Digital Commons Network^™

Differential Longitudinal Effects Of Glucose-Lowering Medications On Glucagon And C-Peptide Responses In The Glycemia Reduction Approaches In Diabetes: A Comparative Effectiveness Study (Grade), Steven E Kahn, Mark Tripputi, John M Lachin, Ashok Balasubramanyam, Mary Ann Banerji, Joshua Barzilay, Robert M Cohen, W Timothy Garvey, Michaela R Gramzinski, Neda Rasouli, Mary Rhee, Jesse C Seegmiller, Vatsala Singh, William I Sivitz, Michael W Steffes, Kristina Utzschneider, Ralph A Defronzo

Faculty, Staff and Students Publications

Objective: To determine the longitudinal effects on α-cell function of four classes of glucose-lowering agents added to metformin in adults with type 2 diabetes.

Research design and methods: In a multicenter, randomized study, 5,047 participants ≥30 years of age with type 2 diabetes taking 1,000-2,000 mg metformin daily, HbA1c 6.8%-8.5%, were randomized to receive insulin glargine U100, glimepiride, liraglutide, or sitagliptin. In a subset of 724 participants, baseline and longitudinal measures of α-cell function were assessed as the fasting glucagon concentration and change in glucagon from fasting to 30 min following oral glucose (glucagon index [GGI]). Whether these measures and …

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3.9 million cells from 125 donors of diverse ancestral backgrounds, including 8 published studies and 2.7 million unpublished data points, to create a comprehensive human retina cell atlas (HRCA) with more than 130 cell types identified.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 …

Hyperglycemia, Receptor For Advanced Glycation End Products, And Small Airways Dysfunction In Asthma, Paula Sierra Salas, Dennis T Villareal, Vickram Tejwani, Amrit Koirala, Cristian Coarfa, Meredith C Mccormack, Nicola A Hanania, Tianshi David Wu

Faculty, Staff and Students Publications

Background: Diabetes and insulin resistance are associated with higher risk of asthma exacerbation and preserved ratio impaired spirometry (PRISm), but the pathophysiology is unclear. These conditions may cause small airways dysfunction (SAD), which is an under-recognized cause of PRISm.

Objective: To determine whether insulin resistance and poor glucose control associate with SAD and to explore whether proteins prognostic of diabetes end-organ complications predict lung function abnormalities.

Methods: We recruited a prospective cohort of adults with physician-diagnosed asthma. Fasting insulin, glucose, hemoglobin A1c, and concentrations of 13 proteins prognostic of diabetes end-organ complications were measured. Static insulin resistance was calculated by …

Multi-Trait And Multi-Ancestry Genetic Analysis Of Comorbid Lung Diseases And Traits Improves Genetic Discovery And Polygenic Risk Prediction, Yixuan He, Wenhan Lu, Yon Ho Jee, Mu-Yi Shih, Ying Wang, Kristin Tsuo, David C Qian, James A Diao, Hailiang Huang, Chirag J Patel, Jinyoung Byun, Bogdan Pasaniuc, Elizabeth G Atkinson, Christopher I Amos, Yen-Chen Anne Feng, Matthew Moll, Michael H Cho, Alicia R Martin

Faculty, Staff and Students Publications

While respiratory diseases such as chronic obstructive pulmonary disease (COPD) and asthma share many risk factors, most studies investigate them in isolation and in predominantly European-ancestry populations. Here, we conducted the most powerful multi-trait and multi-ancestry genetic analysis of respiratory diseases and auxiliary traits to date, identifying 25 new loci associated with lung function in individuals of East Asian ancestry. Using these results, we developed PRSxtra (cross-trait and cross-ancestry), a multi-trait and multi-ancestry polygenic risk score (PRS) approach that leverages shared components of heritable risk via pleiotropic effects. PRSxtra significantly improved the prediction of asthma, COPD and lung cancer compared …

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 …

Technical Considerations And Contemporary Literature Review Of The Gore Thoracic Branch Endoprosthesis®, Bruno P Schmid, Lucas R Kanamori, Hannah V Oden-Brunson, Dora Babocs, Ying Huang, Jorge Miranda, Steven Maximus, Gustavo S Oderich

Faculty, Staff and Students Publications

Thoracic endovascular aortic repair (TEVAR) has become the preferred treatment for various thoracic aortic pathologies, including blunt thoracic aortic injury, aneurysms, and dissections. Involvement of Ishimaru Zone 2 occurs in up to 60% of TEVAR cases requiring extension across the distal aortic arch and left subclavian artery (LSA). Coverage of the LSA without revascularization increases the risk of complications such as upper extremity ischemia, stroke, and spinal cord injury. Therefore, the preservation of LSA perfusion during TEVAR is essential. Cervical debranching remains an effective alternative to preserve flow to the LSA, but it poses risks of bleeding, infection, and nerve …

An Examination Of Racial Bias In Scoring The Autism Diagnostic Observation Schedule (Ados) Module 3: An Item Response Theory Analysis, Yuen Yvonne Yu, Austin Wyman, Calliana J Faulk, Lizzy J Fulop, Rebecca L Greenberg, Rachel M Benecke, Lauren K Steinbeck, Jessica Foy, Caitlyn Kim, George O Emory, Eric A Storch, Casey J Zampella, Benjamin E Yerys, Robert T Schultz, Julia Parish-Morris, John D Herrington, Caitlin C Clements

Faculty, Staff and Students Publications

Given the rising prevalence of autism among racial minority children in the United States, but persistent service use disparities, this study examines potential bias in specific items from the autism diagnostic observation schedule (ADOS), a highly regarded autism evaluation. We leveraged unidimensional item response theory graded response models and a sample of 735 children to analyze the differential item functioning (DIF) of items within ADOS Module 3. Three items showed significant signs of racial bias: A1 (overall language level), A5 (offers information), and D5 (compulsions and rituals). On these items, Black/African American and Asian children were usually more likely to …

Neural Cells Are Susceptible To Historic And Recently Emerged Oropouche Virus Strains, Kaleigh A. Connors, Maris R. Pedlow, Zachary D. Frey, Marjorie Cornejo Pontelli, Sean P. J. Whelan, W. Paul Duprex, Leonardo D'Aiuto, Zachary P. Wills, Amy L. Hartman

2020-Current year OA Pubs

Oropouche fever is a re-emerging global viral threat caused by infection with Oropouche virus (OROV). While disease is generally self-limiting, historical and recent reports of neurologic involvement highlight the importance of understanding the neuropathogenesis of OROV. In this study, we characterize viral replication kinetics in neurons, microglia, and astrocytes derived from immortalized, primary, and induced pluripotent stem cell-derived cells, which are all permissive to infection with the prototypic OROV BeAn19991. We demonstrate cell-type dependent replication kinetics with both historic and recently emerged viral strains. Further, we show that ex vivo rat brain slice cultures can be infected by all OROV …

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 …

Deep Brain Stimulation Response Circuits In Obsessive-Compulsive Disorder, Andreas Horn, Ningfei Li, Garance M Meyer, Ron Gadot, Nicole R Provenza, Sameer A Sheth

Faculty, Staff and Students Publications

In the field of deep brain stimulation (DBS), two major themes are currently making significant progress. First, the framework of connectomic DBS, in which circuits that are associated with improvements of specific symptoms are described and targeted to improve and potentially personalize treatment. Second, the concept of brain sensing and adaptive DBS, which aims at identifying neural biomarkers that may guide stimulation in a closed-loop fashion.

In DBS for Obsessive Compulsive Disorder (OCD), substantial progress has been made on both ends, over the last five years. Together, results begin to draw a picture of exactly which circuit is …

Diagnostic Evaluation And Treatment Of Utis In Children With Neurogenic Bladder, Jacqueline G Holden, Sowdhamini Wallace, Pearl W Chang, Stephanie Davis-Rodriguez, Rana F Hamdy, John M Morrison, Michael J Tchou, Victor Trevisanut, Vijaya Vemulakonda, Catherine S Forster

Faculty, Staff and Students Publications

Objective: Children with neurogenic bladder (NGB) are at increased risk for urinary tract infections (UTIs), but there is a lack of guidelines to assist clinicians in diagnosing and treating these children. Our objective was to describe the presentation and treatment of provider diagnosed UTIs in children with NGB compared to children with vesicoureteral reflux (VUR) and to assess the proportion of children with NGB who met a consortium definition of UTI.

Study design: We included children < 18 years old with either VUR or NGB who were diagnosed in the emergency department with a febrile UTI in our multicenter retrospective cohort study. We extracted and compared UTI symptoms and urinalysis results specific to children with NGB to children with VUR. We measured the proportion of UTI diagnoses concordant with the Urologic Management to Preserve Initial Renal Function (UMPIRE) consensus definition of UTI, defined as ≥ 100,000 CFU/mL of 1 or 2 organisms, pyuria, and ≥ two symptoms of UTI.

Results: The most common symptom among all children in the cohort was vomiting (38.8 %). Of the 215 children with NGB, 41.3 % met …

Artificial Intelligence In Allergy And Immunology: Recent Developments, Implementation Challenges, And The Road Toward Clinical Impact, Merlijn Van Breugel, Matt Greenhawt, Ibon Eguiluz-Gracia, Maria Jose Torres Jaén, Aikaterini Anagnostou, Gerard H Koppelman

Faculty, Staff and Students Publications

Artificial intelligence (AI) is increasingly recognized for its capacity to transform medicine. While publications applying AI in allergy and immunology have increased in number, clinical implementation substantially lags behind other specialties. By mid-2024, over 1,000 US Food and Drug Administration-approved AI-enabled medical devices existed, but none specifically addressed allergy and immunology. This gap partly reflects the field's limited reliance on imaging, which facilitated early AI breakthroughs in radiology and pathology. This narrative review examines recent AI developments, including large language models and AI agents, evaluating their applicability to allergy and immunology practice. We analyze current and potential applications, emphasizing those …

Distribution Of Nematophagous Fungi And Soil-Transmitted Helminths In Outdoor Built Environments Across Latin America, Rojelio Mejia, Eva Mereles Aranda, Leticia Ojeda, Sandra Ocampos Benedetti, Janitzio J Guzman, Barton Slatko, Cristina Almazan, Melisa Diaz-Fernandez, Ruben Cimino, Marisa Juarez, Natalia Montellano Duran, Estefania Lorena Mansilla Flores, Paola Andrea Vargas, Amandeep Kaur, Nestor L Uzcategui, Lucia Estela Mejia, Katherine Elizabeth Keegan, Emilio Rey Mejia, Chiara Cássia Oliveira Amorim, Stefan M Geiger, Ricardo T Fujiwara, Luz Marina Llangarí-Arizo, Andrea Lopez, Natalia Romero-Sandoval, Irene Guadalupe, Liliana E Villanueva-Lizama, Julio Vladimir Cruz-Chan, Maritza Dalí Camones Rivera, Eddyson Montalvo Sabino, Carlos Pineda, Eric J Wetzel, Philip J Cooper

Faculty, Staff and Students Publications

Background: Soil-transmitted helminths (STHs) are among the most common global parasitic infections, represent a significant worldwide public health burden, and remain a source of considerable morbidity in Latin America. Nematophagous fungi (NF), such as Arthrobotrys oligospora, naturally inhabit many soil types and are known for their ability to trap and kill nematodes using specialized hyphal structures or secreted enzymes and metabolites. As they prey on different developmental stages of helminths in soil, they may represent an ecological factor influencing helminth persistence and transmission dynamics.

Methods: Using an in vitro test, Toxocara cati eggs were exposed to A. oligospora. By using …

"He Just Wants Someone To Hear Him And Listen To Him": Barriers And Facilitators To Autistic Youth With Anxiety Receiving Quality Mental Healthcare, Daylin Delgado, Shannon C Lapoint, Grace Lee Simmons, Julia M Heinly, Whitney S Shepherd De, Bridgett Kiernan, Lauren Brookman-Frazee, Eric A Storch, Brenna B Maddox

Faculty, Staff and Students Publications

About half of autistic youth present with clinically interfering anxiety. Psychotherapies with exposure-focused elements are effective in academic clinical settings and controlled trials. However, there is relatively less research examining the implementation of modified interventions for autistic youth with anxiety in community mental health settings. The current study explores community members' perceptions of barriers and facilitators that impact autistic youth with anxiety's receipt of quality mental health services in their community. Semi-structured interviews were conducted with 15 autistic youth, 15 caregivers of autistic youth, 11 community mental health clinicians, and 8 community mental health clinic leaders. Interviews were analyzed thematically. …

Maternal Myo-Inositol Intake And Congenital Heart Defects In Offspring: A Population-Based Case-Control Study, Ruiqi Cen, L Joseph Su, Jun Ying, Mohammed S Orloff, Elijah H Bolin, Xiangyang Lou, Lynn M Almli, Lorenzo D Botto, Marilyn L Browne, Richard H Finnell, Mary M Jenkins, Eirini Nestoridi, Andrew F Olshan, Paul A Romitti, Gary M Shaw, Wendy N Nembhard

Faculty, Staff and Students Publications

Objective: To investigate associations between maternal periconceptional (three months prior through the third pregnancy month) myo-inositol intake and the odds of selected congenital heart defects in offspring.

Design: A population-based case-control study using the National Birth Defects Prevention Study (NBDPS) database.

Setting: United States.

Population or sample: Women with singleton live births without major birth defects (controls) and women with singleton live births, stillbirths, or terminations with selected nonsyndromic congenital heart defects (CHD; cases).

Methods: Descriptive analyses, logistic regression models, ascertainment of myo-inositol intake from supplements and food using a shortened food frequency questionnaire and survey.

Main outcome measures: Odds …

Training In Medications For Opioid Use Disorder And Buprenorphine Prescribing In The Post X-Waiver Era: Insights From A Nationwide, Multispecialty Survey, Sung In H Kim-Vences, Justin Nguyen, Jacqueline M Hirth, Kyle P Suen, Colleen A Keough, Roger Zoorob, Alicia A Kowalchuk

Faculty, Staff and Students Publications

Objective: The January 2023 repeal of the X-waiver aimed to reduce regulatory barriers to buprenorphine prescribing and enhance patient access to medications for opioid use disorder (MOUD). Its impact on prescribing by non-addiction-trained physicians, the integration of MOUD training into residency programs, and the role of mandated training on clinical practice remain unclear.

Methods: A 2024 online survey assessed physicians' awareness of the X-waiver repeal, exposure to MOUD training, and changes in buprenorphine prescribing. Multivariable logistic regression evaluated the independent effect of MOUD training and whether mandatory versus voluntary formats influenced prescribing behavior.

Results: Among 959 physicians (42.7 % residents), …

Divergent Humoral Immune Signatures In Response To Klebsiella Pneumoniae Bacteremia, Paeton L Wantuch, Nadia Wattad, David A Rosen

2020-Current year OA Pubs

OBJECTIVES: Klebsiella pneumoniae is an increasingly threatening global pathogen with high rates of antibiotic resistance and no licensed vaccines available. Despite its worldwide importance, little is known about the human adaptive immune response to K. pneumoniae infection.

METHODS: Herein we observed the longitudinal antibody responses of three immunocompetent patients hospitalized with K. pneumoniae bacteremia. We analyzed the human serum for antibody titers and in vitro functionality. Further, serum function was evaluated via an in vivo mouse model.

RESULTS: We found that in each case, anti-K. pneumoniae antibodies against the infecting strain were still detectable a year after the initial infection. …

Palbociclib With Adjuvant Endocrine Therapy In Early Breast Cancer: 5-Year Follow-Up Analysis Of The Global Multicenter, Open-Label, Randomized Phase Iii Pallas Trial (Abcsg-42/Aft-05/Pre0109/Big-14-13), E L Mayer, K Clifton, Et Al.

2020-Current year OA Pubs

BACKGROUND: In the phase III PALLAS trial, the addition of 2 years of palbociclib to adjuvant endocrine therapy (ET) did not improve short-term invasive disease-free survival (iDFS) compared with ET alone in high-risk early-stage hormone receptor (HR)-positive/human epidermal growth factor receptor 2 (HER2)-negative breast cancer. In this article, we report 5-year efficacy outcomes, including updated iDFS and overall survival (OS).

PATIENTS AND METHODS: PALLAS is an international, open-label, randomized phase III trial evaluating the addition of 2 years of palbociclib to adjuvant ET in patients with stage II-III HR-positive/HER2-negative breast cancer. The primary endpoint was iDFS.

RESULTS: The trial enrolled …

Purpuric Pityriasis Rosea In A 7-Year-Old Girl: A Rare Variant With Generalized Involvement, Ying-Ying Qian, Ya-Fen Wu, Ting Zhang, Ji-Bing Li, Si-Yuan Song, Wei Li

Faculty, Staff and Students Publications

A 7-year-old girl presented with a 10-day history of generalized purpura and petechiae. The eruption began with a solitary violaceous macule on the trunk and progressed within 1 week to multiple oval and round dark-red to violaceous purpuric macules, ecchymoses, and petechiae affecting the face, trunk, and extremities. Lesions were distributed parallel to skin cleavage lines with a characteristic “Christmas-tree” pattern on the back (Fig 1). No oropharyngeal lesions were noted on examination, and the patient denied sore throat or oral discomfort. She reported no pruritus, pain, fever, or systemic symptoms.

Apea: A Type 1 Diabetes Self-Management Ambient-Ai Assistance Tool That Bridges Trajectory Prediction, Interactive Explanation, And Just-In-Time Adaptive Intervention Action., Kun-Yi Chen, Erin M. Tallon, Chi-Ren Shyu

Manuscripts, Articles, Book Chapters and Other Papers

Helping patients self-managing diseases like type 1 diabetes (T1D) requires informatics tools delivering real-time predictions with explainable, actionable guidance. However, many healthcare AI solutions lack actionable recommendations and user-friendly explanations, limiting clinical impacts. We introduce APEA, a pediatric T1D self-management Ambient-AI assistance tool, integrating glucose multi-trajectory-scenarios Prediction, interactive, context-aware large language model Explanations, and just-in-time adaptive intervention policy optimization for Actionable real-time suggestions through reinforcement learning. Using T1DEXIP dataset (262 pediatric T1D patients, multi-center), our results showed improved glucose control outcomes: 45% over human management, 69% over infusion-pump management. Although constrained by small sample size and …

Species-Dependent Gazing Behavior Of Emotional Facial Expressions In Dogs (Canis Familiaris) And Adult Humans (Homo Sapiens)., Heini Törnqvist, Gray S. Atherton, Liam Cross, Sanni Somppi, Jarkko Hautala, Miiamaaria V. Kujala

School of Psychology

Emotional expressions play an important part in social communication of dogs and humans, but comparative studies between dogs and humans are rare. In addition, little is known about how emotions are perceived across species and how attention is divided among different parts of faces. Here, we compared the gazing behavior of dogs and adult humans toward emotional dog and human facial expressions. Dogs mostly gazed at the eye and nose areas, whereas the humans’ focus also included the mouth area. The gazing behavior of both species was affected by the facial expressions and species presented, and they gazed at emotional …

Baseline Characteristics In The Synchronize™-2 Randomized Phase 3 Trial Of Survodutide, A Glucagon Receptor/Glp-1 Receptor Dual Agonist, For Obesity In People With Type 2 Diabetes, Sean Wharton, Carel W Le Roux, Biykem Bozkurt, Elke Platz, Gabriele Bleckert, Samina Ajaz Hussain, Martina Brueckmann, Elena Startseva, Isabel M Kloer, Lee M Kaplan

Faculty, Staff and Students Publications

Aims: Survodutide is an investigational glucagon receptor/glucagon-like peptide-1 receptor dual agonist that has shown promise for treating obesity and its complications in Phase 2 trials. Two double-blind, randomized, global Phase 3 trials are designed to assess the efficacy and safety of survodutide for treatment of obesity-SYNCHRONIZE™-1 in people with obesity without type 2 diabetes (T2D) and SYNCHRONIZE™-2 in people with obesity and T2D. This paper describes the baseline characteristics of participants in SYNCHRONIZE-2 (ClinicalTrials.gov identifier NCT06066528).

Materials and methods: Participants aged ≥18 years with a body mass index (BMI) ≥27 kg/m2 and T2D were randomized 1:1:1 to weekly subcutaneous …

Effects Of Dual-Eligible Integrated Care Plans On Medicaid Enrollment And Retention: Evidence From The Implementation Of Medicare-Medicaid Plans, Eric T Roberts, Eliza Macneal, Kenton J Johnston, José F Figueroa

2020-Current year OA Pubs

Medicare and Medicaid are separate programs that together cover 13 million low-income older adults and people with disabilities, known as dual-eligible individuals. Concern about a lack of coordination across Medicare and Medicaid has prompted the development of Integrated Care Programs (ICPs). Although the primary goal of ICPs is to coordinate financing and care across Medicare and Medicaid, ICPs may also influence whether low-income individuals obtain or keep Medicaid. We evaluated whether the rollout of Medicare-Medicaid Plans (MMPs)-one of the largest ICPs-was associated with changes in Medicaid take-up and retention among Medicare beneficiaries residing in high-poverty zip codes. Using a stacked …

Phenofit: A Framework For Determining Computable Phenotyping Algorithm Fitness For Purpose And Reuse, Laura K Wiley, Luke V Rasmussen, Rebecca T Levinson, Jennnifer Malinowski, Sheila M Manemann, Melissa P Wilson, Martin Chapman, Jennifer A Pacheco, Theresa L Walunas, Justin B Starren, Suzette J Bielinski, Rachel L Richesson

2020-Current year OA Pubs

BACKGROUND: Computational phenotyping from electronic health records (EHRs) is essential for clinical research, decision support, and quality/population health assessment, but the proliferation of algorithms for the same conditions makes it difficult to identify which algorithm is most appropriate for reuse.

OBJECTIVE: To develop a framework for assessing phenotyping algorithm fitness for purpose and reuse.

FITNESS FOR PURPOSE: Phenotyping algorithms are fit for purpose when they identify the intended population with performance characteristics appropriate for the intended application.

FITNESS FOR REUSE: Phenotyping algorithms are fit for reuse when the algorithm is implementable and generalizable-that is, it identifies the same intended population …

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 …

Associations Of Child Amygdala Development With Borderline Personality Symptoms During Adolescence, Anna Constantino-Pettit, Kirsten Gilbert, Kiran Boone, Katherine Luking, Benjamin Geselowitz, Rebecca Tillman, Diana Whalen, Joan Luby, Deanna M Barch, Alecia Vogel

2020-Current year OA Pubs

BACKGROUND: The current understanding of the neural correlates of borderline personality disorder (BPD) is limited, but some evidence suggests that alterations in limbic structures play a role in adult BPD. The developmental course of structural neural differences in BPD is unknown. Whether there is specificity for structural alterations in BPD compared to other psychiatric presentations, such as major depressive disorder (MDD), remains unexplored. In the current study, we examined childhood trajectories of 2 limbic regions that have been implicated in BPD, hippocampal and amygdala volume, as they relate to adolescent BPD symptoms compared to MDD symptoms.

METHODS: Participants (n = …

Intersecting Challenges: Substance Use And Mental Health Disparities Across Self-Reported Disability Status, Jessica Williams, Xiao Li, Hannah S Szlyk, Erin Kasson, Nathaniel A Dell, Alex Ramsey, Patricia A Cavazos-Rehg

2020-Current year OA Pubs

PURPOSE: Substance use and substance use disorders (SUD) disproportionately affect people with disabilities (PWD), yet PWD remain under-represented in addiction treatment literature. While recent work has begun to address SUD prevalence and recovery service gaps, little is known about how disability status shapes substance use outcomes. The present study is the first to our knowledge to investigate how recovery, mental health comorbidities, and barriers to care differ across disability status using structured survey data from people who use substances.

METHODS: 333 participants who use substances and provided information about their disability status in the baseline survey for a digital intervention …

"Another One Bite The Dust-It Happens So Much In Black Neighborhoods": Structural Barriers And Grassroots Resources Among Black Men Who Use Drugs Facing Fentanyl-Era Overdose And Treatment Disparities, Devin E Banks, Kaytryn D Campbell, Maria E Paschke, Rashmi Ghonasgi, Bridget Coffey, Jameala Jones, Brittany Blanchard, Ryan W Carpenter, Daje Bradshaw, Rachel P Winograd

2020-Current year OA Pubs

INTRODUCTION: Black men in the United States have been disproportionately impacted by fatal drug overdose since the proliferation of synthetic opioids like fentanyl. This community based participatory research study examined determinants of overdose risk and substance use treatment disparities among Black men based on their lived experience.

METHODS: Between February and December 2023, we enrolled 35 Black men reporting past-30-day opioid use to complete semi-structured qualitative interviews. Interviews were analyzed by a team of academic and community-based coders with lived experience using an inductive-deductive approach to thematic analysis.

RESULTS: Six key themes were identified. Four themes described racism-related inequities posing …

Ultrasound Applications In The Treatment Of Major Depressive Disorder: A Systematic Review Of Techniques And Therapeutic Potentials In Clinical Trials And Animal Model Studies, Gansheng Tan, Hong Chen, Eric C Leuthardt

2020-Current year OA Pubs

OBJECTIVE: Major depressive disorder (MDD) is a debilitating condition that inflicts significant personal and economic burdens and affects approximately 8% of the US population. Approximately 30% of patients with MDD do not respond to conventional antidepressant and psychotherapeutic treatments. Current treatment options for refractory MDD include transcranial magnetic stimulation (TMS) and invasive surgical procedures such as surgical ablation, vagus nerve stimulation, and deep brain stimulation. In this context, therapeutic ultrasound emerges as a promising alternative for treating refractory MDD, which has the unique advantage of combining noninvasiveness with selective targeting. Over the past ten years, there has been growth in …

Silent Messengers In The Nano-World: Harnessing Extracellular Vesicles As Theranostic Tools For Neonatal Surgical Conditions, Augusto Zani

2020-Current year OA Pubs

Extracellular vesicles (EVs) are lipid bilayer-enclosed nanoparticles secreted by all cells that mediate intercellular communication by transferring proteins, lipids, and nucleic acids. Among their cargo, microRNAs are key post-transcriptional regulators of organogenesis. In fetal lung development, EV-mediated signaling is essential for the coordination of epithelial, mesenchymal, endothelial, and immune cells. In congenital diaphragmatic hernia (CDH), disruption of these interactions leads to pulmonary hypoplasia and pulmonary hypertension, the primary causes of morbidity and mortality. Amniotic fluid stem cell-derived EVs (AFSC-EVs) have emerged as a promising cell-free therapy to restore this impaired communication. In rodent, rabbit, and human models of pulmonary hypoplasia, …