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1. Molecular Transducers of Physical Activity Consortium (MoTrPAC): human studies design and protocol

Author

Group, MoTrPAC Study, Jakicic, John M, Kohrt, Wendy M, Houmard, Joseph A, Miller, Michael E, Radom-Aizik, Shlomit, Rasmussen, Blake B, Ravussin, Eric, Serra, Monica, Stowe, Cynthia L, Trappe, Scott, Abouassi, Hiba, Adkins, Joshua N, Alekel, D Lee, Ashley, Euan, Bamman, Marcas M, Bergman, Bryan C, Bessesen, Daniel H, Broskey, Nicholas T, Buford, Thomas W, Burant, Charles F, Chen, Haiying, Christle, Jeffrey W, Clish, Clary B, Coen, Paul M, Collier, David, Collins, Katherine A, Cooper, Daniel M, Cortes, Tiffany, Cutter, Gary R, Dubis, Gabriel, Fernández, Facundo M, Firnhaber, Jonathon, Forman, Daniel E, Gaul, David A, Gay, Nicole, Gerszten, Robert E, Goodpaster, Bret H, Gritsenko, Marina A, Haddad, Fadia, Huffman, Kim M, Ilkayeva, Olga, Jankowski, Catherine M, Jin, Christopher, Johannsen, Neil M, Johnson, Johanna, Kelly, Leslie, Kershaw, Erin, Kraus, William E, Laughlin, Maren, Lester, Bridget, Lindholm, Malene E, Lowe, Adam, Lu, Ching-Ju, McGowan, Joan, Melanson, Edward L, Montgomery, Stephen, Moore, Samuel G, Moreau, Kerrie L, Muehlbauer, Michael, Musi, Nicolas, Nair, Venugopalan D, Newgard, Christopher B, Newman, Anne B, Nicklas, Barbara, Nindl, Bradley C, Ormond, Kelly, Piehowski, Paul D, Qian, Wei-Jun, Rankinen, Tuomo, Rejeski, W Jack, Robbins, Jeremy, Rogers, Renee J, Rooney, Jessica L, Rushing, Scott, Sanford, James A, Schauer, Irene E, Schwartz, Robert S, Sealfon, Stuart C, Slentz, Cris, Sloan, Ruben, Smith, Kevin S, Snyder, Michael, Spahn, Jessica, Sparks, Lauren M, Stefanovic-Racic, Maja, Tanner, Charles J, Thalacker-Mercer, Anna, Tracy, Russell, Trappe, Todd A, Volpi, Elena, Walsh, Martin J, Wheeler, Matthew T, and Willis, Leslie

Subjects
Biomedical and Clinical Sciences, Health Sciences, Public Health, Sports Science and Exercise, Clinical Sciences, Behavioral and Social Science, Physical Activity, Nutrition, Clinical Research, Obesity, Prevention, Cardiovascular, 6.7 Physical, Generic health relevance, Good Health and Well Being, Humans, Exercise, Adult, Resistance Training, Child, Male, Female, Adolescent, Research Design, Cardiorespiratory Fitness, Muscle Strength, Body Composition, Young Adult, Endurance Training, adipose tissue, biospecimens, molecular transducers, physical activity, skeletal muscle, MoTrPAC Study Group, Biological Sciences, Medical and Health Sciences, Physiology, Biological sciences, Biomedical and clinical sciences, Health sciences
Abstract

Physical activity, including structured exercise, is associated with favorable health-related chronic disease outcomes. Although there is evidence of various molecular pathways that affect these responses, a comprehensive molecular map of these molecular responses to exercise has not been developed. The Molecular Transducers of Physical Activity Consortium (MoTrPAC) is a multicenter study designed to isolate the effects of structured exercise training on the molecular mechanisms underlying the health benefits of exercise and physical activity. MoTrPAC contains both a preclinical and human component. The details of the human studies component of MoTrPAC that include the design and methods are presented here. The human studies contain both an adult and pediatric component. In the adult component, sedentary participants are randomized to 12 wk of Control, Endurance Exercise Training, or Resistance Exercise Training with outcomes measures completed before and following the 12 wk. The adult component also includes recruitment of highly active endurance-trained or resistance-trained participants who only complete measures once. A similar design is used for the pediatric component; however, only endurance exercise is examined. Phenotyping measures include weight, body composition, vital signs, cardiorespiratory fitness, muscular strength, physical activity and diet, and other questionnaires. Participants also complete an acute rest period (adults only) or exercise session (adults, pediatrics) with collection of biospecimens (blood only for pediatrics) to allow for examination of the molecular responses. The design and methods of MoTrPAC may inform other studies. Moreover, MoTrPAC will provide a repository of data that can be used broadly across the scientific community.NEW & NOTEWORTHY The Molecular Transducers of Physical Activity Consortium (MoTrPAC) will be the first large trial to isolate the effects of structured exercise training on the molecular mechanisms underlying the health benefits of exercise and physical activity. By generating a compendium of the molecular responses to exercise, MoTrPAC will lay the foundation for a new era of biomedical research on Precision Exercise Medicine. Presented here is the design, protocols, and procedures for the MoTrPAC human studies.

Published
2024

2. Unique structural configuration of EV-DNA primes Kupffer cell-mediated antitumor immunity to prevent metastatic progression

Author

Wortzel, Inbal, Seo, Yura, Akano, Ife, Shaashua, Lee, Tobias, Gabriel Cardial, Hebert, Jakob, Kim, Kyung-A, Kim, DooA, Dror, Shani, Liu, Yanshen, Azrak, Griffin Campbell, Cioffi, Michele, Johnson, Kofi Ennu, Hennika, Tammy, Twerski, Meshulam Zisha, Kushner, Alexis, Math, Robert, Han, Yoon Dae, Han, Dai Hoon, Jung, Minsun, Park, Juyeong, Paik, Soonmyung, Shin, Jeon-Soo, Lee, Min Goo, Russo, Marco Vincenzo, Zakheim, Daniel, Barnes, Jesse, Mehta, Sunjoy, Manova, Katia, Schwartz, Robert E., Thakur, Basant Kumar, Boudreau, Nancy, Matei, Irina, Zhang, Haiying, Sidoli, Simone, Bromberg, Jacqueline, David, Yael, Kim, Han Sang, and Lyden, David

Published
2024
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3. Physiological Adaptations to Progressive Endurance Exercise Training in Adult and Aged Rats: Insights from the Molecular Transducers of Physical Activity Consortium (MoTrPAC)

Author

Schenk, Simon, Sagendorf, Tyler J, Many, Gina M, Lira, Ana K, de Sousa, Luis GO, Bae, Dam, Cicha, Michael, Kramer, Kyle S, Muehlbauer, Michael, Hevener, Andrea L, Rector, R Scott, Thyfault, John P, Williams, John P, Goodyear, Laurie J, Esser, Karyn A, Newgard, Christopher B, Bodine, Sue C, Adkins, Joshua N, Albertson, Brent G, Amar, David, Amper, Mary Anne S, Ashley, Euan, Bamman, Marcas M, Barnes, Jerry, Bergman, Bryan C, Bessesen, Daniel H, Buford, Thomas W, Burant, Charles F, Cutter, Gary R, De Sousa, Luis Gustavo Oliveria, Fernández, Facundo M, Gaul, David A, Ge, Yongchao, Goodpaster, Bret H, Guevara, Kristy, Hirshman, Michael F, Huffman, Kim M, Jackson, Bailey E, Jankowski, Catherine M, Jimenez-Morales, David, Kohrt, Wendy M, Kraus, William E, Lessard, Sarah J, Lester, Bridget, Lindholm, Malene E, Many, Gina, Marjanovic, Nada, Marshall, Andrea G, Melanson, Edward L, Miller, Michael E, Moreau, Kerrie L, Nair, Venugopalan D, Ortlund, Eric A, Qian, Wei-Jun, Rasmussen, Blake B, Richards, Collyn Z-T, Rushing, Scott, Sanford, James A, Schauer, Irene E, Schwartz, Robert S, Sealfon, Stuart C, Seenarine, Nitish, Sparks, Lauren M, Stowe, Cynthia L, Talton, Jennifer W, Teng, Christopher, Tesfa, Nathan D, Thalacker-Mercer, Anna, Trappe, Scott, Trappe, Todd A, Vasoya, Mital, Wheeler, Matthew T, Walkup, Michael P, Yan, Zhen, and Zhen, Jimmy

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Prevention, Cardiovascular, Physical Activity, Behavioral and Social Science, Animals, Male, Rats, Inbred F344, Female, Physical Conditioning, Animal, Adaptation, Physiological, Rats, Aging, Physical Endurance, Muscle, Skeletal, Endurance Training, training, treadmill, maximal oxygen uptake, body composition, citrate synthase, skeletal muscle, biorepository, aging, MoTrPAC Study Group, Medical physiology
Abstract

While regular physical activity is a cornerstone of health, wellness, and vitality, the impact of endurance exercise training on molecular signaling within and across tissues remains to be delineated. The Molecular Transducers of Physical Activity Consortium (MoTrPAC) was established to characterize molecular networks underlying the adaptive response to exercise. Here, we describe the endurance exercise training studies undertaken by the Preclinical Animal Sites Studies component of MoTrPAC, in which we sought to develop and implement a standardized endurance exercise protocol in a large cohort of rats. To this end, Adult (6-mo) and Aged (18-mo) female (n = 151) and male (n = 143) Fischer 344 rats were subjected to progressive treadmill training (5 d/wk, ∼70%-75% VO2max) for 1, 2, 4, or 8 wk; sedentary rats were studied as the control group. A total of 18 solid tissues, as well as blood, plasma, and feces, were collected to establish a publicly accessible biorepository and for extensive omics-based analyses by MoTrPAC. Treadmill training was highly effective, with robust improvements in skeletal muscle citrate synthase activity in as little as 1-2 wk and improvements in maximum run speed and maximal oxygen uptake by 4-8 wk. For body mass and composition, notable age- and sex-dependent responses were observed. This work in mature, treadmill-trained rats represents the most comprehensive and publicly accessible tissue biorepository, to date, and provides an unprecedented resource for studying temporal-, sex-, and age-specific responses to endurance exercise training in a preclinical rat model.

Published
2024

5. Multi-parametric atlas of the pre-metastatic liver for prediction of metastatic outcome in early-stage pancreatic cancer

Author

Bojmar, Linda, Zambirinis, Constantinos P., Hernandez, Jonathan M., Chakraborty, Jayasree, Shaashua, Lee, Kim, Junbum, Johnson, Kofi Ennu, Hanna, Samer, Askan, Gokce, Burman, Jonas, Ravichandran, Hiranmayi, Zheng, Jian, Jolissaint, Joshua S., Srouji, Rami, Song, Yi, Choubey, Ankur, Kim, Han Sang, Cioffi, Michele, van Beek, Elke, Sigel, Carlie, Jessurun, Jose, Velasco Riestra, Paulina, Blomstrand, Hakon, Jönsson, Carolin, Jönsson, Anette, Lauritzen, Pernille, Buehring, Weston, Ararso, Yonathan, Hernandez, Dylanne, Vinagolu-Baur, Jessica P., Friedman, Madison, Glidden, Caroline, Firmenich, Laetitia, Lieberman, Grace, Mejia, Dianna L., Nasar, Naaz, Mutvei, Anders P., Paul, Doru M., Bram, Yaron, Costa-Silva, Bruno, Basturk, Olca, Boudreau, Nancy, Zhang, Haiying, Matei, Irina R., Hoshino, Ayuko, Kelsen, David, Sagi, Irit, Scherz, Avigdor, Scherz-Shouval, Ruth, Yarden, Yosef, Oren, Moshe, Egeblad, Mikala, Lewis, Jason S., Keshari, Kayvan, Grandgenett, Paul M., Hollingsworth, Michael A., Rajasekhar, Vinagolu K., Healey, John H., Björnsson, Bergthor, Simeone, Diane M., Tuveson, David A., Iacobuzio-Donahue, Christine A., Bromberg, Jaqueline, Vincent, C. Theresa, O’Reilly, Eileen M., DeMatteo, Ronald P., Balachandran, Vinod P., D’Angelica, Michael I., Kingham, T. Peter, Allen, Peter J., Simpson, Amber L., Elemento, Olivier, Sandström, Per, Schwartz, Robert E., Jarnagin, William R., and Lyden, David

Published
2024
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7. Space radiation damage rescued by inhibition of key spaceflight associated miRNAs

Author

McDonald, J. Tyson, Kim, JangKeun, Farmerie, Lily, Johnson, Meghan L., Trovao, Nidia S., Arif, Shehbeel, Siew, Keith, Tsoy, Sergey, Bram, Yaron, Park, Jiwoon, Overbey, Eliah, Ryon, Krista, Haltom, Jeffrey, Singh, Urminder, Enguita, Francisco J., Zaksas, Victoria, Guarnieri, Joseph W., Topper, Michael, Wallace, Douglas C., Meydan, Cem, Baylin, Stephen, Meller, Robert, Muratani, Masafumi, Porterfield, D. Marshall, Kaufman, Brett, Mori, Marcelo A., Walsh, Stephen B., Sigaudo-Roussel, Dominique, Mebarek, Saida, Bottini, Massimo, Marquette, Christophe A., Wurtele, Eve Syrkin, Schwartz, Robert E., Galeano, Diego, Mason, Christopher E., Grabham, Peter, and Beheshti, Afshin

Published
2024
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11. Quantum Gates Between Mesoscopic Spin Ensembles

Author

Niknam, Mohamad, Schwartz, Robert N., and Bouchard, Louis-S.

Subjects
Condensed Matter - Mesoscale and Nanoscale Physics, Quantum Physics
Abstract

Quantum algorithmics with single spins poses serious technological challenges such as precision fabrication, rapid decoherence, atomic-scale addressing and readout. To circumvent atomic-scale challenges, we examine the case of fully polarized mesoscopic spin ensembles (spin-coherent states) whose total angular momenta states map to qudit submanifolds. We show that in the limit where the size of the ensembles is small compared to their separation, it is possible to treat them as qubits with an effective coupling strength that scales with the number of spins. If the spins within each ensemble are decoupled (e.g., via control fields, spinning or diffusional averaging or materials engineering), one- and two-qubit gate operations can be implemented with high fidelities., Comment: 15 pages, 3 figures

Published
2023
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13. America's Hidden Economic Engines: How Community Colleges Can Drive Shared Prosperity. Work and Learning Series

Author

Schwartz, Robert B., Lipson, Rachel, Schwartz, Robert B., and Lipson, Rachel

Abstract

In "America's Hidden Economic Engines," editors Robert B. Schwartz and Rachel Lipson spotlight community and technical colleges as institutions uniquely equipped to foster more equitable economic growth across America's regions. As Schwartz and Lipson show, these colleges are the best-placed institutions to reverse the decades-long rise in US economic inequality by race, class, and geography. In the book, Harvard Project on Workforce researchers introduce detailed case studies of five institutions--Lorain County Community College in Ohio, Mississippi Gulf Coast Community College, Northern Virginia Community College, Pima Community College in Arizona, and San Jacinto Community College in Texas--that show what is possible when governments, employers, and communities invest in their community colleges' economic and workforce development mission. These case studies reveal key institutional policies and practices, leadership behaviors, and organizational structures of successful collaborations between colleges and their regional partners in the public and private sector. Each case underscores how, although community colleges face distinct challenges based on local context, successful schools demonstrate a consistent focus on economic mobility and good jobs across all their programs and activities. In a concluding chapter, the editors champion community colleges as the most critical institutions for the future of US workforce development policy. [Foreword by Harry J. Holzer.]

Published
2023

14. Characteristics and correlates of fentanyl preferences among people with opioid use disorder.

Author

Hochstatter, Karli, Mitchell, Shannon, Schwartz, Robert, Dusek, Kristi, Wireman, Kim, Gryczynski, Jan, and Terplan, Mishka

Subjects
Buprenorphine treatment, Fentanyl preference, Opioid use disorder, Adult, Humans, Fentanyl, Analgesics, Opioid, Heroin, Opioid-Related Disorders, Buprenorphine, Drug Overdose
Abstract

OBJECTIVES: Fentanyl has come to dominate the U.S. illicit opioid supply. We aimed to characterize and examine correlates of preferences for fentanyl vs. other opioids among individuals starting OUD treatment. METHODS: We interviewed 250 adults initiating buprenorphine treatment with positive fentanyl toxicology at intake. We characterized opioid preferences and examined bivariate associations between opioid preference (preference for heroin, fentanyl, heroin-fentanyl mix, or other opioid) and sociodemographic characteristics, psychosocial factors, and substance use behaviors. We then used multinomial logistic regression to examine factors independently associated with fentanyl preferences. RESULTS: Over half (52.0 %) of participants preferred fentanyl (21.2 % fentanyl alone, 30.8 % heroin-fentanyl mix). In bivariate comparisons, participants who preferred fentanyl were a higher acuity group with respect to risks and problems in general. In the multinomial logistic regression, people who preferred fentanyl, either alone or mixed with heroin, used non-prescribed buprenorphine less in the 30 days preceding treatment entry compared to people who preferred heroin or other opioids (RRRalone= 0.88 [0.78, 0.99]; P = 0.037 and RRRmixed= 0.91 [0.84, 0.99]; P = 0.046). People who preferred fentanyl alone were also younger (RRR= 0.93 [0.90, 0.97]; P

Published
2022

15. A comprehensive SARS-CoV-2 and COVID-19 review, Part 2: host extracellular to systemic effects of SARS-CoV-2 infection

Author

Narayanan, S. Anand, Jamison, Jr, David A., Guarnieri, Joseph W., Zaksas, Victoria, Topper, Michael, Koutnik, Andrew P., Park, Jiwoon, Clark, Kevin B., Enguita, Francisco J., Leitão, Ana Lúcia, Das, Saswati, Moraes-Vieira, Pedro M., Galeano, Diego, Mason, Christopher E., Trovão, Nídia S., Schwartz, Robert E., Schisler, Jonathan C., Coelho-dos-Reis, Jordana G. A., Wurtele, Eve Syrkin, and Beheshti, Afshin

Published
2024
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16. Quantum Control of Spin Qubits Using Nanomagnets

Author

Niknam, Mohamad, Chowdhury, Md Fahim F., Rajib, Md Mahadi, Misba, Walid Al, Schwartz, Robert N., Wang, Kang L., Atulasimha, Jayasimha, and Bouchard, Louis-S.

Subjects
Condensed Matter - Mesoscale and Nanoscale Physics, Quantum Physics
Abstract

Single-qubit gates are essential components of a universal quantum computer. Without selective addressing of individual qubits, scalable implementation of quantum algorithms is not possible. When the qubits are discrete points or regions on a lattice, the selective addressing of magnetic spin qubits at the nanoscale remains a challenge due to the difficulty of localizing and confining a classical divergence-free field to a small volume of space. Herein we propose a new technique for addressing spin qubits using voltage-control of nanoscale magnetism, exemplified by the use of voltage control of magnetic anisotropy (VCMA). We show that by tuning the frequency of the nanomagnet's electric field drive to the Larmor frequency of the spins confined to a nanoscale volume, and by modulating the phase of the drive, single-qubit quantum gates with fidelities approaching those for fault-tolerant quantum computing can be implemented. Such single-qubit gate operations have the advantage of remarkable energy efficiency, requiring only tens of femto-Joules per gate operation, and lossless, purely magnetic field control (no E-field over the target volume). Their physical realization is also straightforward using existing foundry manufacturing techniques., Comment: 10 pages, 6 figures

Published
2022
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17. Host protein kinases required for SARS-CoV-2 nucleocapsid phosphorylation and viral replication

Author

Yaron, Tomer M, Heaton, Brook E, Levy, Tyler M, Johnson, Jared L, Jordan, Tristan X, Cohen, Benjamin M, Kerelsky, Alexander, Lin, Ting-Yu, Liberatore, Katarina M, Bulaon, Danielle K, Van Nest, Samantha J, Koundouros, Nikos, Kastenhuber, Edward R, Mercadante, Marisa N, Shobana-Ganesh, Kripa, He, Long, Schwartz, Robert E, Chen, Shuibing, Weinstein, Harel, Elemento, Olivier, Piskounova, Elena, Nilsson-Payant, Benjamin E, Lee, Gina, Trimarco, Joseph D, Burke, Kaitlyn N, Hamele, Cait E, Chaparian, Ryan R, Harding, Alfred T, Tata, Aleksandra, Zhu, Xinyu, Tata, Purushothama Rao, Smith, Clare M, Possemato, Anthony P, Tkachev, Sasha L, Hornbeck, Peter V, Beausoleil, Sean A, Anand, Shankara K, Aguet, François, Getz, Gad, Davidson, Andrew D, Heesom, Kate, Kavanagh-Williamson, Maia, Matthews, David A, tenOever, Benjamin R, Cantley, Lewis C, Blenis, John, and Heaton, Nicholas S

Subjects
Pneumonia & Influenza, Prevention, Immunization, Biotechnology, Vaccine Related, Lung, Emerging Infectious Diseases, Infectious Diseases, Infection, Good Health and Well Being, Animals, Humans, SARS-CoV-2, Phosphorylation, COVID-19, Glycogen Synthase Kinase 3, Virus Replication, Nucleocapsid Proteins, Nucleocapsid, Serine, Threonine, Mammals, Protein Serine-Threonine Kinases, Biochemistry and Cell Biology
Abstract

Multiple coronaviruses have emerged independently in the past 20 years that cause lethal human diseases. Although vaccine development targeting these viruses has been accelerated substantially, there remain patients requiring treatment who cannot be vaccinated or who experience breakthrough infections. Understanding the common host factors necessary for the life cycles of coronaviruses may reveal conserved therapeutic targets. Here, we used the known substrate specificities of mammalian protein kinases to deconvolute the sequence of phosphorylation events mediated by three host protein kinase families (SRPK, GSK-3, and CK1) that coordinately phosphorylate a cluster of serine and threonine residues in the viral N protein, which is required for viral replication. We also showed that loss or inhibition of SRPK1/2, which we propose initiates the N protein phosphorylation cascade, compromised the viral replication cycle. Because these phosphorylation sites are highly conserved across coronaviruses, inhibitors of these protein kinases not only may have therapeutic potential against COVID-19 but also may be broadly useful against coronavirus-mediated diseases.

Published
2022

18. The opioid use disorder core outcomes set (OUD-COS) for treatment research: findings from a Delphi consensus study.

Author

Karnik, Niranjan, Marsden, John, McCluskey, Connor, Boley, Randy, Bradley, Katharine, Campbell, Cynthia, Curtis, Megan, Fiellin, David, Ghitza, Udi, Hefner, Kathryn, Hser, Yih-Ing, McHugh, R, McPherson, Sterling, Mooney, Larissa, Moran, Landhing, Murphy, Sean, Schwartz, Robert, Shmueli-Blumberg, Dikla, Shulman, Matisyahu, Stephens, Kari, Watkins, Katherine, Weiss, Roger, and Wu, Li-Tzy

Subjects
Core outcomes set, Delphi consensus, US National Institute on Drug Abuse, efficacy and effectiveness research, opioid treatment cascade, opioid use disorder, Analgesics, Opioid, Consensus, Delphi Technique, Humans, Opioid-Related Disorders, Outcome Assessment, Health Care, Research Design, United States
Abstract

BACKGROUND AND AIM: There is no gold-standard and considerable heterogeneity in outcome measures used to evaluate treatments for opioid use disorder (OUD) along the opioid treatment cascade. The aim of this study was to develop the US National Institute on Drug Abuse (NIDA) National Drug Abuse Treatment Clinical Trials Network (CTN) opioid use disorder core outcomes set (OUD-COS). DESIGN: Four-round, e-Delphi expert panel consensus study and plenary research group discussion and targeted consultation. SETTING: United States. PARTICIPANTS: A panel of 25 members including clinical practitioners, clinical researchers and administrative staff from the CTN, the networks affiliated clinical and community sites and the NIDA Centre for the CTN. MEASUREMENTS: From a pool of 24 candidate items in four domains (biomedical/disease status; behaviors, symptoms and functioning; opioid treatment cascade; and morbidity and mortality), the panel completed an on-line questionnaire to rank items with defined specification on a 9-point scale for importance, with a standard 70% consensus criterion. FINDINGS: After the fourth round of the questionnaire and subsequent discussion, consensus was reached for five outcomes: two patient-reported (global impression of improvement and incident non-fatal overdose); one clinician-reported (illicit/non-medical drug toxicology); and two from administrative records (duration of treatment and fatal opioid poisoning). CONCLUSIONS: An e-Delphi consensus study has produced the US National Institute on Drug Abuse (NIDA) National Drug Abuse Treatment Clinical Trials Network opioid use disorder core outcomes set (version 1) for opioid use disorder treatment efficacy and effectiveness research.

Published
2022

23. Author Correction: Identification of SARS-CoV-2 inhibitors using lung and colonic organoids

Author

Han, Yuling, Duan, Xiaohua, Yang, Liuliu, Nilsson-Payant, Benjamin E., Wang, Pengfei, Duan, Fuyu, Tang, Xuming, Yaron, Tomer M., Zhang, Tuo, Uhl, Skyler, Bram, Yaron, Richardson, Chanel, Zhu, Jiajun, Zhao, Zeping, Redmond, David, Houghton, Sean, Nguyen, Duc-Huy T., Xu, Dong, Wang, Xing, Jessurun, Jose, Borczuk, Alain, Huang, Yaoxing, Johnson, Jared L., Liu, Yuru, Xiang, Jenny, Wang, Hui, Cantley, Lewis C., tenOever, Benjamin R., Ho, David D., Pan, Fong Cheng, Evans, Todd, Chen, Huanhuan Joyce, Schwartz, Robert E., and Chen, Shuibing

Published
2024
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26. A Thermodynamic Core using Voltage-Controlled Spin-Orbit-Torque Magnetic Tunnel Junctions

Author

Lee, Albert, Dai, Bingqian, Wu, Di, Wu, Hao, Schwartz, Robert N, and Wang, Kang L

Subjects
Computer Science - Emerging Technologies
Abstract

We present a magnetic implementation of a thermodynamic computing fabric. Magnetic devices within computing cores harness thermodynamics through its voltage-controlled thermal stability; while the evolution of network states is guided by the spin-orbit-torque effect. We theoretically derive the dynamics of the cores and show that the computing fabric can successfully compute ground states of a Boltzmann Machine. Subsequently, we demonstrate the physical realization of these devices based on a CoFeB-MgO magnetic tunnel junction structure. The results of this work pave the path towards the realization of highly efficient, high-performance thermodynamic computing hardware. Finally, this paper will also give a perspective of computing beyond thermodynamic computing.

Published
2021
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41. Core outcomes set for research on the treatment of opioid use disorder (COS-OUD): the National Institute on Drug Abuse Clinical Trials Network protocol for an e-Delphi consensus study.

Author

Karnik, Niranjan, Campbell, Cynthia, Curtis, Megan, Fiellin, David, Ghitza, Udi, Hefner, Kathryn, Hser, Yih-Ing, McHugh, R, Murphy, Sean, McPherson, Sterling, Moran, Landhing, Mooney, Larissa, Wu, Li-Tzy, Shmueli-Blumberg, Dikla, Shulman, Matisyahu, Schwartz, Robert, Stephens, Kari, Watkins, Katherine, and Marsden, John

Subjects
Consensus, Core outcome set, E-Delphi survey, Opioid use disorder, Outcome reporting, Patient-reported outcomes, Adolescent, Adult, Aged, Consensus, Delphi Technique, Endpoint Determination, Female, Humans, Male, Middle Aged, National Institute on Drug Abuse (U.S.), Opioid-Related Disorders, Research Design, Treatment Outcome, United States, Young Adult
Abstract

BACKGROUND: A lack of consensus on the optimal outcome measures to assess the efficacy and effectiveness of interventions for the treatment of opioid use disorder (OUD) has hampered the pooling of research data for evidence synthesis and clinical guidelines. A core outcome set (COS) is a minimum set of outcome measures that are recommended for all studies of a particular condition. The National Drug Abuse Treatment Clinical Trials Network (CTN) Core Outcome Set for OUD (COS-OUD) is a development study to identify core constructs, meaningful outcomes, and their optimal measurement for all efficacy and effectiveness studies of OUD treatment and service delivery. METHODS/DESIGN: Overseen by an expert workgroup, a modified, stepwise, e-Delphi methodology will be used to gain consensus among a panel of clinical practitioners and researchers involved in the treatment of OUD, who are members of the CTN. Sequential rounds of anonymous, online questionnaires will be used to identify, rate the importance of, and refine a core outcome set. A consensus threshold will be achieved if at least 70% of the panel rate the measure as critical for inclusion in the COS-OUD. Where consensus is not reached or there are suggestions for new measures, these will be brought forward to a further round of review prior to a consensus meeting. Products from this study will be communicated via peer-reviewed scientific journals and conferences. DISCUSSION: This initiative will develop a COS for OUD intervention trials, treatment studies, and service delivery and will support the pooling of research and clinical practice data and efforts to develop measurement-based care within the OUD treatment cascade. TRIAL REGISTRATION: http://www.comet-initiative.org/Studies/Details/1579.

Published
2021

42. Shotgun transcriptome, spatial omics, and isothermal profiling of SARS-CoV-2 infection reveals unique host responses, viral diversification, and drug interactions

Author

Butler, Daniel, Mozsary, Christopher, Meydan, Cem, Foox, Jonathan, Rosiene, Joel, Shaiber, Alon, Danko, David, Afshinnekoo, Ebrahim, MacKay, Matthew, Sedlazeck, Fritz J, Ivanov, Nikolay A, Sierra, Maria, Pohle, Diana, Zietz, Michael, Gisladottir, Undina, Ramlall, Vijendra, Sholle, Evan T, Schenck, Edward J, Westover, Craig D, Hassan, Ciaran, Ryon, Krista, Young, Benjamin, Bhattacharya, Chandrima, Ng, Dianna L, Granados, Andrea C, Santos, Yale A, Servellita, Venice, Federman, Scot, Ruggiero, Phyllis, Fungtammasan, Arkarachai, Chin, Chen-Shan, Pearson, Nathaniel M, Langhorst, Bradley W, Tanner, Nathan A, Kim, Youngmi, Reeves, Jason W, Hether, Tyler D, Warren, Sarah E, Bailey, Michael, Gawrys, Justyna, Meleshko, Dmitry, Xu, Dong, Couto-Rodriguez, Mara, Nagy-Szakal, Dorottya, Barrows, Joseph, Wells, Heather, O’Hara, Niamh B, Rosenfeld, Jeffrey A, Chen, Ying, Steel, Peter AD, Shemesh, Amos J, Xiang, Jenny, Thierry-Mieg, Jean, Thierry-Mieg, Danielle, Iftner, Angelika, Bezdan, Daniela, Sanchez, Elizabeth, Campion, Thomas R, Sipley, John, Cong, Lin, Craney, Arryn, Velu, Priya, Melnick, Ari M, Shapira, Sagi, Hajirasouliha, Iman, Borczuk, Alain, Iftner, Thomas, Salvatore, Mirella, Loda, Massimo, Westblade, Lars F, Cushing, Melissa, Wu, Shixiu, Levy, Shawn, Chiu, Charles, Schwartz, Robert E, Tatonetti, Nicholas, Rennert, Hanna, Imielinski, Marcin, and Mason, Christopher E

Subjects
Biological Sciences, Biomedical and Clinical Sciences, Clinical Sciences, Infectious Diseases, Vaccine Related, Biodefense, Rare Diseases, Emerging Infectious Diseases, Clinical Research, Prevention, Lung, Pneumonia & Influenza, Aetiology, Development of treatments and therapeutic interventions, 2.1 Biological and endogenous factors, 5.1 Pharmaceuticals, Infection, Good Health and Well Being, Adult, Aged, Angiotensin Receptor Antagonists, Angiotensin-Converting Enzyme Inhibitors, Antiviral Agents, COVID-19, COVID-19 Nucleic Acid Testing, Drug Interactions, Female, Gene Expression Profiling, Genome, Viral, HLA Antigens, Host Microbial Interactions, Humans, Male, Middle Aged, Molecular Diagnostic Techniques, New York City, Nucleic Acid Amplification Techniques, Pandemics, RNA-Seq, SARS-CoV-2, COVID-19 Drug Treatment
Abstract

In less than nine months, the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) killed over a million people, including >25,000 in New York City (NYC) alone. The COVID-19 pandemic caused by SARS-CoV-2 highlights clinical needs to detect infection, track strain evolution, and identify biomarkers of disease course. To address these challenges, we designed a fast (30-minute) colorimetric test (LAMP) for SARS-CoV-2 infection from naso/oropharyngeal swabs and a large-scale shotgun metatranscriptomics platform (total-RNA-seq) for host, viral, and microbial profiling. We applied these methods to clinical specimens gathered from 669 patients in New York City during the first two months of the outbreak, yielding a broad molecular portrait of the emerging COVID-19 disease. We find significant enrichment of a NYC-distinctive clade of the virus (20C), as well as host responses in interferon, ACE, hematological, and olfaction pathways. In addition, we use 50,821 patient records to find that renin-angiotensin-aldosterone system inhibitors have a protective effect for severe COVID-19 outcomes, unlike similar drugs. Finally, spatial transcriptomic data from COVID-19 patient autopsy tissues reveal distinct ACE2 expression loci, with macrophage and neutrophil infiltration in the lungs. These findings can inform public health and may help develop and drive SARS-CoV-2 diagnostic, prevention, and treatment strategies.

Published
2021

43. Molecular Transducers of Physical Activity Consortium (MoTrPAC): Mapping the Dynamic Responses to Exercise

Author

Sanford, James A, Nogiec, Christopher D, Lindholm, Malene E, Adkins, Joshua N, Amar, David, Dasari, Surendra, Drugan, Jonelle K, Fernández, Facundo M, Radom-Aizik, Shlomit, Schenk, Simon, Snyder, Michael P, Tracy, Russell P, Vanderboom, Patrick, Trappe, Scott, Walsh, Martin J, Consortium, the Molecular Transducers of Physical Activity, Evans, Charles R, Fernandez, Facundo M, Li, Yafeng, Tomlinson, Lyl, Alekel, D Lee, Bekirov, Iddil, Boyce, Amanda T, Boyington, Josephine, Fleg, Jerome L, Joseph, Lyndon JO, Laughlin, Maren R, Maruvada, Padma, Morris, Stephanie A, McGowan, Joan A, Nierras, Concepcion, Pai, Vinay, Peterson, Charlotte, Ramos, Ed, Roary, Mary C, Williams, John P, Xia, Ashley, Cornell, Elaine, Rooney, Jessica, Miller, Michael E, Ambrosius, Walter T, Rushing, Scott, Stowe, Cynthia L, Rejeski, W Jack, Nicklas, Barbara J, Pahor, Marco, Lu, Ching-ju, Trappe, Todd, Chambers, Toby, Raue, Ulrika, Lester, Bridget, Bergman, Bryan C, Bessesen, David H, Jankowski, Catherine M, Kohrt, Wendy M, Melanson, Edward L, Moreau, Kerrie L, Schauer, Irene E, Schwartz, Robert S, Kraus, William E, Slentz, Cris A, Huffman, Kim M, Johnson, Johanna L, Willis, Leslie H, Kelly, Leslie, Houmard, Joseph A, Dubis, Gabriel, Broskey, Nick, Goodpaster, Bret H, Sparks, Lauren M, Coen, Paul M, Cooper, Dan M, Haddad, Fadia, Rankinen, Tuomo, Ravussin, Eric, Johannsen, Neil, Harris, Melissa, Jakicic, John M, Newman, Anne B, Forman, Daniel D, Kershaw, Erin, Rogers, Renee J, Nindl, Bradley C, Page, Lindsay C, Stefanovic-Racic, Maja, and Barr, Susan L

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Prevention, Physical Activity, Cardiovascular, Behavioral and Social Science, Generic health relevance, Good Health and Well Being, Adolescent, Adult, Animals, Child, Exercise, Female, Humans, Male, Middle Aged, Oxygen Consumption, Physical Endurance, Research Design, Young Adult, Molecular Transducers of Physical Activity Consortium, Biological Sciences, Medical and Health Sciences, Developmental Biology, Biological sciences, Biomedical and clinical sciences
Abstract

Exercise provides a robust physiological stimulus that evokes cross-talk among multiple tissues that when repeated regularly (i.e., training) improves physiological capacity, benefits numerous organ systems, and decreases the risk for premature mortality. However, a gap remains in identifying the detailed molecular signals induced by exercise that benefits health and prevents disease. The Molecular Transducers of Physical Activity Consortium (MoTrPAC) was established to address this gap and generate a molecular map of exercise. Preclinical and clinical studies will examine the systemic effects of endurance and resistance exercise across a range of ages and fitness levels by molecular probing of multiple tissues before and after acute and chronic exercise. From this multi-omic and bioinformatic analysis, a molecular map of exercise will be established. Altogether, MoTrPAC will provide a public database that is expected to enhance our understanding of the health benefits of exercise and to provide insight into how physical activity mitigates disease.

Published
2020

44. Sex Education by Theatre (SExT): The Impact of a Culturally Empowering, Theatre-Based, Peer Education Intervention on the Sexual Health Self-Efficacy of Newcomer Youth in Canada

Author

Taylor, Shira B., Calzavara, Liviana, Kontos, Pia, and Schwartz, Robert

Abstract

Despite rising rates of sexually transmitted infections (STIs) and inequitable access to education and services, few studies have addressed the unique sex education needs of newcomer youth in Canada and other increasingly demographically diverse Western countries. This study involved the design, implementation and evaluation of a novel and innovative participatory action research project, SExT: Sex Education by Theatre. SExT is a theatre-based, culturally empowering, peer education intervention piloted in a multicultural area of Toronto. Young people were trained as peer educators through participation in theatre-based workshops culminating in the performance of a new play for peers. Mixed methods evaluation involved surveys, focus groups, peer interviews and arts-based data collection. Paired-samples t-tests were conducted to investigate changes in sexual health self-efficacy (protection, STI/HIV testing, sexual limit-setting) over three time-points (pre, post, 4-month follow-up). Thematic analysis was used to gain a deeper understanding of outcomes. Quantitative analysis demonstrated significant improvements in outcome measures from pre- to post-intervention that were maintained at follow-up. Qualitative data indicated increased sexual health self-efficacy attributed to SExT. Pilot study findings suggest that SExT may serve as a model for sexual health interventions in areas populated by newcomer and other priority youth groups.

Published
2022
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45. Secondary Analysis of the Reading Recovery Four-Year i3 Scale-Up

Author

Schwartz, Robert M. and Lomax, Richard

Abstract

This paper provides a secondary analysis of the May, Sirinides, Gray, and Goldsworthy (2016) evaluation of the Reading Recovery scale-up. We extend their findings to include analysis of the six subscales of the "Observation Survey (OS) of Early Literacy Achievement" (Clay, 2013) that the What Works Clearinghouse has previously used to access the beginning reading domains of Alphabets, Reading Fluency, and General Reading Ability. We also provide a sub-group analysis of students whose entry scores predict a severe reading difficulty at the end of first grade. This analysis includes the ITBS subscales reported by May et al. for their main analysis. The May et al. design was a randomized controlled trial with independent samples in each of the four years of the study. In total 3444 pairs of first grade students were matched on the fall OS Text Reading Level measure and then randomly assigned to the treatment or control condition. The secondary analysis presents descriptive statistics and Hedges's d effect size calculations for the total sample and sub-group on each of the subscales of the OS. The analysis for the Text Reading Level measure is calculated for both raw scores and scale scores. The scale scores provide an interval measure that is more appropriate for calculations of effect size (D'Agostino, Rodgers, & Mauck, 2018). The results showed medium to large effects on each of the OS measures for the total groups and severely at-risk subgroup. The appendix includes additional tables for each year of the scale-up, demonstrating replication of these findings over the four independent RCTs. The Institute of Education Sciences (IES, 2016) considers its highest evidence level as "an independent evaluation of a fully-developed education intervention with prior evidence of efficacy, when implemented by the end user under routine conditions" (IES, 2016, p.5). The replication of substantial effects on the ITBS and OS subscales demonstrates the ability of the Reading Recovery network to partner with schools to scale-up and implement an effective early intervention.

Published
2018

49. Recent Developments and Therapeutic Strategies against Hepatocellular Carcinoma

Author

Yarchoan, Mark, Agarwal, Parul, Villanueva, Augusto, Rao, Shuyun, Dawson, Laura A, Karasic, Thomas, Llovet, Josep M, Finn, Richard S, Groopman, John D, El-Serag, Hashem B, Monga, Satdarshan P, Wang, Xin Wei, Karin, Michael, Schwartz, Robert E, Tanabe, Kenneth K, Roberts, Lewis R, Gunaratne, Preethi H, Tsung, Allan, Brown, Kimberly A, Lawrence, Theodore S, Salem, Riad, Singal, Amit G, Kim, Amy K, Rabiee, Atoosa, Resar, Linda, Meyer, Jeffrey, Hoshida, Yujin, He, Aiwu Ruth, Ghoshal, Kalpana, Ryan, Patrick B, Jaffee, Elizabeth M, Guha, Chandan, Mishra, Lopa, Coleman, C Norman, and Ahmed, Mansoor M

Subjects
Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Digestive Diseases, Liver Disease, Liver Cancer, Cancer, Orphan Drug, Rare Diseases, Chronic Liver Disease and Cirrhosis, Evaluation of treatments and therapeutic interventions, 6.1 Pharmaceuticals, Anilides, Antibodies, Monoclonal, Humanized, Carcinoma, Hepatocellular, Chemoembolization, Therapeutic, Clinical Trials as Topic, Humans, Immunotherapy, Liver Neoplasms, Molecular Targeted Therapy, Mutation, Phenylurea Compounds, Protein Kinase Inhibitors, Pyridines, Quinolines, beta Catenin, Oncology & Carcinogenesis, Biochemistry and cell biology, Oncology and carcinogenesis
Abstract

Hepatocellular carcinoma (HCC) has emerged as a major cause of cancer deaths globally. The landscape of systemic therapy has recently changed, with six additional systemic agents either approved or awaiting approval for advanced stage HCC. While these agents have the potential to improve outcomes, a survival increase of 2-5 months remains poor and falls short of what has been achieved in many other solid tumor types. The roles of genomics, underlying cirrhosis, and optimal use of treatment strategies that include radiation, liver transplantation, and surgery remain unanswered. Here, we discuss new treatment opportunities, controversies, and future directions in managing HCC.

Published
2019

50. CRISPR screening uncovers a central requirement for HHEX in pancreatic lineage commitment and plasticity restriction

Author

Yang, Dapeng, Cho, Hyunwoo, Tayyebi, Zakieh, Shukla, Abhijit, Luo, Renhe, Dixon, Gary, Ursu, Valeria, Stransky, Stephanie, Tremmel, Daniel M., Sackett, Sara D., Koche, Richard, Kaplan, Samuel J., Li, Qing V., Park, Jiwoon, Zhu, Zengrong, Rosen, Bess P., Pulecio, Julian, Shi, Zhong-Dong, Bram, Yaron, Schwartz, Robert E., Odorico, Jon S., Sidoli, Simone, Wright, Christopher V., Leslie, Christina S., and Huangfu, Danwei

Published
2022
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