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  1. Article ; Online: The 2019 coronavirus: Learning curves, lessons, and the weakest link.

    Stein, Richard Albert

    International journal of clinical practice

    2020  Volume 74, Issue 4, Page(s) e13488

    Keywords covid19
    Language English
    Publishing date 2020-02-12
    Publishing country England
    Document type Editorial
    ZDB-ID 1386246-7
    ISSN 1742-1241 ; 1368-5031
    ISSN (online) 1742-1241
    ISSN 1368-5031
    DOI 10.1111/ijcp.13488
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  2. Article ; Online: COVID-19: Risk groups, mechanistic insights and challenges.

    Stein, Richard Albert

    International journal of clinical practice

    2020  Volume 74, Issue 8, Page(s) e13512

    MeSH term(s) Betacoronavirus ; COVID-19 ; Coronavirus Infections ; Humans ; Pandemics ; Pneumonia, Viral ; Protease Inhibitors ; SARS-CoV-2
    Chemical Substances Protease Inhibitors
    Keywords covid19
    Language English
    Publishing date 2020-05-12
    Publishing country India
    Document type Letter ; Comment
    ZDB-ID 1386246-7
    ISSN 1742-1241 ; 1368-5031
    ISSN (online) 1742-1241
    ISSN 1368-5031
    DOI 10.1111/ijcp.13512
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  5. Article ; Online: COVID‐19

    Stein, Richard Albert

    International Journal of Clinical Practice

    Risk groups, mechanistic insights and challenges

    2020  Volume 74, Issue 8

    Keywords General Medicine ; covid19
    Language English
    Publisher Wiley
    Publishing country us
    Document type Article ; Online
    ZDB-ID 1386246-7
    ISSN 1742-1241 ; 1368-5031
    ISSN (online) 1742-1241
    ISSN 1368-5031
    DOI 10.1111/ijcp.13512
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  6. Article ; Online: Assessing the clinical viability of micro 3 pronuclei zygotes.

    Canon, Chelsea / Thurman, Anabel / Li, Albert / Hernandez-Nieto, Carlos / Lee, Joseph A / Roth, Rose Marie / Slifkin, Richard / Briton-Jones, Christine / Stein, Daniel / Copperman, Alan B

    Journal of assisted reproduction and genetics

    2023  Volume 40, Issue 7, Page(s) 1765–1772

    Abstract: Purpose: What is the rate of euploidy and clinical viability of embryos resulting from micro 3 pronuclei zygotes?: Methods: Retrospective cohort analysis in a single, academic in vitro fertilization (IVF) center from March 2018 to June 2021. Cohorts ... ...

    Abstract Purpose: What is the rate of euploidy and clinical viability of embryos resulting from micro 3 pronuclei zygotes?
    Methods: Retrospective cohort analysis in a single, academic in vitro fertilization (IVF) center from March 2018 to June 2021. Cohorts were separated by fertilization as either a 2 pronuclear zygote (2PN) or micro 3 pronuclear zygote (micro 3PN). PGT-A was performed to identify embryonic ploidy rates in embryos created from micro 3PN zygotes. The clinical outcomes of all transferred euploid micro 3PN zygotes were evaluated from frozen embryo transfer (FET) cycles.
    Results: During the designated study period, 75,903 mature oocytes were retrieved and underwent ICSI. Of these, 60,161 were fertilized as 2PN zygotes (79.3%) and 183 fertilized as micro 3PN zygotes (0.24%). Of the micro 3PN-derived embryos that underwent biopsy, 27.5% (n=11/42) were deemed euploid by PGT-A, compared to 51.4% (n=12,301/23,923) of 2PN-derived embryos, p=0.06. Four micro 3PN-derived embryos were transferred in subsequent single euploid FET cycles, which includes one live birth and one ongoing pregnancy.
    Conclusion: Micro 3PN zygotes that develop to the blastocyst stage and meet the criteria for embryo biopsy have the potential to be euploid by preimplantation genetic testing for aneuploidy (PGT-A) and if selected for transfer can achieve a live birth. Although there are a significantly lower number of micro 3PN embryos that make it to blastocyst biopsy, the potential to continue to culture abnormally fertilized oocytes may give these patients a chance at pregnancy that they previously did not have.
    MeSH term(s) Pregnancy ; Female ; Humans ; Zygote ; Retrospective Studies ; Preimplantation Diagnosis/methods ; Fertilization in Vitro/methods ; Fertilization ; Genetic Testing/methods ; Aneuploidy ; Blastocyst/pathology
    Language English
    Publishing date 2023-05-25
    Publishing country Netherlands
    Document type Journal Article
    ZDB-ID 1112577-9
    ISSN 1573-7330 ; 1058-0468
    ISSN (online) 1573-7330
    ISSN 1058-0468
    DOI 10.1007/s10815-023-02830-y
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  7. Article ; Online: Sigh Ventilation in Patients With Trauma: The SiVent Randomized Clinical Trial.

    Albert, Richard K / Jurkovich, Gregory J / Connett, John / Helgeson, Erika S / Keniston, Angela / Voelker, Helen / Lindberg, Sarah / Proper, Jennifer L / Bochicchio, Grant / Stein, Deborah M / Cain, Christian / Tesoriero, Ron / Brown, Carlos V R / Davis, James / Napolitano, Lena / Carver, Thomas / Cipolle, Mark / Cardenas, Luis / Minei, Joseph /
    Nirula, Raminder / Doucet, Jay / Miller, Preston R / Johnson, Jeffrey / Inaba, Kenji / Kao, Lillian

    JAMA

    2023  Volume 330, Issue 20, Page(s) 1982–1990

    Abstract: Importance: Among patients receiving mechanical ventilation, tidal volumes with each breath are often constant or similar. This may lead to ventilator-induced lung injury by altering or depleting surfactant. The role of sigh breaths in reducing ... ...

    Abstract Importance: Among patients receiving mechanical ventilation, tidal volumes with each breath are often constant or similar. This may lead to ventilator-induced lung injury by altering or depleting surfactant. The role of sigh breaths in reducing ventilator-induced lung injury among trauma patients at risk of poor outcomes is unknown.
    Objective: To determine whether adding sigh breaths improves clinical outcomes.
    Design, setting, and participants: A pragmatic, randomized trial of sigh breaths plus usual care conducted from 2016 to 2022 with 28-day follow-up in 15 academic trauma centers in the US. Inclusion criteria were age older than 18 years, mechanical ventilation because of trauma for less than 24 hours, 1 or more of 5 risk factors for developing acute respiratory distress syndrome, expected duration of ventilation longer than 24 hours, and predicted survival longer than 48 hours.
    Interventions: Sigh volumes producing plateau pressures of 35 cm H2O (or 40 cm H2O for inpatients with body mass indexes >35) delivered once every 6 minutes. Usual care was defined as the patient's physician(s) treating the patient as they wished.
    Main outcomes and measures: The primary outcome was ventilator-free days. Prespecified secondary outcomes included all-cause 28-day mortality.
    Results: Of 5753 patients screened, 524 were enrolled (mean [SD] age, 43.9 [19.2] years; 394 [75.2%] were male). The median ventilator-free days was 18.4 (IQR, 7.0-25.2) in patients randomized to sighs and 16.1 (IQR, 1.1-24.4) in those receiving usual care alone (P = .08). The unadjusted mean difference in ventilator-free days between groups was 1.9 days (95% CI, 0.1 to 3.6) and the prespecified adjusted mean difference was 1.4 days (95% CI, -0.2 to 3.0). For the prespecified secondary outcome, patients randomized to sighs had 28-day mortality of 11.6% (30/259) vs 17.6% (46/261) in those receiving usual care (P = .05). No differences were observed in nonfatal adverse events comparing patients with sighs (80/259 [30.9%]) vs those without (80/261 [30.7%]).
    Conclusions and relevance: In a pragmatic, randomized trial among trauma patients receiving mechanical ventilation with risk factors for developing acute respiratory distress syndrome, the addition of sigh breaths did not significantly increase ventilator-free days. Prespecified secondary outcome data suggest that sighs are well-tolerated and may improve clinical outcomes.
    Trial registration: ClinicalTrials.gov Identifier: NCT02582957.
    MeSH term(s) Humans ; Male ; Adult ; Adolescent ; Female ; Respiration ; Ventilators, Mechanical ; Inpatients ; Respiratory Distress Syndrome/therapy ; Ventilator-Induced Lung Injury
    Language English
    Publishing date 2023-10-25
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2958-0
    ISSN 1538-3598 ; 0254-9077 ; 0002-9955 ; 0098-7484
    ISSN (online) 1538-3598
    ISSN 0254-9077 ; 0002-9955 ; 0098-7484
    DOI 10.1001/jama.2023.21739
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  8. Article ; Online: A Straightforward Approach to the Analysis of Double Electron-Electron Resonance Data.

    Stein, Richard A / Beth, Albert H / Hustedt, Eric J

    Methods in enzymology

    2015  Volume 563, Page(s) 531–567

    Abstract: Double electron-electron resonance (DEER) is now widely utilized to measure distance distributions in the 20-70Å range. DEER is frequently applied to biological systems that have multiple conformational states leading to complex distance distributions. ... ...

    Abstract Double electron-electron resonance (DEER) is now widely utilized to measure distance distributions in the 20-70Å range. DEER is frequently applied to biological systems that have multiple conformational states leading to complex distance distributions. These complex distributions raise issues regarding the best approach to analyze DEER data. A widely used method utilizes a priori background correction followed by Tikhonov regularization. Unfortunately, the underlying assumptions of this approach can impact the analysis. In this chapter, a method of analyzing DEER data is presented that is ideally suited to obtain these complex distance distributions. The approach allows the fitting of raw experimental data without a priori background correction as well as the rigorous determination of uncertainties for all fitting parameters. This same methodological approach can be used for the simultaneous or global analysis of multiple DEER data sets using variable ratios of a common set of components, thus allowing direct correlation of distance components with functionally relevant conformational and biochemical states. Examples are given throughout to highlight this robust fitting approach.
    MeSH term(s) Electron Spin Resonance Spectroscopy/methods ; Electrons ; Models, Theoretical ; Software ; Spin Labels ; Statistics as Topic
    Chemical Substances Spin Labels
    Language English
    Publishing date 2015-09-15
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ISSN 1557-7988
    ISSN (online) 1557-7988
    DOI 10.1016/bs.mie.2015.07.031
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  9. Article ; Online: Candidate Tidal Disruption Event AT2019fdr Coincident with a High-Energy Neutrino.

    Reusch, Simeon / Stein, Robert / Kowalski, Marek / van Velzen, Sjoert / Franckowiak, Anna / Lunardini, Cecilia / Murase, Kohta / Winter, Walter / Miller-Jones, James C A / Kasliwal, Mansi M / Gilfanov, Marat / Garrappa, Simone / Paliya, Vaidehi S / Ahumada, Tomás / Anand, Shreya / Barbarino, Cristina / Bellm, Eric C / Brinnel, Valéry / Buson, Sara /
    Cenko, S Bradley / Coughlin, Michael W / De, Kishalay / Dekany, Richard / Frederick, Sara / Gal-Yam, Avishay / Gezari, Suvi / Giroletti, Marcello / Graham, Matthew J / Karambelkar, Viraj / Kimura, Shigeo S / Kong, Albert K H / Kool, Erik C / Laher, Russ R / Medvedev, Pavel / Necker, Jannis / Nordin, Jakob / Perley, Daniel A / Rigault, Mickael / Rusholme, Ben / Schulze, Steve / Schweyer, Tassilo / Singer, Leo P / Sollerman, Jesper / Strotjohann, Nora Linn / Sunyaev, Rashid / van Santen, Jakob / Walters, Richard / Zhang, B Theodore / Zimmerman, Erez

    Physical review letters

    2022  Volume 128, Issue 22, Page(s) 221101

    Abstract: The origins of the high-energy cosmic neutrino flux remain largely unknown. Recently, one high-energy neutrino was associated with a tidal disruption event (TDE). Here we present AT2019fdr, an exceptionally luminous TDE candidate, coincident with another ...

    Abstract The origins of the high-energy cosmic neutrino flux remain largely unknown. Recently, one high-energy neutrino was associated with a tidal disruption event (TDE). Here we present AT2019fdr, an exceptionally luminous TDE candidate, coincident with another high-energy neutrino. Our observations, including a bright dust echo and soft late-time x-ray emission, further support a TDE origin of this flare. The probability of finding two such bright events by chance is just 0.034%. We evaluate several models for neutrino production and show that AT2019fdr is capable of producing the observed high-energy neutrino, reinforcing the case for TDEs as neutrino sources.
    Language English
    Publishing date 2022-06-17
    Publishing country United States
    Document type Journal Article
    ZDB-ID 208853-8
    ISSN 1079-7114 ; 0031-9007
    ISSN (online) 1079-7114
    ISSN 0031-9007
    DOI 10.1103/PhysRevLett.128.221101
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  10. Article ; Online: Lipids modulate the conformational dynamics of a secondary multidrug transporter.

    Martens, Chloé / Stein, Richard A / Masureel, Matthieu / Roth, Aurélie / Mishra, Smriti / Dawaliby, Rosie / Konijnenberg, Albert / Sobott, Frank / Govaerts, Cédric / Mchaourab, Hassane S

    Nature structural & molecular biology

    2016  Volume 23, Issue 8, Page(s) 744–751

    Abstract: Direct interactions with lipids have emerged as key determinants of the folding, structure and function of membrane proteins, but an understanding of how lipids modulate protein dynamics is still lacking. Here, we systematically explored the effects of ... ...

    Abstract Direct interactions with lipids have emerged as key determinants of the folding, structure and function of membrane proteins, but an understanding of how lipids modulate protein dynamics is still lacking. Here, we systematically explored the effects of lipids on the conformational dynamics of the proton-powered multidrug transporter LmrP from Lactococcus lactis, using the pattern of distances between spin-label pairs previously shown to report on alternating access of the protein. We uncovered, at the molecular level, how the lipid headgroups shape the conformational-energy landscape of the transporter. The model emerging from our data suggests a direct interaction between lipid headgroups and a conserved motif of charged residues that control the conformational equilibrium through an interplay of electrostatic interactions within the protein. Together, our data lay the foundation for a comprehensive model of secondary multidrug transport in lipid bilayers.
    MeSH term(s) Bacterial Proteins/chemistry ; Cardiolipins/chemistry ; Hydrogen Bonding ; Hydrogen-Ion Concentration ; Kinetics ; Lactococcus lactis ; Membrane Lipids/chemistry ; Membrane Transport Proteins/chemistry ; Models, Molecular ; Protein Binding ; Protein Conformation ; Protein Stability
    Chemical Substances Bacterial Proteins ; Cardiolipins ; LmrP protein, Lactococcus lactis ; Membrane Lipids ; Membrane Transport Proteins
    Language English
    Publishing date 2016-08
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2126708-X
    ISSN 1545-9985 ; 1545-9993
    ISSN (online) 1545-9985
    ISSN 1545-9993
    DOI 10.1038/nsmb.3262
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