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2. Effect of Opaganib on Supplemental Oxygen and Mortality in Patients with Severe SARS-CoV-2 Based upon FIO2 Requirements

Author

Fernando Carvalho Neuenschwander, Ofra Barnett-Griness, Stefania Piconi, Yasmin Maor, Eduardo Sprinz, Nimer Assy, Oleg Khmelnitskiy, Nikita V. Lomakin, Boris Mikhailovich Goloshchekin, Ewelina Nahorecka, Adilson Joaquim Westheimer Calvacante, Anastasia Ivanova, Sergey Vladimirovich Zhuravel, Galina Yurevna Trufanova, Stefano Bonora, Amer Saffoury, Ami Mayo, Yury G. Shvarts, Giuliano Rizzardini, Rogerio Sobroza de Mello, Janaina Pilau, Alexey Klinov, Benjamin Valente-Acosta, Oleg Olegovich Burlaka, Natalia Bakhtina, Maskit Bar-Meir, Ivan Nikolaevich Shishimorov, Jose Oñate-Gutierrez, Cristian Iván García Rincón, Tatiana Ivanovna Martynenko, Ludhmila Abrahão Hajjar, Ana Carolina Nazare de Mendonca Procopio, Krzysztof Simon, Walter Gabriel Chaves Santiago, Adam Fronczak, Conrado Roberto Hoffmann Filho, Osama Hussein, Vladimir Aleksandrovich Martynov, Guido Chichino, Piotr Blewaska, Jacek Wroblewski, Sergio Saul Irizar Santana, Andres Felipe Ocampo Agudelo, Adam Barczyk, Rachael lask Gerlach, Eppie Campbell, Aida Bibliowicz, Reza Fathi, Patricia Anderson, Gilead Raday, Michal Klein, Clara Fehrmann, Gina Eagle, Vered Katz Ben-Yair, and Mark L. Levitt

Subjects
opaganib, COVID-19, sphingosine kinase 2, ABC294640, SARS-CoV-2 pneumonia, trial registration number: NCT04467840, Biology (General), QH301-705.5
Abstract

Once a patient has been diagnosed with severe COVID-19 pneumonia, treatment options have limited effectiveness. Opaganib is an oral treatment under investigation being evaluated for treatment of hospitalized patients with severe COVID-19 pneumonia. A randomized, placebo-controlled, double-blind phase 2/3 trial was conducted in 57 sites worldwide from August 2020 to July 2021. Patients received either opaganib (n = 230; 500 mg twice daily) or matching placebo (n = 233) for 14 days. The primary outcome was the proportion of patients no longer requiring supplemental oxygen by day 14. Secondary outcomes included changes in the World Health Organization Ordinal Scale for Clinical Improvement, viral clearance, intubation, and mortality at 28 and 42 days. Pre-specified primary and secondary outcome analyses did not demonstrate statistically significant benefit (except nominally for time to viral clearance). Post-hoc analysis revealed the fraction of inspired oxygen (FIO2) at baseline was prognostic for opaganib treatment responsiveness and corresponded to disease severity markers. Patients with FIO2 levels at or below the median value (≤60%) had better outcomes after opaganib treatment (n = 117) compared to placebo (n = 134). The proportion of patients with ≤60% FIO2 at baseline that no longer required supplemental oxygen (≥24 h) by day 14 of opaganib treatment increased (76.9% vs. 63.4%; nominal p-value = 0.033). There was a 62.6% reduction in intubation/mechanical ventilation (6.84% vs. 17.91%; nominal p-value = 0.012) and a clinically meaningful 62% reduction in mortality (5.98% vs. 16.7%; nominal p-value = 0.019) by day 42. No new safety concerns were observed. While the primary analyses were not statistically significant, post-hoc analysis suggests opaganib benefit for patients with severe COVID-19 requiring supplemental oxygen with an FIO2 of ≤60%. Further studies are warranted to prospectively confirm opaganib benefit in this subpopulation.

Published
2024
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5. College Student Symptoms as Assessed by a Student Health Survey

Author

Cotler, Joseph, Katz, Ben Z., Torres, Chelsea, and Jason, Leonard A.

Abstract

Objective: We sought to identify the general health of college students. Participants: A total of 4402 university freshmen and sophomores were recruited to report their general health through an online questionnaire. Methods: Responses from the DePaul Symptom Questionnaire were analyzed. We then conducted latent class analyses to evaluate 54 different symptoms among participants. Results: A four class solution was identified, consisting of a group of asymptomatic students (35.65%), a second group of students reporting mild fatigue and sleep symptoms (38.87%), a third group reporting moderate sleep and fatigue symptoms (20.36%), and a group reporting moderate and severe complaints on the majority of symptoms (5.11%). Female students had 2.07 times the relative risk of the severe symptom class of men. Indigenous students have 2.88 times the relative risk of occupying the severe symptom class than non-indigenous students. Conclusions: The results suggest that about 5% of college students have varied symptoms of a moderate to severe degree. Future research is needed to better assess whether there are biological associations with these self-report findings, as well as to determine longer-term implications of these symptoms.

Published
2022
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8. Contributors

Author

Abzug, Mark J., primary, Adderson, Elisabeth E., additional, Agarwal, Aastha, additional, Agwu, Allison L., additional, Albenberg, Lindsey, additional, Albert, Jonathan, additional, Alby, Kevin, additional, Aldrovandi, Grace M., additional, Allen, Upton D., additional, Alvarez-Hernndez, Gerardo, additional, Ampofo, Krow, additional, Anderson, Evan J., additional, Appiah, Grace D., additional, Ardura, Monica I., additional, Arnon, Stephen S., additional, Aronson, Naomi E., additional, Arvin, Ann M., additional, Ashkenazi, Shai, additional, Ashkenazi-Hoffnung, Liat, additional, Asturias, Edwin J., additional, Aukstuolis, Kestutis, additional, Badalyan, Vahe, additional, Baker, Carol J., additional, Balakrishnan, Karthik, additional, Barnett, Elizabeth D., additional, Bechtel, Kirsten, additional, Benitz, William E., additional, Berkovich, Rachel, additional, Berman, David M., additional, Bialek, Stephanie R., additional, Bijker, Else M., additional, Bizzarro, Matthew J., additional, Bloch, Karen C., additional, Bocchini, Joseph A., additional, Boyce, Thomas G., additional, Bradley, John S., additional, Bratcher, Denise F., additional, Braverman, Paula K., additional, Brook, Itzhak, additional, Brown, Kevin Edward, additional, Bryant, Kristina P., additional, Camacho-Gonzalez, Andres F., additional, Caete-Gibas, Connie F., additional, Cantey, Joseph B., additional, Cantey, Paul, additional, Cardemil, Cristina V., additional, Caserta, Mary T., additional, Castagnini, Luis A., additional, Cataldi, Jessica R., additional, Chadwick, Ellen Gould, additional, Chancey, Rebecca J., additional, Cherry, Cara C., additional, Chiang, Silvia S., additional, Choi, Mary, additional, Christenson, John C., additional, Coffin, Susan E., additional, Cohn, Amanda, additional, Contopoulos-Ioannidis, Despina G., additional, Conway, James H., additional, Cortese, Margaret M., additional, Creech, C. Buddy, additional, Crews, Jonathan D., additional, Curtis, Donna, additional, Curtis, Nigel, additional, Danziger-Isakov, Lara A., additional, Darville, Toni, additional, Dasch, Gregory A., additional, Daskalaki, Irini, additional, Davies, H. Dele, additional, Dawood, Fatimah S., additional, Day, J. Christopher, additional, Teresa de la Morena, M., additional, DeMuri, Gregory P., additional, Despommier, Dickson D., additional, Dodson, Daniel S., additional, Dolgner, Stephen J., additional, Dunn, Clinton, additional, Dyal, Jonathan, additional, Edwards, Kathryn M., additional, Edwards, Morven S., additional, Eichenfield, Dawn Z., additional, Eichenfield, Lawrence F., additional, Elston, Dirk M., additional, Emerson, Beth, additional, Enane, Leslie A., additional, Ephros, Moshe, additional, Erdem, Guliz, additional, Eremeeva, Marina E., additional, Esposito, Douglas H., additional, Farley, Monica M., additional, Feingold, Anat R., additional, Feja, Kristina N., additional, Finn, Adam, additional, Fischer, Marc, additional, Fisher, Brian T., additional, Fisher, Randall G., additional, Flynn, Patricia Michele, additional, Foster, Monique A., additional, Fox, LeAnne M., additional, Frank, Michael M., additional, Fredrick, Douglas R., additional, Frenck, Robert W., additional, Gaensbauer, James, additional, Gans, Hayley A., additional, Gauthier, Gregory M., additional, Gavigan, Patrick, additional, Gerber, Jeffrey S., additional, Gernez, Yael, additional, Gigliotti, Francis, additional, Gilger, Mark A., additional, Glaser, Carol A., additional, Gould, Jane M., additional, Graziano, James, additional, Green, Amanda M., additional, Green, Michael, additional, Griffin, Daniel, additional, Griffin, Patricia M., additional, Griffith, David C., additional, Gupta, Piyush, additional, Gutelius, Bruce J., additional, Gutman, Julie R., additional, Hall, Aron J., additional, Hamdy, Rana F., additional, Han, Jin-Young, additional, Handy, Lori K., additional, Hanisch, Benjamin, additional, Harper, Marvin B., additional, Harris, Aaron M., additional, Harrison, Christopher J., additional, Haslam, David B., additional, Haston, Julia C., additional, Hawkes, Sarah.J., additional, Heald-Sargent, Taylor, additional, Hendley, J. Owen, additional, Hersh, Adam L., additional, Hilinski, Joseph A., additional, Hills, Susan L., additional, Hong, David K., additional, Hotez, Peter J., additional, Hsu, Katherine K., additional, Huang, Felicia Scaggs, additional, Hunstad, David A., additional, Hunt, W. Garrett, additional, Hwang, Loris Y., additional, Ilboudo, Christelle M., additional, Jaggi, Preeti, additional, Jean, Sophonie, additional, Jhaveri, Ravi, additional, Jirk-Pomajbkov, Kateina, additional, Kadry, Nadia A., additional, Kamb, Mary L., additional, Kapadia, Ronak K., additional, Katz, Ben Z., additional, Katz, Sophie E., additional, Kaur, Ishminder, additional, Kersh, Gilbert J., additional, Khan, Muhammad Ali, additional, Khurana, Ananta, additional, Kimberlin, David W., additional, Klein, Bruce, additional, Kobayashi, Miwako, additional, Kociolek, Larry K., additional, Koh, Andrew Y., additional, Kotloff, Karen L., additional, Kroger, Andrew T., additional, Kronman, Matthew P., additional, Lalor, Leah, additional, Lauren, Christine T., additional, Leber, Amy, additional, Leshem, Eyal, additional, Lewis, David B., additional, Livingston, Robyn A., additional, Llata, Eloisa, additional, Lloyd, Kevin, additional, Loh, Katrina, additional, Long, Sarah S., additional, Lopman, Benjamin A., additional, Lucero, Yalda C., additional, Lugo, Debra J., additional, Lujn-Zilbermann, Jorge, additional, Maldonado, Yvonne A., additional, Manaloor, John J., additional, Manthiram, Kalpana, additional, Martin, Stacey W., additional, Mathew, Roshni, additional, Mazzulli, Tony, additional, McFarland, Elizabeth J., additional, McGann, Kathleen A., additional, McNamara, Lucy A., additional, Meislich, Debrah, additional, Meissner, H. Cody, additional, Mejias, Asuncion, additional, Mertsola, Jussi, additional, Messacar, Kevin, additional, Mhaissen, Mohammad Nael, additional, Michaels, Marian G., additional, Miller, Melissa B., additional, Miller-Handley, Hilary, additional, Mintz, Eric, additional, Mohan, Parvathi, additional, Montgomery, Susan P., additional, Montoya, Jose G., additional, Moorman, Anne C., additional, Moro, Pedro L., additional, Moscicki, Anna-Barbara, additional, Muller, William J., additional, Myers, Angela L., additional, Nadel, Simon, additional, Nayak, Jennifer Lynn, additional, Neely, Michael Noel, additional, Neil, Karen P., additional, Nelson, Christina A., additional, Nelson, Noele P., additional, Nichols, Megin, additional, Nicholson, William, additional, Nopper, Amy Jo, additional, Norton, Laura E., additional, Ochoa, Theresa J., additional, Olarte, Liset, additional, Onarecker, Timothy R., additional, Orenstein, Walter A., additional, ORyan, Miguel, additional, Otto, William R., additional, Ouellette, Christopher P., additional, Paddock, Christopher D., additional, Palazzi, Debra L., additional, Panuganti, Suresh Kumar, additional, Pappas, Diane E., additional, Paret, Michal, additional, Pastula, Daniel M., additional, Patterson, Thomas F., additional, Petersen, Brett W., additional, Petrosyan, Mikael, additional, Pickering, Larry K., additional, Pindyck, Talia, additional, Pinninti, Swetha, additional, Pittet, Laure F., additional, Planet, Paul J., additional, Pollard, Andrew J., additional, Posfay-Barbe, Klara M., additional, Poulsen, Casper S., additional, Poutanen, Susan M., additional, Powers, Ann M., additional, Prasanphanich, Nina Salinger, additional, Pritt, Bobbi S., additional, Prober, Charles G., additional, Puar, Neha, additional, Quilter, Laura A.S., additional, Ramilo, Octavio, additional, Rao, Suchitra, additional, Ratner, Adam J., additional, Rawstron, Sarah A., additional, Read, Jennifer S., additional, Relich, Ryan F., additional, Reller, Megan E., additional, Robinson, Candice L., additional, Romero, Jos R., additional, Rosen, David A., additional, Ross, Shannon A., additional, Rours, G. Ingrid J.G., additional, Rowe, Peter C., additional, Rowley, Anne H., additional, Rubin, Lorry G., additional, Ryan, Edward T., additional, Sacharok, Alexandra, additional, Sandora, Thomas J., additional, Sapp, Sarah G.H., additional, Sardana, Kabir, additional, Sauberan, Jason B., additional, Schaffzin, Joshua K., additional, Schillie, Sarah, additional, Schuster, Jennifer E., additional, Schwartz, Kevin L., additional, Sederdahl, Bethany K., additional, Serpa-Alvarez, Jose, additional, Shah, Kara N., additional, Shah, Samir S., additional, Shaikh, Nader, additional, Shane, Andi L., additional, Shapiro, Eugene D., additional, Shaw, Jana, additional, Shetty, Avinash K., additional, Shope, Timothy R., additional, Dairiki Shortliffe, Linda M., additional, Shulman, Stanford T., additional, Shust, Gail F., additional, Siberry, George Kelly, additional, Siegel, Jane D., additional, Siegel, Robert David, additional, Simonsen, Kari A., additional, Singh, Upinder, additional, Smith, Christiana, additional, Smith, Lauren L., additional, Song, Eunkyung, additional, Souder, Emily, additional, Spearman, Paul, additional, St. Geme, Joseph W., additional, Staat, Mary Allen, additional, Staples, J. Erin, additional, Starke, Jeffrey R., additional, Statler, Victoria A., additional, Steinbach, William J., additional, Stensvold, Christen Rune, additional, Stokes, Erin K., additional, Stoner, Bradley P., additional, Storch, Gregory A., additional, Straily, Anne, additional, Sullivan, Kathleen E., additional, Swanson, Douglas S., additional, Tanz, Robert R., additional, Taormina, Gillian, additional, Tate, Jacqueline E., additional, Taveras, Jeanette, additional, Tebruegge, Marc, additional, Teshale, Eyasu H., additional, Thompson, George R., additional, Thompson-Stone, Robert, additional, Thomsen, Isaac, additional, Thomson, Richard B., additional, Thorell, Emily A., additional, Tien, Vivian, additional, Tobin, Nicole H., additional, Toltzis, Philip, additional, Treat, James, additional, Troy, Stephanie B., additional, Van Dvke, Russell B., additional, Vaz, Louise Elaine, additional, Vijayan, Vini, additional, Vodzak, Jennifer, additional, Wagner, Thor A., additional, Wald, Ellen R., additional, Wallihan, Rebecca, additional, Wang, Huanyu, additional, Wangu, Zoon, additional, Washam, Matthew, additional, Waters, Valerie, additional, Watson, Joshua R., additional, Weatherhead, Jill E., additional, Weinberg, Geoffrey A., additional, Weng, Mark K., additional, Wiederhold, Nathan P., additional, Wiesenfeld, Harold C., additional, Williams, Cydni, additional, Williams, John V., additional, Willoughby, Rodney E., additional, Wittler, Robert R., additional, Wood, James B., additional, Woods, Charles Reece, additional, Workowski, Kimberly A., additional, Wright, Terry W., additional, Wu, Hsi-Yang, additional, Xu, Huan, additional, Yagupsky, Pablo, additional, Yi, Jumi, additional, Yoder, Jonathan, additional, Young, Edward J., additional, Zaenglein, Andrea L., additional, Zimmermann, Petra, additional, and Zong, Wenjing, additional

Published
2023
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10. Recent Progress in the Development of Opaganib for the Treatment of Covid-19

Author

Smith CD, Maines LW, Keller SN, Katz Ben-Yair V, Fathi R, Plasse TF, and Levitt ML

Subjects
opaganib, abc294640, sphingolipid, sphingosine kinase, dihydroceramide desaturase, glucosylceramide synthase, Therapeutics. Pharmacology, RM1-950
Abstract

Charles D Smith,1 Lynn W Maines,1 Staci N Keller,1 Vered Katz Ben-Yair,2 Reza Fathi,2 Terry F Plasse,2 Mark L Levitt2 1Apogee Biotechnology Corporation, Hummelstown, PA, USA; 2RedHill Biopharma LTD, Tel Aviv, IsraelCorrespondence: Charles D Smith, Apogee Biotechnology Corporation, 1214 Research Blvd, Suite 2015, Hummelstown, PA, 17036, USA, Tel +1 843 814 9257, Email CDSmith@apogee-biotech.comAbstract: The Covid-19 pandemic driven by the SARS-CoV-2 virus continues to exert extensive humanitarian and economic stress across the world. Although antivirals active against mild disease have been identified recently, new drugs to treat moderate and severe Covid-19 patients are needed. Sphingolipids regulate key pathologic processes, including viral proliferation and pathologic host inflammation. Opaganib (aka ABC294640) is a first-in-class clinical drug targeting sphingolipid metabolism for the treatment of cancer and inflammatory diseases. Recent work demonstrates that opaganib also has antiviral activity against several viruses including SARS-CoV-2. A recently completed multinational Phase 2/3 clinical trial of opaganib in patients hospitalized with Covid-19 demonstrated that opaganib can be safely administered to these patients, and more importantly, resulted in a 62% decrease in mortality in a large subpopulation of patients with moderately severe Covid-19. Furthermore, acceleration of the clearance of the virus was observed in opaganib-treated patients. Understanding the biochemical mechanism for the anti-SARS-CoV-2 activity of opaganib is essential for optimizing Covid-19 treatment protocols. Opaganib inhibits three key enzymes in sphingolipid metabolism: sphingosine kinase-2 (SK2); dihydroceramide desaturase (DES1); and glucosylceramide synthase (GCS). Herein, we describe a tripartite model by which opaganib suppresses infection and replication of SARS-CoV-2 by inhibiting SK2, DES1 and GCS. The potential impact of modulation of sphingolipid signaling on multi-organ dysfunction in Covid-19 patients is also discussed.Keywords: opaganib, ABC294640, sphingolipid, sphingosine kinase, dihydroceramide desaturase, glucosylceramide synthase

Published
2022

11. Plasmodium infection is associated with cross-reactive antibodies to carbohydrate epitopes on the SARS-CoV-2 Spike protein

Author

Lapidus, Sarah, Liu, Feimei, Casanovas-Massana, Arnau, Dai, Yile, Huck, John D., Lucas, Carolina, Klein, Jon, Filler, Renata B., Strine, Madison S., Sy, Mouhamad, Deme, Awa B., Badiane, Aida S., Dieye, Baba, Ndiaye, Ibrahima Mbaye, Diedhiou, Younous, Mbaye, Amadou Moctar, Diagne, Cheikh Tidiane, Vigan-Womas, Inés, Mbengue, Alassane, Sadio, Bacary D., Diagne, Moussa M., Moore, Adam J., Mangou, Khadidiatou, Diallo, Fatoumata, Sene, Seynabou D., Pouye, Mariama N., Faye, Rokhaya, Diouf, Babacar, Nery, Jr, Nivison, Costa, Federico, Reis, Mitermayer G., Muenker, M. Catherine, Hodson, Daniel Z., Mbarga, Yannick, Katz, Ben Z., Andrews, Jason R., Campbell, Melissa, Srivathsan, Ariktha, Kamath, Kathy, Baum-Jones, Elisabeth, Faye, Ousmane, Sall, Amadou Alpha, Vélez, Juan Carlos Quintero, Cappello, Michael, Wilson, Michael, Ben-Mamoun, Choukri, Tedder, Richard, McClure, Myra, Cherepanov, Peter, Somé, Fabrice A., Dabiré, Roch K., Moukoko, Carole Else Eboumbou, Ouédraogo, Jean Bosco, Boum, II, Yap, Shon, John, Ndiaye, Daouda, Wisnewski, Adam, Parikh, Sunil, Iwasaki, Akiko, Wilen, Craig B., Ko, Albert I., Ring, Aaron M., and Bei, Amy K.

Published
2022
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12. Somatic, emotional, and gastrointestinal symptom severity are increased among children and adolescents with COVID‐19.

Author

Wechsler, Joshua B., Berken, Jonathan A., Keeley, Kaitlyn, Singer, Wolfgang, Jhaveri, Ravi, Katz, Ben Z., Fortunato, John E., and Saps, Miguel

Subjects
POST-acute COVID-19 syndrome, ELECTRONIC health records, CHILDREN'S hospitals, EOSINOPHILIC esophagitis, DIAGNOSTIC use of polymerase chain reaction
Abstract

Background: Post‐infectious disorders of gut‐brain interaction (PI‐DGBI) have significant impact on children and adolescents. The effect of COVID‐19 on PI‐DGBI‐associated symptoms in this population, however, is unknown. Methods: We performed electronic medical record searches to identify patients 8–17 years old with a SARS‐CoV2 PCR test at Lurie Children's Hospital between November 2020 and March 2021 (cohort 1) and April–October 2021 (cohort 2). Questionnaires were administered to assess symptoms prior to and 3 months following the test. This included the Pediatric Eosinophilic Esophagitis Symptom Score (PEESS), questionnaire of pediatric gastrointestinal symptoms—Rome IV, Nausea Profile (NP), dyspepsia symptom survey (DSS), nausea severity profile (NSP), and Pediatric Quality of Life Inventory (PedsQL). We grouped patients based on the presence of symptoms prior to COVID‐19 test or the test result. Results: One hundred and ninety‐six parent(s) or guardian(s) in cohort 1 and 274 in cohort 2 completed surveys and self‐reported their child's COVID‐19 result. Cohort 1 had increased PEESS and DSS scores, lower PedsQL scores, and increased frequency of abdominal pain disorders among patients with symptoms prior to COVID‐19 testing. Both cohorts had increased NP and NSP scores among patients with symptoms prior to COVID‐19 testing that was highest among patients with a positive COVID‐19 test. Abdominal pain and diarrhea prior to COVID‐19 testing predicted higher NP scores. Conclusions: Among symptomatic COVID‐19 tested children, we found increased severity of nausea‐associated somatic, emotional, and gastrointestinal symptoms in the 3 months following the test that was most increased among patients with a positive COVID‐19 test. [ABSTRACT FROM AUTHOR]

Published
2024
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13. The Prevalence of Pediatric Myalgic Encephalomyelitis/Chronic Fatigue Syndrome in a Community-Based Sample

Author

Jason, Leonard A., Katz, Ben Z., Sunnquist, Madison, Torres, Chelsea, Cotler, Joseph, and Bhatia, Shaun

Abstract

Background: Most pediatric prevalence studies of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) have been based upon data from tertiary care centers, a process known for systematic biases such as excluding youth of lower socioeconomic status and those less likely to have access to health care. In addition, most pediatric ME/CFS epidemiologic studies have not included a thorough medical and psychiatric examination. The purpose of this study was to determine the prevalence of pediatric ME/CFS from an ethnically and sociodemographically diverse community-based random sample. Method: A sample of 10,119 youth aged 5-17 from 5622 households in the Chicagoland area were screened. Following evaluations, a team of physicians made final diagnoses. Youth were given a diagnosis of ME/CFS if they met criteria for three selected case definitions. A probabilistic, multi-stage formula was used for final prevalence calculations. Results: The prevalence of pediatric ME/CFS was 0.75%, with a higher percentage being African American and Latinx than Caucasian. Of the youth diagnosed with ME/CFS, less than 5% had been previously diagnosed with the illness. Conclusions: Many youth with the illness have not been previously diagnosed with ME/CFS. These findings point to the need for better ways to identify and diagnose youth with this illness.

Published
2020
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18. Nociception and pain in humans lacking a functional TRPV1 channel

Author

Katz, Ben, Zaguri, Rachel, Edvardson, Simon, Maayan, Channa, Elpeleg, Orly, Lev, Shaya, Davidson, Elyad, Peters, Maximilian, Kfir-Erenfeld, Shlomit, Berger, Esther, Ghazalin, Shifa, Binshtok, Alexander M., and Minke, Baruch

Subjects
Gene mutations -- Research, Chronic pain -- Causes of -- Genetic aspects -- Care and treatment, Ion channels -- Health aspects -- Genetic aspects, Carrier proteins -- Genetic aspects -- Health aspects, Neurological research, Nociception -- Research, Health care industry
Abstract

BACKGROUND. Chronic pain is a debilitating illness with currently limited therapy, in part due to difficulties in translating treatments derived from animal models to patients. The transient receptor potential vanilloid 1 (TRPV1) channel is associated with noxious heat detection and inflammatory pain, and reports of adverse effects in human trials have hindered extensive efforts in the clinical development of TRPV1 antagonists as novel pain relievers. METHODS. We examined 2 affected individuals (A1 and A2) carrying a homozygous missense mutation in TRPV1, rendering the channel nonfunctional. Biochemical and functional assays were used to analyze the mutant channel. To identify possible phenotypes of the affected individuals, we performed psychophysical and medical examinations. RESULTS. We demonstrated that diverse TRPV1 activators, acting at different sites of the channel protein, were unable to open the cloned mutant channel. This finding was not a consequence of impairment in the expression, cellular trafficking, or assembly of protein subunits. The affected individuals were insensitive to application of capsaicin to the mouth and skin and did not demonstrate aversive behavior toward capsaicin. Furthermore, quantitative sensory testing of A1 revealed an elevated heat-pain threshold but also, surprisingly, an elevated cold-pain threshold and extensive neurogenic inflammatory, flare, and pain responses following application of the TRPA1 channel activator mustard oil. CONCLUSION. Our study provides direct evidence in humans for pain-related functional changes linked to TRPV1, which is a prime target in the development of pain relievers. FUNDING. Supported by the Israel Science Foundation (368/19); Teva's National Network of Excellence in Neuroscience grant (no. 0394886) and Teva's National Network of Excellence in Neuroscience postdoctoral fellowship., Introduction The ability to sense noxious stimuli is crucial for protecting organisms from tissue damage. The discovery of the capsaicin and heat-activated polymodal ion channel transient receptor potential vanilloid 1 [...]

Published
2023
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34. Figure S1 from TRPM2 Mediates Neutrophil Killing of Disseminated Tumor Cells

Author

Gershkovitz, Maya, primary, Caspi, Yaki, primary, Fainsod-Levi, Tanya, primary, Katz, Ben, primary, Michaeli, Janna, primary, Khawaled, Saleh, primary, Lev, Shaya, primary, Polyansky, Lola, primary, Shaul, Merav E., primary, Sionov, Ronit V., primary, Cohen-Daniel, Leonor, primary, Aqeilan, Rami I., primary, Shaul, Yoav D., primary, Mori, Yasuo, primary, Karni, Rotem, primary, Fridlender, Zvi G., primary, Binshtok, Alexander M., primary, and Granot, Zvi, primary

Published
2023
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35. Supplemental figure legends from TRPM2 Mediates Neutrophil Killing of Disseminated Tumor Cells

Author

Gershkovitz, Maya, primary, Caspi, Yaki, primary, Fainsod-Levi, Tanya, primary, Katz, Ben, primary, Michaeli, Janna, primary, Khawaled, Saleh, primary, Lev, Shaya, primary, Polyansky, Lola, primary, Shaul, Merav E., primary, Sionov, Ronit V., primary, Cohen-Daniel, Leonor, primary, Aqeilan, Rami I., primary, Shaul, Yoav D., primary, Mori, Yasuo, primary, Karni, Rotem, primary, Fridlender, Zvi G., primary, Binshtok, Alexander M., primary, and Granot, Zvi, primary

Published
2023
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36. Data from TRPM2 Mediates Neutrophil Killing of Disseminated Tumor Cells

Author

Gershkovitz, Maya, primary, Caspi, Yaki, primary, Fainsod-Levi, Tanya, primary, Katz, Ben, primary, Michaeli, Janna, primary, Khawaled, Saleh, primary, Lev, Shaya, primary, Polyansky, Lola, primary, Shaul, Merav E., primary, Sionov, Ronit V., primary, Cohen-Daniel, Leonor, primary, Aqeilan, Rami I., primary, Shaul, Yoav D., primary, Mori, Yasuo, primary, Karni, Rotem, primary, Fridlender, Zvi G., primary, Binshtok, Alexander M., primary, and Granot, Zvi, primary

Published
2023
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38. Communications

Author

Katz, Ben Zion and Bleich, J. David

Published
2015

42. Contributors

Author

Abzug, Mark J., primary, Adderson, Elisabeth E., additional, Agwu, Allison L., additional, Alby, Kevin, additional, Aldrovandi, Grace M., additional, Allen, Upton D., additional, Alvarez-Hernández, Gerardo, additional, Ampofo, Krow, additional, Anderson, Evan J., additional, Anderson, Margot, additional, Antonara, Stella, additional, Ardura, Monica I., additional, Arguin, Paul M., additional, Arnold, John C., additional, Aronson, Naomi E., additional, Arvin, Ann M., additional, Ashkenazi, Shai, additional, Asturias, Edwin J., additional, Badalyan, Vahe, additional, Baker, Carol J., additional, Balakrishnan, Karthik, additional, Barros, Brittany S., additional, Barson, William J., additional, Bausch, Daniel G., additional, Bechtel, Kirsten, additional, Benjamin, Daniel K., additional, Berman, David M., additional, Blanco, David A., additional, Bloch, Karen C., additional, Blythe, Margaret J., additional, Bocchini, Joseph A., additional, Bowen, Anna, additional, Bowie, William R., additional, Boyce, Thomas G., additional, Bradley, John S., additional, Brady, Michael T., additional, Bratcher, Denise F., additional, Braverman, Paula K., additional, Bresee, Joseph, additional, Brook, Itzhak, additional, Brown, Kevin E., additional, Bryant, Kristina, additional, Buescher, E. Stephen, additional, Burns, Jane L., additional, Byington, Carrie L., additional, Camacho-Gonzalez, Andres F., additional, Cantey, Paul, additional, Carter, Bryan D., additional, Caserta, Mary T., additional, Castagnini, Luis A., additional, Cerini, Chiara, additional, Chadwick, Ellen Gould, additional, Chiang, Silvia S., additional, Christenson, John C., additional, Coffin, Susan E., additional, Collier, Melissa G., additional, Collins, Jennifer P., additional, Conklin, Laurie S., additional, Connelly, Beverly L., additional, Contopoulos-Ioannidis, Despina, additional, Conway, James H., additional, Cortese, Margaret M., additional, Cox, Elaine G., additional, Creech, C. Buddy, additional, Crews, Jonathan D., additional, Cunningham, Dennis J., additional, Curtis, Nigel, additional, Dailey, Natalie J.M., additional, Danziger-Isakov, Lara A., additional, Darville, Toni, additional, Dasch, Gregory A., additional, Daskalaki, Irini, additional, Daum, Robert S., additional, Davenport, Michael, additional, Davies, H. Dele, additional, Dawood, Fatimah S., additional, Day, J. Christopher, additional, de la Morena, Maite, additional, Demmler-Harrison, Gail J., additional, DeMuri, Gregory P., additional, Despommier, Dickson D., additional, Diefenbach, Karen A., additional, Edwards, Kathryn M., additional, Edwards, Morven S., additional, Eichenfield, Lawrence F., additional, Elston, Dirk M., additional, Emerson, Beth, additional, Ephros, Moshe, additional, Erdem, Guliz, additional, Eremeeva, Marina E., additional, Ericson, Jessica E., additional, Esposito, Douglas H., additional, Farley, Monica M., additional, Feingold, Anat R., additional, Feja, Kristina N., additional, Finn, Adam, additional, Fischer, Marc, additional, Flynn, Patricia M., additional, Fox, LeAnne M., additional, Frank, Michael M., additional, Fredrick, Douglas R., additional, Frenck, Robert W., additional, Friedlander, Sheila Fallon, additional, Gans, Hayley A., additional, Gauthier, Gregory M., additional, Gerber, Jeffrey S., additional, Gigliotti, Francis, additional, Gilger, Mark A., additional, Glaser, Carol A., additional, Goddard, Amanda F., additional, Gold, Benjamin D., additional, Gould, Jane M., additional, Green, Michael, additional, Greenberg, David, additional, Greywal, Tanya, additional, Griffin, Daniel, additional, Griffin, Patricia M., additional, Grom, Alexei A., additional, Gutierrez, Kathleen, additional, Gutman, Julie, additional, Guzman-Cottrill, Judith A., additional, Hall, Aron J., additional, Han, Jin-Young, additional, Harper, Marvin B., additional, Harris, Julie R., additional, Harrison, Christopher J., additional, Haslam, David B., additional, Hawkes, Sarah J., additional, Hendley, J. Owen, additional, Henry, Marion C.W., additional, Hilinski, Joseph A., additional, Hills, Susan L., additional, Holmberg, Scott D., additional, Holtzman, Deborah, additional, Hong, David K., additional, Hotez, Peter J., additional, Hsu, Katherine K., additional, Hunstad, David A., additional, Hwang, Loris Y., additional, Jackson, Mary Anne, additional, Jacobs, Richard F., additional, Jhaveri, Ravi, additional, Jirků-Pomajbíková, Kateřina, additional, Jones, Jeffrey L., additional, Karki, Mahima, additional, Karlowicz, M. Gary, additional, Katz, Ben Z., additional, Kaur, Ishminder, additional, Kersh, Gilbert J., additional, Keystone, Jay S., additional, Khan, Muhammad Ali, additional, Kimberlin, David W., additional, Kleiman, Martin B., additional, Klein, Bruce S., additional, Klontz, Karl, additional, Knust, Barbara, additional, Koh, Andrew Y., additional, Korgenski, E. Kent, additional, Krogstad, Paul, additional, Kutty, Preeta Krishnan, additional, Lauren, Christine T., additional, Lawrence, Hillary S., additional, Leber, Amy, additional, Lee, Grace M., additional, Leibovitz, Eugene, additional, Leshem, Eyal, additional, Levasseur, Stéphanie, additional, Lewis, David B., additional, Livingston, Robyn A., additional, Llata, Eloisa, additional, Long, Sarah S., additional, Lopman, Ben A., additional, Lucero, Yalda C., additional, Luján-Zilbermann, Jorge, additional, Luzuriaga, Katherine, additional, MacDonald, Noni E., additional, Maldonado, Yvonne A., additional, Manaloor, John, additional, Mani, Chitra S., additional, Manthiram, Kalpana, additional, Marshall, Gary S., additional, Martin, Stacey W., additional, Matanock, Almea, additional, Matiz, Catalina, additional, Mawle, Alison C., additional, Mazzulli, Tony, additional, McGann, Kathleen A., additional, McIntosh, Kenneth, additional, McNamara, Lucy A., additional, Meir, Michal, additional, Meislich, Debrah, additional, Meissner, H. Cody, additional, Meites, Elissa, additional, Mejías, Asunción, additional, Mertsola, Jussi, additional, Messacar, Kevin, additional, Mhaissen, Mohammed Nael, additional, Michaels, Marian G., additional, Miller, Melissa B., additional, Mintz, Eric D., additional, Modlin, John F., additional, Mohan, Parvathi, additional, Montgomery, Susan P., additional, Montoya, José G., additional, Moro, Pedro L., additional, Moscicki, Anna-Barbara, additional, Moss, R. Lawrence, additional, Myers, Angela L., additional, Nadel, Simon, additional, Neely, Michael N., additional, Neil, Karen P., additional, Nelson, Joanna, additional, Nelson, Noele P., additional, Nicholson, William L., additional, Nizet, Victor, additional, Nopper, Amy Jo, additional, Ochoa, Theresa J., additional, Orenstein, Walter A., additional, O'Ryan, Miguel, additional, Paddock, Christopher D., additional, Pall, Harpreet, additional, Panuganti, Suresh Kumar, additional, Pappas, Diane E., additional, Pass, Robert F., additional, Patterson, Thomas F., additional, Patton, Monica E., additional, Pelton, Stephen I., additional, Petersen, Brett W., additional, Pickering, Larry K., additional, Pinninti, Swetha, additional, Planet, Paul J., additional, Pollard, Andrew J., additional, Posfay-Barbe, Klara M., additional, Poulsen, Casper S., additional, Poutanen, Susan M., additional, Powers, Ann M., additional, Prober, Charles G., additional, Ramilo, Octavio, additional, Rangel, Shawn J., additional, Rao, Suchitra, additional, Rawstron, Sarah A., additional, Read, Jennifer S., additional, Reed, Michael D., additional, Relich, Ryan F., additional, Reller, Megan E., additional, Rellosa, Neil, additional, Rempe, Katherine A., additional, Reyes, Melissa A., additional, Rice-Townsend, Samuel E., additional, Richards, Frank O., additional, Romero, José R., additional, Rosen, David A., additional, Rostad, Christina A., additional, Rours, G. Ingrid J.G., additional, Routh, Janell A., additional, Rowley, Anne H., additional, Rubin, Lorry G., additional, Ryan, Edward T., additional, Saiman, Lisa, additional, Sammons, Julia S., additional, Sass, Laura, additional, Sauberan, Jason B., additional, Schillie, Sarah, additional, Schulert, Grant S., additional, Schuster, Jennifer E., additional, Schwartz, Kevin L., additional, Sederdahl, Bethany K., additional, Serpa, Jose A., additional, Shah, Kara N., additional, Shah, Samir S., additional, Shane, Andi L., additional, Shapiro, Eugene D., additional, Shaw, Jana, additional, Shetty, Avinash K., additional, Dairiki, Linda M., additional, Siberry, George Kelly, additional, Siegel, Jane D., additional, Siegel, Robert David, additional, Simonsen, Kari A., additional, Singh, Nalini, additional, Singh, Upinder, additional, Smith, P. Brian, additional, Snyder, John D., additional, Song, Eunkyung, additional, Sorrell, Jennifer L., additional, Souder, Emily, additional, St. Geme, Joseph W., additional, Staat, Mary Allen, additional, Staples, J. Erin, additional, Starke, Jeffrey R., additional, Steinbach, William J., additional, Stensvold, Christen R., additional, Stoner, Bradley P., additional, Strikas, Raymond A., additional, Strober, Jonathan B., additional, Sue, Paul K., additional, Sutton, Deanna A., additional, Swanson, Douglas, additional, Tate, Jacqueline E., additional, Tebruegge, Marc, additional, Teshale, Eyasu H., additional, Thompson, Amelia B., additional, Thompson, George R., additional, Thompson-Stone, Robert, additional, Thomson, Richard B., additional, Thorell, Emily A., additional, Tobin, Nicole H., additional, Toltzis, Philip, additional, Treat, James, additional, Troy, Stephanie B., additional, Van, Russell B., additional, Vaz, Louise Elaine, additional, Vodzak, Jennifer, additional, Wald, Ellen R., additional, Wallihan, Rebecca, additional, Wangu, Zoon, additional, Washam, Matthew, additional, Watson, Joshua R., additional, Wattier, Rachel L., additional, Weinberg, Geoffrey A., additional, White, A. Clinton, additional, Wiesenfeld, Harold C., additional, Williams, John V., additional, Willoughby, Rodney E., additional, Wingerter, Sarah L., additional, Wittler, Robert R., additional, Wong, Karen K., additional, Workowski, Kimberly A., additional, Wright, Terry W., additional, Yagupsky, Pablo, additional, Yen, Catherine, additional, Yi, Jumi, additional, Yoder, Jonathan S., additional, Young, Edward J., additional, Zaenglein, Andrea L., additional, and Zimmerman, Kanecia, additional

Published
2018
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44. Sulfamate Acetamides as Self-Immolative Electrophiles for Covalent Ligand-Directed Release Chemistry

Author

Reddi, Rambabu N., primary, Rogel, Adi, additional, Gabizon, Ronen, additional, Rawale, Dattatraya Gautam, additional, Harish, Battu, additional, Marom, Shir, additional, Tivon, Barr, additional, Arbel, Yamit Shorer, additional, Gurwicz, Neta, additional, Oren, Roni, additional, David, Keren, additional, Liu, Jingjing, additional, Duberstein, Shirly, additional, Itkin, Maxim, additional, Malitsky, Sergey, additional, Barr, Haim, additional, Katz, Ben-Zion, additional, Herishanu, Yair, additional, Shachar, Idit, additional, Shulman, Ziv, additional, and London, Nir, additional

Published
2023
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49. Comparing Intraperitoneal and Intravenous Personalized ErbB2CAR-T for the Treatment of Epithelial Ovarian Cancer

Author

Deshet-Unger, Naamit, primary, Horn, Galit, additional, Rawet-Slobodkin, Moran, additional, Waks, Tova, additional, Laskov, Ido, additional, Michaan, Nadav, additional, Raz, Yael, additional, Bar, Vered, additional, Zundelevich, Adi, additional, Aharon, Sara, additional, Turovsky, Lubov, additional, Mallel, Giuseppe, additional, Salpeter, Seth, additional, Neev, Guy, additional, Hollander, Kenneth Samuel, additional, Katz, Ben-Zion, additional, Grisaru, Dan, additional, and Globerson Levin, Anat, additional

Published
2022
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