Digital Commons Network^™

Spase: Spatially Resolved Pathology Scores Using Optimal Transport On Spatial Transcriptomics Data, Mohammad Nuwaisir Rahman, Mohammed Abid Abrar, Vikram Rakesh Shaw, James F Martin, M Saifur Rahman, Md Abul Hassan Samee

Faculty, Staff and Students Publications

Pathological events often impact tissue regions in a spatial variable manner, making it challenging to identify therapeutic targets. Spatial transcriptomics (ST) is a powerful technology to map spatially variable molecular mechanisms, yet suitable analytical methods have been lacking. We introduce SPaSE (Spatially-resolved Pathology ScorE), an optimal transport-based algorithm to compare ST data from diseased and control tissues. SPaSE computes a “pathology score” for each spot in the diseased sample, quantifying the pathological impact at that spot. In post-MI (myocardial infarction) mouse hearts, these scores delineated zones that matched independent expert annotations. Modeling pathology scores from gene expression revealed signatures predictive …

Altered Patterning Of Neural Activity In A Neuropathology, Clarissa Hoffman, Jingheng Cheng, Rodrigo Morales, Daoyun Ji, Yuri Dabaghian

Faculty, Staff and Students Publications

The dynamics of neural circuits and their role in mediating cellular and organismal phenomena remain poorly understood, despite numerous efforts to dissect these processes through precise instantaneous measurements or longer-time averages and approximations. We use an alternative approach: we investigate these dynamics at the system's mesoscale by analyzing spike trains and waveforms. These extended activity patterns carry robust, tractable information, are highly responsive to physiological specifics, and enable detailed tracking of circuit behavior. In particular, this methodology allows for characterizing the functionality of tau-pathology-afflicted hippocampal circuits and identifying circuit-level abnormalities that are missed by through traditional analyses. In healthy mice, …

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 …

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 …

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 …

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 …

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 …

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 …

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 …

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.

Epha4 Signaling Dysregulation Links Abnormal Locomotion And The Development Of Idiopathic Scoliosis, Lianlei Wang, Xinyu Yang, Sen Zhao, 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 …

Exploring The Effect Of Led-To-Photodetector Spacing On Subcutaneous Photoplethysmography For Continuous Blood Pressure Measurement, Dario Cabal, Brian Nguyen, David B. Green, Kevin Kilgore, Varun Thakkar, Michael J. Fu, Steve J. Majerus

Student Scholarship

Photoplethysmography (PPG) is widely used to measure heart rate, blood oxygenation, and more recently, blood pressure. Implanted PPG systems offer the possibility to measure similar real-time measures of cardiovascular health, however, the detection method may vary due to a lack of capillary vessels for PPG sensors to observe in muscle tissue. To improve volumetric blood detection in large muscles, without relying on the capillary density of skin, a flexible PPG sensor was developed. The sensor included multiple spacing of illuminating infrared (IR) light emitting diodes (LEDs) and a single IR photodetector. This arrangement was expected to enable detection of blood …

Selective Alanine Transporter Utilization Is A Therapeutic Vulnerability In Arid1a-Mutant Ovarian Cancer, Hao Nie, Liping Liao, Rafal J Zielinski, Javier A Gomez, Akshay V Basi, Erin H Seeley, Lin Tan, Agnes Julia Bilecz, Wei Zhou, Heng Liu, Chen Wang, Shuai Wu, Yuan Qi, Taito Miyamoto, Federica Severi, Aaron R Goldman, Shengqing Gu, Anil K Sood, Amir A Jazaeri, Ronny Drapkin, Daniel T Claiborne, Nan Zhang, Philip L Lorenzi, Jared K Burks, Ernst Lengyel, Eyal Gottlieb, Rugang Zhang

Faculty, Staff and Student Publications

Subunits of the SWI/SNF chromatin remodeling complex are altered in ~20% of human cancers. Exemplifying the alterations is the ARID1A mutation that occurs in ~50% ovarian clear cell carcinoma (OCCC), a disease with limited therapeutic options. Here, we showed that ARID1A mutations create a dependence on alanine by regulating alanine transporters to increase intracellular alanine levels. ARID1A directly repressed alanine importer SLC38A2 and simultaneously promoted alanine exporter SLC7A8. ARID1A inactivation increased alanine utilization predominantly in protein synthesis and passively through the tricarboxylic acid cycle. Indeed, ARID1A-mutant OCCCs were hyper-sensitive to inhibition of SLC38A2. In addition, SLC38A2 inhibition enhanced chimeric antigen …

Spike Timing-Dependent Plasticity And Random Inputs Shape Interspike Interval Regularity Of Model Stn Neurons, Thoa Thieu, Roderick Melnik

School of Mathematical & Statistical Sciences Faculty Publications

Background/Objectives: Neuronal oscillations play a key role in the symptoms of Parkinson’s disease (PD). This study investigates the effects of random synaptic inputs, their correlations, and the interaction with synaptic dynamics and spike timing-dependent plasticity (STDP) on the membrane potential and firing patterns of subthalamic nucleus (STN) neurons, both in healthy and PD-affected states. Methods: We used a modified Hodgkin–Huxley model with a Langevin stochastic framework to study how synaptic conductance, random input fluctuations, and STDP affect STN neuron firing and membrane potential, including sensitivity to refractory period and synaptic depression variability. Results: Our results show that random inputs significantly …

Self-Other Generalisation Shapes Social Interaction And Is Disrupted In Borderline Personality Disorder, Joseph M Barnby, Jen Nguyen, Julia Griem, Magdalena Wloszek, Henry Burgess, Linda J Richards, Jessica Kingston, Gavin Cooper, P Read Montague, Peter Dayan, Tobias Nolte, Peter Fonagy, London Personality And Mood Disorders Consortium

2020-Current year OA Pubs

Generalising information from ourselves to others, and others to ourselves allows for both a dependable source of navigation and adaptability in interpersonal exchange. Disturbances to social development in sensitive periods can cause enduring and distressing damage to lasting healthy relationships. However, identifying the mechanisms of healthy exchange has been difficult. We introduce a theory of self-other generalisation tested with data from a three-phase social value orientation task - the Intentions Game. We involved humans with (

Ablation Of The Evolutionarily Acquired Functions Of The Atp1b4 Gene Increases Metabolic Capacity And Reduces Obesity, Nikolai N Modyanov, Lucia Russo, Sumona Ghosh Lester, Tamara R Castañeda, Himangi G Marathe, Larisa V Fedorova, Raymond E Bourey, Sonia M Najjar, Ivana L De La Serna

2020-Current year OA Pubs

In placental mammals, the co-option of vertebrate orthologous

Exogenous Arginine Differentially Regulates Inflammatory Cytokine And Inducible Nitric Oxide Synthase Expression In Macrophages, Kelsey Stayer, Saliha Pathan, Aalekhya Biswas, Huiqiao Li, Yi Zhu, Fong Wilson Lam, Juan Marini, Sundararajah Thevananther

Faculty, Staff and Students Publications

Immune dysfunction and late mortality from multiorgan failure are hallmarks of severe sepsis. Arginine, a semi-essential amino acid important for protein synthesis, immune response, and circulatory regulation, is deficient in sepsis. However, arginine supplementation in sepsis remains controversial due to the potential to upregulate inducible nitric oxide synthase (iNOS)-mediated excessive nitric oxide (NO) generation in macrophages, leading to vasodilation and hemodynamic catastrophe. Citrulline supplementation has been considered an alternative to replenishing arginine via de novo synthesis, orchestrated by argininosuccinate synthase 1 (ASS1) and argininosuccinate lyase (ASL). However, the functional relevance of the ASS1-ASL pathway in macrophages after endotoxin stimulation is …

Prevalence And Risk Factors Of Concurrent Osteoarthritis And Urolithiasis In Dogs In Thailand (2018–2020), Faiz Ihsanul Kamil, Kumpanart Soontornvipart

The Thai Journal of Veterinary Medicine

Osteoarthritis is a degenerative joint disease that significantly impacts dog health, often leading to chronic pain, reduced mobility, and behavioral changes that may predispose dogs to secondary conditions such as urolithiasis. This study aimed to investigate the association between osteoarthritis and urolithiasis in dogs using radiographic imaging data collected from the Small Animal Teaching Hospital, Chulalongkorn University, Thailand, over a three-year period (January 2018 to December 2020). A total of 16,377 dogs were included, and cases of osteoarthritis, urolithiasis, or the concurrent occurrence of both conditions were identified through a systematic database review. Binary logistic regression models were used to …