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Aloin Isoforms (A And B) Selectively Inhibits Proteolytic And Deubiquitinating Activity Of Papain Like Protease (Plpro) Of Sars-Cov-2 In Vitro., Devin S M Lewis, Joanna Ho, Savannah Wills, Anasha Kawall, Avini Sharma, Krishna Chavada, Maximilian C C J C Ebert, Stefania Evoli, Ajay Singh, Srujana Rayalam, Vicky Mody, Shashidharamurthy Taval Feb 2022

Aloin Isoforms (A And B) Selectively Inhibits Proteolytic And Deubiquitinating Activity Of Papain Like Protease (Plpro) Of Sars-Cov-2 In Vitro., Devin S M Lewis, Joanna Ho, Savannah Wills, Anasha Kawall, Avini Sharma, Krishna Chavada, Maximilian C C J C Ebert, Stefania Evoli, Ajay Singh, Srujana Rayalam, Vicky Mody, Shashidharamurthy Taval

PCOM Scholarly Works

The most common host entry point of human adapted coronaviruses (CoV) including SARS-CoV-2 is through the initial colonization in the nostril and mouth region which is responsible for spread of the infection. Most recent studies suggest that the commercially available oral and nasal rinse products are effective in inhibiting the viral replication. However, the anti-viral mechanism of the active ingredients present in the oral rinses have not been studied. In the present study, we have assessed in vitro enzymatic inhibitory activity of active ingredients in the oral mouth rinse products: aloin A and B, chlorhexidine, eucalyptol, hexetidine, menthol, triclosan, methyl …


A Tranquil Virtual Reality Experience To Reduce Subjective Stress Among Covid-19 Frontline Healthcare Workers., Elizabeth Beverly, Laurie Hommema, Kara Coates, Gary Duncan, Brad Gable, Thomas Gutman, Matthew Love, Carrie Love, Michelle Pershing, Nancy Stevens Feb 2022

A Tranquil Virtual Reality Experience To Reduce Subjective Stress Among Covid-19 Frontline Healthcare Workers., Elizabeth Beverly, Laurie Hommema, Kara Coates, Gary Duncan, Brad Gable, Thomas Gutman, Matthew Love, Carrie Love, Michelle Pershing, Nancy Stevens

Medical Education Articles

OBJECTIVE: The novel coronavirus-19 (COVID-19) has taken an immense physical, social, and emotional toll on frontline healthcare workers. Research has documented higher levels of anxiety, depression, and burnout among healthcare workers during the pandemic. Thus, creative interventions are needed now more than ever to provide brief, accessible support to frontline workers. Virtual reality is a rapidly growing technology with potential psychological applications. In this study, we piloted a three-minute Tranquil Cinematic-VR simulation of a nature scene to lower subjective stress among frontline healthcare workers in COVID-19 treatment units. We chose to film a nature scene because of the extensive empirical …


Selective Elimination Of Pluripotent Stem Cells By Pikfyve Specific Inhibitors., Arup R Chakraborty, Alex Vassilev, Sushil K Jaiswal, Constandina E O'Connell, John F Ahrens, Barbara S Mallon, Martin Pera, Melvin L Depamphilis Feb 2022

Selective Elimination Of Pluripotent Stem Cells By Pikfyve Specific Inhibitors., Arup R Chakraborty, Alex Vassilev, Sushil K Jaiswal, Constandina E O'Connell, John F Ahrens, Barbara S Mallon, Martin Pera, Melvin L Depamphilis

Faculty Research 2022

Inhibition of PIKfyve phosphoinositide kinase selectively kills autophagy-dependent cancer cells by disrupting lysosome homeostasis. Here, we show that PIKfyve inhibitors can also selectively eliminate pluripotent embryonal carcinoma cells (ECCs), embryonic stem cells, and induced pluripotent stem cells under conditions where differentiated cells remain viable. PIKfyve inhibitors prevented lysosome fission, induced autophagosome accumulation, and reduced cell proliferation in both pluripotent and differentiated cells, but they induced death only in pluripotent cells. The ability of PIKfyve inhibitors to distinguish between pluripotent and differentiated cells was confirmed with xenografts derived from ECCs. Pretreatment of ECCs with the PIKfyve specific inhibitor WX8 suppressed their …


The Role Of Urgent Care Centers In Headache Management: A Quality Improvement Project, Mia T. Minen, Dennique Khanns, Jenny Guiracocha, Annika Ehrlich, Fawad A. Khan, Ashhar S. Ali, Marius Birlea, Niranjan N. Singh, Addie Peretz, I. V. Larry Charleston Feb 2022

The Role Of Urgent Care Centers In Headache Management: A Quality Improvement Project, Mia T. Minen, Dennique Khanns, Jenny Guiracocha, Annika Ehrlich, Fawad A. Khan, Ashhar S. Ali, Marius Birlea, Niranjan N. Singh, Addie Peretz, I. V. Larry Charleston

Neurology Articles

BACKGROUND: Patients with headache often seek urgent medical care to treat pain and associated symptoms that do not respond to therapeutic options at home. Urgent Cares (UCs) may be suitable for the evaluation and treatment of such patients but there is little data on how headache is evaluated in UC settings and what types of treatments are available. We conducted a study to evaluate the types of care available for patients with headache presenting to UCs.

DESIGN: Cross-Sectional.

METHODS: Headache specialists across the United States contacted UCs to collect data on a questionnaire. Questions asked about UC staffing (e.g. number …


Dissecting Fc Signatures Of Protection In Neonates Following Maternal Influenza Vaccination In A Placebo-Controlled Trial., Carolyn M Boudreau, John S Burke, Kiel D Shuey, Caitlin Wolf, Joanne Katz, James Tielsch, Subarna Khatry, Steven C Leclerq, Janet A Englund, Helen Y Chu, Galit Alter Feb 2022

Dissecting Fc Signatures Of Protection In Neonates Following Maternal Influenza Vaccination In A Placebo-Controlled Trial., Carolyn M Boudreau, John S Burke, Kiel D Shuey, Caitlin Wolf, Joanne Katz, James Tielsch, Subarna Khatry, Steven C Leclerq, Janet A Englund, Helen Y Chu, Galit Alter

Global Health Faculty Publications

Influenza is an important cause of illness and morbidity for infants. Seasonal influenza vaccination during pregnancy aims to provide protection to mothers, but it can also provide immunity to infants. The precise influence of maternal vaccination on immunity in infants and how vaccine-elicited antibodies provide protection in some but not all infants is incompletely understood. We comprehensively profiled the transfer of functional antibodies and defined humoral factors contributing to immunity against influenza in a clinical trial of maternal influenza vaccination. Influenza-specific antibody subclass levels, Fc ɣ receptor (FCGR) binding levels, and antibody-dependent innate immune functions were all profiled in the …


Parasite Dynamics In Untreated Horses Through One Calendar Year, Ashley E. Steuer, Haley P. Anderson, Taylor Shepherd, Morgan Clark, Jessica A. Scare, Holli S. Gravatte, Martin K. Nielsen Feb 2022

Parasite Dynamics In Untreated Horses Through One Calendar Year, Ashley E. Steuer, Haley P. Anderson, Taylor Shepherd, Morgan Clark, Jessica A. Scare, Holli S. Gravatte, Martin K. Nielsen

Veterinary Science Faculty Publications

BACKGROUND: Horses are host to a plethora of parasites. Knowledge of the seasonality of parasite egg shedding and transmission is important for constructing parasite control programs. However, studies describing these patterns are sparse, and have largely been conducted only in the United Kingdom. This study evaluated strongylid egg shedding patterns and transmission dynamics of Strongylus vulgaris in naturally infected and untreated mares and foals through one calendar year in Kentucky, USA. The study also investigated the existence of a peri-parturient rise (PPR) in strongylid egg counts in foaling mares and collected information about Strongyloides westeri and Parascaris spp. in the …


Myocardial Rev-Erb-Mediated Diurnal Metabolic Rhythm And Obesity Paradox, Paul Basil, Ningxia Zhu, Yingyun Gong, Wenbo Li, Hui Li, Qiying Fan, Jong Min Choi, Weijia Luo, Yanfeng Xue, Rui Cao, Wenjun Zhou, Andrea R Ortiz, Brittany Stork, Vatsala Mundra, Nagireddy Putluri, Brian York, Maoping Chu, Jiang Chang, Sung Yun Jung, Liang Xie, Jiangping Song, Lilei Zhang, Zheng Sun Feb 2022

Myocardial Rev-Erb-Mediated Diurnal Metabolic Rhythm And Obesity Paradox, Paul Basil, Ningxia Zhu, Yingyun Gong, Wenbo Li, Hui Li, Qiying Fan, Jong Min Choi, Weijia Luo, Yanfeng Xue, Rui Cao, Wenjun Zhou, Andrea R Ortiz, Brittany Stork, Vatsala Mundra, Nagireddy Putluri, Brian York, Maoping Chu, Jiang Chang, Sung Yun Jung, Liang Xie, Jiangping Song, Lilei Zhang, Zheng Sun

Faculty, Staff and Students Publications

BACKGROUND: The nuclear receptor Rev-erbα/β, a key component of the circadian clock, emerges as a drug target for heart diseases, but the function of cardiac Rev-erb has not been studied in vivo. Circadian disruption is implicated in heart diseases, but it is unknown whether cardiac molecular clock dysfunction is associated with the progression of any naturally occurring human heart diseases. Obesity paradox refers to the seemingly protective role of obesity for heart failure, but the mechanism is unclear.

METHODS: We generated mouse lines with cardiac-specific Rev-erbα/β knockout (KO), characterized cardiac phenotype, conducted multi-omics (RNA-sequencing, chromatin immunoprecipitation sequencing, proteomics, and metabolomics) …


Study Protocol: Cluster Randomized Trial Of Consultation Strategies For The Sustainment Of Mental Health Interventions In Under-Resourced Urban Schools: Rationale, Design, And Methods., Ricardo Eiraldi, Barry L. Mccurdy, Muniya S Khanna, Courtney Benjamin Wolk, Henry A Glick, Quinn A Rabenau-Mcdonnell, Rachel Comly, Laura E Rutherford, Jayme Banks, Steven A Rufe, Kristina M Popkin, Tara Wilson, Kathryn Henson, Abraham Wandersman, Abbas F Jawad Feb 2022

Study Protocol: Cluster Randomized Trial Of Consultation Strategies For The Sustainment Of Mental Health Interventions In Under-Resourced Urban Schools: Rationale, Design, And Methods., Ricardo Eiraldi, Barry L. Mccurdy, Muniya S Khanna, Courtney Benjamin Wolk, Henry A Glick, Quinn A Rabenau-Mcdonnell, Rachel Comly, Laura E Rutherford, Jayme Banks, Steven A Rufe, Kristina M Popkin, Tara Wilson, Kathryn Henson, Abraham Wandersman, Abbas F Jawad

PCOM Scholarly Works

BACKGROUND: The school is a key setting for the provision of mental health services to children, particularly those underserved through traditional service delivery systems. School-wide Positive Behavioral Interventions and Supports (PBIS) is a tiered approach to service delivery based on the public health model that schools use to implement universal (Tier 1) supports to improve school climate and safety. As our prior research has demonstrated, PBIS is a useful vehicle for implementing mental and behavioral health evidence-based practices (EBPs) at Tier 2 for children with, or at risk for, mental health disorders. Very little research has been conducted regarding the …


Videos Of Sipuleucel-T Programmed T Cells Lysing Cells That Express Prostate Cancer Target Antigens, Adam S Kibel, Brant A Inman, Russell K Pachynski, Tuyen Vu, Nadeem A Sheikh, Daniel P Petrylak Feb 2022

Videos Of Sipuleucel-T Programmed T Cells Lysing Cells That Express Prostate Cancer Target Antigens, Adam S Kibel, Brant A Inman, Russell K Pachynski, Tuyen Vu, Nadeem A Sheikh, Daniel P Petrylak

2020-Current year OA Pubs

Sipuleucel-T, an autologous cellular immunotherapy, was approved to treat metastatic castration-resistant prostate cancer in 2010 in the United States. Treatment with sipuleucel-T primes the immune system to target prostate acid phosphatase, which is expressed by prostate cancer cells, potentially leading to lysis of cancer cells. Expanding on previously reported indirect evidence of cell killing with sipuleucel-T treatment, we sought to provide direct evidence of cell lysis through visualization. We used advanced video technology and available samples of peripheral blood mononuclear cells from subjects enrolled in the STAMP trial (NCT01487863). Isolated CD8+ T cells were used as effector cells and cocultured …


Translating Research Into Practice-Implementation Recommendations For Pediatric Rheumatology; Proceedings Of The Childhood Arthritis And Rheumatology Research Alliance 2020 Implementation Science Retreat, James W Dearing, Gareth Parry, Jon M Burnham, Stacy P Ardoin, Fatima Barbar-Smiley, Joyce C Chang, Peter Chiraseveenuprapund, Vincent Del Gaizo, Guy Eakin, Lisa C Johnson, Yukiko Kimura, Andrea M Knight, Melanie Kohlheim, Erica F Lawson, Mindy S Lo, Nancy Pan, Andrea Ring, Tova Ronis, Emily A Smitherman, Alysha J Taxter, Janalee Taylor, Richard K Vehe, Sheetal S Vora, Jennifer E Weiss, Emily Von Scheven, Mas For The Carra Implementation Science Workgroup Feb 2022

Translating Research Into Practice-Implementation Recommendations For Pediatric Rheumatology; Proceedings Of The Childhood Arthritis And Rheumatology Research Alliance 2020 Implementation Science Retreat, James W Dearing, Gareth Parry, Jon M Burnham, Stacy P Ardoin, Fatima Barbar-Smiley, Joyce C Chang, Peter Chiraseveenuprapund, Vincent Del Gaizo, Guy Eakin, Lisa C Johnson, Yukiko Kimura, Andrea M Knight, Melanie Kohlheim, Erica F Lawson, Mindy S Lo, Nancy Pan, Andrea Ring, Tova Ronis, Emily A Smitherman, Alysha J Taxter, Janalee Taylor, Richard K Vehe, Sheetal S Vora, Jennifer E Weiss, Emily Von Scheven, Mas For The Carra Implementation Science Workgroup

Faculty, Staff and Student Publications

The translation of research findings into clinical practice is challenging, especially fields like in pediatric rheumatology, where the evidence base is limited, there are few clinical trials, and the conditions are rare and heterogeneous. Implementation science methodologies have been shown to reduce the research- to- practice gap in other clinical settings may have similar utility in pediatric rheumatology. This paper describes the key discussion points from the inaugural Childhood Arthritis and Rheumatology Research Alliance Implementation Science retreat held in February 2020. The aim of this report is to synthesize those findings into an Implementation Science Roadmap for pediatric rheumatology research. …


Lipid-Loaded Tumor-Associated Macrophages Sustain Tumor Growth And Invasiveness In Prostate Cancer, Michela Masetti, Roberta Carriero, Federica Portale, Giulia Marelli, Nicolò Morina, Marta Iovino, Marco Erreni, Andrea Ponzetta, Elena Magrini, Piergiuseppe Colombo, Grazia Elefante, Federico Simone Colombo, Joke M M Den Haan, Clelia Peano, Javier Cibella, Alberto Termanini, Paolo Kunderfranco, Jolanda Brummelman, Matthew Wai Heng Chung, Massimo Lazzeri, Rodolfo Hurle, Paolo Casale, Enrico Lugli, Ronald A Depinho, Subhankar Mukhopadhyay, Siamon Gordon, Diletta Di Mitri Feb 2022

Lipid-Loaded Tumor-Associated Macrophages Sustain Tumor Growth And Invasiveness In Prostate Cancer, Michela Masetti, Roberta Carriero, Federica Portale, Giulia Marelli, Nicolò Morina, Marta Iovino, Marco Erreni, Andrea Ponzetta, Elena Magrini, Piergiuseppe Colombo, Grazia Elefante, Federico Simone Colombo, Joke M M Den Haan, Clelia Peano, Javier Cibella, Alberto Termanini, Paolo Kunderfranco, Jolanda Brummelman, Matthew Wai Heng Chung, Massimo Lazzeri, Rodolfo Hurle, Paolo Casale, Enrico Lugli, Ronald A Depinho, Subhankar Mukhopadhyay, Siamon Gordon, Diletta Di Mitri

Faculty, Staff and Student Publications

Tumor-associated macrophages (TAMs) are correlated with the progression of prostatic adenocarcinoma (PCa). The mechanistic basis of this correlation and therapeutic strategies to target TAMs in PCa remain poorly defined. Here, single-cell RNA sequencing was used to profile the transcriptional landscape of TAMs in human PCa, leading to identification of a subset of macrophages characterized by dysregulation in transcriptional pathways associated with lipid metabolism. This subset of TAMs correlates positively with PCa progression and shorter disease-free survival and is characterized by an accumulation of lipids that is dependent on Marco. Mechanistically, cancer cell-derived IL-1β enhances Marco expression on macrophages, and reciprocally, …


Srgn-Triggered Aggressive And Immunosuppressive Phenotype In A Subset Of Ttf-1-Negative Lung Adenocarcinomas, Ichidai Tanaka, Delphine Dayde, Mei Chee Tai, Haruki Mori, Luisa M Solis, Johannes F Fahrmann, Gargy Parhy, Rekha Jain, Edwin R Parra, Yoshiko Murakami, Clemente Aguilar-Bonavides, Barbara Mino, Muge Celiktas, Dilsher Dhillon, Julian Phillip Casabar, Masahiro Nakatochi, Francesco Stingo, Veera Baladandayuthapani, Hong Wang, Hiroyuki Katayama, Jennifer B Dennison, Philip L Lorenzi, Kim-Anh Do, Junya Fujimoto, Carmen Behrens, Edwin J Ostrin, Jaime Rodriguez-Canales, Tetsunari Hase, Takayuki Fukui, Taisuke Kajino, Seiichi Kato, Yasushi Yatabe, Waki Hosoda, Koji Kawaguchi, Kohei Yokoi, Toyofumi F Chen-Yoshikawa, Yoshinori Hasegawa, Adi F Gazdar, Ignacio I Wistuba, Samir Hanash, Ayumu Taguchi Feb 2022

Srgn-Triggered Aggressive And Immunosuppressive Phenotype In A Subset Of Ttf-1-Negative Lung Adenocarcinomas, Ichidai Tanaka, Delphine Dayde, Mei Chee Tai, Haruki Mori, Luisa M Solis, Johannes F Fahrmann, Gargy Parhy, Rekha Jain, Edwin R Parra, Yoshiko Murakami, Clemente Aguilar-Bonavides, Barbara Mino, Muge Celiktas, Dilsher Dhillon, Julian Phillip Casabar, Masahiro Nakatochi, Francesco Stingo, Veera Baladandayuthapani, Hong Wang, Hiroyuki Katayama, Jennifer B Dennison, Philip L Lorenzi, Kim-Anh Do, Junya Fujimoto, Carmen Behrens, Edwin J Ostrin, Jaime Rodriguez-Canales, Tetsunari Hase, Takayuki Fukui, Taisuke Kajino, Seiichi Kato, Yasushi Yatabe, Waki Hosoda, Koji Kawaguchi, Kohei Yokoi, Toyofumi F Chen-Yoshikawa, Yoshinori Hasegawa, Adi F Gazdar, Ignacio I Wistuba, Samir Hanash, Ayumu Taguchi

Faculty, Staff and Student Publications

BACKGROUND: Approximately 20% of lung adenocarcinoma (LUAD) is negative for the lineage-specific oncogene Thyroid transcription factor 1 (TTF-1) and exhibits worse clinical outcome with a low frequency of actionable genomic alterations. To identify molecular features associated with TTF-1-negative LUAD, we compared the transcriptomic and proteomic profiles of LUAD cell lines. SRGN , a chondroitin sulfate proteoglycan Serglycin, was identified as a markedly overexpressed gene in TTF-1-negative LUAD. We therefore investigated the roles and regulation of SRGN in TTF-1-negative LUAD.

METHODS: Proteomic and metabolomic analyses of 41 LUAD cell lines were done using mass spectrometry. The function of SRGN was investigated …


Multiple Approaches Converge On Three Biological Subtypes Of Meningioma And Extract New Insights From Published Studies, Tiemo J Klisch, Akash J Patel Feb 2022

Multiple Approaches Converge On Three Biological Subtypes Of Meningioma And Extract New Insights From Published Studies, Tiemo J Klisch, Akash J Patel

Faculty, Staff and Student Publications

One-fifth of meningiomas classified as benign by World Health Organization (WHO) histopathological grading will behave malignantly. To better diagnose these tumors, several groups turned to DNA methylation, whereas we combined RNA-sequencing (RNA-seq) and cytogenetics. Both approaches were more accurate than histopathology in identifying aggressive tumors, but whether they revealed similar tumor types was unclear. We therefore performed unbiased DNA methylation, RNA-seq, and cytogenetic profiling on 110 primary meningiomas WHO grade I and II). Each technique distinguished the same three groups (two benign and one malignant) as our previous molecular classification; integrating these methods into one classifier further improved accuracy. Computational …


Interplay Between Soluble Cd74 And Macrophage-Migration Inhibitory Factor Drives Tumor Growth And Influences Patient Survival In Melanoma, Yasunari Fukuda, Matias A Bustos, Sung-Nam Cho, Jason Roszik, Suyeon Ryu, Jared K Burks, Elizabeth A Grimm, Dave S B Hoon, Suhendan Ekmekcioglu Feb 2022

Interplay Between Soluble Cd74 And Macrophage-Migration Inhibitory Factor Drives Tumor Growth And Influences Patient Survival In Melanoma, Yasunari Fukuda, Matias A Bustos, Sung-Nam Cho, Jason Roszik, Suyeon Ryu, Jared K Burks, Elizabeth A Grimm, Dave S B Hoon, Suhendan Ekmekcioglu

Faculty, Staff and Student Publications

Soluble forms of receptors play distinctive roles in modulating signal-transduction pathways. Soluble CD74 (sCD74) has been identified in sera of inflammatory diseases and implicated in their pathophysiology; however, few relevant data are available in the context of cancer. Here we assessed the composition and production mechanisms, as well as the clinical significance and biological properties, of sCD74 in melanoma. Serum sCD74 levels were significantly elevated in advanced melanoma patients compared with normal healthy donors, and the high ratio of sCD74 to macrophage-migration inhibitory factor (MIF) conferred significant predictive value for prolonged survival in these patients (p = 0.0035). Secretion of …


Attitudes Among Healthcare Professionals Towards Cardiopulmonary Resuscitation During Covid-19., Safinaz Al-Shiakh, Quincy K Tran, Amy Caggiula, Ivan Berezowski, Basma Barnawi, Ali Pourmand Feb 2022

Attitudes Among Healthcare Professionals Towards Cardiopulmonary Resuscitation During Covid-19., Safinaz Al-Shiakh, Quincy K Tran, Amy Caggiula, Ivan Berezowski, Basma Barnawi, Ali Pourmand

Emergency Medicine Faculty Publications

No abstract provided.


Coronavirus Disease 2019 (Covid-19) Research Agenda For Healthcare Epidemiology, Lona Mody, Hilary M Babcock, Jennie H Kwon, Et Al Feb 2022

Coronavirus Disease 2019 (Covid-19) Research Agenda For Healthcare Epidemiology, Lona Mody, Hilary M Babcock, Jennie H Kwon, Et Al

Open Access Publications

This SHEA white paper identifies knowledge gaps and challenges in healthcare epidemiology research related to coronavirus disease 2019 (COVID-19) with a focus on core principles of healthcare epidemiology. These gaps, revealed during the worst phases of the COVID-19 pandemic, are described in 10 sections: epidemiology, outbreak investigation, surveillance, isolation precaution practices, personal protective equipment (PPE), environmental contamination and disinfection, drug and supply shortages, antimicrobial stewardship, healthcare personnel (HCP) occupational safety, and return to work policies. Each section highlights three critical healthcare epidemiology research questions with detailed description provided in supplementary materials. This research agenda calls for translational studies from laboratory-based …


Liposomal Phytohemagglutinin: In Vivo T-Cell Activator As A Novel Pan-Cancer Immunotherapy, Kinan Alhallak, Jennifer Sun, Barbara Muz, Amanda Jeske, Julie O'Neal, Julie K Ritchey, Samuel Achilefu, John F Dipersio, Abdel Kareem Azab Feb 2022

Liposomal Phytohemagglutinin: In Vivo T-Cell Activator As A Novel Pan-Cancer Immunotherapy, Kinan Alhallak, Jennifer Sun, Barbara Muz, Amanda Jeske, Julie O'Neal, Julie K Ritchey, Samuel Achilefu, John F Dipersio, Abdel Kareem Azab

Open Access Publications

Immunotherapy is an attractive approach for treating cancer. T-cell engagers (TCEs) are a type of immunotherapy that are highly efficacious; however, they are challenged by weak T-cell activation and short persistence. Therefore, alternative solutions to induce greater activation and persistence of T cells during TCE immunotherapy is needed. Methods to activate T cells include the use of lectins, such as phytohemagglutinin (PHA). PHA has not been used to activate T cells in vivo, for immunotherapy, due to its biological instability and toxicity. An approach to overcome the limitations of PHA while also preserving its function is needed. In this study, …


Host Cell-Intrinsic Innate Immune Recognition Of Sars-Cov-2, Emily A Madden, Michael S Diamond Feb 2022

Host Cell-Intrinsic Innate Immune Recognition Of Sars-Cov-2, Emily A Madden, Michael S Diamond

2020-Current year OA Pubs

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) emerged at the end of 2019 and caused the pandemic of coronavirus disease 2019 (COVID-19). Basic and clinical investigations indicate that severe forms of COVID-19 are due in part to dysregulated immune responses to virus infection. The innate immune system is the first line of host defense against most virus infections, with pathogen recognition receptors detecting SARS-CoV-2 RNA and protein components and initiating pro-inflammatory and antiviral responses. Notwithstanding this response, SARS-CoV-2 proteins evade, inhibit, and skew innate immune signaling early in infection. In this review, we highlight the components of cell-based recognition of SARS-CoV-2 …


No Difference In Radiologic Outcomes For Natalizumab Patients Treated With Extended Interval Dosing Compared With Standard Interval Dosing: Real-World Evidence From Ms Paths, Lana Zhovtis Ryerson, Robert T. Naismith, Lauren B. Krupp, Leigh E. Charvet, Shirley Liao, Elizabeth Fisher, Carl De Moor, James R. Williams, Nolan Campbell Feb 2022

No Difference In Radiologic Outcomes For Natalizumab Patients Treated With Extended Interval Dosing Compared With Standard Interval Dosing: Real-World Evidence From Ms Paths, Lana Zhovtis Ryerson, Robert T. Naismith, Lauren B. Krupp, Leigh E. Charvet, Shirley Liao, Elizabeth Fisher, Carl De Moor, James R. Williams, Nolan Campbell

2020-Current year OA Pubs

BACKGROUND: Extended interval dosing (EID; average dosing interval approximately every 6 weeks) of natalizumab is associated with significantly lower risk of progressive multifocal leukoencephalopathy than standard interval dosing (SID; every 4 weeks) in patients with relapsing-remitting multiple sclerosis (MS). Real-world studies, though limited, suggest that natalizumab effectiveness is generally maintained in patients who switch to EID after initiation of stable treatment with SID. MS PATHS (Multiple Sclerosis Partners Advancing Technology and Health Solutions) is a collaborative, multicenter learning health system that generates real-world clinical and MRI data using highly standardized acquisition protocols. We compared MRI outcomes in MS PATHS patients …


Validation Of Actigraphy For Sleep Measurement In Children With Cerebral Palsy, Bing Xue, Amy Licis, Jill Boyd, Catherine R Hoyt, Yo-El S Ju Feb 2022

Validation Of Actigraphy For Sleep Measurement In Children With Cerebral Palsy, Bing Xue, Amy Licis, Jill Boyd, Catherine R Hoyt, Yo-El S Ju

2020-Current year OA Pubs

OBJECTIVES: Sleep issues are common in children with cerebral palsy (CP), although there are challenges in obtaining objective data about their sleep patterns. Actigraphs measure movement to quantify sleep but their accuracy in children with CP is unknown. Our goals were to validate actigraphy for sleep assessment in children with CP and to study their sleep patterns in a cross-sectional cohort study.

METHODS: We recruited children with (N = 13) and without (N = 13) CP aged 2-17 years (mean age 9 y 11mo [SD 4 y 10mo] range 4-17 y; 17 males, 9 females; 54% spastic quadriplegic, 23% spastic …


A Prospective Multicenter Evaluation Of Initial Treatment Choice In Metastatic Renal Cell Carcinoma Prior To The Immunotherapy Era: The Marcc Registry Experience, Brian A. Costello, Russell K. Pachynski, Et Al. Feb 2022

A Prospective Multicenter Evaluation Of Initial Treatment Choice In Metastatic Renal Cell Carcinoma Prior To The Immunotherapy Era: The Marcc Registry Experience, Brian A. Costello, Russell K. Pachynski, Et Al.

2020-Current year OA Pubs

INTRODUCTION: The Metastatic Renal Cell Carcinoma (MaRCC) Registry provides prospective data on real-world treatment patterns and outcomes in patients with metastatic renal cell carcinoma (mRCC).

METHODS AND MATERIALS: Patients with mRCC and no prior systemic therapy were enrolled at academic and community sites. End of study data collection was in March 2019. Outcomes included overall survival (OS). A survey of treating physicians assessed reasons for treatment initiations and discontinuations.

RESULTS: Overall, 376 patients with mRCC initiated first-line therapy; 171 (45.5%) received pazopanib, 75 (19.9%) sunitinib, and 74 (19.7%) participated in a clinical trial. Median (95% confidence interval) OS was longest …


Brain Stimulation Treatments In Epilepsy: Basic Mechanisms And Clinical Advances, Thomas J. Foutz, Michael Wong Feb 2022

Brain Stimulation Treatments In Epilepsy: Basic Mechanisms And Clinical Advances, Thomas J. Foutz, Michael Wong

2020-Current year OA Pubs

Drug-resistant epilepsy, characterized by ongoing seizures despite appropriate trials of anti-seizure medications, affects approximately one-third of people with epilepsy. Brain stimulation has recently become available as an alternative treatment option to reduce symptomatic seizures in short and long-term follow-up studies. Several questions remain on how to optimally develop patient-specific treatments and manage therapy over the long term. This review aims to discuss the clinical use and mechanisms of action of Responsive Neural Stimulation and Deep Brain Stimulation in the treatment of epilepsy and highlight recent advances that may both improve outcomes and present new challenges. Finally, a rational approach to …


What After Bcg Fails In Non-Muscle Invasive Bladder Cancer?, M Hammad Ather Feb 2022

What After Bcg Fails In Non-Muscle Invasive Bladder Cancer?, M Hammad Ather

Section of Urology

No abstract provided.


Longitudinal Changes In Vascular Stiffness And Heart Rate Variability Among Young Adults With Youth-Onset Type 2 Diabetes: Results From The Follow-Up Observational Treatment Options For Type 2 Diabetes In Adolescents And Youth (Today) Study, Amy S Shah, Laure El Ghormli, Samuel S Gidding, Kara S Hughan, Lorraine E Levitt Katz, Dorit Koren, Jeanie B Tryggestad, Fida Bacha, Barbara H Braffett, Silva Arslanian, Elaine M Urbina Feb 2022

Longitudinal Changes In Vascular Stiffness And Heart Rate Variability Among Young Adults With Youth-Onset Type 2 Diabetes: Results From The Follow-Up Observational Treatment Options For Type 2 Diabetes In Adolescents And Youth (Today) Study, Amy S Shah, Laure El Ghormli, Samuel S Gidding, Kara S Hughan, Lorraine E Levitt Katz, Dorit Koren, Jeanie B Tryggestad, Fida Bacha, Barbara H Braffett, Silva Arslanian, Elaine M Urbina

Children’s Nutrition Research Center Staff Publications

Aims: (1) To describe changes in arterial stiffness and heart rate variability (HRV) over a 5-year interval, (2) examine changes by sex and race-ethnicity, and (3) evaluate the risk factors associated with the longitudinal changes in arterial stiffness and HRV.

Methods: Participants with youth-onset type 2 diabetes enrolled in the observational follow-up phase of the Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY) clinical trial had arterial stiffness [(pulse wave velocity, augmentation index, brachial distensibility] and six indices of HRV measured 5 years apart. Multivariable linear regression models assessed risk factors associated with changes in the outcomes …


Dear Reviewers: Responses To Common Reviewer Critiques About Infant Neuroimaging Studies, Marta Korom, M Catalina Camacho, Courtney A Filippi, Roxane Licandro, Lucille A Moore, Alexander Dufford, Lilla Zöllei, Alice M Graham, Marisa Spann, Brittany Howell, Fit'ng, Sarah Shultz, Dustin Scheinost Feb 2022

Dear Reviewers: Responses To Common Reviewer Critiques About Infant Neuroimaging Studies, Marta Korom, M Catalina Camacho, Courtney A Filippi, Roxane Licandro, Lucille A Moore, Alexander Dufford, Lilla Zöllei, Alice M Graham, Marisa Spann, Brittany Howell, Fit'ng, Sarah Shultz, Dustin Scheinost

Open Access Publications

The field of adult neuroimaging relies on well-established principles in research design, imaging sequences, processing pipelines, as well as safety and data collection protocols. The field of infant magnetic resonance imaging, by comparison, is a young field with tremendous scientific potential but continuously evolving standards. The present article aims to initiate a constructive dialog between researchers who grapple with the challenges and inherent limitations of a nascent field and reviewers who evaluate their work. We address 20 questions that researchers commonly receive from research ethics boards, grant, and manuscript reviewers related to infant neuroimaging data collection, safety protocols, study planning, …


Alterations Of Host-Gut Microbiome Interactions In Multiple Sclerosis, Claudia Cantoni, Laura Ghezzi, Emily Evans, Li Deng, Alberto Locca, Robert Mikesell, Kathleen Obert, Amber Salter, Anne H Cross, Phillip I Tarr, Laura Piccio, Yanjiao Zhou, Et Al Feb 2022

Alterations Of Host-Gut Microbiome Interactions In Multiple Sclerosis, Claudia Cantoni, Laura Ghezzi, Emily Evans, Li Deng, Alberto Locca, Robert Mikesell, Kathleen Obert, Amber Salter, Anne H Cross, Phillip I Tarr, Laura Piccio, Yanjiao Zhou, Et Al

Open Access Publications

BACKGROUND: Multiple sclerosis (MS) has a complex genetic, immune and metabolic pathophysiology. Recent studies implicated the gut microbiome in MS pathogenesis. However, interactions between the microbiome and host immune system, metabolism and diet have not been studied over time in this disorder.

METHODS: We performed a six-month longitudinal multi-omics study of 49 participants (24 untreated relapse remitting MS patients and 25 age, sex, race matched healthy control individuals. Gut microbiome composition and function were characterized using 16S and metagenomic shotgun sequencing. Flow cytometry was used to characterize blood immune cell populations and cytokine profiles. Circulating metabolites were profiled by untargeted …


Quantifying Regional Α -Synuclein, Amyloid Β, And Tau Accumulation In Lewy Body Dementia, Rebecca L Miller, Dhruva D Dhavale, Jennifer Y O'Shea, Kristin M Andruska, Jialu Liu, Erin E Franklin, Chandana Buddhala, Susan K Loftin, John R Cirrito, Richard J Perrin, Nigel J Cairns, Meghan C Campbell, Joel S Perlmutter, Paul T Kotzbauer Feb 2022

Quantifying Regional Α -Synuclein, Amyloid Β, And Tau Accumulation In Lewy Body Dementia, Rebecca L Miller, Dhruva D Dhavale, Jennifer Y O'Shea, Kristin M Andruska, Jialu Liu, Erin E Franklin, Chandana Buddhala, Susan K Loftin, John R Cirrito, Richard J Perrin, Nigel J Cairns, Meghan C Campbell, Joel S Perlmutter, Paul T Kotzbauer

Open Access Publications

OBJECTIVE: Parkinson disease (PD) is defined by the accumulation of misfolded α-synuclein (α-syn) in Lewy bodies and Lewy neurites. It affects multiple cortical and subcortical neuronal populations. The majority of people with PD develop dementia, which is associated with Lewy bodies in neocortex and referred to as Lewy body dementia (LBD). Other neuropathologic changes, including amyloid β (Aβ) and tau accumulation, occur in some LBD cases. We sought to quantify α-syn, Aβ, and tau accumulation in neocortical, limbic, and basal ganglia regions.

METHODS: We isolated insoluble protein from fresh frozen postmortem brain tissue samples for eight brains regions from 15 …


Measurement Matters: An Individual Differences Examination Of Family Socioeconomic Factors, Latent Dimensions Of Children's Experiences, And Resting State Functional Brain Connectivity In The Abcd Sample, Meriah L Dejoseph, Max P Herzberg, Robin D Sifre, Daniel Berry, Kathleen M Thomas Feb 2022

Measurement Matters: An Individual Differences Examination Of Family Socioeconomic Factors, Latent Dimensions Of Children's Experiences, And Resting State Functional Brain Connectivity In The Abcd Sample, Meriah L Dejoseph, Max P Herzberg, Robin D Sifre, Daniel Berry, Kathleen M Thomas

Open Access Publications

The variation in experiences between high and low-socioeconomic status contexts are posited to play a crucial role in shaping the developing brain and may explain differences in child outcomes. Yet, examinations of SES and brain development have largely been limited to distal proxies of these experiences (e.g., income comparisons). The current study sought to disentangle the effects of multiple socioeconomic indices and dimensions of more proximal experiences on resting-state functional connectivity (rsFC) in a sample of 7834 youth (aged 9-10 years) from the Adolescent Brain Cognitive Development (ABCD) study. We applied moderated nonlinear factor analysis (MNLFA) to establish measurement invariance …


Safety And Efficacy Of Mass Drug Administration With A Single-Dose Triple-Drug Regimen Of Albendazole + Diethylcarbamazine + Ivermectin For Lymphatic Filariasis In Papua New Guinea: An Open-Label, Cluster-Randomised Trial, Livingstone Tavul, Kobie O'Brian, Gary J. Weil, Charles W. Goss, Et Al Feb 2022

Safety And Efficacy Of Mass Drug Administration With A Single-Dose Triple-Drug Regimen Of Albendazole + Diethylcarbamazine + Ivermectin For Lymphatic Filariasis In Papua New Guinea: An Open-Label, Cluster-Randomised Trial, Livingstone Tavul, Kobie O'Brian, Gary J. Weil, Charles W. Goss, Et Al

Open Access Publications

BACKGROUND: Papua New Guinea (PNG) has a high burden of lymphatic filariasis (LF) caused by Wuchereria bancrofti, with an estimated 4.2 million people at risk of infection. A single co-administered dose of ivermectin, diethylcarbamazine and albendazole (IDA) has been shown to have superior efficacy in sustained clearance of microfilariae compared to diethylcarbamazine and albendazole (DA) in small clinical trials. A community-based cluster-randomised trial of DA versus IDA was conducted to compare the safety and efficacy of IDA and DA for LF in a moderately endemic, treatment-naive area in PNG.

METHODOLOGY: All consenting, eligible residents of 24 villages in Bogia district, …


Pivotal Study Evaluating The Safety And Effectiveness Of The Abre Venous Self-Expanding Stent System In Patients With Symptomatic Iliofemoral Venous Outflow Obstruction., Erin Murphy, Kathleen Gibson, Marc Sapoval, David J Dexter, Raghu Kolluri, Mahmood Razavi, Stephen Black Feb 2022

Pivotal Study Evaluating The Safety And Effectiveness Of The Abre Venous Self-Expanding Stent System In Patients With Symptomatic Iliofemoral Venous Outflow Obstruction., Erin Murphy, Kathleen Gibson, Marc Sapoval, David J Dexter, Raghu Kolluri, Mahmood Razavi, Stephen Black

Heart and Vascular Articles

BACKGROUND: Iliofemoral venous obstruction is recognized with increasing frequency as the underlying cause of lower extremity symptoms including edema, pain, skin changes, and, in advanced cases, ulceration. This study sought to evaluate the safety and effectiveness of the Abre venous self-expanding stent system for the treatment of symptomatic iliofemoral venous outflow obstruction.

METHODS: The ABRE Study (A Multi-Center, Non-Randomized Study to Evaluate the Safety and Effectiveness of the Abre Venous Self-Expanding Stent System in Patients With Symptomatic Iliofemoral Venous Outflow Obstruction) is a single-arm, multicenter, prospective study that included 200 subjects from 24 global sites. The primary end points were …