TASK DEFINITION: In this task, you're given a paragraph from the research paper and your task is to generate a suitable title for the research paper based on the given paper. Under 100 words is a good title length.
PROBLEM: Community-ARI and inpatient-ARI was also combined with mild and severe cases of influenza from a historical prospective study as mild-ARI and severe-ARI respectively to evaluate the performance of clinical case definitions. We analysed 130 community-ARI and 140 inpatient-ARI episodes (5 inpatient-ARI excluded because multiple pathogens were detected), involving 138 and 207 samples respectively. Detection by PCR declined with days post-onset for influenza virus; decrease was faster for community-ARI than for inpatient-ARI. No such patterns were observed for noninfluenza respiratory virus infections. PathChip added substantially to viruses detected for community-ARI only. Clinical case definitions discriminated influenza from other mild-ARI but performed poorly for severe-ARI and for older participants. Rational strategies for diagnosis and surveillance of influenza and other respiratory virus must acknowledge the differences between ARIs presenting in community and hospital settings.

SOLUTION: Detection of viral respiratory pathogens in mild and severe acute respiratory infections in Singapore To investigate the performance of laboratory methods and clinical case definitions in detecting the viral pathogens for acute respiratory infections (ARIs) from a prospective community cohort and hospital inpatients, nasopharyngeal swabs from cohort members reporting ARIs (community-ARI) and inpatients admitted with ARIs (inpatient-ARI) were tested by Singleplex Real Time-Polymerase Chain Reaction (SRT-PCR), multiplex RT-PCR (MRT-PCR) and pathogen-chip system (PathChip) between OPEN

PROBLEM: A new porcine coronavirus SADS-CoV was recently identified from suckling piglets 20 with severe diarrhea in southern China and its genome sequence is most identical (~95% 21 identity) to that of bat -coronavirus HKU2. It again indicates bats are the natural 22 reservoir of many coronaviruses that have great potential for cross-species transmission 23 to animals and humans by recombination and/or mutation. Here we report the cryo-EM 24 structures of HKU2 and SADS-CoV spike glycoprotein trimers at 2.38 A and 2.83 A 25 resolution, respectively. HKU2 and SADS-CoV spikes exhibit very high structural 26 similarity, with subtle differences mainly distributed in the NTD and CTD of the S1 27 subunit responsible for cell attachment and receptor binding. We systematically 28 analyzed and compared the NTD, CTD, SD1 and SD2 domains of the S1 subunit and 29 the S2 subunit of HKU2 spike with those of -, -, -, and -coronavirus spikes. The 30 results show that the NTD and CTD of HKU2/SADS-CoV are probably the most 31 ancestral in the evolution of spike. Although the S2 subunit mediating membrane fusion 32 is highly conserved, the connecting region after fusion peptide in HKU2/SADS-CoV 33 S2 subunit also adopts a conformation distinct from other coronaviruses. These results 34 structurally demonstrate a close evolutionary relationship between HKU2 /SADS-CoV 35 and -coronavirus spikes and provide new insights into the evolution and cross-species 36 transmission of coronaviruses. : bioRxiv preprint 39 Coronaviruses, categorized into the order Nidovirales family Coronaviridae and 40 subfamily Coronavirinae, are a large group of viral pathogens with a wide host range 1 . 41 Their infections in humans, other mammals and birds can cause respiratory, hepatic, 42 enteric and neurological diseases with varying severity 2 . The severe acute respiratory 43 syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus 44 (MERS-CoV) have posed severe threats to human health in the 21 st century 1,3 . In the 45 meantime, coronaviruses infecting domestic animals also bring substantial economic 46 losses 4 . For example, the swine acute diarrhea syndrome coronavirus (SADS-CoV) 47 (also known as SeACoV and PEAV) isolated in 2017 caused outbreaks of severe watery 48 diarrhea of suckling piglets with a mortality up to 90% in several commercial pig farms 49 in Guangdong Province of China 5-10 . SADS-CoV is an -coronavirus and other 50 representative members in the -genus are porcine epidemic diarrhea virus 51 (PEDV), porcine transmissible gastroenteritis coronavirus (TGEV), porcine respiratory 52 coronavirus (PRCV), human NL63 and 229E coronaviruses (HCoV-NL63 and HCoV-53 229E) 1 . Representative members in other three genera include mouse hepatitis 54 coronavirus (MHV), bovine coronavirus (BCoV), SARS-CoV, MERS-CoV, HCoV-55 OC43 and HCoV-HKU1 in the -genus, avian infectious bronchitis virus (IBV) in the 56 -genus and porcine deltacoronavirus (PdCoV) in the -genus 1 . 57 Cross-species transmission promoted by genetic recombination and/or mutations 58 underlies the host range expansion of coronaviruses 3,11-13 . Bats are the natural reservoir 59 of more than 30 different -and -coronaviruses that have great potential for 60 interspecies transmission by recombination and/or mutation 12,14-16 . Data on genetic 61 evolution, receptor binding and pathogenesis have demonstrated that human SARS-62 CoV and MERS-CoV most likely originate from bats 1 . Palm civets and dromedary 63 camels are the intermediate hosts of SARS-CoV and MERS-CoV from bats to humans 1 , 64 respectively. The newly identified porcine SADS-CoV isolates are also found to share 65 ~95% sequence identity with Rhinolophus bat coronavirus HKU2, and this further 66 stressed the severe results of coronavirus spillover from bats to domestic animals 5-10 .

SOLUTION: Cryo-EM structures of HKU2 and SADS-CoV spike 1 glycoproteins and insights into coronavirus evolution 2 3 4

PROBLEM: Coronaviruses (CoVs) continuously threaten human health. However, to date, the evolutionary mechanisms that govern CoV strain persistence in human populations have not been fully understood. In this study, we characterized the evolution of the major antigen-spike (S) gene in the most prevalent human coronavirus (HCoV) OC43 using phylogenetic and phylodynamic analysis. Among the five known HCoV-OC43 genotypes (A to E), higher substitution rates and dN/dS values as well as more positive selection sites were detected in the S gene of genotype D, corresponding to the most dominant HCoV epidemic in recent years. Further analysis showed that the majority of substitutions were located in the S1 subunit. Among them, seven positive selection sites were chronologically traced in the temporal evolution routes of genotype D, and six were located around the critical sugar binding region in the N-terminal domain (NTD) of S protein, an important sugar binding domain of CoV. These findings suggest that the genetic drift of the S gene may play an important role in genotype persistence in human populations, providing insights into the mechanisms of HCoV-OC43 adaptive evolution. Coronaviruses (CoVs) are widely found in humans as well as in mammalian and avian species, causing asymptomatic infections or respiratory tract disorders, and gastroenteritis of varying severity 1 . CoVs belong to the genus Coronavirus of family Coronaviridae, and are classified into four genera, Alphacoronavirus ( -CoV), Betacoronavirus (-CoV), Gammacoronavirus, and Deltacoronavirus based on phylogenetics and serology 1 . To date, -CoV [including human CoV (HCoV)-229E and NL63] and -CoV [including HCoV-OC43, HKU1, Severe Acute Respiratory Syndrome CoV (SARS-CoV) and Middle East Respiratory Syndrome CoV (MERS-CoV)] are known to infect human beings 1 . Interspecies transmission is a common phenomenon for CoVs that may be responsible for generation of new CoV epidemics during viral evolution 2-5 . For instance, the feline CoV (FCoV) type II, a member of -CoV, might be generated by a double recombination between FCoV type I and canine CoV 4 . Interestingly, porcine hemagglutinating encephalomyelitis virus, bovine CoV (BCoV) and HCoV-OC43 of -CoV are thought to have evolved from the same common ancestor 5 . During evolution, high frequencies of homologous RNA recombination and gene mutations are considered the main forces that push CoVs to adapt to specific hosts. Such events can lead to emergence of new strains or genotypes within a certain species, and even to new species, causing epidemic or zoonotic outbreaks that continuously threaten human health 2,3 . This phenomenon is exemplified by the recent emergence of SARS-CoV and MERS-CoV 6,7 . However, the detailed evolutionary mechanism of interspecies transmission and the persistence of CoVs in specific hosts have yet to be fully elucidated.

SOLUTION:
Genetic drift of human coronavirus OC43 spike gene during adaptive evolution OPEN