Medical Sciences Commons^™

Strategies To Increase Attendance In Substance Use Disorder Group Treatment: Results From A Randomized Controlled Trial, Liliane Cambraia Windsor, Heather A Jones, Carla Ellis, Kennya Hooper, Andrea Rucker, Salma Musaad, Moses Okumu

Faculty, Staff and Students Publications

Background: Attendance in substance-use-disorder group-treatment is challenging with only 32% of patients attending at least one session (Substance Abuse and Mental Health Services Administration and Center for Behavioral Health Statistics and Quality. Treatment Episode Data Set (TEDS): 2023 admissions to and discharges from substance use treatment services reported by single state agencies, Bethesda, 2025). The present study tested a set of strategies to increase group session attendance in Community Wise, an innovative evidence-based group-intervention delivered in harm-reduction-community-based agencies and designed to reduce alcohol and substance use among people with substance-use-disorders living in predominantly Black and disinvested communities. We examined: (1) …

A Systematic Literature Review Of Cvid Reveals Pervasive Detrimental Noninfectious Manifestations, Robert B Lindell, Samir U Sayed, Jose S Campos Duran, Sydney A Sheetz, Apoorva Babu, Montana S Knight, Andrea A Mauracher, Ceire A Hay, Peyton E Conrey, Julie C Fitzgerald, Nadir Yehya, Stephen T Famularo, Teresa Arroyo, Richard Tustin, Hossein Fazelinia, Edward M Behrens, David T Teachey, Lisa R Forbes Satter, Alexandra F Freeman, Jenna Re Bergerson, Steven M Holland, Jennifer W Leiding, Scott L Weiss, Mark W Hall, Deanne M Taylor, Rui Feng, E John Wherry, Nuala J Meyer, Sarah E Henrickson

Faculty, Staff and Students Publications

BACKGROUND

Sepsis is a leading cause of morbidity and mortality in critically ill children, yet heterogeneous immune responses complicate the development of targeted therapies and the host immune factors driving sepsis pathobiology remain unclear.

METHODS

We integrated deep immune phenotyping, plasma proteomics, single-cell transcriptomics, and phosphoflow cytometry in a prospective cohort of 88 critically ill children to elucidate the mechanisms underlying immune heterogeneity.

RESULTS

Unsupervised clustering of plasma cytokines identified 3 immunologic subgroups, including a high-severity group (“Group C”) characterized by hypercytokinemia driven by IL-6 and IFN-γ. Group C exhibited distinct alterations in immune cell frequency and activation, with a …

Uncovering Phenotypic Expansion In Axin2-Related Disorders Through Precision Animal Modeling, Nathalie M Aceves-Ewing, Denise G Lanza, Paul C Marcogliese, Di Lu, Chih-Wei Hsu, Hirokazu Hashimoto, Matthew Gonzalez, Audrey E Christiansen, Tara L Rasmussen, Alex J Ho, Angelina Gaspero, Cher Sha, Mary E Dickinson, Bo Yuan, Brian J Shayota, Stephanie Pachter, Xiaolin Hu, Debra Lynn Day-Salvatore, Laura Mackay, Oguz Kanca, Michael F Wangler, Lorraine Potocki, Jill A Rosenfeld, Richard Alan Lewis, Hsiao-Tuan Chao, Brendan Lee, Lauren Blieden, Barry N Wasserman, Dorine A Bax, Nicola K Ragge, Sukyeong Lee, Undiagnosed Diseases Network, Baylor College Of Medicine Center For Precision Medicine Models, Shinya Yamamoto, Hugo J Bellen, Lindsay C Burrage, Jason D Heaney

Faculty, Staff and Students Publications

Purpose: Heterozygous pathogenic variants in AXIN2 (HGNC 904) cause oligodontia-colorectal cancer syndrome (ODCRCS). We identified five individuals with de novo, heterozygous variants (NM_004655.4:c.196G>A p.(Glu66Lys), c.197A>G p.(Glu66Gly), and c.199G>A p.(Gly67Arg)) in AXIN2. Common phenotypes among these individuals included ectodermal dysplasia, global developmental delay, microcephaly, and limb, ophthalmologic, and genitourinary abnormalities.

Methods: Structural modeling was performed to predict the impact of these variants on AXIN2. A prime editing N1 screen of mouse embryos was performed to test whether the p.Glu66Lys variant produces a phenotype. Drosophila models were used to test the effect of this variant on Wnt signaling.

Results: …

Thanks For The Signal-Now What? Program Director Perspectives On How Preference Signals Are Shaping General Surgery Residency Recruitment, John M Woodward, Connie Y Gan, Darci C Foote, Tasha Posid, Nicole M Santucci, Noosha D Deravi, Caitlin Silvestri, Kirstyn E Brownson, Erika Simmerman Mabes, Rondi Gelbard, Milanie Milan, Nina Zhao, Dylan R Nieman, Martha Godfrey, Benjamin D Ferguson, Joseph C L'Huillier, Colleen Mcdermott, Prajjwol Luitel, Olabisi Sheppard, Jennifer H Chen, Emma G Burke, Jenny M Guido, Ladonna Kearse, Jonathan Davies, Trenton Foster, Sarah Lund

Faculty, Staff and Students Publications

Objective: We aimed to explore general surgery program director (PD) experiences with and perspectives on preference signaling in a 15-signal system.

Design: We performed qualitative analysis of de-identified transcripts from semi-structured interviews of general surgery PDs.

Setting: General surgery PDs across the United States.

Participants: All general surgery PDs in the spring of 2025 were invited to participate. Fifteen PDs volunteered to participate in semi-structured interviews (73% university-based, 53% programs with < 8 residents/class).

Results: PDs highlighted that signals saved time when utilized as a screening tool, which gave PDs more time for holistic review of applications. PDs also felt signaling increased equity …

Pneumococcal Colonization In Pediatric Patients Undergoing Hematopoietic Cell Transplantation, Liset Olarte, Jennifer E Schuster, Ibrahim Ahmed, Kristina G Hulten

Faculty, Staff and Students Publications

Despite the increased risk of invasive pneumococcal disease among pediatric hematopoietic cell transplant (HCT) recipients, pneumococcal colonization has not been evaluated in this population. We prospectively assessed longitudinal pneumococcal colonization in 22 pediatric HCT recipients from conditioning therapy to 100 days post-HCT. A higher likelihood of pneumococcal colonization was observed in the late post-HCT period (weeks 9-14) compared with the early post-HCT period (weeks 1-8), with odds increasing with each additional week after conditioning.IMPORTANCEThis is the first study to longitudinally evaluate pneumococcal colonization in pediatric hematopoietic cell transplant (HCT) recipients from the onset of conditioning therapy to 100 days post-HCT. …

Tau Pathology In Epilepsy: Emerging Mechanisms And Translational Opportunities, Arjune Sen, Xin You Tai, Aristea Galanopoulou, Maria Thom, Eleonora Aronica, Lucy Vivash, Martin Hardmeier, Action Amos, Stephan Rueegg, Matthias Koepp, Yaroslav Winter, Christoph Helmstaedter, Jeffrey L Noebels, Hilal A Lashuel, Terence J O'Brien

Faculty, Staff and Students Publications

The onset of epilepsy in adulthood occurs most commonly after 55 years of age. Given the ageing global population, this disorder represents an increasing burden on healthcare and society. The bidirectional link between epilepsy and dementia is a focus of intense research with underlying tau pathology highlighted as a potential mechanistic link. In this review, we examine the evidence for tau-related neurodegenerative processes in epilepsy beginning with how changes in biochemical and structural properties of the tau protein can lead to abnormal phosphorylation and pathological aggregation. We consider the role of tau in seizure occurrence and cognitive difficulties in experimental …

Single-Nucleotide Rna M6a Mapping In Bovine Preimplantation Development Reveals Site-Specific Regulation Of Rpl12 At Zygotic Genome Activation, Rajan Iyyappan, Yichi Niu, Yang Li, Hao Ming, Kinga Pajdzik, Noah R Rakestraw, Piyush K Jain, Chuan He, Chenghang Zong, Zongliang Jiang

Faculty, Staff and Students Publications

RNA N6-methyladenosine (m6A) is a key regulator of gene expression during early embryogenesis. Using SAC-seq (m6A-selective allyl chemical labeling and sequencing), an antibody-independent m6A profiling method, we generated the first single-nucleotide-resolution m6A map of bovine oocytes and preimplantation embryos. We observed both coordinated and uncoupled relationships between m6A modification and expression of protein-coding and noncoding genes. Integrative analysis of the transcriptome, m6A epitranscriptome, and translatome revealed dynamic m6A remodeling, particularly in ribosomal protein genes. Functional interrogation of a specific m6A site within the RPL12 transcript demonstrated that loss of this modification reduces protein synthesis, disrupts translation-related gene expression, impairs zygotic …

Reducing Communicable-Disease Risk After Earthquakes: Vaccination And Prevention Lessons For Venezuela's Doublet, Alfonso J Rodriguez-Morales, Ivan Arturo Rodríguez-Sabogal, Adriana Sucari, Wendy Moncada, Lili Vanessa Hernández-Serrano, Florencia Escarrá, Pasesa Pascuala Quispe-Torrez, Francisco Javier Membrillo, Tomás Orduna, Susana Lloveras, Tânia S S Chaves, Miguel M Cabada, Cecilia Perret, René Echavarría, Ana F Ribeiro, Melinda Tanabe, Fernando Bazzino, Maximiliano Ramirez, Baruch Diaz, Karen Mirna Loro Morejón, Karen Daly, Reinaldo Rosas, Maria Belen Lopez, Cristina Miranda, Marisa Liliana Fernandez, Yasemin Özsürekçi, Wasin Matsee, Yenddy Carrero, Cristian Biscayart, Sergio Cimerman, Maria L Avila-Aguero, Roberto Debbag, Jose Brea, Alejandro Risquez, Jaime David Acosta-España, Rolando Ulloa-Gutierrez, Carlos Espinal, Carlos N Torres-Martinez, Marta González-Sanz, Aula Abbara, Jill Weatherhead, Bernal Cordero, Virgilio Lezcano, Amanda Guerrero, Herberth Maldonado, Luis Cuellar, Ines Ceron, Yori Roque, Melisa Florentin, Rosa Infante, Ana Carvajal, Lily M Soto-Ávila, Marbelys Hernández, Hector Villaroel, Gianmary Miozzi, Rafael Navas, Moraima Hernández, Carlos Pérez-Vega, Manuela Mérida, David A Forero-Peña, Juan-Carlos Navarro, Claudia Beltrán-Arroyave, Mario Masana

Faculty, Staff and Students Publications

No abstract provided.

High-Order Brain Interactions During Ketamine-Induced State Changes: A Functional Marker Of Response In Late-Life Treatment-Resistant Depression?, Krisha Shah, Rubén Herzog, Alan C Swann, Brittany O'Brien, Rahul Balakrishnan, Sanjay J Mathew, Nicholas Murphy

Faculty, Staff and Students Publications

Ketamine is a fast-acting intervention for treatment-resistant depression (TRD), yet only a subset of patients show robust clinical response, and the underlying neural mechanisms remain unclear. High-order interactions (HOI) derived from multivariate information theory provide a framework for examining nonlinear dependencies among brain regions beyond pairwise connectivity. One such metric, the O-information, captures the balance between synergistic and redundant interactions across three or more variables. In this secondary analysis of a randomized, double-blind, midazolam-controlled trial (NCT02556606), we examined EEG-derived HOI in 30 late-life veterans with TRD following a single 40-minute intravenous infusion of ketamine (0.1, 0.25, 0.5 mg/kg; n = …

Multiplexed Plasmon-Enhanced Lateral Flow Assay For Early Diagnosis Of Acute Kidney Injury, Heng Guo, Yuxiong Liu, Ravi Jada, Ying Liu, Carissa Ng, Aquiles Payte, Jiaying Xu, Connor Malone, Jie Zhao, Kedhareswara Sairam Pasupuleti, Arda Aidan Arikan, Sameer Thadani, Srikanth Singamaneni, Ayse Akcan Arikan, Limei Tian

Faculty, Staff and Students Publications

Early diagnosis of acute kidney injury (AKI) remains a major clinical challenge due to the delayed and insensitive nature of conventional markers such as serum creatinine. Urinary protein biomarkers, including neutrophil gelatinase-associated lipocalin (NGAL) and cystatin C (CysC), provide earlier and complementary information on kidney injury, but their clinical translation is limited by the lack of rapid, quantitative, and multiplexed point-of-care (POC) diagnostic tests. Here, we report a multiplexed plasmonic-fluor-based lateral flow assay (p-LFA) that enables sensitive, quantitative, and simultaneous detection of NGAL and CysC. By harnessing ultrabright plasmonic-fluor nanolabels and ratiometric fluorescence analysis, the p-LFA achieves picogram-per-milliliter analytical sensitivity …

Bi-Allelic Loss-Of-Function Variants In Tmem63b Cause Syndromic Surfactant Dysfunction Disorder, Sock Hoai Chan, Audra N Iness, Jill A Rosenfeld, Mir Reza Bekheirnia, Lindsay C Burrage, Matthew Hoi Kin Chau, Chaerish Eint Myet Chae Htoo, Eric C Kao, Shamika Ketkar, Wan Wan Lim, Xi Luo, Rifhan Mazlan, Elizabeth Mizerik, Kein Seong Mun, Kalyani R Patel, Lorraine Potocki, Christina K Rapp, Xavier Roca, Ana Saianda, Ignacio Iglesias-Serrano, Everlyn C Siew, Donald Yuhui Sim, David R Spielberg, Sok-Kun Tae, Jing Xian Teo, Julian Warfsmann, Fan Xia, Child-Eu Registry, Saumya S Jamuar, Ee Shien Tan, Matthias Griese, Weng Khong Lim, Meow-Keong Thong, Keren Machol

Faculty, Staff and Students Publications

Transmembrane protein 63B gene (TMEM63B) encodes a mechanosensitive ion channel expressed in alveolar type II epithelial cells, where it mediates stretch-induced surfactant secretion. While heterozygous gain-of-function variants in TMEM63B have been associated with developmental and epileptic encephalopathy, no human disorder has previously been linked to bi-allelic loss-of-function variants. Here, we report five individuals from four unrelated families with childhood interstitial lung disease and bi-allelic predicted loss-of-function variants in TMEM63B. Affected individuals presented with early-onset respiratory distress, chronic hypoxemia, and diffuse parenchymal lung abnormalities on chest imaging. One individual died in infancy, two underwent bilateral lung transplantation, and two require oxygen …

Incidence And Outcomes Of Treatment-Associated Hepatotoxicity During Pediatric Acute Lymphoblastic Leukemia Induction Therapy: A Reducing Ethnic Disparities In Acute Leukemia (Redial) Consortium Report, Ashley N Chavana, Emily J Mason, John P Woodhouse, Olga A Taylor, Monica M Gramatges, Joanna S Yi, Sandi Pruitt, M Brooke Bernhardt, Kathleen Ludwig, Laura Klesse, Kenneth Heym, Timothy Griffin, Marley Roberts, Rodrigo Erana, Juan Carlos Bernini, Hong Zhu, Philip J Lupo, Karen R Rabin, Michael E Scheurer, Steven D Mittelman, Van Huynh, Etan Orgel, Austin L Brown

Faculty, Staff and Students Publications

No abstract provided.

Nuclear-Specific Reductive Carboxylation Of Alpha-Ketoglutarate Fuels Histone Acetylation To Induce Chromatin Accessibility And Gene Activation, Abhisha Sawant Dessai, Nadya A Elhalawany, Tao Dai, Justine J Jacobi, Christian Prechtl, Alphonse N Dimeck, Sierra R Morton, Mark D Long, Prashant K Singh, Nagireddy Putluri, Mariana Lopes, Song Liu, Dominic J Smiraglia, Katerina V Gurova, Peder J Lund, Leah A Gates, Sung Yun Jung, Subhamoy Dasgupta

Faculty, Staff and Students Publications

Mitochondria remain at the core of cell metabolism, whereas the nucleus integrates cellular and environmental signals to activate genes. However, the mechanisms that directly link cellular metabolism to gene regulation are not well understood. Here we show, a metabolic pathway in the nucleus controls acetylation of histones by nuclear localization of mitochondrial enzymes aconitase (ACO2) and isocitrate dehydrogenase (IDH2). Metabolic tracing studies show that IDH2 and ACO2 catalyze reductive carboxylation of α-ketoglutarate to rapidly synthesize citrate to increase nuclear acetyl-CoA pool. Genetic and proteomic analyses reveal nuclear IDH2 and ACO2 form a complex with KAT2A/GCN5 for acetylation of histones to …

Genetics Of Cerebrotendinous Xanthomatosis, Jennifer Hanson, Penelope E Bonnen

Faculty, Staff and Students Publications

Cerebrotendinous xanthomatosis (CTX) is rare, autosomal recessive inborn error of metabolism caused by biallelic pathogenic variants in CYP27A1, which encodes sterile 27 hydroxylase, a key enzyme in bile acid biosynthesis. Enzyme deficiency results in reduced cholic and chenodeoxycholic acid synthesis with accumulation of cholestanol, bile acid intermediates, and bile alcohols, producing a progressive multisystem disorder characterized by chronic diarrhea, juvenile-onset cataracts, tendons xanthomas, and neurological dysfunction. Although CTX typically begins in childhood, diagnosis is frequently delayed until adulthood, limiting the benefit of effective disease modifying therapy with chenodeoxycholic acid. Since the identification of CYP27A1, more than 200 pathogenic variants have …

Evidence-Based Classification Of Genes Implicated In Skeletal Disorders Using The Clingen Curation Framework, Ryan F Webb, Hannah Mccurry, Amanda Girod, Madeline Hughes, Emma Wilcox, Mayher Patel, Eleanor C Broeren, Kezang C Tshering, Marina Distefano, Lorenzo D Botto, Lindsay C Burrage, Valérie Cormier-Daire, Juan Dong, Nadja Ehmke, Deborah Krakow, Shahida Moosa, Geert Mortier, Sandesh Nagamani, Loren Pena, Pedro A Sanchez-Lara, Andrea Superti-Furga, Sheila Unger, Danita Velasco, Matthew L Warman, Kerry Brown, Deepika D'Cunha Burkardt, Carlos R Ferreira

Faculty, Staff and Students Publications

More than 770 genetic skeletal disorders have been described, most with disease-causing variants reported in 1 of over 550 different genes. The ClinGen Skeletal Disorders Gene Curation Expert Panel was established to determine the strength of the evidence that supports specific gene-disease relationships (GDRs). Such information can assist clinical testing laboratories in choosing genes that should be included on diagnostic panels. Nine genes accounting for the most frequently encountered skeletal dysplasias (COL1A1, COL1A2, COL2A1, FGFR3, SLC26A2, TRPV4, COMP, ALPL, and SOX9) associated in the medical literature with 26 different skeletal disorders were reviewed using a semi-quantitative scoring framework. This framework …

Jak Inhibition In Pnpt1-Related Mitochondrial Interferonopathy: A Case Report And Review Of Mitochondrial-Immune Crosstalk, Dan Ross Brooks, Hyun Yong Koh, Taylor Martin Kerrins, Steven Lang, Emily Bland, Rui Yang, Sarah Kogan Nicholas, Stephanie Jean Sikkink, Stephen Kralik, Christine Eng, Chaya Nautiyal Murali, Seema Lalani, Pilar Lenglet Magoulas, Lisa Emrick, Kristen Sydney Fisher, Fernando Scaglia

Faculty, Staff and Students Publications

Biallelic pathogenic variants in PNPT1 cause combined oxidative phosphorylation deficiency 13 (COXPD13) (MIM #614932), linking mitochondrial dysfunction to type I interferon (IFN) activation through cytosolic leakage of mitochondrial double‐stranded RNA (mt‐dsRNA). This mechanism connects mitochondrial disease to interferonopathies such as Aicardi–Goutières syndrome (AGS). We describe a 7‐month‐old female infant with compound heterozygous PNPT1 variants presenting with severe hypotonia, feeding difficulties necessitating gastrostomy, dystonia, and elevated serum lactate. Brain magnetic resonance imaging (MRI) demonstrated marked cerebellar, brainstem, and basal ganglia atrophy, with a lactate peak on MR spectroscopy (consistent with an inverted doublet). Serum immune profiling revealed a mild but elevated …

Epinephrine Underuse For Anaphylaxis In Infants And Toddlers: A Practical Review For Pediatricians, Stephanie Leeds, Aikaterini Anagnostou, Michael Pistiner, Jay Lieberman, Nicole B Ramsey, Rachael Griffiths, Julie Wang

Faculty, Staff and Students Publications

A recent consensus report defined anaphylaxis as a serious allergic reaction that may involve the skin/mucosa, respiratory, cardiovascular, and/or gastrointestinal systems that can progress rapidly and may cause death. Epinephrine treatment is recommended in suspected anaphylaxis cases; however, numerous barriers exist to consistent, widespread epinephrine use, including difficulty identifying anaphylaxis signs and symptoms; challenges recognizing when to use epinephrine; low propensity of prescribing and filling prescriptions; low epinephrine carrying rates; knowledge gaps in epinephrine administration techniques; fears of contacting emergency medical services; use of antihistamines, inhaled bronchodilators, and other medications as first-line agents over epinephrine; and limited epinephrine device availability …

Age-Appropriate Low Dosing For Food Protein-Induced Enterocolitis Syndrome Oral Food Challenges: Proposing A Standardized Approach, Sara Anvari, Mary Grace Baker, Theresa Bingemann, J Andrew Bird, Terri Brown-Whitehorn, Antonella Cianferoni, Raquel Durban, Malika Gupta, Erin Hosein, George Konstantinou, Stephanie Leonard, Melanie A Ruffner, Allison Schaible, Amy M Scurlock, Pooja Varshney, Antonella Muraro, Alessandro Fiocchi, Alexandra F Santos, Stefania Arasi, Marta Vazquez-Ortiz, Hideaki Morita, Ichiro Nomura, Julia E M Upton, Michael Levin, Eric Lee, Cesar Galvan, Rodrigo Hoyos-Bachiloglu, Pantipa Chatchatee, Kirsten Beyer, George Du Toit, Purificacion Gonzalez-Delgado, Lydia Su Yin Wong, Marion Groetch, Anna Nowak-Wegrzyn

Faculty, Staff and Students Publications

Current oral food challenge (OFC) protocols for food protein-induced enterocolitis syndrome (FPIES) exhibit significant variability, creating potential for inconsistent diagnostic outcomes and severe reactions. Based on the published evidence and our clinical experience, we propose a practical, standardized OFC dosing protocol that emphasizes patient safety, goals based on age-appropriate servings (AASs), and clinical monitoring. A recent systematic review reported that most patients with persistent FPIES who underwent OFCs reacted to just 25% of an AAS, with low rates of severe reactions. Thus, we recommend that most patients undergoing a medically supervised FPIES OFC receive a cumulative dose of 25% AAS, …

Ebneo Commentary: The Lakana Trial: Mass Administration Of Azithromycin To Infants In Mali Did Not Reduce Mortality, Maya I Brasher, Monika S Patil

Faculty, Staff and Students Publications

The LAKANA trial: a randomized control trial evaluating the impact of mass administration of azithromycin to infants 1 to 11 months of age in Mali showed no reduction in mortality.

Longitudinal And Cross-Sectional Evidence That Daily Resting And Activity Energy Expenditures Are Independent In Humans, Andrew K Yegian, Elizabeth Pachus, Leanne M Redman, Steven B Heymsfield, K Falkenhain, Alexandra R Harris, Shaji K Chacko, William W Wong, Daniel E Lieberman

Faculty, Staff and Students Publications

Total energy expenditure (TEE) is commonly modelled as the sum of resting energy expenditure (REE), activity energy expenditure (AEE), and diet-induced thermogenesis (DIT). This additive model has recently been challenged by the constrained energy balance model, which proposes that reductions in mass-adjusted REE compensate to some extent for increases in AEE, rendering mass-adjusted TEE effectively invariant. We tested these competing models using two complementary approaches. First, we conducted a short-term longitudinal, repeated-measures experiment in 12 adults who completed 10-day periods of high and low physical activity separated by a washout period. TEE was measured with doubly labelled water, AEE with …

Human Exposure To Spirochete-Infected Ornithodoros Turicata In A Residential Setting In The Austin, Texas Metropolitan Area, Serhii Filatov, Bonny Mayes, Sarah M Gunter, Alexander R Kneubehl, Job E Lopez

Faculty, Staff and Students Publications

A central Texas resident found an engorged Ornithodoros turicata tick attached to their ankle while at home. The tick tested positive for Borrelia turicatae, an agent for soft tick-borne relapsing fever. Three weeks earlier, the patient started experiencing febrile episodes, rash, and nausea, yet the etiological agent went undiagnosed.

Na-Gst-1 Adsorbed On Alhydrogel Co-Administered With Different Toll-Like Receptor Agonists In Hookworm-Naive Adults Using A Controlled Human Infection Model In The Usa: A Phase 2, Double-Blind, Randomised Controlled Trial, Caroline K Dirosato, Elissa M Malkin, Sean M Lee, Guacyara Erwin, Lara Hoeweler, Larissa Scholte, Maria Elena Bottazzi, David I Pritchard, Peter J Hotez, Jeffrey M Bethony, David J Diemert

Faculty, Staff and Students Publications

Background: Necator americanus glutathione S-transferase-1 (Na-GST-1) performs a crucial enzymatic step in hookworm blood feeding and is a leading target for vaccine development. Phase 1 trials in Brazil, Gabon, and the USA of recombinant Na-GST-1 adsorbed on Alhydrogel (Na-GST-1/Al), co-administered with or without AP 10-701 (Toll-like receptor [TLR] 4 agonist) or CpG 10104 (TLR9 agonist), showed the vaccine was well tolerated, safe, and immunogenic. A controlled human hookworm infection (CHHI) model was previously developed to evaluate the effect of candidate hookworm vaccines on infection. We aimed to assess the effect of vaccination with three different Na-GST-1 vaccine formulations on subsequent …

Helminth-Infected Mozambican Children With Malaria Have Increased Anaemia, Cytokines And Helminth-Specific Antibodies, Inocência Cuamba, Rebeca Santano, Berta Grau-Pujol, Marta Vidal, Anélsio Cossa, Chenjerai Jairoce, Rojelio Mejía, José Muñoz, Ruth Aguilar, Bin Zhan, Augusto Nhabomba, Gemma Moncunill, Carlota Dobaño

Faculty, Staff and Students Publications

Owing to their overlapping geographical distribution and the consequent occurrence of coinfections, several studies have evaluated the impact of helminth infections on malaria immune responses and clinical outcomes. However, little has been reported on how malaria coinfection affects anthelmintic responses in children harbouring worm infections. We therefore aimed to assess the impact of malaria coinfection on helminth-related clinical and immune outcomes in children. Here, we measured in plasma the levels of 30 cytokines, total IgE, and helminth-specific IgM, IgA, IgG, IgG1-4, and IgE antibodies to a panel of 11 helminth antigens by Luminex. Samples were obtained from 441 children aged …

An Examination Of Buprenorphine And Norbuprenorphine Concentrations In Inpatients Receiving Medications For Opioid Use Disorder, Michèle Haykal, Benjamin Li, Andres Avellaneda Ojeda, Roberto Sanchez, Nancy Shenoi, Asim Shah, Nidal Moukaddam

Faculty, Staff and Students Publications

Background: Interpretation of urine buprenorphine and norbuprenorphine concentrations is widely used to assess adherence during treatment for opioid use disorder. However, the relationships between dose, timing of sample collection, and metabolite ratios remain unclear, leading to potential misinterpretation in clinical practice.

Methods: Data were collected from patients on a psychiatry unit who were either inducted on or continued buprenorphine therapy and underwent urine testing for buprenorphine and its metabolite, norbuprenorphine. Urine samples were collected 16 to 786 min after the last buprenorphine dose. Norbuprenorphine-to-buprenorphine ratios were calculated. Data analysis using Python included polynomial regression and random forest models.

Results: Daily …

Hypovascular Aggressive Angiomyxoma In A Pregnant Adolescent: A Case Report And Review Of Its Multimodal Imaging Appearances, Kyler Shin, Kweku Agyepong, Craig Kym, Mohammad Ghasemi-Rad, David Léon

Faculty, Staff and Students Publications

Aggressive angiomyxoma (AAM) is a rare mesenchymal tumor that primarily arises in the perineum and pelvis of young females. It is sometimes identified incidentally on pelvic examination and obstetric imaging. Although asymptomatic at small sizes, AAM is typically hypervascular and can grow large enough to complicate a patient's obstetric and gynecologic course of treatment. While AAM is a rare diagnosis reported in the literature, there are limited descriptions of its multimodal radiologic appearance, and uncommonly, it can present as a hypovascular mass. We describe a rare case of hypovascular AAM in pregnancy that did not respond favorably to targeted embolization, …

Comprehensive Assessment Of Direct And Passive Smoking Across The Pancreatitis Spectrum, Samuel Han, Dhiraj Yadav, Jun Xu, Melena D Bellin, William E Fisher, Evan L Fogel, Chris Forsmark, Phil A Hart, Liang Li, Stephen J Pandol, Walter G Park, Guru Trikudanathan, Stephen K Van Den Eeden, Santhi Swaroop Vege, Darwin L Conwell, Christie Y Jeon, Consortium For The Study Of Chronic Pancreatitis, Diabetes, And Pancreatic Cancer (Cpdpc)

Faculty, Staff and Students Publications

Objectives: Smoking is a key risk factor for pancreatitis, contributing to pathogenesis and disease progression. Data regarding second-hand smoking, or passive smoking (PS) exposure, are lacking. We therefore aimed to assess the impact of PS exposure across the pancreatitis spectrum.

Methods: We analyzed baseline data from the PROCEED study, a multicenter study in the United States including patients with acute (AP), recurrent acute (RAP), and chronic (CP) pancreatitis. Participants detailed their individual smoking history and PS exposure, which was compared between AP, RAP, and CP subgroups. Participant factors and clinical characteristics were compared by level of individual and PS exposure. …

Fluocinolone Acetonide Implant As A Baseline Therapy For Diabetic Macular Edema: Results From The Randomized Phase 4 New Day Study, Michael A Singer, Charles C Wykoff, Christopher D Riemann, Victor H Gonzalez, Christina Y Weng, Kamel Alkhatib, Rohit A Amarshi, Scott Moody, Mary Pao

Faculty, Staff and Students Publications

Purpose: The NEW DAY (ClinicalTrials.gov identifier, NCT04469595) study assessed the efficacy and safety of the fluocinolone acetonide (FAc; 0.19 mg) intravitreal implant as baseline therapy in diabetic macular edema (DME).

Design: Prospective, randomized, single-masked, active-controlled, multicenter, 18-month, phase 4 study.

Participants: Adults with type 1 or 2 diabetes and center-involving DME confirmed by central subfield thickness (CST).

Methods: Treatment regimens were FAc implant followed by rescue supplemental injections of aflibercept if needed (2 mg/0.05 ml) for 17 months versus aflibercept loading dose (2 mg every 4 weeks for 5 consecutive doses) followed by rescue supplemental injections of aflibercept if …

Clinical Features And Dental Pathologies In Maxillary Sinus Fungal Balls And Odontogenic Sinusitis, Eunice Im, Lane Donaldson, Avraham Adelman, Nithin D Adappa, Yi-Wei Chen, Nikita Chapurin, Jennifer E Douglas, Glen E D'Souza, Jacob Eide, Maria Espinosa, Chia-Hsiang Fu, Meha G Fox, Rohit Garg, Edward C Kuan, Michael A Kohanski, Marta Kwiatkowska, Kevin Li, Derek H Liu, Tran Bao Locke, Chih-Feng Lin, Chadi Makary, Alice Ottavi, Peter Papagiannopoulos, James N Palmer, Charles C L Tong, Bobby A Tajudeen, Sanjena Venkatesh, Kimberly Wei, Frederick Yoo, Alison J Yu, Jun Jin, Alberto M Saibene, John R Craig

Faculty, Staff and Students Publications

Objectives: While maxillary sinus fungal balls (MSFB) can be associated with odontogenic conditions (MSFBO), MSFBO clinical and dental features have not been compared to odontogenic sinusitis (ODS). This multicenter study aimed to compare characteristics of MSFB, MSFBO, and ODS.

Methods: A multicenter international retrospective cohort study was conducted on adults with MSFBs and ODS who underwent sinus surgery. First in MSFBs, it was determined whether different dental conditions were more likely in FB versus non-FB sides. Second, clinical features and dental pathologies were compared between MSFBO and ODS. For analyses, dental conditions were considered individually and as two groups: infectious …

Social Determinants As Pathways In Disparities In Oral Cavity Cancer Stage At Diagnosis: A Registry-Based Analysis From 2010–2020, Guillermo A Tortolero, Erich M Sturgis, Itunu O Sokale, Abiodun Oluyomi, Kristina R Dahlstrom, Aaron P Thrift

Faculty, Staff and Students Publications

Purpose: Racial and ethnic differences in oral cavity cancer (OCC) stage at diagnosis are substantial, but the reasons remain unclear. We assessed insurance status and social neighborhood factors as potential pathways.

Methods: Using the Texas Cancer Registry, we identified adults diagnosed with OCC between 2010 and 2020. We examined the crude and multivariable associations of race and ethnicity, insurance status, and social neighborhood factors with stage at diagnosis. We investigated the mediating effects of insurance status and neighborhood-level social factors on racial and ethnic differences in stage at diagnosis using four-way decomposition with modified Poisson regression and robust standard errors. …

Adlm Guidance Document On Incorporating Gender Diversity In Pathology And Laboratory Medicine, Tiffany A Thomas, Gabrielle N Winston-Mcpherson, Ina Amarillo, Alisha D Berry, Caroline J Davidge-Pitts, Sridevi Devaraj, Zil Goldstein, Brad S Karon, Brooke M Katzman, Mahmoud A Khalifa, Hung S Luu, James H Nichols, Tracy L Stockley, Michelle R Stoffel, Dina N Greene, Matthew D Krasowski

Faculty, Staff and Students Publications

Background: The first international clinical standards of care for the gender-diverse population were formulated in the late 1970s. In the last 15 years, multiple subspecialty societies within the United States have developed clinical care guidelines for those with gender dysphoria, including gender-affirming hormone therapy (GAHT) and surgical treatments. To date, there are no pathology- and laboratory medicine-specific recommendations in the United States for the gender-diverse population.

Content: This document outlines pathology- and laboratory medicine-specific recommendations for providing optimal care to the gender-diverse population, with a predominant focus on the adult population. The scope of this document focuses on the following …