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Epha4 Signaling Dysregulation Links Abnormal Locomotion And The Development Of Idiopathic Scoliosis, Pengfei Zheng, Wen Wen, Kexin Xu, Xi Cheng, Qing Li, Anas M Khanshour, Yoshinao Koike, Junjun Liu, Xin Fan, Nao Otomo, Zefu Chen, Yaqi Li, Lulu Li, Haibo Xie, Panpan Zhu, Xiaoxin Li, Yuchen Niu, Shengru Wang, Sen Liu, Suomao Yuan, Chikashi Terao, Ziquan Li, Shaoke Chen, Xiuli Zhao, Pengfei Liu, Jennifer E Posey, Zhihong Wu, Guixing Qiu, Disco Study Group (Deciphering Disorders Involving Scoliosis & Comorbidities), Shiro Ikegawa, James R Lupski, Jonathan J Rios, Carol A Wise, Jianguo T Zhang, Chengtian Zhao, Nan Wu Jul 2025

Epha4 Signaling Dysregulation Links Abnormal Locomotion And The Development Of Idiopathic Scoliosis, Pengfei Zheng, Wen Wen, Kexin Xu, Xi Cheng, Qing Li, Anas M Khanshour, Yoshinao Koike, Junjun Liu, Xin Fan, Nao Otomo, Zefu Chen, Yaqi Li, Lulu Li, Haibo Xie, Panpan Zhu, Xiaoxin Li, Yuchen Niu, Shengru Wang, Sen Liu, Suomao Yuan, Chikashi Terao, Ziquan Li, Shaoke Chen, Xiuli Zhao, Pengfei Liu, Jennifer E Posey, Zhihong Wu, Guixing Qiu, Disco Study Group (Deciphering Disorders Involving Scoliosis & Comorbidities), Shiro Ikegawa, James R Lupski, Jonathan J Rios, Carol A Wise, Jianguo T Zhang, Chengtian Zhao, Nan Wu

Faculty, Staff and Students Publications

Idiopathic scoliosis (IS) is the most common form of spinal deformity with unclear pathogenesis. In this study, we first reanalyzed the loci associated with IS, drawing upon previous studies. Subsequently, we mapped these loci to candidate genes using either location-based or function-based strategies. To further substantiate our findings, we verified the enrichment of variants within these candidate genes across several large IS cohorts encompassing Chinese, East Asian, and European populations. Consequently, we identified variants in the EPHA4 gene as compelling candidates for IS. To confirm their pathogenicity, we generated zebrafish mutants of epha4a. Remarkably, the zebrafish epha4a mutants exhibited …


Pattern Of Cancer Mortality In Basrah Governorate From 2018–2022, Huda Hassan Al-Abboodi, Jafar Fawzi Al Badran, Nada Hasan Abdulraheem Jul 2025

Pattern Of Cancer Mortality In Basrah Governorate From 2018–2022, Huda Hassan Al-Abboodi, Jafar Fawzi Al Badran, Nada Hasan Abdulraheem

Iraqi National Journal of Medicine

Background: Cancer is the second leading cause of death globally, with an estimated 9.6 million fatalities reported in 2018. Thus, understanding the impact of cancer rates and examining how cancer deaths are distributed by age and have changed over the years is crucial. Aim: This descriptive statistical study aimed to identify the most prevalent cancer types responsible for deaths in the Basra Governorate from 2018 to 2022, along with their distribution across various age groups and geographical areas. Methods: The study utilized a descriptive statistical approach based on death certificate data from Basra Governorate, encompassing all cancer-related deaths from 2018 …


Evaluation Of Anatomic And Dosimetric Changes During Simultaneously Integrated Boost Volumetric Modulated Arc Therapy For Head And Neck Cancer, Farah Dirar Yousif, Raad Hefdhi Abedtwfeq Jul 2025

Evaluation Of Anatomic And Dosimetric Changes During Simultaneously Integrated Boost Volumetric Modulated Arc Therapy For Head And Neck Cancer, Farah Dirar Yousif, Raad Hefdhi Abedtwfeq

Iraqi National Journal of Medicine

Background: Volumetric modulated arc therapy (VMAT) is the most commonly used radiotherapy (RT) technique for locally advanced head and neck cancers (HNC), concurrent with chemotherapy. Aim: This study aims to evaluate the anatomical changes that may arise in patients undergoing VMAT treatment. Methods: The study involved 20 patients with locally advanced HNC who received VMAT treatment concurrently with chemotherapy. Prior to the initiation of radiotherapy treatment, computed tomography (CT) simulation was conducted for all patients. The prescribed doses for the primary target (PTVP), high-risk lymph nodes (PTV60), and low-risk lymph nodes (PTV54) were 69.96 Gy, 60 Gy, and 54 Gy, …


Integrated Genomic Analysis Of Nf1-Associated Peripheral Nerve Sheath Tumors: An Updated Biorepository Dataset, Jineta Banerjee, Yang Lyu, Kuangying Yang, Angela C Hirbe, Et Al. Jul 2025

Integrated Genomic Analysis Of Nf1-Associated Peripheral Nerve Sheath Tumors: An Updated Biorepository Dataset, Jineta Banerjee, Yang Lyu, Kuangying Yang, Angela C Hirbe, Et Al.

2020-Current year OA Pubs

Neurofibromatosis type 1 (NF1) is an inherited neurocutaneous condition that predisposes to the development of peripheral nerve sheath tumors (PNST) including cutaneous neurofibromas (CNF), plexiform neurofibromas (PNF), atypical neurofibromatous neoplasms of uncertain biologic potential (ANNUBP), and malignant peripheral nerve sheath tumors (MPNST). The Johns Hopkins NF1 biospecimen repository promotes the successful advancement of therapeutic developments for NF1-associated PNST through acquisition and genomic analysis of human tumor specimens. RNA sequencing (RNAseq) and whole exome sequencing (WES) data were generated from 73 and 114 primary human tumor samples, respectively. These pre-processed data, standardized for immediate computational analysis, are accessible through the NF …


Cancer Vaccination And Immune-Based Approaches In Pancreatic Cancer, Matthew D. Bloom, Ali Raza Shaikh, Zhengyang Sun, Babar Bashir, Adam E. Snook Jul 2025

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 …


Theoretical And Experimental Investigation Of Liquid-Liquid Phase Separation: Characterizing Elastin-Like-Polypeptides, Adam D. Quintana Jul 2025

Theoretical And Experimental Investigation Of Liquid-Liquid Phase Separation: Characterizing Elastin-Like-Polypeptides, Adam D. Quintana

Chemical and Biological Engineering ETDs

This dissertation develops and validates a semi-empirical Flory–Huggins-based interaction model, combined with Cahn–Hilliard simulations, for predicting multi-component liquid–liquid phase separation (LLPS) in elastin-like polypeptide (ELP) systems. Equilibrium droplet compositions, measured using a PDMS-based microfluidic device, enabled direct parameterization of interaction coefficients. The model was applied to generate phase diagrams and assess composition dependence in ternary mixtures. Cahn–Hilliard simulations were conducted to explore potential phase morphologies under different interfacial conditions. Multi-component Lattice Boltzmann simulations were implemented to model droplet morphology evolution under varying interfacial and diffusive parameters, reproducing experimentally relevant morphologies. A three-phase wetting study revealed conditions for selective wetting and …


Sensory Neuron-Expressed Fgf13 Controls Nociceptive Signaling In Diabetic Neuropathy Models, Aditya K Singh, Matteo Bernabucci, Nolan M Dvorak, Zahra Haghighijoo, Jessica Di Re, Feni K Kadakia, 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 Jul 2025

Sensory Neuron-Expressed Fgf13 Controls Nociceptive Signaling In Diabetic Neuropathy Models, Aditya K Singh, Matteo Bernabucci, Nolan M Dvorak, Zahra Haghighijoo, Jessica Di Re, Feni K Kadakia, 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 …


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, Melek Demirhan, Altaf Mohammed, Shizuko Sei, Jacklyn Thompson, Mahira Zaheer, Krishna M Sinha, Powel H Brown, Michelle I Savage, Eduardo Vilar, Praveen Rajendran, Roderick H Dashwood Jul 2025

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, Melek Demirhan, 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.


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, Silvia Menéndez, 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 Jul 2025

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, Silvia Menéndez, 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 …


Facts And Hopes: Toward The Next Quantum Leap In Melanoma, Keith T Flaherty, Andrew E Aplin, Michael A Davies, Nir Hacohen, Meenhard Herlyn, Patrick Hwu, James Mulé, Jennifer A Wargo, David E Fisher Jul 2025

Facts And Hopes: Toward The Next Quantum Leap In Melanoma, Keith T Flaherty, Andrew E Aplin, Michael A Davies, Nir Hacohen, Meenhard Herlyn, Patrick Hwu, 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 …


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, Fumie Tanzawa, Dale L Bixby, Harry P Erba, Nikolai Podoltsev, Gary J Schiller, Prasanna Kumar, Arnaud Lesegretain, Takeshi Isoyama, Takahiko Seki, Naval Daver, Michael Andreeff Jul 2025

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, Fumie Tanzawa, 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, Daniel De La Nava, 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 Jul 2025

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, Daniel De La Nava, 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 …


Ctdna Analysis In Erbb2-Amplified Colorectal Cancer: Biomarker Analysis Of The Mypathway Trial, Funda Meric-Bernstam, Kanwal Pratap Singh Raghav, Christopher J Sweeney, Charles Swanton, David R Spigel, Howard A Burris, Carin R Espenschied, Jessica M Grindheim, Julia Malato, Katja Schulze, Richard Price, Razelle Kurzrock Jul 2025

Ctdna Analysis In Erbb2-Amplified Colorectal Cancer: Biomarker Analysis Of The Mypathway Trial, Funda Meric-Bernstam, Kanwal Pratap Singh Raghav, Christopher J Sweeney, Charles Swanton, David R Spigel, Howard A Burris, Carin R Espenschied, Jessica M Grindheim, Julia Malato, Katja Schulze, Richard Price, Razelle Kurzrock

Faculty, Staff and Student Publications

Purpose: A combination of two HER2-directed antibodies, pertuzumab and trastuzumab (P + T), has antitumor activity in HER2-positive colorectal cancer. Although liquid biopsies are increasingly being used in clinical oncology, the association between tumor and ctDNA ERBB2 status and ctDNA monitoring for early response and resistance are unknown.

Patients and methods: Eighty-five patients with ERBB2-amplified and/or -overexpressed colorectal cancer were treated with P + T in the MyPathway trial; 42 had ctDNA testing at cycle (C) 1 day (D) 1, and 38 had longitudinal plasma tested for ctDNA. We analyzed the ctDNA versus tissue ERBB2 concordance, genomic co-alterations, and ctDNA …


Technology Roadmap Of Micro/Nanorobots, Xiaohui Ju, Chuanrui Chen, Cagatay M Oral, Semih Sevim, Ramin Golestanian, Negin Bouzari, 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 Jul 2025

Technology Roadmap Of Micro/Nanorobots, Xiaohui Ju, Chuanrui Chen, Cagatay M Oral, Semih Sevim, Ramin Golestanian, Negin Bouzari, 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 …


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, Tewodros W Shegute, 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 Jul 2025

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, Tewodros W Shegute, 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 …


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, Lisa Thomas, 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 Jul 2025

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, Lisa Thomas, 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 …


Distribution Of Alkylamines In Surface Waters Around The Antarctic Peninsula And Weddell Sea, Arianna Rocchi, Mark F. Fitzsimons, Preston Chebai Akenga, Ana Sotomayor, Elisabet L. Sà, Queralt Güell-Bujons, Magda Vila, Yaiza M. Castillo, Manuel Dall'osto, Dolors Vaqué, Charel Wohl, Rafel Simó, Elisa Berdalet Jul 2025

Distribution Of Alkylamines In Surface Waters Around The Antarctic Peninsula And Weddell Sea, Arianna Rocchi, Mark F. Fitzsimons, Preston Chebai Akenga, Ana Sotomayor, Elisabet L. Sà, Queralt Güell-Bujons, Magda Vila, Yaiza M. Castillo, Manuel Dall'osto, Dolors Vaqué, Charel Wohl, Rafel Simó, Elisa Berdalet

School of Geography, Earth and Environmental Sciences

Alkylamines, volatile organic nitrogen compounds with low molecular weight, are present in the surface ocean and participate in the marine biogeochemical nitrogen cycle, atmospheric chemistry and cloud formation. Alkylamines have been detected in polar regions, suggesting that these areas constitute emission hotspots of these compounds. However, knowledge of the sea surface distribution patterns and factors modulating alkylamines remain limited due to their high reactivity and low concentrations, which hamper accurate measurements. We investigated the presence and distribution of alkylamines in seawaters around the Antarctic Peninsula and the northern Weddell Sea during the late austral summer and explored their potential links …


Serum Metabolomic Profiling Of Incident Type 2 Diabetes Mellitus In The Multi-Ethnic Study Of Atherosclerosis And Rotterdam Study, Xuanwei Jiang, Fang Zhu, Gonçalo Graça, Xihao Du, Jinjun Ran, Fariba Ahmadizar, Alexis C Wood, Yanqiu Zhou, Denise M Scholtens, Ali Farzaneh, M Arfan Ikram, Alan Kuang, Carel W Le Roux, Meghana D Gadgil, Marilyn C Cornelis, Kent D Taylor, Xiuqing Guo, Mohsen Ghanbari, Laura J Rasmussen-Torvik, Russell P Tracy, Alain G Bertoni, Jerome I Rotter, David M Herrington, Philip Greenland, Maryam Kavousi, Victor W Zhong Jul 2025

Serum Metabolomic Profiling Of Incident Type 2 Diabetes Mellitus In The Multi-Ethnic Study Of Atherosclerosis And Rotterdam Study, Xuanwei Jiang, Fang Zhu, Gonçalo Graça, Xihao Du, Jinjun Ran, Fariba Ahmadizar, Alexis C Wood, Yanqiu Zhou, Denise M Scholtens, Ali Farzaneh, M Arfan Ikram, Alan Kuang, Carel W Le Roux, Meghana D Gadgil, Marilyn C Cornelis, Kent D Taylor, Xiuqing Guo, Mohsen Ghanbari, Laura J Rasmussen-Torvik, Russell P Tracy, Alain G Bertoni, Jerome I Rotter, David M Herrington, Philip Greenland, Maryam Kavousi, Victor W Zhong

Children’s Nutrition Research Center Staff Publications

Objective: This study aimed to investigate serum metabolomic biomarkers associated with incident type 2 diabetes mellitus (T2DM) and evaluate their performance in improving T2DM risk prediction.

Methods: Untargeted proton nuclear magnetic resonance (1H NMR) spectroscopy-based metabolomics analyses were conducted in the Multi-Ethnic Study of Atherosclerosis (MESA; n = 3460; discovery cohort) and The Rotterdam Study (RS; n = 1556; replication cohort). Multivariable cause-specific hazards models were used to analyze the associations between 23 571 serum metabolomic spectral variables and incident T2DM. Replicated metabolites required an false discovery rate-adjusted P < .01 in MESA, P < .05 in RS, and consistent direction of association. Pathway and network analyses were conducted to elucidate biological mechanisms underlying T2DM development. The utility of the replicated metabolites in improving T2DM risk prediction was assessed based on the Framingham Diabetes Risk Score. A 2-sample Mendelian randomization was conducted to assess causal associations.

Results: Nineteen metabolites were significantly associated with incident T2DM. Pathway analyses …


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 Jul 2025

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 …


A Qualitative Case Study On Mental Health Stigma Within Rastafarian Culture, Alecia Douglas Jul 2025

A Qualitative Case Study On Mental Health Stigma Within Rastafarian Culture, Alecia Douglas

Walden Dissertations and Doctoral Studies

Cultural and social factors, such as ethnic and racial backgrounds, religion, and supernatural beliefs, influence mental health utilization among African Americans. Past studies show that Rastafarians underutilize mental health services due to the stigma associated with mental health. However, there remains a gap in the literature regarding the incorporation of culturally sensitive and inclusive approaches in mental illness treatment. Per the biopsychosocial (BPS) pathways framework, biological, psychological, and social factors interact to provide a holistic architype of mental illness. The framework can be applied to understand how mental health stigma is influenced by personal beliefs, experiences, values, cultural, and societal …


Age, Gender, And Length Of Stay For Copd Patients In Florida Community Hospitals For 2019, Dr. Carol-Ann Miller Jul 2025

Age, Gender, And Length Of Stay For Copd Patients In Florida Community Hospitals For 2019, Dr. Carol-Ann Miller

Walden Dissertations and Doctoral Studies

Hospital administrators have been challenged due to length of stay (LOS) among patients suffering with chronic obstructive pulmonary disease (COPD). The purpose of this quantitative study was to examine whether there was a relationship between age, gender, and length of stay for COPD patients in Florida during the year 2019. The dependent variable was COPD length of stay, and independent variables were age and gender in Florida community hospitals during 2019. The Donabedian model was selected as the theoretical framework for this study to address structure, process, and outcomes associated with COPD readmissions. Secondary data was obtained from the Healthcare …


Finding Deepfakes: A Tabletop Exercise About Ai, Decisionmaking, And Algorithmic Performance, Andrea Brennan, Gwyneth Sutherlin, Lisa Pagano-Wallace, Hermie Mendoza Jul 2025

Finding Deepfakes: A Tabletop Exercise About Ai, Decisionmaking, And Algorithmic Performance, Andrea Brennan, Gwyneth Sutherlin, Lisa Pagano-Wallace, Hermie Mendoza

Joint Force Quarterly

This article explores a first-of-its-kind tabletop exercise designed to expose U.S. military and national security professionals to the real-world challenges of using AI tools like deepfake detectors in high-stakes decisionmaking. Set in a fictional scenario involving a flawed AI system, participants confronted algorithmic bias, technical uncertainty, and ethical dilemmas, revealing how AI limitations can erode trust in intelligence products. Drawing from student and faculty reflections, the article highlights the importance of preparing future leaders to scrutinize and manage AI performance failures not only as technical bugs but as complex, systemic issues with social and operational consequences. The exercise underscored the …


Ud Wildlife Ecologist Awarded Odnr Grant To Track Black Bears Recolonizing Ohio, Dave Larsen Jul 2025

Ud Wildlife Ecologist Awarded Odnr Grant To Track Black Bears Recolonizing Ohio, Dave Larsen

College of Arts and Sciences Newsroom

The four-year grant will support the field activities of the faculty member, a doctoral student and undergraduate research technicians.


The Clock Is Ticking: A Systemic Review Of The Literature Informing High School Student Self-Agency In Managing Mental Health Issues For The Purpose Of Staying In Class And Learning, Chantal Ritter-Meserve Jul 2025

The Clock Is Ticking: A Systemic Review Of The Literature Informing High School Student Self-Agency In Managing Mental Health Issues For The Purpose Of Staying In Class And Learning, Chantal Ritter-Meserve

Educational Studies Dissertations

This dissertation grounded in a dual-theoretical framework of Bandura's Self-Efficacy Theory and the Black Panther Party’s Revolutionary Theory of CommunityEmpowerment presents a systematic review of the literature exploring how high school students impacted by trauma, poverty, and systemic inequities utilize self-efficacy to remain engaged in learning, especially when immediate access to school-based mental health support is limited. 150 research articles across educational, psychological and sociopolitical domains were screened and 28 articles were analyzed to answer the three guided research questions:

1. How do mental health challenges affect high school students’ academic engagement?

2. How do high school students with self-efficacy …


Comunidades Y Vacunas: Findings On Vaccine Hesitancy In Latine Families With Autistic Children, Danica Leticia Limon-Mialkowski Jul 2025

Comunidades Y Vacunas: Findings On Vaccine Hesitancy In Latine Families With Autistic Children, Danica Leticia Limon-Mialkowski

Theses and Dissertations

Parent vaccine hesitancy (VH) and subsequent vaccine refusal for children has escalated in the U.S. over the past several years and is more common among parents with an autistic child compared to the general population (Zerbo et al., 2018). This is an important issue to address given that VH has led to a resurgence of vaccine-preventable diseases (DeStefano & Shimabukuro, 2019; Geoghegan, et al., 2020). Research shows that VH is affected by parent cultural background (Fombonne et al., 2020) and that minoritized groups are more likely to experience VH (48.1% in parents of color [POC] groups versus 22.9% in White …


White Students' Perceptions Of Campus Racial Climate And White Racial Identity Development At A Predominately White Liberal Arts Institution, Katie O'Brien Jul 2025

White Students' Perceptions Of Campus Racial Climate And White Racial Identity Development At A Predominately White Liberal Arts Institution, Katie O'Brien

Theses and Dissertations

The purpose of the study is to examine the perceptions of White students about campus racial climate at a predominantly White liberal arts college in connection with students’ White racial identity development and liberal arts curriculum. The research study aims to promote a better understanding of campus racial climate at PWIs from the perspective of White students to provide insights on ways to improve campus racial climate, specifically for students of color. The data for this project were primarily collected through semi-structured qualitative interviews with White students. Quantitative data was also collected in the form of a racial attitudes assessment …


The Potential Of Microbial Fuel Cells As A Dual Solution For Sustainable Wastewater Treatment And Energy Generation: A Case Study, Shajjadur Rahman Shajid, Monjur Mourshed, Md. Golam Kibria, Bahman Shabani Jul 2025

The Potential Of Microbial Fuel Cells As A Dual Solution For Sustainable Wastewater Treatment And Energy Generation: A Case Study, Shajjadur Rahman Shajid, Monjur Mourshed, Md. Golam Kibria, Bahman Shabani

Mechanical and Aerospace Engineering Student Publications and Presentations

Microbial fuel cells (MFCs) are bio-electrochemical systems that harness microorganisms to convert organic pollutants in wastewater directly into electricity, offering a dual solution for sustainable wastewater treatment and renewable energy generation. This paper presents a holistic techno-economic and environmental feasibility assessment of largescale MFC deployment in Dhaka’s industrial zone, Bangladesh, as a relevant case study. Here, treating 100,000 cubic meters of wastewater daily would require a capital investment of approximately USD 500 million, with a total project cost ranging between USD 307.38 million and 1.711 billion, depending on system configurations. This setup has an estimated theoretical energy recovery of 478.4 …


Tightrope Walking: Lived Experiences Of Adult Siblings Of Individuals With Severe Autism, Anna Dega Jul 2025

Tightrope Walking: Lived Experiences Of Adult Siblings Of Individuals With Severe Autism, Anna Dega

ETD Collection

No abstract provided.


Arterial Stiffness In Heart-Healthy Indigenous Tsimane Forager-Horticulturalists, Tianyu Cao, Edhitt Cortez Linares, Raul Quispe Gutierrez, Daniel Eid Rodriguez, Jesus Bani Cuata, Michael I. Miyamoto, Christopher Von Rueden, Daniel K. Cummings, Paul L. Hooper, Benjamin C. Trumble, Jonathan Stieglitz, Randall C. Thompson, Gregory S. Thomas, Hillard S. Kaplan, Daniel A. Duprez, David R. Jacobs Jr., Michael Gurven Jul 2025

Arterial Stiffness In Heart-Healthy Indigenous Tsimane Forager-Horticulturalists, Tianyu Cao, Edhitt Cortez Linares, Raul Quispe Gutierrez, Daniel Eid Rodriguez, Jesus Bani Cuata, Michael I. Miyamoto, Christopher Von Rueden, Daniel K. Cummings, Paul L. Hooper, Benjamin C. Trumble, Jonathan Stieglitz, Randall C. Thompson, Gregory S. Thomas, Hillard S. Kaplan, Daniel A. Duprez, David R. Jacobs Jr., Michael Gurven

ESI Publications

Background

Little is known about arterial stiffness in rural subsistence populations that experience few cardiovascular risk factors. We conducted a cross‐sectional study comparing 3 arterial stiffness metrics among Tsimane forager‐horticulturalists with 2 representative US cohorts.

Methods

Arterial elasticity (the inverse of stiffness) markers C1 (large artery elasticity) and C2 (small artery elasticity) were measured using a tonometry device among 490 Tsimane adults (mean age, 51.2±10.1 years; 55% women), and compared with 6294 multiethnic US adults (mean age, 62.0±10.2 years; 52% women) from MESA (Multi‐Ethnic Study of Atherosclerosis). Carotid‐femoral pulse wave velocity was assessed using the foot‐to‐foot method in a smaller …


Usa V. Erik Harris Jul 2025

Usa V. Erik Harris

2025 Decisions

USDC for the Western District of Pennsylvania