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  1. Article: Training parameters and longitudinal adaptations that most strongly mediate walking capacity gains from high-intensity interval training post-stroke.

    Boyne, Pierce / Miller, Allison / Schwab, Sarah M / Sucharew, Heidi / Carl, Daniel / Billinger, Sandra A / Reisman, Darcy S

    medRxiv : the preprint server for health sciences

    2023  

    Abstract: Background: Locomotor high-intensity interval training (HIIT) has been shown to improve walking capacity more than moderate-intensity aerobic training (MAT) after stroke, but it is unclear which training parameter(s) should be prioritized (e.g. speed, ... ...

    Abstract Background: Locomotor high-intensity interval training (HIIT) has been shown to improve walking capacity more than moderate-intensity aerobic training (MAT) after stroke, but it is unclear which training parameter(s) should be prioritized (e.g. speed, heart rate, blood lactate, step count) and to what extent walking capacity gains are the result of neuromotor versus cardiorespiratory adaptations.
    Objective: Assess which training parameters and longitudinal adaptations most strongly mediate 6-minute walk distance (6MWD) gains from post-stroke HIIT.
    Methods: The HIT-Stroke Trial randomized 55 persons with chronic stroke and persistent walking limitations to HIIT or MAT and collected detailed training data. Blinded outcomes included 6MWD, plus measures of neuromotor gait function (e.g. fastest 10-meter gait speed) and aerobic capacity (e.g. ventilatory threshold). This ancillary analysis used structural equation models to compare mediating effects of different training parameters and longitudinal adaptations on 6MWD.
    Results: Net gains in 6MWD from HIIT versus MAT were primarily mediated by faster training speeds and longitudinal adaptations in neuromotor gait function. Training step count was also positively associated with 6MWD gains, but was lower with HIIT versus MAT, which decreased the net 6MWD gain. HIIT generated higher training heart rate and lactate than MAT, but aerobic capacity gains were similar between groups, and 6MWD changes were not associated with training heart rate, training lactate, or aerobic adaptations.
    Conclusions: To increase walking capacity with post-stroke HIIT, training speed and step count appear to be the most important parameters to prioritize.
    Language English
    Publishing date 2023-02-23
    Publishing country United States
    Document type Preprint
    DOI 10.1101/2023.02.20.23286194
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Evaluating the Neural Underpinnings of Motivation for Walking Exercise.

    Doren, Sarah / Schwab, Sarah M / Bigner, Kaitlyn / Calvelage, Jenna / Preston, Katie / Laughlin, Abigail / Drury, Colin / Tincher, Brady / Carl, Daniel / Awosika, Oluwole O / Boyne, Pierce

    Physical therapy

    2023  Volume 104, Issue 3

    Abstract: Objective: Motivation is critically important for rehabilitation, exercise, and motor performance, but its neural basis is poorly understood. Recent correlational research suggests that the dorsomedial prefrontal cortex (dmPFC) may be involved in ... ...

    Abstract Objective: Motivation is critically important for rehabilitation, exercise, and motor performance, but its neural basis is poorly understood. Recent correlational research suggests that the dorsomedial prefrontal cortex (dmPFC) may be involved in motivation for walking activity and/or descending motor output. This study experimentally evaluated brain activity changes in periods of additional motivation during walking exercise and tested how these brain activity changes relate to self-reported exercise motivation and walking speed.
    Methods: Adults without disability (N = 26; 65% women; 25 [standard deviation = 5] years old) performed a vigorous exercise experiment involving 20 trials of maximal speed overground walking. Half of the trials were randomized to include "extra-motivation" stimuli (lap timer, tracked best lap time, and verbal encouragement). Wearable near-infrared spectroscopy measured oxygenated hemoglobin responses from frontal lobe regions, including the dmPFC, primary sensorimotor, dorsolateral prefrontal, anterior prefrontal, supplementary motor, and dorsal premotor cortices.
    Results: Compared with standard trials, participants walked faster during extra-motivation trials (2.43 vs 2.67 m/s; P < .0001) and had higher oxygenated hemoglobin responses in all tested brain regions, including dmPFC (+842 vs +1694 μM; P < .0001). Greater dmPFC activity was correlated with more self-determined motivation for exercise between individuals (r = 0.55; P = .004) and faster walking speed between trials (r = 0.18; P = .0002). dmPFC was the only tested brain region that showed both of these associations.
    Conclusion: Simple motivational stimuli during walking exercise seem to upregulate widespread brain regions. Results suggest that dmPFC may be a key brain region linking affective signaling to motor output.
    Impact: These findings provide a potential biologic basis for the benefits of motivational stimuli, elicited with clinically feasible methods during walking exercise. Future clinical studies could build on this information to develop prognostic biomarkers and test novel brain stimulation targets for enhancing exercise motivation (eg, dmPFC).
    MeSH term(s) Adult ; Humans ; Female ; Child, Preschool ; Male ; Motivation ; Walking/physiology ; Exercise ; Prefrontal Cortex ; Hemoglobins/metabolism ; Gait/physiology
    Chemical Substances Hemoglobins
    Language English
    Publishing date 2023-11-21
    Publishing country United States
    Document type Randomized Controlled Trial ; Journal Article
    ZDB-ID 415886-6
    ISSN 1538-6724 ; 0031-9023
    ISSN (online) 1538-6724
    ISSN 0031-9023
    DOI 10.1093/ptj/pzad159
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: HSV-2 triggers upregulation of MALAT1 in CD4+ T cells and promotes HIV latency reversal.

    Pierce, Carl A / Loh, Lip Nam / Steach, Holly R / Cheshenko, Natalia / Preston-Hurlburt, Paula / Zhang, Fengrui / Stransky, Stephanie / Kravets, Leah / Sidoli, Simone / Philbrick, William / Nassar, Michel / Krishnaswamy, Smita / Herold, Kevan C / Herold, Betsy C

    The Journal of clinical investigation

    2023  Volume 133, Issue 11

    Abstract: Herpes simplex virus type 2 (HSV-2) coinfection is associated with increased HIV-1 viral loads and expanded tissue reservoirs, but the mechanisms are not well defined. HSV-2 recurrences result in an influx of activated CD4+ T cells to sites of viral ... ...

    Abstract Herpes simplex virus type 2 (HSV-2) coinfection is associated with increased HIV-1 viral loads and expanded tissue reservoirs, but the mechanisms are not well defined. HSV-2 recurrences result in an influx of activated CD4+ T cells to sites of viral replication and an increase in activated CD4+ T cells in peripheral blood. We hypothesized that HSV-2 induces changes in these cells that facilitate HIV-1 reactivation and replication and tested this hypothesis in human CD4+ T cells and 2D10 cells, a model of HIV-1 latency. HSV-2 promoted latency reversal in HSV-2-infected and bystander 2D10 cells. Bulk and single-cell RNA-Seq studies of activated primary human CD4+ T cells identified decreased expression of HIV-1 restriction factors and increased expression of transcripts including MALAT1 that could drive HIV replication in both the HSV-2-infected and bystander cells. Transfection of 2D10 cells with VP16, an HSV-2 protein that regulates transcription, significantly upregulated MALAT1 expression, decreased trimethylation of lysine 27 on histone H3 protein, and triggered HIV latency reversal. Knockout of MALAT1 from 2D10 cells abrogated the response to VP16 and reduced the response to HSV-2 infection. These results demonstrate that HSV-2 contributes to HIV-1 reactivation through diverse mechanisms, including upregulation of MALAT1 to release epigenetic silencing.
    MeSH term(s) Humans ; Herpesvirus 2, Human/genetics ; CD4-Positive T-Lymphocytes ; RNA, Long Noncoding/genetics ; Up-Regulation ; Etoposide ; HIV Infections/genetics ; Virus Latency
    Chemical Substances RNA, Long Noncoding ; Etoposide (6PLQ3CP4P3)
    Language English
    Publishing date 2023-06-01
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
    ZDB-ID 3067-3
    ISSN 1558-8238 ; 0021-9738
    ISSN (online) 1558-8238
    ISSN 0021-9738
    DOI 10.1172/JCI164317
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Efficient Construction of Canonical Polyadic Approximations of Tensor Networks.

    Pierce, Karl / Valeev, Edward F

    Journal of chemical theory and computation

    2022  

    Abstract: We consider the problem of constructing a canonical polyadic (CP) decomposition for a tensor network, rather than a single tensor. We illustrate how it is possible to reduce the complexity of constructing an approximate CP representation of the network ... ...

    Abstract We consider the problem of constructing a canonical polyadic (CP) decomposition for a tensor network, rather than a single tensor. We illustrate how it is possible to reduce the complexity of constructing an approximate CP representation of the network by leveraging its structure in the course of the CP factor optimization. The utility of this technique is demonstrated for the order-4 Coulomb interaction tensor approximated by two order-3 tensors via an approximate generalized square-root (SQ) factorization, such as density fitting or (pivoted) Cholesky. The complexity of constructing a four-way CP decomposition is reduced from
    Language English
    Publishing date 2022-12-09
    Publishing country United States
    Document type Journal Article
    ISSN 1549-9626
    ISSN (online) 1549-9626
    DOI 10.1021/acs.jctc.2c00861
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article: Natural Mucosal Barriers and COVID-19 in Children.

    Pierce, Carl A / Sy, Sharlene / Galen, Benjamin / Goldstein, Doctor Y / Orner, Erika / Keller, Marla / Herold, Kevan C / Herold, Betsy

    medRxiv : the preprint server for health sciences

    2021  

    Abstract: COVID-19 is more benign in children compared to adults for unknown reasons. This contrasts with viruses such as influenza where disease manifestations are often more severe in children1. We hypothesized that a more robust early innate immune response to ... ...

    Abstract COVID-19 is more benign in children compared to adults for unknown reasons. This contrasts with viruses such as influenza where disease manifestations are often more severe in children1. We hypothesized that a more robust early innate immune response to SARS-CoV-2 may protect against severe disease and compared clinical outcomes, viral copies and cellular gene and protein expression in nasopharyngeal swabs from 12 children and 27 adults upon presentation to the Emergency Department. SARS-CoV-2 copies were similar, but compared to adults, children displayed higher expression of genes associated with interferon signaling, NLRP3 inflammasome, and other innate pathways. Higher levels of IFN-alpha2, IFN-gamma, IP-10, IL-8, and IL-1beta were detected in nasal fluid in children versus adults. Anti-SARS-CoV-2 IgA and IgG were detected in nasal fluid from both groups and correlated negatively with mucosal IL-18. These findings suggest that a more robust innate immune response in children compared to adults contributes to favorable clinical outcomes.
    Language English
    Publishing date 2021-02-13
    Publishing country United States
    Document type Preprint
    DOI 10.1101/2021.02.12.21251310
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Preparation of Peripheral Blood Mononuclear Cell Pellets and Plasma from a Single Blood Draw at Clinical Trial Sites for Biomarker Analysis.

    Marco-Casanova, Paola / Lukashchuk, Natalia / Lombardi, Benedetta / Munugalavadla, Veerendra / Frigault, Melanie M / Harrington, Elizabeth A / Barrett, J Carl / Pierce, Andrew J

    Journal of visualized experiments : JoVE

    2021  , Issue 169

    Abstract: Analysis of biomarkers in peripheral blood is becoming increasingly important in clinical trials to establish proof of mechanism to evaluate effects of treatment, and help guide dose and schedule setting of therapeutics. From a single blood draw, ... ...

    Abstract Analysis of biomarkers in peripheral blood is becoming increasingly important in clinical trials to establish proof of mechanism to evaluate effects of treatment, and help guide dose and schedule setting of therapeutics. From a single blood draw, peripheral blood mononuclear cells can be isolated and processed to analyze and quantify protein markers, and plasma samples can be used for the analysis of circulating tumor DNA, cytokines, and plasma metabolomics. Longitudinal samples from a treatment provide information on the evolution of a given protein marker, the mutational status and immunological landscape of the patient. This can only be achieved if the processing of the peripheral blood is carried out effectively in clinical sites and samples are properly preserved from the bedside to bench. Here, we present an optimized general-purpose protocol that can be implemented at clinical sites for obtaining PBMC pellets and plasma samples in multi-center clinical trials, that will enable clinical professionals in hospital laboratories to successfully provide high quality samples, regardless of their level of technical expertise. Alternative protocol variations are also presented that are optimized for more specific downstream analytical methods. We apply this protocol for studying protein biomarkers against DNA damage response (DDR) on X-ray irradiated blood to demonstrate the suitability of the approach in oncology settings where DDR drugs and/or radiotherapy have been practiced as well as in preclinical stages where mechanistic hypothesis testing is required.
    MeSH term(s) Biomarkers/blood ; Humans ; Leukocytes, Mononuclear/immunology ; Plasma/immunology
    Chemical Substances Biomarkers
    Language English
    Publishing date 2021-03-20
    Publishing country United States
    Document type Journal Article ; Video-Audio Media
    ZDB-ID 2259946-0
    ISSN 1940-087X ; 1940-087X
    ISSN (online) 1940-087X
    ISSN 1940-087X
    DOI 10.3791/60776
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: Natural mucosal barriers and COVID-19 in children.

    Pierce, Carl A / Sy, Sharlene / Galen, Benjamin / Goldstein, Doctor Y / Orner, Erika / Keller, Marla J / Herold, Kevan C / Herold, Betsy C

    JCI insight

    2021  Volume 6, Issue 9

    Abstract: BACKGROUNDCoronavirus disease 2019 (COVID-19) is more benign in children compared with adults for unknown reasons. This contrasts with other respiratory viruses where disease manifestations are often more severe in children. We hypothesize that a more ... ...

    Abstract BACKGROUNDCoronavirus disease 2019 (COVID-19) is more benign in children compared with adults for unknown reasons. This contrasts with other respiratory viruses where disease manifestations are often more severe in children. We hypothesize that a more robust early innate immune response to SARS coronavirus 2 (SARS-CoV-2) protects against severe disease.METHODSClinical outcomes, SARS-CoV-2 viral copies, and cellular gene expression were compared in nasopharyngeal swabs obtained at the time of presentation to the emergency department from 12 children and 27 adults using bulk RNA sequencing and quantitative reverse-transcription PCR. Total protein, cytokines, and anti-SARS-CoV-2 IgG and IgA were quantified in nasal fluid.RESULTSSARS-CoV-2 copies, angiotensin-converting enzyme 2, and TMPRSS2 gene expression were similar in children and adults, but children displayed higher expression of genes associated with IFN signaling, NLRP3 inflammasome, and other innate pathways. Higher levels of IFN-α2, IFN-γ, IP-10, IL-8, and IL-1β protein were detected in nasal fluid in children versus adults. Children also expressed higher levels of genes associated with immune cells, whereas expression of those associated with epithelial cells did not differ in children versus adults. Anti-SARS-CoV-2 IgA and IgG were detected at similar levels in nasal fluid from both groups. None of the children required supplemental oxygen, whereas 7 adults did (P = 0.03); 4 adults died.CONCLUSIONThese findings provide direct evidence of a more vigorous early mucosal immune response in children compared with adults and suggest that this contributes to favorable clinical outcomes.FUNDINGNIH grants R01 AI134367, UL1 TR002556, T32 AI007501, T32GM007288, P30 AI124414; an Albert Einstein College of Medicine Dean's COVID-19 Pilot Research Award; and the Eric J. Heyer, MD, PhD Translational Research Pilot Project Award.
    MeSH term(s) Adult ; Aged ; Antibodies, Viral/metabolism ; COVID-19/genetics ; COVID-19/immunology ; Child ; Child, Preschool ; Cytokines/metabolism ; Female ; Humans ; Immunity, Innate/genetics ; Immunity, Mucosal/genetics ; Infant ; Male ; Middle Aged ; Nasal Mucosa/immunology ; Pandemics ; SARS-CoV-2/immunology ; Transcriptome
    Chemical Substances Antibodies, Viral ; Cytokines
    Language English
    Publishing date 2021-05-10
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ISSN 2379-3708
    ISSN (online) 2379-3708
    DOI 10.1172/jci.insight.148694
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article: Preliminary Outcomes of Combined Treadmill and Overground High-Intensity Interval Training in Ambulatory Chronic Stroke.

    Boyne, Pierce / Doren, Sarah / Scholl, Victoria / Staggs, Emily / Whitesel, Dustyn / Carl, Daniel / Shatz, Rhonna / Sawyer, Russell / Awosika, Oluwole O / Reisman, Darcy S / Billinger, Sandra A / Kissela, Brett / Vannest, Jennifer / Dunning, Kari

    Frontiers in neurology

    2022  Volume 13, Page(s) 812875

    Abstract: Purpose: Locomotor high-intensity interval training (HIIT) is a promising intervention for stroke rehabilitation. However, overground translation of treadmill speed gains has been somewhat limited, some important outcomes have not been tested and ... ...

    Abstract Purpose: Locomotor high-intensity interval training (HIIT) is a promising intervention for stroke rehabilitation. However, overground translation of treadmill speed gains has been somewhat limited, some important outcomes have not been tested and baseline response predictors are poorly understood. This pilot study aimed to guide future research by assessing preliminary outcomes of combined overground and treadmill HIIT.
    Materials and methods: Ten participants >6 months post-stroke were assessed before and after a 4-week no-intervention control phase and a 4-week treatment phase involving 12 sessions of overground and treadmill HIIT.
    Results: Overground and treadmill gait function both improved during the treatment phase relative to the control phase, with overground speed changes averaging 61% of treadmill speed changes (95% CI: 33-89%). Moderate or larger effect sizes were observed for measures of gait performance, balance, fitness, cognition, fatigue, perceived change and brain volume. Participants with baseline comfortable gait speed <0.4 m/s had less absolute improvement in walking capacity but similar proportional and perceived changes.
    Conclusions: These findings reinforce the potential of locomotor HIIT research for stroke rehabilitation and provide guidance for more definitive studies. Based on the current results, future locomotor HIIT studies should consider including: (1) both overground and treadmill training; (2) measures of cognition, fatigue and brain volume, to complement typical motor and fitness assessment; and (3) baseline gait speed as a covariate.
    Language English
    Publishing date 2022-02-04
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2564214-5
    ISSN 1664-2295
    ISSN 1664-2295
    DOI 10.3389/fneur.2022.812875
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  9. Article ; Online: COVID-19 and children.

    Pierce, Carl A / Herold, Kevan C / Herold, Betsy C / Chou, Janet / Randolph, Adrienne / Kane, Binita / McFarland, Sammie / Gurdasani, Deepti / Pagel, Christina / Hotez, Peter / Cobey, Sarah / Hensley, Scott E

    Science (New York, N.Y.)

    2022  Volume 377, Issue 6611, Page(s) 1144–1149

    Abstract: There has been substantial research on adult COVID-19 and how to treat it. But how do severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections afflict children? The COVID-19 pandemic has yielded many surprises, not least that children ... ...

    Abstract There has been substantial research on adult COVID-19 and how to treat it. But how do severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections afflict children? The COVID-19 pandemic has yielded many surprises, not least that children generally develop less severe disease than older adults, which is unusual for a respiratory disease. However, some children can develop serious complications from COVID-19, such as multisystem inflammatory syndrome in children (MIS-C) and Long Covid, even after mild or asymptomatic COVID-19. Why this occurs in some and not others is an important question. Moreover, when children do contract COVID-19, understanding their role in transmission, especially in schools and at home, is crucial to ensuring effective mitigation measures. Therefore, in addition to nonpharmaceutical interventions, such as improved ventilation, there is a strong case to vaccinate children so as to reduce possible long-term effects from infection and to decrease transmission. But questions remain about whether vaccination might skew immune responses to variants in the long term. As the experts discuss below, more is being learned about these important issues, but much more research is needed to understand the long-term effects of COVID-19 in children.
    MeSH term(s) Aged ; COVID-19/complications ; COVID-19/therapy ; Child ; Humans ; Pandemics ; SARS-CoV-2 ; Systemic Inflammatory Response Syndrome/therapy ; Systemic Inflammatory Response Syndrome/virology ; Post-Acute COVID-19 Syndrome
    Language English
    Publishing date 2022-09-08
    Publishing country United States
    Document type Journal Article
    ZDB-ID 128410-1
    ISSN 1095-9203 ; 0036-8075
    ISSN (online) 1095-9203
    ISSN 0036-8075
    DOI 10.1126/science.ade1675
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article: Predicting 30-Day Perioperative Outcomes in Adult Spinal Deformity Patients With Baseline Paralysis or Functional Dependence.

    Alas, Haddy / Ihejirika, Rivka C / Kummer, Nicholas / Passfall, Lara / Krol, Oscar / Bortz, Cole / Pierce, Katherine E / Brown, Avery / Vasquez-Montes, Dennis / Diebo, Bassel G / Paulino, Carl B / De la Garza Ramos, Rafael / Janjua, Muhammad B / Gerling, Michael C / Passias, Peter G

    International journal of spine surgery

    2022  Volume 16, Issue 3, Page(s) 427–434

    Language English
    Publishing date 2022-06-20
    Publishing country Netherlands
    Document type Journal Article
    ISSN 2211-4599
    ISSN 2211-4599
    DOI 10.14444/8261
    Database MEDical Literature Analysis and Retrieval System OnLINE

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