Paula Marsland, Rupali Jain, Frank Tverdek, Paul Hendrie, Catherine Liu, Steven A Pergam, Lori Bourassa
{"title":"Ceftriaxone-resistant viridans streptococci bacteraemia among patients treated at a large comprehensive cancer care centre: a retrospective eighteen-year study.","authors":"Paula Marsland, Rupali Jain, Frank Tverdek, Paul Hendrie, Catherine Liu, Steven A Pergam, Lori Bourassa","doi":"10.1093/jacamr/dlae126","DOIUrl":"10.1093/jacamr/dlae126","url":null,"abstract":"<p><strong>Objectives: </strong>Viridans streptococci (VS) are opportunistic oral commensals and a common cause of bacteraemia in neutropenic patients. In this retrospective single centre cohort study, we investigated the prevalence of ceftriaxone resistance in VS (CRO-R VS) blood isolates between January 2005 and December 2022 from patients treated at a tertiary care hospital.</p><p><strong>Methods: </strong>Blood culture isolates were identified using biochemicals and mass spectrometry. Susceptibility testing was performed by Kirby-Bauer and Epsilometer tests. Demographic data, clinical outcomes and antimicrobial use were assessed through electronic medical record review.</p><p><strong>Results: </strong>Among 791 patients with VS bacteraemia, 31 (4%) had confirmed CRO-R VS bacteraemia over the 18-year period; 20/31 (65%) were patients also treated at the Fred Hutchinson Cancer Center and were the focus of this study. Of these 20 patients, 18 (90%) had a known haematologic malignancy; 14 (70%) had undergone haematopoietic cell transplant (HCT); 18 (90%) were neutropenic at the time of culture. Two (10%) patients died within 30 days of CRO-R VS bacteraemia. All the CRO-R isolates (20/20) were members of the <i>Streptococcus mitis</i> group, 12 were multi-drug resistant; all were susceptible to vancomycin. Most patients received vancomycin once blood cultures were positive for a Gram-positive organism.</p><p><strong>Conclusions: </strong>During the study period, the frequency of VS isolate susceptibility testing increased; however, there was no concomitant increase in the percentage of CRO-R isolates at our facility. These data are important in an era where cefepime monotherapy is often used and reinforces the importance of routine resistance testing among VS bacteraemia.</p>","PeriodicalId":14594,"journal":{"name":"JAC-Antimicrobial Resistance","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11299946/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141893412","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Does environmental microbiological surveillance support infection control in veterinary hospitals? A PRO/CON debate.","authors":"Brandy A Burgess","doi":"10.1093/jacamr/dlae115","DOIUrl":"10.1093/jacamr/dlae115","url":null,"abstract":"","PeriodicalId":14594,"journal":{"name":"JAC-Antimicrobial Resistance","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11293427/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141877269","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Guilherme Ximenes, Sajal K Saha, Helio Guterres, Adriano Vieira, Lisa Harris, Michelle Mahony, Agata Dos Santos, Lucia Toto, Elfiana Amaral, Jessie C Spargo, Sze Yen Tay, Salvador Amaral, Karen Champlin, Anthony D K Draper, Joshua R Francis, Jennifer Yan, Sarah A Lynar
{"title":"Antimicrobial prescribing in referral hospitals in Timor-Leste: results of the first two national point prevalence surveys, 2020-21.","authors":"Guilherme Ximenes, Sajal K Saha, Helio Guterres, Adriano Vieira, Lisa Harris, Michelle Mahony, Agata Dos Santos, Lucia Toto, Elfiana Amaral, Jessie C Spargo, Sze Yen Tay, Salvador Amaral, Karen Champlin, Anthony D K Draper, Joshua R Francis, Jennifer Yan, Sarah A Lynar","doi":"10.1093/jacamr/dlae123","DOIUrl":"10.1093/jacamr/dlae123","url":null,"abstract":"<p><strong>Objectives: </strong>To describe antimicrobial use (AMU) in patients admitted to hospitals in Timor-Leste.</p><p><strong>Methods: </strong>In 2020 and 2021, we undertook antimicrobial prescribing point prevalence surveys across all six hospitals in Timor-Leste (one national and five municipal) to describe AMU and appropriateness in admitted patients.</p><p><strong>Results: </strong>In 2020, 291/394 (73.9%) surveyed patients had been prescribed antimicrobials, compared with 260/403 (64.5%) in 2021 (<i>P</i> = 0.004). Most (309/551; 56.1%) were prescribed one antimicrobial, and 179/551 (32.5%) were prescribed two. The most commonly prescribed antibiotics were ceftriaxone (38.5% in 2020, 41.5% in 2021) and ampicillin (35.7% in 2020, 32.3% in 2021), followed by gentamicin, metronidazole and cloxacillin. Reserve antibiotics like meropenem and vancomycin were minimally used. Of all antimicrobial prescriptions, 70.8% were deemed appropriate in 2020 and 69.1% in 2021. Antimicrobial prescriptions for surgical and post-partum prophylaxis were frequently deemed inappropriate [37/50 (74.0%) and 39/44 (88.6%) prescriptions, respectively].</p><p><strong>Conclusions: </strong>Most patients admitted to hospital in Timor-Leste are prescribed antimicrobials, and approximately one-third of these prescriptions are inappropriate. However, this was in the context of limited local guideline availability at the time of surveys and limited microbiological culture capacity outside of the capital, Dili. Improved microbiological guidance, iterative guideline revisions based on local antimicrobial resistance (AMR) surveillance data, and enhanced stewardship activities including further point prevalence studies, could improve antimicrobial use, optimize patient outcomes and reduce AMR in Timor-Leste.</p>","PeriodicalId":14594,"journal":{"name":"JAC-Antimicrobial Resistance","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11293431/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141874819","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"PRO: Environmental microbiological surveillance does support infection control in veterinary hospitals.","authors":"Dorina Timofte, Rosanne E Jepson","doi":"10.1093/jacamr/dlae113","DOIUrl":"10.1093/jacamr/dlae113","url":null,"abstract":"","PeriodicalId":14594,"journal":{"name":"JAC-Antimicrobial Resistance","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11293430/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141877270","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Arianne Lovey, Annie Lee, Allison Yu, Mila Krel, Mingming Wang, Padmaja Paderu, Thomas Brady, Grayson Hough, Qiping Zhao, James M Balkovec, David S Perlin, Yanan Zhao
{"title":"CTC-177, a novel drug-Fc conjugate, shows promise as an immunoprophylactic agent against multidrug-resistant Gram-negative bacterial infections.","authors":"Arianne Lovey, Annie Lee, Allison Yu, Mila Krel, Mingming Wang, Padmaja Paderu, Thomas Brady, Grayson Hough, Qiping Zhao, James M Balkovec, David S Perlin, Yanan Zhao","doi":"10.1093/jacamr/dlae100","DOIUrl":"10.1093/jacamr/dlae100","url":null,"abstract":"<p><strong>Background: </strong>The widespread emergence of antibiotic resistance including MDR in Gram-negative bacterial pathogens poses a critical challenge to the current antimicrobial armamentarium.</p><p><strong>Objectives: </strong>To create a novel drug-Fc conjugate (DFC) that can be delivered at sustained and prolonged levels while simultaneously activating the host immune response to combat MDR Gram-negative infections.</p><p><strong>Methods: </strong>The Cloudbreak™ platform was used to develop DFCs consisting of a targeting moiety (TM) (a polymyxin-derived dimer) attached via a non-cleavable linker to an effector moiety (EM) (the Fc domain of human IgG1). <i>In vitro</i> activities of the DFCs were assessed by MIC testing. Neutropenic mouse models of thigh infection, septicaemia and pneumonia were used to evaluate <i>in vivo</i> efficacy. Pharmacokinetics were evaluated in mice and cynomolgus monkeys.</p><p><strong>Results: </strong>A single prophylactic dose of our lead DFC, CTC-177, resulted in significantly decreased bacterial burdens and reduced inflammation comparable to daily treatment with colistin in septicaemia and pneumonia mouse models. Furthermore, CTC-177 prophylaxis was able to restore colistin efficacy in colistin-resistant septicaemia, reducing bacterial burdens beyond the limit of detection. Finally, CTC-177 displayed a long terminal half-life of over 24 and 65 h in mice and cynomolgus monkeys, respectively.</p><p><strong>Conclusions: </strong>These data support the continued development of Cloudbreak™ DFCs as broad-spectrum prophylactic agents against Gram-negative infections.</p>","PeriodicalId":14594,"journal":{"name":"JAC-Antimicrobial Resistance","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11276960/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141788027","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"CON: Environmental microbiological surveillance does not support infection control in veterinary hospitals.","authors":"Fergus Allerton, Scott Weese","doi":"10.1093/jacamr/dlae114","DOIUrl":"10.1093/jacamr/dlae114","url":null,"abstract":"","PeriodicalId":14594,"journal":{"name":"JAC-Antimicrobial Resistance","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11261388/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141748160","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Rationalizing irrational prescribing-infection-related attitudes and practices across paediatric surgery specialties in a hospital in South India.","authors":"Surya Surendran, Vrinda Nampoothiri, Puneet Dhar, Alison Holmes, Sanjeev Singh, Esmita Charani","doi":"10.1093/jacamr/dlae105","DOIUrl":"10.1093/jacamr/dlae105","url":null,"abstract":"<p><strong>Background and objectives: </strong>Antibiotic use in paediatric surgical specialties is understudied. We investigated the antibiotic prescribing practices of paediatric general and cardiovascular surgical teams in a tertiary hospital in South India.</p><p><strong>Methods: </strong>Mixed-methods study including observations from ward rounds, semi-structured interviews, and review of antibiotic prescribing. Field notes from observations and interview transcripts were coded using NVivo and thematically analysed. Data collection and analysis were iterative and continued until thematic saturation. Quantitative data were analysed using descriptive statistics.</p><p><strong>Results: </strong>Data included 62 h of observation, 24 interviews, one case study and 200 patient chart reviews (100/specialty). Senior surgeons make key decisions, referring to their own experience when prescribing antibiotics. Being outcome-driven, the doctors often prescribe antibiotics at the earliest indication of infection with a reluctance to de-escalate, even when an infection is not diagnosed. This practice is more acute among surgeons who consider themselves responsible for their patients' health and attribute the consistently low surgical site infection rates to this practice.In general surgery, 83.3% (80/96; 4 lost to follow-up) of patients were prescribed antibiotics for the duration of their stay with oral antibiotics prescribed at discharge. The surgeons use antibiotics prophylactically for patients who may be vulnerable to infection. The antimicrobial stewardship team was considered to have limited influence in the decision-making process.</p><p><strong>Conclusions: </strong>Outcome-driven decision-making in surgery leads to overprescription of antibiotics and prolonged surgical prophylaxis. The rationale for suboptimal practices is complicated by the surgeons' beliefs about the contextual determinants of health in India.</p>","PeriodicalId":14594,"journal":{"name":"JAC-Antimicrobial Resistance","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-07-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11245696/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141616397","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
M. Attwood, Pippa Griffins, Alan Noel, Theo Josephs, Karen Adler, Martha Clokie, A. MacGowan
{"title":"Development of antibacterial drug + bacteriophage combination assays","authors":"M. Attwood, Pippa Griffins, Alan Noel, Theo Josephs, Karen Adler, Martha Clokie, A. MacGowan","doi":"10.1093/jacamr/dlae104","DOIUrl":"https://doi.org/10.1093/jacamr/dlae104","url":null,"abstract":"\u0000 \u0000 \u0000 The best methods to study the interactions between phages and antibacterials are unclear. As laboratory methodologies used to assess conventional antibacterials are established, we assessed their ability to evaluate phage plus antibacterial.\u0000 \u0000 \u0000 \u0000 The efficacy of three characterized Escherichia coli phages (UP17, JK08, 113) were tested on a 100 MDR E coli. strains. The phages were assessed individually and in a 1:1:1 cocktail. In a phage microbial inhibitory concentration (PmIC) assay, a range of phage concentrations from 101 to 108 were inoculated with 5 × 105 bacteria/well in 96-well microtitre plates. The first fully lysed well was taken as the PmIC. Amikacin and meropenem MICs were determined by ISO 2776-1:2019 methods alone and in combination with a fixed phage concentration of 105/per well. Time–kill curves (TKCs) were conducted at fosfomycin concentrations of 133, 50 and 5 mg/L, with and without phage.\u0000 \u0000 \u0000 \u0000 The PmIC50/90 values, in plaque-forming units (pfu)/mL, for individual phage titre were >108/>108 for UP17, 107/>108 for JK08, 107/>108 for 113 and 106/>108 for the 1:1:1 phage cocktail, all with a standard deviation (SD) of <0.05. Amikacin and meropenem MIC50/90 (SD) values were 2/8 mg/L (<0.05–9.2) and 0.12/8 mg/L (<0.05–8.7), respectively. The addition of UP17 to amikacin increased amikacin MICs >2-fold in 78 strains, with equivalent trends in 39 strains with JK08, 54 strains with 113 and 45 strains with phage cocktail. Meropenem MICs in the presence of phage were reduced >2-fold in 24 strains with UP17. Equivalent decreases were seen with 34 strains with JK08, 26 strains with 113 and 29 strains with the cocktail. In TKCs, the addition of phage suppressed regrowth.\u0000 \u0000 \u0000 \u0000 Microbroth methodologies based on ISO 2776-1:2019 lend themselves to be viable options for phage assessment, alone or in combination with antibiotics. The reproducibility of PmIC and familiarity of the methodology described allows for laboratory validation for phage and antibiotic combinations.\u0000","PeriodicalId":14594,"journal":{"name":"JAC-Antimicrobial Resistance","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141683543","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Ceftaroline in CNS and ocular infections: a case series.","authors":"Emily A Siegrist, Joseph Sassine","doi":"10.1093/jacamr/dlae095","DOIUrl":"https://doi.org/10.1093/jacamr/dlae095","url":null,"abstract":"<p><strong>Background: </strong>There are limited data describing outcomes of patients treated with ceftaroline for infections with CNS or ocular involvement.</p><p><strong>Objectives: </strong>To describe outcomes of patients treated with ceftaroline for methicillin-resistant staphylococcal infections involving the CNS or eye.</p><p><strong>Patients and methods: </strong>This was a retrospective review of 10 patients at an academic medical centre who received ceftaroline for CNS or ocular infections.</p><p><strong>Results: </strong>All patients were treated with ceftaroline as part of a combination for salvage therapy. Four patients died, whereas six patients experienced clinical cure. Only one experienced microbiological recurrence.</p><p><strong>Conclusions: </strong>These preliminary data suggest that ceftaroline may be an option for salvage therapy of severe staphylococcal infections when used in combination.</p>","PeriodicalId":14594,"journal":{"name":"JAC-Antimicrobial Resistance","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11180797/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141419127","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
María García-Castillo, Marta Hernández-García, Adriana Correa, Marco Coppi, Thomas Griener, Thomas Fritsche, Cristina Pitart, Jorge Sampaio, Harald Seifert, Karen Wake, Mandy Wootton, Jordi Vila, Rafael Cantón
{"title":"<i>In vitro</i> activity of ozenoxacin against <i>Staphylococcus aureus</i> and <i>Streptococcus pyogenes</i> clinical isolates recovered in a worldwide multicentre study (2020-2022).","authors":"María García-Castillo, Marta Hernández-García, Adriana Correa, Marco Coppi, Thomas Griener, Thomas Fritsche, Cristina Pitart, Jorge Sampaio, Harald Seifert, Karen Wake, Mandy Wootton, Jordi Vila, Rafael Cantón","doi":"10.1093/jacamr/dlae088","DOIUrl":"10.1093/jacamr/dlae088","url":null,"abstract":"<p><strong>Objectives: </strong>We performed a multicentre study (2020-2022) to compare the <i>in vitro</i> activity of ozenoxacin and comparator agents against <i>Staphylococcus aureus</i> and <i>Streptococcus pyogenes</i> clinical isolates from skin and soft-tissue infections (SSTI).</p><p><strong>Methods: </strong>A total of 1725 isolates (1454 <i>S. aureus</i> and 271 <i>S. pyogenes</i>) were collected in 10 centres from eight countries between January 2020 and December 2022. Antimicrobial susceptibility testing was determined (microdilution-SENSITITRE). Results were interpreted following European Committee on Antimicrobial Susceptibility Testing (EUCAST) 2023 (clinical breakpoints, ECOFF) and CLSI criteria.</p><p><strong>Results: </strong>Ozenoxacin exhibited high <i>in vitro</i> activity against <i>S. aureus</i> (MIC<sub>50/90</sub> = 0.002/0.12 mg/L) and <i>S. pyogenes</i> (MIC<sub>50/90</sub> = 0.015/0.03 mg/L), inhibiting 99% of the isolates at MIC ≤ 0.5 mg/L and at MIC ≤ 0.06, respectively. The most active comparators against <i>S. aureus</i> were retapamulin (MIC<sub>90</sub> = 0.12 mg/L), fusidic acid (MIC<sub>90</sub> = 0.25 mg/L) and mupirocin (MIC<sub>90</sub> = 0.5 mg/L); and against <i>S. pyogenes</i> were retapamulin (MIC<sub>90</sub> = 0.03 mg/L), clindamycin (MIC<sub>90</sub> = 0.12 mg/L) and mupirocin (MIC<sub>90</sub> = 0.25 mg/L). Ciprofloxacin and methicillin resistant rates for <i>S. aureus</i> were 31.3% (455/1454) and 41% (598/1454), respectively. Additionally, 62% (373/598) of the MRSA were also ciprofloxacin non-susceptible, whereas only 10% (23/271) of the MSSA were ciprofloxacin resistant. Ozenoxacin was more active against ciprofloxacin-susceptible <i>S. aureus</i> than against ciprofloxacin-resistant isolates, and showed a slightly higher MIC in MRSA isolates than in MSSA. However, ozenoxacin activity was comparable in both ciprofloxacin-resistant MSSA and MRSA subsets. On the other hand, ozenoxacin had similar activity in ciprofloxacin-susceptible and resistant <i>S. pyogenes</i> isolates.</p><p><strong>Conclusions: </strong>Ozenoxacin is a potent antimicrobial agent of topic use against Gram-positive bacteria causing SSTI, including MRSA isolates non-susceptible to ciprofloxacin.</p>","PeriodicalId":14594,"journal":{"name":"JAC-Antimicrobial Resistance","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11170484/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141317356","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}