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Omicron and its subvariants have steadily gained greater capability of immune escape compared to other variants of concern, resulting in an increased incidence of reinfections even among vaccinated individuals. We evaluated the antibody response to Omicron BA.1, BA.2, and BA.4/5 in US military members vaccinated with the primary 2-dose series of Moderna mRNA-1273 in a cross-sectional study. While nearly all vaccinated participants had sustained spike (S) IgG and neutralizing antibodies (ND50) to the ancestral strain, only 7.7% participants had detectable ND50 to Omicron BA.1 at 8 months postvaccination. The neutralizing antibody response to BA.2 and BA.5 was similarly reduced. The reduced antibody neutralization of Omicron correlated with the decreased antibody binding to the receptor-binding domain. The participants' seropositivity to the nuclear protein positively correlated with ND50. Our data emphasizes the need for continuous vigilance in monitoring for emerging variants and the need to identify potential alternative targets for vaccine design. [ABSTRACT FROM AUTHOR]

Background The development of memory B cells after asymptomatic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is not well understood. Methods We compared spike antibody titers, pseudovirus neutralizing antibody titers, and memory B-cell responses among SARS-CoV-2 PCR-positive Marine recruits who either reported asymptomatic or symptomatic infection. Results Thirty-six asymptomatic participants exhibited similar spike IgG titers, spike IgA titers, and pseudovirus neutralization titers compared to 30 symptomatic participants. Pseudovirus neutralization and spike IgG titers showed significant positive correlations with frequency of memory B cells. Conclusions Among young adults, asymptomatic SARS-CoV-2 infection induced antibody and memory B-cell responses comparable to mild symptomatic infection. [ABSTRACT FROM AUTHOR]

Dynamic trimethylation of histone H3 at Lys27 (H3K27me3) affects gene expression and controls plant development and environmental responses. In Arabidopsis thaliana , RELATIVE OF EARLY FLOWERING 6 (REF6)/JUMONJI DOMAIN-CONTAINING PROTEIN 12 demethylates H3K27me3 by recognizing a specific DNA motif. However, little is known about how REF6 activates target gene expression after recognition, especially in environmental responses. In response to warm ambient temperature, plants undergo thermomorphogenesis, which involves accelerated growth, early flowering and changes in morphology. Here we show that REF6 regulates thermomorphogenesis and cooperates with the transcription factor PHYTOCHROME INTERACTING FACTOR 4 to synergistically activate thermoresponsive genes under warm ambient temperature. The ref6 loss-of-function mutants exhibited attenuated hypocotyl elongation at warm temperature, partially due to downregulation of GIBBERELLIN 20-OXIDASE 2 and BASIC HELIX-LOOP-HELIX 87. REF6 enzymatic activity is necessary for warm ambient temperature responses. Together, our results provide direct evidence of an epigenetic modifier and a transcription factor working together to respond to the environment. [ABSTRACT FROM AUTHOR]

Background The association between the clinical severity of hand, foot, and mouth disease (HFMD) inpatients and socioeconomic status (SES) is important for quantifying SES inequality in HFMD disease burden and informing decision-makers regarding medical subsidy and reimbursement policies. Here, this association was investigated using a quantitative SES measurement. Methods Laboratory-confirmed HFMD cases hospitalized at Henan Children's Hospital from February 15, 2017, to February 15, 2018, were invited. We utilized the revised Family Affluence Scale for family affluence–based SES measurement. Clinical severity was diagnosed based on central nervous system (CNS) complications, treatments, and length of stay. We applied logistic regression for association analyses and multiple imputation for missing data. Results A total of 1229 laboratory-confirmed HFMD inpatients responded. Adjusted by age, sex, rural residence, EV-A71 infection, and health-seeking behavior, CNS complications (odds ratio [OR], 2.72; 95% CI, 1.41–5.31), intensive care unit (ICU) admission (OR, 7.30; 95% CI, 2.21–25.97), and prolonged hospitalization (OR, 4.28; 95% CI, 2.44–7.58) were significantly associated with lower family affluence–based SES. These associations increased as the SES category descended. For EV-A71-infected inpatients, severe HFMD was significantly associated with low and intermediate SES. For non-EV-A71-infected inpatients, only the association of prolonged hospitalization with low SES increased significantly. Also, severe HFMD inpatients, especially those admitted to the ICU, incurred high hospitalization costs. Conclusions The clinical severity of HMFD inpatients was significantly associated with family affluence–based SES. Severe HFMD inpatients were more likely to have lower SES than nonsevere inpatients and suffered a heavy economic burden. Therefore, medical subsidy and reimbursement policies should offer sufficient monetary support to severe HFMD inpatients to alleviate economic burden in low-SES populations and reduce potential SES inequality. [ABSTRACT FROM AUTHOR]

Background To assess the case fatality risk (CFR) of COVID-19 in mainland China, stratified by region and clinical category, and estimate key time-to-event intervals. Methods We collected individual information and aggregated data on COVID-19 cases from publicly available official sources from 29 December 2019 to 17 April 2020. We accounted for right-censoring to estimate the CFR and explored the risk factors for mortality. We fitted Weibull, gamma, and log-normal distributions to time-to-event data using maximum-likelihood estimation. Results We analyzed 82 719 laboratory-confirmed cases reported in mainland China, including 4632 deaths and 77 029 discharges. The estimated CFR was 5.65% (95% confidence interval [CI], 5.50–5.81%) nationally, with the highest estimate in Wuhan (7.71%) and lowest in provinces outside Hubei (0.86%). The fatality risk among critical patients was 3.6 times that of all patients and 0.8–10.3-fold higher than that of mild-to-severe patients. Older age (odds ratio [OR], 1.14 per year; 95% CI, 1.11–1.16) and being male (OR, 1.83; 95% CI, 1.10–3.04) were risk factors for mortality. The times from symptom onset to first healthcare consultation, to laboratory confirmation, and to hospitalization were consistently longer for deceased patients than for those who recovered. Conclusions Our CFR estimates based on laboratory-confirmed cases ascertained in mainland China suggest that COVID-19 is more severe than the 2009 H1N1 influenza pandemic in hospitalized patients, particularly in Wuhan. Our study provides a comprehensive picture of the severity of the first wave of the pandemic in China. Our estimates can help inform models and the global response to COVID-19. [ABSTRACT FROM AUTHOR]

Study Question: Does an artificially induced FSH surge at the time of hCG trigger improve IVF/ICSI outcomes?Summary Answer: An additional FSH bolus administered at the time of hCG trigger has no effect on clinical pregnancy rate, embryo quality, fertilization rate, implantation rate and live birth rate in women undergoing the long GnRH agonist (GnRHa) protocol for IVF/ICSI.What Is Known Already: Normal ovulation is preceded by a surge in both LH and FSH. Few randomized clinical trials have specifically investigated the role of the FSH surge. Some studies indicated that FSH given at hCG ovulation trigger boosts fertilization rate and even prevents ovarian hyperstimulation syndrome (OHSS).Study Design, Size, Duration: This was a randomized, double-blinded, placebo-controlled trial conducted at a single IVF center, from June 2012 to November 2013. A sample size calculation indicated that 347 women per group would be adequate. A total of 732 women undergoing IVF/ICSI were randomized, using electronically randomized tables, to the intervention or placebo groups. Participants and clinical doctors were blinded to the treatment allocation.Participants/materials, Setting, Methods: Patients aged ≤42 years who were treated with IVF/ICSI owing to tubal factor, male factor, unexplained, endometriosis and multiple factors were enrolled in this trial. Subjects all received a standard long GnRHa protocol for IVF/ICSI and hCG 6000-10 000 IU to trigger oocyte maturation. A total of 364 and 368 patients were randomized to receive a urinary FSH (uFSH) bolus (6 ampules, 450 IU) and placebo, respectively, at the time of the hCG trigger. The primary outcome measure was clinical pregnancy rate. The secondary outcome measures were FSH level on the day of oocyte retrieval, number of oocytes retrieved, good-quality embryo rate, live birth rate and rate of OHSS.Main Results and the Role Of Chance: There were no significant differences in the baseline demographic characteristics between the two study groups. There were also no significant differences between groups in cycle characteristics, such as the mean number of stimulation days, total gonadotrophin dose and peak estradiol. The clinical pregnancy rate was 51.6% in the placebo group and 52.7% in the FSH co-trigger group, with an absolute rate difference of 1.1% (95% CI -6.1% to 8.3%). The number of oocytes retrieved was 10.47 ± 4.52 and 10.74 ± 5.01 (P = 0.44), the rate of good-quality embryos was 37% and 33.9% (P = 0.093) and the implantation rate was 35% and 36% (P = 0.7) in the placebo group and the FSH co-trigger group, respectively.Limitations, Reasons For Caution: This was a single-center study, which may limit its effectiveness. The use of uFSH is a limitation, as this is not the same as the natural FSH. We did not collect follicular fluid for further study of molecular changes after the use of uFSH as a co-trigger.Wider Implications Of the Findings: Based on previous data and our results, an additional FSH bolus administered at the time of hCG trigger has no benefit on clinical pregnancy rates in women undergoing the long GnRHa protocol in IVF/ICSI: a single hCG trigger is sufficient.Study Funding/competing Interest(s): This study was supported by the National Key Research and Development Program of China (2016YFC1000205); Sun Yat-Sen University Clinical Research 5010 Program (2016004); the Science and Technology Project of Guangdong Province (2016A020216011 and 2017A020213028); and Science Technology Research Project of Guangdong Province (S2011010004662). There are no conflicts of interest to declare.Trial Registration Number: The trial was registered in the Chinese Clinical Trial Registry (ChiCTR-TRC-12002246).Trial Registration Date: 20 May 2012.Date Of First Patient’s Enrolment: 10 June 2012. [ABSTRACT FROM AUTHOR]

In chromatin, histone methylation affects the epigenetic regulation of multiple processes in animals and plants and is modulated by the activities of histone methyltransferases and histone demethylases. The jumonji domain-containing histone demethylases have diverse functions and can be classified into several subfamilies. In humans, the jumonji domain-containing Lysine (K)-Specific Demethylase 5/Jumonji and ARID Domain Protein (KDM5/JARID) subfamily demethylases are specific for histone 3 lysine 4 trimethylation (H3K4me3) and are important drug targets for cancer treatment. In Arabidopsis thaliana , the KDM5/JARID subfamily H3K4me3 demethylase JUMONJI14 (JMJ14) plays important roles in flowering, gene silencing, and DNA methylation. Here, we report the crystal structures of the JMJ14 catalytic domain in both substrate-free and bound forms. The structures reveal that the jumonji and C5HC2 domains contribute to the specific recognition of the H3R2 and H3Q5 to facilitate H3K4me3 substrate specificity. The critical acidic residues are conserved in plants and animals with the corresponding mutations impairing the enzyme activity of both JMJ14 and human KDM5B, indicating a common substrate recognition mechanism for KDM5 subfamily demethylases shared by plants and animals and further informing efforts to design targeted inhibitors of human KDM5. [ABSTRACT FROM AUTHOR]