Abstract: Little is known about the natural history of asymptomatic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Methods We conducted a prospective study at a quarantine center for coronavirus disease 2019 in Ho Chi Minh City, Vietnam. We enrolled quarantined people with reverse-transcription polymerase chain reaction (RT-PCR)–confirmed SARS-CoV-2 infection, collecting clinical data, travel and contact history, and saliva at enrollment and daily nasopharyngeal/throat swabs (NTSs) for RT-PCR testing. We compared the natural history and transmission potential of asymptomatic and symptomatic individuals. Results Between 10 March and 4 April 2020, 14 000 quarantined people were tested for SARS-CoV-2; 49 were positive. Of these, 30 participated in the study: 13 (43%) never had symptoms and 17 (57%) were symptomatic. Seventeen (57%) participants imported cases. Compared with symptomatic individuals, asymptomatic people were less likely to have detectable SARS-CoV-2 in NTS collected at enrollment (8/13 [62%] vs 17/17 [100%] ; P = .02). SARS-CoV-2 RNA was detected in 20 of 27 (74%) available saliva samples (7 of 11 [64%] in the asymptomatic group and 13 of 16 [81%] in the symptomatic group; P = .56). Analysis of RT-PCR positivity probability showed that asymptomatic participants had faster viral clearance than symptomatic participants (P  & lt; .001 for difference over the first 19 days). This difference was most pronounced during the first week of follow-up. Two of the asymptomatic individuals appeared to transmit SARS-CoV-2 to 4 contacts. Conclusions Asymptomatic SARS-CoV-2 infection is common and can be detected by analysis of saliva or NTSs. The NTS viral loads fall faster in asymptomatic individuals, but these individuals appear able to transmit the virus to others.

Abstract: In people with human immunodeficiency virus (PWH), the World Health Organization–recommended tuberculosis (TB) 4-symptom screen (W4SS) targeting those who need molecular rapid testing may be suboptimal. We assessed the performance of different TB screening approaches in severely immunosuppressed PWH enrolled in the guided-treatment group of the STATIS trial (NCT02057796). Methods Ambulatory PWH with no overt evidence of TB and CD4 count & lt;100 cells/µL were screened for TB prior to antiretroviral therapy (ART) initiation with W4SS, chest radiograph (CXR), urine lipoarabinomannan (LAM) test, and sputum Xpert MTB/RIF (Xpert). Correctly and wrongly identified cases by screening approaches were assessed overall and by CD4 count threshold (≤50 and 51–99 cells/µL). Results Of 525 enrolled participants (median CD4 count, 28 cells/µL), 48 (9.9%) were diagnosed with TB at enrollment. Among participants with a negative W4SS, 16% had either a positive Xpert, a CXR suggestive of TB, or a positive urine LAM test. The combination of sputum Xpert and urine LAM test was associated with the highest proportion of participants correctly identified as TB (95.8%) and non-TB cases (95.4%), with proportions equally high among participants with CD4 counts above or below 50 cells/µL. Restricting the use of sputum Xpert, urine LAM test, or CXR to participants with a positive W4SS reduced the proportion of wrongly and correctly identified cases. Conclusions There is a clear benefit to perform both sputum Xpert and urine LAM tests as TB screening in all severely immunosuppressed PWH prior to ART initiation, not only in those with a positive W4SS. Clinical Trials Registration. NCT02057796.

Abstract: One hundred days after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first reported in Vietnam on 23 January, 270 cases were confirmed, with no deaths. We describe the control measures used by the government and their relationship with imported and domestically acquired case numbers, with the aim of identifying the measures associated with successful SARS-CoV-2 control. Methods Clinical and demographic data on the first 270 SARS-CoV-2 infected cases and the timing and nature of government control measures, including numbers of tests and quarantined individuals, were analyzed. Apple and Google mobility data provided proxies for population movement. Serial intervals were calculated from 33 infector-infectee pairs and used to estimate the proportion of presymptomatic transmission events and time-varying reproduction numbers. Results A national lockdown was implemented between 1 and 22 April. Around 200 000 people were quarantined and 266 122 reverse transcription polymerase chain reaction (RT-PCR) tests conducted. Population mobility decreased progressively before lockdown. In total, 60% (163/270) of cases were imported; 43% (89/208) of resolved infections remained asymptomatic for the duration of infection. The serial interval was 3.24 days, and 27.5% (95% confidence interval [CI], 15.7%-40.0%) of transmissions occurred presymptomatically. Limited transmission amounted to a maximum reproduction number of 1.15 (95% CI, .·37–2.·36). No community transmission has been detected since 15 April. Conclusions Vietnam has controlled SARS-CoV-2 spread through the early introduction of mass communication, meticulous contact tracing with strict quarantine, and international travel restrictions. The value of these interventions is supported by the high proportion of asymptomatic and imported cases, and evidence for substantial presymptomatic transmission.

Abstract: MDR bacteria including carbapenem-resistant Pseudomonas aeruginosa are recognized as an important cause of hospital-acquired infections worldwide. This investigation seeks to determine the molecular characterization and antibiotic resistance genes associated with carbapenem-resistant P. aeruginosa. Methods We conducted WGS and phylogenetic analysis of 72 carbapenem-resistant P. aeruginosa isolated from hospital-acquired infection patients from August 2011 to March 2015 in three major hospitals in Hanoi, Vietnam. Results We identified three variants of IMP gene, among which blaIMP-15 was the most frequent (n = 34) in comparison to blaIMP-26 (n = 2) and blaIMP-51 (n = 12). We observed two isolates with imipenem MIC & gt;128 mg/L that co-harboured blaIMP-15 and blaDIM-1 genes and seven isolates (imipenem MIC  & gt; 128 mg/L) with a blaKPC-1 gene from the same hospital. MLST data shows that these 72 isolates belong to 18 STs and phylogenetic tree analysis has divided these isolates into nine groups. Conclusions Our results provide evidence that not only blaIMP-26 but other IMP variants such as blaIMP-15 and blaIMP-51 genes and several STs (ST235, ST244, ST277, ST310, ST773 and ST3151) have been disseminating in healthcare settings in Vietnam. In addition, we report the emergence of two isolates belonging to ST1240 and ST3340 that harboured two important carbapenemase genes (blaIMP-15 and blaDIM-1) and seven isolates belonging to ST3151 of P. aeruginosa that carried the blaKPC-1 gene in Vietnam, which could potentially cause serious restricted availability of treatment options in healthcare settings.

Abstract: The extent to which influenza recurrence depends upon waning immunity from prior infection is undefined. We used antibody titers of Ha-Nam cohort participants to estimate protection curves and decay trajectories. Methods Households (270) participated in influenza-like–illness (ILI) surveillance and provided blood at intervals spanning laboratory–confirmed virus transmission. Sera were tested in hemagglutination inhibition assay. Infection was defined as influenza virus-positive ILI and/or seroconversion. Median protective titers were estimated using scaled-logistic regression to model pretransmission titer against infection status in that season, limiting analysis to households with infection(s). Titers were modelled against month since infection using mixed-effects linear regression to estimate decay and when titers fell below protection thresholds. Results From December 2008–2012, 295 and 314 participants were infected with H1N1pdm09-like and A/Perth/16/09-like (H3N2Pe09) viruses, respectively. The proportion protected rose more steeply with titer for H1N1pdm09 than for H3N2Pe09, and estimated 50% protection titers were 19.6 and 37.3, respectively. Postinfection titers started higher against H3N2Pe09 but decayed more steeply than against H1N1pdm09. Seroprotection was estimated to be sustained against H1N1pdm09 but to wane by 8-months for H3N2Pe09. Conclusions Estimates indicate that infection induces durable seroprotection against H1N1pdm09 but not H3N2Pe09, which could in part account for the younger age of A(H1N1) versus A(H3N2) cases.

Abstract: Does use of medium containing amphiregulin improve meiotic maturation efficiency in oocytes of women with polycystic ovary syndrome (PCOS) undergoing in vitro maturation (IVM) preceded by a capacitation culture step capacitation IVM (CAPA-IVM)? SUMMARY ANSWER Use of medium containing amphiregulin significantly increased the maturation rate from oocytes retrieved from follicles with diameters & lt;6 or ≥6 mm pre-cultured in capacitation medium. WHAT IS KNOWN ALREADY Amphiregulin concentration in follicular fluid is correlated with human oocyte developmental competence. Amphiregulin added to the meiotic trigger has been shown to improve outcomes of IVM in a range of mammalian species. STUDY DESIGN, SIZE, DURATION This prospective, randomized cohort study included 30 patients and was conducted at an academic infertility centre in Vietnam from April to December 2019. Patients with PCOS were included. PARTICIPANTS/MATERIALS, SETTING, METHODS In the first stage, sibling oocytes from each patient (671 in total) were allocated in equal numbers to maturation in medium with (CAPA-AREG) or without (CAPA-Control) amphiregulin 100 ng/ml. After a maturation check and fertilization using intracytoplasmic sperm injection (ICSI), all good quality Day 3 embryos were vitrified. Cumulus cells (CCs) from both groups were collected at the moment of ICSI denudation and underwent a molecular analysis to quantify key transcripts of oocyte maturation and to relate these to early embryo development. On return for frozen embryo transfer (second stage), patients were randomized to have either CAPA-AREG or CAPA-Control embryo(s) implanted. Where no embryo(s) from the randomized group were available, embryo(s) from the other group were transferred. The primary endpoint of the study was meiotic maturation efficiency (proportion of metaphase II [MII] oocytes; maturation rate). MAIN RESULTS AND THE ROLE OF CHANCE In the per-patient analysis, the number of MII oocytes was significantly higher in the CAPA-AREG group versus the CAPA-Control group (median [interquartile range] 7.0 [5.3, 8.0] versus 6.0 [4.0, 7.0]; P = 0.01). When each oocyte was evaluated, the maturation rate was also significantly higher in the CAPA-AREG group versus the CAPA-Control group (67.6% versus 55.2%; relative risk [RR] 1.22 [95% confidence interval (CI) 1.08–1.38]; P = 0.001). No other IVM or embryology outcomes differed significantly between the two groups. Rates of clinical pregnancy (66.7% versus 42.9%; RR 1.56 [95% CI 0.77–3.14] ), ongoing pregnancy (53.3% versus 28.6%; RR 1.87 [95% CI 0.72–4.85]) and live birth (46.7% versus 28.6%; RR 1.63 [95% CI 0.61–4.39] ) were numerically higher in the patients who had CAPA-AREG versus CAPA-Control embryos implanted, but each fertility and obstetric outcome did not differ significantly between the groups. In the CAPA-AREG group, there were significant shifts in CC expression of genes involved in steroidogenesis (STAR, 3BHSD), the ovulatory cascade (DUSP16, EGFR, HAS2, PTGR2, PTGS2, RPS6KA2), redox and glucose metabolism (CAT, GPX1, SOD2, SLC2A1, LDHA) and transcription (NRF2). The expression of three genes (TRPM7, VCAN and JUN) in CCs showed a significant correlation with embryo quality. LIMITATIONS, REASONS FOR CAUTION This study included only Vietnamese women with PCOS, limiting the generalizability. Although 100 ng/ml amphiregulin addition to the maturation culture step significantly improved the MII rate, the sample size in this study was small, meaning that these findings should be considered as exploratory. Therefore, a larger patient cohort is needed to confirm whether the positive effects of amphiregulin translate into improved fertility outcomes in patients undergoing IVM. WIDER IMPLICATIONS OF THE FINDINGS Data from this study confirm the beneficial effects of amphiregulin during IVM with respect to the trigger of oocyte maturation. The gene expression findings in cumulus indicate that multiple pathways might contribute to these beneficial effects and confirm the key role of the epidermal growth factor system in the stepwise acquisition of human oocyte competence. STUDY FUNDING/COMPETING INTEREST(S) This work was funded by the Vietnam National Foundation for Science and Technology Development (NAFOSTED; grant number FWO.106-YS.2017.02) and by the Fund for Research Flanders (FWO; grant number G.OD97.18N). L.N.V. has received speaker and conference fees from Merck, grants, speaker and conference fees from Merck Sharpe and Dohme, and speaker, conference and scientific board fees from Ferring. T.M.H. has received speaker fees from Merck, Merck Sharp and Dohme and Ferring. J.S. reports speaker fees from Ferring Pharmaceuticals and Biomérieux Diagnostics and grants from FWO Flanders, is co-inventor on granted patents on CAPA-IVM methodologies in USA (US10392601B2), Europe (EP3234112B1) and Japan (JP 6806683 registered 08-12-2020) and is a co-shareholder of Lavima Fertility Inc., a spin-off company of the Vrije Universiteit Brussel (VUB, Brussels, Belgium). NA, TDP, AHL, MNHN, SR, FS, EA and UDTH report no financial relationships with any organizations that might have an interest in the submitted work in the previous three years, and no other relationships or activities that could appear to have influenced the submitted work. TRIAL REGISTRATION NUMBER NCT03915054.

Abstract: Since plants are sessile organisms, developmental plasticity in response to environmental stresses is essential for their survival. Upon exposure to drought, lateral root development is suppressed to induce drought tolerance. However, the molecular mechanism by which the development of lateral roots is inhibited by drought is largely unknown. In this study, the auxin signaling repressor IAA15 was identified as a novel substrate of mitogen-activated protein kinases (MPKs) and was shown to suppress lateral root development in response to drought through stabilization by phosphorylation. Both MPK3 and MPK6 directly phosphorylated IAA15 at the Ser-2 and Thr-28 residues. Transgenic plants overexpressing a phospho-mimicking mutant of IAA15 (IAA15DD OX) showed reduced lateral root development due to a higher accumulation of IAA15. In addition, MPK-mediated phosphorylation strongly increased the stability of IAA15 through the inhibition of polyubiquitination. Furthermore, IAA15DD OX plants showed the transcriptional downregulation of two key transcription factors LBD16 and LBD29, responsible for lateral root development. Overall, this study provides the molecular mechanism that explains the significance of the MPK-Aux/IAA module in suppressing lateral root development in response to drought.

Abstract: Construction managers often face with projects containing multiple units wherein activities repeat from unit to unit. Therefore effective resource management is crucial in terms of project duration, cost and quality. Accordingly, researchers have developed several models to aid planners in developing practical and near-optimal schedules for repetitive projects. Despite their undeniable benefits, such models lack the ability of pure simultaneous optimization because existing methodologies optimize the schedule with respect to a single factor, to achieve minimum duration, total cost, resource work breaks or various combinations, respectively. This study introduces a novel approach called “opposition multiple objective symbiotic organisms search” (OMOSOS) for scheduling repetitive projects. The proposed algorithm used an opposition-based learning technique for population initialization and for generation jumping. Further, this study integrated a scheduling module (M1) to determine all project objectives including time, cost, quality and interruption. The proposed algorithm was implemented on two application examples in order to demonstrate its capabilities in optimizing the scheduling of repetitive construction projects. The results indicate that the OMOSOS approach is a powerful optimization technique and can assist project managers in selecting appropriate plan for project. Highlights This study presents an advanced multiple optimization algorithm OMOSOS. Opposition technique is utilized to spreading the initial population and generation jumping. OMOSOS is applied to solve time, cost, quality and work continuity tradeoff problem. The model performance is demonstrated in the experimental results.