DNA-Programmed Four-Bit Quaternary Fluorescence Encoding (FLUCO) Enables 51-Colored Bioimaging Analysis.

Color encoding plays a crucial role in painting, digital photography, and spectral analysis. Achieving accurate, target-responsive color encoding at the molecular level has the potential to revolutionize scientific research and technological innovation, but significant challenges persist. Here, we propose a multibit DNA self-assembly system based on computer-aided design (CAD) technology, enabling accurate, target-responsive, amplified color encoding at the molecular level, termed fluorescence encoding (FLUCO). As a model, we establish a quaternary FLUCO system using four-bit DNA self-assembly, which can accurately encode 51 colors, presenting immense potential in applications such as spatial proteomic imaging and multitarget analysis. Notably, FLUCO enables the simultaneous imaging of multiple targets exceeding the limitations of channels using conventional imaging equipment, and marks the integration of computer science for molecular encoding and decoding. Overall, our work paves the way for target-responsive, controllable molecular encoding, facilitating spatial omics analysis, exfoliated cell analysis, and high-throughput liquid biopsy.

Heterogeneity of comprehensive clinical phenotype and longitudinal adaptive function and correlation with computational predictions of severity of missense genotypes in KIF1A-associated neurological disorder.

PURPOSE: Pathogenic variants in kinesin family member 1A (KIF1A) are associated with KIF1A-associated neurological disorder. We report the clinical phenotypes and correlate genotypes of individuals with KIF1A-associated neurological disorder. METHODS: Medical history and adaptive function were assessed longitudinally. In-person evaluations included neurological, motor, ophthalmologic, and cognitive assessments. RESULTS: We collected online data on 177 individuals. Fifty-seven individuals were also assessed in-person. Most individuals had de novo heterozygous missense likely pathogenic/pathogenic KIF1A variants. The most common characteristics were hypotonia, spasticity, ataxia, seizures, optic nerve atrophy, cerebellar atrophy, and cognitive impairment. Mean Vineland adaptive behavior composite score (VABS-ABC) was low (M = 62.9, SD = 19.1). The mean change in VABS-ABC over time was -3.1 (SD = 7.3). The decline in VABS-ABC was associated with the age at first assessment and abnormal electroencephalogram/seizure. There was a positive correlation between evolutionary scale model (ESM) score for the variants and final VABS-ABC (P = .003). Abnormal electroencephalogram/seizure, neuroimaging result, and ESM explain 34% of the variance in final VABS-ABC (P < .001). CONCLUSION: In-person assessment confirmed caregiver report and identified additional visual deficits. Adaptive function declined over time consistent with both the neurodevelopmental and neurodegenerative nature of the condition. Using ESM score assists in predicting phenotype across a wide range of unique variants.

IRF11 synergizes with STAT1 and STAT2 to promote type I IFN production.

Interferon regulatory factor 11 (IRF11), a fish specific member of IRF family, is a transcription factor known for its positive role in teleost antiviral defense by regulating IFN expression. Despite its recognized function, the precise mechanism of IRF11 in type I IFNs production remains largely unknown. In this study, we identified IRF11 in Japanese eel, Anguilla japonica, (AjIRF11) and determined its involvement in the later phase of fish IFN production. Our results demonstrate that IRF11-induced IFN production operates through ISRE binding. Mutations in each ISRE site within the promoter of AjIFN2 or AjIFN4 abolished IRF11-mediated activation of IFN promoters. In addition, the overexpression of AjIRF11 does not significantly impact the activation of AjIFN promoters induced by RLR-related signaling pathway proteins. Furthermore, IRF11-knockdown in ZFLs (zebrafish liver cells) has no effect on the RLRs-induced expression of zebrafish IFN-φ1 and IFN-φ3, indicating that IRF11 is not involved in the RLR-mediated IFN production. However, AjIRF11 can form transcription complexes with AjSTAT1 or AjSTAT2, or form homo- or heterodimers with AjIRF1 to stimulate the transcription of type I IFNs. Overall, it is shown in this study that IRF11 can act synergistically with STAT1 and/or STAT2 for the induction of IFN.

Trophic Transfer and Toxic Potency of Rare Earth Elements along a Terrestrial Plant-Herbivore Food Chain.

Extensive rare earth element (REE) mining activities have caused REE contamination of ambient agricultural soils, posing threats to associated food webs. Here, a simulated lettuce-snail food chain was conducted to evaluate the trophic transfer characteristics and the consequent effects of REEs on consumers. After 50-day exposure to soil, lettuce roots dose-dependently accumulated 9.4-76 mg kg-1 REEs and translocated 3.7-20 mg kg-1 REEs to shoots. Snails feeding on REE-contaminated shoots accumulated 3.0-6.7 mg kg-1 REEs with trophic transfer factors of 0.20-0.98, indicating trophic dilution in the lettuce-snail system. REE profiles in lettuce and snails indicated light REE (LREE) enrichment only in snails and the varied REE profiles along the food chain. This was corroborated by toxicokinetics. Estimated uptake (Ku) and elimination (Ke) parameters were 0.010-2.9 kgshoot kgsnail-1 day-1 and 0.010-1.8 day-1, respectively, with higher Ku values for LREE and HREE. The relatively high Ke, compared to Ku, indicating a fast REE elimination, supports the trophic dilution. Dietary exposure to REEs dose-dependently affected gut microbiota and metabolites in snails. These effects are mainly related to oxidative damage and energy expenditure, which are further substantiated by targeted analysis. Our study provides essential information about REE bioaccumulation characteristics and its associated risks to terrestrial food chains near REE mining areas.

Genome-Wide Identification and Expression Analysis of the DA1 Gene Family in Sweet Potato and Its Two Diploid Relatives.

The DA1-like gene family plays a crucial role in regulating seed and organ size in plants. The DA1 gene family has been identified in several species but has not yet been reported in sweet potatoes. In this study, nine, eleven, and seven DA1s were identified in cultivated sweet potato (Ipomoea batatas, 2n = 6x = 90) and its two diploid wild relatives, I. trifida (2n = 2x = 30) and I. triloba (2n = 2x = 30), respectively. The DA1 genes were classified into three subgroups based on their phylogenetic relationships with Arabidopsis thaliana and Oryza sativa (rice). Their protein physiological properties, chromosomal localization, phylogenetic relationships, gene structure, promoter cis-elements, and expression patterns were systematically analyzed. The qRT-PCR results showed that the expression levels of four genes, IbDA1-1, IbDA1-3, IbDA1-6, and IbDA1-7, were higher in the sweet potato leaves than in the roots, fiber roots, and stems. In our study, we provide a comprehensive comparison and further the knowledge of DA1-like genes in sweet potatoes, and provide a theoretical basis for functional studies.

An Intelligent DNA Nanoreactor for Easy-to-Read In Vivo Tumor Imaging and Precise Therapy.

Nanomaterial-based in vivo tumor imaging and therapy have attracted extensive attention; however, they suffer from the unintelligent "always ON" or single-parameter responsive signal output, substantial off-target effects, and high cost. Therefore, achieving in vivo easy-to-read tumor imaging and precise therapy in a multi-parameter responsive and intelligent manner remains challenging. Herein, an intelligent DNA nanoreactor (iDNR) was constructed following the "AND" Boolean logic algorithm to address these issues. iDNR-mediated in situ deposition of photothermal substance polydopamine (PDA) can only be satisfied in tumor tissues with abundant membrane protein biomarkers "AND" hydrogen peroxide (H2 O2 ). Therefore, intelligent temperature-based in vivo easy-to-read tumor imaging is realized without expensive instrumentation, and its diagnostic performance matches with that of flow cytometry, and photoacoustic imaging. Moreover, precise photothermal therapy (PTT) of tumors could be achieved via intelligent heating of tumor tissues. The precise PTT of primary tumors in combination with immune checkpoint blockade (ICB) therapy suppresses the growth of distant tumors and inhibits tumor recurrence. Therefore, highly programmable iDNR is a powerful tool for intelligent biomedical applications.

Effects of Fusarium solani on the Growth and Development of Anoplophora glabripennis Larvae.

Anoplophora glabripennis (Asian longhorned beetle) is a wood-boring pest that can inhabit a wide range of healthy deciduous host trees in native and non-native habitats. Lignocellulose degradation plays a major role in the acquisition of nutrients during the growth and development of A. glabripennis larvae. In this study, the lignocellulose degradation capacity of Fusarium solani, a fungal symbiont of A. glabripennis, was investigated in fermentation culture and in four host tree species. The impact of F. solani on larval growth and survival parameters was assessed. Fermentation culture demonstrated continuous and stable production of lignocellulolytic enzymes over the cultivation period. Furthermore, F. solani was able to degrade host tree lignocellulose, as shown by decreased soluble sugar and cellulose contents and an increase in protein content. No significant differences in larval survival were observed in larvae fed with or without F. solani. However, weight and head capsule width were higher in larvae fed on F. solani, and gut lignocellulose activities were elevated in fed larvae. Our results indicate a role for F. solani in the predigestion of lignocellulose during the colonization and parasitic stages of A. glabripennis larval development, and also the F. solani an important symbiotic partner to A. glabripennis, lowering barriers to colonization and development in a range of habitats.

Differential Evolution Optimization of Microwave Focused Hyperthermia Phased Array Excitation for Targeted Breast Cancer Heating.

Microwave hyperthermia using the phased array applicator is a non-invasive treatment modality for breast cancer. Hyperthermia treatment planning (HTP) is critical to accurately treating breast cancer and avoiding damage to the patient's healthy tissue. A global optimization algorithm, differential evolution (DE) algorithm, has been applied to optimize HTP for breast cancer and its ability to improve the treatment effect was proved by electromagnetic (EM) and thermal simulation results. DE algorithm is compared to time reversal (TR) technology, particle swarm optimization (PSO) algorithm, and genetic algorithm (GA) in HTP for breast cancer in terms of convergence rate and treatment results, such as treatment indicators and temperature parameters. The current approaches in breast cancer microwave hyperthermia still have the problem of hotspots in healthy tissue. DE enhances focused microwave energy absorption into the tumor and reduces the relative energy of healthy tissue during hyperthermia treatment. By comparing the treatment results of each objective function used in DE, the DE algorithm with hotspot to target quotient (HTQ) as the objective function has outstanding performance in HTP for breast cancer, which can increase the focused microwave energy of the tumor and decrease the damage to healthy tissue.

Design of Ultra-Wideband Phased Array Applicator for Breast Cancer Hyperthermia Therapy.

Focused microwave-hyperthermia therapy has recently emerged as a key technology in the treatment of breast cancer due to non-invasive treatment. An applicator of a three-ring phased array consisting of ultra-wideband (UWB) microstrip antennas was designed for breast cancer therapy and operates at 0.915 GHz and 2.45 GHz. The proposed antenna has an ultra-wideband from 0.7 GHz to 5.5 GHz with resonant frequencies of 0.915 GHz and 2.45 GHz and dimensions of 15 × 43.5 × 1.575 mm3. The number of each ring was chosen to be 12 based on the SAR distribution and the performance indicators of tumor off-center focusing results for four different numbers of single-ring arrays. The homogeneous breast model is applied to a three-ring phased array consisting of 36 elements for focused simulation, and 1 cm3 and 2 cm3 tumors are placed in three different locations in the breast. The simulation results show that the proposed phased array has good performance and the capability to raise the temperature of different volumes of breast cancer above 42.5 °C after choosing a suitable operating frequency. The proposed applicator allows for precise treatment of tumors by selecting the appropriate operating frequency based on the size of the malignant tumor.

Cytotoxic Indole Diterpenoids from a Sphagneticola trilobata-Derived Fungus Aspergillus sp. PQJ-1.

Two new indole diterpene derivatives, 5S-hydroxy-ß-aflatrem (1) and 14R-hydroxy-ß-aflatrem (2), along with one known analogue, 14-(N,N-dimethl-L-valyloxy)paspalinine (3), were isolated from the fermentation broth of the fungus Aspergillus sp. PQJ-1 derived from Sphagneticola trilobata. The structures of the new compounds were elucidated from spectroscopic data and ECD spectroscopic analyses. All the compounds (1-3) were evaluated for their cytotoxicity against A549, Hela, Hep G2, and MCF-7 cell lines. Compounds 1 and 2 exhibited selective inhibition against Hela cells. Further studies showed that 1 significantly induced apoptosis and suppressed migration and invasion in Hela cells. Moreover, 1 could up-regulate pro-apoptotic genes BAX and Caspase-3 and down-regulate anti-apoptotic genes Bcl-xL and XIXP.

Magnetism-Controllable Catalytic Activity of DNAzyme.

Controllable regulation of enzyme activity is an important prerequisite for the in-depth application of enzymes, especially in today's intelligent era. However, irreversible regulation and cumbersome operation make this goal difficult to achieve. Here, by adopting magnetism and a harmless, noncontact, and time- and space-controllable physical element, we developed a system that could conveniently and reversibly regulate the activity of DNAzyme. In this system, the strands of the DNAzyme could be stretched or folded by applying or removing a magnetic field. Thereby, the conformation-dependent endonuclease activity of the DNAzyme could be facilely switched between an "OFF" and "ON" state. This system provides a reusable platform for the control of enzyme catalytic activity through magnetism, which provides guidance for further application in some related scientific research, especially the regulation of the activity of conformation-dependent polymers (DNAzymes, aptamers, and peptides).

CASA: a comprehensive database resource for the COVID-19 Alternative Splicing Atlas.

BACKGROUND: As a key process in transcriptional regulatory mechanisms, alternative splicing (AS) plays a crucial role in maintaining the diversity of RNA and protein expression, and mediates the immune response in infectious diseases, especially for the COVID-19. Therefore, urgent data gathering and more research of AS profiles in microbe-infected human cells are needed to improve understanding of COVID-19 and related infectious diseases. Herein, we have created CASA, the COVID-19 Alternative Splicing Atlas to provide a convenient computing platform for studies of AS in COVID-19 and COVID-19-related infectious diseases. METHODS: In CASA, we reanalyzed thousands of RNA-seq datasets generated from 65 different tissues, organoids and cell lines to systematically obtain quantitative data on AS events under different conditions. A total of 262,994 AS events from various infectious diseases with differing severity were detected and visualized in this database. In order to explore the potential function of dynamics AS events, we performed analysis of functional annotations and drug-target interactions affected by AS in each dataset. RNA-binding proteins (RBPs), which may regulate these dynamic AS events are also provided for users in this database. RESULTS: CASA displays microbe-induced alterations of the host cell splicing landscape across different virus families and helps users identify condition-specific splicing patterns, as well as their potential regulators. CASA may greatly facilitate the exploration of AS profiles and novel mechanisms of host cell splicing by viral manipulation. CASA is freely available at http://www.splicedb.net/casa/ .

Advanced lung cancer inflammation index (ALI) predicts prognosis of patients with gastric cancer after surgical resection.

INTRODUCTION: Advanced lung cancer inflammation index (ALI) has been implicated in the prognosis of many types of tumors. But few studies elucidate its role in gastric cancer (GC). MATERIALS AND METHODS: We consecutively recruited 615 GC patients who underwent radical gastrectomy. Patients were grouped according to ALI status. Risk factors for overall survival (OS) and disease-free survival (DFS) in overall and sex-stratified cohorts were determined using multivariate cox regression analysis. We also compared survival differences between the two groups after one-to-one propensity score matching (PSM). RESULTS: Patients with low ALI showed larger tumor size, more advanced TNM staging, shorter OS (median: 37 vs 42 months) and DFS (median: 37 vs 42 months) (all P < 0.001). Multivariate analysis showed that elevated ALI was independently associated with longer OS and DFS. After stratification by sex, low ALI was an independent risk factor for OS and DFS in male patients but not in female patients. But our further PSM analysis showed prognostic value of ALI in both male and female subgroups. CONCLUSION: Preoperative ALI is an independent prognostic factor for GC patients undergoing curative gastrectomy.

Commonwealth of Soil Health: How Do Earthworms Modify the Soil Microbial Responses to CeO2 Nanoparticles?

Soil ecotoxicological assays on nanoparticles (NPs) have mainly investigated single components (e.g., plants, fauna, and microbes) within the ecosystem, neglecting possible effects resulting from the disturbance of the interactions between these components. Here, we investigated soil microbial responses to CeO2 NPs in the presence and absence of earthworms from the perspectives of microbial functions (i.e., enzyme activities), the community structure, and soil metabolite profiles. Exposure to CeO2 NPs (50, 500 mg/kg) alone decreased the activities of enzymes (i.e., acid protease and acid phosphatase) participating in soil N and P cycles, while the presence of earthworms ameliorated these inhibitory effects. After the CeO2 NP exposure, the earthworms significantly altered the relative abundance of some microbes associated with the soil N and P cycles (Flavobacterium, Pedobacter, Streptomyces, Bacillus, Bacteroidota, Actinobacteria, and Firmicutes). This was consistent with the pattern found in the significantly changed metabolites which were also involved in the microbial N and P metabolism. Both CeO2 NPs and earthworms changed the soil bacterial community and soil metabolite profiles. Larger alterations of soil bacteria and metabolites were found under CeO2 NP exposure with earthworms. Overall, our study indicates that the top-down control of earthworms can drastically modify the microbial responses to CeO2 NPs from all studied biological aspects. This clearly shows the importance of the holistic consideration of all soil ecological components to assess the environmental risks of NPs to soil health.

Metal resistant gut microbiota facilitates snails feeding on metal hyperaccumulator plant Sedum alfredii in the phytoremediation field.

The interactions between hyperaccumulators and their associated herbivores have been mostly investigated in their natural habitats and largely ignored in the phytoremediation practice. Herein, we investigated the herbivory status of Zn/Cd-hyperaccumulating plant Sedum alfredii from both their natural habitats and their applied remediation field, and inspected the adaptive strategies of the herbivores from the perspective of their facilitative gut microbiota. Field investigations showed that snail species Bradybaena ravida was the dominant herbivore feeding on S. alfredii and they can be only found in sites with lower levels of heavy metals compared with the plant natural habitat. Gut microbial community was analyzed using two sequencing methods (16S rRNA and czcA-Zn/Cd resistant gene) to comparatively understand the effect of gut microbes in facilitating snail feeding on the hyperaccumulators. The results revealed significant differences in the diversity and richness between the gut microbiota of the two snail populations, which was more pronounced by the czcA sequencing method. Despite of the compositional differences, their functions seemed to converge into three categories as metal-tolerant and contaminant degraders, gut symbionts, and pathogens. Further function potentials predicted by Tax4Fun based on 16 S sequencing data were in accordance with this categorization as the most abundant metabolic pathways were two-component system and ABC transporter, which was closely related to metal stress adaptation. The prevalence of positive interactions (~80%) indicated by the co-occurrence network analysis based on czcA sequencing data in both groups of gut microbiota further suggested the facilitative effect of these metal-tolerant gut microbes in coping with the high metal diet, which ultimately assist the snails to successfully feed on S. alfredii plants and thrive. This work for the first time provides evidence that the herbivore adaptation to hyperaccumulators were also associated with their gut microbial adaptation to metals.

Integrated Analysis of lncRNAs and mRNAs Identifies a Potential Driver lncRNA FENDRR in Lung Cancer in Xuanwei, China.

This study was to screen out potential driver long non-coding RNAs (lncRNAs) in lung cancer in Xuanwei (LCXW) differently expressed mRNAs and lncRNAs were detected by gene expression microarrays in 23 paired lung adenocarcinoma and adjacent tissues. Combined bioinformatics analysis was performed to identify potential driver lncRNAs and their potential regulatory relationships. Transcriptome and clinical data in TCGA-LUAD were used as comparison and validation dataset. The comparison of LCXW and TCGA-LUAD revealed significant differences in expression of some genes, signaling pathways affected by differentially expressed genes, and the 5-year survival rate of patients. We identified 14 consistently deregulated mRNAs and 5 lncRNAs as candidate genes, which affected multiple cancer-related pathways and influenced patients' overall survival. By combined bioinformatics analysis, we further identified a potential driver lncRNA fetal-lethal non-coding developmental regulatory RNA (FENDRR) and proposed its possible regulation mechanism. The low expression of FENDRR was positively correlated with Krüppel-like factor4 (KLF4), KLF4 down-regulation may loss the activation function of cyclin-dependent kinase inhibitor 1A (CDKN1A) and cyclin-dependent kinase inhibitor 1C (CDKN1C) and the inhibition function of CyclinB1 (CCNB1), eventually cause excessive cell cycle activation and lead to lung cancer. This study revealed a potential FENDRR-KLF4-cell cycle regulation axis. These results lay an important foundation for further research on the pathogenesis of LCXW and identification of potential novel biomarkers or therapeutic targets.

Maternal intake of caffeinated products and birth defects: a systematic review and meta-analysis of observational studies.

Caffeinated products are frequently consumed by women of childbearing age worldwide. It still unclear that whether maternal intake of caffeine associated with an increased risk of birth defects. We searched the databases of PubMed, Embase, the Cochrane Library, and Web of Science for eligible studies through July 2020. All studies examining the association between maternal consumption of caffeine or caffeinated products and birth defects were included. Twenty-nine studies were included in this meta-analysis. Among all the birth defects, maternal caffeine consumption was associated with a higher risk of cardiovascular defects, [odds ratio (OR) 1.17; 95% confidence interval (CI), 1.07-1.28], craniofacial defects (OR 1.09; 95% CI, 1.02-1.17), alimentary tract defects (OR 1.35; 95% CI, 1.16-1.56), and abdominal-wall defects and hernia (OR 1.13; 95% CI, 1.03-1.25). No association was found between maternal caffeine intake and musculoskeletal system defects, genitourinary system defects, nervous system defects, or chromosomal abnormalities. Meanwhile, all three of the caffeine consumption categories (low, moderate, and high) were associated with a higher risk of cardiovascular defects and alimentary tract defects.

Nanocluster-assisted protein-film voltammetry for direct electrochemical signal acquisition.

Acquisition of the direct electrochemical response of protein is the cornerstone for the development of the third generation of electrochemical biosensors. In this work, we developed a nanocluster-assisted protein-film voltammetry technique (NCA-PFV) which can achieve the acquisition of the electrochemical signal and maintain the activity without affecting of the protein's structure. With this strategy, a lipid bilayer membrane is used to immobilize the membrane protein so as to maintain its natural state. Copper nanoclusters with a size smaller than most proteins are then used to function at sub-protein scale and to mediate the electron hopping from the electroactive center of the electrode. As a model, the direct electrochemical signal of cyclooxygenase (COX) is successfully obtained, with a pair of well-defined redox peaks located at -0.39 mV and -0.31 mV, which characterize the heme center of the enzyme. Its catalytic activity towards the substrate arachidonic acid (AA) is also retained. The detection range for AA is 10-1000 µM and the detection limit is 2.4 µM. Electrochemical monitoring of the regulation of the catalytic activity by an inhibitor DuP-697 is also achieved. This work provides a powerful tool for the fabrication of enzyme-based electrochemical biosensors, and is also of great significance for promoting the development and application of next-generation electrochemical biosensors.

Clinical characteristics of severe neonatal enterovirus infection: a systematic review.

BACKGROUND: Enterovirus (EV) is a common cause of infection in neonates. Neonates are at high risk of enterovirus infection with serious clinical manifestations and high lethality. This review systematically summarized the clinical characteristics of neonates with severe enteroviral infection to provide evidence for the identification and treatment of severe neonatal EV infection. METHODS: PubMed, Embase, and Web of Science were searched for original studies on neonates with severe EV infections from January 1, 2000, to November 27, 2020. Two reviewers independently screened the literature, extracted the data, and performed a descriptive analysis. RESULTS: In total, 66 articles with 237 cases of severe neonatal enterovirus infection were included. All neonates developed severe complications. Among them, 46.0% neonates had hepatitis or coagulopathy, 37.1% had myocarditis, 11.0% had meningoencephalitis, and 5.9% had other complications such as hemophagocytic lymphohistiocytosis and pulmonary hemorrhage. The lethality rate of neonates with severe infection was 30.4%. The highest lethality rate was 38.6%, which was observed in neonates with myocarditis. In 70.5% neonates, the age at the onset of symptoms was less than 7 days. Coxsackievirus B infection was seen in 52.3% neonates. The most common symptoms included temperature abnormalities (127, 53.6%), rash (88, 37.1%), poor feeding (58, 24.5%), and respiratory symptoms (52, 21.9%). The main treatment included transfusion of empirical antibiotics (127, 53.6%), blood components (100, 42.2%), intravenous immunoglobulin (IVIG; 97, 40.9%), mechanical ventilation (51, 21.5%), and extracorporeal membrane oxygenation (ECMO; 43, 18.1%). Additionally, antiviral medications pleconaril (14, 5.9%) and pocapavir (3, 1.3%) were administered. CONCLUSIONS: Lethality was high in neonates with severe enterovirus infection, especially in those complicated with myocarditis. The most common symptoms included temperature abnormalities, rash, and poor feeding. The chief supportive treatment consisted of transfusion of blood components, mechanical ventilation, and ECMO. Empirical antibiotics and IVIG were widely used. Antiviral medications included pocapavir and pleconaril; however, more clinical evidence regarding their efficacy is needed.

Correction to: FastMM: an efficient toolbox for personalized constraint-based metabolic modeling.

An amendment to this paper has been published and can be accessed via the original article.