, and Taiwan (pembrolizumab, n = 22; chemotherapy, n = 26) were included. At FA, median time from randomization to data cutoff (February 19, 2021) was 45.3 (range 38.1–57.8) months with pembrolizumab and 43.9 (range 36.6–55.1) months with chemotherapy. Median PFS was not reached (NR; 95% confidence interval [CI] 1.9 months–NR) with pembrolizumab versus 10.4 (95% CI 6.3–22.0) months with chemotherapy (hazard ratio [HR] 0.56, 95% CI 0.26–1.20). Median OS was NR (range 13.8 months–NR) versus 30.0 (14.7–NR) months (HR 0.65, 95% CI 0.27–1.55) and ORR was 50% (95% CI 28–72) versus 46% (95% CI 27–67). Grade 3/4 treatment‐related adverse events (TRAEs) were reported by two patients (9%) in the pembrolizumab arm and 20 (80%) in the chemotherapy arm. Immune‐mediated adverse events or infusion reactions were reported by six patients (27%) and 10 patients (40%), respectively. No deaths due to TRAEs occurred. These data support first‐line pembrolizumab as a standard of care for patients from Asia with MSI‐H/dMMR mCRC. ClinicalTrials.gov identifier: {"type":"clinical-trial","attrs":{"text":"NCT02563002","term_id":"NCT02563002"}}NCT02563002.     

COVID-19 vaccine acceptance and its determinants among Vietnamese teachers: a web-based cross-sectional survey

ObjectivesThis paper aimed to describe acceptance of the COVID-19 vaccine and its determinants among Vietnamese teachers.MethodsThis was a web-based cross-sectional survey with a sample of 17,176 teachers from kindergarten to high school who currently reside in Vietnam. A participant who exhibited “acceptance” towards the vaccine gave the following response: “have the readiness to get COVID-19 vaccine”.ResultsAbout 88% of all participants were accepting of the COVID-19 vaccine, while 70.4% were willing to pay (WTP) for it. The vaccine acceptance rate increased by age with odds ratios (OR) of 1.65 (1.41–1.93), 1.96 (1.67–2.29), and 2.4 (1.95–2.95) for the age groups 30–39, 40–49, and 50–59 respectively, when compared to the 18–29 age group. Male were found to be more likely to accept the vaccination than females (OR = 1.16; 95% CI: 1.02–1.31); teachers without a chronic disease were 4.13 times (95% CI: 2.67–6.37) more likely to accept the vaccine than those with an underlying condition. Willingness to pay and beliefs about the safety and efficacy of the vaccine were major factors in driving participants'' responses.ConclusionA high proportion of COVID-19 vaccine acceptance is a promising indicator of high coverage among this priority group for vaccination. Communication campaigns should consider addressing determinants uncovered by this study to achieve better vaccine acceptance.     

Pembrolizumab in Asian patients with microsatellite-instability-high/mismatch-repair-deficient colorectal cancer

The phase 3 KEYNOTE-177 study evaluated pembrolizumab versus chemotherapy with or without bevacizumab or cetuximab in patients with newly diagnosed, microsatellite-instability-high (MSI-H)/mismatch-repair-deficient (dMMR) metastatic colorectal cancer (mCRC). Primary endpoints were progression-free survival (PFS) per RECIST v1.1 by blinded independent central review (BICR) and overall survival (OS). Secondary endpoints were overall response rate (ORR) per RECIST v1.1 by BICR and safety. Here, we report results from the post hoc analysis of patients who were enrolled in Asia from the final analysis (FA) of KEYNOTE-177. A total of 48 patients from Japan, Korea, Singapore, and Taiwan (pembrolizumab, n = 22; chemotherapy, n = 26) were included. At FA, median time from randomization to data cutoff (February 19, 2021) was 45.3 (range 38.1–57.8) months with pembrolizumab and 43.9 (range 36.6–55.1) months with chemotherapy. Median PFS was not reached (NR; 95% confidence interval [CI] 1.9 months–NR) with pembrolizumab versus 10.4 (95% CI 6.3–22.0) months with chemotherapy (hazard ratio [HR] 0.56, 95% CI 0.26–1.20). Median OS was NR (range 13.8 months–NR) versus 30.0 (14.7–NR) months (HR 0.65, 95% CI 0.27–1.55) and ORR was 50% (95% CI 28–72) versus 46% (95% CI 27–67). Grade 3/4 treatment-related adverse events (TRAEs) were reported by two patients (9%) in the pembrolizumab arm and 20 (80%) in the chemotherapy arm. Immune-mediated adverse events or infusion reactions were reported by six patients (27%) and 10 patients (40%), respectively. No deaths due to TRAEs occurred. These data support first-line pembrolizumab as a standard of care for patients from Asia with MSI-H/dMMR mCRC. ClinicalTrials.gov identifier: NCT02563002.     

A rare,pediatric, fourth-ventricular,anaplastic astrocytoma

Anaplastic astrocytoma, a diffusely infiltrating, malignant, astrocytic, primary brain tumor, is most commonly observed between 30 and 50 years of age. Anaplastic astrocytomas are now classified as WHO grade III lesions, with imaging characteristics and prognosis between diffuse low-grade astrocytomas (WHO grade II) and glioblastomas (WHO IV). Anaplastic astrocytoma can appear mostly in the cerebrum followed by cerebellum. However, it is rarely observed in the fourth ventricle. In this article, we aimed to describe an uncommon case of a pediatric, fourth-ventricular, anaplastic astrocytoma. A 9-year-old male who underwent MRI brain then adopted gross-total tumor eradication. The final histopathology findings were consistent with an anaplastic astrocytoma.