A frequency selection network for medical image segmentation.

Existing medical image segmentation methods may only consider feature extraction and information processing in spatial domain, or lack the design of interaction between frequency information and spatial information, or ignore the semantic gaps between shallow and deep features, and lead to inaccurate segmentation results. Therefore, in this paper, we propose a novel frequency selection segmentation network (FSSN), which achieves more accurate lesion segmentation by fusing local spatial features and global frequency information, better design of feature interactions, and suppressing low correlation frequency components for mitigating semantic gaps. Firstly, we propose a global-local feature aggregation module (GLAM) to simultaneously capture multi-scale local features in the spatial domain and exploits global frequency information in the frequency domain, and achieves complementary fusion of local details features and global frequency information. Secondly, we propose a feature filter module (FFM) to mitigate semantic gaps when we conduct cross-level features fusion, and makes FSSN discriminatively determine which frequency information should be preserved for accurate lesion segmentation. Finally, in order to make better use of local information, especially the boundary of lesion region, we employ deformable convolution (DC) to extract pertinent features in the local range, and makes our FSSN can focus on relevant image contents better. Extensive experiments on two public benchmark datasets show that compared with representative medical image segmentation methods, our FSSN can obtain more accurate lesion segmentation results in terms of both objective evaluation indicators and subjective visual effects with fewer parameters and lower computational complexity.

Sargassum mcclurei Mitigating Methane Emissions and Affecting Rumen Microbial Community in In Vitro Rumen Fermentation.

Methane emissions from ruminants significantly contribute to greenhouse gases. This study explores the methane mitigation effect and mechanism of S. mcclurei through in vitro rumen fermentation, aiming to establish its potential as a feed additive. We investigated the effects of freeze-dried and dried S. mcclurei at supplementation levels of 2%, 5%, and 10% of dry matter on nutrient degradation, ruminal fermentation, methane inhibition, and microbial community structure in in vitro rumen fermentation. The freeze-dried S. mcclurei at 2% supplementation significantly reduced CH4 emissions by 18.85% and enhanced crude protein degradability. However, total VFA and acetate concentrations were lower in both treatments compared to the control. The microbial shifts included a decrease in Lachnospiraceae_NK3A20_group and Ruminococcus and an increase in Selenomonas, Succinivibrio, and Saccharofermentans, promoting propionate production. Additionally, a significant reduction in Methanomicrobium was observed, indicating direct methane mitigation. Freeze-dried S. mcclurei at a 2% supplementation level shows potential as an effective methane mitigation strategy with minimal impact on rumen fermentation, supported by detailed insights into microbial community changes.

Association of gastrointestinal microbiome and obesity with gestational diabetes mellitus-an updated globally based review of the high-quality literatures.

OBJECTIVES: The purpose of this review is to investigate the relationship between gastrointestinal microbiome, obesity, and gestational diabetes mellitus (GDM) in an objective manner. METHODS: We conducted a thorough and comprehensive search of the English language literatures published in PubMed, Web of Science, and the Cochrane Library from the establishment of the library until 12 December 2023. Our search strategy included both keywords and free words searches, and we strictly applied inclusion and exclusion criteria. Meta-analyses and systematic reviews were prepared. RESULTS: Six high-quality literature sources were identified for meta-analysis. However, after detailed study and analysis, a certain degree of heterogeneity was found, and the credibility of the combined analysis results was limited. Therefore, descriptive analyses were conducted. The dysbiosis of intestinal microbiome, specifically the ratio of Firmicutes/Bacteroides, is a significant factor in the development of metabolic diseases such as obesity and gestational diabetes. Patients with intestinal dysbiosis and obesity are at a higher risk of developing GDM. CONCLUSIONS: During pregnancy, gastrointestinal microbiome disorders and obesity may contribute to the development of GDM, with all three factors influencing each other. This finding could aid in the diagnosis and management of patients with GDM through further research on their gastrointestinal microbiome.

Enrichment and Evaluation of Antitumor Properties of Total Flavonoids from Juglans mandshurica Maxim.

Flavonoids are important secondary metabolites found in Juglans mandshurica Maxim., which is a precious reservoir of bioactive substances in China. To explore the antitumor actions of flavonoids (JMFs) from the waste branches of J. mandshurica, the following optimized purification parameters of JMFs by macroporous resins were first obtained. The loading concentration, flow rate, and loading volume of raw flavonoid extracts were 1.4 mg/mL, 2.4 BV/h, and 5 BV, respectively, and for desorption, 60% ethanol (4 BV) was selected to elute JMFs-loaded AB-8 resin at a flow rate of 2.4 BV/h. This adsorption behavior can be explained by the pseudo-second-order kinetic model and Langmuir isotherm model. Subsequently, JMFs were identified using Fourier transform infrared combined with high-performance liquid chromatography and tandem mass spectrometry, and a total of 156 flavonoids were identified. Furthermore, the inhibitory potential of JMFs on the proliferation, migration, and invasion of HepG2 cells was demonstrated. The results also show that exposure to JMFs induced apoptotic cell death, which might be associated with extrinsic and intrinsic pathways. Additionally, flow cytometry detection found that JMFs exposure triggered S phase arrest and the generation of reactive oxygen species in HepG2 cells. These findings suggest that the JMFs purified in this study represent great potential for the treatment of liver cancer.

Novel intertypic recombination of Echovirus 11 in the Enterovirus species B.

Enteroviruses (EVs), single-stranded, positive-sense RNA viruses, can be classified into four species (A-D), which have previously been linked to a diverse range of disease manifestations and infections affecting the central nervous system. In the Enterovirus species B (EV-B), Echovirus type 11 (E11) has been observed to occasionally circulate in Taiwan, which was responsible for an epidemic of enterovirus infections in 2018. Here, 48 clinical specimens isolated in 2003, 2004, 2009, and 2018 were collected for the high-throughput sequencing. Notably, we identified 2018 Taiwanese strains having potential recombinations in the 3D gene, as well as one 2003 strain having a double recombination with E6 and Coxsackievirus B5 in the P2 and P3 regions, respectively. Additionally, one amino acid signature mutated from the Histidine (H) in throat swab specimens to the Tyrosine (Y) in cerebral spinal fluid specimens was detected at position 1496 (or 57) of the genomic coordinate (or 3A gene) to further demonstrate intra-host evolution in different organs. In conclusion, this study identifies potential intertypic recombination events and an intra-host signature mutation in E11 strains, isolated during a 2018 neurological disease outbreak in Taiwan, contributing to our understanding of its evolution and pathogenesis.

Cuproptosis: emerging biomarkers and potential therapeutics in cancers.

The sustenance of human life activities depends on copper, which also serves as a crucial factor for vital enzymes. Under typical circumstances, active homeostatic mechanisms keep the intracellular copper ion concentration low. Excess copper ions cause excessive cellular respiration, which causes cytotoxicity and cell death as levels steadily rise above a threshold. It is a novel cell death that depends on mitochondrial respiration, copper ions, and regulation. Cuproptosis is now understood to play a role in several pathogenic processes, including inflammation, oxidative stress, and apoptosis. Copper death is a type of regulatory cell death(RCD).Numerous diseases are correlated with the development of copper homeostasis imbalances. One of the most popular areas of study in the field of cancer is cuproptosis. It has been discovered that cancer angiogenesis, proliferation, growth, and metastasis are all correlated with accumulation of copper ions. Copper ion concentrations can serve as a crucial marker for cancer development. In order to serve as a reference for clinical research on the product, diagnosis, and treatment of cancer, this paper covers the function of copper ion homeostasis imbalance in malignant cancers and related molecular pathways.

The spatial dissimilarities and connections of the microbiota in the upper and lower respiratory tract of beef cattle.

Bovine respiratory disease (BRD) causes morbidity and mortality in cattle. The critical roles of the respiratory microbiota in BRD have been widely studied. The nasopharynx was the most popular sampling niche for BRD pathogen studies. The oral cavity and other niches within the respiratory tract, such as nostrils and lung, are less assessed. In this study, oropharyngeal swabs (OS), nasal swabs (NS), nasopharyngeal swabs (NP), and bronchoalveolar lavage (BAL) were collected from calves located in four countries and analyzed for investigation of the dissimilarities and connections of the respiratory microbiota. The results showed that the microbial diversity, structure, and composition in the upper and lower respiratory tract in beef cattle from China, the USA, Canada, and Italy were significantly different. The microbial taxa for each sampling niche were specific and associated with their local physiology and geography. The signature microbiota for OS, NS, NP, and BAL were identified using the LEfSe algorithm. Although the spatial dissimilarities among the respiratory niches existed, the microbial connections were observed in beef cattle regardless of geography. Notably, the nostril and nasopharynx had more similar microbiomes compared to lung communities. The major bacterial immigration patterns in the bovine respiratory tract were estimated and some of them were associated with geography. In addition, the contribution of oral microbiota to the nasal and lung ecosystems was confirmed. Lastly, microbial interactions were characterized to reveal the correlation between the commercial microbiota and BRD-associated pathogens. In conclusion, shared airway microbiota among niches and geography provides the possibility to investigate the common knowledge for bovine respiratory health and diseases. In spite of the dissimilarities of the respiratory microbiota in cattle, the spatial connections among these sampling niches not only allow us to deeply understand the airway ecosystem but also benefit the research and development of probiotics for BRD.

Realizing tunneling electroresistance effect in the Au/h-BN/In2Se3/Au vertical ferroelectric tunnel junction.

Two-dimensional (2D) ferroelectric tunnel junctions (FTJs) have great potential in the design of non-volatile memory devices due to the tunneling electroresistance (TER) effect and the fact that it is not constrained by critical thickness. Incorporation of 2D ferroelectric materials in realistic FTJs inevitably involves the contacts to the traditional three-dimensional (3D) metals. However, how to design the FTJs by combining the 2D ferroelectric materials with the 3D metals still needs to be studied. In this work, we design a vertical 3D FTJ by adopting the 3D metal Au as the left and right electrodes and the 2D ferroelectric material In2Se3 together with h-BN as the central scattering region. By density functional theory combined with the non-equilibrium Green's function (NEGF) method, we demonstrate that the h-BN intercalation with a large bandgap plays the role of good "insulator," which breaks the symmetry of the left and right electrodes. As a result, we obtain the TER ratio of about 170%, and it can be further improved to about 1200% if two layers of In2Se3 (2L-In2Se3) are adopted as the tunneling barrier layer. Our results provide another way for the design and application of ferroelectric memory devices based on 2D ferroelectric materials.

Impact of patient characteristics on innate immune responses and inflammasome activation in ex vivo human lung tissues infected with influenza A virus.

Background: Influenza A virus (IAV) infection poses a persistent global health challenge, necessitating a nuanced grasp of host immune responses for optimal interventions. While the interplay between aging, immunosenescence, and IAV is recognized as key in severe lower respiratory tract infections, the role of specific patient attributes in shaping innate immune reactions and inflammasome activity during IAV infection remains under-investigated. In this study, we utilized an ex vivo infection model of human lung tissues with H3N2 IAV to discern relationships among patient demographics, IAV nucleoprotein (NP) expression, toll-like receptor (TLR) profiles, PD-1/PD-L1 markers, and cytokine production. Methods: Our cohort consisted of thirty adult patients who underwent video-assisted thoracoscopic surgery during 2018-2019. Post-surgical lung tissues were exposed to H3N2 IAV for ex vivo infections, and the ensuing immune responses were profiled using flow cytometry. Results: We observed pronounced IAV activity within lung cells, as indicated by marked NP upregulation in both epithelial cells (P = 0.022) and macrophages (P = 0.003) in the IAV-exposed group relative to controls. Notably, interleukin-2 levels correlated with variations in TLR1 expression on epithelial cells and PD-L1 markers on macrophages. Age emerged as a modulating factor, dampening innate immune reactions, as evidenced by reduced interleukin-2 and interferon-γ concentrations (both adjusted P < 0.05). Intriguingly, a subset of participants with pronounced tumor necrosis factor-alpha post-mock infection (Cluster 1) showed attenuated cytokine responses in contrast to their counterparts in Cluster 2 and Cluster 3 (all adjusted P < 0.05). Individuals in Cluster 2, characterized by a low post-mock infection NP expression in macrophages, exhibited reduced variations in both NP and TLR1-3 expressions on these cells and a decreased variation in interleukin-2 secretion in comparison to their Cluster 3 counterparts, who were identified by their elevated NP macrophage expression (all adjusted P < 0.05). Conclusion: Our work elucidates the multifaceted interplay of patient factors, innate immunity, and inflammasome responses in lung tissues subjected to ex vivo H3N2 IAV exposure, reflecting real-world lower respiratory tract infections. While these findings provide a foundation for tailored therapeutic strategies, supplementary studies are requisite for thorough validation and refinement.

Biogenesis and function of exosome lncRNAs and their role in female pathological pregnancy.

Preeclampsia, gestational diabetes mellitus, and recurrent spontaneous abortion are common maternal pregnancy complications that seriously endanger women's lives and health, and their occurrence is increasing year after year with a rejuvenation trend. In contrast to biomarkers found freely in tissues or body fluids, exosomes exist in a relatively independent environment and provide a higher level of stability. As backbone molecules, guidance molecules, and signaling molecules in the nucleus, lncRNAs can regulate gene expression. In the cytoplasm, lncRNAs can influence gene expression levels by modifying mRNA stability, acting as competitive endogenous RNAs to bind miRNAs, and so on. Exosomal lncRNAs can exist indefinitely and are important in intercellular communication and signal transduction. Changes in maternal serum exosome lncRNA expression can accurately and timely reflect the progression and regression of pregnancy-related diseases. The purpose of this paper is to provide a reference for clinical research on the pathogenesis, diagnosis, and treatment methods of pregnancy-related diseases by reviewing the role of exosome lncRNAs in female pathological pregnancy and related molecular mechanisms.

Prognostic role of the peritoneal cancer index in ovarian cancer patients who undergo cytoreductive surgery: a meta-analysis.

Advanced-stage ovarian cancer is usually associated with peritoneal carcinomatosis. This study evaluates the prognostic role of the Peritoneal Cancer Index (PCI) in predicting the survival of patients with ovarian cancer. A literature search was conducted in electronic databases (Google Scholar, PubMed, Ovid, and Science Direct) and study selection was based on precise eligibility criteria. Random-effects meta-analyses were performed to estimate survival with low and high PCI scores and to pool hazard ratios (HR) of survival between lower and higher PCI scores. A total of 20 studies (2588 patients) were included. Median follow-up was 39 months [95%CI: 25, 54]. Complete cytoreduction rate was 80% [95% CI: 73, 87]. The median PCI score was 11.3 [95% CI: 9.9, 12.7]. Median survival was 56.7 months [95% CI: 45.2, 68.2] with below and 28.8 months [95% CI: 23.0, 34.6] with above any PCI cutoff. Most studies used PCI cutoffs between 10 and 20. The median progression-free survival was 23.7 months [95% CI: 16.5, 30.8] with below and 11.9 months [95% CI: 5.9, 17.9] with above any PCI cutoff. 5-year survival rates were 61.3% [95% CI: 49.9, 72.8] with PCI<10 cutoffs, 21.7% [95% CI: 11.6, 31.8] with PCI>10 cutoffs, 50.1% [95% CI: 39.0, 61.2] with PCI<20 cutoffs, and 21.7% [95% CI: 16.2, 27.1] with PCI>20 cutoffs. Pooled analysis of HRs showed that a higher PCI score was associated with worse survival in both univariate (HR 2.14 [95%CI: 1.63, 2.66]) and multivariate (HR 1.10 [95% CI: 1.02, 1.18]) analyses. In a set of studies that used varying PCI cutoffs, the PCI has been found to have a significant inverse association with the survival of patients with advanced ovarian cancer who underwent cytoreductive surgery.

Exploring the elevation dynamics of rumen bacterial communities in Barn feeding cattle from 900 to 3,600 meters by full-length 16S sequencing.

The diversity and abundance of rumen microorganisms serve as indicators not only of the host's digestive and metabolic capacity but also of its health status. The complex microbial communities in the rumen are influenced to varying degrees by environmental adaptability. In this study, we collected 24 rumen fluid samples from 24 healthy male cattle in three regions of Yunnan, China. Using 16S rRNA amplicon sequencing data analysis, we examined the variations in rumen microorganisms among cattle fed at altitudes of 900 m, 1800 m, and 3,600 m. Altitude-related environmental factors did not surpass phylogeny as the main driving force behind the convergent evolution of yellow cattle rumen microbiome composition. However, they did have an impact on the alpha diversity of the rumen microbiome and the coevolution of the core microbiome. The change in altitude noticeably influenced the diversity and richness of the rumen microbiota, highlighting the environmental effect of altitude. As altitude increased, there was an observed increase in the abundance of Firmicutes and Bacteroidetes, while the abundance of ruminal Proteobacteria and Kiritimatiellaeota decreased. Importantly, at the genus level, the core genus exhibited distinct dynamic changes as altitude increased. Ruminants exhibit the ability to adapt their gut type in accordance with altitude, thereby optimizing energy utilization, especially in high-altitude settings. These discoveries offer valuable insights into the coevolution of host-microbe interactions during ruminant adaptation to various altitudinal environments.

Exploring the temporal dynamics of rumen bacterial and fungal communities in yaks (Bos grunniens) from 5 days after birth to adulthood by full-length 16S and 18S rRNA sequencing.

The rumen of ruminants is inhabited by complex and diverse microorganisms. Young animals are exposed to a variety of microorganisms from their mother and the environment, and a few colonize and survive in their digestive tracts, forming specific microflora as the young animals grow and develop. In this study, we conducted full-length sequencing of bacterial and fungal communities in the rumen of pastured yaks of different ages (from 5 days after birth to adulthood) using amplified sequencing technology. The results showed that the rumen microflora of Zhongdian yaks changed gradually from 5 to 180 days after birth and tended to stabilize at 2 years of age. The rumen of adult yaks was the most suitable for the growth and reproduction of most bacteria. Bactria diversity of the yak rumen increased gradually from 5 days after birth to adulthood. With the growth of yaks, different dominated bacteria were enriched in different groups, but Prevotella remained highly abundant in all groups. The yak rumen at 90 days of age was the most suitable for the growth and reproduction of most fungi, and 90 days of age could be a cut-off point for the distribution of fungal communities. Fungal Thelebolus was the firstly reported in yak rumen and was enriched in the yak rumen of 90 days after birth. The most abundant and balanced fungal genera were found in adult yaks, and most of them were only detected in adult yaks. Our study reported on the rumen bacterial and fungal communities of Zhongdian yaks grazed at different ages and provided insights into the dynamic changes of dominant microflora with yak growth.

A comprehensive overview of exosome lncRNAs: emerging biomarkers and potential therapeutics in endometriosis.

Endometriosis is a gynecological condition that significantly impacting women's daily lives. In recent years, the incidence of endometriosis has been rising yearly and is now an essential contributor to female infertility. Exosomes are extracellular vesicles (EVs) that carry long noncoding RNA (lncRNA) and shield lncRNA from the outside environment thanks to their vesicle-like structure. The role of exosome-derived lncRNAs in endometriosis is also receiving more study as high-throughput sequencing technology develops. Several lncRNAs with variable expression may be crucial to the emergence and growth of endometriosis. The early diagnosis of endometriosis will be considerably improved by further high specificity and sensitivity Exosome lncRNA screening. Exosomes assist lncRNAs in carrying out their roles, offering a new target for creating endometriosis-specific medications. In order to serve as a reference for clinical research on the pathogenesis, diagnosis, and treatment options of endometriosis, this paper covers the role of exosome lncRNAs in endometriosis and related molecular mechanisms.

Factors influencing neutralizing antibody titers elicited by coronavirus disease 2019 vaccines.

The World Health Organization has highlighted the importance of an international standard (IS) for severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) neutralizing antibody titer detection to calibrate diagnostic techniques. We applied an IS to calibrate neutralizing antibody titers (NTs) (international units/mL) in response to coronavirus disease 2019 (COVID-19) vaccination. Moreover, the association between different factors and neutralizing antibodies was analyzed. A total of 1667 serum samples were collected from participants receiving different COVID-19 vaccines. Antibody titers were determined by a microneutralization assay using live viruses in a biosafety level 3 (BSL-3) laboratory and a commercial serological MeDiPro kit. The titer determined using the MeDiPro kit was highly correlated with the NT determined using live viruses and calibrated using IS. Fever and antipyretic analgesic treatment were related to neutralizing antibody responses in ChAdOx1-S and BNT162b2 vaccinations. Individuals with diabetes showed a low NT elicited by MVC-COV1901. Individuals with hypertension receiving the BNT162b2 vaccine had lower NTs than those without hypertension. Our study provided the international unit (IU) values of NTs in vaccinated individuals for the development of vaccines and implementation of non-inferiority trials. Correlation of the influencing factors with NTs can provide an indicator for selecting COVID-19 vaccines based on personal attributes.

Dietary ß-hydroxybutyric acid improves the growth performance of young ruminants based on rumen microbiota and volatile fatty acid biosynthesis.

Introduction: The ketone body ß-hydroxybutyric acid (BHB) plays critical roles in cellular proliferation and metabolic fuel utilization; however, its effects on the rumen microbiota remain unknown. Methods: Here, three doses of BHB (low, medium, and high) were supplemented to early-weaned goat kids. Results: Compared with controls, the beneficial effects of BHB on growth and rumen development were observed in goats at 90 days of age (d). The low dose of dietary BHB increased the concentration of rumen acetate, propionate, and butyrate on d90. The sequencing results of the rumen microbiota revealed marked shifts in rumen microbial community structure after early-weaned goat kids consumed BHB for 2 months. The signature bacterial ASVs for each treatment were identified and were the main drivers contributing to microbial interactions in the rumen. The bacteria associated with rumen weight were also correlated with body weight. Some classified bacterial signatures, including Prevotella, Olsenella umbonate, and Roseburia faecis, were related to rumen volatile fatty acids and host development. Conclusion: Overall, dietary BHB altered rumen microbiota and environments in young goats, which contributed to rumen development and growth.

Congenital dysfibrinogenemia misdiagnosed and inappropriately treated as acute fatty liver in pregnancy: A case report and review of literature.

BACKGROUND: The purpose of this study was to report the rare case of a pregnant woman with congenital dysfibrinogenemia (CD) misdiagnosed as acute fatty liver. She was treated according to the principles of acute fatty liver but achieved good clinical results. CASE SUMMARY: A 30-year-old woman presented with 39 (6/7) wk of menopause and 6 h of irregular abdominal pain and attended our hospital. Emergency surgery was performed due to fetal distress. Postoperative management followed the treatment principle of acute fatty liver. DNA sequencing was carried out on the pregnant woman and her pedigree. Coagulation values of the patient on admission were prothrombin time 33.7 s, activated partial thromboplastin time 60.4 s, thrombin time 45.2 s, and fibrinogen 0.60 g/L. DNA sequencing results showed that the woman carried a pathogenic heterozygous variation of the fibrinogen alpha chain gene (FGA), which is closely related to hereditary fibrinogen abnormality, and the mutation site was located in p.R350H. After a follow-up period of 12 mo, the mother and her newborn had a good prognosis without bleeding or thrombosis. CONCLUSION: Pregnant women with CD may have atypical symptoms, which can easily lead to misdiagnosis. In addition, treatment can be attempted according to the principles of acute fatty liver management. This rare pregnant patient with CD was caused by a novel FGA (p.R350H) gene mutation.

De Novo Transcriptome Dataset Generation of the Swamp Buffalo Brain and Non-Brain Tissues.

The sequenced data availability opened new horizons related to buffalo genetic control of economic traits and genomic diversity. The visceral organs (brain, liver, etc.) significantly involved in energy metabolism, docility, or social interactions. We performed swamp buffalo transcriptomic profiling of 24 different tissues (brain and non-brain) to identify novel transcripts and analyzed the differentially expressed genes (DEGs) of brain vs. non-brain tissues with their functional annotation. We obtained 178.57 Gb clean transcriptomic data with GC contents 52.77%, reference genome alignment 95.36%, exonic coverage 88.49%. Totally, 26363 mRNAs transcripts including 5574 novel genes were obtained. Further, 7194 transcripts were detected as DEGs by comparing brain vs. non-brain tissues group, of which 3,999 were upregulated and 3,195 downregulated. These DEGs were functionally associated with cellular metabolic activities, signal transduction, cytoprotection, and structural and binding activities. The related functional pathways included cancer pathway, PI3k-Akt signaling, axon guidance, JAK-STAT signaling, basic cellular metabolism, thermogenesis, and oxidative phosphorylation. Our study provides an in-depth understanding of swamp buffalo transcriptomic data including DEGs potentially involved in basic cellular activities and development that helped to maintain their working capacity and social interaction with humans, and also, helpful to disclose the genetic architecture of different phenotypic traits and their gene expression regulation.

Titers and breadth of neutralizing antibodies against SARS-CoV-2 variants after heterologous booster vaccination in health care workers primed with two doses of ChAdOx1 nCov-19: A single-blinded, randomized clinical trial.

OBJECTIVES: We conducted a single-blinded, randomized trial to evaluate the safety, reactogenicity, and immunogenicity of heterologous booster vaccination in health care workers (HCW) who had received two doses of ChAdOx1 nCov-19. METHODS: HCW who had at least 90 days after the second dose were enrolled to receive one of the four vaccines: BNT162b2 (30 µg), half-dose mRNA-1273 (50 µg), mRNA-1273 (100 µg), and MVC-COV1901 (15 µg). The primary outcomes were humoral and cellular immunogenicity and secondary outcomes assessed safety and reactogenicity at 28 days post-booster. RESULTS: MVC-COV1901 Three hundred and forty HCW were enrolled: 83 received BNT162b2 (2 excluded), 85 half-dose mRNA-1273, 85 mRNA-1273, and 85 MVC-COV1901. mRNA vaccines had more reactogenicity than protein vaccine. The fold-rise of anti-spike IgG geometric mean titer was 8.4 (95% CI 6.8-10.4) for MVC-COV1901, 32.2 (27.2-38.1) for BNT162b2, 47.6 (40.8-55.6) for half-dose mRNA-1273 and 63.2 (53.6-74.6) for mRNA-1273. The live virus microneutralization assays (LVMNA) against the wild type, alpha and delta variants were consistent with anti-spike IgG for all booster vaccines. The LVMNA in the four groups against omicron BA.1 variant were 6.4 to 13.5 times lower than those against the wild type. All booster vaccines induced a comparable T cell response. CONCLUSIONS: Third dose booster not only increases neutralizing antibody titer but also enhances antibody breadth against SARS-CoV-2 variants. mRNA vaccines are preferred booster vaccines for those who received primary series of ChAdOx1 nCov-19.