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Oxidation Of Hydrogen Sulfide To Polysulfide And Thiosulfate By A Carbon Nanozyme: Therapeutic Implications With An Emphasis On Down Syndrome, Paul J Derry, Anton V Liopo, Karthik Mouli, Emily A Mchugh, Anh T T Vo, Ann Mckelvey, Larry J Suva, Gang Wu, Yan Gao, Kenneth R Olson, James M Tour, Thomas A Kent Mar 2024

Oxidation Of Hydrogen Sulfide To Polysulfide And Thiosulfate By A Carbon Nanozyme: Therapeutic Implications With An Emphasis On Down Syndrome, Paul J Derry, Anton V Liopo, Karthik Mouli, Emily A Mchugh, Anh T T Vo, Ann Mckelvey, Larry J Suva, Gang Wu, Yan Gao, Kenneth R Olson, James M Tour, Thomas A Kent

Faculty, Staff and Student Publications

Hydrogen sulfide (H2S) is a noxious, potentially poisonous, but necessary gas produced from sulfur metabolism in humans. In Down Syndrome (DS), the production of H2S is elevated and associated with degraded mitochondrial function. Therefore, removing H2S from the body as a stable oxide could be an approach to reducing the deleterious effects of H2S in DS. In this report we describe the catalytic oxidation of hydrogen sulfide (H2S) to polysulfides (HS2+n−) and thiosulfate (S2O32−) by poly(ethylene glycol) hydrophilic carbon clusters (PEG-HCCs) and poly(ethylene glycol) oxidized activated charcoal (PEG-OACs), examples of oxidized carbon nanozymes (OCNs). We show that OCNs oxidize H2S …


Treatment Outcomes With Standard Of Care In Relapsed/Refractory Diffuse Large B-Cell Lymphoma: Real-World Data Analysis, Andrew Ip, Alex Mutebi, Tongsheng Wang, Monika Jun, Anupama Kalsekar, Fernando Rivas Navarro, Anthony Wang, Rajesh Kamalakar, Mariana Sacchi, Brian Elliott Mar 2024

Treatment Outcomes With Standard Of Care In Relapsed/Refractory Diffuse Large B-Cell Lymphoma: Real-World Data Analysis, Andrew Ip, Alex Mutebi, Tongsheng Wang, Monika Jun, Anupama Kalsekar, Fernando Rivas Navarro, Anthony Wang, Rajesh Kamalakar, Mariana Sacchi, Brian Elliott

Faculty, Staff and Student Publications

INTRODUCTION: Despite new therapies for relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL), treatments with chemotherapy, single-agent rituximab/obinutuzumab, single-agent lenalidomide, or combinations of these agents continue to be commonly used.

METHODS: This retrospective study utilized longitudinal data from 4226 real-world electronic health records to characterize outcomes in patients with R/R DLBCL. Eligible patients were diagnosed with DLBCL between January 2010 and March 2022 and had R/R disease treated with ≥ 1 prior systemic line of therapy (LOT), including ≥ 1 anti-CD20-containing regimen.

RESULTS: A total of 573 patients treated with ≥ 1 prior LOT were included (31.2% and 13.4% …


Case Series: Stenotrophomonas Maltophilia In Pediatric Oncology Patients, Sanila Sarkar, Lea M Stitzlein, Emily Rav, Miriam B Garcia, Shehla Razvi, Michael Chang, Ramia Zakhour Mar 2024

Case Series: Stenotrophomonas Maltophilia In Pediatric Oncology Patients, Sanila Sarkar, Lea M Stitzlein, Emily Rav, Miriam B Garcia, Shehla Razvi, Michael Chang, Ramia Zakhour

Faculty, Staff and Student Publications

Background: Stenotrophomonas maltophilia is a bacterial pathogen that can be fatal in hospitalized and immunocompromised patients with mortality as high as 69%. Pediatric cancer patients often have risk factors that are common for this infection, making them particularly susceptible. Managing S. maltophilia is especially challenging as it has inherent resistance to several antibiotics. Furthermore, soft tissue infections in neutropenic patients may deviate from the typical clinical presentation of S. maltophilia.

Case details: This case series describes an in-depth examination of three cases involving immunocompromised pediatric patients with S. maltophilia infections. Each case exhibited a distinct clinical presentation, encompassing infection of …


Incongruity Between T Cell Receptor Recognition Of Breast Cancer Hotspot Mutations Esr1 Y537s And D538g Following Exogenous Peptide Loading Versus Endogenous Antigen Processing, Paul Shafer, Wingchi K Leung, Mae Woods, Jong Min Choi, Carlos M Rodriguez-Plata, Arushana Maknojia, Andres Mosquera, Lauren K Somes, Jarrett Joubert, Anthony Manliguez, Rashi Ranjan, Bryan Burt, Hyun-Sung Lee, Bing Zhang, Suzanne Fuqua, Cliona Rooney, Ann M Leen, Valentina Hoyos Mar 2024

Incongruity Between T Cell Receptor Recognition Of Breast Cancer Hotspot Mutations Esr1 Y537s And D538g Following Exogenous Peptide Loading Versus Endogenous Antigen Processing, Paul Shafer, Wingchi K Leung, Mae Woods, Jong Min Choi, Carlos M Rodriguez-Plata, Arushana Maknojia, Andres Mosquera, Lauren K Somes, Jarrett Joubert, Anthony Manliguez, Rashi Ranjan, Bryan Burt, Hyun-Sung Lee, Bing Zhang, Suzanne Fuqua, Cliona Rooney, Ann M Leen, Valentina Hoyos

Faculty, Staff and Students Publications

T cell receptor engineered T cell (TCR T) therapies have shown recent efficacy against certain types of solid metastatic cancers. However, to extend TCR T therapies to treat more patients across additional cancer types, new TCRs recognizing cancer-specific antigen targets are needed. Driver mutations in AKT1, ESR1, PIK3CA, and TP53 are common in patients with metastatic breast cancer (MBC) and if immunogenic could serve as ideal tumor-specific targets for TCR T therapy to treat this disease. Through IFN-γ ELISpot screening of in vitro expanded neopeptide-stimulated T cell lines from healthy donors and MBC patients, we identified reactivity towards 11 of …


Tuberculosis In People Of Ukrainian Origin In The European Union And The European Economic Area, 2019 To 2022, Krista Stoycheva, Veronica Cristea, Csaba Ködmön, Senia Rosales-Klintz, Dominik Zenner, Anca Vasiliu, Marieke Van Der Werf, Christoph Lange Mar 2024

Tuberculosis In People Of Ukrainian Origin In The European Union And The European Economic Area, 2019 To 2022, Krista Stoycheva, Veronica Cristea, Csaba Ködmön, Senia Rosales-Klintz, Dominik Zenner, Anca Vasiliu, Marieke Van Der Werf, Christoph Lange

Faculty, Staff and Students Publications

Approximately five million Ukrainians were displaced to the EU/EEA following the Russian invasion of Ukraine. While tuberculosis (TB) notification rates per 100,000 Ukrainians in the EU/EEA remained stable, the number of notified TB cases in Ukrainians increased almost fourfold (mean 2019-2021: 201; 2022: 780). In 2022, 71% cases were notified in three countries, and almost 20% of drug-resistant TB cases were of Ukrainian origin. Targeted healthcare services for Ukrainians are vital for early diagnosis and treatment, and preventing transmission.


Novel Avenues Of Tau Research, Claire E Sexton, Gal Bitan, Kathryn R Bowles, Miroslaw Brys, Luc Buée, Mahmoud Bukar Maina, Claire D Clelland, Ann D Cohen, John F Crary, Jeffrey L Dage, Kristophe Diaz, Bess Frost, Li Gan, Alison M Goate, Lawrence I Golbe, Oskar Hansson, Celeste M Karch, Hartmuth C Kolb, Renaud La Joie, Suzee E Lee, Diana Matallana, Bruce L Miller, Chiadi U Onyike, Yakeel T Quiroz, Jessica E Rexach, Jonathan D Rohrer, Amy Rommel, Ghazaleh Sadri-Vakili, Suzanne E Schindler, Julie A Schneider, Reisa A Sperling, Charlotte E Teunissen, Stacie C Weninger, Susan L Worley, Hui Zheng, Maria C Carrillo Mar 2024

Novel Avenues Of Tau Research, Claire E Sexton, Gal Bitan, Kathryn R Bowles, Miroslaw Brys, Luc Buée, Mahmoud Bukar Maina, Claire D Clelland, Ann D Cohen, John F Crary, Jeffrey L Dage, Kristophe Diaz, Bess Frost, Li Gan, Alison M Goate, Lawrence I Golbe, Oskar Hansson, Celeste M Karch, Hartmuth C Kolb, Renaud La Joie, Suzee E Lee, Diana Matallana, Bruce L Miller, Chiadi U Onyike, Yakeel T Quiroz, Jessica E Rexach, Jonathan D Rohrer, Amy Rommel, Ghazaleh Sadri-Vakili, Suzanne E Schindler, Julie A Schneider, Reisa A Sperling, Charlotte E Teunissen, Stacie C Weninger, Susan L Worley, Hui Zheng, Maria C Carrillo

Faculty, Staff and Students Publications

INTRODUCTION: The pace of innovation has accelerated in virtually every area of tau research in just the past few years.

METHODS: In February 2022, leading international tau experts convened to share selected highlights of this work during Tau 2022, the second international tau conference co-organized and co-sponsored by the Alzheimer's Association, CurePSP, and the Rainwater Charitable Foundation.

RESULTS: Representing academia, industry, and the philanthropic sector, presenters joined more than 1700 registered attendees from 59 countries, spanning six continents, to share recent advances and exciting new directions in tau research.

DISCUSSION: The virtual meeting provided an opportunity to foster cross-sector collaboration …


Genomic Data In The All Of Us Research Program, All Of Us Research Program Genomics Investigators Mar 2024

Genomic Data In The All Of Us Research Program, All Of Us Research Program Genomics Investigators

Faculty, Staff and Students Publications

Comprehensively mapping the genetic basis of human disease across diverse individuals is a long-standing goal for the field of human genetics1–4. The All of Us Research Program is a longitudinal cohort study aiming to enrol a diverse group of at least one million individuals across the USA to accelerate biomedical research and improve human health5,6. Here we describe the programme’s genomics data release of 245,388 clinical-grade genome sequences. This resource is unique in its diversity as 77% of participants are from communities that are historically under-represented in biomedical research and 46% are …


Determining A Urinary-Specific Antibiogram And Risk Factors Of Trimethoprim/Sulfamethoxazole, Ciprofloxacin And Multidrug Resistance Among Enterobacterales In Primary Care, Marissa Valentine-King, Michael A Hansen, Roger Zoorob, Matthew Schlueter, Jennifer L Matas, Samuel E Willis, Lisa C K Danek, Kenneth Muldrew, Mohammad Zare, Forrest Hudson, Robert L Atmar, Andrew Chou, Barbara W Trautner, Larissa Grigoryan Mar 2024

Determining A Urinary-Specific Antibiogram And Risk Factors Of Trimethoprim/Sulfamethoxazole, Ciprofloxacin And Multidrug Resistance Among Enterobacterales In Primary Care, Marissa Valentine-King, Michael A Hansen, Roger Zoorob, Matthew Schlueter, Jennifer L Matas, Samuel E Willis, Lisa C K Danek, Kenneth Muldrew, Mohammad Zare, Forrest Hudson, Robert L Atmar, Andrew Chou, Barbara W Trautner, Larissa Grigoryan

Faculty, Staff and Student Publications

Background: Risk factors for ciprofloxacin or MDR in primary care urine specimens are not well defined.

Objectives: We created a primary care-specific antibiogram for Escherichia coli isolates from cases with complicated and uncomplicated urinary tract infection (UTI) and evaluated risk factors for ciprofloxacin, trimethoprim/sulfamethoxazole and MDR among Enterobacterales.

Methods: We conducted a cross-sectional study to determine resistance and risk factors by collecting urine cultures from all patients (≥18 years) presenting with provider-suspected UTI at two primary care, safety-net clinics in Houston, TX, USA between November 2018 and March 2020.

Results: Among 1262 cultures, 308 cultures grew 339 uropathogens. Patients with …


Declining Prevalence Of Trichomonas Vaginalis Diagnosed By Wet Mount In A Cohort Of U.S. Women With And Without Hiv, Elizabeth M Daubert, Jodie Dionne, Jessica Atrio, Andrea K Knittel, Seble G Kassaye, Dominika Seidman, Amanda Long, Susan Brockmann, Igho Ofotokun, Margaret A Fischl, L Stewart Massad, Kathleen M Weber Mar 2024

Declining Prevalence Of Trichomonas Vaginalis Diagnosed By Wet Mount In A Cohort Of U.S. Women With And Without Hiv, Elizabeth M Daubert, Jodie Dionne, Jessica Atrio, Andrea K Knittel, Seble G Kassaye, Dominika Seidman, Amanda Long, Susan Brockmann, Igho Ofotokun, Margaret A Fischl, L Stewart Massad, Kathleen M Weber

2020-Current year OA Pubs

No abstract provided.


Altered Larval Activation Response Associated With Multidrug Resistance In The Canine Hookworm Ancylostoma Caninum, Elise L Mckean, Emilia Grill, Young-Jun Choi, Makedonka Mitreva, Damien M O'Halloran, John M Hawdon Mar 2024

Altered Larval Activation Response Associated With Multidrug Resistance In The Canine Hookworm Ancylostoma Caninum, Elise L Mckean, Emilia Grill, Young-Jun Choi, Makedonka Mitreva, Damien M O'Halloran, John M Hawdon

2020-Current year OA Pubs

Parasitic gastrointestinal nematodes pose significant health risks to humans, livestock, and companion animals, and their control relies heavily on the use of anthelmintic drugs. Overuse of these drugs has led to the emergence of resistant nematode populations. Herein, a naturally occurring isolate (referred to as BCR) of the dog hookworm,


Extramedullary Hematopoiesis In Cancer, Derek A G Barisas, Kyunghee Choi Mar 2024

Extramedullary Hematopoiesis In Cancer, Derek A G Barisas, Kyunghee Choi

2020-Current year OA Pubs

Hematopoiesis can occur outside of the bone marrow during inflammatory stress to increase the production of primarily myeloid cells at extramedullary sites; this process is known as extramedullary hematopoiesis (EMH). As observed in a broad range of hematologic and nonhematologic diseases, EMH is now recognized for its important contributions to solid tumor pathology and prognosis. To initiate EMH, hematopoietic stem cells (HSCs) are mobilized from the bone marrow into the circulation and to extramedullary sites such as the spleen and liver. At these sites, HSCs primarily produce a pathological subset of myeloid cells that contributes to tumor pathology. The EMH …


Efficacy And Safety Of Rezafungin And Caspofungin In Candidaemia And Invasive Candidiasis: Pooled Data From Two Prospective Randomised Controlled Trials, George R Thompson 3rd, Marin Kollef, Et Al. Mar 2024

Efficacy And Safety Of Rezafungin And Caspofungin In Candidaemia And Invasive Candidiasis: Pooled Data From Two Prospective Randomised Controlled Trials, George R Thompson 3rd, Marin Kollef, Et Al.

2020-Current year OA Pubs

BACKGROUND: Rezafungin, a new US Food and Drug Administration-approved, long-acting echinocandin to treat candidaemia and invasive candidiasis, was efficacious with a similar safety profile to caspofungin in clinical trials. We conducted pooled analyses of the phase 2 STRIVE and phase 3 ReSTORE rezafungin trials.

METHODS: ReSTORE was a multicentre, double-blind, double-dummy, randomised phase 3 trial conducted at 66 tertiary care centres in 15 countries. STRIVE was a multicentre, double-blind, double-dummy, randomised phase 2 trial conducted at 44 centres in 10 countries. Adults (≥18 years) with candidaemia or invasive candidiasis were treated with once-a-week intravenous rezafungin (400 mg and 200 mg) …


Impact Of Diagnostic Stewardship Interventions In The Collection Process Of Fungal Blood Cultures, Miguel A Chavez, Satish Munigala, Carey-Ann D Burnham, Melanie L Yarbrough, Crystal Squires, Josephine Fox, Heather Gasama, Kevin Hsueh, David K Warren Mar 2024

Impact Of Diagnostic Stewardship Interventions In The Collection Process Of Fungal Blood Cultures, Miguel A Chavez, Satish Munigala, Carey-Ann D Burnham, Melanie L Yarbrough, Crystal Squires, Josephine Fox, Heather Gasama, Kevin Hsueh, David K Warren

2020-Current year OA Pubs

We implemented 2 interventions to improve utilization and contamination at our institution: kits to improve appropriate sample collection and an electronic order alert displaying appropriate indications of fungal blood cultures. An electronic order alert when ordering fungal blood cultures was associated with decreased utilization without decrease in positivity rate.


Biological Insights From Plasma Proteomics Of Non-Small Cell Lung Cancer Patients Treated With Immunotherapy, Jair Bar, Raya Leibowitz, Niels Reinmuth, Astrid Ammendola, Eyal Jacob, Mor Moskovitz, Adva Levy-Barda, Michal Lotem, Rivka Katsenelson, Abed Agbarya, Mahmoud Abu-Amna, Maya Gottfried, Tatiana Harkovsky, Ido Wolf, Ella Tepper, Gil Loewenthal, Ben Yellin, Yehuda Brody, Nili Dahan, Maya Yanko, Coren Lahav, Michal Harel, Shani Raveh Shoval, Yehonatan Elon, Itamar Sela, Adam Dicker, Yuval Shaked Feb 2024

Biological Insights From Plasma Proteomics Of Non-Small Cell Lung Cancer Patients Treated With Immunotherapy, Jair Bar, Raya Leibowitz, Niels Reinmuth, Astrid Ammendola, Eyal Jacob, Mor Moskovitz, Adva Levy-Barda, Michal Lotem, Rivka Katsenelson, Abed Agbarya, Mahmoud Abu-Amna, Maya Gottfried, Tatiana Harkovsky, Ido Wolf, Ella Tepper, Gil Loewenthal, Ben Yellin, Yehuda Brody, Nili Dahan, Maya Yanko, Coren Lahav, Michal Harel, Shani Raveh Shoval, Yehonatan Elon, Itamar Sela, Adam Dicker, Yuval Shaked

Department of Radiation Oncology Faculty Papers

INTRODUCTION: Immune checkpoint inhibitors have made a paradigm shift in the treatment of non-small cell lung cancer (NSCLC). However, clinical response varies widely and robust predictive biomarkers for patient stratification are lacking. Here, we characterize early on-treatment proteomic changes in blood plasma to gain a better understanding of treatment response and resistance.

METHODS: Pre-treatment (T0) and on-treatment (T1) plasma samples were collected from 225 NSCLC patients receiving PD-1/PD-L1 inhibitor-based regimens. Plasma was profiled using aptamer-based technology to quantify approximately 7000 plasma proteins per sample. Proteins displaying significant fold changes (T1:T0) were analyzed further to identify associations with clinical outcomes using …


Interim Estimates Of 2023-24 Seasonal Influenza Vaccine Effectiveness - United States, Aaron M Frutos, Ashley M Price, Elizabeth Harker, Emily L Reeves, Haris M Ahmad, Vel Murugan, Emily T Martin, Stacey House, Elie A Saade, Richard K Zimmerman, Manjusha Gaglani, Karen J Wernli, Emmanuel B Walter, Marian G Michaels, Mary A Staat, Geoffrey A Weinberg, Rangaraj Selvarangan, Julie A Boom, Eileen J Klein, Natasha B Halasa, Adit A Ginde, Kevin W Gibbs, Yuwei Zhu, Wesley H Self, Sara Y Tartof, Nicola P Klein, Kristin Dascomb, Malini B Desilva, Zachary A Weber, Duck-Hye Yang, Sarah W Ball, Diya Surie, Jennifer Decuir, Fatimah S Dawood, Heidi L Moline, Ariana P Toepfer, Benjamin R Clopper, Ruth Link-Gelles, Amanda B Payne, Jessie R Chung, Brendan Flannery, Nathaniel M Lewis, Samantha M Olson, Katherine Adams, Mark W Tenforde, Shikha Garg, Lisa A Grohskopf, Carrie Reed, Sascha Ellington, Cdc Influenza Vaccine Effectiveness Collaborators Feb 2024

Interim Estimates Of 2023-24 Seasonal Influenza Vaccine Effectiveness - United States, Aaron M Frutos, Ashley M Price, Elizabeth Harker, Emily L Reeves, Haris M Ahmad, Vel Murugan, Emily T Martin, Stacey House, Elie A Saade, Richard K Zimmerman, Manjusha Gaglani, Karen J Wernli, Emmanuel B Walter, Marian G Michaels, Mary A Staat, Geoffrey A Weinberg, Rangaraj Selvarangan, Julie A Boom, Eileen J Klein, Natasha B Halasa, Adit A Ginde, Kevin W Gibbs, Yuwei Zhu, Wesley H Self, Sara Y Tartof, Nicola P Klein, Kristin Dascomb, Malini B Desilva, Zachary A Weber, Duck-Hye Yang, Sarah W Ball, Diya Surie, Jennifer Decuir, Fatimah S Dawood, Heidi L Moline, Ariana P Toepfer, Benjamin R Clopper, Ruth Link-Gelles, Amanda B Payne, Jessie R Chung, Brendan Flannery, Nathaniel M Lewis, Samantha M Olson, Katherine Adams, Mark W Tenforde, Shikha Garg, Lisa A Grohskopf, Carrie Reed, Sascha Ellington, Cdc Influenza Vaccine Effectiveness Collaborators

Faculty, Staff and Students Publications

In the United States, annual influenza vaccination is recommended for all persons aged ≥6 months. Using data from four vaccine effectiveness (VE) networks during the 2023-24 influenza season, interim influenza VE was estimated among patients aged ≥6 months with acute respiratory illness-associated medical encounters using a test-negative case-control study design. Among children and adolescents aged 6 months-17 years, VE against influenza-associated outpatient visits ranged from 59% to 67% and against influenza-associated hospitalization ranged from 52% to 61%. Among adults aged ≥18 years, VE against influenza-associated outpatient visits ranged from 33% to 49% and against hospitalization from 41% to 44%. VE …


The Card8 Inflammasome Dictates Hiv/Siv Pathogenesis And Disease Progression, Qiankun Wang, Kolin M Clark, Ritudhwaj Tiwari, Nagarajan Raju, Gregory K Tharp, Jeffrey Rogers, R Alan Harris, Muthuswamy Raveendran, Steven E Bosinger, Tricia H Burdo, Guido Silvestri, Liang Shan Feb 2024

The Card8 Inflammasome Dictates Hiv/Siv Pathogenesis And Disease Progression, Qiankun Wang, Kolin M Clark, Ritudhwaj Tiwari, Nagarajan Raju, Gregory K Tharp, Jeffrey Rogers, R Alan Harris, Muthuswamy Raveendran, Steven E Bosinger, Tricia H Burdo, Guido Silvestri, Liang Shan

Faculty, Staff and Students Publications

While CD4+ T-cell depletion is key to disease progression in people living with HIV and SIV-infected macaques, the mechanisms underlying this depletion remain incompletely understood, with most cell death involving uninfected cells. In contrast, SIV infection of “natural” hosts such as sooty mangabeys do not cause CD4+ depletion and AIDS despite high-level viremia. Here, we report that the CARD8 inflammasome is activated immediately after HIV entry by the viral protease encapsulated in incoming virions. Sensing of HIV protease activity by CARD8 leads to rapid pyroptosis of quiescent cells without productive infection, while T-cell activation abolishes CARD8 function and increases permissiveness …


Paired Single-B-Cell Transcriptomics And Receptor Sequencing Reveal Activation States And Clonal Signatures That Characterize B Cells In Acute Myeloid Leukemia, Shengnan Guo, Gopi S Mohan, Bofei Wang, Tianhao Li, Naval Daver, Yuting Zhao, Patrick K Reville, Dapeng Hao, Hussein A Abbas Feb 2024

Paired Single-B-Cell Transcriptomics And Receptor Sequencing Reveal Activation States And Clonal Signatures That Characterize B Cells In Acute Myeloid Leukemia, Shengnan Guo, Gopi S Mohan, Bofei Wang, Tianhao Li, Naval Daver, Yuting Zhao, Patrick K Reville, Dapeng Hao, Hussein A Abbas

Faculty, Staff and Student Publications

BACKGROUND: Acute myeloid leukemia (AML) is associated with a dismal prognosis. Immune checkpoint blockade (ICB) to induce antitumor activity in AML patients has yielded mixed results. Despite the pivotal role of B cells in antitumor immunity, a comprehensive assessment of B lymphocytes within AML's immunological microenvironment along with their interaction with ICB remains rather constrained.

METHODS: We performed an extensive analysis that involved paired single-cell RNA and B-cell receptor (BCR) sequencing on 52 bone marrow aspirate samples. These samples included 6 from healthy bone marrow donors (normal), 24 from newly diagnosed AML patients (NewlyDx), and 22 from 8 relapsed or …


Current And Emerging Antiviral Agents In The Prevention And Treatment Of Cytomegalovirus In Pediatric Transplant Recipients, Kristen G Valencia Deray, Lara A Danziger-Isakov, Kevin J Downes Feb 2024

Current And Emerging Antiviral Agents In The Prevention And Treatment Of Cytomegalovirus In Pediatric Transplant Recipients, Kristen G Valencia Deray, Lara A Danziger-Isakov, Kevin J Downes

Faculty, Staff and Students Publications

Despite current prophylaxis regimens, cytomegalovirus (CMV) is common in hematopoietic cell transplantation (HCT) and solid organ transplantation (SOT) and remains a significant cause of morbidity and mortality. Newer antiviral medications are reshaping the landscape for prevention and treatment of CMV DNAemia, infection, and disease. Letermovir is approved for CMV prevention in adult HCT patients and is attractive due to the absence of marrow suppression seen with ganciclovir/valganciclovir. Letermovir should not be routinely used for CMV treatment due to its low threshold for resistance. Maribavir is approved for the treatment of refractory or resistant CMV disease in HCT and SOT recipients …


Gamma Delta T Cells In Acute Myeloid Leukemia: Biology And Emerging Therapeutic Strategies, Adishwar Rao, Akriti Agrawal, Gautam Borthakur, Venkata Lokesh Battula, Abhishek Maiti Feb 2024

Gamma Delta T Cells In Acute Myeloid Leukemia: Biology And Emerging Therapeutic Strategies, Adishwar Rao, Akriti Agrawal, Gautam Borthakur, Venkata Lokesh Battula, Abhishek Maiti

Faculty, Staff and Student Publications

γδ T cells play an important role in disease control in acute myeloid leukemia (AML) and have become an emerging area of therapeutic interest. These cells represent a minor population of T lymphocytes with intrinsic abilities to recognize antigens in a major histocompatibility complex-independent manner and functionally straddle the innate and adaptive immunity interface. AML shows high expression of phosphoantigens and UL-16 binding proteins that activate the Vδ2 and Vδ1 subtypes of γδ T cells, respectively, leading to γδ T cell-mediated cytotoxicity. Insights from murine models and clinical data in humans show improved overall survival, leukemia-free survival, reduced risk of …


Notes From The Field: Reemergence Of Mycoplasma Pneumoniae Infections In Children And Adolescents After The Covid-19 Pandemic, United States, 2018-2024., Chris Edens, Benjamin R. Clopper, Jourdan Devies, Alvaro Benitez, Erin R. Mckeever, Dylan Johns, Bernard Wolff, Rangaraj Selvarangan, Jennifer E. Schuster, Geoffrey A. Weinberg, Peter G. Szilagyi, Fatimah S. Dawood, Lakshmi Radhakrishnan, Christina Quigley, Leila C. Sahni, Natasha Halasa, Laura S. Stewart, Meredith L. Mcmorrow, Brett Whitaker, Danielle M. Zerr, Vasanthi Avadhanula, John V. Williams, Marian G. Michaels, Aaron Kite-Powell, Janet A. Englund, Mary Allen Staat, Kathleen Hartnett, Heidi L. Moline, Adam L. Cohen, Maureen Diaz Feb 2024

Notes From The Field: Reemergence Of Mycoplasma Pneumoniae Infections In Children And Adolescents After The Covid-19 Pandemic, United States, 2018-2024., Chris Edens, Benjamin R. Clopper, Jourdan Devies, Alvaro Benitez, Erin R. Mckeever, Dylan Johns, Bernard Wolff, Rangaraj Selvarangan, Jennifer E. Schuster, Geoffrey A. Weinberg, Peter G. Szilagyi, Fatimah S. Dawood, Lakshmi Radhakrishnan, Christina Quigley, Leila C. Sahni, Natasha Halasa, Laura S. Stewart, Meredith L. Mcmorrow, Brett Whitaker, Danielle M. Zerr, Vasanthi Avadhanula, John V. Williams, Marian G. Michaels, Aaron Kite-Powell, Janet A. Englund, Mary Allen Staat, Kathleen Hartnett, Heidi L. Moline, Adam L. Cohen, Maureen Diaz

Manuscripts, Articles, Book Chapters and Other Papers

No abstract provided.


Immunotherapy Resistance In Solid Tumors: Mechanisms And Potential Solutions, Daniel Lefler, Steven Manobianco, Babar Bashir Feb 2024

Immunotherapy Resistance In Solid Tumors: Mechanisms And Potential Solutions, Daniel Lefler, Steven Manobianco, Babar Bashir

Kimmel Cancer Center Faculty Papers

While the emergence of immunotherapies has fundamentally altered the management of solid tumors, cancers exploit many complex biological mechanisms that result in resistance to these agents. These encompass a broad range of cellular activities - from modification of traditional paradigms of immunity via antigen presentation and immunoregulation to metabolic modifications and manipulation of the tumor microenvironment. Intervening on these intricate processes may provide clinical benefit in patients with solid tumors by overcoming resistance to immunotherapies, which is why it has become an area of tremendous research interest with practice-changing implications. This review details the major ways cancers avoid both natural …


A Stool Based Qpcr For The Diagnosis Of Tb In Children And People Living With Hiv In Uganda, Eswatini And Mozambique (Stool4tb): A Protocol For A Multicenter Diagnostic Evaluation, Lucia Carratala-Castro, Willy Ssengooba, Alex Kay, Sozinho Acácio, Joanna Ehrlich, Andrew R Dinardo, Nosisa Shiba, Joachim K Nsubuga, Shilzia Munguambe, Belén Saavedra-Cervera, Patricia Manjate, Durbbin Mulengwa, Busizwe Sibandze, Mangaliso Ziyane, George Kasule, Edson Mambuque, Moorine Penninah Sekadde, Eric Wobudeya, Moses L Joloba, Jan Heyckendorf, Christoph Lange, Sabine Hermans, Anna Mandalakas, Alberto L García-Basteiro, Elisa Lopez-Varela, Stool4tb Global Partnership Feb 2024

A Stool Based Qpcr For The Diagnosis Of Tb In Children And People Living With Hiv In Uganda, Eswatini And Mozambique (Stool4tb): A Protocol For A Multicenter Diagnostic Evaluation, Lucia Carratala-Castro, Willy Ssengooba, Alex Kay, Sozinho Acácio, Joanna Ehrlich, Andrew R Dinardo, Nosisa Shiba, Joachim K Nsubuga, Shilzia Munguambe, Belén Saavedra-Cervera, Patricia Manjate, Durbbin Mulengwa, Busizwe Sibandze, Mangaliso Ziyane, George Kasule, Edson Mambuque, Moorine Penninah Sekadde, Eric Wobudeya, Moses L Joloba, Jan Heyckendorf, Christoph Lange, Sabine Hermans, Anna Mandalakas, Alberto L García-Basteiro, Elisa Lopez-Varela, Stool4tb Global Partnership

Faculty, Staff and Students Publications

BACKGROUND: Tuberculosis (TB) is a major cause of mortality worldwide. Children and people living with HIV (PLHIV) have an increased risk of mortality, particularly in the absence of rapid diagnosis. The main challenges of diagnosing TB in these populations are due to the unspecific and paucibacillary disease presentation and the difficulty of obtaining respiratory samples. Thus, novel diagnostic strategies, based on non-respiratory specimens could improve clinical decision making and TB outcomes in high burden TB settings. We propose a multi-country, prospective diagnostic evaluation study with a nested longitudinal cohort evaluation to assess the performance of a new stool-based qPCR, developed …


The Pathogenicity Of Vancomycin-Resistant Enterococcus Faecalis To Colon Cancer Cells, Li Zhang, Mingxia Deng, Jing Liu, Jiajie Zhang, Fangyu Wang, Wei Yu Feb 2024

The Pathogenicity Of Vancomycin-Resistant Enterococcus Faecalis To Colon Cancer Cells, Li Zhang, Mingxia Deng, Jing Liu, Jiajie Zhang, Fangyu Wang, Wei Yu

Faculty, Staff and Student Publications

BACKGROUND: The aim of this study was to investigate the pathogenicity of vancomycin-resistant Enterococcus faecalis (VREs) to human colon cells in vitro.

METHODS: Three E. faecalis isolates (2 VREs and E. faecalis ATCC 29212) were cocultured with NCM460, HT-29 and HCT116 cells. Changes in cell morphology and bacterial adhesion were assessed at different time points. Interleukin-8 (IL-8) and vascular endothelial growth factor A (VEGFA) expression were measured via RT-qPCR and enzyme-linked immunosorbent assay (ELISA), respectively. Cell migration and human umbilical vein endothelial cells (HUVECs) tube formation assays were used for angiogenesis studies. The activity of PI3K/AKT/mTOR signaling pathway was measured …


Novel Ancestry-Specific Primary Open-Angle Glaucoma Loci And Shared Biology With Vascular Mechanisms And Cell Proliferation, Valeria Lo Faro, Arjun Bhattacharya, Wei Zhou, Dan Zhou, Ying Wang, Kristi Läll, Masahiro Kanai, Esteban Lopera-Maya, Peter Straub, Priyanka Pawar, Ran Tao, Xue Zhong, Shinichi Namba, Global Biobank Meta-Analysis Initiative, Serena Sanna, Ilja M Nolte, Yukinori Okada, Nathan Ingold, Stuart Macgregor, Harold Snieder, Ida Surakka, Jonathan Shortt, Chris Gignoux, Nicholas Rafaels, Kristy Crooks, Anurag Verma, Shefali S Verma, Lindsay Guare, Daniel J Rader, Cristen Willer, Alicia R Martin, Milam A Brantley, Eric R Gamazon, Nomdo M Jansonius, Karen Joos, Nancy J Cox, Jibril Hirbo Feb 2024

Novel Ancestry-Specific Primary Open-Angle Glaucoma Loci And Shared Biology With Vascular Mechanisms And Cell Proliferation, Valeria Lo Faro, Arjun Bhattacharya, Wei Zhou, Dan Zhou, Ying Wang, Kristi Läll, Masahiro Kanai, Esteban Lopera-Maya, Peter Straub, Priyanka Pawar, Ran Tao, Xue Zhong, Shinichi Namba, Global Biobank Meta-Analysis Initiative, Serena Sanna, Ilja M Nolte, Yukinori Okada, Nathan Ingold, Stuart Macgregor, Harold Snieder, Ida Surakka, Jonathan Shortt, Chris Gignoux, Nicholas Rafaels, Kristy Crooks, Anurag Verma, Shefali S Verma, Lindsay Guare, Daniel J Rader, Cristen Willer, Alicia R Martin, Milam A Brantley, Eric R Gamazon, Nomdo M Jansonius, Karen Joos, Nancy J Cox, Jibril Hirbo

Faculty, Staff and Student Publications

Primary open-angle glaucoma (POAG), a leading cause of irreversible blindness globally, shows disparity in prevalence and manifestations across ancestries. We perform meta-analysis across 15 biobanks (of the Global Biobank Meta-analysis Initiative) (n = 1,487,441: cases = 26,848) and merge with previous multi-ancestry studies, with the combined dataset representing the largest and most diverse POAG study to date (n = 1,478,037: cases = 46,325) and identify 17 novel significant loci, 5 of which were ancestry specific. Gene-enrichment and transcriptome-wide association analyses implicate vascular and cancer genes, a fifth of which are primary ciliary related. We perform an extensive statistical analysis of …


Adaptation Of Chagas Disease Screening Recommendations For A Community Of At-Risk Hiv In The United States, Jesica Hayon, Sofia Lupo, Cristina Poveda, Kathryn M Jones, Qian Qian, Hulin Wu, Thomas P Giordano, Charles J Fleischmann, Caryn Bern, Jeffrey D Whitman, Eva H Clark Feb 2024

Adaptation Of Chagas Disease Screening Recommendations For A Community Of At-Risk Hiv In The United States, Jesica Hayon, Sofia Lupo, Cristina Poveda, Kathryn M Jones, Qian Qian, Hulin Wu, Thomas P Giordano, Charles J Fleischmann, Caryn Bern, Jeffrey D Whitman, Eva H Clark

Faculty, Staff and Students Publications

Chagas disease (CD), caused by Trypanosoma cruzi, is underdiagnosed in the United States. Improved screening strategies are needed, particularly for people at risk for life-threatening sequelae of CD, including people with human immunodeficiency virus (HIV, PWH). Here we report results of a CD screening strategy applied at a large HIV clinic serving an at-risk population.


Clinical Outcomes And Bacterial Characteristics Of Carbapenem-Resistant Acinetobacter Baumannii Among Patients From Different Global Regions., Minggui Wang, Lizhao Ge, Liang Chen, Lauren Komarow, Blake Hanson, Jinnethe Reyes, Eric Cober, Thamer Alenazi, Zhiyong Zong, Qing Xie, Zhengyin Liu, Lanjuan Li, Yunsong Yu, Hainv Gao, Souha S Kanj, Jairo Figueroa, Erica Herc, Ezequiel Cordova, Gregory Weston, Paul Ananth Tambyah, Julia Garcia-Diaz, Keith S Kaye, Sorabh Dhar, Jose M Munita, Robert A Salata, Samuel Vilchez, Martin E Stryjewski, Maria Virginia Villegas Botero, Alina Iovleva, Scott R Evans, Keri Baum, Carol Hill, Barry N Kreiswirth, Robin Patel, David L Paterson, Cesar A Arias, Robert A Bonomo, Henry F Chambers, Vance G Fowler, Michael J Satlin, David Van Duin, Yohei Doi Feb 2024

Clinical Outcomes And Bacterial Characteristics Of Carbapenem-Resistant Acinetobacter Baumannii Among Patients From Different Global Regions., Minggui Wang, Lizhao Ge, Liang Chen, Lauren Komarow, Blake Hanson, Jinnethe Reyes, Eric Cober, Thamer Alenazi, Zhiyong Zong, Qing Xie, Zhengyin Liu, Lanjuan Li, Yunsong Yu, Hainv Gao, Souha S Kanj, Jairo Figueroa, Erica Herc, Ezequiel Cordova, Gregory Weston, Paul Ananth Tambyah, Julia Garcia-Diaz, Keith S Kaye, Sorabh Dhar, Jose M Munita, Robert A Salata, Samuel Vilchez, Martin E Stryjewski, Maria Virginia Villegas Botero, Alina Iovleva, Scott R Evans, Keri Baum, Carol Hill, Barry N Kreiswirth, Robin Patel, David L Paterson, Cesar A Arias, Robert A Bonomo, Henry F Chambers, Vance G Fowler, Michael J Satlin, David Van Duin, Yohei Doi

Faculty, Staff and Student Publications

Background: Carbapenem-resistant Acinetobacter baumannii (CRAb) is 1 of the most problematic antimicrobial-resistant bacteria. We sought to elucidate the international epidemiology and clinical impact of CRAb.

Methods: In a prospective observational cohort study, 842 hospitalized patients with a clinical CRAb culture were enrolled at 46 hospitals in five global regions between 2017 and 2019. The primary outcome was all-cause mortality at 30 days from the index culture. The strains underwent whole-genome analysis.

Results: Of 842 cases, 536 (64%) represented infection. By 30 days, 128 (24%) of the infected patients died, ranging from 1 (6%) of 18 in Australia-Singapore to 54 (25%) …


Description Of Cryptococcosis Following Sars-Cov-2 Infection: A Disease Survey Through The Mycosis Study Group Education And Research Consortium (Msg-19), Jeremey Walker, Todd Mccarty, Gerald Mcgwin, Eloy E Ordaya, Paschalis Vergidis, Luis Ostrosky-Zeichner, Mehriban Mammadova, Andrej Spec, Adriana M Rauseo, John Perfect, Julia Messina, Gabriel Vilchez, Rachel Mcmullen, Carolynn T Jones, Peter G Pappas Feb 2024

Description Of Cryptococcosis Following Sars-Cov-2 Infection: A Disease Survey Through The Mycosis Study Group Education And Research Consortium (Msg-19), Jeremey Walker, Todd Mccarty, Gerald Mcgwin, Eloy E Ordaya, Paschalis Vergidis, Luis Ostrosky-Zeichner, Mehriban Mammadova, Andrej Spec, Adriana M Rauseo, John Perfect, Julia Messina, Gabriel Vilchez, Rachel Mcmullen, Carolynn T Jones, Peter G Pappas

Faculty, Staff and Student Publications

BACKGROUND: Invasive fungal infections have been described throughout the COVID-19 pandemic. Cryptococcal disease after infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been reported in several isolated case reports and 1 larger case series. We sought to describe cryptococcal infections following SARS-CoV-2 through establishing a database to investigate underlying risk factors, disease manifestations, and outcomes.

METHODS: We created a crowdsourced call for cases solicited through the Mycoses Study Group Education and Research Consortium, the Centers for Disease Control and Prevention Emerging Infectious Diseases Network, and infectious diseases Twitter groups. Data were collected in a web-based and secure REDCap …


Deciphering Early-Stage Molecular Mechanisms Of Negative Pressure Wound Therapy In A Murine Model, Yu-Chiau Shyu, Ting-Shuo Huang, Hua-Sheng Chiu, Pavel Sumazin, Xin-Yu Lin, Po-Cheng Liao, Cai-Cin Liou, Fang-Chia Hsu, Jyuan-Siou Lin, Chih-Chin Hsu, Pang-Hung Hsu, Chi-Chin Sun, Chien-Tzung Chen Feb 2024

Deciphering Early-Stage Molecular Mechanisms Of Negative Pressure Wound Therapy In A Murine Model, Yu-Chiau Shyu, Ting-Shuo Huang, Hua-Sheng Chiu, Pavel Sumazin, Xin-Yu Lin, Po-Cheng Liao, Cai-Cin Liou, Fang-Chia Hsu, Jyuan-Siou Lin, Chih-Chin Hsu, Pang-Hung Hsu, Chi-Chin Sun, Chien-Tzung Chen

Faculty, Staff and Students Publications

Negative Pressure Wound Therapy (NPWT) is a commonly employed clinical strategy for wound healing, yet its early-stage mechanisms remain poorly understood. To address this knowledge gap and overcome the limitations of human trials, we establish an NPWT C57BL/6JNarl mouse model to investigate the molecular mechanisms involved in NPWT. In this study, we investigate the intricate molecular mechanisms through which NPWT expedites wound healing. Our focus is on NPWT's modulation of inflammatory immune responses and the concurrent orchestration of multiple signal transduction pathways, resulting in shortened coagulation time and reduced inflammation. Notably, we observe a significant rise in dickkopf-related protein 1 …


Description Of Cryptococcosis Following Sars-Cov-2 Infection: A Disease Survey Through The Mycosis Study Group Education And Research Consortium (Msg-19), Jeremey Walker, Andrej Spec, Adriana M Rauseo, Et Al. Feb 2024

Description Of Cryptococcosis Following Sars-Cov-2 Infection: A Disease Survey Through The Mycosis Study Group Education And Research Consortium (Msg-19), Jeremey Walker, Andrej Spec, Adriana M Rauseo, Et Al.

2020-Current year OA Pubs

BACKGROUND: Invasive fungal infections have been described throughout the COVID-19 pandemic. Cryptococcal disease after infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been reported in several isolated case reports and 1 larger case series. We sought to describe cryptococcal infections following SARS-CoV-2 through establishing a database to investigate underlying risk factors, disease manifestations, and outcomes.

METHODS: We created a crowdsourced call for cases solicited through the Mycoses Study Group Education and Research Consortium, the Centers for Disease Control and Prevention Emerging Infectious Diseases Network, and infectious diseases Twitter groups. Data were collected in a web-based and secure REDCap …


Generalizable Pipeline For Constructing Hiv Risk Prediction Models Across Electronic Health Record Systems, Sarah B May, Thomas P Giordano, Assaf Gottlieb Feb 2024

Generalizable Pipeline For Constructing Hiv Risk Prediction Models Across Electronic Health Record Systems, Sarah B May, Thomas P Giordano, Assaf Gottlieb

Faculty, Staff and Student Publications

OBJECTIVE: The HIV epidemic remains a significant public health issue in the United States. HIV risk prediction models could be beneficial for reducing HIV transmission by helping clinicians identify patients at high risk for infection and refer them for testing. This would facilitate initiation on treatment for those unaware of their status and pre-exposure prophylaxis for those uninfected but at high risk. Existing HIV risk prediction algorithms rely on manual construction of features and are limited in their application across diverse electronic health record systems. Furthermore, the accuracy of these models in predicting HIV in females has thus far been …