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(1) Purpose: This study aimed to analyze coronavirus disease 2019 (COVID-19) vaccine policies and their effectiveness in Italy, India, and South Africa to provide empirical experience for vaccination and COVID-19 pandemic control. (2) Methods: The study systematically summarized the COVID-19 vaccine policies in Italy, India, and South Africa through public information available on the official websites of the World Health Organization and the ministries of health in these three countries. Total vaccinations, COVID-19 vaccination rates, rates of fully vaccinated, rates of booster-vaccinated, and total confirmed cases were selected for cross-sectional comparison of COVID-19 vaccination in these three countries. Daily cases per million, daily deaths per million, and the effective reproduction rate were calculated to measure the effectiveness of COVID-19 vaccine policies implementation in each of these three countries. (3) Results: Italy, India, and South Africa differ in the start date of COVID-19 vaccination, vaccine types, vaccine appointments, and whether vaccinations are free. The COVID-19 vaccination rates in these three countries varied widely, with Italy having the highest and South Africa the lowest. COVID-19 vaccination has had a positive effect on reducing daily deaths and stabilizing the effective reproduction rate. The three countries had experienced more than one outbreak spike due to the spread of new mutated strains since the start of COVID-19 vaccination. (4) Conclusions: This study concluded that responding to the COVID-19 pandemic requires active promotion of basic and booster vaccinations to comprehensively build up the population immune barrier. Promoting equitable distribution of COVID-19 vaccine internationally and solidarity and cooperation among countries maximizes global common interests. By combining vaccination with non-pharmaceutical interventions, the pandemic can be prevented and controlled comprehensively and systematically in three aspects: detection of the source of infection, reduction of transmission routes, and protection of susceptible populations.

Metallic glass (MG) usually exhibits poor fatigue property, limiting its application as structural materials. Shear bands play a key role in fatigue crack initiation and propagation of MG. In this work, to enhance the fatigue property of MG, we proposed and verified a new strategy of suppressing the shear band initiation and then impeding the fatigue crack formation through relaxing the microstructure, in contrast to the previous one of proliferating shear bands through toughening MG. Moreover, simple quasi-static tests including uniaxial tension, compression and notch tension, are employed as feedback to estimate the best microstructure after relaxing and then the optimal fatigue property of MG. It is found that if the relaxed samples exhibit higher compressive elastic limit and tensile strength, but only slightly decreased notch toughness than the as-cast samples, the fatigue property of relaxed samples can be obviously enhanced. The present strategy provides a promising way for enhancing the fatigue endurance property of MGs without the requirement of intrinsically large plasticity, which may thus be beneficial for the structural application of most MGs with high glass forming ability.

Background: Sudden unexplained death in childhood (SUDC) is an understudied public health issue with multiple potential risk factors, including undiagnosed cardiac and seizure disorders, for which genetic risk factors can contribute. Methods: We studied whole exome sequence data from 124 consecutively ascertained trios (decedent child and unaffected parents) to test for excessive de novo mutations in cardiac, epilepsy and other genes. Findings: Among SUDC decedents, nonsynonymous mutations were enriched in genes associated with cardiac and seizure disorders relative to non-sudden death controls (odds ratio=9.76, p=2.15x10-4). Beyond these genes there was a trend for excess loss-of-function mutations in genes that are loss-of-function intolerant (odds ratio=2.34, p=0.08). In our cohort, two genes had recurrent missense mutations, RYR2 and CACNA1C. Both RYR2 mutations are known as pathogenic (p=1.7x10-7). Both CACNA1C mutations are within a short (104 nucleotide) exon (p=1.0x10-7). We found evidence for over-transmission of loss-of-function or pathogenic variants within cardiac and seizure disorder genes (11/14 transmitted, p=0.03). Interpretation: Eleven of 124 (8.9%) decedents carried likely pathogenic or pathogenic variants associated with sudden death via a lethal cardiac or seizure disorder. Of these, 7 were de novo in origin, 1 was a transmitted parental mosaic mutation, and 3 were transmitted from heterozygous parents. Funding Statement: This study was supported by funding from the SUDC Foundation and Finding A Cure for Epilepsy and Seizures (NYU). RWT was supported by NIH grants R01 DA040484 and R01 MH71739. MJA and DJT were supported by the Mayo Clinic Windland Smith Rice Comprehensive Sudden Cardiac Death Program. Declaration of Interests: MJA is a consultant for Audentes Therapeutics, Boston Scientific, Gilead Sciences, Invitae, Medtronic, Myokardia, and St. Jude Medical. MJA and Mayo Clinic have an equity/royalty relationship with AliveCor, Blue Ox Health, and StemoniX. However, none of these entities are related to study. DG reports he is cofounder and holds equity in Q State – Pairnomix and Praxis Therapeutics, and equity in Apostle Inc. He receives personal fees from AstraZeneca, outside the submitted work. RT reports his participation on the Scientific Advisory boards of Howard Hughes Medical Institute, the Institute of Neuroscience (Shanghai), and the Institute of Science and Technology (Vienna). RT also reports his participation in the Actelion Scientific Advisory Board (Basel) with no compensation during 3 year span. OD reports equity interest in Empatica and receive funding from NINDS on SUDEP research. MJA, OD and PL are members of the SUDC Foundation’s scientific advisory board. LGC is President of the SUDC Foundation. MJA, OD, PL and LGC do not participate in grant funding decisions or negotiations by the SUDC Foundation to NYU Langone Health. PL, DMH, RR, XW, JP have no declarations of interests. Ethics Approval Statement: Parental consent was obtained in this NYU Institutional Review Board approved study (# S14-01061).

In vertebrates, hematopoiesis occurring in different niches is orchestrated by intrinsic and extrinsic regulators, which are indispensable for the maintenance of homeostasis in a whole organism. Previous studies have revealed a large number of linear and planar regulatory mechanisms. However, a multi-dimensional transcriptomic atlas of any given hematopoietic organ has not been yet established. Here, we use multiple RNA-seq approaches, including cell type-specific temporal bulk RNA-seq, in vivo GEO-seq, and single-cell RNA-seq (scRNA-seq), to characterize the detailed spatiotemporal transcriptome during hematopoietic stem and progenitor cell (HSPC) expansion in the caudal hematopoietic tissue (CHT) of zebrafish. Combinatorial expression profiling reveals that in the CHT niche, HSPCs and their neighboring supporting cells are co-regulated by shared signaling pathways and intrinsic factors, such as integrin signaling and Smchd1. Moreover, scRNA-seq analysis unveils the strong association between cell cycle status and HSPC differentiation. Taken together, we report a global transcriptome landscape that provides valuable insights and a rich resource for understanding HSPC development, particularly on HSPC expansion in an intact hematopoietic organ. The key signaling pathways and factors identified here would contribute to HSPC expansion in vitro.