Publications by authors named "Rafael Delgado"

145 Publications

Potent Neutralizing Activity of Polyclonal Equine Antibodies against SARS-CoV-2 Variants of Concern.

J Infect Dis 2022 Aug 3. Epub 2022 Aug 3.

Instituto de Investigación Hospital 12 de Octubre (Imas12). Madrid. Spain.

Several monoclonal anti-SARS-CoV-2 antibodies (mAbs) have received emergency authorization for COVID-19 treatment. However, most of these mAbs are not active against the highly mutated Omicron SARS-CoV-2 subvariants. We have tested a polyclonal approach of equine anti-SARS-CoV-2 F(ab')2 antibodies that achieved a high level of neutralizing potency against all SARS-CoV-2 VoCs tested including Omicron BA.1, BA.2, BA.2.12 and BA.4/5. A repertoire of antibodies targeting conserved epitopes in different regions of the spike protein could plausibly account for this remarkable breadth of neutralization. These results warrant the clinical investigation of equine polyclonal F(ab')2 antibodies as a novel therapeutic strategy against COVID-19.
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http://dx.doi.org/10.1093/infdis/jiac331DOI Listing
August 2022

Topological and Multivalent Effects in Glycofullerene Oligomers as EBOLA Virus Inhibitors.

Int J Mol Sci 2022 May 3;23(9). Epub 2022 May 3.

Departamento de Química Orgánica, Facultad de Química, Universidad Complutense, 28040 Madrid, Spain.

The synthesis of new biocompatible antiviral materials to fight against the development of multidrug resistance is being widely explored. Due to their unique globular structure and excellent properties, [60]fullerene-based antivirals are very promising bioconjugates. In this work, fullerene derivatives with different topologies and number of glycofullerene units were synthesized by using a SPAAC copper free strategy. This procedure allowed the synthesis of compounds -, containing from 20 to 40 mannose units, in a very efficient manner and in short reaction times under MW irradiation. The glycoderivatives were studied in an infection assay by a pseudotyped viral particle with Ebola virus GP1. The results obtained show that these glycofullerene oligomers are efficient inhibitors of EBOV infection with ICs in the nanomolar range. In particular, compound , with four glycofullerene moieties, presents an outstanding relative inhibitory potency (RIP). We propose that this high RIP value stems from the appropriate topological features that efficiently interact with DC-SIGN.
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http://dx.doi.org/10.3390/ijms23095083DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9131134PMC
May 2022

Reply to R. Lakhotia et al.

J Clin Oncol 2022 Jun 4;40(18):2064-2066. Epub 2022 Apr 4.

G.A. Amos Burke, MBChB, PhD, Department of Paediatric Haematology, Oncology and Palliative Care, Cambridge University Hospitals NHS Foundation Trust, Addenbrooke's Hospital, Cambridge, United Kingdom; Veronique Minard-Colin, MD, PhD, Department of Pediatric and Adolescent Oncology, INSERM 1015, Gustave Roussy, Université Paris-Saclay, Villejuif, France; Anne Aupérin, MD, PhD, Unit of Biostatistics and Epidemiology, Gustave Roussy, Oncostat 1018 INSERM, Labeled Ligue Contre le Cancer, Université Paris-Saclay, Villejuif, France; Sarah Alexander, MD, Division of Haematology/Oncology, Hospital for Sick Children, Toronto, ON, Canada; Marta Pillon, MD, PhD, Pediatric Hematology and Oncology, University of Padova, Padova, Italy; Rafael Delgado, MD, PhD, Pediatric Hematology and Oncology, University of Valencia, Valencia, Spain; József Zsíros, MD, PhD, Princess Máxima Center for Pediatric Oncology, Utrecht, the Netherlands; Anne Uyttebroeck, MD, PhD, Department of Pediatric Hematology and Oncology, University Hospitals Leuven, Leuven, Belgium; Peggy Dartigues, MD, Department of Biopathology, Gustave Roussy, Université Paris-Saclay, Villejuif, France; Rodney R. Miles, MD, PhD, Department of Pathology and ARUP Laboratories and Huntsman Cancer Institute, Salt Lake City, UT; Bernarda Kazanowska, MD, PhD, Department of Pediatric Bone Marrow Transplantation, Oncology, and Hematology, Wroclaw Medical University, Wroclaw, Poland; Alan K. Chiang, MD, PhD, Department of Paediatrics and Adolescent Medicine, Li Ka Shing Faculty of Medicine, Queen Mary Hospital, The University of Hong Kong, Hong Kong; Stéphanie Haouy, MD, Department of Paediatric Haematology, Oncology, CHU Arnaud de Villeneuve, Montpellier, France; Catherine M. Bollard, MBChB, MD, Center for Cancer and Immunology Research, Children's National Hospital and The George Washington University, Washington, DC; Monika Csoka, MD, PhD, Pediatric Hematology and Oncology, Semmelweis University, Budapest, Hungary; Keith Wheatley, PhD, Cancer Research UK Clinical Trials Unit, Institute of Cancer and Genomic Sciences, College of Medical and Dental Sciences, University of Birmingham, Birmingham, United Kingdom; Donald A. Barkauskas, PhD, Department of Preventive Medicine, Keck School of Medicine of the University of Southern California, Los Angeles, CA; Peter C. Adamson, MD, Global Head, Oncology Development and Pediatric Innovation at Sanofi, Cambridge, MA; Gilles Vassal, MD, PhD, Department of Clinical Research, Gustave Roussy, Université Paris-Saclay, Villejuif, France; Catherine Patte, MD, Department of Pediatric and Adolescent Oncology, INSERM 1015, Gustave Roussy, Université Paris-Saclay, Villejuif, France; and Thomas G. Gross, MD, PhD, Department of Pediatrics, Center for Cancer and Blood Diseases, Children's Hospital Colorado, Aurora, CO.

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http://dx.doi.org/10.1200/JCO.21.02912DOI Listing
June 2022

Poxvirus MVA Expressing SARS-CoV-2 S Protein Induces Robust Immunity and Protects Rhesus Macaques From SARS-CoV-2.

Front Immunol 2022 16;13:845887. Epub 2022 Mar 16.

Department of Molecular and Cellular Biology, Centro Nacional de Biotecnología (CNB), Consejo Superior de Investigaciones Científicas (CSIC), Madrid, Spain.

Novel safe, immunogenic, and effective vaccines are needed to control the COVID-19 pandemic, caused by SARS-CoV-2. Here, we describe the safety, robust immunogenicity, and potent efficacy elicited in rhesus macaques by a modified vaccinia virus Ankara (MVA) vector expressing a full-length SARS-CoV-2 spike (S) protein (MVA-S). MVA-S vaccination was well tolerated and induced S and receptor-binding domain (RBD)-binding IgG antibodies and neutralizing antibodies against SARS-CoV-2 and several variants of concern. S-specific IFNγ, but not IL-4, -producing cells were also elicited. After SARS-CoV-2 challenge, vaccinated animals showed a significant strong reduction of virus loads in bronchoalveolar lavages (BAL) and decreased levels in throat and nasal mucosa. Remarkably, MVA-S also protected macaques from fever and infection-induced cytokine storm. Computed tomography and histological examination of the lungs showed reduced lung pathology in MVA-S-vaccinated animals. These findings favor the use of MVA-S as a potential vaccine for SARS-CoV-2 in clinical trials.
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http://dx.doi.org/10.3389/fimmu.2022.845887DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8966779PMC
March 2022

A Single Dose of an MVA Vaccine Expressing a Prefusion-Stabilized SARS-CoV-2 Spike Protein Neutralizes Variants of Concern and Protects Mice From a Lethal SARS-CoV-2 Infection.

Front Immunol 2021 27;12:824728. Epub 2022 Jan 27.

Department of Molecular and Cellular Biology, Centro Nacional de Biotecnología (CNB), Consejo Superior de Investigaciones Científicas (CSIC), Madrid, Spain.

We generated an optimized COVID-19 vaccine candidate based on the modified vaccinia virus Ankara (MVA) vector expressing a full-length prefusion-stabilized SARS-CoV-2 spike (S) protein, termed MVA-CoV2-S(3P). The S(3P) protein was expressed at higher levels (2-fold) than the non-stabilized S in cells infected with the corresponding recombinant MVA viruses. One single dose of MVA-CoV2-S(3P) induced higher IgG and neutralizing antibody titers against parental SARS-CoV-2 and variants of concern than MVA-CoV2-S in wild-type C57BL/6 and in transgenic K18-hACE2 mice. In immunized C57BL/6 mice, two doses of MVA-CoV2-S or MVA-CoV2-S(3P) induced similar levels of SARS-CoV-2-specific B- and T-cell immune responses. Remarkably, a single administration of MVA-CoV2-S(3P) protected all K18-hACE2 mice from morbidity and mortality caused by SARS-CoV-2 infection, reducing SARS-CoV-2 viral loads, histopathological lesions, and levels of pro-inflammatory cytokines in the lungs. These results demonstrated that expression of a novel full-length prefusion-stabilized SARS-CoV-2 S protein by the MVA poxvirus vector enhanced immunogenicity and efficacy against SARS-CoV-2 in animal models, further supporting MVA-CoV2-S(3P) as an optimized vaccine candidate for clinical trials.
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http://dx.doi.org/10.3389/fimmu.2021.824728DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8829548PMC
February 2022

Full efficacy and long-term immunogenicity induced by the SARS-CoV-2 vaccine candidate MVA-CoV2-S in mice.

NPJ Vaccines 2022 Feb 9;7(1):17. Epub 2022 Feb 9.

Department of Molecular and Cellular Biology, Centro Nacional de Biotecnología (CNB), Consejo Superior de Investigaciones Científicas (CSIC), 28049, Madrid, Spain.

Two doses of the MVA-CoV2-S vaccine candidate expressing the SARS-CoV-2 spike (S) protein protected K18-hACE2 transgenic mice from a lethal dose of SARS-CoV-2. This vaccination regimen prevented virus replication in the lungs, reduced lung pathology, and diminished levels of pro-inflammatory cytokines. High titers of IgG antibodies against S and receptor-binding domain (RBD) proteins and of neutralizing antibodies were induced against parental virus and variants of concern, markers that correlated with protection. Similar SARS-CoV-2-specific antibody responses were observed at prechallenge and postchallenge in the two-dose regimen, while the single-dose treatment does not avoid vaccine breakthrough infection. All vaccinated animals survived infection and were also protected to SARS-CoV-2 reinfection. Furthermore, two MVA-CoV2-S doses induced long-term memory S-specific humoral and cellular immune responses in C57BL/6 mice, 6 months after immunization. The efficacy and immunological benefits of the MVA-CoV2-S vaccine candidate against COVID-19 supports its consideration for human clinical trials.
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http://dx.doi.org/10.1038/s41541-022-00440-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8828760PMC
February 2022

New insights into the role of endosomal proteins for African swine fever virus infection.

PLoS Pathog 2022 01 26;18(1):e1009784. Epub 2022 Jan 26.

Departmento de Biotecnología, INIA-CSIC, Centro Nacional Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria, Madrid, Spain.

African swine fever virus (ASFV) infectious cycle starts with the viral adsorption and entry into the host cell. Then, the virus is internalized via clathrin/dynamin mediated endocytosis and macropinocytosis. Similar to other viruses, ASF virion is then internalized and incorporated into the endocytic pathway. While the endosomal maturation entails luminal acidification, the decrease in pH acts on the multilayer structure of the virion dissolving the outer capsid. Upon decapsidation, the inner viral membrane is exposed to interact with the limiting membrane of the late endosome for fusion. Viral fusion is then necessary for the egress of incoming virions from endosomes into the cytoplasm, however this remains an intriguing and yet essential process for infection, specifically for the egress of viral nucleic acid into the cytoplasm for replication. ASFV proteins E248R and E199L, located at the exposed inner viral membrane, might be implicated in the fusion step. An interaction between these viral proteins and cellular endosomal proteins such as the Niemann-Pick C type 1 (NPC1) and lysosomal membrane proteins (Lamp-1 and -2) was shown. Furthermore, the silencing of these proteins impaired ASFV infection. It was also observed that NPC1 knock-out cells using CRISPR jeopardized ASFV infection and that the progression and endosomal exit of viral cores was arrested within endosomes at viral entry. These results suggest that the interactions of ASFV proteins with some endosomal proteins might be important for the membrane fusion step. In addition to this, reductions on ASFV infectivity and replication in NPC1 KO cells were accompanied by fewer and smaller viral factories. Our findings pave the way to understanding the role of proteins of the endosomal membrane in ASFV infection.
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http://dx.doi.org/10.1371/journal.ppat.1009784DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8820605PMC
January 2022

Twenty-year impact of fire foci and its relationship with climate variables in Brazilian regions.

Environ Monit Assess 2022 Jan 12;194(2):90. Epub 2022 Jan 12.

Postgraduate Program in Management and Regulation of Water Resources - Profagua, State University of Mato Grosso (UNEMAT), Cuiaba, Mato Grosso, Brazil.

In recent years, Brazil has become a major global contributor to the occurrence of national fires and greenhouse gas emissions. Therefore, this study aimed to evaluate the fire foci data of the past 20 years to determine their relationship with climatic variables in various Brazilian regions. The variables evaluated included fire foci, land surface temperature, rainfall, and standardized precipitation index, which were obtained via remote sensing from 2000 to 2019. The data were subjected to trend analyses (Mann-Kendall and Pettitt tests) and a multivariate analysis of canonical variables for evaluation. The results showed that the Midwest and North regions had the highest occurrence of fire foci throughout the study period, and that the North region had the highest accumulated annual rainfall. Thus, these regions require specific public policies to prevent future fires. Overall, the Midwest, Southeast, and South regions exhibit significant increasing fire foci tendencies. Our results reveal that this trend is related to the El Niño-Southern Oscillation (ENSO) phenomena, which alter climatic variables such as precipitation, land surface temperature, and the standardized precipitation index. Finally, the sugarcane growing area had a significant linear relationship with fire foci in the Southeast region, especially in the state of São Paulo, the major national sugarcane producer.
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http://dx.doi.org/10.1007/s10661-021-09702-xDOI Listing
January 2022

Neutralizing Response Against SARS-CoV-2 Variants 8 Months After BNT162b2 Vaccination in Naive and COVID-19-Convalescent Individuals.

J Infect Dis 2022 06;225(11):1905-1908

Instituto de Investigación Hospital 12 de Octubre, Madrid, Spain.

We have investigated the evolution of the neutralizing response against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants at 8 months after Pfizer-BNT162b2 vaccination in coronavirus disease 2019 (COVID-19)-naive (n = 21) and COVID-19-convalescent (n = 21) individuals. Neutralizing levels declined for all variants (range 2- to 3.7-fold). Eight months after vaccination, a significant proportion (4/21) of naive individuals lacked detectable neutralizing activity against the highly transmissible SARS-CoV-2 delta variant. In the convalescent group, the impressive high initial humoral response resulted in detectable neutralizing antibody levels against all variants throughout this period.
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http://dx.doi.org/10.1093/infdis/jiab634DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8755312PMC
June 2022

DNA methylation-based classification of malformations of cortical development in the human brain.

Acta Neuropathol 2022 01 19;143(1):93-104. Epub 2021 Nov 19.

Department of Neuropathology, Affiliated Partner of the ERN EpiCARE, Universitätsklinikum Erlangen, Friedrich-Alexander University Erlangen-Nürnberg (FAU), Erlangen, Germany.

Malformations of cortical development (MCD) comprise a broad spectrum of structural brain lesions frequently associated with epilepsy. Disease definition and diagnosis remain challenging and are often prone to arbitrary judgment. Molecular classification of histopathological entities may help rationalize the diagnostic process. We present a retrospective, multi-center analysis of genome-wide DNA methylation from human brain specimens obtained from epilepsy surgery using EPIC 850 K BeadChip arrays. A total of 308 samples were included in the study. In the reference cohort, 239 formalin-fixed and paraffin-embedded (FFPE) tissue samples were histopathologically classified as MCD, including 12 major subtype pathologies. They were compared to 15 FFPE samples from surgical non-MCD cortices and 11 FFPE samples from post-mortem non-epilepsy controls. We applied three different statistical approaches to decipher the DNA methylation pattern of histopathological MCD entities, i.e., pairwise comparison, machine learning, and deep learning algorithms. Our deep learning model, which represented a shallow neuronal network, achieved the highest level of accuracy. A test cohort of 43 independent surgical samples from different epilepsy centers was used to test the precision of our DNA methylation-based MCD classifier. All samples from the test cohort were accurately assigned to their disease classes by the algorithm. These data demonstrate DNA methylation-based MCD classification suitability across major histopathological entities amenable to epilepsy surgery and age groups and will help establish an integrated diagnostic classification scheme for epilepsy-associated MCD.
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http://dx.doi.org/10.1007/s00401-021-02386-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8732912PMC
January 2022

Update and latest advances in antiretroviral therapy.

Trends Pharmacol Sci 2022 01 3;43(1):16-29. Epub 2021 Nov 3.

Laboratory of Molecular Microbiology. Instituto de Investigación Hospital 12 de Octubre (Imas12) and The University Complutense School of Medicine, Madrid, Spain. Electronic address:

Since the first cases of AIDS appeared in 1981, human immunodeficiency virus type 1 (HIV-1) infection has reached pandemic proportions. Forty years later, research has led to the approval of more than 30 antiretroviral drugs, while combination therapies have turned HIV-1 infection into a chronic, but manageable disease. Still, drug toxicity and acquired and transmitted drug resistance remain as major threats to therapy success. In this review, we provide an overview on currently available anti-HIV drugs and the latest developments in antiretroviral therapy, focused on new antiretroviral agents acting on known and unexploited antiviral targets, prevention therapies aimed to improve available drug combinations, and research on new long-acting therapies, particularly those involving novel drug candidates such as lenacapavir or islatravir.
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http://dx.doi.org/10.1016/j.tips.2021.10.004DOI Listing
January 2022

Prime-Boost Vaccination With BNT162b2 Induces High Neutralizing Activity Against SARS-CoV-2 Variants in Naïve and COVID-19-Convalescent Individuals.

Open Forum Infect Dis 2021 Oct 24;8(10):ofab468. Epub 2021 Sep 24.

Instituto de Investigacion Hospital 12 de Octubre (imas12), Madrid, Spain.

Background: The objective of this study was to investigate the neutralizing response against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern (VoC) during coronavirus disease 2019 (COVID-19) convalescence and after vaccination.

Methods: COVID-19-convalescent and -naïve individuals were tested for neutralizing activity against SARS-CoV-2 VoC Alpha, Beta, Gamma, and Delta at 1 and 7 months postinfection and 4-6 weeks after BNT162b2 vaccination.

Results: Vaccination induced a high neutralizing response in naïve individuals. Interestingly, vaccination of convalescent patients induced a boosted response that was able to neutralize all VoC at high titers.

Conclusions: Vaccination with BNT162b2 induced high levels of neutralization against SARS-CoV-2 VoC in most patients; this is especially beneficial in COVID-19-convalescent individuals.
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http://dx.doi.org/10.1093/ofid/ofab468DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8500154PMC
October 2021

Dose-Adjusted Etoposide, Doxorubicin, and Cyclophosphamide With Vincristine and Prednisone Plus Rituximab Therapy in Children and Adolescents With Primary Mediastinal B-Cell Lymphoma: A Multicenter Phase II Trial.

J Clin Oncol 2021 11 27;39(33):3716-3724. Epub 2021 Sep 27.

Department of Pediatrics, Center for Cancer and Blood Diseases, Children's Hospital Colorado, Aurora, CO.

Purpose: A dose-adjusted etoposide, doxorubicin, and cyclophosphamide with vincristine and prednisone plus rituximab (DA-EPOCH-R) regimen has been shown to deliver excellent survival for adults with primary mediastinal large B-cell lymphoma (PMLBL) without the use of radiotherapy. No international prospective evaluation of this regimen has previously been reported in children and adolescents.

Patients And Methods: We conducted an international single-arm phase II trial involving patients younger than age 18 years with PMLBL who were to receive six courses of DA-EPOCH-R. The primary end point was event-free survival (EFS). Overall survival and toxicity were also assessed. This trial was registered (ClinicalTrials.gov identifier: NCT01516567).

Results: Analyses were based on 46 patients. The median age was 15.4 years (interquartile range: 14-16 years). The median follow-up was 59.0 months (interquartile range: 52.6-69.2 months). Fourteen events were observed (eight relapses or progressions (including three parenchymal CNS relapses), four residual lymphoma, and two second malignancies). The 4-year EFS was 69.6% (95% CI, 55.2 to 80.9), which did not differ from the rate observed historically ( = .59). Seven deaths occurred (six disease-related and one second malignancy). The overall survival was 84.8% (95% CI, 71.8 to 92.4). Twenty-two patients (48%) reached dose levels ≥ 4. Nonhematologic adverse events grade ≥ 3 or cardiac adverse events grade ≥ 2 occurred in 47 of 276 (17%) courses and 30 of 46 patients (65%).

Conclusion: DA-EPOCH-R did not improve the EFS compared with a historical control in this first prospective multisite international study of children and adolescents with PMLBL. Further studies are required to determine the optimum therapy for children and adolescents with this lymphoma.
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http://dx.doi.org/10.1200/JCO.21.00920DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9150887PMC
November 2021

Low-Valent Calix[4]arene Glycoconjugates Based on Hydroxamic Acid Bearing Linkers as Potent Inhibitors in a Model of Ebola Virus Cis-Infection and HCMV-gB-Recombinant Glycoprotein Interaction with MDDC Cells by Blocking DC-SIGN.

J Med Chem 2021 10 15;64(19):14332-14343. Epub 2021 Sep 15.

Laboratoire de Glycochimie des Antimicrobiens et des Agroressources (LG2A-UMR7378-CNRS), Université de Picardie Jules Verne, 10 Rue Baudelocque, Amiens, 80039 Cédex, France.

In addition to a variety of viral-glycoprotein receptors (e.g., heparan sulfate, Niemann-Pick C1, etc.), dendritic cell-specific intercellular adhesion molecule-3-grabbing nonintegrin (DC-SIGN), from the C-type lectin receptor family, plays one of the most important pathogenic functions for a wide range of viruses (e.g., Ebola, human cytomegalovirus (HCMV), HIV-1, severe acute respiratory syndrome coronavirus 2, etc.) that invade host cells before replication; thus, its inhibition represents a relevant extracellular antiviral therapy. We report two novel -Bu-calixarene glycoclusters and , bearing tetrahydroxamic acid groups, which exhibit micromolar inhibition of soluble DC-SIGN binding and provide nanomolar IC inhibition of both DC-SIGN-dependent Jurkat cis-cell infection by viral particle pseudotyped with Ebola virus glycoprotein and the HCMV-gB-recombinant glycoprotein interaction with monocyte-derived dendritic cells expressing DC-SIGN. A unique cooperative involvement of sugar, linker, and calixarene core is likely behind the strong avidity of DC-SIGN for these low-valent systems. We claim herein new promising candidates for the rational development of a large spectrum of antiviral therapeutics.
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http://dx.doi.org/10.1021/acs.jmedchem.1c00818DOI Listing
October 2021

Detection of archived lamivudine-associated resistance mutations in virologically suppressed, lamivudine-experienced HIV-infected adults by different genotyping techniques (GEN-PRO study).

J Antimicrob Chemother 2021 11;76(12):3263-3271

Infectious Diseases Unit, Internal Medicine Department, Hospital Universitario La Paz-IdiPAZ, Paseo de la Castellana 261, 28046 Madrid, Spain.

Background: Previously selected lamivudine resistance-associated mutations (RAMs) may remain archived within the proviral HIV-DNA.

Objectives: To evaluate the ability of proviral DNA genotyping to detect lamivudine RAMs in HIV-1 virologically suppressed participants; the correlation between Sanger and next generation sequencing (NGS); and predictive factors for detection of lamivudine RAMs in proviral DNA.

Methods: Cross-sectional study of participants on stable antiretroviral therapy and suppressed for ≥1 year. Analysis of proviral DNA was performed by Sanger sequencing in whole blood and by NGS in PBMCs.

Results: We analysed samples from 102 subjects (52 with and 50 without lamivudine RAMs in historical plasma RNA-genotypes). Among participants with previous lamivudine resistance, Sanger sequencing detected RAMs in 26.9%. Detection rates significantly increased using NGS: 47.9%, 64.6%, 75% and 87.5% with the 20%, 10%, 5% and 1% thresholds, respectively. As for participants without historical lamivudine resistance, Sanger detected the RAMs in 1/49 (2%), and NGS (5% threshold) in 8/45 (17.8%). Multivariate models fitted to the whole population revealed that having a history of lamivudine resistance was a risk factor for detection of lamivudine RAMs by NGS. Among participants with historical lamivudine resistance, multivariate analysis showed that a longer time since HIV diagnosis was associated with persistence of archived mutations by NGS at thresholds of >10% [OR 1.10 (95% CI: 1.00-1.24)] and >5% [OR 1.16 (95% CI: 1.02-1.32)].

Conclusions: Proviral DNA Sanger sequencing does not detect the majority of historical lamivudine RAMs. NGS increases the sensitivity of detection at lower thresholds, although the relevance of these minority populations with lamivudine RAMs needs further evaluation.
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http://dx.doi.org/10.1093/jac/dkab323DOI Listing
November 2021

Modeling susceptibility to forest fires in the Central Corridor of the Atlantic Forest using the frequency ratio method.

J Environ Manage 2021 Oct 23;296:113343. Epub 2021 Jul 23.

Department of Agricultural and Environmental Sciences at the State University of Santa Cruz, Investigador Asociado Ao CESIMAR/CENPAT, Puerto Madryn, Chubut, Argentina.

Fire is one of the main disturbances of tropical forests. Understanding the spatial and temporal dynamics of forest fires is of fundamental importance for the conservation of tropical forests. We used a frequency ratio model to identify those areas most susceptible to forest fires in the Central Corridor of the Atlantic Forest, from 2001 to 2019. We used data from the burned area of MODIS MCD64A1 to create the dependent variable grouped as climatic, topographic and human and landscape variables. The receiver operating characteristic (ROC) curve and area under the curve (AUC) were used to assess the model's performance. Land use and relief orientation were the most and least important variables in the model, respectively. The model showed good AUC values, ranging from 0.72 to 0.96, with an average of 0.81 for the study period. The average distribution of susceptibility classes was low (19.62 %), medium (24.45 %) and high (20.55 %). The northwestern region of the CAFC was the one that presented the greatest susceptibility to the occurrence of forest fires. The frequency ratio proved to be a good model for mapping areas susceptible to forest fires in an area of the Atlantic Forest.
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http://dx.doi.org/10.1016/j.jenvman.2021.113343DOI Listing
October 2021

Newborn Auditory Brainstem Responses in Children with Developmental Disabilities.

J Autism Dev Disord 2021 Jun 28. Epub 2021 Jun 28.

Department of Health Systems Management, Ben-Gurion University of the Negev, Beer Sheva, Israel.

We integrated data from a newborn hearing screening database and a preschool disability database to examine the relationship between newborn click evoked auditory brainstem responses (ABRs) and developmental disabilities. This sample included children with developmental delay (n = 2992), speech impairment (SI, n = 905), language impairment (n = 566), autism spectrum disorder (ASD, n = 370), and comparison children (n = 128,181). We compared the phase of the ABR waveform, a measure of sound processing latency, across groups. Children with SI and children with ASD had greater newborn ABR phase values than both the comparison group and the developmental delay group. Newborns later diagnosed with SI or ASD have slower neurological responses to auditory stimuli, suggesting sensory differences at birth.
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http://dx.doi.org/10.1007/s10803-021-05126-1DOI Listing
June 2021

Potential pharmacological strategies targeting the Niemann-Pick C1 receptor and Ebola virus glycoprotein interaction.

Eur J Med Chem 2021 Nov 19;223:113654. Epub 2021 Jun 19.

Centro de Investigaciones Biológicas Margarita Salas (CSIC), Ramiro de Maeztu 9, 28040 Madrid, Spain. Electronic address:

Niemann-Pick C1 (NPC1) receptor is an intracellular protein located in late endosomes and lysosomes whose main function is to regulate intracellular cholesterol trafficking. Besides being postulated as necessary for the infection of highly pathogenic viruses in which the integrity of cholesterol transport is required, this protein also allows the entry of the Ebola virus (EBOV) into the host cells acting as an intracellular receptor. EBOV glycoprotein (EBOV-GP) interaction with NPC1 at the endosomal membrane triggers the release of the viral material into the host cell, starting the infective cycle. Disruption of the NPC1/EBOV-GP interaction could represent an attractive strategy for the development of drugs aimed at inhibiting viral entry and thus infection. Some of the today available EBOV inhibitors were proposed to interrupt this interaction, but molecular and structural details about their mode of action are still preliminary thus more efforts are needed to properly address these points. Here, we provide a critical discussion of the potential of NPC1 and its interaction with EBOV-GP as a therapeutic target for viral infections.
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http://dx.doi.org/10.1016/j.ejmech.2021.113654DOI Listing
November 2021

DC/L-SIGN recognition of spike glycoprotein promotes SARS-CoV-2 trans-infection and can be inhibited by a glycomimetic antagonist.

PLoS Pathog 2021 05 20;17(5):e1009576. Epub 2021 May 20.

Univ. Grenoble Alpes, CNRS, CEA, Institut de Biologie Structurale, Grenoble, France.

The efficient spread of SARS-CoV-2 resulted in a unique pandemic in modern history. Despite early identification of ACE2 as the receptor for viral spike protein, much remains to be understood about the molecular events behind viral dissemination. We evaluated the contribution of C-type lectin receptors (CLRS) of antigen-presenting cells, widely present in respiratory mucosa and lung tissue. DC-SIGN, L-SIGN, Langerin and MGL bind to diverse glycans of the spike using multiple interaction areas. Using pseudovirus and cells derived from monocytes or T-lymphocytes, we demonstrate that while virus capture by the CLRs examined does not allow direct cell infection, DC/L-SIGN, among these receptors, promote virus transfer to permissive ACE2+ Vero E6 cells. A glycomimetic compound designed against DC-SIGN, enable inhibition of this process. These data have been then confirmed using authentic SARS-CoV-2 virus and human respiratory cell lines. Thus, we described a mechanism potentiating viral spreading of infection.
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http://dx.doi.org/10.1371/journal.ppat.1009576DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8136665PMC
May 2021

First confirmation of importation and transmission in Spain of the newly identified SARS-CoV-2 B.1.1.7 variant.

Enferm Infecc Microbiol Clin (Engl Ed) 2021 Feb 19. Epub 2021 Feb 19.

Servicio de Microbiología Clínica y Enfermedades Infecciosas, Gregorio Marañón General University Hospital, Spain; Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Madrid, Spain; CIBER Enfermedades Respiratorias (CIBERES), Spain. Electronic address:

Introduction: A newly identified SARS-CoV-2 variant, VOC202012/01 originating lineage B.1.1.7, recently emerged in the United Kingdom. The rapid spread in the UK of this new variant has caused other countries to be vigilant.

Material And Methods: We based our initial screening of B.1.1.7 on the dropout of the S gene signal in the TaqPath assay, caused by the 69/70 deletion. Subsequently, we confirmed the B.1.1.7 candidates by whole genome sequencing.

Results: We describe the first three imported cases of this variant from London to Madrid, subsequent post-arrival household transmission to three relatives, and the two first cases without epidemiological links to UK. One case required hospitalization. In all cases, drop-out of gene S was correctly associated to the B.1.1.7 variant, as all the corresponding sequences carried the 17 lineage-marker mutations.

Conclusion: The first identifications of the SARS-CoV-2 B.1.1.7 variant in Spain indicate the role of independent introductions from the UK coexisting with post-arrival transmission in the community, since the early steps of this new variant in our country.
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http://dx.doi.org/10.1016/j.eimc.2021.02.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7894114PMC
February 2021

Genomic Epidemiology of SARS-CoV-2 in Madrid, Spain, during the First Wave of the Pandemic: Fast Spread and Early Dominance by D614G Variants.

Microorganisms 2021 Feb 22;9(2). Epub 2021 Feb 22.

Servicio de Microbiología, Hospital Universitario La Paz and Instituto de Investigación Hospital Universitario La Paz (IdiPAZ), 28046 Madrid, Spain.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first detected in Madrid, Spain, on 25 February 2020. It increased in frequency very fast and by the end of May more than 70,000 cases had been confirmed by reverse transcription-polymerase chain reaction (RT-PCR). To study the lineages and the diversity of the viral population during this first epidemic wave in Madrid we sequenced 224 SARS-CoV-2 viral genomes collected from three hospitals from February to May 2020. All the known major lineages were found in this set of samples, though B.1 and B.1.5 were the most frequent ones, accounting for more than 60% of the sequences. In parallel with the B lineages and sublineages, the D614G mutation in the Spike protein sequence was detected soon after the detection of the first coronavirus disease 19 (COVID-19) case in Madrid and in two weeks became dominant, being found in 80% of the samples and remaining at this level during all the study periods. The lineage composition of the viral population found in Madrid was more similar to the European population than to the publicly available Spanish data, underlining the role of Madrid as a national and international transport hub. In agreement with this, phylodynamic analysis suggested multiple independent entries before the national lockdown and air transportation restrictions.
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http://dx.doi.org/10.3390/microorganisms9020454DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7926973PMC
February 2021

Prolonged SARS-CoV-2 cell culture replication in respiratory samples from patients with severe COVID-19.

Clin Microbiol Infect 2021 Jun 22;27(6):886-891. Epub 2021 Feb 22.

Department of Clinical Microbiology, Hospital Universitario 12 de Octubre, Madrid, Spain; Research Institute Hospital 12 de Octubre, imas12, Madrid, Spain; Department of Medicine, Complutense University of Madrid, School of Medicine, Madrid, Spain.

Objectives: This study compares the infectivity of SARS-CoV-2 in respiratory samples from patients with mild COVID-19 with those from hospitalized patients with severe bilateral pneumonia. In severe COVID-19, we also analysed the presence of neutralizing activity in paired sera.

Methods: We performed cell cultures on 193 real-time reverse transcription polymerase chain reaction respiratory samples, positive for SARS-CoV-2, obtained from 189 patients at various times, from clinical diagnosis to follow-up. Eleven samples were obtained from asymptomatic individuals, 91 samples from 91 outpatients with mild forms of COVID-19 and 91 samples from 87 inpatients with severe pneumonia. In these patients, neutralizing activity was analysed in 30 paired sera collected after symptom onset >10 days.

Results: We detected a cytopathic effect (CPE) in 91/193 (47%) samples. Viral viability was maintained for up to 10 days in patients with mild COVID-19. In patients with severe COVID-19, the virus remained viable for up to 32 days after the onset of symptoms. Patients with severe COVID-19 presented infectious virus at a significantly higher rate in the samples with moderate to low viral load (cycle threshold value ≥ 26): 32/75 (43%) versus 14/63 (22%) for mild cases (p < 0.01). We observed a positive CPE despite the presence of clear neutralizing activity (NT50 > 1:1024 in 10% (3/30) of samples.

Discussion: Patients with severe COVID-19 might shed viable virus during prolonged periods of up to 4 weeks after symptom onset, even when presenting high cycle threshold values in their respiratory samples and despite having developed high neutralizing antibody titres.
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http://dx.doi.org/10.1016/j.cmi.2021.02.014DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7898982PMC
June 2021

Fever without source as the first manifestation of SARS-CoV-2 infection in infants less than 90 days old.

Eur J Pediatr 2021 Jul 19;180(7):2099-2106. Epub 2021 Feb 19.

Red de Investigación Translacional en Infectología Pediátrica (RITIP), Madrid, Spain.

Fever without source (FWS) in infants is a frequent cause of consultation at the emergency department, and the emergence of SARS-CoV-2 could affect the approach to those infants. The aim of this study is to define the clinical characteristics and rates of bacterial coinfections of infants < 90 days with FWS as the first manifestation of SARS-CoV-2 infection. This is a cross-sectional study of infants under 90 days of age with FWS and positive SARS-CoV2 PCR in nasopharyngeal swab/aspirate, attended at the emergency departments of 49 Spanish hospitals (EPICO-AEP cohort) from March 1 to June 26, 2020. Three hundred and thirty-three children with COVID-19 were included in EPICO-AEP. A total of 67/336 (20%) were infants less than 90 days old, and 27/67(40%) presented with FWS. Blood cultures were performed in 24/27(89%) and were negative in all but one (4%) who presented a Streptococcus mitis bacteremia. Urine culture was performed in 26/27(97%) children and was negative in all, except in two (7%) patients. Lumbar puncture was performed in 6/27(22%) cases, with no growth of bacteria. Two children had bacterial coinfections: 1 had UTI and bacteremia, and 1 had UTI. C-reactive was protein over 20 mg/L in two children (one with bacterial coinfection), and procalcitonin was normal in all. One child was admitted to the pediatric intensive care unit because of apnea episodes. No patients died.Conclusion: FWS was frequent in infants under 90 days of age with SARS-CoV-2 infection. Standardized markers to rule out bacterial infections remain useful in this population, and the outcome is generally good. What is Known: • Fever without source (FWS) in infants is a common cause of consultation at the emergency department, and young infants have a higher risk of serious bacterial infections (SBI). • The emergence of the new coronavirus SARS-CoV-2 could affect the approach to young infants with FWS in the emergency department. management of those children is a challenge because information about bacterial coinfection and prognosis is scarce. What is New: • SARS-CoV-2 infection should be ruled out in young infants (< 90 days of age) with FWS in areas with community transmission. • Bacterial coinfection rarely coexists in those infants. • Inflammatory markers were not increased in children without bacterial coinfection. • Outcome is good in most patients.
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http://dx.doi.org/10.1007/s00431-021-03973-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7893843PMC
July 2021

Identification of potential inhibitors of protein-protein interaction useful to fight against Ebola and other highly pathogenic viruses.

Antiviral Res 2021 02 8;186:105011. Epub 2021 Jan 8.

Centro de Investigaciones Biológicas Margarita Salas (CSIC), Ramiro de Maeztu 9, 28040, Madrid, Spain. Electronic address:

Despite the efforts to develop new treatments against Ebola virus (EBOV) there is currently no antiviral drug licensed to treat patients with Ebola virus disease (EVD). Therefore, there is still an urgent need to find new drugs to fight against EBOV. In order to do this, a virtual screening was done on the druggable interaction between the EBOV glycoprotein (GP) and the host receptor NPC1 with a subsequent selection of compounds for further validation. This screening led to the identification of new small organic molecules with potent inhibitory action against EBOV infection using lentiviral EBOV-GP-pseudotype viruses. Moreover, some of these compounds have shown their ability to interfere with the intracellular cholesterol transport receptor NPC1 using an ELISA-based assay. These preliminary results pave the way to hit to lead optimization programs that lead to successful candidates.
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http://dx.doi.org/10.1016/j.antiviral.2021.105011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7833471PMC
February 2021

Evaluation of the MOD11A2 product for canopy temperature monitoring in the Brazilian Atlantic Forest.

Environ Monit Assess 2021 Jan 7;193(1):45. Epub 2021 Jan 7.

Department of Soils, Federal Rural University of Rio de Janeiro (UFRRJ), Seropédica, Rio de Janeiro, 23897-000, Brazil.

Forest canopies have an important influence on the global climate balance. Through the analysis of the temperature of the canopy, it is possible to infer about the physiological aspects of the plants, helping to understand the behavior of the vegetation and, consequently, in the environmental monitoring and management of green areas. This study aims to validate the MOD11A2 V006 product from canopy surface temperature data obtained by an infrared radiation sensor. For the validation of the MOD11A2 product, a comparative analysis was performed between the land surface temperature (LST) data, obtained by the MODIS sensor, and the canopy temperature data, obtained by the SI-111 infrared radiation sensor coupled to the Itatiaia National Park (PNI) micrometeorological tower. Meteorological variables and land surface temperature collected from January to December 2018 in the PNI were also analyzed. The results reveal that the MOD11A2 product overestimates the canopy temperature in the daytime (MB ranging from 1.56 to 3.57 °C) and underestimates in the night time (MB ranging from - 0.18 to - 4.22 °C). During daytime, the months corresponding to the dry season presented a very high correlation (r = 0.74 and 0.86) and the highest values for the Willmott index (d = 0.70 and 0.64). At nighttime, the MOD11A2 product did not present a good performance for the LST estimation, especially in the rainy season. Therefore, we observed that the MOD11A2 product has limitations to estimate the land surface temperature and that possible changes in the algorithm of this product can be performed for high atmospheric humidity conditions.
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http://dx.doi.org/10.1007/s10661-020-08788-zDOI Listing
January 2021

Prolonged administration of maraviroc reactivates latent HIV in vivo but it does not prevent antiretroviral-free viral rebound.

Sci Rep 2020 12 18;10(1):22286. Epub 2020 Dec 18.

Servicio de Enfermedades Infecciosas, Instituto Ramón Y Cajal de Investigación Sanitaria (IRYCIS) - Hospital Universitario Ramón Y Cajal, Carretera de Colmenar, Km 9.100, 28034, Madrid, Spain.

Human immunodeficiency virus (HIV) remains incurable due to latent viral reservoirs established in non-activated CD4 T cells that cannot be eliminated via antiretroviral therapy. Current efforts to cure HIV are focused on identifying drugs that will induce viral gene expression in latently infected cells, commonly known as latency reversing agents (LRAs). Some drugs have been shown to reactivate latent HIV but do not cause a reduction in reservoir size. Therefore, finding new LRAs or new combinations or increasing the round of stimulations is needed to cure HIV. However, the effects of these drugs on viral rebound after prolonged treatment have not been evaluated. In a previous clinical trial, antiretroviral therapy intensification with maraviroc for 48 weeks caused an increase in residual viremia and episomal two LTR-DNA circles suggesting that maraviroc could reactivate latent HIV. We amended the initial clinical trial to explore additional virologic parameters in stored samples and to evaluate the time to viral rebound during analytical treatment interruption in three patients. Maraviroc induced an increase in cell-associated HIV RNA during the administration of the drug. However, there was a rapid rebound of viremia after antiretroviral therapy discontinuation. HIV-specific T cell response was slightly enhanced. These results show that maraviroc can reactivate latent HIV in vivo but further studies are required to efficiently reduce the reservoir size.
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http://dx.doi.org/10.1038/s41598-020-79002-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7749169PMC
December 2020

Seroprevalence analysis of SARS-CoV-2 in pregnant women along the first pandemic outbreak and perinatal outcome.

PLoS One 2020 30;15(11):e0243029. Epub 2020 Nov 30.

Instituto de Investigación Hospital 12 de Octubre (imas12), Madrid, Spain.

Objectives: To evaluate the progression of the seroprevalence of SARS-CoV-2 in the pregnant population of the south of Madrid during the first wave of the COVID-19 pandemic. Secondarily we aimed to evaluate maternal and perinatal outcomes.

Study Design: Retrospective cohort study conducted at Hospital Universitario 12 de Octubre during weeks 10 to 19 of 2020, coinciding with the Spanish lockdown. We tested 769 serum samples obtained from routine serological testing during the first and third trimesters of pregnancy for specific IgG anti SARS-CoV-2 RBD and S proteins. RT-PCR tests were performed in suspected cases according to clinical practice. We compared maternal and perinatal outcomes in those with delivered pregnancies (n = 578) according to the presence or absence of specific IgG antibodies. Those with positive IgG were subdivided by the presence or absence of Covid-19 related symptoms at any time and the results of RT-PCR testing if performed. Therefore, we had 4 study groups: G1 (IgG negative), G2 (IgG positive, asymptomatic, RT-PCR testing negative or not done), G3 (IgG positive, symptomatic, RT-PCR testing negative or not done), and G4 (IgG positive, symptomatic, RT-PCR positive).

Results: Seropositivity increased from 0% to 21.4% (95% CI 11.8-31.0) during the study period, of which 27.9% had an asymptomatic course. Overall outcomes were favorable with a significant increased rate of preterm birth in G4 vs G1 (21.4% vs 6.7%) and cesarean/operative delivery (50% vs 26.9%). Asymptomatic and mild cases did not have differences regarding pregnancy course when compared to seronegative women. There were no documented cases of vertical or horizontal transmission.

Conclusion: Seroprevalence in pregnant women in southern Madrid went up to 21.4% of which 27.9% had an asymptomatic course. Overall perinatal results were favorable, especially in those asymptomatic.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0243029PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7703887PMC
December 2020

Long-term efficacy of dolutegravir plus lamivudine for maintenance of HIV viral suppression in adults with and without historical resistance to lamivudine: Week 96 results of ART-PRO pilot study.

J Antimicrob Chemother 2021 02;76(3):738-742

Hospital Universitario La Paz - IdiPAZ, Paseo de la Castellana 261 28046, Madrid, Spain.

Background: In the ART-PRO pilot trial there were no virological failures through 48 weeks of treatment with dolutegravir plus lamivudine in suppressed individuals with and without archived lamivudine resistance-associated mutations (RAMs) detected through next-generation sequencing (NGS) but without evidence of lamivudine RAMs in baseline proviral DNA population sequencing.

Objectives: To present 96 week results from ART-PRO.

Methods: Open-label, single-arm pilot trial. At baseline, all participants switched to dolutegravir plus lamivudine. Participants were excluded if proviral DNA population genotyping detected lamivudine RAMs. To detect resistance minority variants, proviral DNA NGS was retrospectively performed from baseline samples. For this analysis the efficacy endpoint was the proportion of participants with <50 HIV-1 RNA copies/mL at week 96. Safety and tolerability outcomes were incidence of adverse events and treatment discontinuations.

Results: Forty-one participants were included, 21 with lamivudine RAMs in historical plasma RNA genotypes. Baseline proviral DNA NGS detected lamivudine RAMs (M184V/I and/or K65R/E/N) above a 5% threshold in 71.4% (15/21) and 15% (3/20) of participants with and without history of lamivudine resistance, respectively. At 96 weeks, 90.2% of participants achieved the efficacy endpoint. Between week 48 and 96 there was one discontinuation due to consent withdrawal and no discontinuations related to adverse events. Two participants had a transient viral rebound, both re-suppressed on dolutegravir plus lamivudine. Through week 96, there were no virological failures.

Conclusions: In this pilot trial, dolutegravir plus lamivudine maintained virological suppression at 96 weeks despite historical lamivudine resistance and persisting archived minority lamivudine RAMs.
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http://dx.doi.org/10.1093/jac/dkaa479DOI Listing
February 2021

Prolonged Auditory Brainstem Response in Universal Hearing Screening of Newborns with Autism Spectrum Disorder.

Autism Res 2021 01 2;14(1):46-52. Epub 2020 Nov 2.

Department of Biomedical Informatics, Harvard Medical School, Boston, Massachusetts, USA.

Previous studies report prolonged auditory brainstem response (ABR) in children and adults with autism spectrum disorder (ASD). Despite its promise as a biomarker, it is unclear whether healthy newborns who later develop ASD also show ABR abnormalities. In the current study, we extracted ABR data on 139,154 newborns from their Universal Newborn Hearing Screening, including 321 newborns who were later diagnosed with ASD. We found that the ASD newborns had significant prolongations of their ABR phase and V-negative latency compared with the non-ASD newborns. Newborns in the ASD group also exhibited greater variance in their latencies compared to previous studies in older ASD samples, likely due in part to the low intensity of the ABR stimulus. These findings suggest that newborns display neurophysiological variation associated with ASD at birth. Future studies with higher-intensity stimulus ABRs may allow more accurate predictions of ASD risk, which could augment the universal ABR test that currently screens millions of newborns worldwide. LAY SUMMARY: Children with autism spectrum disorder (ASD) have slow brain responses to sounds. We examined these brain responses from newborns' hearing tests and found that newborns who were later diagnosed with autism also had slower brain responses to sounds. Future studies might use these findings to better predict autism risk, with a hearing test that is already used on millions of newborns worldwide.
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http://dx.doi.org/10.1002/aur.2422DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7894135PMC
January 2021

Persistent fire foci in all biomes undermine the Paris Agreement in Brazil.

Sci Rep 2020 10 1;10(1):16246. Epub 2020 Oct 1.

Postgraduate Program in Management and Regulation of Water Resources - ProfÁgua, State University of Mato Grosso (UNEMAT), Cuiabá, Mato Grosso, Brazil.

Brazil is one of the world's biggest emitters of greenhouse gases (GHGs). Fire foci across the country contributes to these emissions and compromises emission reduction targets pledged by Brazil under the Paris Agreement. In this paper, we quantify fire foci, burned areas, and carbon emissions in all Brazilian biomes (i.e., Amazon, Cerrado, Caatinga, Atlantic Forest, Pantanal and Pampa). We analyzed these variables using cluster analysis and non-parametric statistics to predict carbon and CO emissions for the next decade. Our results showed no increase in the number of fire foci and carbon emissions for the evaluated time series, whereby the highest emissions occur and will persist in the Amazon and Cerrado biomes. The Atlantic Forest, Pantanal, Caatinga and Pampa biomes had low emissions compared to the Amazon and Cerrado. Based on 2030 projections, the sum of emissions from fire foci in the six Brazilian biomes will exceed 5.7 Gt CO2, compromising the national GHG reduction targets. To reduce GHG emissions, Brazil will need to control deforestation induced by the expansion of the agricultural frontier in the Amazon and Cerrado biomes. This can only be achieved through significant political effort involving the government, entrepreneurs and society as a collective.
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http://dx.doi.org/10.1038/s41598-020-72571-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7529887PMC
October 2020
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