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ACE Score Identifies HBeAg-negative Inactive Carriers at a Single-point Evaluation,Regardless of HBV Genotype

Journal of Clinical and Translational Hepatology 2022年第6期10卷 1068-1076页

作者： Luisa Roade Mar Riveiro-Barciela Adriana Palom francisco rodríguez-frías Marta Bes Ariadna Rando María Teresa Salcedo Rosario Casillas Elena Vargas-Accarino David Tabernero Silvia Sauleda Rafael Esteban María Buti Liver Unit Internal Medicine DepartmentHospital Universitari Vall d’HebronVall d’Hebron Barcelona Hospital CampusBarcelonaSpain Universitat Autònoma de Barcelona(UAB) Department of MedicineBarcelonaSpain Universitat Au-tònoma de Barcelona(UAB) Department of Biochemistry and Molecular BiologyBarcelonaSpain Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas(CIBERehd) Instituto de Salud Carlos IIIMadridSpain Liver Pathology Lab Biochemistry and Microbiology Departments(Clinical Laboratories)Hospital Universitari Vall d’HebronVall d’Hebron Barcelona Hospital CampusBarcelonaSpain Vall d’Hebron Institut de Recerca(VHIR) Liver Diseases GroupBarcelonaSpain Transfusion Safety Laboratory Banc de Sang i TeixitsServei Catalàde la SalutBarcelonaSpain De-partment of Pathology Hospital Universitari Vall d’HebronUniversitat Autònoma de BarcelonaBarcelonaSpain

Background and Aims:Hepatitis B virus(HBV)biomark-ers have been used for a better categorization of patients,even though the lack of simple algorithms and the impact of genotypes limit their application.Our aim was to assess the usefulness of noninvasive markers for the identification of HBV inactive carriers(ICs)in a single-point evaluation and to design a predictive model for their identification.Meth-ods:This retrospective-prospective study included 343 consecutive HBeAg-negative individuals.Clinical,analytical,and virological data were collected,and a liver biopsy was performed if needed.Subjects were classified at the end of follow-up as ICs,chronic hepatitis B and gray zone.A pre-dictive model was constructed,and validated by 1000-boot-strap samples.Results:After 39 months of follow-up,298 subjects were ICs,36 were chronic hepatitis B CHB,and nine were gray zone.Eighty-nine(25.9%)individuals re-quired a liver biopsy.Baseline HBV DNA hazard ratio(HR)6.0,p<0.001),HBV core-related antigen(HBcrAg)(HR 6.5,p<0.001),and elastography(HR 4.6,p<0.001)were inde-pendently associated with the IC stage.The ACE score(HBV DNA,HBcrAg,elastography),obtained by bootstrapping,yielded an area under the receiver operating characteris-tics(AUROC)of 0.925(95%CI:0.880-0.970,p<0.001)for identification of ICs.The AUROC for genotype D was 0.95,0.96 for A,0.90 for E,and 0.88 for H/F.An ACE score of<1 had a positive predictive value of 99.5%,and a score≤12 points had a diagnostic accuracy of 93.8%.Conclusions:Low baseline HBV DNA,HBcrAg,and liver stiffness were in-dependently associated with the IC phase.A score including those variables identified ICs at a single-point evaluation,and might be applied to implement less intensive follow-up strategies.

关键词： Hepatitis B virus Inactive carrier Liver stiffness HBV DNA Quan-titative HBsAg Core-related antigen.

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Analysis of hepatitis B virus preS1 variability and prevalence of the rs2296651 polymorphism in a Spanish population

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World Journal of Gastroenterology 2018年第6期24卷 680-692页

作者： Rosario Casillas David Tabernero Josep Gregori Irene Belmonte Maria francesca Cortese Carolina González Mar Riveiro-Barciela Rosa Maria López Josep Quer Rafael Esteban Maria Buti francisco rodríguez-frías Liver Pathology Unit Departments of Biochemistry and MicrobiologyHospital Universitari Vall d’HebronUniversitat Autònoma de BarcelonaBarcelona 08035Spain Liver Unit Liver Disease Laboratory-Viral HepatitisVall d’Hebron Institut Recerca-Hospital Universitari Vall d’HebronUniversitat Autònoma de BarcelonaBarcelona 08035Spain Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas(CIBERehd) Instituto de Salud Carlos IIIMadrid 28029Spain Roche Diagnostics SL Sant Cugat del Vallès 08174Spain Liver Unit Department of Internal MedicineHospital Universitari Vall d'HebronUniversitat Autònoma de BarcelonaBarcelona 08035Spain

AIM To determine the variability/conservation of the domain of hepatitis B virus(HBV) pre S1 region that interacts with sodium-taurocholate cotransporting polypeptide(hereafter, NTCP-interacting domain) and the prevalence of the rs2296651 polymorphism(S267 F, NTCP variant) in a Spanish population. METHODS Serum samples from 246 individuals were included and divided into 3 groups: patients with chronic HBV infection(CHB)(n = 41, 73% Caucasians), patients with resolved HBV infection(n = 100, 100% Caucasians) and an HBV-uninfected control group(n = 105, 100% Caucasians). Variability/conservation of the amino acid(aa) sequences of the NTCPinteracting domain,(aa 2-48 in viral genotype D) and a highly conserved pre S1 domain associated with virion morphogenesis(aa 92-103 in viral genotype D) were analyzed by next-generation sequencing and compared in 18 CHB patients with viremia > 4 log IU/mL. The rs2296651 polymorphism was determined in all individuals in all 3 groups using an in-house real-time PCR melting curve analysis.RESULTS The HBV pre S1 NTCP-interacting domain showed a high degree of conservation among the examined viral genomes especially between aa 9 and 21(in the genotype D consensus sequence). As compared with the virion morphogenesis domain, the NTCPinteracting domain had a smaller proportion of HBV genotype-unrelated changes comprising > 1% of the quasispecies(25.5% vs 31.8%), but a larger proportion of genotype-associated viral polymorphisms(34% vs 27.3%), according to consensus sequences from Gen Bank patterns of HBV genotypes A to H. Variation/conservation in both domains depended on viral genotype, with genotype C being the most highly conserved and genotype E the most variable(limited finding, only 2 genotype E included). Of note, proline residues were highly conserved in both domains, and serine residues showed changes only to threonine or tyrosine in the virion morphogenesis domain. The rs2296651 polymorphism was not detected in any participant.CONCLUSION In our CHB population, the NTCP-interactin

关键词： Hepatitis B virus Hepatitis B virus preS1 region sodium-taurocholate co-transporting polypeptide NTCP-interacting domain virion morphogenesis domain SNP rs2296651 next-generation sequencing real-time PCR melting curves

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Detection of hyper-conserved regions in hepatitis B virus X gene potentially useful for gene therapy

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World Journal of Gastroenterology 2018年第19期24卷 2095-2107页

作者： Carolina González David Tabernero Maria francesca Cortese Josep Gregori Rosario Casillas Mar Riveiro-Barciela Cristina Godoy Sara Sopena Ariadna Rando Marcal Yll Rosa Lopez-Martinez Josep Quer Rafael Esteban Maria Buti francisco rodríguez-frías Liver Pathology Unit Departments of Biochemistry and MicrobiologyHospital Universitari Vall d’HebronUniversitat Autònoma de BarcelonaBarcelona 08035Spain Liver Unit Liver Disease Laboratory-Viral HepatitisVall d’Hebron Institut Recerca-Hospital Universitari Vall d’HebronUniversitat Autònoma de BarcelonaBarcelona 08035Spain Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas(CIBERehd) Instituto de Salud Carlos IIIMadrid 28029Spain Roche Diagnostics SL Sant Cugat del Vallès 08174Spain Liver Unit Department of Internal MedicineHospital Universitari Vall d'HebronUniversitat Autònoma de BarcelonaBarcelona 08035Spain

AIM To detect hyper-conserved regions in the hepatitis B virus(HBV) X gene(HBX) 5' region that could be candidates for gene therapy.METHODS The study included 27 chronic hepatitis B treatmentnaive patients in various clinical stages(from chronic infection to cirrhosis and hepatocellular carcinoma, both HBeA g-negative and HBeA g-positive), and infected with HBV genotypes A-F and H. In a serum sample from each patient with viremia > 3.5 log IU/m L, the HBX 5' end region [nucleotide(nt) 1255-1611] was PCRamplified and submitted to next-generation sequencing(NGS). We assessed genotype variants by phylogenetic analysis, and evaluated conservation of this region by calculating the information content of each nucleotide position in a multiple alignment of all unique sequences(haplotypes) obtained by NGS. Conservation at the HBx protein amino acid(aa) level was also analyzed.RESULTS NGS yielded 1333069 sequences from the 27 samples, with a median of 4578 sequences/sample(2487-9279, IQR 2817). In 14/27 patients(51.8%), phylogenetic analysis of viral nucleotide haplotypes showed a complex mixture of genotypic variants. Analysis of the information content in the haplotype multiple alignments detected 2 hyper-conserved nucleotide regions, one in the HBX upstream non-coding region(nt 1255-1286) and the other in the 5' end coding region(nt 1519-1603). This last region coded for a conserved amino acid region(aa 63-76) that partially overlaps a Kunitz-like domain.CONCLUSION Two hyper-conserved regions detected in the HBX 5' end may be of value for targeted gene therapy, regardless of the patients' clinical stage or HBV genotype.

关键词： Hepatitis B virus Hepatitis B X gene Hepatitis B X protein Gene therapy Next-generation sequencing HBV conserved regions Small interference RNA

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Characterization of hepatitis B virus X gene quasispecies complexity in mono-infection and hepatitis delta virus superinfection

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World Journal of Gastroenterology 2019年第13期25卷 1566-1579页

作者： Cristina Godoy David Tabernero Sara Sopena Josep Gregori Maria francesca Cortese Carolina González Rosario Casillas Mar?al Yll Ariadna Rando Rosa López-Martínez Josep Quer Gloria González-Aseguinolaza Rafael Esteban Mar Riveiro-Barciela Maria Buti francisco rodríguez-frías Liver Pathology Unit Departments of Biochemistry and Microbiology Hospital Universitari Vall d’Hebron Universitat Autònoma de Barcelona Liver Unit Liver Disease Laboratory-Viral Hepatitis Vall d’Hebron Institut Recerca-Hospital Universitari Vall d'Hebron Universitat Autònoma de Barcelona Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd) Instituto de Salud Carlos Ⅲ Roche Diagnostics SL Centro de Investigación Médica Aplicada (CIMA) Universidad de Navarra Liver Unit Department of Internal MedicineHospital Universitari Vall d’Hebron Universitat Autònoma de Barcelona (UAB)

Hepatitis delta virus(HDV) seems to strongly suppress hepatitis B virus(HBV)replication, although little is known about the mechanism of this interaction. Both these viruses show a dynamic distribution of mutants, resulting in viral quasispecies. Next-generation sequencing is a viable approach for analyzing the composition of these mutant spectra. As the regulatory hepatitis B X protein(HBx) is essential for HBV replication, determination of HBV X gene(HBX)quasispecies complexity in HBV/HDV infection compared to HBV monoinfection may provide information on the interactions between these two viruses.AIM To compare HBV quasispecies complexity in the HBX 5' region between chronic hepatitis delta(CHD) and chronic HBV mono-infected patients.METHODS Twenty-four untreated patients were included: 7/24(29.2%) with HBeAgnegative chronic HBV infection(CI, previously termed inactive carriers), 8/24(33.3%) with HBeAg-negative chronic hepatitis B(CHB) and 9/24(37.5%) with CHD. A serum sample from each patient was first tested for HBV DNA levels.The HBX 5' region [nucleotides(nt) 1255-1611] was then PCR-amplified for subsequent next-generation sequencing(MiSeq, Illumina, United States). HBV quasispecies complexity in the region analyzed was evaluated using incidencebased indices(number of haplotypes and number of mutations), abundancebased indices(Hill numbers of order 1 and 2), and functional indices(mutation frequency and nucleotide diversity). We also evaluated the pattern of nucleotide changes to investigate which of them could be the cause of the quasispecies complexity.RESULTS CHB patients showed higher median HBV-DNA levels [5.4 logIU/mL,interquartile range(IQR) 3.5-7.9] than CHD(3.4 logIU/mL, IQR 3-7.6)(P = n.s.)or CI(3.2 logIU/mL, IQR 2.3-3.5)(P < 0.01) patients. The incidence and abundance indices indicated that HBV quasispecies complexity was significantly greater in CI than CHB. A similar trend was observed in CHD patients, although only Hill numbers of order 2 showed statistically significant differences(CHB2.81, I

关键词： Hepatitis B virus Hepatitis delta virus Hepatitis B X gene Next-generation sequencing Viral quasispecies Hepatitis B virus-hepatitis delta virus interaction

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Conservation and variability of hepatitis B core at different chronic hepatitis stages

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World Journal of Gastroenterology 2020年第20期26卷 2584-2598页

作者： Marcal Yll Maria francesca Cortese Mercedes Guerrero-Murillo Gerard Orriols Josep Gregori Rosario Casillas Carolina González Sara Sopena Cristina Godoy Marta Vila David Tabernero Josep Quer Ariadna Rando Rosa Lopez-Martinez Rafael Esteban Mar Riveiro-Barciela Maria Buti francisco rodríguez-frías Liver Pathology Unit Departments of Biochemistry and MicrobiologyHospital Universitari Vall d'HebronUniversitat Autònoma de BarcelonaBarcelona 08035Spain Liver Unit Liver Disease Laboratory-Viral HepatitisVall d'Hebron Institut Recerca-Hospital Universitari Vall d'HebronUniversitat Autònoma de BarcelonaBarcelona 08035Spain Department of Microbiology Hospital Universitari Vall d'HebronUniversitat Autònoma de BarcelonaBarcelona 08035Spain Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas Instituto de Salud Carlos ⅢMadrid 28029Spain Liver Unit Department of Internal MedicineHospital Universitari Vall d'HebronUniversitat Autónoma de BarcelonaBarcelona 08035Spain

BACKGROUND Since it is currently not possible to eradicate hepatitis B virus(HBV)infection with existing treatments,research continues to uncover new therapeutic strategies.HBV core protein,encoded by the HBV core gene(HBC),intervenes in both structural and functional processes,and is a key protein in the HBV life cycle.For this reason,both the protein and the gene could be valuable targets for new therapeutic and diagnostic strategies.Moreover,alterations in the protein sequence could serve as potential markers of disease progression.AIM To detect,by next-generation sequencing,HBC hyper-conserved regions that could potentially be prognostic factors and targets for new therapies.METHODS Thirty-eight of 45 patients with chronic HBV initially selected were included and grouped according to liver disease stage[chronic hepatitis B infection without liver damage(CHB,n=16),liver cirrhosis(LC,n=5),and hepatocellular carcinoma(HCC,n=17)].HBV DNA was extracted from patients’plasma.A region between nucleotide(nt)1863 and 2483,which includes HBC,was amplified and analyzed by next-generation sequencing(Illumina Mi Seq platform).Sequences were genotyped by distance-based discriminant analysis.General and intergroup nt and amino acid(aa)conservation was determined by sliding window analysis.The presence of nt insertion and deletions and/or aa substitutions in the different groups was determined by aligning the sequences with genotype-specific consensus sequences.RESULTS Three nt(nt 1900-1929,2249-2284,2364-2398)and 2 aa(aa 117-120,159-167)hyper-conserved regions were shared by all the clinical groups.All groups showed a similar pattern of conservation,except for five nt regions(nt 1946-1992,2060-2095,2145-2175,2230-2250,2270-2293)and one aa region(aa 140-160),where CHB and LC,respectively,were less conserved(P<0.05).Some group-specific conserved regions were also observed at both nt(2306-2334 in CHB and 1935-1976 and 2402-2435 in LC)and aa(between aa 98-103 in CHB and 28-30 and 51-54 in LC)levels.No differences in insertion an

关键词： Hepatitis B virus Hepatitis B core gene Next-generation sequencing Genetic conservation Amino acid substitution Gene therapy Small interfering RNA

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Cross-sectional evaluation of circulating hepatitis B virus RNA and DNA: Different quasispecies?

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World Journal of Gastroenterology 2021年第41期27卷 7144-7158页

作者： Selene Garcia-Garcia Maria francesca Cortese David Tabernero Josep Gregori Marta Vila Beatriz Pacín Josep Quer Rosario Casillas Laura Castillo-Ribelles Roser Ferrer-Costa Ariadna Rando-Segura Jesús Trejo-Zahínos Tomas Pumarola Ernesto Casis Rafael Esteban Mar Riveiro-Barciela Maria Buti francisco rodríguez-frías Clinical Biochemistry Research Group Department of BiochemistryVall d'Hebron Institut Recerca-Hospital Universitari Vall d'HebronUniversitat Autònoma de BarcelonaBarcelona 08035Spain Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas Instituto de Salud Carlos IIIMadrid 28029Spain Liver Unit Liver Disease Laboratory-Viral HepatitisVall d'Hebron Institut Recerca-Hospital Universitari Vall d'HebronVall d’Hebron Barcelona Hospital CampusBarcelona 08035Spain Liver Pathology Unit Departments of Biochemistry and MicrobiologyHospital Universitari Vall d’HebronUniversitat Autònoma de BarcelonaBarcelona 08035Spain Department of Microbiology Hospital Universitari Vall d'HebronVall d'Hebron Barcelona Hospital CampusBarcelona 08035Spain Liver Unit Department of Internal MedicineHospital Universitari Vall d'HebronUniversitat Autónoma de BarcelonaBarcelona 08035Spain

BACKGROUND Different forms of pregenomic and other hepatitis B virus(HBV)RNA have been detected in patients’sera.These circulating HBV-RNAs may be useful for monitoring covalently closed circular DNA activity,and predicting hepatitis B eantigen seroconversion or viral rebound after nucleos(t)ide analog cessation.Data on serum HBV-RNA quasispecies,however,is scarce.It is therefore important to develop methodologies to thoroughly analyze this quasispecies,ensuring the elimination of any residual HBV-DNA.Studying circulating HBV-RNA quasispecies may facilitate achieving functional cure of HBV infection.AIM To establish a next-generation sequencing(NGS)methodology for analyzing serum HBV-RNA and comparing it with DNA quasispecies.METHODS Thirteen untreated chronic hepatitis B patients,showing different HBV-genotypes and degrees of severity of liver disease were enrolled in the study and a serum sample with HBV-DNA>5 Log10 IU/mL and HBV-RNA>4 Log10 copies/mL was taken from each patient.HBV-RNA was treated with DNAse I to remove any residual DNA,and the region between nucleotides(nt)1255-1611 was amplified using a 3-nested polymerase chain reaction protocol,and analyzed with NGS.Variability/conservation and complexity was compared between HBV-DNA and RNA quasispecies.RESULTS No HBV-DNA contamination was detected in cDNA samples from HBV-RNA quasispecies.HBV quasispecies complexity showed heterogeneous behavior among patients.The Rare Haplotype Load at 1%was greater in DNA than in RNA quasispecies,with no statistically significant differences(P=0.1641).Regarding conservation,information content was equal in RNA and DNA quasispecies in most nt positions[218/357(61.06%)].In 102 of the remaining 139(73.38%),HBV-RNA showed slightly higher variability.Sliding window analysis identified 4 hyper-conserved sequence fragments in each quasispecies,3 of them coincided between the 2 quasispecies:nts 1258-1286,1545-1573 and 1575-1604.The 2 hyper-variable sequence fragments also coincided:nts 1311-1344 and 1461-1485.Sequences between

关键词： Hepatitis B virus RNA Hepatitis B X gene Quasispecies Next-generation sequencing Quasispecies conservation Quasispecies complexity

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Molecular epidemiology and putative origin of hepatitis C virus in random volunteers from Argentina

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World Journal of Gastroenterology 2013年第35期19卷 5813-5827页

作者： Noemí del Pino José Raúl Oubia francisco rodríguez-frías Juan Ignacio Esteban María Buti Teresa Otero Josep Gregori Damir García-Cehic Silvia Camos María Cubero Rosario Casillas Jaume Guàrdia Rafael Esteban Josep Quer Apunlab Laboratories Institute of Medical Microbiology and Parasitology (IMPAM) UBA-CONICET Department of MicrobiologyParasitology and Immunology Faculty of Medicine University of Buenos Aires CIBER de Enfermedades Hepáticas y Digestivas (CIBERehd) del Instituto de Salud Carlos Ⅲ and Biochemistry Department Hospital Universitari Vall d’Hebrón (HUVH) CIBERehd del Instituto de Salud Carlos Ⅲ Autonomous University of Barcelona and Liver Unit Internal Medicine Lab. Malalties Hepatiques Vall d’Hebron Institut de Recerca (VHIR) Hospital Universitari Vall d’Hebrón (HUVH) Unitat de Diagnostic Molecular HUVH Liver Unit Internal Medicine Lab Malalties Hepatiques VHIR-HUVH Roche Diagnostics SL CIBERehd del Instituto de Salud Carlos Ⅲ Liver Unit Internal Medicine Lab MalaltiesHepatiques VHIR-HUVH Liver Unit and Biochemistry Department HUVH

AIM:To study the subtype prevalence and the phylogenetic relatedness of hepatitis C virus(HCV)sequences obtained from the Argentine general population,a large cohort of individuals was analyzed.METHODS:Healthy Argentinian volunteers(n=6251)from 12 provinces representing all geographical regions of the country were studied.All parents or legal guardians of individuals younger than 18 years provided informed written consent for participation.The corresponding written permission from all municipal authorities was obtained from each city or town where subjects were to be included.HCV RNA reverse transcription-polymerase chain reaction products were sequenced and phylogenetically analyzed.The 5’untranslated region(5’UTR)was used for RNA detection and initial genotype classification.The NS5B polymerase region,encompassing nt 8262-8610,was used for subtyping.RESULTS:An unexpectedly low prevalence of HCV infection in the general population(0.32%)was observed.Our data contrasted with previous studies that reported rates ranging from 1.5%to 2.5%,mainly performed in selected populations of blood donors or vulnerable groups.The latter values are in keeping with the prevalence reported by the 2007 Argentinian HCV Consensus(approximately 2%).HCV subtypes weredistributed as follows:1a(25%),1b(25%),2c(25%),3a(5%),and 2j(5%).Two isolates ascribed either to genotype 1(5%)or to genotype 3(5%)by 5’UTR phylogenetic analysis could not be subtyped.Subtype 1a sequences comprised a highly homogeneous population and clustered with United States sequences.Genotype1b sequences represented a heterogeneous population,suggesting that this genotype might have been introduced from different sources.Most subtype 2c sequences clustered close to the 2c reported from Italy and Southern france.CONCLUSION:HCV has a low prevalence of 0.32%in the studied general population of Argentina.The pattern of HCV introduction and transmission in Argentina appears to be a consequence of multiple events and different for each subtype.

关键词： Hepatitis C virus NS5B subtyping Molecular epidemiology Hepatitis C virus Argentina Hepatitis C virus 5’ untranslated region

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Latest developments in early diagnosis and specific treatment of severe influenza infection

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Journal of Intensive Medicine 2024年第2期4卷 160-174页

作者： francisco Valenzuela-Sánchez Blanca Valenzuela-Méndez Juan francisco rodríguez-Gutiérrez Ángel Estella Intensive Care Unit University Hospital of JerezRonda de Circunvalación s/nJerez de la FronteraSpain Haematology Department University Hospital of JerezRonda de Circunvalación s/nJerez de la FronteraSpain Centro de Investigación Biomédica en Red Enfermedades respiratoriasCIBERESInstituto de Salud Carlos IIIAv.de Monforte de LemosMadridSpain Department of Oncological Surgery Institut du Cancer de Montpellier(ICM)Parc Euromédecine208 Av.des ApothicairesMontpellierFrance Department of Medicine Faculty of MedicineUniversity of CádizCalle Doctor MarañónCádizSpain Instituto de Investigación e Innovación Biomédica de Cádiz(INIBiCA) Avenida Ana de Viya 21CádizSpain

Influenza pandemics are unpredictable recurrent events with global health,economic,and social consequences.The objective of this review is to provide an update on the latest developments in early diagnosis and specific treatment of the disease and its complications,particularly with regard to respiratory organ failure.Despite advances in treatment,the rate of mortality in the intensive care unit remains approximately 30%.Therefore,early identification of potentially severe viral pneumonia is extremely important to optimize treatment in these patients.The pathogenesis of influenza virus infection depends on viral virulence and host response.Thus,in some patients,it is associated with an excessive systemic response mediated by an authentic cytokine storm.This process leads to severe primary pneumonia and acute respiratory distress syndrome.Initial prognostication in the emergency department based on comorbidities,vital signs,and biomarkers(e.g.,procalcitonin,ferritin,human leukocyte antigen-DR,mid-regional proadrenomedullin,and lactate)is important.Identification of these biomarkers on admission may facilitate clinical decision-making to determine early admission to the hospital or the intensive care unit.These decisions are reached considering pathophysiological circumstances that are associated with a poor prognosis(e.g.,bacterial co-infection,hyperinflammation,immune paralysis,severe endothelial damage,organ dysfunction,and septic shock).Moreover,early implementation is important to increase treatment efficacy.Based on a limited level of evidence,all current guidelines recommend using oseltamivir in this setting.The possibility of drug resistance should also be considered.Alternative options include other antiviral drugs and combination therapies with monoclonal antibodies.Importantly,it is not recommended to use corticosteroids in the initial treatment of these patients.Furthermore,the implementation of supportive measures for respiratory failure is essential.Current recommendations are limited,heterogeneous,an

关键词： Influenza Pandemic Respiratory failure Acute respiratory distress syndrome Intensive care unit admission

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Chiral forces in longitudinally invariant dielectric photonic waveguides

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Photonics Research 2024年第3期12卷 431-443页

作者： JOSEP MARTÍNEZ-ROMEU IAGO DIEZ SEBASTIAN GOLAT francisco J.rodrÍguez-FORTUÑO ALEJANDRO MARTÍNEZ Nanophotonics Technology Center Universitat Politècnica de ValènciaValencia 46022Spain Department of Physics King’s College LondonLondon WC2R 2LSUK

We calculate numerically the optical chiral forces in rectangular cross-section dielectric waveguides for potential enantiomer separation.Our study considers force strength and time needed for separating chiral nanoparticles,mainly via quasi-TE guided modes at short wavelengths(405 nm)and the 90°-phase-shifted combination of quasi-TE and quasi-TM modes at longer wavelengths(1310 nm).Particle tracking simulations show successful enantiomer separation within two seconds.These results suggest the feasibility of enantiomeric separation of nanoparticles displaying sufficient chirality using simple silicon photonic integrated circuits,with wavelength selection based on the nanoparticle size.

关键词： dielectric forces quasi

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Diplopoda in the world fossil record

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Zoological Systematics 2024年第3期 185-245页

作者： Michelle álvarez-rodríguez francisco Riquelme Miguel Hernández-Patricio Fabio Cupul-Maga?a Laboratorio de Sistemática Molecular Escuela de Estudios Superiores del Jicarero Universidad Autónoma del Estado de Morelos MMRN Centro de Investigaciones Biológicas Universidad Autónoma del Estado de Morelos Unafíliate Centro Universitario de la Costa Universidad de Guadalajara

We present a comprehensive catalog with an updated database of the fossil record of Diplopoda in the world. Taxonomic data was collected from descriptions and reports published from 1854 to the present. We also include new records from Mexican amber(Upper Oligocene-Lower Miocene), counting 83 unknown fossil inclusions, with the first records of the orders Polyxenida, Platydesmida, and Julida, as well as the families Sphaeriodesmidae and Trichopolydesmidae within Polydesmida. According to our results, Diplopoda counts 413 records featuring 299 distinct taxa ranging from the Middle Silurian to the Upper Pleistocene, representing three subclasses, two subterclasses, six superorders, 25 orders, 15 superfamilies, 55 families, 93 genera, and 161 fossil species. To date, no fossils of the order Siphonocryptida have been reported. The fossil record extends over three geological eras: the Paleozoic, with 161 taxa, including 97 species; the Mesozoic, with 53 taxa and 22 species; and the Cenozoic, with 85 taxa and 42 species. The referred material shows different forms of fossil preservation. It comprises 123 impressions, 99 compressions, 26 ichnites, predominantly from Paleozoic and Mesozoic sediments, and 165 amber inclusions from late Mesozoic and Cenozoic sites. Thus, this catalog allows us to estimate the size and taxonomic composition of Diplopoda in the fossil record worldwide.

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