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Aerobic Exercise Reverses Aging-Induced Depth-Dependent Decline In Cerebral Microcirculation, Paul Shin, Ikbal Şencan-Eğilmez, Et Al. Jul 2023

Aerobic Exercise Reverses Aging-Induced Depth-Dependent Decline In Cerebral Microcirculation, Paul Shin, Ikbal Şencan-Eğilmez, Et Al.

2020-Current year OA Pubs

Aging is a major risk factor for cognitive impairment. Aerobic exercise benefits brain function and may promote cognitive health in older adults. However, underlying biological mechanisms across cerebral gray and white matter are poorly understood. Selective vulnerability of the white matter to small vessel disease and a link between white matter health and cognitive function suggests a potential role for responses in deep cerebral microcirculation. Here, we tested whether aerobic exercise modulates cerebral microcirculatory changes induced by aging. To this end, we carried out a comprehensive quantitative examination of changes in cerebral microvascular physiology in cortical gray and subcortical white …


Age-Related Alterations In Meningeal Immunity Drive Impaired Cns Lymphatic Drainage, Justin Rustenhoven, Georgios Pavlou, Steffen E Storck, Taitea Dykstra, Siling Du, Zhengpeng Wan, Daniel Quintero, Joshua P Scallan, Igor Smirnov, Roger D Kamm, Jonathan Kipnis Jul 2023

Age-Related Alterations In Meningeal Immunity Drive Impaired Cns Lymphatic Drainage, Justin Rustenhoven, Georgios Pavlou, Steffen E Storck, Taitea Dykstra, Siling Du, Zhengpeng Wan, Daniel Quintero, Joshua P Scallan, Igor Smirnov, Roger D Kamm, Jonathan Kipnis

2020-Current year OA Pubs

The meningeal lymphatic network enables the drainage of cerebrospinal fluid (CSF) and facilitates the removal of central nervous system (CNS) waste. During aging and in Alzheimer's disease, impaired meningeal lymphatic drainage promotes the buildup of toxic misfolded proteins in the CNS. Reversing this age-related dysfunction represents a promising strategy to augment CNS waste clearance; however, the mechanisms underlying this decline remain elusive. Here, we demonstrate that age-related alterations in meningeal immunity underlie this lymphatic impairment. Single-cell RNA sequencing of meningeal lymphatic endothelial cells from aged mice revealed their response to IFNγ, which was increased in the aged meninges due to …


A Rapid Cell-Free Expression And Screening Platform For Antibody Discovery, Andrew C Hunt, Bastian Vögeli, Ahmed O Hassan, Laura Guerrero, Weston Kightlinger, Danielle J Yoesep, Antje Krüger, Madison Dewinter, Michael S Diamond, Ashty S Karim, Michael C Jewett Jul 2023

A Rapid Cell-Free Expression And Screening Platform For Antibody Discovery, Andrew C Hunt, Bastian Vögeli, Ahmed O Hassan, Laura Guerrero, Weston Kightlinger, Danielle J Yoesep, Antje Krüger, Madison Dewinter, Michael S Diamond, Ashty S Karim, Michael C Jewett

2020-Current year OA Pubs

Antibody discovery is bottlenecked by the individual expression and evaluation of antigen-specific hits. Here, we address this bottleneck by developing a workflow combining cell-free DNA template generation, cell-free protein synthesis, and binding measurements of antibody fragments in a process that takes hours rather than weeks. We apply this workflow to evaluate 135 previously published antibodies targeting the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), including all 8 antibodies previously granted emergency use authorization for coronavirus disease 2019 (COVID-19), and demonstrate identification of the most potent antibodies. We also evaluate 119 anti-SARS-CoV-2 antibodies from a mouse immunized with the SARS-CoV-2 spike …


T-Bet And Eomes Sustain Mature Human Nk Cell Identity And Antitumor Function, Pamela Wong, Jennifer A. Foltz, Lily Chang, Carly C. Neal, Tony Yao, Celia C. Cubitt, Jennifer Tran, Samantha Kersting-Schadek, Sathvik Palakurty, Natalia Jaeger, David A. Russler-Germain, Nancy D. Marin, Margery Gang, Julia A. Wagner, Alice Y. Zhou, Miriam T. Jacobs, Mark Foster, Timothy Schappe, Lynne Marsala, Ethan Mcclain, Patrick Pence, Michelle Becker-Hapak, Bryan Fisk, Allegra A. Petti, Obi L. Griffith, Malachi Griffith, Melissa M. Berrien-Elliott, Todd A. Fehniger Jul 2023

T-Bet And Eomes Sustain Mature Human Nk Cell Identity And Antitumor Function, Pamela Wong, Jennifer A. Foltz, Lily Chang, Carly C. Neal, Tony Yao, Celia C. Cubitt, Jennifer Tran, Samantha Kersting-Schadek, Sathvik Palakurty, Natalia Jaeger, David A. Russler-Germain, Nancy D. Marin, Margery Gang, Julia A. Wagner, Alice Y. Zhou, Miriam T. Jacobs, Mark Foster, Timothy Schappe, Lynne Marsala, Ethan Mcclain, Patrick Pence, Michelle Becker-Hapak, Bryan Fisk, Allegra A. Petti, Obi L. Griffith, Malachi Griffith, Melissa M. Berrien-Elliott, Todd A. Fehniger

2020-Current year OA Pubs

Since the T-box transcription factors (TFs) T-BET and EOMES are necessary for initiation of NK cell development, their ongoing requirement for mature NK cell homeostasis, function, and molecular programming remains unclear. To address this, T-BET and EOMES were deleted in unexpanded primary human NK cells using CRISPR/Cas9. Deleting these TFs compromised in vivo antitumor response of human NK cells. Mechanistically, T-BET and EOMES were required for normal NK cell proliferation and persistence in vivo. NK cells lacking T-BET and EOMES also exhibited defective responses to cytokine stimulation. Single-cell RNA-Seq revealed a specific T-box transcriptional program in human NK cells, which …


Genetic Characterization Of Primary And Metastatic High-Grade Serous Ovarian Cancer Tumors Reveals Distinct Features Associated With Survival, Emilee N Kotnik, Mary M Mullen, Nicholas C Spies, Tiandao Li, Matthew Inkman, Jin Zhang, Fernanda Martins-Rodrigues, Ian S Hagemann, Carolyn K Mccourt, Premal H Thaker, Andrea R Hagemann, Matthew A Powell, David G Mutch, Dineo Khabele, Gregory D Longmore, Christopher A Maher, Christopher A Miller, Katherine C Fuh, Et Al. Jul 2023

Genetic Characterization Of Primary And Metastatic High-Grade Serous Ovarian Cancer Tumors Reveals Distinct Features Associated With Survival, Emilee N Kotnik, Mary M Mullen, Nicholas C Spies, Tiandao Li, Matthew Inkman, Jin Zhang, Fernanda Martins-Rodrigues, Ian S Hagemann, Carolyn K Mccourt, Premal H Thaker, Andrea R Hagemann, Matthew A Powell, David G Mutch, Dineo Khabele, Gregory D Longmore, Christopher A Maher, Christopher A Miller, Katherine C Fuh, Et Al.

2020-Current year OA Pubs

High-grade serous ovarian cancer (HGSC) is the most lethal histotype of ovarian cancer and the majority of cases present with metastasis and late-stage disease. Over the last few decades, the overall survival for patients has not significantly improved, and there are limited targeted treatment options. We aimed to better characterize the distinctions between primary and metastatic tumors based on short- or long-term survival. We characterized 39 matched primary and metastatic tumors by whole exome and RNA sequencing. Of these, 23 were short-term (ST) survivors (overall survival (OS) < 3.5 years) and 16 were long-term (LT) survivors (OS > 5 years). We compared somatic mutations, copy number alterations, mutational burden, differential gene …


Blood Neurofilament Light Levels Predict Non-Relapsing Progression Following Anti-Cd20 Therapy In Relapsing And Primary Progressive Multiple Sclerosis: Findings From The Ocrelizumab Randomised, Double-Blind Phase 3 Clinical Trials, Amit Bar-Or, Anne H Cross, Et Al. Jul 2023

Blood Neurofilament Light Levels Predict Non-Relapsing Progression Following Anti-Cd20 Therapy In Relapsing And Primary Progressive Multiple Sclerosis: Findings From The Ocrelizumab Randomised, Double-Blind Phase 3 Clinical Trials, Amit Bar-Or, Anne H Cross, Et Al.

2020-Current year OA Pubs

BACKGROUND: Neurofilament light chain (NfL), a neuronal cytoskeletal protein that is released upon neuroaxonal injury, is associated with multiple sclerosis (MS) relapsing activity and has demonstrated some prognostic ability for future relapse-related disease progression, yet its value in assessing non-relapsing disease progression remains unclear.

METHODS: We examined baseline and longitudinal blood NfL levels in 1421 persons with relapsing MS (RMS) and 596 persons with primary progressive MS (PPMS) from the pivotal ocrelizumab MS trials. NfL treatment-response and risk for disease worsening (including disability progression into the open-label extension period and slowly expanding lesions [SELs] on brain MRI) at baseline and …


An Atlas Of Healthy And Injured Cell States And Niches In The Human Kidney, Blue B Lake, Amanda Knoten, Bo Zhang, Diane Salamon, Anitha Vijayan, Eric H Kim, Joseph P Gaut, Sanjay Jain, Et Al. Jul 2023

An Atlas Of Healthy And Injured Cell States And Niches In The Human Kidney, Blue B Lake, Amanda Knoten, Bo Zhang, Diane Salamon, Anitha Vijayan, Eric H Kim, Joseph P Gaut, Sanjay Jain, Et Al.

2020-Current year OA Pubs

Understanding kidney disease relies on defining the complexity of cell types and states, their associated molecular profiles and interactions within tissue neighbourhoods


Identifying The Neural Correlates Of Anticipatory Postural Control: A Novel Fmri Paradigm, Jo Armour Smith, Rongwen Tain, Kelli G Sharp, Laura M Glynn, Linda R Van Dillen, Korinne Henslee, Jesse V Jacobs, Steven C Cramer Jul 2023

Identifying The Neural Correlates Of Anticipatory Postural Control: A Novel Fmri Paradigm, Jo Armour Smith, Rongwen Tain, Kelli G Sharp, Laura M Glynn, Linda R Van Dillen, Korinne Henslee, Jesse V Jacobs, Steven C Cramer

2020-Current year OA Pubs

Altered postural control in the trunk/hip musculature is a characteristic of multiple neurological and musculoskeletal conditions. Previously it was not possible to determine if altered cortical and subcortical sensorimotor brain activation underlies impairments in postural control. This study used a novel fMRI-compatible paradigm to identify the brain activation associated with postural control in the trunk and hip musculature. BOLD fMRI imaging was conducted as participants performed two versions of a lower limb task involving lifting the left leg to touch the foot to a target. For the supported leg raise (SLR) the leg is raised from the knee while the …


Characteristics Of Patients With Pulmonary Arterial Hypertension From An Innovative, Comprehensive Real-World Patient Data Repository, Harrison W Farber, Murali M Chakinala, Michelle Cho, Robert P Frantz, Andrew Frick, Lisa Lancaster, Scott Milligan, Ronald Oudiz, Sumeet Panjabi, Yuen Tsang, Steven D Nathan Jul 2023

Characteristics Of Patients With Pulmonary Arterial Hypertension From An Innovative, Comprehensive Real-World Patient Data Repository, Harrison W Farber, Murali M Chakinala, Michelle Cho, Robert P Frantz, Andrew Frick, Lisa Lancaster, Scott Milligan, Ronald Oudiz, Sumeet Panjabi, Yuen Tsang, Steven D Nathan

2020-Current year OA Pubs

Pulmonary arterial hypertension (PAH) is a rare, life-limiting disease. PAH registries provide real-world data that complement clinical trial data and inform treatment decisions. The TRIO comprehensive, integrated patient data repository (TRIO CIPDR), is an innovative US repository capturing data on contemporary patients diagnosed with pulmonary hypertension and receiving US Food and Drug Administration-approved PAH therapies. This repository uniquely combines clinical data from electronic medical records with the ability to track drug-prescription and drug-dispensing characteristics, and includes 946 adult patients with PAH (data collected January 2019 to December 2020) enrolled from nine representative US specialist tertiary care centers. Potentially eligible patients …


Autologous Humanized Pdx Modeling For Immuno-Oncology Recapitulates Features Of The Human Tumor Microenvironment, Michael Chiorazzi, Bradley Krasnick, Keenan J Robbins, Zachary Skidmore, Jacqueline Mudd, Ye Bi, S Peter Goedegebuure, Malachi Griffith, Obi Griffith, Abimbola Oyedeji, Ryan C Fields, Et Al. Jul 2023

Autologous Humanized Pdx Modeling For Immuno-Oncology Recapitulates Features Of The Human Tumor Microenvironment, Michael Chiorazzi, Bradley Krasnick, Keenan J Robbins, Zachary Skidmore, Jacqueline Mudd, Ye Bi, S Peter Goedegebuure, Malachi Griffith, Obi Griffith, Abimbola Oyedeji, Ryan C Fields, Et Al.

2020-Current year OA Pubs

BACKGROUND: Interactions between immune and tumor cells are critical to determining cancer progression and response. In addition, preclinical prediction of immune-related drug efficacy is limited by interspecies differences between human and mouse, as well as inter-person germline and somatic variation. To address these gaps, we developed an autologous system that models the tumor microenvironment (TME) from individual patients with solid tumors.

METHOD: With patient-derived bone marrow hematopoietic stem and progenitor cells (HSPCs), we engrafted a patient's hematopoietic system in MISTRG6 mice, followed by transfer of patient-derived xenograft (PDX) tissue, providing a fully genetically matched model to recapitulate the individual's TME. …


Enhanced 3d Visualization Of Human Fallopian Tube Morphology Using A Miniature Optical Coherence Tomography Catheter, Hongbo Luo, Shuying Li, Sitai Kou, Yixiao Lin, Ian S Hagemann, Quing Zhu Jul 2023

Enhanced 3d Visualization Of Human Fallopian Tube Morphology Using A Miniature Optical Coherence Tomography Catheter, Hongbo Luo, Shuying Li, Sitai Kou, Yixiao Lin, Ian S Hagemann, Quing Zhu

2020-Current year OA Pubs

We demonstrate the use of our miniature optical coherence tomography catheter to acquire three-dimensional human fallopian tube images. Images of the fallopian tube's tissue morphology, vasculature, and tissue heterogeneity distribution are enhanced by adaptive thresholding, masking, and intensity inverting, making it easier to differentiate malignant tissue from normal tissue. The results show that normal fallopian tubes tend to have rich vasculature accompanied by a patterned tissue scattering background, features that do not appear in malignant cases. This finding suggests that miniature OCT catheters may have great potential for fast optical biopsy of the fallopian tube.


Real-World Outcomes Associated With Poly(Adp-Ribose) Polymerase Inhibitor Monotherapy Maintenance In Patients With Primary Advanced Ovarian Cancer, John K Chan, Jinan Liu, Jinlin Song, Cheryl Xiang, Eric Wu, Linda Kalilani, Jean A. Hurteau, Premal H. Thaker Jul 2023

Real-World Outcomes Associated With Poly(Adp-Ribose) Polymerase Inhibitor Monotherapy Maintenance In Patients With Primary Advanced Ovarian Cancer, John K Chan, Jinan Liu, Jinlin Song, Cheryl Xiang, Eric Wu, Linda Kalilani, Jean A. Hurteau, Premal H. Thaker

2020-Current year OA Pubs

OBJECTIVE: This study used real-world population data to assess the trends of first-line (1L) poly(ADP-ribose) polymerase inhibitor (PARPi) maintenance treatment uptake and outcomes in patients with primary advanced ovarian cancer (AOC).

METHODS: Patients diagnosed with AOC between January 1, 2017, and June 30, 2021, who completed 1L chemotherapy were selected from a real-world database. Descriptive analyses were performed to evaluate patient demographics, clinicopathological characteristics, and 1L treatment patterns. Time to next treatment or death was used as a proxy for real-world progression-free survival (rwPFS). Kaplan-Meier methods and Cox models were used for statistical analyses.

RESULTS: Of 705 patients who completed …


Accelerated Infliximab Infusion Safety And Tolerability Is Non-Inferior To Standard Infusion Protocol In Inflammatory Bowel Disease Patients: A Randomized Controlled Study, Suha Abushamma, Ted Walker, Kevin Garza, Ling Chen, Darren Nix, Chien-Huan Chen Jul 2023

Accelerated Infliximab Infusion Safety And Tolerability Is Non-Inferior To Standard Infusion Protocol In Inflammatory Bowel Disease Patients: A Randomized Controlled Study, Suha Abushamma, Ted Walker, Kevin Garza, Ling Chen, Darren Nix, Chien-Huan Chen

2020-Current year OA Pubs

BACKGROUND AND AIM: Infliximab is typically given over an infusion time of 2 hours, leading to a significant burden in inflammatory bowel disease (IBD) patients. We aimed to determine the safety and cost-effectiveness of an accelerated infliximab infusion of 1 hour, compared with the standard 2-hour infusion.

METHODS: Open-label randomized trial where IBD patients receiving maintenance infliximab infusions were randomly assigned to 1- and 2-hour infusion groups, corresponding to study and control groups, respectively. The primary outcome was the rate of infusion reactions. Secondary outcomes were assessment of the effect of premedications and immunomodulators on the rate of infusion reactions, …


Delphi Consensus On Reporting Standards In Clinical Studies For Endovascular Treatment Of Acute Iliofemoral Venous Thrombosis And Chronic Iliofemoral Venous Obstruction, Suresh Vedantham, Peter Gloviczki, Teresa L. Carman, Sandra Zelman Lewis, Peter A. Schneider, Saher S. Sabri, Raghu Kolluri Jul 2023

Delphi Consensus On Reporting Standards In Clinical Studies For Endovascular Treatment Of Acute Iliofemoral Venous Thrombosis And Chronic Iliofemoral Venous Obstruction, Suresh Vedantham, Peter Gloviczki, Teresa L. Carman, Sandra Zelman Lewis, Peter A. Schneider, Saher S. Sabri, Raghu Kolluri

2020-Current year OA Pubs

Acute iliofemoral deep vein thrombosis and chronic iliofemoral venous obstruction cause substantial patient harm and are increasingly managed with endovascular venous interventions, including percutaneous mechanical thrombectomy and stent placement. However, studies of these treatment elements have not been designed and reported with sufficient rigor to support confident conclusions about their clinical utility. In this project, the Trustworthy consensus-based statement approach was utilized to develop, via a structured process, consensus-based statements to guide future investigators of venous interventions. Thirty statements were drafted to encompass major topics relevant to venous study description and design, safety outcome assessment, efficacy outcome assessment, and topics …


Nitric Oxide-Mediated S-Nitrosylation Of Iaa17 Protein In Intrinsically Disordered Region Represses Auxin Signaling, Hongwei Jing, Xiaolu Yang, Ryan J Emenecker, Jian Feng, Jian Zhang, Marcelo Rodrigues Alves De Figueiredo, Patarasuda Chaisupa, R Clay Wright, Alex S Holehouse, Lucia C Strader, Jianru Zuo Jul 2023

Nitric Oxide-Mediated S-Nitrosylation Of Iaa17 Protein In Intrinsically Disordered Region Represses Auxin Signaling, Hongwei Jing, Xiaolu Yang, Ryan J Emenecker, Jian Feng, Jian Zhang, Marcelo Rodrigues Alves De Figueiredo, Patarasuda Chaisupa, R Clay Wright, Alex S Holehouse, Lucia C Strader, Jianru Zuo

2020-Current year OA Pubs

The phytohormone auxin plays crucial roles in nearly every aspect of plant growth and development. Auxin signaling is activated through the phytohormone-induced proteasomal degradation of the Auxin/INDOLE-3-ACETIC ACID (Aux/IAA) family of transcriptional repressors. Notably, many auxin-modulated physiological processes are also regulated by nitric oxide (NO) that executes its biological effects predominantly through protein S-nitrosylation at specific cysteine residues. However, little is known about the molecular mechanisms in regulating the interactive NO and auxin networks. Here, we show that NO represses auxin signaling by inhibiting IAA17 protein degradation. NO induces the S-nitrosylation of Cys-70 located in the intrinsically disordered region of …


An Rrna Fragment In Extracellular Vesicles Secreted By Human Airway Epithelial Cells Increases The Fluoroquinolone Sensitivity Of P. Aeruginosa, Katja Koeppen, Thomas H Hampton, Roxanna Barnaby, Carolyn Roche, Scott A Gerber, Young Ah Goo, Byoung-Kyu Cho, Danielle M Vermilyea, Deborah A Hogan, Bruce A Stanton Jul 2023

An Rrna Fragment In Extracellular Vesicles Secreted By Human Airway Epithelial Cells Increases The Fluoroquinolone Sensitivity Of P. Aeruginosa, Katja Koeppen, Thomas H Hampton, Roxanna Barnaby, Carolyn Roche, Scott A Gerber, Young Ah Goo, Byoung-Kyu Cho, Danielle M Vermilyea, Deborah A Hogan, Bruce A Stanton

2020-Current year OA Pubs

Lung infections caused by antibiotic-resistant strains of


Dietary Patterns Are Not Associated With Disease Activity Among Patients With Inflammatory Conditions Of The Pouch In A Prospective Cohort, Edward L Barnes, Poonam Beniwal-Patel, Parakkal Deepak, Laura Raffals, Maia Kayal, Marla Dubinsky, Shannon Chang, Peter D R Higgins, Jennifer I Barr, Chelsea Anderson, Raymond K Cross, Millie D Long, Hans H Herfarth Jul 2023

Dietary Patterns Are Not Associated With Disease Activity Among Patients With Inflammatory Conditions Of The Pouch In A Prospective Cohort, Edward L Barnes, Poonam Beniwal-Patel, Parakkal Deepak, Laura Raffals, Maia Kayal, Marla Dubinsky, Shannon Chang, Peter D R Higgins, Jennifer I Barr, Chelsea Anderson, Raymond K Cross, Millie D Long, Hans H Herfarth

2020-Current year OA Pubs

BACKGROUND: Evidence-based recommendations regarding the influence of diet on inflammatory conditions of the pouch after restorative proctocolectomy with ileal pouch-anal anastomosis (IPAA) are limited.

METHODS: We analyzed dietary patterns at enrollment in a prospective registry of patients with 1 of 4 inflammatory conditions of the pouch (acute pouchitis, chronic antibiotic-dependent pouchitis, chronic antibiotic refractory pouchitis, and Crohn's disease of the pouch). We analyzed dietary intake by disease activity at enrollment and then compared dietary patterns among patients who remained in remission throughout the 12-month follow-up to those patients who experienced a disease relapse. We also compared dietary patterns among patients …


Healthcare Costs Of Clostridioides Difficile Infection In Commercially Insured Younger Adults, John M Sahrmann, Margaret A Olsen, Matthew R Keller, Holly Yu, Erik R Dubberke Jul 2023

Healthcare Costs Of Clostridioides Difficile Infection In Commercially Insured Younger Adults, John M Sahrmann, Margaret A Olsen, Matthew R Keller, Holly Yu, Erik R Dubberke

2020-Current year OA Pubs

In a US adult population aged <65 years, attributable costs due to


Ethanolaminephosphate Cytidylyltransferase Is Essential For Survival, Lipid Homeostasis And Stress Tolerance In Leishmania Major, Somrita Basu, Mattie C. Pawlowic, Fong-Fu Hsu, Geoff Thomas, Kai Zhang Jul 2023

Ethanolaminephosphate Cytidylyltransferase Is Essential For Survival, Lipid Homeostasis And Stress Tolerance In Leishmania Major, Somrita Basu, Mattie C. Pawlowic, Fong-Fu Hsu, Geoff Thomas, Kai Zhang

2020-Current year OA Pubs

Glycerophospholipids including phosphatidylethanolamine (PE) and phosphatidylcholine (PC) are vital components of biological membranes. Trypanosomatid parasites of the genus Leishmania can acquire PE and PC via de novo synthesis and the uptake/remodeling of host lipids. In this study, we investigated the ethanolaminephosphate cytidylyltransferase (EPCT) in Leishmania major, which is the causative agent for cutaneous leishmaniasis. EPCT is a key enzyme in the ethanolamine branch of the Kennedy pathway which is responsible for the de novo synthesis of PE. Our results demonstrate that L. major EPCT is a cytosolic protein capable of catalyzing the formation of CDP-ethanolamine from ethanolamine-phosphate and cytidine triphosphate. …


Exploring The Natural History Of Intrinsic Capacity Impairments: Longitudinal Patterns In The 10/66 Study, Emmanuel Gonzalez-Bautista, Jorge Jesus Llibre-Guerra, Ana L Sosa, Isaac Acosta, Sandrine Andrieu, Daisy Acosta, Juan De Jesús Llibre-Rodríguez, Matthew Prina Jul 2023

Exploring The Natural History Of Intrinsic Capacity Impairments: Longitudinal Patterns In The 10/66 Study, Emmanuel Gonzalez-Bautista, Jorge Jesus Llibre-Guerra, Ana L Sosa, Isaac Acosta, Sandrine Andrieu, Daisy Acosta, Juan De Jesús Llibre-Rodríguez, Matthew Prina

2020-Current year OA Pubs

BACKGROUND: intrinsic capacity (IC) is a construct encompassing people's physical and mental abilities. There is an implicit link amongst IC domains: cognition, locomotion, nutrition, sensory and psychological. However, little is known about the integration of the domains.

OBJECTIVES: to investigate patterns in the presentation and evolution of IC domain impairments in low-and-middle-income countries and if such patterns were associated with adverse outcomes.

METHODS: secondary analyses of the first two waves of the 10/66 study (population-based surveys conducted in eight urban and four rural catchment areas in Cuba, Dominican Republic, Puerto Rico, Venezuela, Peru, Mexico and China). We applied latent transition …


Plasma Proteomic Patterns Show Sex Differences In Early Concentric Left Ventricular Remodeling, Anne-Mar Van Ommen, Ernest Diez Benavente, N. Charlotte Onland-Moret, Gideon B. Valstar, Maarten J. Cramer, Frans H. Rutten, Arco J. Teske, Roxana Menken, Leonard Hofstra, Igor I. Tulevski, Nancy Sweitzer, G. Aernout Somsen, Hester M. Den Ruijter Jul 2023

Plasma Proteomic Patterns Show Sex Differences In Early Concentric Left Ventricular Remodeling, Anne-Mar Van Ommen, Ernest Diez Benavente, N. Charlotte Onland-Moret, Gideon B. Valstar, Maarten J. Cramer, Frans H. Rutten, Arco J. Teske, Roxana Menken, Leonard Hofstra, Igor I. Tulevski, Nancy Sweitzer, G. Aernout Somsen, Hester M. Den Ruijter

2020-Current year OA Pubs

BACKGROUND: Concentric remodeling (cRM) can precede heart failure with preserved ejection fraction (HFpEF), a condition prevalent in women.

METHODS: Patients (n=60 593, 54.2% women) visiting outpatient clinics of Cardiology Centers of the Netherlands were analyzed for cRM, HFpEF development, and mortality risk. We studied risk factors for relative wall thickness both sex-stratified and in women and men combined. Biomarker profiling was performed (4534 plasma proteins) in a substudy involving 557 patients (65.4% women) to identify pathways involved in cRM.

RESULTS: cRM was present in 23.5% of women and 27.6% of men and associated with developing HFpEF (HR, 2.15 [95% CI, …


Epigenetic Reprogramming Of Cell Cycle Genes By Ack1 Promotes Breast Cancer Resistance To Cdk4/6 Inhibitor, Mithila Sawant, Audrey Wilson, Dhivya Sridaran, Kiran Mahajan, Christopher J O'Conor, Ian S Hagemann, Jingqin Luo, Cody Weimholt, Tiandao Li, Juan Carlos Roa, Akhilesh Pandey, Xinyan Wu, Nupam P Mahajan Jul 2023

Epigenetic Reprogramming Of Cell Cycle Genes By Ack1 Promotes Breast Cancer Resistance To Cdk4/6 Inhibitor, Mithila Sawant, Audrey Wilson, Dhivya Sridaran, Kiran Mahajan, Christopher J O'Conor, Ian S Hagemann, Jingqin Luo, Cody Weimholt, Tiandao Li, Juan Carlos Roa, Akhilesh Pandey, Xinyan Wu, Nupam P Mahajan

2020-Current year OA Pubs

Hormone receptor-positive, HER2-negative advanced breast cancers exhibit high sensitivity to CDK4/6 inhibitors such as palbociclib. However, most patients inevitably develop resistance, thus identification of new actionable therapeutic targets to overcome the recurrent disease is an urgent need. Immunohistochemical studies of tissue microarray revealed increased activation of non-receptor tyrosine kinase, ACK1 (also known as TNK2) in most of the breast cancer subtypes, independent of their hormone receptor status. Chromatin immunoprecipitation studies demonstrated that the nuclear target of activated ACK1, pY88-H4 epigenetic marks, were deposited at cell cycle genes, CCNB1, CCNB2 and CDC20, which in turn initiated their efficient transcription. Pharmacological inhibition …


Organization Of The Human Intestine At Single-Cell Resolution, John W Hickey, Zhengyan Zhang, Yiing Lin, Et Al. Jul 2023

Organization Of The Human Intestine At Single-Cell Resolution, John W Hickey, Zhengyan Zhang, Yiing Lin, Et Al.

2020-Current year OA Pubs

The intestine is a complex organ that promotes digestion, extracts nutrients, participates in immune surveillance, maintains critical symbiotic relationships with microbiota and affects overall health


Toward Peripheral Nerve Mechanical Characterization Using Brillouin Imaging Spectroscopy, Vsevolod Cheburkanov, Junwei Du, David M. Brogan, Mikhail Y. Berezin, Vladislav V. Yakovlev Jul 2023

Toward Peripheral Nerve Mechanical Characterization Using Brillouin Imaging Spectroscopy, Vsevolod Cheburkanov, Junwei Du, David M. Brogan, Mikhail Y. Berezin, Vladislav V. Yakovlev

2020-Current year OA Pubs

SIGNIFICANCE: Peripheral nerves are viscoelastic tissues with unique elastic characteristics. Imaging of peripheral nerve elasticity is important in medicine, particularly in the context of nerve injury and repair. Elasticity imaging techniques provide information about the mechanical properties of peripheral nerves, which can be useful in identifying areas of nerve damage or compression, as well as assessing the success of nerve repair procedures.

AIM: We aim to assess the feasibility of Brillouin microspectroscopy for peripheral nerve imaging of elasticity, with the ultimate goal of developing a new diagnostic tool for peripheral nerve injury

APPROACH: Viscoelastic properties of the peripheral nerve were …


Associated Radiation Exposure From Medical Imaging And Excess Lifetime Risk Of Developing Cancer In Pediatric Patients With Pulmonary Hypertension, Malini Mahendra, Philip Chu, Elena K Amin, Hythem Nawaytou, James R Duncan, Jeffrey R Fineman, Rebecca Smith-Bindman Jul 2023

Associated Radiation Exposure From Medical Imaging And Excess Lifetime Risk Of Developing Cancer In Pediatric Patients With Pulmonary Hypertension, Malini Mahendra, Philip Chu, Elena K Amin, Hythem Nawaytou, James R Duncan, Jeffrey R Fineman, Rebecca Smith-Bindman

2020-Current year OA Pubs

Pediatric patients with pulmonary hypertension (PH) receive imaging studies that use ionizing radiation (radiation) such as computed tomography (CT) and cardiac catheterization to guide clinical care. Radiation exposure is associated with increased cancer risk. It is unknown how much radiation pediatric PH patients receive. The objective of this study is to quantify radiation received from imaging and compute associated lifetime cancer risks for pediatric patients with PH. Electronic health records between 2012 and 2022 were reviewed and radiation dose data were extracted. Organ doses were estimated using Monte Carlo modeling. Cancer risks for each patient were calculated from accumulated exposures …


Exploratory Genome-Wide Analyses Of Cortical Inhibition, Facilitation, And Plasticity In Late-Life Depression, Rafae A Wathra, Xiaoyu Men, Samar S M Elsheikh, Victoria S Marshe, Tarek K Rajji, Jennifer I Lissemore, Benoit H Mulsant, Jordan F Karp, Charles F Reynolds 3rd, Eric J Lenze, Zafiris J Daskalakis, Daniel J Müller, Daniel M Blumberger Jun 2023

Exploratory Genome-Wide Analyses Of Cortical Inhibition, Facilitation, And Plasticity In Late-Life Depression, Rafae A Wathra, Xiaoyu Men, Samar S M Elsheikh, Victoria S Marshe, Tarek K Rajji, Jennifer I Lissemore, Benoit H Mulsant, Jordan F Karp, Charles F Reynolds 3rd, Eric J Lenze, Zafiris J Daskalakis, Daniel J Müller, Daniel M Blumberger

2020-Current year OA Pubs

Late-life depression (LLD) is a heterogenous mood disorder influenced by genetic factors. Cortical physiological processes such as cortical inhibition, facilitation, and plasticity may be markers of illness that are more strongly associated with genetic factors than the clinical phenotype. Thus, exploring the relationship between genetic factors and these physiological processes may help to characterize the biological mechanisms underlying LLD and improve diagnosis and treatment selection. Transcranial magnetic stimulation (TMS) combined with electromyography was used to measure short interval intracortical inhibition (SICI), cortical silent period (CSP), intracortical facilitation (ICF), and paired associative stimulation (PAS) in 79 participants with LLD. We used …


Microrna-145 And Microrna-486 Are Potential Serum Biomarkers For Vascular Calcification, Sara Fernández-Villabrille, Beatriz Martín-Carro, Julia Martín-Vírgala, Cristina Alonso-Montes, Carmen Palomo-Antequera, Raúl García-Castro, Susana López-Ongil, Adriana S Dusso, José Luis Fernández-Martín, Manuel Naves-Díaz, Jorge B Cannata-Andía, Natalia Carrillo-López, Sara Panizo Jun 2023

Microrna-145 And Microrna-486 Are Potential Serum Biomarkers For Vascular Calcification, Sara Fernández-Villabrille, Beatriz Martín-Carro, Julia Martín-Vírgala, Cristina Alonso-Montes, Carmen Palomo-Antequera, Raúl García-Castro, Susana López-Ongil, Adriana S Dusso, José Luis Fernández-Martín, Manuel Naves-Díaz, Jorge B Cannata-Andía, Natalia Carrillo-López, Sara Panizo

2020-Current year OA Pubs

INTRODUCTION: MicroRNAs (miRs) regulate vascular calcification (VC), and their quantification may contribute to suspicion of the presence of VC.

METHODS: The study was performed in four phases. Phase 1: miRs sequencing of rat calcified and non-calcified aortas. Phase 2: miRs with the highest rate of change, plus miR-145 [the most abundant miR in vascular smooth muscle cells (VSMCs)], were validated in aortas and serum from rats with and without VC. Phase 3: the selected miRs were analyzed in epigastric arteries from kidney donors and recipients, and serum samples from general population. Phase 4: VSMCs were exposed to different phosphorus concentrations, …


Benefits Of A 12-Week Non-Drug "Brain Fitness Program" For Patients With Attention-Deficit/Hyperactive Disorder, Post-Concussion Syndrome, Or Memory Loss, Majid Fotuhi, Noah D Khorrami, Cyrus A Raji Jun 2023

Benefits Of A 12-Week Non-Drug "Brain Fitness Program" For Patients With Attention-Deficit/Hyperactive Disorder, Post-Concussion Syndrome, Or Memory Loss, Majid Fotuhi, Noah D Khorrami, Cyrus A Raji

2020-Current year OA Pubs

BACKGROUND: Non-pharmacologic interventions can potentially improve cognitive function, sleep, and/or mood in patients with attention-deficit/hyperactive disorder (ADHD), post-concussion syndrome (PCS), or memory loss.

OBJECTIVE: We evaluated the benefits of a brain rehabilitation program in an outpatient neurology practice that consists of targeted cognitive training, lifestyle coaching, and electroencephalography (EEG)-based neurofeedback, twice weekly (90 minutes each), for 12 weeks.

METHODS: 223 child and adult patients were included: 71 patients with ADHD, 88 with PCS, and 64 with memory loss (mild cognitive impairment or subjective cognitive decline). Patients underwent a complete neurocognitive evaluation, including tests for Verbal Memory, Complex Attention, Processing Speed, …


Neuraminidase Activity Modulates Cellular Coinfection During Influenza A Virus Multicycle Growth, Zijian Guo, Yuanyuan He, Jian Xu, Ananya N. Benegal, Steven L. Brody, Michael D. Vahey Jun 2023

Neuraminidase Activity Modulates Cellular Coinfection During Influenza A Virus Multicycle Growth, Zijian Guo, Yuanyuan He, Jian Xu, Ananya N. Benegal, Steven L. Brody, Michael D. Vahey

2020-Current year OA Pubs

Infection of individual cells by multiple virions plays critical roles in the replication and spread of many viruses, but mechanisms that control cellular coinfection during multicycle viral growth remain unclear. Here, we investigate virus-intrinsic factors that control cellular coinfection by influenza A virus (IAV). Using quantitative fluorescence to track the spread of virions from single infected cells, we identify the IAV surface protein neuraminidase (NA) as a key determinant of cellular coinfection. We map this effect to NA's ability to deplete viral receptors from both infected and neighboring uninfected cells. In cases in which viral infectious potential is low, genetic …


Il-11 Induces Nlrp3 Inflammasome Activation In Monocytes And Inflammatory Cell Migration To The Central Nervous System, Maryamsadat Seyedsadr, Tabish H Khan, Ulrike Lorenz, Et Al. Jun 2023

Il-11 Induces Nlrp3 Inflammasome Activation In Monocytes And Inflammatory Cell Migration To The Central Nervous System, Maryamsadat Seyedsadr, Tabish H Khan, Ulrike Lorenz, Et Al.

2020-Current year OA Pubs

The objective of this study is to examine IL-11-induced mechanisms of inflammatory cell migration to the central nervous system (CNS). We report that IL-11 is produced at highest frequency by myeloid cells among the peripheral blood mononuclear cell (PBMC) subsets. Patients with relapsing-remitting multiple sclerosis (RRMS) have an increased frequency of IL-11