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Rationale and design of the pragmatic clinical trial tREatment with Beta-blockers after myOcardial infarction withOut reduced ejection fracTion (REBOOT)

Rossello, Xavier ; Raposeiras-Roubin, Sergio ; Latini, Roberto ; [et al.]

Oxford University Press (OUP) ; 2022

In: European Heart Journal - Cardiovascular Pharmacotherapy Vol. 8, No. 3 ( 2022-05-05), p. 291-301

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In: European Heart Journal - Cardiovascular Pharmacotherapy, Oxford University Press (OUP), Vol. 8, No. 3 ( 2022-05-05), p. 291-301

Abstract: There is a lack of evidence regarding the benefits of β-blocker treatment after invasively managed acute myocardial infarction (MI) without reduced left ventricular ejection fraction (LVEF). Methods and results The tREatment with Beta-blockers after myOcardial infarction withOut reduced ejection fracTion (REBOOT) trial is a pragmatic, controlled, prospective, randomized, open-label blinded endpoint (PROBE design) clinical trial testing the benefits of β-blocker maintenance therapy in patients discharged after MI with or without ST-segment elevation. Patients eligible for participation are those managed invasively during index hospitalization (coronary angiography), with LVEF & gt;40%, and no history of heart failure (HF). At discharge, patients will be randomized 1:1 to β-blocker therapy (agent and dose according to treating physician) or no β-blocker therapy. The primary endpoint is a composite of all-cause death, non-fatal reinfarction, or HF hospitalization over a median follow-up period of 2.75 years (minimum 2 years, maximum 3 years). Key secondary endpoints include the incidence of the individual components of the primary composite endpoint, the incidence of cardiac death, and incidence of malignant ventricular arrhythmias or resuscitated cardiac arrest. The primary endpoint will be analysed according to the intention-to-treat principle. Conclusion The REBOOT trial will provide robust evidence to guide the prescription of β-blockers to patients discharged after MI without reduced LVEF.

Type of Medium: Online Resource

ISSN: 2055-6837 , 2055-6845

URL: Article

DOI: 10.1093/ehjcvp/pvab060

Language: English

Publisher: Oxford University Press (OUP)

Publication Date: 2022

detail.hit.zdb_id: 2808613-2

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Rational Design of Chemically Controlled Antibodies and Protein Therapeutics

Marchand, Anthony ; Bonati, Lucia ; Shui, Sailan ; [et al.]

American Chemical Society (ACS) ; 2023

In: ACS Chemical Biology Vol. 18, No. 6 ( 2023-06-16), p. 1259-1265

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In: ACS Chemical Biology, American Chemical Society (ACS), Vol. 18, No. 6 ( 2023-06-16), p. 1259-1265

Type of Medium: Online Resource

ISSN: 1554-8929 , 1554-8937

URL: Article

DOI: 10.1021/acschembio.3c00012

DOI: 10.1021/acschembio.3c00012.s001

Language: English

Publisher: American Chemical Society (ACS)

Publication Date: 2023

detail.hit.zdb_id: 2221735-6

SSG: 12

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Algorithms for protein design

Gainza, Pablo ; Nisonoff, Hunter M ; Donald, Bruce R

Elsevier BV ; 2016

In: Current Opinion in Structural Biology Vol. 39 ( 2016-08), p. 16-26

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In: Current Opinion in Structural Biology, Elsevier BV, Vol. 39 ( 2016-08), p. 16-26

Type of Medium: Online Resource

ISSN: 0959-440X

URL: Article

DOI: 10.1016/j.sbi.2016.03.006

Language: English

Publisher: Elsevier BV

Publication Date: 2016

detail.hit.zdb_id: 2019233-2

SSG: 12

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Computational protein design — the next generation tool to expand synthetic biology applications

Gainza-Cirauqui, Pablo ; Correia, Bruno Emanuel

Elsevier BV ; 2018

In: Current Opinion in Biotechnology Vol. 52 ( 2018-08), p. 145-152

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In: Current Opinion in Biotechnology, Elsevier BV, Vol. 52 ( 2018-08), p. 145-152

Type of Medium: Online Resource

ISSN: 0958-1669

URL: Article

DOI: 10.1016/j.copbio.2018.04.001

Language: English

Publisher: Elsevier BV

Publication Date: 2018

detail.hit.zdb_id: 2019676-3

SSG: 12

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Elective Cancer Surgery in COVID-19–Free Surgical Pathways During the SARS-CoV-2 Pandemic: An International, Multicenter, Comparative Cohort Study

Glasbey, James C. ; Nepogodiev, Dmitri ; Simoes, Joana F.F. ; [et al.]

American Society of Clinical Oncology (ASCO) ; 2021

In: Journal of Clinical Oncology Vol. 39, No. 1 ( 2021-01-01), p. 66-78

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In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 39, No. 1 ( 2021-01-01), p. 66-78

Abstract: As cancer surgery restarts after the first COVID-19 wave, health care providers urgently require data to determine where elective surgery is best performed. This study aimed to determine whether COVID-19–free surgical pathways were associated with lower postoperative pulmonary complication rates compared with hospitals with no defined pathway. PATIENTS AND METHODS This international, multicenter cohort study included patients who underwent elective surgery for 10 solid cancer types without preoperative suspicion of SARS-CoV-2. Participating hospitals included patients from local emergence of SARS-CoV-2 until April 19, 2020. At the time of surgery, hospitals were defined as having a COVID-19–free surgical pathway (complete segregation of the operating theater, critical care, and inpatient ward areas) or no defined pathway (incomplete or no segregation, areas shared with patients with COVID-19). The primary outcome was 30-day postoperative pulmonary complications (pneumonia, acute respiratory distress syndrome, unexpected ventilation). RESULTS Of 9,171 patients from 447 hospitals in 55 countries, 2,481 were operated on in COVID-19–free surgical pathways. Patients who underwent surgery within COVID-19–free surgical pathways were younger with fewer comorbidities than those in hospitals with no defined pathway but with similar proportions of major surgery. After adjustment, pulmonary complication rates were lower with COVID-19–free surgical pathways (2.2% v 4.9%; adjusted odds ratio [aOR], 0.62; 95% CI, 0.44 to 0.86). This was consistent in sensitivity analyses for low-risk patients (American Society of Anesthesiologists grade 1/2), propensity score–matched models, and patients with negative SARS-CoV-2 preoperative tests. The postoperative SARS-CoV-2 infection rate was also lower in COVID-19–free surgical pathways (2.1% v 3.6%; aOR, 0.53; 95% CI, 0.36 to 0.76). CONCLUSION Within available resources, dedicated COVID-19–free surgical pathways should be established to provide safe elective cancer surgery during current and before future SARS-CoV-2 outbreaks.

Type of Medium: Online Resource

ISSN: 0732-183X , 1527-7755

URL: Article

DOI: 10.1200/JCO.20.01933

RVK:

XA 52760

RVK:

XA 10000

Language: English

Publisher: American Society of Clinical Oncology (ASCO)

Publication Date: 2021

detail.hit.zdb_id: 2005181-5

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Compact Representation of Continuous Energy Surfaces for More Efficient Protein Design

Hallen, Mark A. ; Gainza, Pablo ; Donald, Bruce R.

American Chemical Society (ACS) ; 2015

In: Journal of Chemical Theory and Computation Vol. 11, No. 5 ( 2015-05-12), p. 2292-2306

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In: Journal of Chemical Theory and Computation, American Chemical Society (ACS), Vol. 11, No. 5 ( 2015-05-12), p. 2292-2306

Type of Medium: Online Resource

ISSN: 1549-9618 , 1549-9626

URL: Article

DOI: 10.1021/ct501031m

Language: English

Publisher: American Chemical Society (ACS)

Publication Date: 2015

detail.hit.zdb_id: 2166976-4

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Protein design algorithms predict viable resistance to an experimental antifolate

Reeve, Stephanie M. ; Gainza, Pablo ; Frey, Kathleen M. ; [et al.]

Proceedings of the National Academy of Sciences ; 2015

In: Proceedings of the National Academy of Sciences Vol. 112, No. 3 ( 2015-01-20), p. 749-754

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In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 112, No. 3 ( 2015-01-20), p. 749-754

Abstract: Methods to accurately predict potential drug target mutations in response to early-stage leads could drive the design of more resilient first generation drug candidates. In this study, a structure-based protein design algorithm (K* in the OSPREY suite) was used to prospectively identify single-nucleotide polymorphisms that confer resistance to an experimental inhibitor effective against dihydrofolate reductase (DHFR) from Staphylococcus aureus . Four of the top-ranked mutations in DHFR were found to be catalytically competent and resistant to the inhibitor. Selection of resistant bacteria in vitro reveals that two of the predicted mutations arise in the background of a compensatory mutation. Using enzyme kinetics, microbiology, and crystal structures of the complexes, we determined the fitness of the mutant enzymes and strains, the structural basis of resistance, and the compensatory relationship of the mutations. To our knowledge, this work illustrates the first application of protein design algorithms to prospectively predict viable resistance mutations that arise in bacteria under antibiotic pressure.

Type of Medium: Online Resource

ISSN: 0027-8424 , 1091-6490

URL: Article

DOI: 10.1073/pnas.1411548112

RVK:

TA 1000

RVK:

WA 15000

Language: English

Publisher: Proceedings of the National Academy of Sciences

Publication Date: 2015

detail.hit.zdb_id: 209104-5

detail.hit.zdb_id: 1461794-8

SSG: 11

SSG: 12

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Chiral evasion and stereospecific antifolate resistance in Staphylococcus aureus

Wang, Siyu ; Reeve, Stephanie M. ; Holt, Graham T. ; [et al.]

Public Library of Science (PLoS) ; 2022

In: PLOS Computational Biology Vol. 18, No. 2 ( 2022-2-10), p. e1009855-

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In: PLOS Computational Biology, Public Library of Science (PLoS), Vol. 18, No. 2 ( 2022-2-10), p. e1009855-

Abstract: Antimicrobial resistance presents a significant health care crisis. The mutation F98Y in Staphylococcus aureus dihydrofolate reductase (SaDHFR) confers resistance to the clinically important antifolate trimethoprim (TMP). Propargyl-linked antifolates (PLAs), next generation DHFR inhibitors, are much more resilient than TMP against this F98Y variant, yet this F98Y substitution still reduces efficacy of these agents. Surprisingly, differences in the enantiomeric configuration at the stereogenic center of PLAs influence the isomeric state of the NADPH cofactor. To understand the molecular basis of F98Y-mediated resistance and how PLAs’ inhibition drives NADPH isomeric states, we used protein design algorithms in the osprey protein design software suite to analyze a comprehensive suite of structural, biophysical, biochemical, and computational data. Here, we present a model showing how F98Y SaDHFR exploits a different anomeric configuration of NADPH to evade certain PLAs’ inhibition, while other PLAs remain unaffected by this resistance mechanism.

Type of Medium: Online Resource

ISSN: 1553-7358

URL: Article

DOI: 10.1371/journal.pcbi.1009855

DOI: 10.1371/journal.pcbi.1009855.g001

DOI: 10.1371/journal.pcbi.1009855.g002

DOI: 10.1371/journal.pcbi.1009855.g003

DOI: 10.1371/journal.pcbi.1009855.g004

DOI: 10.1371/journal.pcbi.1009855.g005

DOI: 10.1371/journal.pcbi.1009855.g006

DOI: 10.1371/journal.pcbi.1009855.g007

DOI: 10.1371/journal.pcbi.1009855.g008

DOI: 10.1371/journal.pcbi.1009855.t001

DOI: 10.1371/journal.pcbi.1009855.t002

DOI: 10.1371/journal.pcbi.1009855.s001

DOI: 10.1371/journal.pcbi.1009855.s002

DOI: 10.1371/journal.pcbi.1009855.s003

DOI: 10.1371/journal.pcbi.1009855.s004

DOI: 10.1371/journal.pcbi.1009855.s005

DOI: 10.1371/journal.pcbi.1009855.s006

DOI: 10.1371/journal.pcbi.1009855.s007

DOI: 10.1371/journal.pcbi.1009855.s008

DOI: 10.1371/journal.pcbi.1009855.s009

DOI: 10.1371/journal.pcbi.1009855.s010

DOI: 10.1371/journal.pcbi.1009855.s011

DOI: 10.1371/journal.pcbi.1009855.s012

DOI: 10.1371/journal.pcbi.1009855.s013

DOI: 10.1371/journal.pcbi.1009855.r001

DOI: 10.1371/journal.pcbi.1009855.r002

DOI: 10.1371/journal.pcbi.1009855.r003

DOI: 10.1371/journal.pcbi.1009855.r004

Language: English

Publisher: Public Library of Science (PLoS)

Publication Date: 2022

detail.hit.zdb_id: 2193340-6

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Tétanos secundario a mordedura y arañazo de gato en una paciente previamente vacunada

Fica, Alberto ; Gaínza, Daniela ; Ortigosa, Pablo

SciELO Agencia Nacional de Investigacion y Desarrollo (ANID) ; 2017

In: Revista chilena de infectología Vol. 34, No. 2 ( 2017-04), p. 181-185

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In: Revista chilena de infectología, SciELO Agencia Nacional de Investigacion y Desarrollo (ANID), Vol. 34, No. 2 ( 2017-04), p. 181-185

Type of Medium: Online Resource

ISSN: 0716-1018

URL: Article

DOI: 10.4067/S0716-10182017000200012

Language: English

Publisher: SciELO Agencia Nacional de Investigacion y Desarrollo (ANID)

Publication Date: 2017

detail.hit.zdb_id: 2048815-4

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Rules and mechanisms governing G protein coupling selectivity of GPCRs

Masuho, Ikuo ; Kise, Ryoji ; Gainza, Pablo ; [et al.]

Elsevier BV ; 2023

In: Cell Reports Vol. 42, No. 10 ( 2023-10), p. 113173-

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In: Cell Reports, Elsevier BV, Vol. 42, No. 10 ( 2023-10), p. 113173-

Type of Medium: Online Resource

ISSN: 2211-1247

URL: Article

DOI: 10.1016/j.celrep.2023.113173

Language: English

Publisher: Elsevier BV

Publication Date: 2023

detail.hit.zdb_id: 2649101-1

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