Digital Commons Network^™

Costs Of Single Maintenance And Reliever Therapy Vs Traditional Therapy For Asthma, Tri Pham, Abigail R Barker, Sarah A Eisenstein, Eliot Jost, Anna Volerman, Krutika Chauhan, Ross C Brownson, Timothy Mcbride, Mark D Huffman, Kaharu Sumino, Lynn B Gerald, Mario Castro, Anne E Dixon, James G Krings

2020-Current year OA Pubs

IMPORTANCE: Despite strong guideline support, single maintenance and reliever therapy (SMART) for asthma is underused in the US. Limited insurance coverage of SMART-compatible inhalers remains a major barrier to its adoption.

OBJECTIVE: To compare the annual asthma management costs of SMART vs traditional therapy from a US health care payer perspective.

DESIGN, SETTING, AND PARTICIPANTS: This economic evaluation used a probabilistic decision-tree model with Monte Carlo simulations to compare the total asthma management costs for patients prescribed SMART vs traditional therapy, conducting analyses from September 1, 2024, to March 13, 2025. Input data were extracted through a systematic review of …

An Itpr1 Variant In The Ip3-Itpr1 Binding Pocket Associated With A Clinical Phenotype Of Athetoid Cerebral Palsy., Thania Ordaz, Jagadish Chandrabose Sundaramurthi, Adam S Arterbery, Anita M Bagley, Michael A Gargano, Jeremy P Bauer, Daniel Danis, Philip Giampietro, Ellen Raney, Lauren Rekerle, Mallory Shingle, Jon R Davids, Peter N Robinson

Faculty Research 2026

A de novo, missense variant in ITPR1-inositol 1,4,5-trisphosphate receptor type 1 (ITPR1), p.(Tyr567Cys), was identified by trio whole-genome sequencing in an individual diagnosed with Spinocerebellar ataxia 29 (SCA29) who was affected by cerebral palsy and global developmental delay. The variant affects a residue involved in Inositol 1,4,5-trisphosphate (IP3)-ITPR1 binding. Genotype-Phenotype correlation analysis of the set of missense variants affecting nine residues involved in IP3-ITPR1 binding in the current case and 170 reports of individuals with ITPR1 variants showed a significantly higher frequency of phenotypic features related to neurodevelopmental delay in these variants than in other ITPR1 variants. Our proband was …

Beyond The Streetlight: A Treat-Ad Perspective On Where To Find New Alzheimer's Targets., Gregory Cary, Jesse C Wiley, Gregory W. Carter, Allan I Levey

Faculty Research 2026

Despite extensive investments in Alzheimer's disease (AD) therapeutic development, progress toward effective interventions remains modest. The landscape of potential novel therapeutic strategies is rapidly growing, but prioritization, validation, and tools to advance targets to trial are lagging. The Target Enablement to Accelerate Therapy Development for Alzheimer's Disease (TREAT-AD) consortium has integrated systems-level data from large-scale studies profiling thousands of human brains, yielding target-specific risk scores that partition disease risk into discrete biological domains and enable data-driven target interrogation. Here, we compared clinical trial targets with top-ranked TREAT-AD targets and found a limited overlap as well as differences in the biology …

Beyond The Streetlight: A Treat-Ad Perspective On Where To Find New Alzheimer's Targets., Gregory Cary, Jesse C Wiley, Gregory W. Carter, Allan I Levey

Faculty Research 2026

Despite extensive investments in Alzheimer's disease (AD) therapeutic development, progress toward effective interventions remains modest. The landscape of potential novel therapeutic strategies is rapidly growing, but prioritization, validation, and tools to advance targets to trial are lagging. The Target Enablement to Accelerate Therapy Development for Alzheimer's Disease (TREAT-AD) consortium has integrated systems-level data from large-scale studies profiling thousands of human brains, yielding target-specific risk scores that partition disease risk into discrete biological domains and enable data-driven target interrogation. Here, we compared clinical trial targets with top-ranked TREAT-AD targets and found a limited overlap as well as differences in the biology …

Flare Guns And Trauma: Patterns, Severity, And Clinical Implications From Case And National Surveillance Data, Ramsay Hafer, Andrew Huff, Lara Phillips

Department of Emergency Medicine Faculty Papers

Flare guns are pyrotechnic devices capable of causing serious injury due to high-temperature combustion and projectile discharge. Though intended for signaling in maritime or wilderness settings, improper use can result in trauma patterns distinct from those seen with typical burns or fireworks. Despite their severity, flare gun injuries remain underreported and poorly characterized. We conducted a scoping review of PubMed, Scopus, and Ovid to identify 12 case reports involving 13 patients, and reviewed US National Electronic Injury Surveillance System records from 2015 to 2024, identifying 18 flare gun-specific injuries for a combined total of 31 injuries. Demographic, injury mechanism, body …

Cultural Influences On Camouflaging And Autistic Burnout: Examining The Experiences Of Latino Autistic Young Adults, Antonio F Pagán, Katherine A Loveland, Ron Acierno

Faculty, Staff and Student Publications

The present study explored the relationship between camouflaging, autistic burnout, and cultural factors in Latino young adults with autism spectrum disorder (ASD). While autistic burnout and camouflaging have been widely studied in general ASD populations, limited research has focused on Latino individuals, who may experience unique pressures due to cultural values such as collectivism, familism, and traditional gender roles. Participants (N = 56) from the ¡Iniciando! la Adultez therapy program completed measures assessing burnout, camouflaging, acculturation, and cultural values. Results indicate that participants reported moderate to high levels of autistic burnout, with the highest levels observed in heightened self-awareness …

Loss Of Ctlh Component Maea Impairs Dna Repair And Replication And Leads To Developmental Delay., Søren H. Hough, Satpal S. Jhujh, Samah W. Awwad, Oliver E. Lewis, Simon Lam, John C. Thomas, Thorsten Mosler, Aldo Bader, Lauren E. Bartik, Shane Mckee, Shivarajan Amudhavalli, Estelle Colin, Nadirah Damseh, Emma Clement, Pilar Cacheiro, Anirban Majumdar, Damian Smedley, Joël Fluss, Rosalinda Giannini, Isabelle Thiffault, Guido Zagnoli Vieira, Rimma Belotserkovskaya, Stephen J Smerdon, Petra Beli, Yaron Galanty, Christopher J. Carnie, Grant S. Stewart, Stephen P. Jackson

Manuscripts, Articles, Book Chapters and Other Papers

Ubiquitin E3 ligases play crucial roles in the DNA damage response (DDR) by modulating the turnover, localization, activation, and interactions of DDR and DNA replication proteins. We performed a CRISPR-Cas9 knockout screen focused on ubiquitin E3 ligases and related proteins with the DNA topoisomerase I inhibitor camptothecin. This led us to establish that MAEA, a core subunit of the CTLH E3 ligase complex, is a critical regulator of homologous recombination and the replication stress response. In tandem, we identified eight patients with variants in MAEA who present with a neurodevelopmental disorder that we term DIADEM (Developmental delay and Intellectual disability …

Factors Associated With Rare Pediatric Cancer Trial Enrollment: A Report From The Children's Oncology Group Rare Tumors Committee, Brian R Englum, Jin Piao, Lindsay Younis, Reto M Baertschiger, Kenneth S Chen, Emily Christison-Lagay, Hetal Dholaria, Robyn Gartrell, M John Hicks, Junne Kamihara, Sarah G Mitchell, Manuela Orjuela-Grimm, Farzana Pashankar, Samara L Potter, Jennifer H Aldrink, Jeremy Rosenblum, Michael R Sargen, Kris Ann P Schultz, Brittani K N Seynnaeve, Mary Wedekind, Theodore W Laetsch

Faculty, Staff and Students Publications

Background: Over 90% of US children with cancer are treated at Children's Oncology Group (COG) centers, which seek to maximize enrollment in therapeutic and biobanking studies. Rare cancers have demonstrated lower than expected COG enrollment. We evaluated trends in COG rare cancer enrollment compared to US incidence from Surveillance, Epidemiology, and End Results (SEER) registries, examining the impact of COG therapeutic trials and Project:EveryChild, a cancer biobank/registry.

Procedure: COG and SEER data from 2002 to 2020 were queried for US patients younger than 18 years old with adrenocortical carcinoma (ACC), nasopharyngeal carcinoma (NPC), retinoblastoma (RB), thyroid carcinoma, and melanoma. We …

Single-Cell Atlas Of The Transcriptome And Chromatin Accessibility In The Human Retina, Jin Li, Jun Wang, Ignacio L Ibarra, Xuesen Cheng, Malte D Luecken, Jiaxiong Lu, Aboozar Monavarfeshani, Wenjun Yan, Yiqiao Zheng, Zhen Zuo, Samantha Lynn Zayas Colborn, Berenice Sarahi Cortez, Leah A Owen, Brittney Wick, Xuan Bao, Jongsu Choi, Maximilian Haeussler, Nicholas M Tran, Karthik Shekhar, Joshua R Sanes, J Timothy Stout, Shiming Chen, Yumei Li, Margaret M Deangelis, Fabian J Theis, Rui Chen

Faculty, Staff and Students Publications

Single-cell sequencing has revolutionized the scale and resolution of molecular profiling of tissues and organs. Here we present an integrated dual-modal reference atlas of the most accessible portion of the mammalian central nervous system, the retina. We compiled around 3.9 million cells from 125 donors of diverse ancestral backgrounds, including 8 published studies and 2.7 million unpublished data points, to create a comprehensive human retina cell atlas (HRCA) with more than 130 cell types identified. We annotated each cluster, identified marker genes and characterized cis-regulatory elements and gene regulatory networks. Our analysis uncovered differences in transcriptome, chromatin and gene regulatory …

Rethinking The Centrality Of Brain Areas In Understanding Functional Organization, Benjamin Yost Hayden, Sarah R Heilbronner, Seng Bum Michael Yoo

Faculty, Staff and Students Publications

Parcellation of the cerebral cortex into functionally modular brain areas is foundational to cognitive and systems neuroscience. Here, we question the central status of brain areas from the perspectives of neuroanatomy and electrophysiology. We argue that the major ostensible determinants of brain function, such as cytoarchitecture and connectivity, seldom produce convergent parcellations. Brain areas themselves are just one of several equally important organizing principles; others include macroscale gradients, distributed networks, layers, columns and patches. We further argue that the evidence for a close correspondence between areal parcellation and cognitive function is weaker than is generally supposed. Indeed, many important cognitive …

Identification Of Raptor And Gli1 As Usp37 Substrates Highlight Its Context-Specific Function In Medulloblastoma Cells, Ashutosh Singh, Donghang Cheng, Amanda R Haltom, Yanwen Yang, Tara Dobson, Rashieda Hatcher, Veena Rajaram, Vidya Gopalakrishnan

Faculty, Staff and Student Publications

The USP37 gene encodes a deubiquitylase (DUB), which catalyzes the proteolytic removal of ubiquitin moieties from proteins to modulate their stability, cellular localization or activity. Its expression is downregulated in a subgroup of medulloblastomas driven by constitutive activation of sonic hedgehog (SHH) signaling. Patients with SHH-driven medulloblastomas with elevated expression of the RE1 silencing transcription factor (REST) and reduced expression of USP37 have poor outcomes. In previous studies, we showed sustained proliferation of SHH-medulloblastoma cells due to blockade of terminal cell cycle exit and neuronal differentiation stemming from a failure in USP37-dependent stabilization of its target, the cyclin-dependent kinase inhibitor …

Who Classification Of Skin Tumours: Key Updates In The Fifth Edition, Gabrielle Goldman-Lévy, Raymond Barnhill, Boris C Bastian, Werner Kempf, David Elder, Pedram Gerami, Wayne Grayson, Dmitry Kazakov, Daniela Massi, Jane Messina, Arnaud De La Fouchardière, Alexander J Lazar, Thomas Brenn, Brian Rous, Andrew Field, Anthony Gill, Jennelle C Hodge, Joseph D Khoury, Katia Leite, Shahin Sayed, Puay Hoon Tan, Rosalie Elenitsas, Eduardo Calonje, Lyn M Duncan, Liang Zhiyong, Holger Moch, Rajendra Singh, Harshima Wijesinghe, Ian Cree, Dilani Lokuhetty

Faculty, Staff and Student Publications

The 5th edition of the World Health Organization Classification of Tumours (WCT) serves as a foundation for global diagnostic standards in tumour pathology. Similar to other volumes in this series, the Skin Tumours (Skin5) edition follows a standardized approach. This edition introduces two new chapters: 'Tumours of the nail unit' and 'Metastases to skin', along with new entities across relevant chapters. This review article provides an overview of the updates in Skin5 based on currently published evidence, with emphasis on newly introduced chapters and newly described entities that involve the skin, in particular, epidermal, melanocytic and appendageal tumours.

A Guide To Transcriptomic Deconvolution In Cancer, Yaoyi Dai, Shuai Guo, Yidan Pan, Carla Castignani, Matthew D Montierth, Peter Van Loo, Wenyi Wang

Faculty, Staff and Student Publications

Cancer tissues are heterogeneous mixtures of tumour, stromal and immune cells, where each component comprises multiple distinct cell types and/or states. Mapping this heterogeneity and understanding the unique contributions of each cell type to the tumour transcriptome is crucial for advancing cancer biology, yet high-throughput expression profiles from tumour tissues only represent combined signals from all cellular sources. Computational deconvolution of these mixed signals has emerged as a powerful approach to dissect both cellular composition and cell-type-specific expression patterns. Here, we provide a comprehensive guide to transcriptomic deconvolution, specifically tailored for cancer researchers, presenting a systematic framework for selecting and …

Phase 1 Study Of Inbrx-105, A Tnfrsf9 (4-1bb) And Pd-L1 Bispecific Antibody, In Patients With Select Solid Tumors, Jong Chul Park, Doug R Adkins, Et Al.

2020-Current year OA Pubs

PURPOSE: INBRX-105, a tetravalent, PD-L1-targeted TNFRSF9 (4-1BB) agonist, demonstrated preclinical antitumor activity. This first-in-human study evaluated INBRX-105 in solid tumors.

PATIENTS AND METHODS: This open-label, 4-part, phase 1 study evaluated INBRX-105 alone or with pembrolizumab in adults with locally advanced/metastatic, unresectable solid tumors (NCT03809624). INBRX-105 was administered intravenously once every 2 weeks or 4 weeks in parts 1 (single-agent dose escalation; 0.001-3 mg/kg) and 2 (single-agent expansion) or once every 3 weeks in parts 3 (combination dose escalation; INBRX-105 0.03-1.0 mg/kg) and 4 (combination expansion). Part 2 enrolled patients with checkpoint inhibitor-relapsed/refractory (CPI-R/R) tumors. Part 4 enrolled patients with CPI-R/R …

Epidermal Growth Factor Receptor Regulates Beclin-1 In Hyperoxic Acute Lung Injury., Zachary M Harris, Asawari Korde, Johad Khoury, Edward P Manning, Gail Stanley, Yosep Shin, Kennedy Mitchell, Alexa Von Der Schulenburg, Ying Sun, Buqu Hu, Hyeon Jun Shin, John Joerns, Brian Clark, Lindsey Placek, Derya Unutmaz, Aigul Moldobaeva, Lokesh Sharma, Maor Sauler, Govindarajan Rajagopalan, Xuchen Zhang, He Wang, Mahboobe Ghaedi, Min-Jong Kang, Jonathan L Koff

Faculty Research 2026

BACKGROUND: While delivery of supplemental oxygen is a life-saving therapy, exposure to high oxygen, called hyperoxia, leads to increased intensive care unit mortality. Hyperoxia induces oxidant-mediated acute lung injury (ALI) and pulmonary cell death, called hyperoxic ALI (HALI). Elucidating molecular mechanisms in HALI could identify therapeutic targets in ALI.

METHODS: In the current study, we examined in vivo effects of HALI on Beclin-1 (BCN1), which regulates autophagy, and modulation of BCN1 by epidermal growth factor receptor (EGFR). Effects of HALI on BCN1 and autophagy were examined in mice with genetically decreased EGFR (EGFR

RESULTS: In WT, HALI led to increased …

Differentiation In The Human Urothelia Is Defined By Distinct Alternative Polyadenylation, Ninh B Le, Surbhi Sona, Briana Santo, Yi Zhang, Rosie Ou, R Allen Schweickart, Veena Kochat, William I Padron, Kunal Rai, Shih-Han Lee, Joo Mi Yi, Oliver Wessely, Byron H Lee, Angela H Ting

Faculty, Staff and Student Publications

Distinct epithelial cell states arise during differentiation, but mechanisms generating transcriptomic diversity among them remain poorly defined. The human ureter urothelium contains basal progenitor, intermediate cells, and terminally differentiated umbrella cells. Prior single-cell RNA sequencing revealed similar global gene expression profiles across these states, raising the question of how distinct identities emerge. Here, we show that alternative cleavage and polyadenylation (APA) introduces a major layer of transcriptomic diversity during urothelial differentiation, largely independent of changes in mRNA levels. Analysis of 13,544 urothelial cells identified hundreds of differentiation-associated APA events. Single-cell imaging revealed spatially specific APA patterns, and reporter assays demonstrated …

Differentiation In The Human Urothelia Is Defined By Distinct Alternative Polyadenylation, Ninh B Le, Surbhi Sona, Briana Santo, Yi Zhang, Rosie Ou, R Allen Schweickart, Veena Kochat, William I Padron, Kunal Rai, Shih-Han Lee, Joo Mi Yi, Oliver Wessely, Byron H Lee, Angela H Ting

Faculty, Staff and Student Publications

Distinct epithelial cell states arise during differentiation, but mechanisms generating transcriptomic diversity among them remain poorly defined. The human ureter urothelium contains basal progenitor, intermediate cells, and terminally differentiated umbrella cells. Prior single-cell RNA sequencing revealed similar global gene expression profiles across these states, raising the question of how distinct identities emerge. Here, we show that alternative cleavage and polyadenylation (APA) introduces a major layer of transcriptomic diversity during urothelial differentiation, largely independent of changes in mRNA levels. Analysis of 13,544 urothelial cells identified hundreds of differentiation-associated APA events. Single-cell imaging revealed spatially specific APA patterns, and reporter assays demonstrated …

Ai-Enabled Ecg Analysis Improves Diagnostic Accuracy And Reduces False Stemi Activations: A Multicenter U.S. Registry, Robert Herman, Bryn E Mumma, Jake D Hoyne, Benjamin L Cooper, Nils P Johnson, Timea Kisova, Anthony Demolder, Adam Rafajdus, Andrej Iring, Timotej Palus, Marta Belmonte, Emanuele Barbato, Suzanne J Baron, Robert Hatala, Stephen W Smith, H Pendell Meyers, Scott W Sharkey, Jozef Bartunek, Timothy D Henry

Faculty, Staff and Student Publications

Background: Timely reperfusion is critical in reducing mortality in ST-segment elevation myocardial infarction (STEMI). Although electrocardiography-guided cardiac catheterization laboratory (CCL) activation on the basis of first medical contact recognition improves system-level response, diagnostic uncertainty, particularly in atypical presentations, contributes to false positive activations (FPAs) and reperfusion delays.

Objectives: The aim of this study was to evaluate the diagnostic performance and operational impact of artificial intelligence (AI)-based electrocardiographic (ECG) analysis in real-world STEMI triage across a multicenter U.S. registry.

Methods: A total of 1,032 patients with suspected STEMI who triggered emergent CCL activation at 3 geographically diverse percutaneous coronary intervention centers …

Nutrition Assistance Programs And Pediatric Weight Outcomes: A Systematic Review, Dan Ferris, Genevieve Davison, Tyler Frank, Amanda Gilbert, Fanice Thomas, Sydney Rothman, Kim Lipsey, Sarah Moreland-Russell

2020-Current year OA Pubs

BACKGROUND/OBJECTIVES: Food insecurity and pediatric obesity have increased concurrently in the U.S., raising questions about the role of Federal Nutrition Assistance Programs (FNAPs) in shaping weight outcomes. This systematic review examined evidence on relationships between FNAP participation and pediatric weight outcomes.

METHODS: Six databases were searched for U.S.-based, peer-reviewed studies published through July 2024 that assessed FNAP participation and pediatric weight outcomes.

RESULTS: Seventy-five studies met the inclusion criteria, and no consistent pattern indicated that any single FNAP or program type (educational setting-based or direct financial support) reliably reduced or increased childhood overweight or obesity risk. Twenty studies found statistically …

Intestinal Epithelial Tlr5 Signaling Promotes Barrier-Supportive Macrophages, Ming-Ting Tsai, Ryann Callaghan, Charles Ng, Lisette Peres-Tintin, Dean B Matthews, Nikketa Stanford, Karuna Ganesh, Mary K Estes, Gretchen E Diehl

Faculty, Staff and Students Publications

Intestinal macrophages are essential for epithelial barrier repair. In homeostasis, macrophages are continuously replenished by recruitment of circulating CCR2+ monocytes into the intestinal lamina propria. This requires the commensal microbiota, however, the specific microbial factors and downstream host pathways that coordinate macrophage replenishment are inadequately understood. Here, we show that colonization with an E. coli isolate increased CCR2+ macrophages in the intestine and ameliorated pathology in a colitis model. Using human colonic organoids, we showed E. coli colonization induced CCL2 secretion by intestinal epithelial stem cells which promoted monocyte migration. In vivo, protection was abolished in the absence of epithelial …

De Novo Variants In The Splicing Factor Gene Sf3b1 Are Associated With Neurodevelopmental Disorders, Kevin Uguen, Tiffany Bergot, Marie-Pier Scott-Boyer, Solène Chapalain, Camille Desdouets, Séverine Commet, Changlian Zhu, Yiran Xu, Yangong Wang, Tony Roscioli, Frederic Tran-Mau-Them, Laurence Faivre, Julien Maraval, Julian Delanne, Anne-Sophie Denommé-Pichon, Antonio Vitobello, Céline Jost, Marc Planes, Susan Hiatt, Patricia Wheeler, Claudia Gonzaga-Jauregui, Heng Wang, Baozhong Xin, Valerie Sency, Michael C Kruer, Somayeh Bakhtiari, Patrick Sulem, Cynthia Curry, Trine Prescott, Gertrud Strobl-Wildemann, Theresa Brunet, Martine Doco Fenzy, Thomas Courtin, Céline Poirsier, Trine Bjørg Hammer, Christina D Fenger, Melissa Macpherson, Kosuke Izumi, Jacqueline Leonard, Dong Li, Elaine H Zackai, Ian A Glass, Scott Ward, Philippe M Campeau, Maria Carla Hermida Borroto, Laurence Le Moigno, Hilde Van Esch, Liesbeth De Waele, Daniel G Calame, James R Lupski, Giulia Barcia, Cristina Peduto, Pauline Planté-Bordeneuve, Lucie Dupuis, Roberto Mendoza-Londono, Dimitri J Stavropoulos, Jennifer Gillibert-Duplantier, Thomas Besnard, Laura Do Souto Ferreira, Benjamin Cogné, Stéphane Bézieau, Arnaud Droit, Laurent Corcos, Eric Lippert, Claude Férec, Sebastien Küry, Delphine G Bernard

Faculty, Staff and Students Publications

SF3B1 is an essential and ubiquitous splicing factor that plays a pivotal role in the early steps of pre-mRNA splicing. Recurrent somatic missense mutations in SF3B1 are frequent in cancers, but no constitutional variant has been reported so far. We describe here a cohort of 26 individuals with neurodevelopmental disorders, harbouring SF3B1 constitutional heterozygous variants that appeared mostly de novo. Patients present with a global developmental delay, associated with variable neurological and facial dysmorphic traits. A dichotomy may emerge between patients harbouring predicted loss of function (n = 9) and missense variants (n = 17), the latter being associated with …

Maturity-Onset Diabetes Of The Young (Mody) In A Racially/Ethnically Diverse Pediatric Population, Shilpi Relan, Guido Alarcon, Danielle Guffey, Charles G Minard, Mary E Fang, Kelly Timmons, Rona Y Sonabend, Mustafa Tosur, Maria J Redondo, Jennifer E Posey

Faculty, Staff and Students Publications

Context: Current practice guidelines recommend considering a diagnosis of maturity-onset diabetes of the young (MODY) in patients with diabetes with an affected parent but without typical features of type 1 or type 2 diabetes.

Objective: To test if these criteria apply to a real-world cohort of racially/ethnically diverse children with diabetes.

Methods: We performed a retrospective case review of electronic medical records of youth diagnosed with MODY in a large academic pediatric hospital in Southwestern United States. Cases were ascertained based on the identification of a molecular diagnosis of MODY.

Results: We studied 50 genetically confirmed cases of MODY: 60% …

Ionic Mechanisms Of Two-Pore Channel Regulation Of Vesicle Trafficking, Heng Zhang, Michael X Zhu

Faculty, Staff and Student Publications

The endolysosomal system plays a pivotal role in cellular function. Before reaching lysosomes for degradation, the endocytosed cargoes are sorted at various stages of endosomal trafficking for recycling and/or rerouting. The proper execution of these processes depends on tightly regulated ion fluxes across endolysosomal membranes. Recent studies have demonstrated the importance of two-pore channels (TPCs), including TPC1 and TPC2, in endolysosomal trafficking. These channels are expressed in the membranes of distinct populations of endosomes and lysosomes, where they respond to nicotinic acid adenine dinucleotide phosphate (NAADP) and phosphatidylinositol 3,5-bisphosphate [PI(3,5)P2] to conduct Ca2+ and Na+ release from these acidic organelles. …

Attitudes Toward Patients' Safety Among Healthcare Professionals In The United Arab Emirates: A Cross-Sectional Study, Moien Khan, Amiri Sohrab, Iffat Elbarazi, Mohammed Salaheldin Elsayed, Reem Al Falasi, Debasish Kar

Peninsula Medical School

This research aims to investigate healthcare professionals’ (HCPs) attitudes towards patient safety and to explore the role ofvarious work-related factors that could be the barriers to safety-events reporting to modify these attitudes. A cross-sectionalsurvey was conducted, involving 629 HCPs who are working across health care sectors in the United Arab Emirates. HCPs in theUnited Arab Emirates, comprising 71.5% women and 27.8% men, displayed a generally positive attitude towards patient safety(mean score = 3.91). Sub-comparisons indicated high scores for team functioning (4.58 ± 0.62) and low scores for professionalincompetence as an error cause (2.86 ± 0.50). Common barriers to reporting safety …

A Programmable Genetic Platform For Engineering Noninvasive Biosensors, Asish N Chacko, Kaamini M Dhanabalan, Jinyang Wan, Roy Chien, Nolan T Anderson, Binzhi Xu, Katie Pham, Ritu Tiwari, Arnab Mukherjee

Faculty, Staff and Student Publications

Creating genetic sensors for noninvasive visualization of biological activities in optically opaque tissues holds immense potential for basic research and the development of genetic and cell-based therapies. Magnetic resonance imaging (MRI) stands out among deep tissue imaging methods for its ability to generate high-resolution images without ionizing radiation. However, the adoption of MRI as a mainstream biomolecular technology has been hindered by the lack of adaptable methods to link molecular events with genetically encodable contrast. Here, we introduce modular aquaporin-based protease-activatable probes for enhanced reporting (MAPPER), a platform for the systematic creation of genetic sensors for MRI. To develop MAPPER, …

Rab5c Increases Endothelial Release Of Vwf By Regulating Vesicle Trafficking, Paula Reventun, Pablo Toledano-Sanz, Maria Delgado-Marin, Maria Viskadourou, D Brian Foster, Paul S De Vries, Maria Sabater-Lleal, Nunzio Alcharani, Claudia Gonzalez-Cucharero, William O Osburn, Alanna C Morrison, Alisa S Wolberg, Nicholas L Smith, Marios Arvanitis, Charles J Lowenstein

Faculty, Staff and Student Publications

Background: Abnormal levels of VWF (von Willebrand Factor) are a risk factor for venous thromboembolism (VTE) and bleeding. Genome-wide association studies for VWF have identified novel candidate genes that may regulate VWF levels in humans, including RAB5C (RAS-associated protein RAB5C). We hypothesized that RAB5C regulates VWF release from endothelial cells.

Methods: We studied the effect of RAB5C on vesicle trafficking in human endothelial cells. We performed CRISPR (clustered regularly interspaced short palindromic repeats) interference targeting 2 genetic variants linked to altered VWF levels and evaluated RAB5C expression by reverse transcription-quantitative polymerase chain reaction. We silenced RAB5C or overexpressed RAB5C wild-type, …

Bridging Hypoxia And Vision Loss: The Emerging Role Of Connexins In Local And Systemic Eye Diseases, Xianping Zhang, Yalong Cheng, Jean X Jiang, Yuting Li

Faculty, Staff and Student Publications

Hypoxic eye diseases represent a pivotal yet often underappreciated contributor to the onset and progression of many retinal disorders. When hypoxia persists or exceeds the tissue's compensatory capacity, it triggers pathological retinal neovascularization, blood-retinal barrier disruption, and neuronal apoptosis, ultimately resulting in irreversible visual impairment. Connexins (Cxs) form gap junction channels and hemichannels and regulate retinal cell proliferation, differentiation, and survival, thereby playing a central regulatory role in the pathogenesis of hypoxic ocular diseases. In addition to gap junctions, Cx hemichannels promote transmission of molecules between intra- and extracellular environments, further influencing retinal homeostasis under hypoxic stress. This review synthesizes …

Dna Methyltransferase Inhibitors In Hematological Malignancies And Solid Tumors, Valentin Wenger, Guillermo Garcia-Manero, Robert Zeiser, Michael Lübbert

Faculty, Staff and Student Publications

Epigenetic modifications such as DNA methylation play a fundamental role in oncogenesis and the progression of neoplasms neoplasias. DNA methyltransferase inhibitors (DNMTi) constitute a family of therapeutic agents that impede the methylation at the 5-position on cytosine nucleotides, thereby modulating the epigenetic regulation of tumor suppressor genes, oncogenes, and other key regulatory genes. The first-generation DNMTi azacitidine and decitabine have demonstrated substantial efficacy in the treatment of medically non-fit, older patients with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) ineligible for intensive chemotherapy (IC), by virtue of their favorable safety profile. Despite these clinical achievements, however, single-agent DNMTi treatment …

The Impact Of Skin Tone On Performance Of Pulse Oximeters Used By Nhs England Covid Oximetry @Home Scheme: Measurement And Diagnostic Accuracy Study, Exakt Study Investigators, Daniel S Martin, James C Doidge, Doug Gould, Tasnin Shahid, Alex Cowden, Walton N Charles, Amelia Francis Johnson, Roger Garrett, Catherine Mbema, Olusegun Olusanya, Eugene Healy, Kathryn Rowan, Paul Mouncey, David A Harrison

Peninsula Medical School

OBJECTIVES: To assess the impact of skin tone on the measurement and diagnostic accuracy of five fingertip pulse oximeters used by patients in the NHS (National Health Service) England COVID Oximetry @home scheme.

DESIGN: Measurement and diagnostic accuracy study (exploring pulse oximeter accuracy across skin tones-EXAKT).

SETTING: Twenty four intensive care units in England between June 2022 and August 2024.

PARTICIPANTS: 903 critically ill adults admitted to intensive care units screened for or enrolled into a trial evaluating different approaches to oxygen therapy.

INTERVENTIONS: Pulse oximetry derived peripheral oxygen saturation (SpO2) measurements were compared with paired arterial oxygen saturation (SaO2) …

Identifying Priority Research Questions For Decentralized Wastewater, Bryan W Brooks, Timothy Callahan, Jacob K Stanley, Jamie Holodak, Kevin M Stroski, Alissa H Cox, Thomas W Groves, Anish Jantrania, Jeff C Moeller, Kris Neset, Christopher Walker, Harry Zhang, Amal Bakchan, Kelly D Alley, Jim Bell, Allison Blodig, Eric Casey, Donna Cosper, Victor D'Amato, Mark A Elliott, Greg Graves, Roxanne Groover, Robert Himschoot, Mary G Lusk, Jillian Maxcy-Brown, David Meints, Rojelio Mejia, Matt Pace, Benjamin J Ryan, Brian Scheffe, Tom Schimelfenig, June E Wolfe, Sara F Heger

Faculty, Staff and Students Publications

Decentralized wastewater treatment and reuse represent critical infrastructure across the rural-periurban-urban continuum around the world. Effective, efficient, resilient, and equitable implementation of on-premise technologies and management systems is part of a One Water approach and necessary to protect public health and the environment, yet inconsistent delivery of essential public health services persists in many regions, including across states, tribes, and territories of the United States. We initiated a groundbreaking effort to understand challenges and to identify research opportunities related to the science and practice of decentralized wastewater. A horizon scanning exercise using a bottom up and transparent key questions approach …