Digital Commons Network^™

Considerations For Reporting Variants In Novel Candidate Genes Identified During Clinical Genomic Testing, Jessica X Chong, Seth I Berger, Samantha Baxter, Erica Smith, Changrui Xiao, Daniel G Calame, Megan H Hawley, E Andres Rivera-Munoz, Stephanie Ditroia, Genomics Research To Elucidate The Genetics Of Rare Diseases (Gregor) Consortium, Michael J Bamshad, Heidi L Rehm

Faculty, Staff and Students Publications

Since the first novel gene discovery for a Mendelian condition was made via exome sequencing, the rapid increase in the number of genes known to underlie Mendelian conditions coupled with the adoption of exome (and more recently, genome) sequencing by diagnostic testing labs has changed the landscape of genomic testing for rare diseases. Specifically, many individuals suspected to have a Mendelian condition are now routinely offered clinical ES. This commonly results in a precise genetic diagnosis but frequently overlooks the identification of novel candidate genes. Such candidates are also less likely to be identified in the absence of large-scale gene …

Unraveling The Link: Seizure Characteristics And Ammonia Levels In Urea Cycle Disorder During Hyperammonemic Crises, Mongkol Chanvanichtrakool, John M Schreiber, Wei-Liang Chen, John Barber, Anqing Zhang, Nicholas Ah Mew, Andreas Schulze, Greta Wilkening, Sandesh C S Nagamani, Andrea Gropman, Urea Cycle Disease Consortium

Faculty, Staff and Students Publications

Background: This retrospective clinical study performed at a single clinical center aimed to identify the prevalence of seizures in individuals with urea cycle disorders (UCDs) with and without hyperammonemic (HA) crises. In addition, we sought to correlate the utility of biochemical markers and electroencephalography (EEG) in detecting subclinical seizures during HA.

Methods: Medical records of individuals with UCDs enrolled in Urea Cycle Disorders Consortium Longitudinal Study (UCDC-LS) (NCT00237315) at Children's National Hospital between 2006 and 2022 were reviewed for evidence of clinical and subclinical seizuress during HA crises, and initial biochemical levels concurrently.

Results: Eighty-five individuals with UCD …

Construction Contracting In The Zero Emission Transportation Sector: Evidence From Underrepresented Businesses, Gökçe Soydemir, Orestis P. Panagopoulos

Mineta Transportation Institute

This study investigates the degree to which underrepresented construction contractors face challenges in California's zero-emission transportation sector to devise a simpler and more efficient bonding structure. Using a survey dispersed over underrepresented businesses across the state, the study provides several suggestions for a statewide bonding program that caters to the needs of contractors. Both qualitative and quantitative methods are used in the study. The survey data are evaluated using econometric tools to analyze whether there are any statistically significant associations between contractors' characteristics and their industry experiences. Focus groups and focused interviews are conducted to identify those perspectives the survey …

Are California’S Local Jurisdictions Disproportionately Directing Growth Toward Existing Disadvantaged Communities? Evidence From The Southern California And San Francisco Bay Area Regions, Shishir Mathur, Christopher Ferrell

Mineta Transportation Institute

Communities across the United States are striving to promote smart urban growth through compact urban infill residential development. They are doing so to mitigate sprawl's negative fiscal, environmental, social, and physical impacts, strengthen land use-housing-transportation linkages, and develop at densities needed for well-functioning public transit. Some states, such as California, have gone a step further by linking compact urban infill development as critical to meeting greenhouse gas (GHG) reduction targets. Anecdotal evidence suggests some California local jurisdictions are planning disproportionately large amounts of new urban development in disadvantaged communities (DACs). However, empirical evidence is lacking. This study aims to fill …

Hospital Acquired Venous Thromboembolism In Children With Sickle Cell Disease, Shreya Agarwal, Kayla L Foster, Shaniqua J Anum, Mary C Shapiro, Hyojeong Han, Michael E Scheurer, Gladstone Airewele, Sarah E Sartain

Faculty, Staff and Students Publications

Sickle cell disease (SCD) is well recognized as a hypercoagulablestate, however, it remains unclear whether a subgroup of children with SCD at higher risk of venous thromboembolic event (VTE) during hospitalization may benefit from thromboprophylaxis. Our objectives were to describe the clinical characteristics, outcomes and recurrence of hospital acquired VTE in patients with SCD younger than 21 years. This was a single center retrospective study. Data regarding demographics, reason for admission, location of VTE, risk factors like central venous catheter (CVC), intensive care unit (ICU) admission among others were extracted from electronic medical records over a 10-year study period (2011-2021). …

What Would Happen In The United States If There Were No Cow Milk-Based Preterm Infant Nutritional Products: Historical Perspective And Evaluation Of Nutrient-Related Challenges, Steven A Abrams, Robert J Shulman

Faculty, Staff and Students Publications

Recent litigation has led to a situation where preterm cow milk-based infant nutritional products (PCMBPs) may soon have limited or no availability in the United States. Given their limited availability, similar products based only on human milk are unlikely to meet the needs of most preterm infants requiring such products, especially those born >1500 g or very preterm infants born at < 1500 g after they reach 34-35 wk postmenstrual age. Alternative nutritional strategies, used before the introduction of specialized preterm products, would require modular nutrient additions to a formula designed for full-term infants and donor or maternal milk. The addition of modular products would require careful calibration to provide needed macro and micronutrients which would expose infants to risks of contamination, poor growth, and limited bioavailability of some of these modulars. Substantial risks of metabolic derangements, and ultimately, poor outcomes would occur. In the long-term greater availability and support for the use of human milk-based products is needed. However, policymakers cannot assume that PCMBPs will not be critically needed and should identify strategies for their continued marketplace availability.

Isolated Psychiatric Symptoms In Children With Anti-N-Methyl-D Aspartate Receptor Encephalitis, Grace Gombolay, J Nicholas Brenton, Jennifer H Yang, Coral M Stredny, Ryan Kammeyer, Kristen S Fisher, Alexander J Sandweiss, Timothy A Erickson, Varun Kannan, Catherine Otten, Claude Steriade, Ngochanh Vu, Jonathan D Santoro, Karla Robles-Lopez, Robert Goodrich, Scott Otallah, Janetta Arellano, Andrew Christiana, Morgan Morris, Mark P Gorman, Alexandra B Kornbluh, Ilana Kahn, Leigh Sepeta, Yike Jiang, Eyal Muscal, Kristy O Murray, Manikum Moodley, Duriel Hardy

Faculty, Staff and Students Publications

Background: Isolated psychiatric symptoms can be the initial symptom of pediatric anti-N-methyl-d-aspartate (NMDA) receptor autoimmune encephalitis (pNMDARE). Here we report on the prevalence of isolated psychiatric symptoms in pNMDARE. We also assess whether initial neurodiagnostic tests (brain magnetic resonance imaging [MRI], electroencephalography [EEG], and/or cerebrospinal fluid [CSF] white blood cell count) are abnormal in children with isolated psychiatric symptoms and pNMDARE.

Methods: This multicenter retrospective cohort study from CONNECT (Conquering Neuroinflammation and Epilepsies Consortium) from 14 institutions included children under age 18 years who were diagnosed with pNMDARE. Descriptive statistics using means, medians, and comparisons for continuous versus discrete data …

The Fallacy Of Electronic Cigarettes For Tobacco Dependence, Harold J Farber, Carlos Rábade Castedo, Carlos A Jimenez-Ruiz, Manuel Conrado Pacheco

Faculty, Staff and Students Publications

No abstract provided.

Anger Outbursts In Youth With Asd And Anxiety: Phenomenology And Relationship With Family Accommodation, Allie N Townsend, Andrew G Guzick, Alyssa G Hertz, Connor M Kerns, Wayne K Goodman, Leandra N Berry, Philip C Kendall, Jeffrey J Wood, Eric A Storch

Faculty, Staff and Students Publications

Anger outbursts (AO) are associated with severe symptoms, impairment and poorer treatment outcomes for anxious children, though limited research has examined AO in youth with co-occurring autism and anxiety disorders. This study examined AO in children with autism and anxiety by evaluating clinical characteristics, family accommodation, and changes in AO following anxiety-focused treatment. The sample comprised 167 youth with autism and anxiety enrolled in a multi-site randomized clinical trial comparing standard care CBT for anxiety, CBT adapted for youth with autism, and usual care. Most participants (60%) had AO, which contributed to impairment above and beyond anxiety and autism. AO …

Psychometric Evaluation Of Clinician- And Caregiver-Reported Clinical Severity Assessments For Individuals With Cdkl5 Deficiency Disorder, Jacinta M Saldaris, Peter Jacoby, Jenny Downs, Eric D Marsh, Helen Leonard, Elia Pestana-Knight, Rajsekar Rajaraman, Judith Weisenberg, Bernhard Suter, Heather E Olson, Dana Price, William Hong, Erin Prange, Tim A Benke, Scott Demarest

Faculty, Staff and Students Publications

Objective: The CDKL5 Clinical Severity Assessment (CCSA) is a comprehensive, content-validated measurement tool capturing the diverse challenges of cyclin-dependent kinase-like 5 (CDKL5) deficiency disorder (CDD), a genetically caused developmental epileptic encephalopathy (DEE). The CCSA is divided into clinician-reported (CCSA-Clinician) and caregiver-reported (CCSA-Caregiver) assessments. The aim of this study was to evaluate the factor structure of these measures through confirmatory factor analysis (CFA) and evaluate their validity and reliability.

Methods: Participants were recruited from the International CDKL5 Clinical Research Network to take part in an in-clinic CCSA-Clinician evaluation (n = 148) and/or complete the CCSA-Caregiver questionnaire (n = 198). CFA was …

Dsm-5 Criterion-A-Based Trauma Types In Service Members And Veterans Seeking Treatment For Posttraumatic Stress Disorder, Natasha Benfer, Breanna Grunthal, Katherine A Dondanville, Stacey Young-Mccaughan, Abby Blankenship, Chadi G Abdallah, Sudie E Back, Julianne Flanagan, Edna B Foa, Peter T Fox, John H Krystal, Brian P Marx, Donald D Mcgeary, Carmen P Mclean, Kristi E Pruiksma, Patricia A Resick, John D Roache, Paulo Shiroma, Denise M Sloan, Daniel J Taylor, Jennifer Schuster Wachen, Argelio L López-Roca, Karin L Nicholson, Richard P Schobitz, Christian C Schrader, Allah-Fard M Sharrieff, Jeffrey S Yarvis, Jim Mintz, Terence M Keane, Alan L Peterson, Brett T Litz

Faculty, Staff and Students Publications

Objective: In posttraumatic stress disorder (PTSD), the assumption of the equipotentiality of traumas ignores potentially unique contexts and consequences of different traumas. Accordingly, Stein et al. (2012) developed a reliable typing scheme in which assessors categorized descriptions of traumatic events into six "types": life threat to self (LTS), life threat to other, aftermath of violence (AV), traumatic loss, moral injury by self (MIS), and moral injury by other (MIO). We extended this research by validating the typing scheme using participant endorsements of type, rather than assesor-based types. We examined the concordance of participant and assesor types, frequency, and validity …

Cumulative Radiation Exposure And Lifetime Cancer Risk In Patients With Tetralogy Of Fallot Requiring Early Intervention, Jeannette R Wong-Siegel, Andrew C Glatz, Courtney Mccracken, Choonsik Lee, Cari M Kitahara, Lene H S Veiga, Yun Zhang, Bryan H Goldstein, Christopher J Petit, Athar M Qureshi, George T Nicholson, Mark A Law, Jeffery Meadows, Shabana Shahanavaz, Michael L O'Byrne, Sarosh P Batlivala, Joelle Pettus, Asaad Beshish, Christopher E Mascio, Jennifer C Romano, Kathyrn O Stack, Ivor Asztalos, Tacy E Downing, Jeffrey D Zampi

Faculty, Staff and Students Publications

Background: Neonates with tetralogy of Fallot and symptomatic cyanosis (sTOF) require early intervention, utilizing either a staged repair (SR) or primary repair (PR) approach. They are exposed to several sources of low-dose ionizing radiation, which may contribute to increased cancer risk.

Objectives: The purpose of this study was to compare cumulative radiation exposure and associated lifetime attributable risk (LAR) of cancer between treatment strategies in sTOF.

Methods: Neonates with sTOF who underwent SR or PR from 2012 to 2017 were retrospectively reviewed from the Congenital Cardiac Research Collaborative. Radiation exposure from all radiologic studies prior to 18 months of age …

Demystifying Hispanic Versus Latino/A Versus Latinx: Which Do Emergency Department Patients Prefer?, Melanie F Molina, Anita N Chary, Karen Reyes, James S Ford, Brian Chinnock, Robert M Rodriguez

Faculty, Staff and Students Publications

No abstract provided.

Long Covid Among Undocumented Latino Immigrant Populations In The Emergency Department, Karen P Reyes, Zubaid Rafique, Brian Chinnock, Vijaya Arun Kumar, Michael Gottlieb, Kristin L Rising, Robert M Rodriguez

Faculty, Staff and Students Publications

This cross-sectional study assesses the understanding of and access to care for long COVID symptoms among undocumented Latino immigrants in US emergency departments (EDs).

Dcrm 20: Multispecialty Practice Recommendations For The Management Of Diabetes, Cardiorenal, And Metabolic Diseases, Yehuda Handelsman, John E Anderson, George L Bakris, Christie M Ballantyne, Deepak L Bhatt, Zachary T Bloomgarden, Biykem Bozkurt, Matthew J Budoff, Javed Butler, David Z I Cherney, Ralph A Defronzo, Stefano Del Prato, Robert H Eckel, Gerasimos Filippatos, Gregg C Fonarow, Vivian A Fonseca, W Timothy Garvey, Francesco Giorgino, Peter J Grant, Jennifer B Green, Stephen J Greene, Per-Henrik Groop, George Grunberger, Ania M Jastreboff, Paul S Jellinger, Kamlesh Khunti, Samuel Klein, Mikhail N Kosiborod, Pamela Kushner, Lawrence A Leiter, Norman E Lepor, Christos S Mantzoros, Chantal Mathieu, Christian W Mende, Erin D Michos, Javier Morales, Jorge Plutzky, Richard E Pratley, Kausik K Ray, Peter Rossing, Naveed Sattar, Peter E H Schwarz, Eberhard Standl, P Gabriel Steg, Lale Tokgözoğlu, Jaakko Tuomilehto, Guillermo E Umpierrez, Paul Valensi, Matthew R Weir, John Wilding, Eugene E Wright

Faculty, Staff and Students Publications

The spectrum of cardiorenal and metabolic diseases comprises many disorders, including obesity, type 2 diabetes (T2D), chronic kidney disease (CKD), atherosclerotic cardiovascular disease (ASCVD), heart failure (HF), dyslipidemias, hypertension, and associated comorbidities such as pulmonary diseases and metabolism dysfunction-associated steatotic liver disease and metabolism dysfunction-associated steatohepatitis (MASLD and MASH, respectively, formerly known as nonalcoholic fatty liver disease and nonalcoholic steatohepatitis [NAFLD and NASH]). Because cardiorenal and metabolic diseases share pathophysiologic pathways, two or more are often present in the same individual. Findings from recent outcome trials have demonstrated benefits of various treatments across a range of conditions, suggesting a need …

The Undiagnosed Diseases Network: Characteristics Of Solvable Applicants And Diagnostic Suggestions For Nonaccepted Ones, John J Mulvihill, Laura Findley, Weihong Ni, Janet S Sinsheimer, F Session Cole, Cecilia Esteves, Jonathan A Bernstein, John H Newman, Matthew T Wheeler, Jill R Mokry, Undiagnosed Diseases Network

Faculty, Staff and Students Publications

Purpose: Can certain characteristics identify as solvable some undiagnosed patients who seek extensive evaluation and thorough record review, such as by the Undiagnosed Diseases Network (UDN)?

Methods: The UDN is a national research resource to solve medical mysteries through team science. Applicants provide informed consent to access to their medical records. After review, expert panels assess if applicants meet inclusion and exclusion criteria to select participants. When not accepting applicants, UDN experts may offer suggestions for diagnostic efforts. Using minimal information from initial applications, we compare features in applicants who are not accepted with those who are accepted and either …

Stareg: Statistical Replicability Analysis Of High Throughput Experiments With Applications To Spatial Transcriptomic Studies, Yan Li, Xiang Zhou, Rui Chen, Xianyang Zhang, Hongyuan Cao

Faculty, Staff and Students Publications

Replicable signals from different yet conceptually related studies provide stronger scientific evidence and more powerful inference. We introduce STAREG, a statistical method for replicability analysis of high throughput experiments, and apply it to analyze spatial transcriptomic studies. STAREG uses summary statistics from multiple studies of high throughput experiments and models the the joint distribution of p-values accounting for the heterogeneity of different studies. It effectively controls the false discovery rate (FDR) and has higher power by information borrowing. Moreover, it provides different rankings of important genes. With the EM algorithm in combination with pool-adjacent-violator-algorithm (PAVA), STAREG is scalable to datasets …

Contemporary Epidemiology Of Hepatocellular Carcinoma: Understanding Risk Factors And Surveillance Strategies, Fouad Jaber, George Cholankeril, Hashem B El-Serag

Faculty, Staff and Students Publications

The contemporary epidemiology of hepatocellular carcinoma (HCC) shows a shift in the main etiological risk factors from less common but highly virulent (eg, hepatitis C and B) to more common but weak risk factors (eg, alcohol and metabolic syndrome). Therefore, we are in a seemingly paradoxical state of declining overall incidence rates of HCC-related to improved prevention and treatment of viral hepatitis but burgeoning number of people at an elevated risk of HCC. Several geographic regions have reported an increase in HCC attributable to alcoholic liver disease and metabolic dysfunction associated with steatotic liver disease (MASLD). The importance of risk …

Changes In Conjunctival Mononuclear Phagocytes And Suppressive Activity Of Regulatory Macrophages In Desiccation Induced Dry Eye, Jehan Alam, Ebru Yaman, Cintia S De Paiva, De-Quan Li, Gerda Cristal Villalba Silva, Zhen Zuo, Stephen C Pflugfelder

Faculty, Staff and Students Publications

Purpose: To evaluate the effects of dry eye on conjunctival immune cell number and transcriptional profiles with attention to mononuclear phagocytes.

Methods: Expression profiling was performed by single-cell RNA sequencing on sorted conjunctival immune cells from non-stressed and C57BL/6 mice subjected to desiccating stress (DS). Monocle 3 modeled cell trajectory, scATAC-seq assessed chromatin accessibility and IPA identified canonical pathways. Inflammation and goblet cells were measured after depletion of MRC1+ MΦs with mannosylated clodronate liposomes.

Results: Mononuclear phagocytes (monocytes, MΦs, DCs) comprised 72 % of immune cells and showed the greatest changes with DS. Distinct DS induced gene expression patterns were …

Novel Genes Of The Male Reproductive System: Potential Roles In Male Reproduction And As Non-Hormonal Male Contraceptive Targets, Thomas X Garcia, Martin M Matzuk

Faculty, Staff and Students Publications

The development of novel non-hormonal male contraceptives represents a pivotal frontier in reproductive health, driven by the need for safe, effective, and reversible contraceptive methods. This comprehensive review explores the genetic underpinnings of male fertility, emphasizing the crucial roles of specific genes and structural variants (SVs) identified through advanced sequencing technologies such as long-read sequencing (LRS). LRS has revolutionized the detection of structural variants and complex genomic regions, offering unprecedented precision and resolution over traditional next-generation sequencing (NGS). Key genetic targets, including those implicated in spermatogenesis and sperm motility, are highlighted, showcasing their potential as non-hormonal contraceptive targets. The review …

Addressing Platelet Insecurity – A National Call To Action, Eric A Gehrie, Pampee P Young, Sridhar V Basavaraju, Arthur W Bracey, Andrew P Cap, Liz Culler, Nancy M Dunbar, Mary Homer, Iris Isufi, Rob Macedo, Tanya Petraszko, Glenn Ramsey, Christopher A Tormey, Richard M Kaufman, Edward L Snyder

Faculty, Staff and Students Publications

No abstract provided.

Are Veterans At Increased Risk Of Myeloproliferative Neoplasms?, Christin B Destefano, Nicholas Burwick, Drew A Helmer

Faculty, Staff and Students Publications

No abstract provided.

Evaluating Progress And Accountability For Achieving Cop26 Health Programme International Ambitions For Sustainable, Low-Carbon, Resilient Health-Care Systems, Iris Martine Blom, Fawzia N Rasheed, Hardeep Singh, Matthew J Eckelman, Meghnath Dhimal, Martin Hensher, Renzo R Guinto, Alice Mcgushin, Xuejuan Ning, Poornima Prabhakaran, Marina Romanello, Dana Van Alphen, Nick Watts, Jessica C Yu, Carol Zavaleta-Cortijo, Andrea J Macneill, Jodi D Sherman

Faculty, Staff and Students Publications

A global initiative to develop low-carbon, resilient health systems-the COP26 Health Programme-launched at the UN Framework Convention on Climate Change 26th Conference of the Parties (COP26) in 2021. As of May, 2024, 83 nations have committed to participate in this initiative. This analysis evaluates the effectiveness of existing and proposed indicators towards public monitoring and accountability to these commitments. Our findings reveal substantial gaps in data availability and indicator relevance, with many countries reporting process indicators that do not reflect actual progress towards achieving sustainable health-care systems. We found a dearth of suitable indicators and an urgent need to develop …

Integrated Safety And Efficacy Analyses Of Phase 3 Trials Of A Microbiome Therapeutic For Recurrent Cdi, Colleen S Kraft, Matthew Sims, Michael Silverman, Thomas J Louie, Paul Feuerstadt, Edward S Huang, Sahil Khanna, Charles S Berenson, Elaine E L Wang, Stuart H Cohen, Louis Korman, Christine Lee, Colleen R Kelly, Alberto Odio, Paul P Cook, Bret Lashner, Mayur Ramesh, Princy Kumar, Ananya De, Asli Memisoglu, David A Lombardi, Brooke R Hasson, Barbara H Mcgovern, Lisa Von Moltke, Darrell S Pardi, Ecospor Iii And Ecospor Iv Investigators

Faculty, Staff and Students Publications

INTRODUCTION: Recurrent Clostridioides difficile infection (rCDI) often occurs after standard-of-care antibiotics. VOWST oral spores (VOS, previously SER-109), an FDA-approved orally administered microbiome therapeutic, is indicated to prevent rCDI following antibiotics for rCDI.

OBJECTIVE, DESIGN, AND PATIENTS: To evaluate safety and efficacy of VOS from two phase 3 trials, (randomized, placebo-controlled [ECOSPOR III: NCT03183128] and open-label, single arm [ECOSPOR IV: NCT03183141]) of 349 adults with rCDI and prevalent comorbidities.

METHODS: VOS or placebo [ECOSPOR III only] (4 capsules once daily for 3 days). Integrated analysis of treatment-emergent adverse events (TEAEs) collected through week 8; serious TEAEs and TEAEs of special interest …

Perineuronal Nets’ Role In Metabolism, Nan Zhang, Beite Song, Peng Bai, Li Du, Lulu Chen, Yong Xu, Tianshu Zeng

Faculty, Staff and Students Publications

Perineuronal nets (PNNs), specialized extracellular matrix (ECM) structures that envelop neurons, have recently been recognized as key players in the regulation of metabolism. This review explores the growing body of knowledge concerning PNNs and their role in metabolic control, drawing insights from recent research and relevant studies. The pivotal role of PNNs in the context of energy balance and whole body blood glucose is examined. This review also highlights novel findings, including the effects of astroglia, microglia, sex and gonadal hormones, nutritional regulation, circadian rhythms, and age on PNNs dynamics. These findings illuminate the complex and multifaceted role of PNNs …

Characterization And Visualization Of Tandem Repeats At Genome Scale, Egor Dolzhenko, Adam English, Harriet Dashnow, Guilherme De Sena Brandine, Tom Mokveld, William J Rowell, Caitlin Karniski, Zev Kronenberg, Matt C Danzi, Warren A Cheung, Chengpeng Bi, Emily Farrow, Aaron Wenger, Khi Pin Chua, Verónica Martínez-Cerdeño, Trevor D Bartley, Peng Jin, David L Nelson, Stephan Zuchner, Tomi Pastinen, Aaron R Quinlan, Fritz J Sedlazeck, Michael A Eberle

Faculty, Staff and Students Publications

Tandem repeat (TR) variation is associated with gene expression changes and numerous rare monogenic diseases. Although long-read sequencing provides accurate full-length sequences and methylation of TRs, there is still a need for computational methods to profile TRs across the genome. Here we introduce the Tandem Repeat Genotyping Tool (TRGT) and an accompanying TR database. TRGT determines the consensus sequences and methylation levels of specified TRs from PacBio HiFi sequencing data. It also reports reads that support each repeat allele. These reads can be subsequently visualized with a companion TR visualization tool. Assessing 937,122 TRs, TRGT showed a Mendelian concordance of …

Metabolic Dependencies Of Acute Myeloid Leukemia Stem Cells, Xiangguo Shi, Mengdie Feng, Daisuke Nakada

Faculty, Staff and Students Publications

Acute myeloid leukemia (AML) is a heterogeneous hematologic malignancy primarily driven by an immature population of AML cells termed leukemia stem cells (LSCs) that are implicated in AML development, chemoresistance, and relapse. An emerging area of research in AML focuses on identifying and targeting the aberrant metabolism in LSCs. Dysregulated metabolism is involved in sustaining functional properties of LSCs, impeding myeloid differentiation, and evading programmed cell death, both in the process of leukemogenesis and in response to chemotherapy. This review discusses recent discoveries regarding the aberrant metabolic processes of AML LSCs that have begun to change the therapeutic landscape of …

Cancer Drug-Tolerant Persister Cells: From Biological Questions To Clinical Opportunities, Mariangela Russo, Mengnuo Chen, Elisa Mariella, Haoning Peng, Sumaiyah K Rehman, Elena Sancho, Alberto Sogari, Tzen S Toh, Nathalie Q Balaban, Eduard Batlle, Rene Bernards, Mathew J Garnett, Matthew Hangauer, Eleonora Leucci, Jean-Christophe Marine, Catherine A O'Brien, Yaara Oren, E Elizabeth Patton, Caroline Robert, Susan M Rosenberg, Shensi Shen, Alberto Bardelli

Faculty, Staff and Students Publications

The emergence of drug resistance is the most substantial challenge to the effectiveness of anticancer therapies. Orthogonal approaches have revealed that a subset of cells, known as drug-tolerant 'persister' (DTP) cells, have a prominent role in drug resistance. Although long recognized in bacterial populations which have acquired resistance to antibiotics, the presence of DTPs in various cancer types has come to light only in the past two decades, yet several aspects of their biology remain enigmatic. Here, we delve into the biological characteristics of DTPs and explore potential strategies for tracking and targeting them. Recent findings suggest that DTPs exhibit …

Perspectives On Hand Hygiene In Belizean Healthcare Facilities During The Covid-19 Pandemic: A Qualitative Evaluation With Healthcare Workers, Kelsey Mcdavid, Christina Craig, Anh N Ly, Nicholas Bivens, Francis Morey, Russell Manzanero, Gerhaldine Morazan, Ella Hawes, Alexandra Medley, Kristy Murray, Matthew Lozier

Faculty, Staff and Students Publications

The World Health Organization recommends healthcare workers (HCWs) practice hand hygiene (HH) while providing care. Making alcohol-based hand rub (ABHR) available at points of care is recommended during times of high patient volume, such as the COVID-19 pandemic. In low- and middle-income countries, such as Belize, there may be limited access to HH materials within healthcare facilities (HCF). This paper examines the motivators and barriers to HH among HCWs in the 11 largest public healthcare facilities in Belize and HCWs' experiences with an intervention. In 2021, focus group discussions (FGDs) gathered HCWs' HH perceptions and preferences. An intervention was then …

Does Delaying Levodopa Prevent Motor Complications In Parkinson's Disease? A Meta-Analysis, Luis Guilherme Ramanzini, Julia M Frare, Luís F M Camargo, Juliana O F Silveira, Joseph Jankovic

Faculty, Staff and Students Publications

Background: There has been a long debate whether delaying treatment with levodopa prevents motor complications in Parkinson's disease (PD).

Objectives: We performed a meta-analysis on randomized clinical trials (RCTs) that compared early- versus delayed-start treatment with levodopa in PD.

Methods: A systematic review was conducted in PubMed, EMBASE, and Web of Science databases from inception to July 1, 2023. Only RCTs that compared early and delayed levodopa treatment in PD were included. Non-randomized comparisons from follow-up studies were included as well. Our primary outcomes were occurrence of overall motor complications, motor fluctuations, and dyskinesias.

Results: Seven studies with a total …