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  1. Article: A Clinical Model to Predict the Occurrence of Select High-risk Infections in the First Year Following Heart Transplantation.

    Perry, Whitney A / Chow, Jennifer K / Nelson, Jason / Kent, David M / Snydman, David R

    Transplantation direct

    2023  Volume 9, Issue 12, Page(s) e1542

    Abstract: Background: Invasive infection remains a dangerous complication of heart transplantation (HT). No objectively defined set of clinical risk factors has been established to reliably predict infection in HT. The aim of this study was to develop a clinical ... ...

    Abstract Background: Invasive infection remains a dangerous complication of heart transplantation (HT). No objectively defined set of clinical risk factors has been established to reliably predict infection in HT. The aim of this study was to develop a clinical prediction model for use at 1 mo post-HT to predict serious infection by 1 y.
    Methods: A retrospective cohort study of HT recipients (2000-2018) was performed. The composite endpoint included cytomegalovirus (CMV), herpes simplex or varicella zoster virus infection, blood stream infection, invasive fungal, or nocardial infection occurring 1 mo to 1 y post-HT. A least absolute shrinkage and selection operator regression model was constructed using 10 candidate variables. A concordance statistic, calibration curve, and mean calibration error were calculated. A scoring system was derived for ease of clinical application.
    Results: Three hundred seventy-five patients were analyzed; 93 patients experienced an outcome event. All variables remained in the final model: aged 55 y or above, history of diabetes, need for renal replacement therapy in first month, CMV risk derived from donor and recipient serology, use of induction and/or early lymphodepleting therapy in the first month, use of trimethoprim-sulfamethoxazole prophylaxis at 1 mo, lymphocyte count under 0.75 × 10
    Conclusion: This model synthesizes multiple highly relevant clinical parameters, available at 1 mo post-HT, into a unified, objective, and clinically useful prediction tool for occurrence of serious infection by 1 y post-HT.
    Language English
    Publishing date 2023-11-02
    Publishing country United States
    Document type Journal Article
    ISSN 2373-8731
    ISSN 2373-8731
    DOI 10.1097/TXD.0000000000001542
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Validating a tool to measure spiritual beliefs, needs and resources in serious illness: The I-SPIRIT.

    Steinhauser, Karen E / Jeffreys, Amy S / Perry, Kathleen / Parker, Ryan P / Nieuwsma, Jason / Olsen, Maren K / Johnson, Kimberly S / Kirshner, Miriam A / Majette, Nadya / King, Heather A

    Journal of the American Geriatrics Society

    2024  

    Abstract: Background: Seriously ill patients rely on spiritual and existential beliefs to support coping and approach crucial treatment and healthcare decisions. Yet, we lack gold standard, validated approaches to gathering information on those spiritual beliefs. ...

    Abstract Background: Seriously ill patients rely on spiritual and existential beliefs to support coping and approach crucial treatment and healthcare decisions. Yet, we lack gold standard, validated approaches to gathering information on those spiritual beliefs. Therefore, we developed I-SPIRIT, a spiritual needs and beliefs inventory for those with serious illness (IIR-10-050).
    Methods: In prior work to develop measure content, we interviewed a total of 74 participants: 20 patients (veterans with Stage IV cancer, CHF, COPD, ESRD), 19 caregivers, 14 chaplains, 10 social workers, 12 nurses, and 5 physicians. Using directed content analyses, we identified over 50 attributes of spiritual experience comprising five domains: overall importance of spirituality; affiliations and practices; impact on decisions; spiritual needs; and spiritual resources. We then translated these attributes into individual items with Likert response scales. In the quantitative validation of I-SPIRIT, we administered the instrument and a battery of comparison measures to 249 seriously ill veterans. The comparison measures captured general spiritual well-being, religious coping, and emotional functioning. Convergent and discriminant validity was examined with the FACIT-sp (faith, meaning, and purpose), BMMRS (religious/spirituality), POMS and PHQ-8 (emotional function), and FACT-G (quality of life). We administered the I-SPIRIT a week later, for test-retest reliability.
    Results: Psychometric analyses yielded a final I-SPIRIT Tool including 30 items. Results demonstrated reliability and validity and yielded a tool with three main components: Spiritual Beliefs (seven items); Spiritual Needs (nine items); and Spiritual Resources (14 items). The Spiritual Beliefs items include key practices and affiliations, and impact of beliefs on healthcare. Higher levels of Spiritual Needs were associated with higher anxiety and depression.
    Conclusion: The I-Spirit measures relevance of spirituality, spiritual needs and spiritual resources and demonstrates validity, reliability, and acceptability for patients with serious illness.
    Language English
    Publishing date 2024-04-26
    Publishing country United States
    Document type Journal Article
    ZDB-ID 80363-7
    ISSN 1532-5415 ; 0002-8614
    ISSN (online) 1532-5415
    ISSN 0002-8614
    DOI 10.1111/jgs.18887
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: fNIRS is capable of distinguishing laterality of lower body contractions.

    MacLennan, Rob J / Hernandez-Sarabia, Jesus A / Reese, Shawn M / Shields, JoCarol E / Smith, Claire M / Stute, Katharina / Collyar, Jordyn / Olmos, Alex A / Danielson, Tyler L / MacLennan, Demi L / Pagan, Jason I / Girts, Ryan M / Harmon, Kylie K / Coker, Nicholas / Carr, Joshua C / Ye, Xin / Perry, Jonathan W / Stock, Matt S / DeFreitas, Jason M

    Experimental brain research

    2024  

    Abstract: The use of functional near-infrared spectroscopy (fNIRS) for brain imaging during human movement continues to increase. This technology measures brain activity non-invasively using near-infrared light, is highly portable, and robust to motion artifact. ... ...

    Abstract The use of functional near-infrared spectroscopy (fNIRS) for brain imaging during human movement continues to increase. This technology measures brain activity non-invasively using near-infrared light, is highly portable, and robust to motion artifact. However, the spatial resolution of fNIRS is lower than that of other imaging modalities. It is unclear whether fNIRS has sufficient spatial resolution to differentiate nearby areas of the cortex, such as the leg areas of the motor cortex. Therefore, the purpose of this study was to determine fNIRS' ability to discern laterality of lower body contractions. Activity in the primary motor cortex was recorded in forty participants (mean = 23.4 years, SD = 4.5, female = 23, male = 17) while performing unilateral lower body contractions. Contractions were performed at 30% of maximal force against a handheld dynamometer. These contractions included knee extension, knee flexion, dorsiflexion, and plantar flexion of the left and right legs. fNIRS signals were recorded and stored for offline processing and analysis. Channels of fNIRS data were grouped into regions of interest, with five tolerance conditions ranging from strict to lenient. Four of five tolerance conditions resulted in significant differences in cortical activation between hemispheres. During right leg contractions, the left hemisphere was more active than the right hemisphere. Similarly, during left leg contractions, the right hemisphere was more active than the left hemisphere. These results suggest that fNIRS has sufficient spatial resolution to distinguish laterality of lower body contractions. This makes fNIRS an attractive technology in research and clinical applications in which laterality of brain activity is required during lower body activity.
    Language English
    Publishing date 2024-03-14
    Publishing country Germany
    Document type Journal Article
    ZDB-ID 1201-4
    ISSN 1432-1106 ; 0014-4819
    ISSN (online) 1432-1106
    ISSN 0014-4819
    DOI 10.1007/s00221-024-06798-8
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Correction: Template-dependent inhibition of coronavirus RNA-dependent RNA polymerase by remdesivir reveals a second mechanism of action.

    Tchesnokov, Egor P / Gordon, Calvin J / Woolner, Emma / Kocincova, Dana / Perry, Jason K / Feng, Joy Y / Porter, Danielle P / Götte, Matthias

    The Journal of biological chemistry

    2021  Volume 297, Issue 2, Page(s) 101048

    Language English
    Publishing date 2021-08-06
    Publishing country United States
    Document type Published Erratum
    ZDB-ID 2997-x
    ISSN 1083-351X ; 0021-9258
    ISSN (online) 1083-351X
    ISSN 0021-9258
    DOI 10.1016/j.jbc.2021.101048
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Pre-pandemic Executive Function Protects Against Pandemic Anxiety in Children with and Without Autism Spectrum Disorder.

    Romero, Celia / Kupis, Lauren / Goodman, Zachary T / Dirks, Bryce / Baez, Adriana / Beaumont, Amy L / Cardona, Sandra M / Parlade, Meaghan V / Alessandri, Michael / Nomi, Jason S / Perry, Lynn K / Uddin, Lucina Q

    Journal of autism and developmental disorders

    2023  

    Abstract: The COVID-19 pandemic may have exacerbated depression, anxiety, and executive function (EF) difficulties in children with autism spectrum disorder (ASD). EF skills have been positively associated with mental health outcomes. Here, we probed the ... ...

    Abstract The COVID-19 pandemic may have exacerbated depression, anxiety, and executive function (EF) difficulties in children with autism spectrum disorder (ASD). EF skills have been positively associated with mental health outcomes. Here, we probed the psychosocial impacts of pandemic responses in children with and without ASD by relating pre-pandemic EF assessments with anxiety and depression symptoms several months into the pandemic. We found that pre-pandemic inhibition and shifting difficulties, measured by the Behavior Rating Inventory of Executive Function, predicted higher risk of anxiety symptoms. These findings are critical for promoting community recovery and maximizing clinical preparedness to support children at increased risk for adverse psychosocial outcomes.
    Language English
    Publishing date 2023-12-01
    Publishing country United States
    Document type Journal Article
    ZDB-ID 391999-7
    ISSN 1573-3432 ; 0162-3257
    ISSN (online) 1573-3432
    ISSN 0162-3257
    DOI 10.1007/s10803-023-06175-4
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Awakening and Breathing Coordination: A Mixed-Methods Analysis of Determinants of Implementation.

    Olsen, Griffin H / Gee, Perry M / Wolfe, Doug / Winberg, Carrie / Carpenter, Lori / Jones, Chris / Jacobs, Jason R / Leither, Lindsay / Peltan, Ithan D / Singer, Sara J / Asch, Steven M / Grissom, Colin K / Srivastava, Rajendu / Knighton, Andrew J

    Annals of the American Thoracic Society

    2023  Volume 20, Issue 10, Page(s) 1483–1490

    Abstract: Rationale: ...

    Abstract Rationale:
    MeSH term(s) Humans ; Middle Aged ; Ventilator Weaning/methods ; Pandemics ; Respiration, Artificial/methods ; Respiration ; Intensive Care Units
    Language English
    Publishing date 2023-07-06
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2717461-X
    ISSN 2325-6621 ; 1943-5665 ; 2325-6621
    ISSN (online) 2325-6621 ; 1943-5665
    ISSN 2325-6621
    DOI 10.1513/AnnalsATS.202212-1048OC
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: Viral Resistance Analyses From the Remdesivir Phase 3 Adaptive COVID-19 Treatment Trial-1 (ACTT-1).

    Hedskog, Charlotte / Rodriguez, Lauren / Roychoudhury, Pavitra / Huang, Meei-Li / Jerome, Keith R / Hao, Linhui / Ireton, Renee C / Li, Jiani / Perry, Jason K / Han, Dong / Camus, Gregory / Greninger, Alexander L / Gale, Michael / Porter, Danielle P

    The Journal of infectious diseases

    2023  Volume 228, Issue 9, Page(s) 1263–1273

    Abstract: Background: Remdesivir is approved for treatment of coronavirus disease 2019 (COVID-19) in nonhospitalized and hospitalized adult and pediatric patients. Here we present severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) resistance analyses ... ...

    Abstract Background: Remdesivir is approved for treatment of coronavirus disease 2019 (COVID-19) in nonhospitalized and hospitalized adult and pediatric patients. Here we present severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) resistance analyses from the phase 3 ACTT-1 randomized placebo-controlled trial conducted in adult participants hospitalized with COVID-19.
    Methods: Swab samples were collected at baseline and longitudinally through day 29. SARS-CoV-2 genomes were sequenced using next-generation sequencing. Phenotypic analysis was conducted directly on participant virus isolates and/or using SARS-CoV-2 subgenomic replicons expressing mutations identified in the Nsp12 target gene.
    Results: Among participants with both baseline and postbaseline sequencing data, emergent Nsp12 substitutions were observed in 12 of 31 (38.7%) and 12 of 30 (40.0%) participants in the remdesivir and placebo arms, respectively. No emergent Nsp12 substitutions in the remdesivir arm were observed in more than 1 participant. Phenotyping showed low to no change in susceptibility to remdesivir relative to wild-type Nsp12 reference for the substitutions tested: A16V (0.8-fold change in EC50), P323L + V792I (2.2-fold), C799F (2.5-fold), K59N (1.0-fold), and K59N + V792I (3.4-fold).
    Conclusions: The similar rate of emerging Nsp12 substitutions in the remdesivir and placebo arms and the minimal change in remdesivir susceptibility among tested substitutions support a high barrier to remdesivir resistance development in COVID-19 patients. Clinical Trials Registration. NCT04280705.
    MeSH term(s) Adult ; Humans ; Child ; COVID-19 ; SARS-CoV-2/genetics ; COVID-19 Drug Treatment ; Adenosine Monophosphate/therapeutic use ; Alanine/therapeutic use ; Antiviral Agents/therapeutic use
    Chemical Substances remdesivir (3QKI37EEHE) ; Adenosine Monophosphate (415SHH325A) ; Alanine (OF5P57N2ZX) ; Antiviral Agents
    Language English
    Publishing date 2023-07-19
    Publishing country United States
    Document type Randomized Controlled Trial ; Clinical Trial, Phase III ; Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 3019-3
    ISSN 1537-6613 ; 0022-1899
    ISSN (online) 1537-6613
    ISSN 0022-1899
    DOI 10.1093/infdis/jiad270
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  8. Article ; Online: In Vitro

    Checkmahomed, Liva / Carbonneau, Julie / Du Pont, Venice / Riola, Nicholas C / Perry, Jason K / Li, Jiani / Paré, Bastien / Simpson, Shawn M / Smith, Martin A / Porter, Danielle P / Boivin, Guy

    Antimicrobial agents and chemotherapy

    2022  Volume 66, Issue 7, Page(s) e0019822

    Abstract: ... In ... ...

    Abstract In vitro
    MeSH term(s) Adenosine Monophosphate/analogs & derivatives ; Adenosine Monophosphate/chemistry ; Alanine/analogs & derivatives ; Alanine/metabolism ; Antiviral Agents/chemistry ; COVID-19/drug therapy ; Humans ; SARS-CoV-2
    Chemical Substances Antiviral Agents ; remdesivir (3QKI37EEHE) ; Adenosine Monophosphate (415SHH325A) ; Alanine (OF5P57N2ZX)
    Language English
    Publishing date 2022-06-16
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 217602-6
    ISSN 1098-6596 ; 0066-4804
    ISSN (online) 1098-6596
    ISSN 0066-4804
    DOI 10.1128/aac.00198-22
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  9. Article ; Online: Ensemble cryo-EM reveals conformational states of the nsp13 helicase in the SARS-CoV-2 helicase replication-transcription complex.

    Chen, James / Wang, Qi / Malone, Brandon / Llewellyn, Eliza / Pechersky, Yakov / Maruthi, Kashyap / Eng, Ed T / Perry, Jason K / Campbell, Elizabeth A / Shaw, David E / Darst, Seth A

    Nature structural & molecular biology

    2022  Volume 29, Issue 3, Page(s) 250–260

    Abstract: The SARS-CoV-2 nonstructural proteins coordinate genome replication and gene expression. Structural analyses revealed the basis for coupling of the essential nsp13 helicase with the RNA-dependent RNA polymerase (RdRp) where the holo-RdRp and RNA ... ...

    Abstract The SARS-CoV-2 nonstructural proteins coordinate genome replication and gene expression. Structural analyses revealed the basis for coupling of the essential nsp13 helicase with the RNA-dependent RNA polymerase (RdRp) where the holo-RdRp and RNA substrate (the replication-transcription complex or RTC) associated with two copies of nsp13 (nsp13
    MeSH term(s) COVID-19 ; Cryoelectron Microscopy ; Humans ; RNA Helicases/chemistry ; SARS-CoV-2 ; Viral Nonstructural Proteins/chemistry ; Virus Replication
    Chemical Substances Viral Nonstructural Proteins ; RNA Helicases (EC 3.6.4.13)
    Language English
    Publishing date 2022-03-08
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 2126708-X
    ISSN 1545-9985 ; 1545-9993
    ISSN (online) 1545-9985
    ISSN 1545-9993
    DOI 10.1038/s41594-022-00734-6
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  10. Article ; Online: Mechanism and spectrum of inhibition of a 4′-cyano modified nucleotide analog against diverse RNA polymerases of prototypic respiratory RNA viruses

    Gordon, Calvin J. / Walker, Simon M. / Tchesnokov, Egor P. / Kocincova, Dana / Pitts, Jared / Siegel, Dustin S. / Perry, Jason K. / Feng, Joy Y. / Bilello, John P. / Gotte, Matthias

    bioRxiv

    Abstract: The development of safe and effective broad-spectrum antivirals that target the replication machinery of respiratory viruses is of high priority in pandemic preparedness programs. Here, we studied the mechanism of action of a newly discovered nucleotide ... ...

    Abstract The development of safe and effective broad-spectrum antivirals that target the replication machinery of respiratory viruses is of high priority in pandemic preparedness programs. Here, we studied the mechanism of action of a newly discovered nucleotide analog against diverse RNA-dependent RNA polymerases (RdRp) of prototypic respiratory viruses. GS-646939 is the active 5′-triphosphate (TP) metabolite of a 4ʹ-cyano modified C-adenosine analog phosphoramidate prodrug GS-7682. Enzyme kinetics show that the RdRps of human rhinovirus type 16 (HRV-16) and enterovirus 71 (EV-71) incorporate GS-646939 with unprecedented selectivity; GS-646939 is incorporated 20-50-fold more efficiently than its natural ATP counterpart. The RdRp complex of respiratory syncytial virus (RSV) and human metapneumovirus (HMPV) incorporate GS-646939 and ATP with similar efficiency. In contrast, influenza B RdRp shows a clear preference for ATP and human mitochondrial RNA polymerase (h-mtRNAP) does not show significant incorporation of GS-646939. Once incorporated into the nascent RNA strand, GS-646939 acts as a chain-terminator although higher NTP concentrations can partially overcome inhibition for some polymerases. Modeling and biochemical data suggest that the 4ʹ-modification inhibits RdRp translocation. Comparative studies with GS-443902, the active triphosphate form of the 1′-cyano modified prodrugs remdesivir and obeldesivir, reveal not only different mechanisms of inhibition, but also differences in the spectrum of inhibition of viral polymerases. In conclusion, 1ʹ-cyano and 4ʹ-cyano modifications of nucleotide analogs provide complementary strategies to target the polymerase of several families of respiratory RNA viruses.
    Keywords covid19
    Language English
    Publishing date 2024-04-23
    Publisher Cold Spring Harbor Laboratory
    Document type Article ; Online
    DOI 10.1101/2024.04.22.590607
    Database COVID19

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