Digital Commons Network^™

Determining Accurate Pore Structures Of Polypropylene Membrane For Ecmo Using Fe-Sem Under Optimized Conditions, Makoto Fukuda, Yoshiaki Nishite, Eri Murata, Koki Namekawa, Tomohiro Mori, Tsutomu Tanaka, Kiyotaka Sakai

Children’s Nutrition Research Center Staff Publications

Long-term ECMOs are expected to be put into practical use in order to prepare for the next emerging severe infectious diseases after the novel coronavirus pandemic in 2019-2023. While polypropylene (PP) and polymethylpentene (PMP) are currently the mainstream materials for the hollow fiber membranes of ECMO, the PP membrane coated with a silicone layer on the outer surface has also been commercialized. In this study, we sought a method to accurately observe the detailed pore morphologies of the PP membrane by suppressing irreversible changes in the morphology in SEM observation, which is a general-purpose observation with higher resolution. As a …

Regulation Of Myogenesis By Mechanomir-200c/Foxo3 Axis, Junaith S Mohamed, Aladin M Boriek

Faculty, Staff and Students Publications

Cyclic mechanical stretch has been shown to inhibit myoblast differentiation while promoting proliferation. However, the underlying molecular mechanisms are not well understood. Here, we report that mechanical stretch inhibits the differentiation of mouse primary myoblasts by promoting the cell cycle program and by inhibiting the expression of the myogenic regulator MyoD. Stretch alters the miRNA expression profile as evidenced by miRNA microarray analysis. We identified miR-200c as one of the highly downregulated mechanosensitive miRNAs (mechanomiRs) whose expression level was increased during differentiation. This suggests that mechanomiRs-200c is a myogenic miRNA. Overexpression of mechanomiR-200c revoked the effect of stretch on myoblast …

A Forward Genetic Screen Identifies Potassium Channel Essentiality In Shh Medulloblastoma Maintenance, Jerry J Fan, Anders W Erickson, Julia Carrillo-Garcia, Xin Wang, Patryk Skowron, Xian Wang, Xin Chen, Guanqiao Shan, Wenkun Dou, Shahrzad Bahrampour, Yi Xiong, Weifan Dong, Namal Abeysundara, Michelle A Francisco, Ronwell J Pusong, Wei Wang, Miranda Li, Elliot Ying, Raúl A Suárez, Hamza Farooq, Borja L Holgado, Xiaochong Wu, Craig Daniels, Adam J Dupuy, Juan Cadiñanos, Allan Bradley, Anindya Bagchi, Branden S Moriarity, David A Largaespada, A Sorana Morrissy, Vijay Ramaswamy, Stephen C Mack, Livia Garzia, Peter B Dirks, Xuejun Li, Siyi Wanggou, Sean Egan, Yu Sun, Michael D Taylor, Xi Huang

Faculty, Staff and Students Publications

Distinguishing tumor maintenance genes from initiation, progression, and passenger genes is critical for developing effective therapies. We employed a functional genomic approach using the Lazy Piggy transposon to identify tumor maintenance genes in vivo, and applied this to SHH medulloblastoma (MB). Combining Lazy Piggy screening in mice and transcriptomic profiling of human MB, we identified the voltage-gated potassium channel KCNB2 as a candidate maintenance driver. KCNB2 governs cell volume of MB-propagating cells, with KCNB2 depletion causing osmotic swelling, decreased plasma membrane tension, and elevated endocytic internalization of EGFR, thereby mitigating proliferation of MB-propagating cells to ultimately impair MB growth. …

Radiotherapy Promotes Cuproptosis And Synergizes With Cuproptosis Inducers To Overcome Tumor Radioresistance, Guang Lei, Mingchuang Sun, Jun Cheng, Rui Ye, Zhengze Lu, Amber Horbath, David Huo, Shengrong Wu, Anagha Alapati, Sadhna Aggarwal, Zhihao Xu, Chao Mao, Yuelong Yan, Jun Yao, Qidong Li, Xiong Chen, Hyemin Lee, Li Zhuang, Dadi Jiang, Apar Pataer, Jack A Roth, Nicholas Navin, Albert C Koong, Mingjian James You, Steven H Lin, Boyi Gan

Faculty, Staff and Student Publications

Cuproptosis is a recently identified form of copper-dependent cell death. Here, we reveal that radiotherapy (RT) induces cuproptosis in cancer cells, independent of apoptosis and ferroptosis, and depletes lipoylated proteins and iron-sulfur (Fe-S) cluster proteins-both hallmarks of cuproptosis-in patient tumors. Mechanistically, RT elevates mitochondrial copper levels by upregulating copper transporter 1 (CTR1) and depleting mitochondrial glutathione, a copper chelator, thereby triggering cuproptosis. Integrated analyses of RNA sequencing (RNA-seq) from radioresistant esophageal cancer cells and single-cell RNA-seq from esophageal tumors of patients unresponsive to RT link radioresistance to the downregulation of BTB and CNC homology 1 (BACH1). This downregulation de-represses the …

Transformative Integration: Navigating Opportunities And Challenges In A Medical School's Evolution Into Integrated Service Units, Chelsea Chang, Everardo Cobos, Michael Sander, Beatriz Tapia, Michael Hocker

School of Medicine Publications

Medical schools must evolve with the changing healthcare landscape and financial pressures. Academic Health Centers have responded to these changes with a novel organizational model known as an integrated service line. Traditional medical school departments often create silos, lack of alignment, and financial burdens. To our knowledge, we were the first medical school to implement an integrated structure combining the tripartite missions of academics, research, and clinical services.

The University of Texas Rio Grande Valley School of Medicine accepted its charter class of 55 medical students in 2016 with a traditional medical school department model. By 2023, it had 154 …

Spatial And Multiomics Analysis Of Human And Mouse Lung Adenocarcinoma Precursors Reveals Tim-3 As A Putative Target For Precancer Interception, Bo Zhu, Pingjun Chen, Muhammad Aminu, Jian-Rong Li, Junya Fujimoto, Yanhua Tian, Lingzhi Hong, Hong Chen, Xin Hu, Chenyang Li, Natalie Vokes, Andre L Moreira, Don L Gibbons, Luisa M Solis Soto, Edwin Roger Parra Cuentas, Ou Shi, Songhui Diao, Jie Ye, Frank R Rojas, Eduardo Vilar, Anirban Maitra, Ken Chen, Nicolas Navin, Monique Nilsson, Beibei Huang, Simon Heeke, Jianhua Zhang, Cara L Haymaker, Vamsidhar Velcheti, Daniel H Sterman, Veena Kochat, William I Padron, Ludmil B Alexandrov, Zhubo Wei, Xiuning Le, Linghua Wang, Junya Fukuoka, J Jack Lee, Ignacio I Wistuba, Harvey I Pass, Mark Davis, Samir Hanash, Chao Cheng, Steven Dubinett, Avrum Spira, Kunal Rai, Scott M Lippman, P Andrew Futreal, John V Heymach, Alexandre Reuben, Jia Wu, Jianjun Zhang

Faculty, Staff and Student Publications

How tumor microenvironment shapes lung adenocarcinoma (LUAD) precancer evolution remains poorly understood. Spatial immune profiling of 114 human LUAD and LUAD precursors reveals a progressive increase of adaptive response and a relative decrease of innate immune response as LUAD precursors progress. The immune evasion features align the immune response patterns at various stages. TIM-3-high features are enriched in LUAD precancers, which decrease in later stages. Furthermore, single-cell RNA sequencing (scRNA-seq) and spatial immune and transcriptomics profiling of LUAD and LUAD precursor specimens from 5 mouse models validate high TIM-3 features in LUAD precancers. In vivo TIM-3 blockade at precancer stage, …

Radiotherapy Promotes Cuproptosis And Synergizes With Cuproptosis Inducers To Overcome Tumor Radioresistance, Guang Lei, Mingchuang Sun, Jun Cheng, Rui Ye, Zhengze Lu, Amber Horbath, David Huo, Shengrong Wu, Anagha Alapati, Sadhna Aggarwal, Zhihao Xu, Chao Mao, Yuelong Yan, Jun Yao, Qidong Li, Xiong Chen, Hyemin Lee, Li Zhuang, Dadi Jiang, Apar Pataer, Jack A Roth, Nicholas Navin, Albert C Koong, Mingjian James You, Steven H Lin, Boyi Gan

Faculty, Staff and Student Publications

Cuproptosis is a recently identified form of copper-dependent cell death. Here, we reveal that radiotherapy (RT) induces cuproptosis in cancer cells, independent of apoptosis and ferroptosis, and depletes lipoylated proteins and iron-sulfur (Fe-S) cluster proteins-both hallmarks of cuproptosis-in patient tumors. Mechanistically, RT elevates mitochondrial copper levels by upregulating copper transporter 1 (CTR1) and depleting mitochondrial glutathione, a copper chelator, thereby triggering cuproptosis. Integrated analyses of RNA sequencing (RNA-seq) from radioresistant esophageal cancer cells and single-cell RNA-seq from esophageal tumors of patients unresponsive to RT link radioresistance to the downregulation of BTB and CNC homology 1 (BACH1). This downregulation de-represses the …

Assessing The Efficacy Of Eutectic Mixture Of Local Anesthesia Cream And Vapocoolant Spray In Mitigating The Pain Associated With Ear-Tagging In Pre-Weaned Calves, Yu-Jhe Lo, Thomas Chia-Tang Ho, Jacky Peng-Wen Chan

The Thai Journal of Veterinary Medicine

This study evaluated the efficacy of a eutectic mixture of local anesthetics (EMLA) cream and vapocoolant spray (VS) in preventing pain in calves following ear-tagging. Thirty-four calves were randomly assigned to three groups: no anesthesia control (CON, n=11), EMLA applied 60 minutes prior (EMLA, n=11), and five-second VS application immediately prior (VS, n=12). Pain pressure threshold (PPT) was measured at 18±1 days of age, with the left ear of the CON group serving as the sham group (Sham, n=11), followed by ear-tagging at 21±1 days. Post-tagging assessments included pain-related behaviors, serum cortisol levels, heart rate, and wound scores. The PPT …

Simple And Complex Phonic Tics In Tourette Syndrome, José Fidel Baizabal-Carvallo, Joseph Jankovic

Faculty, Staff and Students Publications

Tourette syndrome (TS) is the most common cause of tics. Tics are classified as motor and phonic tics. The latter (previously also referred to as “vocal tics”) are manifested by simple sounds (simple phonic tics) or complex, often semantically meaningful utterances (complex phonic tics). Methods: We compared the clinical and demographic features of consecutive patients with TS who exhibited simple and complex phonic tics. Results: There were 149 patients, 117 (78.5%) of whom were males; the mean age at evaluation was 19.61 ± 12.97 years. In total, 35 (23.5%) of these manifested complex phonic tics, and 26 (17.4%) had verbalizations. …

Uncovering The Efficacy Of A Natural Homemade Sunscreen In Protection From Ultraviolet Radiation, Furkan Akif Ince, Julianne Clare Nayar, Alicia Lauren Wong, James Andrew Mcclelland, Andrew J.A. Holland, Harvey Stern, Myriam Abboud, Rebecca Sara Mason, Katie Marie Dixon

All Works

In Australia, skin cancer has the highest incidence of all cancer types, where Therapeutic Goods Association-approved, broad-spectrum sunscreens are recommended to prevent skin carcinogenesis. Commercial sunscreen ingredients, however, have been associated with negative impacts on human health, animal health and the environment. Together, the perceived harmful effects of commercial sunscreens have driven a trend towards home formulation of natural sunscreens, recipes for which are widely available online. Scientific evidence to support the efficacy of natural sunscreens, however, is lacking. We tested the efficacy of a natural homemade sunscreen (NHSS) published online by a wellness blogger with the aim to determine …

Evaluating Impacts Of Improved Flooring On Enteric And Parasitic Infections In Rural Households In Kenya: Study Protocol For A Cluster-Randomised Controlled Trial, Katherine E. Halliday, Stella Kepha, Hugo Legge, Elizabeth Allen, Robert Dreibelbis, Lynne Elson, Beatrice K. Kakoi, Carlos Mcharo, Sharon Muli, Jacinta Mwongeli, Doris Njomo, Margaret M. Njoroge, Victoria Ochwal, William E. Oswald, Martin Rono, Tuva K. Safari, Ulrike Filinger, James Wambua Kaluli, Charles S. Mwandawiro, Rachel L. Pullan

All Peer-Reviewed Publications

Introduction Earthen floors are often damp or dusty and difficult to clean, providing an ideal environment for faecal pathogens and parasites. Observational studies have revealed associations between household flooring and health outcomes, but robust experimental evidence is scant. This study will evaluate the impact of an improved household flooring intervention on enteric infections, soil-transmitted helminth (STH) infections and tungiasis through implementation of a cluster-randomised trial in two rural settings in Kwale and Bungoma Counties, Kenya. Methods and analyses 440 clusters (households) across both sites are allocated to control or intervention group, in which a low-cost, sealed, washable, cement-based floor is …

Translation Suppresses Exogenous Target Rna-Mediated Microrna Decay, Tianqi Li, Lu Li, Nicholas M Hiers, Peike Sheng, Yuzhi Wang, Conner M Traugot, Jessi F Effinger-Morris, Pitchaporn Akaphan, Yanyan Liu, Jiang Bian, Kotaro Fujii, Mingyi Xie

Faculty, Staff and Student Publications

MicroRNAs (miRNAs) interact with the target mRNAs to induce translational repression and mRNA degradation. Interestingly, miRNAs themselves can turnover rapidly when binding to a target RNA with extensive complementarity, a phenomenon called target-directed miRNA degradation (TDMD). To date, all validated TDMD "triggers" can induce miRNA degradation reside in non-coding regions of the RNA. We found that TDMD triggers placed in the 3' untranslated region (UTR) of a reporter degraded miRNAs more effectively than those in the coding sequence (CDS). Inhibiting translation of the reporter enhanced miRNA degradation by the CDS trigger, indicating that ribosome-free CDS triggers are more accessible to …

Cognition And Behavior In Neurofibromatosis Type 1: Report And Perspective From The Cognition And Behavior In Nf1 (Cabin) Task Force, David H Gutmann, Corina Anastasaki, Aditi Gupta, Yang Hou, Stephanie M Morris, Jonathan M Payne, Jacob Raber, Seth M Tomchik, Linda Van Aelst, James A Walker, Kaleb H Yohay

2020-Current year OA Pubs

Individuals with neurofibromatosis type 1 (NF1) are prone to the evolution of neurodevelopmental symptomatology including motor delays, learning disabilities, autism, and attention deficits. Caused by heterozygous germline mutations in the

A Literature-Informed Nutrition Patient Communication Toolkit For Hashimoto’S Thyroiditis, Kieren Ritter

Department of Nutrition Student Projects

This project is intended to help bridge the gap in nutrition education and treatment for the autoimmune disease Hashimoto’s thyroiditis (HT). Current research was synthesized and converted into a communication tool for adults diagnosed with HT. The toolkit was based on 33 articles, from three databases, that passed the inclusion and exclusion criteria for analysis. The education toolkit was intended to be practical and valuable for below a high school reading level. The aforementioned articles reviewed the effects of dietary changes on HT with vitamin D, selenium, gluten removal, dietary patterns such as the Mediterranean diet and Autoimmune Protocol, and …

A Pre–Post Study Evaluating An Online Cbt-Based Intervention To Improve Academic Performance In Students With Low Mood, Suheir Awadalla, E. Bethan Davies, Cris Glazebrook

All Works

Online cognitive-behavioural therapy (CBT)-based interventions have shown the potential to improve the mental health of university students. However, their impact on West Asian cultures and educational achievement has yet to be fully investigated. This study explores the feasibility, acceptability, and potential effectiveness of a self-directed, internet-delivered, cognitive–behavioural skills training programme (MoodGYM) in reducing depression and improving academic performance among university students in the United Arab Emirates (UAE). This exploratory pre- and postintervention study with a historical control group recruited 50 students, having a GPA <2 and self-reporting at least one of two key depressive symptoms, from one UAE university. The results demonstrated that the total Hospital Depression and Anxiety Scale (HADS) depression score (HADS-D) decreased after the intervention (P = 0.004), and the proportion of participants scoring above the cutoff for depression (HADS-D ≥8) decreased from 77.2 to 27.3% (p < 0.001). There was also a significant reduction in HADS-anxiety scores (p < 0.001), and the proportion of participants above the cut-off for anxiety (HADS-A ≥8) decreased from 50% to 11.4% (p = 0.001). GPA improved significantly over time (p < 0.001, d = 1.3), and attendance warnings decreased (p = 0.008, d = 0.6). Most students (79.6%) evaluated MoodGYM as useful, and all students completed at least two MoodGYM modules. This study shows that MoodGYM, a web-based mental health promotion intervention, improves academic achievement in university students with depressive symptoms. Further research is needed to explore how MoodGYM can be best implemented within university settings.

Loss Of Function Of The Zinc Finger Homeobox 4 Gene, Zfhx4, Underlies A Neurodevelopmental Disorder, María Del Rocío Pérez Baca, María Palomares-Bralo, Michiel Vanhooydonck, Lisa Hamerlinck, Eva D'Haene, Sebastian Leimbacher, Eva Z Jacobs, Laurenz De Cock, Erika D'Haenens, Annelies Dheedene, Zoë Malfait, Lies Vantomme, Ananilia Silva, Kathleen Rooney, Xiaonan Zhao, Amir Hossein Saeidian, Nichole Marie Owen, Fernando Santos-Simarro, Roser Lleuger-Pujol, Sixto García-Miñaúr, Itsaso Losantos-García, Björn Menten, Gaia Gestri, Nicola Ragge, Bekim Sadikovic, Elke Bogaert, Kris Vleminckx, Thomas Naert, Delfien Syx, Bert Callewaert, Sarah Vergult

Faculty, Staff and Students Publications

8q21.11 microdeletions involving ZFHX4 have previously been associated with a syndromic form of intellectual disability, hypotonia, unstable gait, and hearing loss. We report on 63 individuals-57 probands and 6 affected family members-with protein-truncating variants (n = 41), (micro)deletions (n = 21), or an inversion (n = 1) affecting ZFHX4. Probands display variable developmental delay and intellectual disability, distinctive facial characteristics, morphological abnormalities of the central nervous system, behavioral alterations, short stature, hypotonia, and occasionally cleft palate and anterior segment dysgenesis. The phenotypes associated with 8q21.11 microdeletions and ZFHX4 intragenic loss-of-function (LoF) variants largely overlap, although leukocyte-derived DNA shows a mild …

Senescence Caused By Telomerase Inactivation In Myeloid, Mesenchymal, And Endothelial Cells Has Distinct Effects On Cancer Progression, Joseph Rupert, Zhanguo Gao, Yongmei Yu, Mikhail G Kolonin

Faculty, Staff and Student Publications

The effects of cell senescence in individual cell populations of the tumor microenvironment (TME) on cancer progression remain unclear. Here, we investigated the effects of cell senescence caused by inactivation of the catalytic subunit of telomerase (Tert) in distinct TME components. We generated genetic Tert knockout (KO) mice driven by the LysM promoter in myeloid cells, by the Pdgfra or Pdgfrb promoter in mesenchymal cells, and by the Tie2e promoter in endothelial cells. We compared the effect of the Tert KOs in syngeneic models of orthotopically grafted E0771 breast adenocarcinoma, RM1 prostate adenocarcinoma, and KPC pancreatic adenocarcinoma. Tumors in LysM-Tert …

Swi/Snf Atpase Silenced Hlf Potentiates Lung Metastasis In Solid Cancers, Jin Zhou, Austin Hepperla, Jeremy M Simon, Kangsan Kim, Qing Hu, Chuanhai Zhang, Lei Dong, Lianxin Hu, Cheng Zhang, Chengheng Liao, Alice Fang, Yayoi Adachi, Haoyong Fu, Tao Wang, Qian Liang, Fangzhou Zhao, Hongyi Liu, Masashi Takeda, Jun Fang, Hua Zhong, Peter Ly, Lu Wang, Payal Kapur, Lin Xu, Liwei Jia, Srinivas Malladi, James Brugarolas, M Celeste Simon, Bo Li, Qing Zhang

Faculty, Staff and Student Publications

Metastasis is the main cause of cancer-related deaths, yet the underlying mechanisms remain elusive. Here, using clear cell renal cell carcinoma (ccRCC), a tumor type with frequent lung metastases, we conduct an in vivo genome-wide CRISPR-Cas9 screen and identify HLF as a potent suppressor of lung metastasis. HLF depletion enhances ccRCC cell migration and lung metastasis, whereas HLF overexpression abrogates these effects. In ccRCC patients, HLF expression is reduced at metastatic sites and associates with epigenetic silencing mediated by the SWI/SNF ATPase subunit BRG1. HLF levels negatively correlate with migration potential in collagen. Mechanistically, HLF regulates LPXN expression, modulating the …

Childhood Myopia Part Ii: Treatment Mechanisms, Emerging Options, And Considerations, Safal Khanal Dr, Erin S. Tomiyama Dr, Síofra Harrington Dr

Articles

Abstract

The rapidly increasing prevalence of myopia and its association with vision-threatening complications in later life has intensified efforts to identify treatments that can prevent the onset and slow the progression of myopia in children. These efforts have led to the development of several optical, environmental, and pharmacological myopia control treatments. Investigations of additional treatment options are ongoing and have shown great promise for clinical translation. Although significant progress has been made in identifying potential pathways and modes of action of these treatments, a complete mechanistic understanding is still lacking. This critical review article explores the potential mechanisms underlying the …

A Cascading Effects Model Of Early Sensory Development In Autism, Natalie Russo, Carissa J. Cascio, Grace T. Baranek, Tiffany G. Woynaroski, Zachary J. Williams, Shulamite A. Green, Roseann Schaaf

Department of Occupational Therapy Faculty Papers

Autism has historically been defined by the presence of differences in social communication and restricted, repetitive patterns of behavior, interests, or activities (RRBs). Since 2013 when the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders was published, sensory features were added as one of the polythetic restricted and repetitive behavior diagnostic criteria of autism, though it has remained understudied. Here, we summarize theory and research to provide support for the perspective that early sensory functions and experiences play a primary role in autism and have downstream effects on social communication and repetitive behavioral features of autism. The …

Triterpenoid Cddo-Ea Protects From Hyperglycemia, Hyperinsulinemia, And Obesity By Decreasing Energy Intake, Austin E. Cantu, Cordelia Rasa, Shizue Mito, Denae Cantu, Juan Lopez-Alvarenga, Leslie L. Rivera-Lopez, Israel Rios, Ashley Abrego-Gonzalez, Sara M. Reyna

School of Medicine Publications

Obesity is a significant factor in the development of type 2 diabetes (T2D). Treatment of obesity is pivotal in the prevention and management of T2D, and the development of new pharmacological therapies are studied for improving insulin resistance and glucose intolerance. Oleanolic acid-derived triterpenoids, 2-cyano-3,12-dioxoolean-1,9-dien-28-oic acids (CDDOs), are studied to elucidate the mechanisms by which they protect against obesity. However, fundamental knowledge gaps remain regarding the physiological and molecular mechanisms by which CDDOs protect against obesity. Our recently published studies showed that CDDO-ethyl amide (CDDO-EA) prevents skeletal muscle inflammation by inhibiting activation of nuclear factor-kappa B (NF-κB) signaling. Moreover, CDDO-EA …

Advances In Molecular Imaging Of Vegfrs: Innovations In Imaging And Therapeutics, Hanieh Karimi, Sarah Lee, Wenqi Xu, Sigrid A. Langhans, David K. Johnson, Erik Stauff, Heidi H. Kecskemethy, Lauren W. Averill, Xuyi Yue

Department of Radiology Faculty Papers

Vascular endothelial growth factor receptors (VEGFRs) are key regulators of angiogenesis, lymphangiogenesis, and vascular permeability, playing essential roles in both physiological and pathological processes. The VEGFR family, including VEGFR-1, VEGFR-2, and VEGFR-3, interacts with structurally related VEGF ligands (VEGFA, VEGFB, VEGFC, VEGFD, and placental growth factor [PlGF]), activating downstream signaling pathways that mediate critical cellular processes, including proliferation, migration, and survival. Dysregulation of VEGFR signaling has been implicated in numerous diseases, such as cancer, cardiovascular conditions, and inflammatory disorders. Targeting VEGFRs with radiopharmaceuticals, such as radiolabeled peptides, antibodies, and specific tracers like 64Cu-bevacizumab and 89Zr-ramucirumab, has emerged as a powerful …

Effects Of Cerebral Tumor Necrosis Factor Alpha On Systemic Glucose Homeostasis In Obese Mice, Gabriela Griepp

Honors Projects

Type 2 diabetes mellitus (T2DM) is a metabolic disorder characterized by impaired blood glucose regulation and persistent hyperglycemia. The central nervous system functions as a key regulator in the maintenance of peripheral normoglycemia. Obesity, commonly associated with T2DM, often leads to chronic inflammation in the hypothalamus, a critical brain center for integrating metabolic feedback and controlling outputs to peripheral organs. However, the physiological mechanisms through which obesity-induced brain inflammation affects glucose regulation remain somewhat unclear. Previous studies have linked one key pro-inflammatory cytokine, tumor necrosis factor alpha (TNF-α), to metabolic function and glycemic control; however, the exact nature of its …

Importance Of Outbreak Response Research In Bridging Knowledge Gaps On Emerging Infectious Diseases, Robert F Breiman, David Wang, Michael Diamond, Adrianus C M Boon, Et Al.

2020-Current year OA Pubs

An important outcome of the devastating 2014 West African Ebola virus disease outbreak and the 2020 COVID-19 pandemic has been the growing promotion of conducting research during outbreaks of emerging infectious diseases (EIDs) as a valuable and acceptable process of acquiring knowledge to enhance our ability to better prevent and control these diseases in the future. Recognising the unique opportunity during outbreaks to leverage increases in cases over a short time interval and in a circumscribed area, we articulate a systematic process of conducting EID outbreak response research, highlighting knowledge gaps that should be prioritised, and measures that can be …

Oxygen Saturation Targeting In The Neonatal Intensive Care Unit, Faeq Almudares, Bheru Gandhi, Jonathan Davies, Xanthi Couroucli, Natalie Villafranco, Nidhy Paulose Varghese, Milenka Cuevas Guaman, Charleta Guillory, Binoy Shivanna

Faculty, Staff and Students Publications

Oxygen (O2) is vital for cellular development, function, proliferation, and repair, underscoring its critical role in organogenesis. Both hypoxia (reduced tissue O2) and hyperoxia (excess tissue O2), when prolonged, can trigger inflammation and oxidative stress, contributing to acute and long-term cardiopulmonary and neurodevelopmental morbidity. In sick neonates, immature defense mechanisms and coexisting morbidities demand nuanced and sometimes opposing strategies for O2 saturation targets and therapeutic titration. Most current neonatal O2 targeting guidelines are based on animal models or small clinical studies, resulting in recommendations with limited evidence. This narrative review aims to provide an updated overview of the physiological roles …

177lu-Labeled Antibody-Drug Conjugate: A Dual-Mechanistic Treatment Modality In Solid Tumors, Aiko Yamaguchi, Chisato M Yamazaki, Yasuaki Anami, Summer Y Y Ha, Wei Xiong, Robert T Ta, Ningyan Zhang, H Charles Manning, Zhiqiang An, Kyoji Tsuchikama

The Brown Foundation: Institute of Molecular Medicine

To explore the potential of site-selectively radiolabeled antibody-drug conjugates (ADC) against solid tumors, we constructed and evaluated radiolabeled ADCs equipped with lutetium-177 (177Lu) and a membrane-permeable antimitotic agent. Site-selective 177Lu-labeled ADCs [anti-trophoblast cell-surface antigen 2 (TROP2) 177Lu-DTPA ADCs or anti-HER2 177Lu-DO3A ADCs], a 177Lu-labeled homogeneous radioimmunoconjugate (homogeneous RIC), and 177Lu-labeled conventional RIC (heterogeneous RIC) were constructed. We confirmed that 177Lu-labeled ADCs and the homogeneous RIC were obtained with high homogeneity and defined chelator/payload-to-antibody ratios. Next, we performed biodistribution studies and treatment efficacy studies in xenograft mouse models bearing orthotopic breast tumors. Compared with the heterogeneous RIC, the 177Lu-DTPA TROP2 ADC …

Race, Resources, And American Adolescents’ Mental Health During The Covid-19 Pandemic, Chineze Nkemeh

Walden Dissertations and Doctoral Studies

During the COVID-19 pandemic, African American adolescents experienced reduced access to needed resources and may have suffered poorer mental health outcomes as a result. The purpose of this quantitative study was to examine the association between race and the availability of mental health resources, food, medical health resources and mental health outcomes among African American adolescents in the United States during the COVID-19 pandemic compared to their White counterparts. The theoretical framework that grounded this study was the Socio Ecological Model. Secondary data from the Centers for Disease Control and Prevention’s Adolescent Behaviors and Experiences Survey database were analyzed. These …

Nitrate And Nitrite Levels In Cattle Feed, Drinking Water, Rumen Content, And Blood Methemoglobin Levels In Burdur Province Of Türkiye, Reyda Kiyici, Hasan Altan Akkan, Mehmet Karaca, Esra Zeybek, Bayram Kudret Karaayvaz, Fi̇rdevs Mor Savaş, Yahya Öztürk, Asim Kart, Ramazan Yildiz, Murat Bayezi̇t

Turkish Journal of Veterinary & Animal Sciences

This study was conducted to determine the risk factors associated with nitrate/nitrite poisoning in cattle in the Burdur region. Feed and water samples were collected from 10 different farms randomly selected from 9 districts. A total of 33 feed samples, 13 water samples, 21 rumen contents, and 20 blood samples were collected for analysis. Nitrate and nitrite levels in feed, drinking water, and rumen fluid, as well as methemoglobin levels in blood samples, were determined using a spectrophotometric method. The average nitrate and nitrite levels in feed samples were 3.06 mg/kg and 3.54 mg/kg, respectively. The mean nitrate and nitrite …

Eph Receptors Activate Myeloid Checkpoint Receptor Lilrb5 To Support Tumor Development, Yubo He, Chengcheng Zhang, Lingxiao Tan, Mi Deng, Xiaoye Liu, Ryan Huang, Xing Yang, Jingjing Xie, Qi Lou, Meng Fang, Caroline Smith, Samuel John, Wei Xiong, Xin Li, Cheryl Lewis, Jade Homsi, Ankit Gupta, Ningyan Zhang, Zhiqiang An, Cheng Cheng Zhang

Faculty, Staff and Student Publications

Immunosuppressive myeloid cells are critical obstacles to T cell-centered immune checkpoint blockade therapies, which have been successful in treating a fraction of patients with cancer. How tumor cells interact with myeloid cells to regulate immune responses and tumor development is unclear. In this study, we report that certain membrane tyrosine kinase Eph receptors, including EphA7 and EphB1, specifically bind the immune inhibitory receptors leukocyte Ig-like receptor family B 5 (LILRB5) and LILRB2. These Eph receptors induce LILRB5-mediated signaling activation, and LILRB5 also activates Eph receptor signaling. Activation of LILRB5 promoted immunosuppressive marker expression and inhibited activating marker expression on myeloid …

Olaparib And Radiotherapy Induce Type I Interferon- And Cd8+ T Cell-Dependent Sensitization To Immunotherapy In Pancreatic Cancer, Victoria M Valvo, Qiang Zhang, Long Jiang, Erin A Holcomb, Ashley N Pearson, Anna G Edmunds, Hailey G Faulkner, Jadyn G James, Akshay Tate, Amanda K Huber, Zhuwen Wang, Yupei Guo, David Karnak, Leslie A Parsels, Joshua D Parsels, Yu L Lei, Alnawaz Rehemtulla, Heng Lin, Eileen S Carpenter, Daniel R Wahl, Vaibhav Sahai, Theodore S Lawrence, Michael D Green, Meredith A Morgan

Faculty, Staff and Student Publications

PARP inhibitors sensitize pancreatic ductal adenocarcinoma (PDAC) to radiation by inducing DNA damage and replication stress. These mechanisms also have the potential to enhance radiation-induced type I interferon (T1IFN) mediated anti-tumoral immune responses. We hypothesized that the PARP inhibitor olaparib would also potentiate radiation-induced T1IFN to promote anti-tumor immune responses and sensitization of otherwise resistant PDAC to immunotherapy. To test this hypothesis, we assessed the effects of olaparib and radiation on T1IFN production and sensitivity to αPD-L1 immunotherapy, as well as on the tumor microenvironment by single-cell RNA sequencing (scRNA-seq). We found that olaparib enhanced T1IFN production following radiation and …