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Il-12-Producing Cytokine Factories Induce Precursor Exhausted T Cells And Elimination Of Primary And Metastatic Tumors, Bertha Castillo, Boram Kim, Fangheng Hu, Courtney Chambers, Annie Nguyen, Andrea Hernandez, Zeshi Wang, Peter D Rios, Sofia Ghani, Ira Joshi, Douglas Isa, Ningbo Zheng, Weiyi Peng, Oleg A Igoshin, Jose Oberholzer, H Courtney Hodges, Nathan Reticker-Flynn, Omid Veiseh Apr 2025

Il-12-Producing Cytokine Factories Induce Precursor Exhausted T Cells And Elimination Of Primary And Metastatic Tumors, Bertha Castillo, Boram Kim, Fangheng Hu, Courtney Chambers, Annie Nguyen, Andrea Hernandez, Zeshi Wang, Peter D Rios, Sofia Ghani, Ira Joshi, Douglas Isa, Ningbo Zheng, Weiyi Peng, Oleg A Igoshin, Jose Oberholzer, H Courtney Hodges, Nathan Reticker-Flynn, Omid Veiseh

Faculty, Staff and Students Publications

Background: Curative responses to immunotherapy require the generation of robust systemic immunity with limited toxicity. Recruitment of T cell populations such as precursor exhausted T cells (Tpex) from lymphoid tissues to tumors is a hallmark of effective treatment. However, the ability to efficiently induce this recruitment is lacking in current immunotherapy approaches. Furthermore, systemic administration of immunotherapies frequently results in dose-limiting toxicities, yielding an inadequate therapeutic window for eliciting durable responses.

Methods: In this investigation, we evaluated the safety and antitumor efficacy of locally administered interleukin 12 (IL-12) using a clinically translatable cytokine delivery platform (NCT05538624) to identify …


Psychometric Properties Of The Postpartum Thoughts And Behaviors Checklist, Nisha Jagannathan, Jonathan S Abramowitz, Mary C Kimmel, Rashelle Musci, Gerald Nestadt, Paul Nestadt, Lauren M Osborne, Jack Samuels, Eric A Storch Apr 2025

Psychometric Properties Of The Postpartum Thoughts And Behaviors Checklist, Nisha Jagannathan, Jonathan S Abramowitz, Mary C Kimmel, Rashelle Musci, Gerald Nestadt, Paul Nestadt, Lauren M Osborne, Jack Samuels, Eric A Storch

Faculty, Staff and Students Publications

Obsessive compulsive disorder (OCD) has an increased prevalence throughout pregnancy and in the postpartum period relative to non-peripartum periods. While some obsessive-compulsive symptoms in this period present in the same manner to those in non-postpartum OCD, others are more specific to the postpartum period (e.g., obsessions related to sudden infant death syndrome [SIDS]). However, there are few validated scales assessing obsessive-compulsive symptoms during the postpartum period. This study examined the psychometric properties of the Postpartum Thoughts and Behaviors Checklist (PTBC), a semi-structured interview of intrusive thoughts and repetitive, neutralizing behaviors developed to address this gap. In a sample of 257 …


Environmental Health Disparities In Pediatric Cancer: A Report From The Fourth Symposium On Childhood Cancer Health Disparities, Manish Arora, Stephen H Linder, Leticia M Nogueira, Amy E Hughes, Lindsay A Williams, Jeremy M Schraw, Michael E Scheurer, Philip J Lupo Apr 2025

Environmental Health Disparities In Pediatric Cancer: A Report From The Fourth Symposium On Childhood Cancer Health Disparities, Manish Arora, Stephen H Linder, Leticia M Nogueira, Amy E Hughes, Lindsay A Williams, Jeremy M Schraw, Michael E Scheurer, Philip J Lupo

Faculty, Staff and Student Publications

The 4th Symposium on Childhood Cancer Health Disparities was held at Texas Children's Hospital in Houston, Texas, on September 26, 2023. The symposium registered 94 attendees from different backgrounds (e.g. clinicians, epidemiologists, exposure assessment scientists, geospatial experts) with an interest in environmental health disparities of pediatric cancer susceptibility and treatment outcomes. The focus of the symposium was to provide an overview of the role of environmental risk factors in studies of pediatric cancer, introduce novel exposure assessment tools that can be applied to the field, and highlight opportunities to study the impact of environmental health disparities in pediatric cancer susceptibility …


Unleashing The Power Of Multiomics: Unraveling The Molecular Landscape Of Peripheral Neuropathy, Elvisa Mehinovic, Simone Thomas, Ahmet Höke, Sheng Chih Jin Apr 2025

Unleashing The Power Of Multiomics: Unraveling The Molecular Landscape Of Peripheral Neuropathy, Elvisa Mehinovic, Simone Thomas, Ahmet Höke, Sheng Chih Jin

Faculty, Staff and Student Publications

Peripheral neuropathies (PNs) affect over 20 million individuals in the United States, manifesting as a wide range of sensory, motor, and autonomic nerve symptoms. While various conditions such as diabetes, metabolic disorders, trauma, autoimmune disease, and chemotherapy-induced neurotoxicity have been linked to PN, approximately one-third of PN cases remain idiopathic, underscoring a critical gap in our understanding of these disorders. Over the years, considerable efforts have focused on unraveling the complex molecular pathways underlying PN to advance diagnosis and treatment. Traditional methods such as linkage analysis, fluorescence in situ hybridization, polymerase chain reaction, and Sanger sequencing identified initial genetic variants …


Llm-Ie: A Python Package For Biomedical Generative Information Extraction With Large Language Models Apr 2025

Llm-Ie: A Python Package For Biomedical Generative Information Extraction With Large Language Models

Faculty, Staff and Student Publications

Objectives: Despite the recent adoption of large language models (LLMs) for biomedical information extraction (IE), challenges in prompt engineering and algorithms persist, with no dedicated software available. To address this, we developed LLM-IE: a Python package for building complete IE pipelines.

Materials and methods: The LLM-IE supports named entity recognition, entity attribute extraction, and relation extraction tasks. We benchmarked it on the i2b2 clinical datasets.

Results: The sentence-based prompting algorithm resulted in the best 8-shot performance of over 70% strict F1 for entity extraction and about 60% F1 for entity attribute extraction.

Discussion: We developed a Python package, LLM-IE, …


The Impact Of Success Coaching On Psychological Well-Being And Sense Of Belonging In First-Year College Students, Lashay Y. Mcqueen Apr 2025

The Impact Of Success Coaching On Psychological Well-Being And Sense Of Belonging In First-Year College Students, Lashay Y. Mcqueen

Educational Leadership & Workforce Development Theses & Dissertations

As higher education institutions seek to assist students with the first-year transition, coaching is one intervention shown to increase academic performance and retention rates (Capstick et al., 2019). Along with academics, fostering student success from a holistic perspective is imperative (Bentrim & Henning, 2022). The purpose of this study was to determine the impact of participation in success coaching on the psychological well-being and sense of belonging for first-year college students. The study also investigated the impact of success coaching on first-generation students. Existing data were used to compare participation in success coaching to overall psychological well-being and sense of …


Inked Insight: A Consensual Qualitative Research Study Exploring The Perspectives Of Visibly Tattooed Counselors, Megan Ashley Lalonde-Pittman Apr 2025

Inked Insight: A Consensual Qualitative Research Study Exploring The Perspectives Of Visibly Tattooed Counselors, Megan Ashley Lalonde-Pittman

Counseling & Human Services Theses & Dissertations

This study explored the experiences of visibly tattooed mental health counselors (VTMHC) through consensual qualitative research (CQR), examining how visible tattoos were perceived to have impacted the participants (N=14) professional experiences, development, and relationships within the counseling field. Seven domains arose from the data: Prejudices experienced by VTMHC, VTMHC Interactions with others, Culture experienced by VTMHC, Appearances of the VTMHC, Professional therapeutic work of the VTMHC, Workplace environment of the VTMHC, Processing the experience of being a VTMHC The implications for multicultural education and future research are explored.


The Cellular Trafficking And Targeting Of Angiotensin-Converting-Enzyme-2 (Ace2) And Neutral-Amino-Acid-Transporter (B0at1) Variants: Implications For The Pathogenesis Of Associated Diseases And Therapy, Nesreen Fayyad Alkhofash Apr 2025

The Cellular Trafficking And Targeting Of Angiotensin-Converting-Enzyme-2 (Ace2) And Neutral-Amino-Acid-Transporter (B0at1) Variants: Implications For The Pathogenesis Of Associated Diseases And Therapy, Nesreen Fayyad Alkhofash

Dissertations

Angiotensin-converting enzyme 2 (ACE2) and the neutral amino acid transporter B0AT1, encoded by SLC6A19, are membrane proteins with pivotal roles in human physiology. ACE2 is involved in regulating blood pressure and serves as the cellular entry receptor for SARS-CoV-2, while B0AT1 facilitates amino acid absorption in the intestine. The interplay between ACE2 and B0AT1, particularly their physical interaction and co-expression in the intestine, underscores their relevance in both normal physiology and disease. Dysregulation of these proteins has been implicated in conditions such as hypertension, and Hartnup disease and they have been usurped by SARS-CoV-2 to cause COVID-19. Despite their …


Science And Politics In Public Health Regulation, Samuel R. Bagenstos Apr 2025

Science And Politics In Public Health Regulation, Samuel R. Bagenstos

University of Michigan Journal of Law Reform

Much of American public discourse takes for granted a distinction between science and politics. People describe and understand that distinction in contradictory ways, however. And those contradictions themselves underscore how closely entwined science and politics actually are.


Statins And Middle Meningeal Artery Embolization: A Literature Review In The Treatment Of Chronic Subdural Hematoma, Basel Musmar, Joanna M. Roy, Samantha Spellicy, Stavropoula I. Tjoumakaris, Michael R. Gooch, Robert H. Rosenwasswer, David Hasan, Pascal Jabbour Apr 2025

Statins And Middle Meningeal Artery Embolization: A Literature Review In The Treatment Of Chronic Subdural Hematoma, Basel Musmar, Joanna M. Roy, Samantha Spellicy, Stavropoula I. Tjoumakaris, Michael R. Gooch, Robert H. Rosenwasswer, David Hasan, Pascal Jabbour

Department of Neurosurgery Faculty Papers

Chronic subdural hematoma (cSDH) presents a multifaceted challenge in contemporary neurological practice, necessitating innovative therapeutic strategies. This comprehensive review explores the convergence of two promising interventions: statins and middle meningeal artery (MMA) Embolization. With cSDH incidence on the rise, particularly among the aging population and those with long-term anticoagulant usage, the traditional surgical avenues face limitations in recurrence rates and associated risk factors. Statins, heralded for their anti-inflammatory, vasculogenic, and angiogenic properties, are emerging as potential allies in cSDH management. Concurrently, MMA embolization offers a nuanced approach to target the neomembrane's blood supply, with evidence supporting its efficacy and safety. …


Short-Course Subcutaneous Alemtuzumab Induces Clinical Responses In Relapsed T-Cell Large Granular Leukemia, Miguel Ruiz, Zachary Braunstein, Eric Mclaughlin, Anjali Mishra, Pierluigi Porcu, Jonathan E. Brammer Apr 2025

Short-Course Subcutaneous Alemtuzumab Induces Clinical Responses In Relapsed T-Cell Large Granular Leukemia, Miguel Ruiz, Zachary Braunstein, Eric Mclaughlin, Anjali Mishra, Pierluigi Porcu, Jonathan E. Brammer

Department of Medical Oncology Faculty Papers

No abstract provided.


Metamaterial Structure Effect On Printed Antenna For Lte/Wifi /Cancer Diagnosis, Fatma Taher, A. M.M.A. Allam, Ahmed F. Miligy, Mohamed A. Mohamed, Mohamed Fathy Abo Sree, Sara Yehia Abdel Fatah Apr 2025

Metamaterial Structure Effect On Printed Antenna For Lte/Wifi /Cancer Diagnosis, Fatma Taher, A. M.M.A. Allam, Ahmed F. Miligy, Mohamed A. Mohamed, Mohamed Fathy Abo Sree, Sara Yehia Abdel Fatah

All Works

This paper explores the influence of metamaterial structures on the performance of LTE/Wi-Fi printed antennas, examining two antenna versions. One version integrates a metamaterial ground layer, representing the traditional antenna, while the other incorporates a metamaterial load attached to the modified antenna. The inclusion of the metamaterial ground layer supports the unit cell with the MTM structure, enabling an analysis of how the MTM structure impacts antenna performance. Testing is conducted using Roger 5880 substrate with a thickness of 1.575 mm and a dielectric constant of 2.2. The antenna's overall dimensions are 60×49×1.575mm, with a loss tangent of 0.0009. Once …


A Semi-Mechanistic Model Of Immune Tolerance Induction To Support Preclinical Development Of A Human Monoclonal Antibody, Paridhi Gupta Apr 2025

A Semi-Mechanistic Model Of Immune Tolerance Induction To Support Preclinical Development Of A Human Monoclonal Antibody, Paridhi Gupta

Alternative Theses and Dissertations (AETDs)

Administration of human monoclonal antibodies (mAb) in preclinical species often triggers an immunogenic response, leading to the formation of anti-drug antibodies (ADA). ADA can bind to the mAb and reduce their systemic exposure by enhancing immune-complex mediated clearance. Thus, ADA complicates the accurate assessment of preclinical pharmacokinetics and toxicology studies. To mitigate this effect, we explored short-term immunosuppressive therapy (methotrexate or combination of tacrolimus and sirolimus) to induce prolonged immune tolerance towards a human mAb, erenumab, in rats. The results demonstrated that tacrolimus/sirolimus but not the methotrexate regimens prevented ADA formation in all treated animals relative to the non-immunocompromised control …


Deciphering Genotype-Phenotype Connections: Leveraging Pangenomes And Comprehensive Genome Variation, Flavia Villani Apr 2025

Deciphering Genotype-Phenotype Connections: Leveraging Pangenomes And Comprehensive Genome Variation, Flavia Villani

Alternative Theses and Dissertations (AETDs)

My thesis explores the application of advanced techniques for discovery of genetic variation and pangenomic approaches to enhance our understanding of genetic variation and genotype-phenotype relationships in two key model organisms: the HXB/BXH recombinant inbred rat family and the BXD mouse family. Through deep sequencing and innovative computational methods, I constructed com- prehensive pangenome graphs that captured genetic diversity beyond what is accessible through conventional single-reference approaches. In the HXB rat family, I identified approximately 200 million base pairs of sequence absent from the reference genome and discovered novel variants associated with glucose metabolism and chromogranin expression through phenome-wide association …


Unraveling Early Onset Disparities And Determinants: An Analysis Of Colorectal Cancer Outcomes And Trends In Texas, Tyler Torres, Elias Arellano Villanueva, Yossef Alsabawi, Demba Fofana, Manish Tripathi Apr 2025

Unraveling Early Onset Disparities And Determinants: An Analysis Of Colorectal Cancer Outcomes And Trends In Texas, Tyler Torres, Elias Arellano Villanueva, Yossef Alsabawi, Demba Fofana, Manish Tripathi

School of Medicine Publications

Introduction: Colorectal cancer (CRC) is the second leading cause of cancer-related deaths in the U.S., with disparities in incidence, survival, and age at diagnosis across racial, ethnic, and socioeconomic groups. The rising incidence of early-onset CRC (< 50 years) has amplified concerns regarding access to care, screening disparities, and outcomes, particularly among minorities. This study examines the impact of race, ethnicity, socioeconomic status (SES), and sex on CRC survival and age at diagnosis in Texas from 1995 to 2016.

Methods: This retrospective cohort study utilized Texas Cancer Registry (TCR) data, including 235,076 CRC cases diagnosed between 1995 and 2016. Kaplan-Meier analysis and log-rank tests assessed 10-year survival by race and ethnicity and time period (1995-2005 vs. 2006-2016). Kruskal-Wallis tests with Bonferroni correction were used to compare survival years between racial/ethnic groups within each period. Age at diagnosis was analyzed by race and …


Small-Molecule Mitotic Inhibitors As Anticancer Agents: Discovery, Classification, Mechanisms Of Action, And Clinical Trials, Yazmin Salinas, Subhash Chauhan, Debasish Bandyopadhyay Apr 2025

Small-Molecule Mitotic Inhibitors As Anticancer Agents: Discovery, Classification, Mechanisms Of Action, And Clinical Trials, Yazmin Salinas, Subhash Chauhan, Debasish Bandyopadhyay

School of Medicine Publications

Despite decades of research, cancer continues to be a disease of great concern to millions of people around the world. It has been responsible for a total of 609,820 deaths in the U.S. alone in 2023. Over the years, many drugs have been developed to remove or reduce the disease’s impact, all with varying mechanisms of action and side effects. One class of these drugs is small-molecule mitotic inhibitors. These drugs inhibit cancer cell mitosis or self-replication, impeding cell proliferation and eventually leading to cell death. In this paper, small-molecule mitotic inhibitors are discussed and classified through their discovery, underlying …


Baseline Associations Of Office And Ambulatory Blood Pressure Monitoring With Cognitive Function And Dementia Prevalence, Jesus Melgarejo, Dhrumil Patil, Sokratis Charisis, Kristina P. Vatcheva, Silvia Mejia-Arango, Luis J. Mena, Claudia Satizabal, Eron G. Manusov, Sudha Seshadri, Gladys E. Maestre Apr 2025

Baseline Associations Of Office And Ambulatory Blood Pressure Monitoring With Cognitive Function And Dementia Prevalence, Jesus Melgarejo, Dhrumil Patil, Sokratis Charisis, Kristina P. Vatcheva, Silvia Mejia-Arango, Luis J. Mena, Claudia Satizabal, Eron G. Manusov, Sudha Seshadri, Gladys E. Maestre

School of Medicine Publications

Background: High blood pressure has been associated with dementia prevalence and incident. However, it is unclear the relationship of office and ambulatory BP monitoring with cognitive function and dementia and in particular, it remains unknown whether ambulatory BP variability relates to dementia.

Objective: To investigate the associations of office and 24-h blood pressure (BP) with cognitive function and dementia prevalence.MethodsCross-sectional population-based study of 1435 participants aged ≥40 years with office BP/24-h BP, and cognitive assessments (Mini-Mental State Examination [MMSE] and Selective Reminding Test [SRT]). Dementia was diagnosed with a clinical dementia rating ≥1.0. Statistics included logistic and linear regression models. …


Evaluation Of Marginal Gap And Fracture Resistance Of Different Cad/Cam Blocks For Indirect Restorations Of Mutilated Molar Teeth, Hend Sayed Ahmed, Hossam El Mandouh Tawfeek, Ahmed Refaat Mohamed Apr 2025

Evaluation Of Marginal Gap And Fracture Resistance Of Different Cad/Cam Blocks For Indirect Restorations Of Mutilated Molar Teeth, Hend Sayed Ahmed, Hossam El Mandouh Tawfeek, Ahmed Refaat Mohamed

Dentistry

No abstract provided.


Gastroesophageal Reflux And Gastrointestinal Symptoms After Metabolic And Bariatric Surgery In Adolescents: An 8-Year Follow-Up Analysis, John B Rode, Suhail A Zeineddin, Jane C Khoury, Todd M Jenkins, Stephanie R Sisley, Anita P Courcoulas, Justin R Ryder, Marc P Michalsky, Thomas H Inge Apr 2025

Gastroesophageal Reflux And Gastrointestinal Symptoms After Metabolic And Bariatric Surgery In Adolescents: An 8-Year Follow-Up Analysis, John B Rode, Suhail A Zeineddin, Jane C Khoury, Todd M Jenkins, Stephanie R Sisley, Anita P Courcoulas, Justin R Ryder, Marc P Michalsky, Thomas H Inge

Children’s Nutrition Research Center Staff Publications

Importance: Vertical sleeve gastrectomy (VSG) and Roux-en-Y gastric bypass (RYGB) are the most commonly performed metabolic and bariatric surgery (MBS) procedures in adolescents and adults. Despite their safety and effectiveness, there is concern over postoperative gastrointestinal symptoms (GIS), especially gastroesophageal reflux symptoms (GERS), in those undergoing VSG.

Objective: To evaluate the long-term prevalence of GIS in adolescents who underwent RYGB or VSG.

Design, setting, and participants: This is a prospective, multicenter, observational cohort study at five academic referral centers in the United States. Patients were enrolled from February 28, 2007, through December 30, 2011. The analysis included 228 adolescents: 161 …


Glucose Uptake In Pigment Glia Suppresses Tau-Induced Inflammation And Photoreceptor Degeneration, Mikiko Oka, Sho Nakajima, Emiko Suzuki, Shinya Yamamoto, Kanae Ando Apr 2025

Glucose Uptake In Pigment Glia Suppresses Tau-Induced Inflammation And Photoreceptor Degeneration, Mikiko Oka, Sho Nakajima, Emiko Suzuki, Shinya Yamamoto, Kanae Ando

Duncan NRI Faculty and Staff Publications

Brain inflammation contributes to the pathogenesis of neurodegenerative diseases, such as Alzheimer's disease (AD). Glucose hypometabolism and glial activation are pathological features seen in AD brains; however, the connection between the two is not fully understood. Using a Drosophila model of AD, we identified that glucose metabolism in glia plays a critical role in neuroinflammation under disease conditions. Expression of human MATP (hereafter referred to as Tau) in the retinal cells, including photoreceptor neurons and pigment glia, causes photoreceptor degeneration accompanied by the formation of dark-stained round inclusion-like structures and swelling of the lamina cortex. We found that inclusion-like structures …


Single-Cell Transcriptomic Analysis Of Kaposi Sarcoma, Daniel A. Rauch, Paula Valiño Ramos, Mariam Khanfar, John Harding, Ancy Joseph, Anam Fahad, Paul Simonson, Isabel Risch, Obi Griffith, Malachi Griffith, Lee Ratner Apr 2025

Single-Cell Transcriptomic Analysis Of Kaposi Sarcoma, Daniel A. Rauch, Paula Valiño Ramos, Mariam Khanfar, John Harding, Ancy Joseph, Anam Fahad, Paul Simonson, Isabel Risch, Obi Griffith, Malachi Griffith, Lee Ratner

2020-Current year OA Pubs

Kaposi Sarcoma (KS) is a complex tumor caused by KS-associated herpesvirus 8 (KSHV). Histological analysis reveals a mixture of "spindle cells", vascular-like spaces, extravasated erythrocytes, and immune cells. In order to elucidate the infected and uninfected cell types in KS tumors, we examined twenty-five skin and blood samples from sixteen subjects by single cell RNA sequence analyses. Two populations of KSHV-infected cells were identified, one of which represented a CD34-negative proliferative fraction of endothelial cells, and the second representing CD34-positive cells expressing endothelial genes found in a variety of cell types including high endothelial venules, fenestrated capillaries, and endothelial tip …


Dynein Light Chains 1 And 2 Are Auxiliary Proteins Of Ph-Sensitive Kir4.1 Channels, Sun-Joo Lee, Jian Gao, Ellen Thompson, Jonathan Mount, Colin G Nichols Apr 2025

Dynein Light Chains 1 And 2 Are Auxiliary Proteins Of Ph-Sensitive Kir4.1 Channels, Sun-Joo Lee, Jian Gao, Ellen Thompson, Jonathan Mount, Colin G Nichols

2020-Current year OA Pubs

Inward rectifier Kir4.1 potassium channels are abundantly expressed in cells that are important for electrolyte homeostasis. Dysregulation of Kir4.1 underlies various neurological disorders. Here, through biochemical and structural studies of full-length Kir4.1, we show that dynein light chain 1 and 2 proteins, also as known as LC8, copurify with Kir4.1 at stoichiometric levels. Direct interaction between Kir4.1 and LC8 is supported by in vitro binding assays and reiterated with native Kir4.1 proteins from mouse brain. Notably, we identify a LC8 binding motif in the unstructured N terminus of Kir4.1. Among Kir subtypes, the motif is unique to Kir4.1 and is …


Applying Results Of Extended Genotyping To Management Of Positive Cervicovaginal Human Papillomavirus Test Results: Enduring Guidelines, L. Stewart Massad, Megan A. Clarke, Rebecca B. Perkins, Francisco Garcia, David Chelmow, Li C. Cheung, Teresa M. Darragh, Didem Egemen, Thomas S. Lorey, Ritu Nayar, Morgan Newman, Carolann Risley, Robert A. Smith, Nicolas Wentzensen, Enduring Consensus Cervical Cancer Screening And Management Guidelines Committee Apr 2025

Applying Results Of Extended Genotyping To Management Of Positive Cervicovaginal Human Papillomavirus Test Results: Enduring Guidelines, L. Stewart Massad, Megan A. Clarke, Rebecca B. Perkins, Francisco Garcia, David Chelmow, Li C. Cheung, Teresa M. Darragh, Didem Egemen, Thomas S. Lorey, Ritu Nayar, Morgan Newman, Carolann Risley, Robert A. Smith, Nicolas Wentzensen, Enduring Consensus Cervical Cancer Screening And Management Guidelines Committee

2020-Current year OA Pubs

OBJECTIVE: The Enduring Consensus Cervical Cancer Screening and Management Guidelines Committee developed recommendations for the use of extended genotyping results in cervical cancer prevention programs.

METHODS: Risks of cervical intraepithelial neoplasia grade 3 or worse were calculated using data obtained with the Onclarity HPV Assay from large cohorts. Management recommendations were based on clinical action thresholds developed for the 2019 American Society for Colposcopy and Cervical Pathology Risk-Based Management Consensus Guidelines. Risk estimates were reviewed in relation to clinical action thresholds and used as the basis for draft recommendations. After an open comment period, recommendations were finalized and ratified through …


First-In-Human Phase I Study Of A Cd16a Bispecific Innate Cell Engager, Afm24, Targeting Egfr-Expressing Solid Tumors, Anthony El-Khoueiry, Todd A Fehniger, Mark Foster, Melissa M Berrien-Elliott, Et Al. Apr 2025

First-In-Human Phase I Study Of A Cd16a Bispecific Innate Cell Engager, Afm24, Targeting Egfr-Expressing Solid Tumors, Anthony El-Khoueiry, Todd A Fehniger, Mark Foster, Melissa M Berrien-Elliott, Et Al.

2020-Current year OA Pubs

PURPOSE: Innate immune cell-based therapies have shown promising antitumor activity against solid and hematologic malignancies. AFM24, a bispecific innate cell engager, binds CD16A on NK cells/macrophages and EGFR on tumor cells, redirecting antitumor activity toward tumors. The safety and tolerability of AFM24 were evaluated in this phase I/IIa dose-escalation/dose-expansion study in patients with recurrent or persistent, advanced solid tumors known to express EGFR.

PATIENTS AND METHODS: The main objective in phase I was to determine the MTD and/or recommended phase II dose. The primary endpoint was the incidence of dose-limiting toxicities during the observation period. Secondary endpoints included the incidence …


Genomic Analysis Of 11,555 Probands Identifies 60 Dominant Congenital Heart Disease Genes, Michael C Sierant, Sheng Chih Jin, Et Al. Apr 2025

Genomic Analysis Of 11,555 Probands Identifies 60 Dominant Congenital Heart Disease Genes, Michael C Sierant, Sheng Chih Jin, Et Al.

2020-Current year OA Pubs

Congenital heart disease (CHD) is a leading cause of infant mortality. We analyzed de novo mutations (DNMs) and very rare transmitted/unphased damaging variants in 248 prespecified genes in 11,555 CHD probands. The results identified 60 genes with a significant burden of heterozygous damaging variants. Variants in these genes accounted for CHD in 10.1% of probands with similar contributions from de novo and transmitted variants in parent-offspring trios that showed incomplete penetrance. DNMs in these genes accounted for 58% of the signal from DNMs. Thirty-three genes were linked to a single CHD subtype while 12 genes were associated with 2 to …


Acute Trem2 Inhibition Depletes Mafb-High Microglia And Hinders Remyelination, Jinchao Hou, Roberta Magliozzi, Yun Chen, Junjie Wu, John Wulf Ii, Gregory Strout, Xiangming Fang, Marco Colonna Apr 2025

Acute Trem2 Inhibition Depletes Mafb-High Microglia And Hinders Remyelination, Jinchao Hou, Roberta Magliozzi, Yun Chen, Junjie Wu, John Wulf Ii, Gregory Strout, Xiangming Fang, Marco Colonna

2020-Current year OA Pubs

We investigated the role of Triggering Receptor Expressed on Myeloid cells 2 (TREM2) in myelin regeneration in the brain. TREM2 is a receptor that activates microglia, which are crucial for clearing myelin debris and promoting remyelination. Previous studies in a mouse model of demyelination induced by the copper-chelating agent Cuprizone (CPZ) have shown that stimulation of TREM2 with a monoclonal antibody reduces demyelination, while deleting the


Bcl-Xl Protects Ass1-Deficient Cancers From Arginine Starvation-Induced Apoptosis, Prashanta Kumar Panda, Ana Carolina Paschoalini Mafra, Alliny C S Bastos, Li Cao, Maria Serra Bonet, Caitlyn B Brashears, Ethan Yang Chen, Heather M Benedict-Hamilton, William Ehrhardt, John Bomalaski, Carina Dehner, Leonard C Rogers, Toshinao Oyama, Brian A Van Tine Apr 2025

Bcl-Xl Protects Ass1-Deficient Cancers From Arginine Starvation-Induced Apoptosis, Prashanta Kumar Panda, Ana Carolina Paschoalini Mafra, Alliny C S Bastos, Li Cao, Maria Serra Bonet, Caitlyn B Brashears, Ethan Yang Chen, Heather M Benedict-Hamilton, William Ehrhardt, John Bomalaski, Carina Dehner, Leonard C Rogers, Toshinao Oyama, Brian A Van Tine

2020-Current year OA Pubs

PURPOSE: Argininosuccinate synthetase 1 (ASS1) silencing in carcinomas and sarcomas leads to a dependence on extracellular arginine for survival. Arginine deprivation therapies, such as PEGylated arginine deiminase (ADI-PEG20), have shown limited effectiveness, which may be due to underlying mechanisms that inhibit apoptosis.

EXPERIMENTAL DESIGN: The effects of ADI-PEG20 on cell-cycle regulation, apoptosis, and BCL-XL-mediated survival pathways in ASS1-deficient cancer cells were determined. The mechanism of cell death protection was determined by assessing caspase and PARP cleavage, CDK2 activity, MCL1 expression, and the interactions among BCL-XL, BAX, and BAK. In vitro synergy was determined, and in vivo efficacy was modeled.

RESULTS: …


Safety And Efficacy Of Fecal Microbiota, Live-Jslm, In Preventing Recurrent Clostridioides Difficile Infection In Participants Who Were Mildly To Moderately Immunocompromised In The Phase 3 Punch Cd3-Ols Study, Carolyn D Alonso, Glenn S Tillotson, Monique R Bidell, Beth Guthmueller, Frederikke Hoeyer, Monika Fischer, Erik R Dubberke Apr 2025

Safety And Efficacy Of Fecal Microbiota, Live-Jslm, In Preventing Recurrent Clostridioides Difficile Infection In Participants Who Were Mildly To Moderately Immunocompromised In The Phase 3 Punch Cd3-Ols Study, Carolyn D Alonso, Glenn S Tillotson, Monique R Bidell, Beth Guthmueller, Frederikke Hoeyer, Monika Fischer, Erik R Dubberke

2020-Current year OA Pubs

BACKGROUND: Fecal microbiota, live-jslm (RBL; Rebyota), is the first Food and Drug Administration-approved, single-dose, microbiota-based live biotherapeutic to prevent recurrent

METHODS: Participants with rCDI who had immunocompromising conditions and/or were taking immunosuppressive medications were included. Treatment-emergent adverse events (TEAEs) were collected for up to 6 months following RBL administration. Efficacy outcomes included treatment success at 8 weeks and sustained clinical response at 6 months.

RESULTS: Overall, 793 participants were enrolled in PUNCH CD3-OLS and 697 received RBL; 141 were included in the immunocompromised subgroup. TEAEs within 8 weeks were reported by 44.7% and 48.0% of participants in the immunocompromised and …


Patient- And Community-Level Characteristics Associated With Respiratory Syncytial Virus Vaccination, Diya Surie, Jennie H Kwon, Et Al. Apr 2025

Patient- And Community-Level Characteristics Associated With Respiratory Syncytial Virus Vaccination, Diya Surie, Jennie H Kwon, Et Al.

2020-Current year OA Pubs

IMPORTANCE: In 2023, the first respiratory syncytial virus (RSV) vaccines were recommended for US adults 60 years or older, but few data are available about which patients were most likely to receive vaccine to inform future RSV vaccine outreach efforts.

OBJECTIVE: To assess patient- and community-level characteristics associated with RSV vaccine receipt and patient knowledge and attitudes related to RSV disease and RSV vaccines.

DESIGN, SETTING, AND PARTICIPANTS: During the first season of RSV vaccine use from October 1, 2023, to April 30, 2024, adults 60 years or older hospitalized with RSV-negative acute respiratory illness were enrolled in this cross-sectional …


Patients' Attitudes To Magnetic Resonance Imaging In Perianal Fistulizing Crohn's Disease: A Global Survey, Easan Anand, Jalpa Devi, Anna Antoniou, Shivani Joshi, Jaap Stoker, Phillip Lung, Ailsa Hart, Phil Tozer, David H Ballard, Parakkal Deepak Apr 2025

Patients' Attitudes To Magnetic Resonance Imaging In Perianal Fistulizing Crohn's Disease: A Global Survey, Easan Anand, Jalpa Devi, Anna Antoniou, Shivani Joshi, Jaap Stoker, Phillip Lung, Ailsa Hart, Phil Tozer, David H Ballard, Parakkal Deepak

2020-Current year OA Pubs

BACKGROUND: There is limited patient involvement in radiological research for perianal fistulizing Crohn's disease (pfCD), despite magnetic resonance imaging (MRI)'s critical role in diagnosis and management. Patient and public involvement is essential for aligning research with patient priorities. This study aimed to gather patient perspectives on the use of MRI in pfCD.

METHODS: A mixed-methods approach was used, following Guidance for Reporting Involvement of Patients and the Public (GRIPP2) guidelines. An online survey, co-developed with a patient representative, included open and closed questions on MRI experiences, advantages, challenges, and the potential for Artificial Intelligence (AI)-generated reports. This was followed by …