[Show abstract][Hide abstract] ABSTRACT: Clostridium difficile ribotype 002 with hypersporulating capacity has been increasingly identified in Hong Kong. Proactive infection control measures are important to prevent the establishment of endemicity of C. difficile ribotype 002. A total of 329 patients with healthcare-associated C. difficile infection (CDI) were recruited in our healthcare network between 1 January 2008 and 30 June 2012 in this study. The incidence rates of healthcare-associated CDI per 10,000 admissions and 10,000 patient-days increased significantly by 15.3 and 17.0 %, respectively, per quarter (p < 0.001) from 2008 1Q to 2010 1Q by segmented Poisson regression. With the full implementation of enhanced infection control interventions, there was an immediate significant reduction in both healthcare-associated CDI rates per 10,000 admissions and per 10,000 patient-days by 47 % (p < 0.001) in 2010 2Q, followed by a further decline of CDI per 10,000 admissions and CDI per 10,000 patient-days by -19.4 and -19.8 % from 2010 2Q to 2012 2Q, respectively (p < 0.001), despite a replacement of hand washing with soap and water by alcohol-based hand rub in the healthcare network. The proportion of C. difficile ribotype 002 was not statistically different (34/177, 19.2 % vs. 25/152, 16.4 %, p = 0.515), and the consumption of broad-spectrum antibiotics presented as divided daily dose per 1,000 acute bed-day occupancy per quarter remained unchanged (140.9 vs. 152.3) before and after infection control interventions. Our results suggested that the reduction of healthcare-associated CDI was attributable to infection control interventions instead of replacement of ribotypes or reduction in antimicrobial selective pressure.
European Journal of Clinical Microbiology 03/2015; 34(7). DOI:10.1007/s10096-015-2362-5 · 2.67 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: OBJECTIVE To assess the effectiveness of infection control preparedness for human infection with influenza A H7N9 in Hong Kong. DESIGN A descriptive study of responses to the emergence of influenza A H7N9. SETTING A university-affiliated teaching hospital. PARTICIPANTS Healthcare workers (HCWs) with unprotected exposure (not wearing N95 respirator during aerosol-generating procedure) to a patient with influenza A H7N9. METHODS A bundle approach including active and enhanced surveillance, early airborne infection isolation, rapid molecular diagnostic testing, and extensive contact tracing for HCWs with unprotected exposure was implemented. Seventy HCWs with unprotected exposure to an index case were interviewed especially regarding their patient care activities. RESULTS From April 1, 2013, through May 31, 2014, a total of 126 (0.08%) of 163,456 admitted patients were tested for the H7 gene by reverse transcription-polymerase chain reaction per protocol. Two confirmed cases were identified. Seventy (53.8%) of 130 HCWs had unprotected exposure to an index case, whereas 41 (58.6%) and 58 (82.9%) of 70 HCWs wore surgical masks and practiced hand hygiene after patient care, respectively. Sixteen (22.9%) of 70 HCWs were involved in high-risk patient contacts. More HCWs with high-risk patient contacts received oseltamivir prophylaxis (P=0.088) and significantly more had paired sera collected for H7 antibody testing (P<0.001). Ten (14.3%) of 70 HCWs developed influenza-like illness during medical surveillance, but none had positive results by reverse transcription-polymerase chain reaction. Paired sera was available from 33 of 70 HCWs with unprotected exposure, and none showed seroconversion against H7N9. CONCLUSIONS Despite the delay in airborne precautions implementation, no patient-to-HCW transmission of influenza A H7N9 was demonstrated. Infect Control Hosp Epidemiol 2015;36(1): 87-92.
Infection Control and Hospital Epidemiology 01/2015; 36(1):87-92. DOI:10.1017/ice.2014.2 · 3.94 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: An increasing endemicity of multiple-drug-resistant Acinetobacter baumannii (MRAB) ST457 was noted in Hong Kong. The epidemiology, risk factors, and infection control measures to prevent nosocomial transmission of this epidemic clone were analyzed. A total of 5,058 patients cultured positive with A. baumannii between 1 January 2004 and 30 June 2014 were included, of which 297 (5.9 %) had bacteremia. The first case of MRAB bacteremia emerged in 2009, with an incidence that increased from 0.27 (one case) in 2009 to 1.86 (14 cases) per 100,000 patient-days in 2013 (p < 0.001). With the implementation of strict contact precautions and directly observed hand hygiene in conscious patients immediately before receiving meals and medications in July 2013, the incidence of MRAB bacteremia reduced from its peak to 0.77 (one case) per 100,000 patient-days in the first 6 months of 2014 (p < 0.001). Patients from long-term care facilities for the elderly [odds ratio (OR) 18.6, confidence interval (CI) 2.1-162.4, p = 0.008] and history of carbapenem (OR 7.0, CI 1.7-28.0, p = 0.006) and beta-lactam/beta-lactamase use (OR 5.6, CI 1.1-28.7, p = 0.038) 90 days prior to admission were independent risk factors for MRAB bacteremia by logistic regression when compared with carbapenem-susceptible A. baumannii bacteremia.
European Journal of Clinical Microbiology 11/2014; 34(4). DOI:10.1007/s10096-014-2281-x · 2.67 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Quantitative polymerase chain reaction on nasopharyngeal aspirate (NPA) can achieve high sensitivity and specificity in diagnosing Pneumocystis pneumonia (PCP) when compared to microscopic examination of bronchoscopic specimens in a population with low HIV prevalence. Since NPA is a minimally invasive procedure, it is ideal as a screening test for PCP.
[Show abstract][Hide abstract] ABSTRACT: Pneumocystis colonization has been associated with airway inflammation and obstruction. We conducted a retrospective cohort study to investigate the clinical significance of Pneumocystis in the airway of patients with active tuberculosis. Of the 108 respiratory specimens tested positive for M. tuberculosis by polymerase chain reaction (PCR), 11 (10.2%) were also positive for Pneumocystis by PCR. Compared with patients tested negative for Pneumocystis, those with Pneumocystis had a higher serum alanine transaminase level, a greater likelihood of requiring oxygen supplementation, and a worse 30-day mortality. The proportion of patients with chronic obstructive pulmonary disease was not significantly different between the 2 groups, but lung malignancy was more prevalent among patients with Pneumocystis. Multivariate analysis showed that Pneumocystis was independently associated with oxygen supplementation. Our study has shown an association between the detection of Pneumocystis in lower respiratory tract specimens and greater impairment of pulmonary function among patients with active tuberculosis.
[Show abstract][Hide abstract] ABSTRACT: Although coronaviruses are known to infect various animals by adapting to new hosts, interspecies transmission events are still poorly understood. During a surveillance study from 2005 to 2010, a novel alphacoronavirus, BatCoV HKU10, was detected in two very different bat species, Ro-BatCoV HKU10 in Leschenault's rousettes (Rousettus leschenaulti) (fruit bats in the suborder Megachiroptera) in Guangdong and Hi-BatCoV HKU10 in Pomona leaf-nosed bats (Hipposideros pomona) (insectivorous bats in the suborder Microchiroptera) in Hong Kong. Although infected bats appeared to be healthy, Pomona leaf-nosed bats carrying Hi-BatCoV HKU10 had lower body weights than uninfected bats. To investigate possible interspecies transmission between the two bat species, the complete genomes of two Ro-BatCoV HKU10 and six Hi-BatCoV HKU10 strains were sequenced. Genome and phylogenetic analyses showed that Ro-BatCoV HKU10 and Hi-BatCoV HKU10 represented a novel alphacoronavirus species, sharing highly similar genomes except in the genes encoding spike proteins, which had only 60.5% amino acid identities. Evolution of the spike protein was also rapid in Hi-BatCoV HKU10 strains from 2005 to 2006 but stabilized thereafter. Molecular-clock analysis dated the most recent common ancestor of all BatCoV HKU10 strains to 1959 (highest posterior density regions at 95% [HPDs], 1886 to 2002) and that of Hi-BatCoV HKU10 to 1986 (HPDs, 1956 to 2004). The data suggested recent interspecies transmission from Leschenault's rousettes to Pomona leaf-nosed bats in southern China. Notably, the rapid adaptive genetic change in BatCoV HKU10 spike protein by ∼40% amino acid divergence after recent interspecies transmission was even greater than the ∼20% amino acid divergence between spike proteins of severe acute respiratory syndrome-related Rhinolophus bat coronavirus (SARSr-CoV) in bats and civets. This study provided the first evidence for interspecies transmission of coronavirus between bats of different suborders.
Journal of Virology 08/2012; 86(21):11906-18. DOI:10.1128/JVI.01305-12 · 4.65 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Dirofilariasis is globally the commonest manifestation of zoonotic filariasis. We report the detection of a novel canine species causing human and canine dirofilariasis in Hong Kong. Three human cases occurring over 10 months were identified, one presenting with cervical lymphadenopathy, one with an abdominal subcutaneous mass, and one with a subconjunctival nodule. Transected worms recovered from the resected abdominal subcutaneous mass were morphologically compatible with Dirofilaria. The cox1 gene sequences of the three human isolates were identical; however, they were only 96.2% and 89.3% identical to the cox1 gene of Dirofilaria repens and Dirofilaria immitis, respectively. Sequencing of the 18S-ITS1-5.8S gene cluster was successful in the intact worm, and the nucleotide sequences were 94.0% and 94.9% identical to those of D. repens and D. immitis, respectively. Screening of the blood samples from 200 dogs and 100 cats showed the presence of the novel Dirofilaria species in 3% (6/200) of the dogs' but none of the cats' blood samples. Nucleotide sequences of the cox1 gene and 18S-ITS1-5.8S gene clusters of the dogs' samples were identical to those in the human samples. The sera of canines infected by this novel Dirofilaria species were negative when tested with the SNAP 4Dx D. immitis detection kit, except in the case of dogs with a mixed infection with D. immitis as detected by PCR. The results from this study suggest that this novel Dirofilaria species is a cause of filarial infection in humans and dogs in Hong Kong. We propose to name this Dirofilaria species "Candidatus Dirofilaria hongkongensis."
[Show abstract][Hide abstract] ABSTRACT: Intraerythrocytic Babesia-like trophozoites were seen in postmortem kidney sections of a free-roaming cat in Hong Kong. DNA sequences of the 18S rRNA and mitochondrial cytochrome b genes had only 96.7% and 90.4% nucleotide identity with known Babesia sequences. We propose that this new species be named Babesia hongkongensis.
[Show abstract][Hide abstract] ABSTRACT: The newly described brittle tail syndrome causes weakening and breakage of the tail hair of horses. Extensive mycological and molecular studies showed that a novel fungus Equicapillimyces hongkongensis gen. nov., sp. nov. is the most likely cause of this syndrome. It is a septate branching hyaline mould which grows optimally at 30°C, requires nicotinic acid but is inhibited by cycloheximide, and specifically infects horse hair. Hyphae fill the core of infected hair shafts with short-necked structures resembling ascomata containing banana-shaped septate ascospore-like structures perforating the hair cortex from within. Compared to asymptomatic horses (n=31), horses with clinical signs of the syndrome (n=22) are significantly more likely to have positive E. hongkongensis gen. nov., sp. nov. smear (6.5% vs. 100%), culture (6.5% vs. 72.7%), and PCR (32.3% vs. 100%, P<0.001 for all). No other potential pathogens were found on bacteriological and mycological culture or PCR (for Trichophyton, Microsporum and Epidermophyton). Genotyping of pure E. hongkongensis gen. nov., sp. nov. isolates and their corresponding direct specimens by PCR and sequencing of the 18S rRNA, ITS1-5.8S-ITS2, 28S rRNA, beta-actin, beta-tubulin, and elongation factor 1 alpha showed that they are all identical but unique, and related distantly to fungi mostly in the class Sordariomycetes and the family Ophiostomataceae. Its geographical distribution, environmental or animal reservoirs are still unknown. Besides the ugly appearance of infected horse tails, this fungus may emerge as another equine pathogen if it affects the skin and hoof of horses.
[Show abstract][Hide abstract] ABSTRACT: We discovered a novel paramyxovirus, Tailam virus, of subfamily Paramyxovirinae, in the kidneys and spleens of Sikkim rats. The coding potential of its genome (3'-N-P/V/C-M-F-SH-TM-G-L-5') is similar to those of Beilong virus and J virus, with putative proteins having 59.1 to 94.4% and 23.8 to 80.1% amino acid identities to those of Beilong virus and J virus, respectively.
Journal of Virology 12/2011; 85(24):13473-4. DOI:10.1128/JVI.06356-11 · 4.65 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: There are no comprehensive studies on the performance of commonly used point-of-care diagnostic enzyme immunoassay for common arthropod-borne canine pathogens. A comparative evaluation of an immunochromatographic test for these infections with a comprehensive polymerase chain reaction (PCR) test panel was performed on 100 pet dogs and 100 stray dogs without obvious clinical symptoms. Of the 162 positive test results from both immunochromatographic test and PCR, there was 85.2% concordance. The 24 discordant results between serology and PCR occurred in tests involving Ehrlichia canis (14) and Anaplasma platys (10), which may be related to the time of infection. No positive cases of borreliosis or rickettsiosis were detected. One important limitation of the immunochromatographic test was its lack of testing for babesiosis and hepatozoonosis. The former is the most prevalent arthropod-borne canine infection in our cohort (41%). Coinfections were found in 19% stray dogs and 6% of pet dogs with both tests (p < 0.01). Seventeen and 8 samples from stray and pet dogs, respectively, were initially positive in the PCR test for Ehrlichia. However, on sequencing of the PCR amplicon, 10 from stray and 2 from pet dogs were found to be Wolbachia sequences instead, with 100% nucleotide identity to the 16S rRNA sequence of Wolbachia endosymbiont of Dirofilaria immitis. The presence of Wolbachia DNAemia (6%) correlated well with the molecular test and immunochromatographic antigen test for D. immitis.
[Show abstract][Hide abstract] ABSTRACT: Rousettus bat coronavirus HKU9 (Ro-BatCoV HKU9), a recently identified coronavirus of novel Betacoronavirus subgroup D, from Leschenault's rousette, was previously found to display marked sequence polymorphism among genomes of four strains. Among 10 bats with complete RNA-dependent RNA polymerase (RdRp), spike (S), and nucleocapsid (N) genes sequenced, three and two sequence clades for all three genes were codetected in two and five bats, respectively, suggesting the coexistence of two or three distinct genotypes of Ro-BatCoV HKU9 in the same bat. Complete genome sequencing of the distinct genotypes from two bats, using degenerate/genome-specific primers with overlapping sequences confirmed by specific PCR, supported the coexistence of at least two distinct genomes in each bat. Recombination analysis using eight Ro-BatCoV HKU9 genomes showed possible recombination events between strains from different bat individuals, which may have allowed for the generation of different genotypes. Western blot assays using recombinant N proteins of Ro-BatCoV HKU9, Betacoronavirus subgroup A (HCoV-HKU1), subgroup B (SARSr-Rh-BatCoV), and subgroup C (Ty-BatCoV HKU4 and Pi-BatCoV HKU5) coronaviruses were subgroup specific, supporting their classification as separate subgroups under Betacoronavirus. Antibodies were detected in 75 (43%) of 175 and 224 (64%) of 350 tested serum samples from Leschenault's rousette bats by Ro-BatCoV HKU9 N-protein-based Western blot and enzyme immunoassays, respectively. This is the first report describing coinfection of different coronavirus genotypes in bats and coronavirus genotypes of diverse nucleotide variation in the same host. Such unique phenomena, and the unusual instability of ORF7a, are likely due to recombination which may have been facilitated by the dense roosting behavior and long foraging range of Leschenault's rousette.
Journal of Virology 11/2010; 84(21):11385-94. DOI:10.1128/JVI.01121-10 · 4.65 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: In this territory-wide molecular epidemiology study of picornaviruses, involving 6765 dead wild birds from 201 species in 50 families over a 12 month period, three novel picornaviruses, turdiviruses 1, 2 and 3 (TV1, TV2 and TV3), were identified from birds of different genera in the family Turdidae. In contrast to many other viruses in birds of the family Turdidae or viruses of the family Picornaviridae, TV1, TV2 and TV3 were found exclusively in the autumn and winter months. Two genomes each of TV1, TV2 and TV3 were sequenced. Regions P1, P2 and P3 of the three turdiviruses possessed, respectively, <40, <40 and <50 % amino acid identities with those of other picornaviruses. Moreover, P1, P2 and P3 of TV1 also possessed, respectively, <40, <40 and <50 % amino acid identities with those of TV2 and TV3. Phylogenetic analysis revealed that TV1, TV2 and TV3 were distantly related to members of the genus Kobuvirus. Among the three turdiviruses, TV2 and TV3 were always clustered together, with high bootstrap supports of 1000. The genomic features of TV2 and TV3 were also distinct from TV1, including lower G+C contents, shorter leader protein and a preference for codon sequence NNT rather than NNC for amino acids that can use either NNT or NNC as codons (P<0.001 by χ(2)-test). Based on our results we propose two novel genera, Orthoturdivirus for TV1, and Paraturdivirus for TV2 and TV3, in the family Picornaviridae. The type of internal ribosomal entry site for TV1, TV2 and TV3 remains to be determined.
Journal of General Virology 10/2010; 91(Pt 10):2433-48. DOI:10.1099/vir.0.021717-0 · 3.53 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Among 489 bats of 11 species in China, three novel paramyxoviruses [Tuhokovirus 1, 2 and 3 (ThkPV-1, ThkPV-2 and ThkPV-3)] were discovered in 15 Leschenault's rousettes. Phylogenetically, the three viruses are most closely related to Menangle and Tioman virus. Genome analysis showed that their 3'-leader sequences are unique by possessing GA instead of AG at the 5th and 6th positions. Unlike Menangle and Tioman virus, key amino acids for neuraminidase activity characteristic of rubulavirus attachment proteins are present. The genome of ThkPV-1 represents the largest rubulavirus genome. Unique features between the three viruses include perfect complementary 5'-trailer and 3'-leader sequence and a unique cysteine pair in attachment protein of ThkPV-1, G at +1 position in all predicted mRNA sequences of ThkPV-2, and amino acid substitutions in the conserved N-terminal motif of nucleocapsid of ThkPV-3. Analysis of phosphoprotein gene mRNA products confirmed mRNA editing. Antibodies to the viruses were detected in 48-60% of Leschenault's rousettes.
[Show abstract][Hide abstract] ABSTRACT: To determine the antibiotic susceptibility patterns of 60 strains of Laribacter hongkongensis isolated from humans and fish to eight antibiotics and compare the results obtained from broth microdilution, Etest and disc diffusion susceptibility testing.
The susceptibilities of 60 isolates of L. hongkongensis from humans with gastroenteritis and fish to eight antibiotics were tested by three methods [broth microdilution (reference method), Etest and disc diffusion] and their results were compared.
All isolates were susceptible to imipenem and ciprofloxacin by all three methods, except for one strain which was resistant to ciprofloxacin by broth microdilution. All were susceptible to ampicillin/sulbactam by Etest and disc diffusion, but eight were resistant by broth microdilution. By broth microdilution, 90%, 100%, 46.7%, 100% and 8.3% of isolates were resistant to ampicillin, ceftriaxone, cefuroxime, erythromycin and tetracycline, respectively. Although broth microdilution generally yielded higher MICs of beta-lactams, MICs obtained with Etest were in good correlation with broth microdilution for all drugs except ampicillin/sulbactam, with >90% agreement within 2 log(2) dilutions for imipenem, ciprofloxacin, erythromycin and tetracycline. Comparison of susceptibilities between broth microdilution and the other two methods showed the highest (>95%) percentage agreement for imipenem, ciprofloxacin and tetracycline. The highest discrepancies were observed with erythromycin (58.3% agreement), with an apparent increase in susceptibility by disc diffusion. A higher proportion of human isolates than fish isolates were tetracycline-resistant by all three tests (P=0.022).
Etest and disc diffusion appear to be reliable for evaluation of susceptibilities of L. hongkongensis to imipenem, ciprofloxacin and tetracycline. However, these methods may underestimate resistance to other beta-lactams.
[Show abstract][Hide abstract] ABSTRACT: Twelve complete genomes of three novel coronaviruses-bat coronavirus HKU4 (bat-CoV HKU4), bat-CoV HKU5 (putative group 2c), and bat-CoV HKU9 (putative group 2d)-were sequenced. Comparative genome analysis showed that the various open reading frames (ORFs) of the genomes of the three coronaviruses had significantly higher amino acid identities to those of other group 2 coronaviruses than group 1 and 3 coronaviruses. Phylogenetic trees constructed using chymotrypsin-like protease, RNA-dependent RNA polymerase, helicase, spike, and nucleocapsid all showed that the group 2a and 2b and putative group 2c and 2d coronaviruses are more closely related to each other than to group 1 and 3 coronaviruses. Unique genomic features distinguishing between these four subgroups, including the number of papain-like proteases, the presence or absence of hemagglutinin esterase, small ORFs between the membrane and nucleocapsid genes and ORFs (NS7a and NS7b), bulged stem-loop and pseudoknot structures downstream of the nucleocapsid gene, transcription regulatory sequence, and ribosomal recognition signal for the envelope gene, were also observed. This is the first time that NS7a and NS7b downstream of the nucleocapsid gene has been found in a group 2 coronavirus. The high Ka/Ks ratio of NS7a and NS7b in bat-CoV HKU9 implies that these two group 2d-specific genes are under high selective pressure and hence are rapidly evolving. The four subgroups of group 2 coronaviruses probably originated from a common ancestor. Further molecular epidemiological studies on coronaviruses in the bats of other countries, as well as in other animals, and complete genome sequencing will shed more light on coronavirus diversity and their evolutionary histories.
Journal of Virology 03/2007; 81(4):1574-85. DOI:10.1128/JVI.02182-06 · 4.65 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The existence of coronaviruses in bats is unknown until the recent discovery of bat-SARS-CoV in Chinese horseshoe bats and a novel group 1 coronavirus in other bat species. Among 309 bats of 13 species captured from 20 different locations in rural areas of Hong Kong over a 16-month period, coronaviruses were amplified from anal swabs of 37 (12%) bats by RT-PCR. Phylogenetic analysis of RNA-dependent-RNA-polymerase (pol) and helicase genes revealed six novel coronaviruses from six different bat species, in addition to the two previously described coronaviruses. Among the six novel coronaviruses, four were group 1 coronaviruses (bat-CoV HKU2 from Chinese horseshoe bat, bat-CoV HKU6 from rickett's big-footed bat, bat-CoV HKU7 from greater bent-winged bat and bat-CoV HKU8 from lesser bent-winged bat) and two were group 2 coronaviruses (bat-CoV HKU4 from lesser bamboo bats and bat-CoV HKU5 from Japanese pipistrelles). An astonishing diversity of coronaviruses was observed in bats.
[Show abstract][Hide abstract] ABSTRACT: Recently, we described the discovery of a novel group 2 coronavirus, coronavirus HKU1 (CoV-HKU1), from a patient with pneumonia. However, the clinical and molecular epidemiological features of CoV-HKU1-associated pneumonia are unknown.
Prospectively collected (during a 12-month period) nasopharyngeal aspirates (NPAs) from patients with community-acquired pneumonia from 4 hospitals were subjected to reverse-transcription polymerase chain reaction, for detection of CoV-HKU1. The epidemiological, clinical, and laboratory characteristics of patients with CoV-HKU1-associated pneumonia were analyzed. The pol, spike (S), and nucleocapsid (N) genes were also sequenced.
NPAs from 10 (2.4%) of 418 patients with community-acquired pneumonia were found to be positive for CoV-HKU1. All 10 cases occurred in spring and winter. Nine of these patients were adults, and 4 had underlying diseases of the respiratory tract. In the 6 patients from whom serum samples were available, all had a 4-fold change in immunoglobulin (Ig) G titer and/or presence of IgM against CoV-HKU1. The 2 patients who died had significantly lower hemoglobin levels, monocyte counts, albumin levels, and oxygen saturation levels on admission and had more-extensive involvement visible on chest radiographs. Sequence analysis of the pol, S, and N genes revealed 2 genotypes of CoV-HKU1.
CoV-HKU1 accounts for 2.4% of community-acquired pneumonia, with 2 genotypes in the study population. Without performance of diagnostic tests, the illness was clinically indistinguishable from other community-acquired pneumonia illnesses.
The Journal of Infectious Diseases 01/2006; 192(11):1898-907. DOI:10.1086/497151 · 5.78 Impact Factor