Explore the vast range of titles available.

As part of the accelerated development of vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), we report a dose-finding and adjuvant justification study of SCB-2019, a protein subunit vaccine candidate containing a stabilised trimeric form of the spike (S)-protein (S-Trimer) combined with two different adjuvants. Our study is a phase 1, randomised, double-blind placebo-controlled trial at a specialised clinical trials centre in Australia. We enrolled healthy adult volunteers in two age groups: younger adults (aged 18–54 years) and older adults (aged 55–75 years). Participants were randomly allocated either vaccine or placebo using a list prepared by the study funder. Participants were to receive two doses of SCB-2019 (either 3 μg, 9 μg, or 30 μg) or a placebo (0·9% NaCl) 21 days apart. SCB-2019 either had no adjuvant (S-Trimer protein alone) or was adjuvanted with AS03 or CpG/Alum. The assigned treatment was administered in opaque syringes to maintain masking of assignments. Reactogenicity was assessed for 7 days after each vaccination. Humoral responses were measured as SCB-2019 binding IgG antibodies and ACE2-competitive blocking IgG antibodies by ELISA and as neutralising antibodies by wild-type SARS-CoV-2 microneutralisation assay. Cellular responses to pooled S-protein peptides were measured by flow-cytometric intracellular cytokine staining. This trial is registered with ClinicalTrials.gov, NCT04405908; this is an interim analysis and the study is continuing. Between June 19 and Sept 23, 2020, 151 volunteers were enrolled; three people withdrew, two for personal reasons and one with an unrelated serious adverse event (pituitary adenoma). 148 participants had at least 4 weeks of follow-up after dose two and were included in this analysis (database lock, Oct 23, 2020). Vaccination was well tolerated, with two grade 3 solicited adverse events (pain in 9 μg AS03-adjuvanted and 9 μg CpG/Alum-adjuvanted groups). Most local adverse events were mild injection-site pain, and local events were more frequent with SCB-2019 formulations containing AS03 adjuvant (44–69%) than with those containing CpG/Alum adjuvant (6–44%) or no adjuvant (3–13%). Systemic adverse events were more frequent in younger adults (38%) than in older adults (17%) after the first dose but increased to similar levels in both age groups after the second dose (30% in older and 34% in younger adults). SCB-2019 with no adjuvant elicited minimal immune responses (three seroconversions by day 50), but SCB-2019 with fixed doses of either AS03 or CpG/Alum adjuvants induced high titres and seroconversion rates of binding and neutralising antibodies in both younger and older adults (anti-SCB-2019 IgG antibody geometric mean titres at day 36 were 1567–4452 with AS03 and 174–2440 with CpG/Alum). Titres in all AS03 dose groups and the CpG/Alum 30 μg group were higher than were those recorded in a panel of convalescent serum samples from patients with COVID-19. Both adjuvanted SCB-2019 formulations elicited T-helper-1-biased CD4+ T-cell responses. The SCB-2019 vaccine, comprising S-Trimer protein formulated with either AS03 or CpG/Alum adjuvants, elicited robust humoral and cellular immune responses against SARS-CoV-2, with high viral neutralising activity. Both adjuvanted vaccine formulations were well tolerated and are suitable for further clinical development. Clover Biopharmaceuticals and the Coalition for Epidemic Preparedness Innovations.

Zika virus, a flavivirus transmitted by Aedes aegypti and Aedes albopictus mosquitoes, is associated with cases of congenital malformations and neurological complications. Absence of specific treatment makes a prophylactic Zika virus vaccine an unmet medical need. We assessed safety and immunogenicity of three doses of a purified, inactivated, Zika virus vaccine candidate in healthy flavivirus-naive and flavivirus-primed adults. This two-part, multicentre, observer-blind, randomised, placebo-controlled, phase 1 trial was done at seven medical clinics in the USA and two in Puerto Rico. Eligible participants were healthy adults aged 18–49 years. Participants were randomly assigned (1:1:1:1), using a sponsor-supplied randomisation scheme, to four groups to receive two intramuscular injections, 28 days apart, of saline placebo or TAK-426 containing 2 μg, 5 μg, or 10 μg antigen. Participants, investigators, and vaccine administrating personnel were masked to group assignment. Part 1 of the study assessed flavivirus-naive participants and part 2 assessed flavivirus-primed participants. The primary outcomes were safety, tolerability, and immunogenicity based on solicited local reactions and solicited systemic adverse events in the 7 days after each dose; unsolicited adverse events and serious adverse events in the 28 days after each dose; and geometric mean titres (GMTs) of neutralising anti-Zika virus antibodies at 28 days after the second dose. Safety assessments were done in all participants who received at least one dose of vaccine. Immunogenicity assessments were in the per-protocol set, comprising all participants who received at least one dose of vaccine and provided valid serology results at baseline and at least one post-vaccination timepoint, with no major protocol violations. The trial is ongoing and is registered at ClinicalTrials.gov (NCT03343626). Between Nov 13, 2017, and Oct 24, 2018, 894 volunteers were screened and 271 enrolled (125 flavivirus-naive and 146 flavivirus-primed participants). All TAK-426 doses were well tolerated with no deaths, no vaccine-related serious adverse events, and similar rates of mainly mild to moderate adverse events. TAK-426 elicited dose-dependent increases in antibody GMTs in both flavivirus-naive and flavivirus-primed participants. 28 days after dose 2, plaque-reduction neutralisation test GMTs in flavivirus-naive participants were 1130 (95% CI 749–1703) in the 2 μg TAK-426 group, 1992 (1401–2833) in the 5 μg TAK-426 group, and 3690 (2677–5086) in the 10 μg TAK-426 group. In pairwise comparisons, responses after two vaccinations in the 10 μg group were significantly greater than in the 2 μg group (GMT ratio 3·27 [95% CI 1·98–5·39], p<0·0001) and the 5 μg group (GMT ratio 1·85 [1·15–2·98], p=0·012). TAK-426 was well tolerated, with an acceptable safety profile, and was immunogenic in both flavivirus-naive and flavivirus-primed adults. Based on the safety and immunogenicity profiles of all TAK-426 doses assessed, the 10 μg TAK-426 dose was selected for further clinical development. Takeda Vaccines and the US Biomedical Advanced Research and Development Authority. For the Spanish translation of the abstract see Supplementary Materials section.

Opisthorchis viverrini is endemic in the South East Asian region, especially in Cambodia, Lao People's Democratic Republic, Vietnam and Thailand, but there have been no previous records from Myanmar. During stool surveys of rural populations in three regions of Lower Myanmar, Opisthorchis-like eggs were found in 34 out of 364 (9.3%) participants by stool microscopy after using the modified formalin-ether concentration technique. DNA was extracted from these positive stool samples and a portion of the mitochondrial cytochrome c oxidase subunit I (cox1) gene was amplified using the polymerase chain reaction and then sequenced. DNA sequences, successfully obtained from 18 of 34 positive samples (Bago Region, n = 13; Mon State, n = 3; Yangon Region, n = 2), confirmed that the eggs were of O. viverrini. Sequences showed 99.7% identity with O. viverrini mitochondrial cox1 (GenBank accession no. JF739555) but 95%, 88.7%, 82.6% and 81.4% identities with those of Opisthorchis lobatus from Lao People's Democratic Republic (GenBank accession nos. HQ328539-HQ328541), Metorchis orientalis from China (KT239342), Clonorchis sinensis from China (JF729303) and Opisthorchis felineus from Russia (EU921260), respectively. When alignement with other Opisthorchiidae trematodes, 81% similarity with Metorchis bilis from Czech Republic (GenBank accession nos. KT740966, KT740969, KT740970) and Slovakia (GenBank accession nos. KT740971-KT740973), 84.6% similarity with Metorchis xanthosomus from Czech Republic (GenBank accession no. KT740974), 78.6% similarity with M. xanthosomus from Poland (GenBank accession no. KT740968) and 82.2% similarity with Euamphimerus pancreaticus from Czech Republic (GenBank accession no. KT740975) were revealed. This study demonstrated, for the first time, O. viverrini from rural people in Myanmar using molecular methods and is an urgent call for surveillance and control activities against opisthorchiasis in Myanmar.

Key messageThis review contains functional roles of MYB transcription factors in the transcriptional regulation of anthocyanin biosynthesis in horticultural plants. This review describes potential uses of MYB TFs as tools for metabolic engineering for anthocyanin production.Anthocyanins (ranging from red to blue) are controlled by specific branches of the anthocyanin biosynthetic pathway and are mostly visible in ornamentals, fruits, and vegetables. In the present review, we describe which R2R3-MYB transcription factors (TFs) control the transcriptional regulation of anthocyanin structural genes involved in the specific branches of the anthocyanin biosynthetic pathway in various horticultural plants (e.g., ornamentals, fruits, and vegetables). In addition, some MYBs responsible for anthocyanin accumulation in specific tissues are described. Moreover, we highlight the phylogenetic relationships of the MYBs that suppress or promote anthocyanin synthesis in horticultural crops. Enhancement of anthocyanin synthesis via metabolic genetic engineering of anthocyanin MYBs, which is described in the review, is indicative of the potential use of the mentioned anthocyanin-related MYBs as tools for anthocyanin production. Therefore, the MYBs would be suitable for metabolic genetic engineering for improvement of flower colors, fruit quality, and vegetable nutrients.

In 2017, the Myanmar National Action Plan for Containment of Antimicrobial Resistance (AMR) (2017–2022) was endorsed by the Ministry of Health and Sports, Myanmar; one of its objectives was to increase public awareness of AMR to accelerate appropriate antibiotic use. This survey aimed to assess the public knowledge, practices and awareness concerning antibiotics and AMR awareness among adults in Myanmar. We conducted a nationwide cross-sectional mobile phone panel survey in January and February 2020. Participants were randomly selected from the mobile phone panel in each of three groups stratified by gender, age group, and residential area urbanity; they were interviewed using a structured questionnaire. Collected data were weighted based on the population of each stratum from the latest national census and analyzed using descriptive and inferential statistics. Two thousand and forty-five adults from 12 regions and states participated in this survey. Overall, 89.5% of participants had heard about antibiotics; however, only 0.9% provided correct answers to all five questions about antibiotics, whereas 9.7% provided all incorrect answers. More than half of participants (58.5%) purchased antibiotics without a prescription, mainly from medical stores or pharmacies (87.9%); this was more frequent in age group (18–29 years) and those in rural areas (p = 0.004 and p < 0.001, respectively). Only 56.3% were aware of antibiotic resistance and received their information from medical professionals (46.3%), family members or friends (38.9%), or the media (26.1%). Less than half (42.4%) knew that antibiotics were used in farm animals. Most did not know that using antibiotics in farm animals could develop resistance (73.2%) and is banned for the purposes of growth stimulation (64.1%). This survey identifies considerable gaps in the knowledge, practices, and awareness about antibiotics among the general population in Myanmar. Continuous public education and awareness campaigns must be urgently conducted to fulfill these gaps, which would aid in promoting antibiotic stewardship, leading to combating AMR in Myanmar.

We previously reported the efficacy of the adjuvanted-protein COVID-19 vaccine candidate S-Trimer (SCB-2019) in adults who showed no evidence of previous exposure to SARS-CoV-2. In this study, we aimed to investigate the extent of protection afforded by previous exposure to SARS-CoV-2 on subsequent COVID-19 infection, as well as the efficacy, safety, and reactogenicity of SCB-2019 in participants who were enrolled in the Study evaluating Protective-Efficacy and safety of Clover's Trimeric Recombinant protein-based and Adjuvanted COVID-19 vaccine (SPECTRA) trial who had already been exposed to SARS-CoV-2 before vaccination. In a phase 2 and 3 multicentre, double-blind, randomised, placebo-controlled trial (SPECTRA) done at 31 sites in five countries, participants were randomly assigned 1:1 using the Cenduit Interactive Response Technology system (IQVIA, Durham, NC, USA), with a block size of six, to receive two doses of either SCB-2019 or placebo 21 days apart. The primary outcomes of the SPECTRA trial were vaccine efficacy, measured by real-time PCR (rtPCR)-confirmed COVID-19 of any severity, with onset from 14 days after the second vaccine dose, as well as the safety and solicited local and systemic adverse events in the phase 2 subset. Here, we present secondary analyses to calculate the protective efficacy due to previous exposure to SARS-CoV-2 against reinfection with COVID-19 according to severity in SPECTRA participants who had evidence of exposure to SARS-CoV-2 at baseline, including efficacy against identified viral variants, as well as efficacy of SCB-2019 vaccination in this population. We enrolled 30 174 participants between March 24, 2021, and Aug 10, 2021. In the 14 670 participants who were randomly assigned to receive placebo, there were 418 (2·8%) confirmed cases of COVID-19; 65 (0·9%) of 7339 SARS-CoV-2-exposed participants, and 353 (4·8%) of 7331 SARS-CoV-2-naive participants (attack rates of 5·5 cases per 100 person-years for SARS-CoV-2-exposed participants and 32·4 cases per 100 person-years for SARS-CoV-2-naive participants). Protective efficacy due to previous exposure to SARS-CoV-2 was 83·2% (95% CI 78·0–87·3) against any COVID-19, 92·5% (82·9–97·3) against moderate-to-severe COVID-19, and 100% (59·3–100) against severe COVID-19; no SARS-CoV-2-exposed participants had hospitalisation associated with COVID-19. Protective efficacy against variants were 100% for alpha (B.1.1.7) and lambda (C.37) variants, 88·6% (14·9–99·7) for B.1.623, 93·6% (80·1–98·7) for gamma (P.1), and 92·4% (81·2–97·6) for mu (B.1.621) variants, and lowest against beta (B.1.351; 72·2% [33·1–89·9]) and delta (B.1.617.2; 77·2% [61·3–87·2]) variants. In addition, one dose of SCB-2019 had 49·9% (1·5–75·6) efficacy against any symptomatic COVID-19, and two doses had 64·2% (26·5–83·8) efficacy. SCB-2019 was well tolerated in SARS-CoV-2-exposed participants, but was associated with higher rates of injection site pain (89 [33·8%] of 263 participants) than placebo (16 [6·7%] of 239 participants). Rates of solicited systemic adverse events, severe adverse events, and serious adverse events were similar between vaccine and placebo groups, and with rates in SARS-CoV-2-naive vaccine recipients. Previous exposure to SARS-CoV-2 decreased the risk and severity of subsequent COVID-19 infection, even against newly emerging variants. Protection is further enhanced by one or two doses of SCB-2019. Clover Biopharmaceuticals, The Coalition for Epidemic Preparedness Innovations (CEPI).

During public health crises like the COVID-19 pandemic, populations can experience worsening mental health. Prior reports have suggested that Black Americans experienced lower rates of anxiety and depression than White Americans before the pandemic; however, during the pandemic, outcomes may be different as Black Americans have been disproportionately affected in terms of mortality, hospitalization, COVID-19 infection, and job loss. We documented the differential mental health impact of COVID-19 on Black and Non-Black Americans. We analyzed nationally representative longitudinal data from the Understanding America Study COVID-19 Tracking Survey spanning March through November of 2020 to assess differences over time in prevalence of anxiety and depression between Black and non-Black Americans. We found that Black Americans were significantly less likely to report symptoms for anxiety, depression, or both during the pandemic. In a given month between March through November of 2020, the odds of Black Americans reporting such symptoms was on average about half that of Non-Black Americans. We also found that in September 2020, the gap in reporting symptoms for depression began to widen gradually. Specifically, since that time, prevalence of depression remained stable among non-Black Americans while it declined gradually among Black Americans. Our main results were robust to adjusting for demographics, risk perceptions, and baseline pre-pandemic mental health status. Black Americans maintained significantly better mental health than Non-Black Americans despite their struggle against economic, health, and racial inequalities during the pandemic. We discuss the significance and implications of our results and identify opportunities for future research.

When the novel coronavirus entered the US, most US states implemented lockdown measures. In April—May 2020, state governments started political discussions about whether it would be worth the risk to reduce protective measures. In a highly politicized environment, risk perceptions and preferences for risk mitigation may vary by political inclinations. In April—May 2020, we surveyed a nationally representative sample of 5517 members of the University of Southern California's Understanding America Study. Of those, 37% identified as Democrats, 32% as Republican, and 31% as Third Party/Independent. Overall, Democrats perceived more risk associated with COVID-19 than Republicans, including for getting infected, being hospitalized and dying if infected, as well as running out of money as a result of the pandemic. Democrats were also more likely than Republicans to express concerns that states would lift economic restrictions too quickly, and to report mask use and social distancing. Generally, participants who identified as Third Party/Independent fell in between. Democrats were more likely to report watching MSNBC or CNN (vs. not), while Republicans were more likely to report watching Fox News (vs. not), and Third Party/Independents tended to watch neither. However, political inclinations predicted reported policy preferences, mask use, and social distancing, in analyses that accounted for differences in use of media sources, risk perceptions, and demographic background. In these analyses, participants' reported media use added to the partisan divide in preferences for the timing of lifting economic restrictions and reported protective behaviors. Implications for risk communication are discussed.

A community outbreak of human influenza A(H1N1)pdm09 virus strains was observed in Myanmar in 2017. We investigated the circulation patterns, antigenicity, and drug resistance of 2017 influenza A(H1N1)pdm09 viruses from Myanmar and characterized the full genome of influenza virus strains in Myanmar from in-patients and out-patients to assess the pathogenicity of the viruses. Nasopharyngeal swabs were collected from out-patients and in-patients with acute respiratory tract infections in Yangon and Pyinmana City in Myanmar during January-December 2017. A total of 215 out-patients and 18 in-patients infected with A(H1N1)pdm09 were detected by virus isolation and real-time RT-PCR. Among the positive patients, 90.6% were less than 14 years old. Hemagglutination inhibition (HI) antibody titers against A(H1N1)pdm09 viruses in Myanmar were similar to the recommended Japanese influenza vaccine strain for 2017-2018 seasons (A/Singapore/GP1908/2015) and WHO recommended 2017 southern hemisphere vaccine component (A/Michigan/45/2015). Phylogenetic analysis of the hemagglutinin sequence showed that the Myanmar strains belonged to the genetic subclade 6B.1, possessing mutations of S162N and S164T at potential antigenic sites. However, the amino acid mutation at position 222, which may enhance the severity of disease and mortality, was not found. One case with no prior history of oseltamivir treatment possessed H275Y mutated virus in neuraminidase (NA), which confers resistance to oseltamivir and peramivir with elevated IC50 values. The full genome sequence of Myanmar strains showed no difference between samples from in-patients and out-patients, suggesting no additional viral mutations associated with patient severity. Several amino acid changes were observed in PB2, PB1, and M2 of Myanmar strains when compared to the vaccine strain and other Asian strains. However, no mutations associated with pathogenicity were found in the Myanmar strains, suggesting that viral factors cannot explain the underlying reasons of the massive outbreak in Myanmar. This study reported the first detection of an oseltamivir-resistant influenza virus in Myanmar, highlighting the importance of continuous antiviral monitoring and genetic characterization of the influenza virus in Myanmar.

An extensive literature studies the relation between demographic and socio-economic characteristics and attrition in longitudinal studies. In this study, we analyze the independent effects of non-demographic variables—respondent personality traits, panel tenure, and survey topics, using unique datasets from two recently completed high-frequency online longitudinal studies conducted in the U.S. We used latent class analysis to group respondents into various classes based on similarities in their nonresponse patterns across all survey waves, which revealed substantial variations in patterns of nonresponse. Our results indicate that respondent personality traits were strong predictors of nonresponse patterns. Specifically, conscientiousness is positively associated with a lower likelihood of wave nonresponses. In contrast, more open, extroverted, neurotic, and agreeable respondents are more likely to exhibit higher wave nonresponses, but with effect sizes smaller than that of conscientiousness. We found no significant demographic effects on wave nonresponse in one of the studies focused on aging and well-being. However, in the study primarily focused on COVID-19-related topics conducted during the pandemic, we found a few significant demographic effects. Collectively, our findings suggest that personality traits may play a more significant role than conventional demographic and household variables in predicting nonresponse patterns in high frequency (at least one survey per month) online surveys.