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Cytomegalovirus Reactivation And Acute And Chronic Complications In Children With Cerebral Malaria: A Prospective Cohort Study, Jonathan A. A. Mayhew, Andrew J. Witten, Caitlin A. Bond, Robert Opoka, Paul Bangirana, Andrea L. Conroy, Nelmary Hernandez-Alvarado, Mark R. Schleiss, Chandy C. John C. John Feb 2025

Cytomegalovirus Reactivation And Acute And Chronic Complications In Children With Cerebral Malaria: A Prospective Cohort Study, Jonathan A. A. Mayhew, Andrew J. Witten, Caitlin A. Bond, Robert Opoka, Paul Bangirana, Andrea L. Conroy, Nelmary Hernandez-Alvarado, Mark R. Schleiss, Chandy C. John C. John

Paediatrics and Child Health, East Africa

Background: Virus co-infection or reactivation may modify the host response during cerebral malaria. Cytomegalovirus (CMV) DNAemia has been associated with increased morbidity and mortality in adults with sepsis; however, the impact of CMV DNAemia on adverse outcomes in children with cerebral malaria is unknown.: Clinical, physiological, and neurocognitive outcomes were compared in children aged 18 months to 12 years with cerebral malaria (N = 242) based on the presence or absence of CMV DNAemia 24 h after admission. The primary study outcome was subsequent in-hospital mortality. Secondary outcomes included the presence of acute kidney injury, neurocognitive impairment over a …


Association Between Early Immunosuppression Center Variability And One-Year Outcomes After Pediatric Liver Transplant., Vikram K. Raghu, Scott D. Rothenberger, James E. Squires, Elizabeth Eisenberg, Anna L. Peters, Jennifer Halma, Swati Antala, Irini D. Batsis, Ke-You Zhang, Amy G. Feldman, Daniel H. Leung, Steven J. Lobritto, John Bucuvalas, Simon P. Horslen, George V. Mazariegos, Emily R. Perito Feb 2025

Association Between Early Immunosuppression Center Variability And One-Year Outcomes After Pediatric Liver Transplant., Vikram K. Raghu, Scott D. Rothenberger, James E. Squires, Elizabeth Eisenberg, Anna L. Peters, Jennifer Halma, Swati Antala, Irini D. Batsis, Ke-You Zhang, Amy G. Feldman, Daniel H. Leung, Steven J. Lobritto, John Bucuvalas, Simon P. Horslen, George V. Mazariegos, Emily R. Perito

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Despite the existence of institutional protocols, liver transplant centers often have variability in early immunosuppression practices. We aimed to measure within-center variability in early immunosuppression after pediatric liver transplant (LT) and examine its association with one-year outcomes.

METHODS: We analyzed pediatric LTs from 2013 to 2018 in the United Network for Organ Sharing registry, with data aggregated by center. We categorized induction regimen as corticosteroids only vs. T-cell depleting antibody vs. non-T-cell depleting antibody. Primary exposures were coefficient of immunosuppression variability (CIV) in (1) induction and (2) mycophenolate mofetil (MMF) use. Primary outcomes were one-year graft survival, patient survival, …


Uncovering Specific Genetic-Respiratory Disease Endotypes For Rheumatoid Arthritis Risk, Vanessa L Kronzer, Katrina A Williamson, Keigo Hayashi, Elizabeth J Atkinson, Cynthia S Crowson, Xiaosong Wang, Jing Cui, James R Cerhan, Jennifer A Sletten, Gregory C Mcdermott, Elena K Joerns, Robert Vassallo, John M Davis, Jeffrey A Sparks Feb 2025

Uncovering Specific Genetic-Respiratory Disease Endotypes For Rheumatoid Arthritis Risk, Vanessa L Kronzer, Katrina A Williamson, Keigo Hayashi, Elizabeth J Atkinson, Cynthia S Crowson, Xiaosong Wang, Jing Cui, James R Cerhan, Jennifer A Sletten, Gregory C Mcdermott, Elena K Joerns, Robert Vassallo, John M Davis, Jeffrey A Sparks

Faculty, Staff and Students Publications

Objective: We aimed to identify specific genetic-respiratory disease endotypes for rheumatoid arthritis (RA) risk.

Methods: This case-control study used the Mass General Brigham (MGB) and Mayo Clinic (MC) Biobanks for discovery and replication, respectively. We matched criteria-confirmed incident RA cases to four non-RA controls on age, sex and health record history. Genetic exposures included the top 11 RA risk alleles, and a validated human leucocyte antigen (HLA) genetic risk score (GRS). We identified seven respiratory diseases by codes. Using logistic regression models adjusting for potential confounders, we estimated Rs with 95% CIs for the interactions between genetic and respiratory exposures …


Unprecedented Female Mutation Bias In The Aye-Aye, A Highly Unusual Lemur From Madagascar, Richard J Wang, Yadira Peña-García, Muthuswamy Raveendran, R Alan Harris, Thuy-Trang Nguyen, Marie-Claude Gingras, Yifan Wu, Lesette Perez, Anne D Yoder, Joe H Simmons, Jeffrey Rogers, Matthew W Hahn Feb 2025

Unprecedented Female Mutation Bias In The Aye-Aye, A Highly Unusual Lemur From Madagascar, Richard J Wang, Yadira Peña-García, Muthuswamy Raveendran, R Alan Harris, Thuy-Trang Nguyen, Marie-Claude Gingras, Yifan Wu, Lesette Perez, Anne D Yoder, Joe H Simmons, Jeffrey Rogers, Matthew W Hahn

Faculty, Staff and Students Publications

Every mammal studied to date has been found to have a male mutation bias: male parents transmit more de novo mutations to offspring than female parents, contributing increasingly more mutations with age. Although male-biased mutation has been studied for more than 75 years, its causes are still debated. One obstacle to understanding this pattern is its near universality-without variation in mutation bias, it is difficult to find an underlying cause. Here, we present new data on multiple pedigrees from two primate species: aye-ayes (Daubentonia madagascariensis), a member of the strepsirrhine primates, and olive baboons (Papio anubis). In stark contrast to …


Historical Demography And Species Distribution Models Shed Light On Speciation In Primates Of Northeast India, Mihir Trivedi, Kunal Arekar, Shivakumara Manu, Lukas F K Kuderna, Jeffrey Rogers, Kyle Kai-How Farh, Tomas Marques Bonet, Govindhaswamy Umapathy Feb 2025

Historical Demography And Species Distribution Models Shed Light On Speciation In Primates Of Northeast India, Mihir Trivedi, Kunal Arekar, Shivakumara Manu, Lukas F K Kuderna, Jeffrey Rogers, Kyle Kai-How Farh, Tomas Marques Bonet, Govindhaswamy Umapathy

Faculty, Staff and Students Publications

Past climate change is one of the important factors influencing primate speciation. Populations of various species could have risen or declined in response to these climatic fluctuations. Northeast India harbors a rich diversity of primates, where such fluctuations can be implicated. Recent advances in climate modeling as well as genomic data analysis has paved the way for understanding how species accumulate at a particular geographic region. We utilized these methods to explore the primate diversity in this unique region in relation to past climate change. To ascertain the population level changes, we inferred the demographic history of nine species of …


Beyond Traditional Body Composition Metrics: Load-Capacity Indices Emerge As Predictors Of Cardiometabolic Outcomes—A Systematic Review And Meta-Analysis, Zhongyang Guan, Marianna Minnetti, Steven B. Heymsfield, Eleonora Poggiogalle, Carla M. Prado, Marc Sim, Blossom C.M. Stephan, Jonathan C.K. Wells, Lorenzo M. Donini, Mario Siervo Feb 2025

Beyond Traditional Body Composition Metrics: Load-Capacity Indices Emerge As Predictors Of Cardiometabolic Outcomes—A Systematic Review And Meta-Analysis, Zhongyang Guan, Marianna Minnetti, Steven B. Heymsfield, Eleonora Poggiogalle, Carla M. Prado, Marc Sim, Blossom C.M. Stephan, Jonathan C.K. Wells, Lorenzo M. Donini, Mario Siervo

Research outputs 2022 to 2026

The adaptive and independent interrelationships between different body composition components have been identified as crucial determinants of disease risk. On the basis of this concept, the load-capacity model of body composition, which utilizes measurements obtained through nonanthropometric techniques such as dual-energy X-ray absorptiometry, was proposed. This model is typically operationalized as the ratio of metabolic load (adipose mass) to metabolic capacity (lean mass). In recent years, a series of load-capacity indices (LCIs) have been utilized to identify abnormal body composition phenotypes such as sarcopenic obesity (SO) and to predict the risk of metabolic, cardiovascular, and cognitive disorders. In this review, …


The Mascc Cog-Impact: An Unmet Needs Assessment For Cancer-Related Cognitive Impairment Impact Developed By The Multinational Association Of Supportive Care In Cancer, Darren Haywood, Alexandre Chan, Raymond J. Chan, Frank D. Baughman, Evan Dauer, Haryana M. Dhillon, Ashley M. Henneghan, Blake J. Lawrence, Maryam B. Lustberg, Moira O’Connor, Janette L. Vardy, Susan L. Rossell, Nicolas H. Hart Feb 2025

The Mascc Cog-Impact: An Unmet Needs Assessment For Cancer-Related Cognitive Impairment Impact Developed By The Multinational Association Of Supportive Care In Cancer, Darren Haywood, Alexandre Chan, Raymond J. Chan, Frank D. Baughman, Evan Dauer, Haryana M. Dhillon, Ashley M. Henneghan, Blake J. Lawrence, Maryam B. Lustberg, Moira O’Connor, Janette L. Vardy, Susan L. Rossell, Nicolas H. Hart

Research outputs 2022 to 2026

Purpose: Cancer-related cognitive impairment (CRCI) can have a profound impact on the lives of cancer survivors. A multitude of subjective and objective assessment tools exist to assess the presence and severity of CRCI. However, no purpose-built tool exists to assess the unmet needs of cancer survivors directly relating to CRCI. This paper details the development and initial validation of the Multinational Association of Supportive Care in Cancer - Unmet Needs Assessment of Cancer-Related Cognitive Impairment Impact (the MASCC COG-IMPACT).

Methods: A multistep mixed-methods measurement development and validation approach was taken with a strong emphasis on co-design. Qualitative interviews were conducted …


Trajectories Of Supportive Care Needs For People Who Travel To Receive Cancer Treatment: A Longitudinal Study In Australia, Susannah K. Ayre, Elizabeth A. Johnston, Michael Ireland, Sonja March, Jeff Dunn, Suzanne Chambers, Belinda C. Goodwin Feb 2025

Trajectories Of Supportive Care Needs For People Who Travel To Receive Cancer Treatment: A Longitudinal Study In Australia, Susannah K. Ayre, Elizabeth A. Johnston, Michael Ireland, Sonja March, Jeff Dunn, Suzanne Chambers, Belinda C. Goodwin

Research outputs 2022 to 2026

Objective: To describe trajectories of change in unmet supportive care needs over a two-year period among people diagnosed with cancer and assess whether these trajectories vary as a function of sociodemographic and clinical characteristics. Methods: This analysis used data from a longitudinal study of people in Queensland, Australia who travelled largely from regional and remote areas to metropolitan centres to receive cancer care (N = 784). Supportive care needs were measured at baseline, then at 3-, 12-, and 24-month post-baseline across five domains (‘psychological’, ‘physical and daily living’, ‘health systems and information’, ‘patient care and support’, ‘sexuality’) using the Supportive …


Gestational Weight Gain And Increased Risk Of Cesarean Delivery Across Body Mass Index Categories., Pearl A Mcelfish, Britni L Ayers, Nicola L Hawley, Aaron Caldwell, Austin Porter, Michael D Macechko, Donya Watson, Jennifer A Callaghan-Koru, James P Selig, Jennifer A Andersen, Nirvana Manning, Lanita White, Enrique Gomez-Pomar, Clare C Brown Feb 2025

Gestational Weight Gain And Increased Risk Of Cesarean Delivery Across Body Mass Index Categories., Pearl A Mcelfish, Britni L Ayers, Nicola L Hawley, Aaron Caldwell, Austin Porter, Michael D Macechko, Donya Watson, Jennifer A Callaghan-Koru, James P Selig, Jennifer A Andersen, Nirvana Manning, Lanita White, Enrique Gomez-Pomar, Clare C Brown

Pediatrics Faculty Publications

BACKGROUND: Unnecessary cesarean delivery can have negative implications for both mothers and infants. In the United States, the proportion of women undergoing cesarean delivery exceeds the acceptable World Health Organization proportion. Reducing cesarean deliveries is a national goal of Centers for Disease Control and Prevention Healthy People 2030, the American College of Obstetricians and Gynecologists, and the Alliance for Innovation on Maternal Health.

OBJECTIVE: This study aimed to examine if excessive gestational weight gain is associated with increased risk of cesarean delivery across multiple body mass index categories.

STUDY DESIGN: Analysis was conducted using vital records data from the National …


Gestational Weight Gain And Increased Risk Of Cesarean Delivery Across Body Mass Index Categories., Pearl A Mcelfish, Britni L Ayers, Nicola L Hawley, Aaron Caldwell, Austin Porter, Michael D Macechko, Donya Watson, Jennifer A Callaghan-Koru, James P Selig, Jennifer A Andersen, Nirvana Manning, Lanita White, Enrique Gomez-Pomar, Clare C Brown Feb 2025

Gestational Weight Gain And Increased Risk Of Cesarean Delivery Across Body Mass Index Categories., Pearl A Mcelfish, Britni L Ayers, Nicola L Hawley, Aaron Caldwell, Austin Porter, Michael D Macechko, Donya Watson, Jennifer A Callaghan-Koru, James P Selig, Jennifer A Andersen, Nirvana Manning, Lanita White, Enrique Gomez-Pomar, Clare C Brown

Pediatrics Faculty Publications

BACKGROUND: Unnecessary cesarean delivery can have negative implications for both mothers and infants. In the United States, the proportion of women undergoing cesarean delivery exceeds the acceptable World Health Organization proportion. Reducing cesarean deliveries is a national goal of Centers for Disease Control and Prevention Healthy People 2030, the American College of Obstetricians and Gynecologists, and the Alliance for Innovation on Maternal Health.

OBJECTIVE: This study aimed to examine if excessive gestational weight gain is associated with increased risk of cesarean delivery across multiple body mass index categories.

STUDY DESIGN: Analysis was conducted using vital records data from the National …


Ecmo In Pediatric Oncologic And Hsct Patients: A Descriptive And Comparative Analysis, Michelle Brown Feb 2025

Ecmo In Pediatric Oncologic And Hsct Patients: A Descriptive And Comparative Analysis, Michelle Brown

Presentations

Introduction: Pediatric oncologic and hematopoietic stem cell transplant (HSCT) recipients are vulnerable to development of respiratory failure due to chemotherapy, radiation, surgery, and immunosuppression. Yet, providing extracorporeal membrane oxygenation (ECMO) support in these patient populations remains controversial with heterogenous utilization across pediatric institutions. The aim of this study is to characterize and compare outcomes in pediatric oncologic and HSCT patients with respiratory failure in the presence and absence of ECMO support. Methods: This study was a retrospective matched comparative analysis between two tertiary care pediatric institutions. Patients less than 18 years old with an underlying oncologic diagnosis and/or HSCT with …


D-Transposition Of The Great Arteries With Right Aortic Arch, Bilateral Ductus With Ductal Origin Of The Left Subclavian Artery And Abnormal Aortic Origin Of The Left Coronary Artery, Jenna Schermerhorn, Anmol Goyal, Param Vora, Braidyn Wells, Edo Bedzra, Sanket Shah Feb 2025

D-Transposition Of The Great Arteries With Right Aortic Arch, Bilateral Ductus With Ductal Origin Of The Left Subclavian Artery And Abnormal Aortic Origin Of The Left Coronary Artery, Jenna Schermerhorn, Anmol Goyal, Param Vora, Braidyn Wells, Edo Bedzra, Sanket Shah

Posters

We present a case of prenatally diagnosed d-transposition of the great arteries (d-TGA) with intact ventricular septum (IVS), postnatally found to have bilateral patent ductus arteriosus (PDA) with potential for isolation of the left subclavian artery (LSA) and an abnormal left coronary artery (LCA) course. Isolation of the LSA is a rare occurrence and defined as an anomalous origin from the pulmonary artery via PDA and apparent discontinuation from the arch following PDA closure. It is exceedingly rare in association with d-TGA. Coronary artery anatomy is particularly important in d-TGA given most patients undergo the arterial switch operation (ASO).


National Prescribing Practices For Pediatric Dystonia Among Providers In The United States., Sarah Paige Davis, Natalie J. Kane, Haley E. Botteron, Rose N. Gelineau-Morel Feb 2025

National Prescribing Practices For Pediatric Dystonia Among Providers In The United States., Sarah Paige Davis, Natalie J. Kane, Haley E. Botteron, Rose N. Gelineau-Morel

Manuscripts, Articles, Book Chapters and Other Papers

While multiple oral medications are used to treat dystonia, limited information exists on current prescribing practices. This study analyzes real-world prescribing practices for pediatric dystonia in the United States, evaluating prescription frequency, dosing, and the impact of comorbidities. Oracle electronic health record real-world data were queried from 2014 to 2019 for encounters of patients under age 18 with a dystonia diagnosis and available medication records. Information was extracted on prescriptions for dystonia medications (baclofen, clonidine, carbidopa-levodopa, gabapentin, tetrabenazine, trihexyphenidyl, and select benzodiazepines), dosing, and comorbid diagnoses of cerebral palsy (CP), epilepsy, or spasticity. A total of 4010 pediatric patients with …


Immediate Postplacental Intrauterine Device Placement: Retrospective Cohort Study Of Expulsion And Associated Risk Factors, Emily Leubner, Brooke Levandowski, Sage Mikami, Theresa Green, Sarah Betstadt Feb 2025

Immediate Postplacental Intrauterine Device Placement: Retrospective Cohort Study Of Expulsion And Associated Risk Factors, Emily Leubner, Brooke Levandowski, Sage Mikami, Theresa Green, Sarah Betstadt

Abington Jefferson Health Papers

BACKGROUND: Postpartum contraception is typically provided during postpartum visits. When desired and accessible, the immediate postpartum period provides an additional opportunity to increase the use of more effective contraceptive methods to potentially reduce subsequent unintended pregnancies and improve pregnancy outcomes. In New York State, recent policy changes expanded Medicaid coverage to include immediate postplacental intrauterine device insertion. OBJECTIVE: This study aimed to investigate clinically documented intrauterine device expulsion within 12 months of placement in patients who depend on state-funded health insurance. STUDY DESIGN: This retrospective cohort study included Medicaid patients with an immediate postplacental intrauterine device placed after third-trimester delivery, …


Evidence Based Quality Improvement For Prescribing Stewardship In Icu (Equips-Icu): Protocol For Type Iii Hybrid Implementation-Effectiveness Study, Duncan Wagstaff, John Amausi, Sumaiya Arfin, Diptesh Aryal, Mohd Basri Mat Nor, Joseph Bonney, Arjen Dondorp, David Dongelmans, Layoni Dullawe, Wangari Siika Feb 2025

Evidence Based Quality Improvement For Prescribing Stewardship In Icu (Equips-Icu): Protocol For Type Iii Hybrid Implementation-Effectiveness Study, Duncan Wagstaff, John Amausi, Sumaiya Arfin, Diptesh Aryal, Mohd Basri Mat Nor, Joseph Bonney, Arjen Dondorp, David Dongelmans, Layoni Dullawe, Wangari Siika

Anaesthesiology, East Africa

Approximately half of all antimicrobial prescriptions in intensive care units (ICUs) may be inappropriate, including those prescribed when not needed, in unnecessary combinations or for longer durations than needed. Inappropriate prescribing is costly, exposes patients to unnecessary side-effects and drives population-level antimicrobial resistance, the prevalence and consequences of which are greatest in low- and middle-income countries. However, the implementation of interventions to improve the appropriateness of antimicrobial prescribing has been variable and requires further study..


Outcomes Of Pregnant Icu Patients With Severe Covid-19 Pneumonia In Qatar During The Three Waves Of The Covid-19 Pandemic: A Retrospective Cohort Study, Layla J.M Kily, Sohel M.G Ahmed, Tamam A.K.M Alhusban, Mohammed J. Orompurath, Marcus Lance, Mogahed I.H Hussein, Salwa M. Abuyaqoub, Huda A. Saleh, Eynas Abdalla, Santhosh Gopalakrishnan Feb 2025

Outcomes Of Pregnant Icu Patients With Severe Covid-19 Pneumonia In Qatar During The Three Waves Of The Covid-19 Pandemic: A Retrospective Cohort Study, Layla J.M Kily, Sohel M.G Ahmed, Tamam A.K.M Alhusban, Mohammed J. Orompurath, Marcus Lance, Mogahed I.H Hussein, Salwa M. Abuyaqoub, Huda A. Saleh, Eynas Abdalla, Santhosh Gopalakrishnan

Anaesthesiology, East Africa

Introduction: Pregnant women are considered a high-risk group for COVID-19 infection/pneumonia as they are known to be more vulnerable to viral infections. They require close monitoring and appropriate timely intervention to minimize the impact on both the mother and the fetus. Although the more prevalent Omicron variant led to fewer severe infections and fewer intensive care unit (ICU) admissions globally during the third wave, the effect on pregnant women and pregnancy outcomes was unknown. The vaccination campaign was thoroughly established by the third wave of the pandemic in Qatar. This retrospective descriptive cohort study investigates the characteristics, hospital stay, interventions, …


Acute Carpal Tunnel Syndrome Secondary To Handcuffs Necessitating Emergency Orthopedic Consultation And Operative Intervention, Fabian Jano, Kelly Mackenzie, Vivek Biololikar, David Goldberger, Andrei Tuluca Feb 2025

Acute Carpal Tunnel Syndrome Secondary To Handcuffs Necessitating Emergency Orthopedic Consultation And Operative Intervention, Fabian Jano, Kelly Mackenzie, Vivek Biololikar, David Goldberger, Andrei Tuluca

Department of Emergency Medicine Faculty Papers

We present a case of acute carpal tunnel syndrome secondary to tight handcuffs in a detained patient. The severity of the motor and sensory deficits prompted consultation with orthopedic specialists and admission for an observation period with ultimate emergency operative intervention. Handcuff neuropathies are well documented in the literature, mainly involving the superficial branch of the radial nerve, which has strict sensory input into the dorsum of the hand. Less common median nerve neuropathies have also been documented following handcuff injury; however, none have required emergency intervention. We aim to highlight this unusual presentation and the emergency nature of the …


Multi-Cancer Early Detection Tests: Attributes For Clinical Implementation, Jon O. Ebbert, Ernest T. Hawk, Christopher V. Chambers, Margaret A. Tempero, Elliot K. Fishman, Jospeh E. Ravenell, Tomasz M. Beer, Seema P. Rego Feb 2025

Multi-Cancer Early Detection Tests: Attributes For Clinical Implementation, Jon O. Ebbert, Ernest T. Hawk, Christopher V. Chambers, Margaret A. Tempero, Elliot K. Fishman, Jospeh E. Ravenell, Tomasz M. Beer, Seema P. Rego

Department of Family & Community Medicine Faculty Papers

Guideline-recommended screening programs exist for only a few single-cancer types, and these cancers represent less than one-half of all new cancer cases diagnosed each year in the U.S. In addition, these "single-cancer" standard of care (SoC) screening tests vary in accuracy, adherence, and effectiveness, though all are generally understood to lead to reductions in cancer-related mortality. Recent advances in high-throughput technologies and machine learning have facilitated the development of blood-based multi-cancer early detection (MCED) tests. The opportunity for early detection of multiple cancers with a single blood test holds promise in addressing the current unmet need in cancer screening. By …


Gdp-Mannose 4,6-Dehydratase Is A Key Driver Of Mycn-Amplified Neuroblastoma Core Fucosylation And Tumorigenesis, Beibei Zhu, Michelle G. Pitts, Michael D. Buoncristiani, Lindsay T. Bryant, Oscar Lopez-Nunez, Juan P. Gurria, Cameron Shedlock, Roberto Ribas, Shannon Keohane, Jinpeng Liu, Chi Wang, Matthew S. Gentry, Nathan R. Shelman, Derek B. Allison, B. Mark Evers, Ramon C. Sun, Eric J. Rellinger Feb 2025

Gdp-Mannose 4,6-Dehydratase Is A Key Driver Of Mycn-Amplified Neuroblastoma Core Fucosylation And Tumorigenesis, Beibei Zhu, Michelle G. Pitts, Michael D. Buoncristiani, Lindsay T. Bryant, Oscar Lopez-Nunez, Juan P. Gurria, Cameron Shedlock, Roberto Ribas, Shannon Keohane, Jinpeng Liu, Chi Wang, Matthew S. Gentry, Nathan R. Shelman, Derek B. Allison, B. Mark Evers, Ramon C. Sun, Eric J. Rellinger

Markey Cancer Center Faculty Publications

MYCN-amplification is a genetic hallmark of ~40% of high-risk neuroblastomas (NBs). Altered glycosylation is a common feature of adult cancer progression, but little is known about how genetic signatures such as MYCN-amplification alter glycosylation profiles. Herein, matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) revealed increased core fucosylated glycan abundance within neuroblast-rich regions of human MYCN-amplified NB tumors. GDP-mannose 4,6-dehydratase (GMDS) is responsible for the first-committed and rate-limiting step of de novo GDP-fucose synthesis. High GMDS expression was found to be associated with poor patient survival, advanced stage disease, and MYCN-amplification in human NB tumors. Chromatin immunoprecipitation and promoter reporter assays …


A Microrna-Regulated Transcriptional State Defines Intratumoral Cd8+ T Cells That Respond To Immunotherapy, William W. Tang, Ben Battistone, Kaylyn M. Bauer, Allison M. Weis, Cindy Barba, Muhammad Zaki Hidayatullah Fadlullah, Arevik Ghazaryan, Van B. Tran, Soh-Hyun Lee, Z. Busra Agir, Morgan C. Nelson, Emmanuel Stephen Victor, Amber Thibeaux, Colton Hernandez, Jacob Tantalla, Aik C. Tan, Dinesh Rao, Matthew Williams, Micah J. Drummond, Ellen J. Beswick, June L. Round, H. Atakan Ekiz, Warren P/ Voth, Ryan M. O’Connell Feb 2025

A Microrna-Regulated Transcriptional State Defines Intratumoral Cd8+ T Cells That Respond To Immunotherapy, William W. Tang, Ben Battistone, Kaylyn M. Bauer, Allison M. Weis, Cindy Barba, Muhammad Zaki Hidayatullah Fadlullah, Arevik Ghazaryan, Van B. Tran, Soh-Hyun Lee, Z. Busra Agir, Morgan C. Nelson, Emmanuel Stephen Victor, Amber Thibeaux, Colton Hernandez, Jacob Tantalla, Aik C. Tan, Dinesh Rao, Matthew Williams, Micah J. Drummond, Ellen J. Beswick, June L. Round, H. Atakan Ekiz, Warren P/ Voth, Ryan M. O’Connell

Markey Cancer Center Faculty Publications

The rising incidence of advanced-stage colorectal cancer (CRC) and poor survival outcomes necessitate new and effective therapies. Immune checkpoint inhibitors (ICIs), specifically anti-PD-1 therapy, show promise, yet clinical determinants of a positive response are suboptimal. Here, we identify microRNA-155 (miR-155) as necessary for CD8 + T cell-infiltrated tumors through an unbiased in vivo CRISPR-Cas9 screen identifying functional tumor antigen-specific CD8+ T cell-expressed microRNAs. T cell miR-155 is required for anti-PD-1 responses and for a vital intratumor CD8 + T cell differentiation cascade by repressing Ship-1, inhibiting Tcf-1 and stemness, and subsequently enhancing Cxcr6 expression, anti-tumor immunity, and effector functions. Based …


Staying Sane In The Membrane: Neutral Sphingomyelinase 2 As A Master Regulator Of Plasma Membrane Ceramide, Zainuddin Quadri, Erhard Bieberich Feb 2025

Staying Sane In The Membrane: Neutral Sphingomyelinase 2 As A Master Regulator Of Plasma Membrane Ceramide, Zainuddin Quadri, Erhard Bieberich

Markey Cancer Center Faculty Publications

Ceramide, a key signaling sphingolipid in the plasma membrane, plays a pivotal role in fundamental cellular processes such as adhesion, polarity, and programmed cell death. The generation of plasma membrane ceramide is largely attributed to the activity of two types of sphingomyelinases: neutral sphingomyelinase 2 (nSMase2, Smpd3) and acid sphingomyelinase (aSMase, Smpd1). While many studies have explored ceramide generation following experimental activation of these enzymes, the mechanisms governing basal or steady- state ceramide levels have remained poorly understood. Using an innovative mass spectrometry approach developed in the Canals’ lab, the team has quantified the distinct contributions of nSMase2 and aSMase …


Bilirubin Bioconversion To Urobilin In The Gut-Liver-Kidney Axis: A Biomarker For Insulin Resistance In The Cardiovascular-Kidney-Metabolic (Ckm) Syndrome, Zachary A. Kipp, Olufunto O. Badmus, David E. Stec, Brantley Hall, Terry D. Hinds Jr. Feb 2025

Bilirubin Bioconversion To Urobilin In The Gut-Liver-Kidney Axis: A Biomarker For Insulin Resistance In The Cardiovascular-Kidney-Metabolic (Ckm) Syndrome, Zachary A. Kipp, Olufunto O. Badmus, David E. Stec, Brantley Hall, Terry D. Hinds Jr.

Markey Cancer Center Faculty Publications

The rising rates of obesity worldwide have increased the incidence of cardiovascular disease (CVD), making it the number one cause of death. Higher plasma bilirubin levels have been shown to prevent metabolic dysfunction and CVD. However, reducing levels leads to deleterious outcomes, possibly due to reduced bilirubin half-life that escalates the production of its catabolized product, urobilinogen, produced by gut bacteria and naturally oxidized to urobilin. Recent findings suggest that the involvement of the microbiome catabolism of bilirubin to urobilin and its absorption via the hepatic portal vein contributes to CVD, suggesting a liver-gut axis involvement. We discuss the studies …


Ddo-Adjuvanted Influenza A Virus Nucleoprotein Mrna Vaccine Induces Robust Humoral And Cellular Type 1 Immune Responses And Protects Mice From Challenge, Victoria Gnazzo, Hanaa Saleh, Ítalo A. Castro, Adrianus C. M. Boon, Amelia K. Pinto, James D. Brien, Carolina B. López Feb 2025

Ddo-Adjuvanted Influenza A Virus Nucleoprotein Mrna Vaccine Induces Robust Humoral And Cellular Type 1 Immune Responses And Protects Mice From Challenge, Victoria Gnazzo, Hanaa Saleh, Ítalo A. Castro, Adrianus C. M. Boon, Amelia K. Pinto, James D. Brien, Carolina B. López

Markey Cancer Center Faculty Publications

A challenge in viral vaccine development is to produce vaccines that generate both neutralizing antibodies to prevent infection and cytotoxic CD8+ T-cells that target conserved viral proteins and can eliminate infected cells to control virus spread. mRNA technology offers an opportunity to design vaccines based on conserved CD8-targeting epitopes, but achieving robust antigen-specific CD8+ T-cells remains a challenge. Here, we tested the viral-derived oligonucleotide DDO268 as an adjuvant in the context of a model influenza A virus (IAV) nucleoprotein (NP) mRNA vaccine in C57BL/6 mice. DDO268 when co-packaged with mRNA in lipid nanoparticles is sensed by RIG I-like receptors and …


The Mitochondria As An Emerging Target Of Self- Renewal In T-Cell Acute Lymphoblastic Leukemia, Majd Al-Hamaly, Evelyn Winter, Jessica S. Blackburn Feb 2025

The Mitochondria As An Emerging Target Of Self- Renewal In T-Cell Acute Lymphoblastic Leukemia, Majd Al-Hamaly, Evelyn Winter, Jessica S. Blackburn

Markey Cancer Center Faculty Publications

Acute lymphocytic leukemia (ALL) is the most common leukemia in children, with the T-cell subtype (T- ALL) accounting for 15% of those cases. Despite advancements in the treatment of T-ALL, patients still face a dismal prognosis following their first relapse. Relapse can be attributed to the inability of chemotherapy agents to eradicate leukemia stem cells (LSC), which possess self-renewal capabilities and are responsible for the long-term maintenance of the disease. Mitochondria have been recognized as a therapeutic vulnerability for cancer stem cells, including LSCs. Mitocans have shown promise in T-ALL both in vitro and in vivo, with some currently in …


Gdp-Mannose 4,6-Dehydratase Is A Key Driver Of Mycn- Amplified Neuroblastoma Core Fucosylation And Tumorigenesis, Beibei Zhu, Michelle G. Pitts, Michael D. Buoncristiani, Lindsay T. Bryant, Oscar Lopez-Nunez, Juan P. Gurria, Cameron Shedlock, Roberto Ribas, Shannon Keohane, Jinpeng Liu, Chi Wang, Matthew S. Gentry, Nathan R. Shelman, Derek B. Allison, B. Mark Evers, Ramon C. Sun, Eric J. Rellinger Feb 2025

Gdp-Mannose 4,6-Dehydratase Is A Key Driver Of Mycn- Amplified Neuroblastoma Core Fucosylation And Tumorigenesis, Beibei Zhu, Michelle G. Pitts, Michael D. Buoncristiani, Lindsay T. Bryant, Oscar Lopez-Nunez, Juan P. Gurria, Cameron Shedlock, Roberto Ribas, Shannon Keohane, Jinpeng Liu, Chi Wang, Matthew S. Gentry, Nathan R. Shelman, Derek B. Allison, B. Mark Evers, Ramon C. Sun, Eric J. Rellinger

Markey Cancer Center Faculty Publications

MYCN-amplification is a genetic hallmark of ~40% of high-risk neuroblastomas (NBs). Altered glycosylation is a common feature of adult cancer progression, but little is known about how genetic signatures such as MYCN-amplification alter glycosylation profiles. Herein, matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) revealed increased core fucosylated glycan abundance within neuroblast-rich regions of human MYCN-amplified NB tumors. GDP-mannose 4,6-dehydratase (GMDS) is responsible for the first-committed and rate-limiting step of de novo GDP-fucose synthesis. High GMDS expression was found to be associated with poor patient survival, advanced stage disease, and MYCN-amplification in human NB tumors. Chromatin immunoprecipitation and promoter reporter assays …


Duration Of Labor And Umbilical Artery Acidosis In Critical Congenital Heart Disease, Sarah Gwazdacz, Teresa Nguyen, Henry Yeh, Mary T. Donofrio, Timothy Bennett, Amanda Mcintosh Feb 2025

Duration Of Labor And Umbilical Artery Acidosis In Critical Congenital Heart Disease, Sarah Gwazdacz, Teresa Nguyen, Henry Yeh, Mary T. Donofrio, Timothy Bennett, Amanda Mcintosh

Posters

• Background (83 words): Standard delivery protocols for most prenatally diagnosed CCHD is induction of labor at 39 weeks with aims of a vaginal delivery (VD) near a tertiary care center. There is no benefit to planned Cesarean delivery (CD) over VD for most infants with CCHD. However, longer durations of labor (DOL) in CCHD have been described as a risk factor for umbilical artery (UA) acidosis. We aim to describe the relationship between DOL and UA pH and neonatal outcomes in those with prenatally diagnosed CCHD. • Methods (150 words): Retrospective chart review of prenatally diagnosed with CCHD born …


The Case For An International Severity Of Illness Scoring System, Alexander Tracy, Jorge Ibrain Figueira Salluh, Eirik Alnes Buanes, Dave A. Dongelmans, Stefano Finazz, Bharath Kumar Tirupakuzhi Vijayaraghavan, Nazir Lone, David Pilcher, Matti Reinikainen, Wangari Siika Feb 2025

The Case For An International Severity Of Illness Scoring System, Alexander Tracy, Jorge Ibrain Figueira Salluh, Eirik Alnes Buanes, Dave A. Dongelmans, Stefano Finazz, Bharath Kumar Tirupakuzhi Vijayaraghavan, Nazir Lone, David Pilcher, Matti Reinikainen, Wangari Siika

Anaesthesiology, East Africa

Severity of illness scores in the critical care context have evolved to serve multiple functions. These scores enable risk-adjusted outcomes to be benchmarked for the assessment of intensive care unit (ICU) performance, inform resource allocation, and enable the characterization of disease severity. Numerous illness severity scores have been developed to optimize calibration at the national level, but few studies have examined the international application of such scores.()

The COVID-19 pandemic demonstrated the value of benchmarking outcomes across heterogeneous populations and across various health care systems. Severity of illness scores were widely used to describe trial populations, assess treatment effects and …


Amputation Eras, Children's Mercy Kansas City Feb 2025

Amputation Eras, Children's Mercy Kansas City

Clinical Pathways

No abstract provided.


Investing In Limb Preservation: A Case Report In Avoiding Bilateral Amputation In A Vasculopathy Patient, Stephanie N. Campbell, Craig J. Verdin, Heather V. Tran, Nikita Gambhir Feb 2025

Investing In Limb Preservation: A Case Report In Avoiding Bilateral Amputation In A Vasculopathy Patient, Stephanie N. Campbell, Craig J. Verdin, Heather V. Tran, Nikita Gambhir

School of Podiatric Medicine Publications

Limb salvage and prosthetics play vital roles in restoring function and mobility for patients with severe injuries or metabolic conditions. Limb salvage involves surgical techniques aimed at preserving a limb rather than resorting to amputation, while prosthetics provide artificial devices to replace lost limbs. Key considerations for limb salvage include restoring a functional foot, maintaining patient independence, minimizing hospitalizations, and avoiding bilateral lower limb amputations.


Validation Of A Novel Landmark-Guided Intra-Articular Postero-Medial Surgeon-Administered Injection Technique, Nicolas S. Piuzzi, Andrew I. Spitzer, Jason Mussell, Ignacio Pasqualini, Stan Dysart, Jeffrey Gonzales, Michael A. Mont, Jess H. Lonner, William Mihalko Feb 2025

Validation Of A Novel Landmark-Guided Intra-Articular Postero-Medial Surgeon-Administered Injection Technique, Nicolas S. Piuzzi, Andrew I. Spitzer, Jason Mussell, Ignacio Pasqualini, Stan Dysart, Jeffrey Gonzales, Michael A. Mont, Jess H. Lonner, William Mihalko

School of Medicine Faculty Publications

Background: This study aimed to define an intra-articular surgeon-administered technique that may be comparable to ultrasound (US)-guided adductor canal block (ACB). Methods: Five cadaver lower limbs were examined. An anesthesiologist administered a US-guided ACB using 20 mL of dilute indocyanine dye. An orthopedic surgeon performed a medial parapatellar arthrotomy and introduced an 18-gauge needle 1-2 cm proximal to the palpated adductor tubercle angled posteromedially. Needle position and dye spread were fluoroscopically documented. Results: This technique consistently reached the infrapatellar branch of the saphenous nerve, nerve to the vastus medialis muscle, and posterior capsule, with minimal proximal dye spread. Conclusions: This …