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Following Painting's Quiet Call To Adventure, Kelly Allen

The Open Journal of Occupational Therapy

Yael Goverover, OTR/L, Ph.D., professor and post-professional program director of occupational therapy at New York University at Steinhardt (NYU), provided the cover art for the summer issue of the Open Journal of Occupational Therapy. This oil painting on canvas, titled, Still Life, 2024, features an arrangement of everyday objects with vibrant tones of gold, yellow, orange, and green found in the vase, and a coffeepot, fruits, and botanicals set against a backdrop of scarlet and striped patterned fabrics. She created this piece while on sabbatical in Israel as she studied under the tutelage of a seasoned oil …

Environmental Advocacy As An Occupation: Perceived Self-Efficacy And Occupational Justice In Community Programming, Emma Sims, Laura H. Vanpuymbrouck

The Open Journal of Occupational Therapy

Background: Current occupational therapy literature demonstrates a gap in knowledge of environmental advocacy as an occupation, which directly impacts occupational justice in those experiencing environmental racism or discrimination. This study’s purpose was to provide foundational information on the importance of advocacy work in the sphere of environmental and occupational justice through the lived experiences of those directly involved in community environmental advocacy.

Method: Qualitative data was collected via three focus groups using semi-structured interviews focused on perceptions of participant experiences in environmental advocacy occupations. Thematic analysis was used to identify themes relating to research questions.

Results: When …

The Usage Of Robot In The Scale Of Islamic Jurisprudence, Ali Ahmed Salem Farahat

UB Journal for Humanities

The study aimed to investigate the concept of the robot, its types, importance, the ruling of its use in contracting, transactions, sexual relations, and the civil and criminal liability resulting from the misuse of the robot. The study relied on the descriptive methodology. Besides, it used the deductive method. Many findings emerged from the study as follows: first: Using the robot in everyday life is permissible in general; second: it is permissible to use the robot in contracting provided that it abides by the principles of the Islamic Sharia; third: using robot in making sexual intercourse is forbidden and punishable. …

Evicted From The Outside, Colleen Cosgriff

Maine Law Review

In recent years, Maine has seen an increase in the number of people experiencing homelessness who are living outdoors. People living in these circumstances often shelter together in groups of tents or other temporary structures commonly referred to as “encampments.”As municipalities across Maine struggled with how best to respond to the increase in encampments across the state, the United States Supreme Court decided City of Grants Pass v. Johnson, a case originating in Grants Pass, Oregon. Grants Pass wanted to issue civil and criminal fines to people for sleeping outdoors, even when no alternative shelter was available. The city ultimately …

Implementation Of Mindfulness-Based Interventions And Weekly Visits To Reduce Loneliness In Older Adults, Victoria E. Cobb

Dissertations

Implementation of Mindfulness-Based Interventions and Weekly Visits to Reduce Loneliness in Older Adults

Abstract:

Problem: Social isolation and loneliness have emerged as a significant public health issue for the older adult population. Loneliness has been linked to both physical and mental health effects. According to current literature, there is no standard intervention to treat loneliness in the older adult population.

Methods: This quality improvement (QI) project utilized a descriptive cohort design and the Visit-A-Bit screening assessment instrument. Undergraduate nursing students implemented mindfulness interventions during weekly visits over an eight-week period at an independent living facility located in the Midwest. Descriptive …

Depression Screening In The Adult Inpatient Oncology Population, Erica Bizub

Dissertations

Routinely screening oncology patients for depression is recommended due to the higher rates of depression in this population as well as the negative impact of untreated depression. The goal of this QI project is to implement a standard depression screening protocol for patients admitted to this hospital, where there is currently no standard screening protocol. There were 110 patients included in this study, and 67 (60.91%) of patients received a PHQ-9 screening. Of the patients who completed the PHQ-9, 21 (19.09%) had a positive screening, which was a score of seven or higher. While there were high rates of provider …

Research And Preliminary Application Of A Rapid Immunoassay Method For Eugenol Based On Quantum Dots, Junjie Sun, Xiaoxia Liu, Ziyi Chen, Yinlai Li, Lu Zhai, Qinzhou Chen, Renyao Jin

Journal of Food Science and Biotechnology

[Objective ] This study aims to establish a rapid immunoassay method for the quantitative detection of eugenol.[Method ] The eugenol monoclonal antibody was conjugated to the surface of quantum dots by the 1-ethyl- 3- (3-dimethylaminopropyl ) carbodiimide (EDC ) and N-hydroxy-succinamide (NHS ) (EDC-NHS ) coupling method,with quantum dots as fluorescent markers.Bovine serum albumin (BSA ) was used for blocking,and fluorescence microscopy,agarose gel electrophoresis,and a microplate reader were used for identification.Furthermore,the established method was compared with high performance liquid chromatography (HPLC ).[Result ] The optimal synthesis conditions were as follows:quantum dot activation time of 30 min,conjugation pH with 8.0,antibody addition …

Nanoporous Gold Nanoparticles And Model Membrane Systems Applied To The Study Of Lipopolysaccharide (Lps), Dhanbir Lingden

Dissertations

Lipopolysaccharide (LPS), a key structural component of Gram-negative bacteria, is a major trigger of sepsis and septic shock, the systemic inflammatory conditions responsible for millions of deaths annually. Even at concentrations as low as 1 ng/mL, LPS can activate the immune system and initiate inflammatory cascades. According to the Global Burden of Disease Study 2017, sepsis accounted for 48.9 million cases globally, with 11 million deaths, emphasizing the urgent need for improved diagnostic and therapeutic strategies.

Accurate and rapid detection of LPS is vital for early intervention and improved clinical outcomes. While traditional detection methods are still widely used, modern …

Screen Foundations: How Pediatric Nurse Practitioners Can Implement ‘Family Media Use Plans’ In Primary Care To Reduce Pediatric Behavior Concerns, Katie Anderson

Dissertations

Abstract for:

Screen Foundations: How Pediatric Nurse Practitioners Can Implement ‘Family Media Use Plans’ in Primary Care to Reduce Pediatric Behavior Concerns

Problem: Parents of children 2-5 years-old increasingly reach out to PCPs for escalating behavior concerns, including when the child doesn’t listen well, is inattentive, having tantrums, meltdowns, hitting, yelling, etc. Referrals to psychiatry and/or play therapy result in long waits, or referrals not accepted. Coincidingly, toddler and preschool aged children continue to exceed daily screen time recommendations. This results in a gap of care for families with young children and externalizing behavior.

Methods: This quality improvement project addressed …

Research Progress In Thermo-Reversible Polysaccharide Gels, Dongxin Zhou, Ziao Zhang, Su Chen, Weimin Yang, Jiajun Sun, Shengzu Han, Anning Xie, Xiaoxiao Li, Yuxiang Bai

Journal of Food Science and Biotechnology

Thermo-reversible gels are widely applied in the processing of baking,meat,and snack products including cakes,candies,jelly,aspic,and steamed custard buns.Currently,the most effective thermo-reversible gel is gelatin,which can combine with water to form a transparent gel that melts when it is close to the temperature of the human oral cavity.However,gelatin is expensive.Therefore,researchers have turned their attention to polysaccharide gels,hoping to obtain more thermo-reversible food raw materials with different properties.The author reviews thermo-reversible polysaccharide gels from natural sources such as plants,algae,and microorganisms and those modified by physical,chemical,and enzymatic methods and summarizes the sources,structures,gelatinization mechanisms,and product applications of polysaccharide gels.It is expected to provide a reference …

Establishment And Application Of An Immunomagnetic Bead-Based Melisa Method For Olaquindox, Ziyi Chen, Yanling Song, Junjie Sun, Yinlai Li, Lu Zhai, Yaofeng Zhang, Junli Feng, Renyao Jin

Journal of Food Science and Biotechnology

[Objective ] This study aims to establish a magnetic bead enzyme-linked immunosorbent assay (MELISA ) method for olaquindox (OLA ) based on immunomagnetic beads.[Method ] First,olaquindox-hapten conjugated with horseradish peroxidase (OLA-HS-HRP ) and immunomagnetic beads were synthesized.Then,the conjugated immunomagnetic beads and OLA-HS-HRP were used to screen and optimize the reaction conditions of MELISA.[Result ] The optimal working dilution factors for the immunomagnetic beads and OLA-HS-HRP were 100 times and 8 000 times,respectively,with the antibody dilution buffer being PBS solution (0.010 mol/L,pH 7.0) containing methanol at a volume fraction of 5%.Under the optimized conditions,the established standard equation was y=13.593ln x+17.173 (R2=0.994 …

Establishment And Application Of A Uplc-Ms/Ms Method For Simultaneous Determination Of 39 Veterinary Drugs And Their Metabolites In Black Bone Chicken, Jiawei Du, Yongqin Li, Shuangyuan Jin, Xueyan Wang, Hongwu Wen, Xuelian Guo, Hao Li, Lihua Xu

Journal of Food Science and Biotechnology

[Objective ] This study aims to comprehensively investigate the risk of veterinary drug residues in black bone chicken.[Method ] A method for rapid and simultaneous analysis of 39 veterinary drugs and their metabolites in three categories was established based on low-temperature ultrasonic extraction,solid-phase extraction pretreatment,and ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS ).The samples were extracted by Mcllvaine-Na 2EDTA and phosphate buffer via ultrasonic treatment at low temperatures,purified by Oasis HLB solid-phase extraction column,separated by T 3 chromatographic column,and quantified by the matrix matching external standard method.[Result ] The 39 veterinary drugs and their metabolites showed good linear relationships in …

Online Citizen Science In Higher Education Courses, Stacy Cotey, Amy K. Dunbar-Wallis, Yaela N. Golumbic, Pankaj Mehrotra, David A. Beamer, Heather D. Vance-Chalcraft

Michigan Tech Publications

Climate change and biodiversity loss require us to engage the next generation of scientists in addressing global ecological issues. Introducing undergraduate students to citizen science allows them to learn scientific processes and content while contributing to real-world applications. We conducted a systematic review of literature to (1) identify what types of undergraduate courses and institutions use citizen science, (2) list the projects and platforms that have been implemented in online courses in undergraduate education, (3) examine how students participated in the projects through online courses, and (4) summarize learning objectives and reported benefits of student participation. In all, 44 studies …

The Call Of Cucurrucucú, Rachel Olivia Blair

Dissertations and Theses

This is a site of geologic excavation; where charged voices like porous monoliths and forked-tongue shapeshifters call out in fragmented polyphony. What lies broken or misshapen, what can be pieced back together.

What is purity when the body that is being inherited is drowning in murky waters.

Targeting Triple-Negative Breast Cancer With Momordicine-I For Therapeutic Gain In Preclinical Models, Kousik Kesh, Ellen T Tran, Ruchi A Patel, Cynthia X Ma, Ratna B Ray

2020-Current year OA Pubs

No abstract provided.

Wildlife Science Education For Grades 3–12, Natalie J. Carroll, Theodore Leuenberger, Katherine Leuenberger

Purdue University Press Books

Wildlife Science Education for Grades 3–12 guides and encourages youth to learn about the wildlife around them. The first section introduces the basic wildlife groups to youth in upper elementary school using hands-on and other activity-based learning techniques. Young learners will understand the similarities and differences between mammals, birds, fish, and herptiles. The activities for middle schoolers expand the study to interactions within and between them. The lessons for high school students are based on topics of importance to homeowners, residents of a watershed, food and fiber producers (farmers), mayors, teachers, and policy makers. This section delves deeper into the …

Ethnicizing Europe: Hate And Violence After Versailles, Éva Kovács, Raul Cârstocea, Gábor Egry

Central European Studies

Ethnicizing Europe focuses on the dynamics of interethnic violence in Europe between the two world wars. The new international system that was enshrined by the Versailles peace treaties after World War I did not bring stability to East-Central Europe. Rather, it resulted in a host of conditions like self-determination, international oversight, revolutionary political ideas, and democratic processes, which eventually gave new meaning to already established conflicts, as well as igniting new conflicts in the region. This book opens with a discussion of the theoretical scholarship on ethnicity before proceeding to specific case studies investigating the different ways in which ethnicity …

Cancer Vaccination And Immune-Based Approaches In Pancreatic Cancer, Matthew D. Bloom, Ali Raza Shaikh, Zhengyang Sun, Babar Bashir, Adam E. Snook

Department of Medical Oncology Faculty Papers

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy with high recurrence rates even after curative resection and adjuvant chemotherapy. Although immunotherapeutic approaches, such as immune checkpoint blockade (ICB), have revolutionized the treatment of some solid tumor malignancies, this has not been the case for PDAC. Several characteristics of PDAC, including its distinctive desmoplastic tumor microenvironment (TME), intratumor heterogeneity, and poor antigenicity and immune cell infiltration, contribute to its dismal immunotherapeutic landscape. Cancer vaccines offer one approach to overcoming these barriers, particularly in the resectable or borderline resectable settings, where tumor burden is low and immunosuppression is less pronounced. Various vaccination …

Effect Of Vitamin  C As An Iron-Supporting Supplement In Adolescents With Suspected Iron Deficiency Anemia: Is It Effective For Increasing Hemoglobin Levels?, Ryan Pramana Putra, Nany Hairunisa, Refia Putri Restiana, Husnun Amalia, Emad Yousif

Iraqi National Journal of Medicine

Background: Anemia is a global health problem that affects adolescents, adults, and children in both developed and developing countries. Anemia in adolescent girls (10–19 years of age) is defined as a hemoglobin level in the blood of <12 g/dL. In Indonesia, the prevalence of iron deficiency anemia in adolescent girls reaches 48.9%. Iron supplementation can be enhanced with vitamin C as a companion supplement. Vitamin C increases iron absorption in the body by reducing Fe3+ to Fe2+, which requires an acidic environment for optimal dissolution and absorption. Aim: This study aims to assess the comparative effectiveness of iron supplementation with or without vitamin C in increasing hemoglobin levels. Methodology: An experimental design with consecutive sampling was conducted in September 2023 at Junior High School 1 Prambon, Nganjuk, East Java. The total sample consisted of 52 girls aged 12–13 years with anemia. The first group received iron and vitamin C, while the second group received iron only. Hemoglobin levels were  by the fingerstick method. Results: There were 32 samples (53.33%) aged 13 years. The average change in hemoglobin levels before and after intervention in group 1 was 2.238 g/dL with < 0.05, while in group 2 it was 0.661 g/dL with <0.05. The average difference in changes in hemoglobin levels between groups 1 and 2 after intervention was 1.303 g/dL with <0.05. Conclusion: Iron supplementation with vitamin C results in more significant increases in hemoglobin levels.

Assessment Of Knowledge About Toxoplasmosis Among Nursing College Students, Zainab Hassan, Saba Adnan, Abdulameer Abdullah Al- Musawi

Iraqi National Journal of Medicine

Background: Toxoplasmosis is a parasitic disease caused by Toxoplasma gondii. Humans acquire toxoplasmosis by consuming infected meat containing cysts of T. gondii or through contact with cat feces. Toxoplasmosis is known to cause miscarriage, also referred to as spontaneous abortion or pregnancy loss, which pertains to an unviable intrauterine pregnancy occurring during the first trimester and is the most common type of miscarriage. Aim: The aim of this study is to assess the level of knowledge of nursing students about toxoplasmosis. Methods: A questionnaire was administered to 90 nursing students. The self-completed questionnaire consisted of 17 questions covering the parasite, …

Septoplasty Without Packing Or Splints: Our Experience, Jafar Fawzi Al Badran, Huda Hassan Al Abboodi

Iraqi National Journal of Medicine

Background: Septoplasty is a common surgical procedure performed in otorhinolaryngology departments to correct nasal septum deviation. Traditionally, nasal packing or splints used to stabilize the septal mucosal flaps and promote adhesion. However, these can cause complications such as nasal obstruction until removal, dry mouth, watering of eyes, severe pain during pack removal, headache, difficulty swallowing, and hypoxia. Methods: This prospective longitudinal observational study conducted on 50 patients undergoing septoplasty for nasal obstruction without the use of nasal packing or splints. This study included 50 patients who presented to the ENT department with nasal obstruction over one year (October 2021 to …

Facts And Hopes: Toward The Next Quantum Leap In Melanoma, Keith T Flaherty, Andrew E Aplin, Michael A Davies, Nir Hacohen, Meenhard Herlyn, Dave Hoon, Patrick Hwu, Michal Lotem, James Mulé, Jennifer A Wargo, David E Fisher

Faculty, Staff and Student Publications

Outcomes from advanced melanoma, the deadliest of the skin cancers arising from melanocytes and capable of widely metastasizing, have greatly improved, with death rates decreasing for patients with American Joint Committee on Cancer stage 4 melanoma by 3% to 5% annually over the past 10 years. This improvement is a result of advances in both targeted therapy and immunotherapy. BRAF and MEK inhibitors for advanced melanoma have led the way for targeted cancer strategies and first-in-class approvals for immune checkpoint blockers targeting CTLA4, PD-1, and LAG3; T-cell engager therapy targeting the antigen gp100; and tumor-infiltrating lymphocyte therapy. All of these …

Technology Roadmap Of Micro/Nanorobots, Xiaohui Ju, Chuanrui Chen, Cagatay M Oral, Semih Sevim, Ramin Golestanian, Mengmeng Sun, Negin Bouzari, Xiankun Lin, Mario Urso, Jong Seok Nam, Yujang Cho, Xia Peng, Fabian C Landers, Shihao Yang, Azin Adibi, Nahid Taz, Raphael Wittkowski, Daniel Ahmed, Wei Wang, Veronika Magdanz, Mariana Medina-Sánchez, Maria Guix, Naimat Bari, Bahareh Behkam, Raymond Kapral, Yaxin Huang, Jinyao Tang, Ben Wang, Konstantin Morozov, Alexander Leshansky, Sarmad Ahmad Abbasi, Hongsoo Choi, Subhadip Ghosh, Bárbara Borges Fernandes, Giuseppe Battaglia, Peer Fischer, Ambarish Ghosh, Beatriz Jurado Sánchez, Alberto Escarpa, Quentin Martinet, Jérémie Palacci, Eric Lauga, Jeffrey Moran, Miguel A Ramos-Docampo, Brigitte Städler, Ramón Santiago Herrera Restrepo, Gilad Yossifon, James D Nicholas, Jordi Ignés-Mullol, Josep Puigmartí-Luis, Yutong Liu, Lauren D Zarzar, C Wyatt Shields, Longqiu Li, Shanshan Li, Xing Ma, David H Gracias, Orlin Velev, Samuel Sánchez, Maria Jose Esplandiu, Juliane Simmchen, Antonio Lobosco, Sarthak Misra, Zhiguang Wu, Jinxing Li, Alexander Kuhn, Amir Nourhani, Tijana Maric, Ze Xiong, Amirreza Aghakhani, Yongfeng Mei, Yingfeng Tu, Fei Peng, Eric Diller, Mahmut Selman Sakar, Ayusman Sen, Junhui Law, Yu Sun, Abdon Pena-Francesch, Katherine Villa, Huaizhi Li, Donglei Emma Fan, Kang Liang, Tony Jun Huang, Xiang-Zhong Chen, Songsong Tang, Xueji Zhang, Jizhai Cui, Hong Wang, Wei Gao, Vineeth Kumar Bandari, Oliver G Schmidt, Xianghua Wu, Jianguo Guan, Metin Sitti, Bradley J Nelson, Salvador Pané, Li Zhang, Hamed Shahsavan, Qiang He, Il-Doo Kim, Joseph Wang, Martin Pumera

Faculty, Staff and Student Publications

Inspired by Richard Feynman’s 1959 lecture and the 1966 film Fantastic Voyage, the field of micro/nanorobots has evolved from science fiction to reality, with significant advancements in biomedical and environmental applications. Despite the rapid progress, the deployment of functional micro/nanorobots remains limited. This review of the technology roadmap identifies key challenges hindering their widespread use, focusing on propulsion mechanisms, fundamental theoretical aspects, collective behavior, material design, and embodied intelligence. We explore the current state of micro/nanorobot technology, with an emphasis on applications in biomedicine, environmental remediation, analytical sensing, and other industrial technological aspects. Additionally, we analyze issues related to …

The Integrated Stress Response Pathway Coordinates Translational Control Of Multiple Immune Checkpoints In Lung Cancer, Shayna Thomas-Jardin, Shruthy Suresh, Ariana Arce, Nicole Novaresi, Qing Deng, Emily Stein, Lisa Thomas, Cheryl Lewis, Chul Ahn, Bret M Evers, Esra A Akbay, Maria E Salvatierra, Wei Lu, Khaja Khan, Luisa M Solis Soto, Ignacio I Wistuba, John D Minna, Kathryn A O'Donnell

Faculty, Staff and Student Publications

The integrated stress response (ISR) is an adaptive pathway hijacked by cancer cells to survive cellular stresses in the tumor microenvironment. ISR activation potently induces PD-L1, leading to suppression of antitumor immunity. In this study, we sought to uncover additional immune checkpoint proteins regulated by the ISR to elucidate mechanisms of tumor immune escape. The ISR coordinately induced cluster of differentiation 155 (CD155) and PD-L1, enhancing translation of both immune checkpoint proteins through bypass of inhibitory upstream open reading frames in their 5' untranslated regions. Analysis of primary human lung tumors identified a significant correlation between expression of PD-L1 and …

Met Pathway Inhibition Increases Chemo-Immunotherapy Efficacy In Small Cell Lung Cancer, Raúl Del Rey-Vergara, Miguel Alejandro Galindo-Campos, Pedro Rocha, Marina Carpes, Carlos Martínez, Laura Masfarré, Silvia Menéndez, Fabricio Quimis, Adrià Rossell, Albert Iñañez, Sandra Pérez-Buira, Federico Rojo, Ramon Gimeno, Dolores Isla, Jon Zugazagoitia, Cristina Martí Blanco, Rosario García-Campelo, Alberto Moreno-Vega, Luis León-Mateos, Ángel Callejo Mellén, Kwon-Sik Park, Simon Heeke, John V Heymach, Álvaro Taus, Luis Paz-Ares, Ana Rovira, Edurne Arriola

Faculty, Staff and Student Publications

The introduction of immunotherapy as a first-line treatment for advanced small cell lung cancer (SCLC) represents significant progress, yet there remains an opportunity to further improve patient outcomes. Hepatocyte growth factor (HGF) receptor (MET) pathway activation promotes epithelial-mesenchymal transition, driving chemoresistance and potentially impairing the efficacy of immunotherapy. In SCLC mouse models, adding MET inhibition to chemo-immunotherapy (anti-PD-L1) reduces tumor growth, extends survival, and reshapes the tumor microenvironment by decreasing suppressive myeloid cell infiltration and enhancing the immune response. Analysis of pretreatment human SCLC tumor samples reveals that myeloid-enriched immune infiltrates may contribute to chemo-immunotherapy resistance. Elevated serum HGF levels …

Synergistic Activity Of Combined Flt3-Itd And Mdm2 Inhibition With Quizartinib And Milademetan In Flt3-Itd Mutant/Tp53 Wild-Type Acute Myeloid Leukemias, Weiguo Zhang, Li Li, Muharrem Muftuoglu, Mahesh Basyal, Noriko Togashi, Koichi Iwanaga, Fumie Tanzawa, Masashi Numata, Dale L Bixby, Harry P Erba, Nikolai Podoltsev, Gary J Schiller, Prasanna Kumar, Arnaud Lesegretain, Takeshi Isoyama, Takahiko Seki, Naval Daver, Michael Andreeff

Faculty, Staff and Student Publications

Purpose: Acute myeloid leukemia (AML) is characterized by frequent mutations in FMS-like tyrosine kinase 3 (FLT3), overexpression of murine double minute 2 (MDM2), and TP53 wild-type (WT). Monotherapies targeting FLT3 frequently result in the development of resistant disease. In this study, we investigated the antileukemic efficacy of co-targeting FLT3 and MDM2 with quizartinib and milademetan (Q/M) in FLT3 internal tandem duplication (FLT3-ITD) AML cell lines, xenograft and patient-derived xenograft (PDX) models, and a phase I clinical trial.

Experimental design: Preclinical studies used human and murine cell lines carrying FLT3-ITD and/or tyrosine kinase domain mutations, TP53 WT/knockdown, leukemia cell xenograft models, …

Targeting The Cd40 Costimulatory Receptor To Improve Virotherapy Efficacy In Diffuse Midline Gliomas, Sara Labiano, Javier Marco-Sanz, Iker Ausejo-Mauleon, Virginia Laspidea, Reyes Hernández-Osuna, Marc Garcia-Moure, Daniel De La Nava, Sara Nuin, Marisol Gonzalez-Huarriz, Timothy N Phoenix, Ibon Tamayo, Marta Zalacain, Andrea Lacalle, Lucía Marrodan, Montserrat Puigdelloses, Irati Hervás-Corpión, Maria C Ochoa, Noelia Casares, Oren J Becher, Candelaria Gomez-Manzano, Juan Fueyo, Jaime Gallego Perez-Larraya, Ana Patiño-Garcia, Marta M Alonso

Faculty, Staff and Student Publications

Diffuse midline glioma (DMG) is a devastating pediatric brain tumor. The oncolytic adenovirus Delta-24-RGD has shown promising efficacy and safety in DMG patients but is not yet curative. Thus, we hypothesized that activating dendritic cells (DCs) through the CD40 costimulatory receptor could increase antigen presentation and enhance the anti-tumor effect of the virus, resulting in long-term responses. This study shows that the intratumoral co-administration of Delta-24-RGD and a CD40 agonistic antibody is well tolerated and induces long-term anti-tumor immunity, including complete responses (up to 40%) in DMG preclinical models. Mechanistic studies revealed that this therapy increased tumor-proliferating T lymphocytes and …

Antitumor Efficacy Of Intermittent Low-Dose Erlotinib Plus Sulindac Via Mhc Upregulation And Remodeling Of The Immune Cell Niche, Chakrapani Tripathi, Jorge E Tovar Perez, Sabeeta Kapoor, Ahmed Muhsin, Wan Mohaiza Dashwood, Yunus Demirhan, Melek Demirhan, Alessandro Shapiro, Altaf Mohammed, Shizuko Sei, Jacklyn Thompson, Mahira Zaheer, Krishna M Sinha, Powel H Brown, Michelle I Savage, Eduardo Vilar, Praveen Rajendran, Roderick H Dashwood

Faculty, Staff and Student Publications

A previously reported clinical trial in familial adenomatous polyposis (FAP) patients treated with erlotinib plus sulindac (ERL + SUL) highlighted immune response/interferon-γ signaling as a key pathway. In this study, we combine intermittent low-dose ERL ± SUL treatment in the polyposis in rat colon (Pirc) model with mechanistic studies on tumor-associated immune modulation. At clinically relevant doses, short-term (16 weeks) and long-term (46 weeks) ERL ± SUL administration results in near-complete tumor suppression in Pirc colon and duodenum (p < 0.0001). We identify a low-dose threshold for significant antitumor activity in Pirc rats given SUL at 125 ppm in the diet plus ERL at 5 mg/kg body weight via twice-weekly oral gavage (SUL125 + ERL5 × 2). Longitudinal analyses show diminished expression of MHC class I and II genes in polyps larger than Grade 5, a novel finding in the Pirc model. Treatment with ERL ± SUL upregulates the corresponding MHC and immune-associated factors in a subset of Pirc colon polyps, Pirc tumor cell lines, murine colon carcinoma cells, and FAP patient-derived organoids, with Nlrc5 playing a critical role in this effect. Imaging mass cytometry reveals that SUL125 + ERL5 × 2 increases tumor-associated Cd4+ T cells by ~2.6-fold (p < 0.05), with no apparent effect on Cd8+ T cells. The treatment also increases tumor-associated Cd68+ cells (p < 0.05) and decreases Foxp3+ (p < 0.01) and Arg1+ (p < 0.05) cells. Thus, intermittent low-dose ERL + SUL treatment enhances tumor-associated MHC expression and remodels the immune cell niche toward a more permissive "helper" immune microenvironment. We conclude that early immune-interception strategies targeting interferon-γ signaling may benefit FAP patients at drug doses below the clinical standard of care.

Sensory Neuron-Expressed Fgf13 Controls Nociceptive Signaling In Diabetic Neuropathy Models, Aditya K Singh, Matteo Bernabucci, Nolan M Dvorak, Zahra Haghighijoo, Jessica Di Re, Nana A Goode, Feni K Kadakia, Laura A Maile, Olumarotimi O Folorunso, Paul A Wadsworth, Cynthia M Tapia, Pingyuan Wang, Jigong Wang, Haiying Chen, Yu Xue, Jully Singh, Kali Hankerd, Isaac J Gamez, Makenna Kager, Vincent Truong, Patrick Walsh, Stephanie I Shiers, Nishka Kuttanna, Hanyue Liao, Margherita Marchi, Erika Salvi, Ilaria D'Amato, Daniela D'Amico, Parsa Arman, Catharina G Faber, Rayaz A Malik, Marina De Tommaso, Dan Ziegler, Krishna Rajarathnam, Thomas A Green, Peter M Grace, Matthew R Sapio, Michael J Iadarola, Gregory D Cuny, Diana S Chow, Giuseppe Lauria Pinter, Steve Davidson, Dustin P Green, Jun-Ho La, Jin Mo Chung, Jia Zhou, Theodore J Price, Elizabeth Salisbury, Subo Yuan, Fernanda Laezza

Faculty, Staff and Student Publications

Nociception involves complex signaling, yet intrinsic mechanisms bidirectionally regulating this process remain unexplored. Here, we show that the fibroblast growth factor 13 (FGF13)/Nav1.7 protein-protein interaction (PPI) complex bidirectionally modulates nociception, and that the FGF13/Nav1.7 ratio is upregulated in type 2 diabetic neuropathy (T2DN). PW164, an FGF13/Nav1.7 channel C-terminal tail domain (CTD) PPI interface inhibitor, which reduces complex assembly, selectively suppressed Na+ currents sensitized by capsaicin-induced activation of TRPV1 channels in human induced pluripotent stem cell-derived (hIPSC-derived) sensory neurons and inhibited mechanical and thermal hyperalgesia in mice. FGF13 silencing mimics PW164 activity in culture and in vivo. Conversely, ZL192, an FGF13 …

Fgfr3-Induced Y158 Parp1 Phosphorylation Promotes Parp Inhibitor Resistance Via Brg1/Mre11-Mediated Dna Repair In Breast Cancer Models, Mei-Kuang Chen, Hirohito Yamaguchi, Yuan Gao, Weiya Xia, Jeffrey T Chang, Yu-Chun Hsiao, Tewodros W Shegute, Zong-Shin Lin, Chen-Shiou Wu, Yu-Han Wang, Jennifer K Litton, Qingqing Ding, Yongkun Wei, Yu-Yi Chu, Funda Meric-Bernstam, Helen Piwnica-Worms, Banu Arun, Jordi Rodon Ahnert, Jinsong Liu, Jun Yao, Wei-Chao Chang, Hung-Ling Wang, Coya Tapia, Constance T Albarracin, Khandan Keyomarsi, Shao-Chun Wang, Ying-Nai Wang, Gabriel N Hortobagyi, Chunru Lin, Liuqing Yang, Dihua Yu, Mien-Chie Hung

Faculty, Staff and Student Publications

Poly(ADP-ribose) polymerase (PARP) inhibitors (PARPis) are used to treat BRCA-mutated (BRCAm) cancer patients; however, resistance has been observed. Therefore, biomarkers to indicate PARPi resistance and combination therapy to overcome that are urgently needed. We identified a high prevalence of activated FGF receptor 3 (FGFR3) in BRCAm triple-negative breast cancer (TNBC) cells with intrinsic and acquired PARPi resistance. FGFR3 phosphorylated PARP1 at tyrosine 158 (Y158) to recruit BRG1 and prolong chromatin-loaded MRE11, thus promoting homologous recombination (HR) to enhance PARPi resistance. FGFR inhibition prolonged PARP trapping and synergized with PARPi in vitro and in vivo. High-level PARP1 Y158 phosphorylation (p-Y158) positively …