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Articles 631 - 660 of 24671
Full-Text Articles in Entire DC Network
Immunoregulatory Effects Of Choerospondias Axillaris (Roxb.) B.L.Burtt & A.W.Hill Fruit Extract In Mice With Insights On In Vitro Mechanism, Ravi Gautam, Anju Maharjan, Jaehee Lee, Sujeong Yang, Jihun Jo, Manju Acharya, Daeun Lee, Narayan Prasad Ghimire, Saroj Lamichhane, Byungsun Min, Changyul Kim, Hyoungah Kim, Yong Heo
Immunoregulatory Effects Of Choerospondias Axillaris (Roxb.) B.L.Burtt & A.W.Hill Fruit Extract In Mice With Insights On In Vitro Mechanism, Ravi Gautam, Anju Maharjan, Jaehee Lee, Sujeong Yang, Jihun Jo, Manju Acharya, Daeun Lee, Narayan Prasad Ghimire, Saroj Lamichhane, Byungsun Min, Changyul Kim, Hyoungah Kim, Yong Heo
Department of Microbiology and Immunology Faculty Papers
BACKGROUND: Lapsi (Choerospondias axillaris), a plant native to Nepal, has been traditionally used in Asian countries to treat cardiovascular conditions. However, its effects on immune regulatory function remain largely unexplored. This study aimed to in vivo evaluate the immunoregulatory properties of Lapsi fruit extract in mice on immunotoxic responses with analysis on in vitro mechanism for immune suppression, oxidative stress, and inflammatory response. Male Balb/c mice were intragastrically administered various doses of the extract for 21 days. In some mice, immune suppression was induced with cyclophosphamide, and subsequent immune recovery was assessed. In addition, RAW264.7 cells and THP-1-derived macrophages were …
Pulmonary Complications Of Cancer Therapy: Clinical Presentations, Imaging Patterns, And Management Strategies, Bilal Zafar, Tasmea Haque, Miranda Tan, Ritika Singh, Lara Bashoura, Ajay Sheshadri, Maria Azhar, Saadia A Faiz
Pulmonary Complications Of Cancer Therapy: Clinical Presentations, Imaging Patterns, And Management Strategies, Bilal Zafar, Tasmea Haque, Miranda Tan, Ritika Singh, Lara Bashoura, Ajay Sheshadri, Maria Azhar, Saadia A Faiz
Faculty, Staff and Student Publications
Background and objectives: Therapeutic agents for cancer can cause unique pulmonary toxicities and mimic other conditions. The advent of new targeted molecular and immune therapies has changed the landscape of cancer treatment. These adverse events pose diagnostic and therapeutic challenges. This review aims to summarize the clinical presentations, radiographic patterns, and management strategies for noninfectious pulmonary complications associated with cancer therapies.
Materials and methods: A literature review was conducted focusing on drug-induced lung injury (DILI), radiation-induced lung injury (RILI), pleural disease, pulmonary vascular complications, and other inflammatory conditions in patients with cancer. The data sources included clinical trials, guideline recommendations, …
Self-Clustering Of Three Cbx2 Molecules Drives Prc2 To Promote Facultative Heterochromatinization Of Polycomb Target Genes, Steven Ingersoll, Abby Trouth, J Carlos Angel, Xinlong Luo, Axel Espinoza, Joey Wen, Chengjie Zhu, Joseph Tucker, Kalkidan Astatike, Christopher J Phiel, Hatim Sabaawy, Tatiana G Kutateladze, Tao P Wu, Tingting Yao, Chao Lu, Srinivas Ramachandran, Xiaojun Ren
Self-Clustering Of Three Cbx2 Molecules Drives Prc2 To Promote Facultative Heterochromatinization Of Polycomb Target Genes, Steven Ingersoll, Abby Trouth, J Carlos Angel, Xinlong Luo, Axel Espinoza, Joey Wen, Chengjie Zhu, Joseph Tucker, Kalkidan Astatike, Christopher J Phiel, Hatim Sabaawy, Tatiana G Kutateladze, Tao P Wu, Tingting Yao, Chao Lu, Srinivas Ramachandran, Xiaojun Ren
Faculty, Staff and Students Publications
Phase separation is increasingly recognized in facultative heterochromatinization of Polycomb target genes; however, the mechanisms underlying this process remain obscure. Using single-molecule imaging and tracking, we show that individual condensates in mouse embryonic stem cells (mESCs) contain approximately 3 CBX2 molecules and numerous Polycomb repressive complex (PRC)1 and PRC2 subunits and indicate that the composition and dynamics of condensates are developmentally regulated. We reveal that CBX2 clusters PRC2 and controls the spatial distribution of both PRC2 and H3K27me3. Using genomic approaches, we demonstrate that CBX2 binds to condensate initiation sites, which are enriched for PRC2 nucleation sites. CBX2 deletion causes …
Role Of Plants And Phytochemicals In Promoting Proliferation And Osteogenic Differentiation Of Dental Mesenchymal Stem Cells: A Comprehensive Review, Hala El-Zahar, Essam Abdel-Sattar, Marwa Yousry Moustafa Issa, Shereen N. Raafat, Noha Swilam
Role Of Plants And Phytochemicals In Promoting Proliferation And Osteogenic Differentiation Of Dental Mesenchymal Stem Cells: A Comprehensive Review, Hala El-Zahar, Essam Abdel-Sattar, Marwa Yousry Moustafa Issa, Shereen N. Raafat, Noha Swilam
Dentistry
Abstract Objectives Dental mesenchymal stem cells (MSCs) represent a promising source for regenerative medicine due to their accessibility and capacity to differentiate into osteoblasts and other lineages. Osteogenic differentiation of dental MSCs is essential for bone formation and is regulated by multiple signaling pathways, cytokines, growth fac‑ tors, and transcription factors. This review aims to summarize the effects of plant-derived extracts and phytochemicals on the proliferation and osteogenic differentiation of dental MSCs. Methods In this review, an extensive literature search was conducted covering studies from the past 10 years, using different online databases (SCOPUS, Google Scholar, PubMed, Web of Science, …
The Agreement Between Pulse Oximetry And Measured Arterial Oxygen Saturations In Postoperative Functionally Univentricular Patients, Fabio Savorgnan, Sebastian Acosta, Joshua Prabhu, Pranathi Pilla, Vikram Shah, Saul Flores, Rohit S Loomba
The Agreement Between Pulse Oximetry And Measured Arterial Oxygen Saturations In Postoperative Functionally Univentricular Patients, Fabio Savorgnan, Sebastian Acosta, Joshua Prabhu, Pranathi Pilla, Vikram Shah, Saul Flores, Rohit S Loomba
Faculty, Staff and Students Publications
Background: Pulse oximetry is widely used to estimate arterial oxygen saturation, yet accuracy may vary for a number of reasons. Data on children with functionally univentricular circulation are limited. The primary aim of this study was to evaluate the agreement between arterial oxygen saturation measured by blood gas and pulse oximetry in children with functionally univentricular circulations. Methods: A retrospective analysis was performed of paired arterial blood gas and pulse oximetry oxygen saturation measurements following Norwood, Glenn, or Fontan procedures. Signed difference was defined as arterial oxygen saturation by blood gas-arterial oxygen saturation by pulse oximetry. Bland-Altman analyses, …
Visdb 20: A Manually Curated Resource Of Viral Integration Sites And Their Regulatory Maps In Human Diseases, Citu Citu, Ajeet Singh, Xinyi Liu, Mounika Ashannagari, Rinki Ratnapriya, Zhongming Zhao
Visdb 20: A Manually Curated Resource Of Viral Integration Sites And Their Regulatory Maps In Human Diseases, Citu Citu, Ajeet Singh, Xinyi Liu, Mounika Ashannagari, Rinki Ratnapriya, Zhongming Zhao
Faculty, Staff and Student Publications
The integration of viral sequence into the human genome plays critical role in the onset of various diseases, especially cancers. To facilitate systematic analysis of these events, we present VISDB 2.0, an expanded and updated database of human viral integration sites (VISs). The current release contains more than 270,000 manually curated VISs derived from 209 peer-reviewed publications, covering 11 viruses, including four retroviruses and seven DNA viruses. This represents a 3.5-fold increase in VIS entries compared with the previous version. Each VIS record includes standardized genomic coordinates and annotations describing local genomic context, CpG islands, repetitive elements, chromosomal fragile sites, …
Disrupted Nuclear Function And Nucleocytoplasmic Transport In Parkinson’S Disease, Ichiro M. Matoba
Disrupted Nuclear Function And Nucleocytoplasmic Transport In Parkinson’S Disease, Ichiro M. Matoba
The Cardinal Edge
No abstract provided.
An Exploration Into Network Analyses Of Motor Behavior, Brain-Computer Interface Control, Arousal States, And An Ischemic Lesion Model, Shashank Anand
An Exploration Into Network Analyses Of Motor Behavior, Brain-Computer Interface Control, Arousal States, And An Ischemic Lesion Model, Shashank Anand
McKelvey School of Engineering Graduate Student Theses & Dissertations
Network-level modelling of neural function incorporates activity in specific brain regions along with a measure of the interactions between these regions (“connectivity”). Connectivity can be assessed through several means, for example through tractography (structural connectivity) or correlated temporal evolution of neural activity (functional connectivity). These analyses have provided valuable insight into several aspects of brain function, such as top-down control, memory, and navigation. This work focuses on studying neural activity within and between several brain regions across different brain states: namely, during motor actions, sensory perception, brain-computer interface engagement, task-free fluctuations in arousal state, and ischemic injury. High gamma (70-170 …
Nonlinear Bivariate Associations And Mononuclear Cell‐Type‐Specific Expression Level Differences In The Sting Signalling Pathway, David Kaplan
Faculty Scholarship
Understanding intracellular signalling pathways is crucial since they regulate essential functional activities. Bivariate relationships have been useful in delineating these pathways in clinical samples. In our previous studies, we have found many linear associations between pathway components, and we have interpreted these correlations as rheostatic regulators. Increases in an upstream component are correlated with a commensurate downstream increase. Here, we report a quantitative analysis of molecules in the STING pathway by assessing the variance in human peripheral blood mononuclear cell-type-specific molecular expression from patients with atherosclerotic coronary artery disease. The induction of the type I interferon track by this pathway …
Lifestyle Intervention Therapy Modulates Global Dna Methylation And Adipogenic Gene Expression In Severely Obese Hypogonadal Men, Siresha Bathina, Virginia Fuenmayor Lopez, Mia Prado, Salina Biene Teo, Dennis T Villareal, Rui Chen, Clifford Qualls, Reina Armamento-Villareal
Lifestyle Intervention Therapy Modulates Global Dna Methylation And Adipogenic Gene Expression In Severely Obese Hypogonadal Men, Siresha Bathina, Virginia Fuenmayor Lopez, Mia Prado, Salina Biene Teo, Dennis T Villareal, Rui Chen, Clifford Qualls, Reina Armamento-Villareal
Faculty, Staff and Students Publications
Background/Objectives: Previous studies have suggested that lifestyle intervention (LSI) therapies involving diet and exercise can modulate DNA methylation; however, whether this occurs in severely obese hypogonadal men undergoing weight loss from diet and exercise remains unclear.
Methods: In this study, we investigated the effects of weight loss from diet and exercise on global DNA methylation as well as on the mRNA expression of specific demethylation enzymes, DNMT1, DNMT3A, and DNMT3B—in peripheral blood mononuclear cells (PBMCs) and DNA methylation markers in DNA of severely obese hypogonadal men. This is a secondary analysis of samples of severely obese (body …
Radiation Doses To Cardiac Substructures Predict Elevation In High-Sensitivity Cardiac Troponin T Levels In Radiation Therapy For Lung Cancer, Xinru Chen, Xiaodong Zhang, Ting Xu, Radhe Mohan, Ruitao Lin, Mei Chen, Rachel C Maguire, Yao Zhao, Efstratios Koutroumpakis, Nicolas L Palaskas, Anita Deswal, Ali Ajdari, Joshua S Niedzielski, Sanjay S Shete, Laurence E Court, Jinzhong Yang, Zhongxing Liao
Radiation Doses To Cardiac Substructures Predict Elevation In High-Sensitivity Cardiac Troponin T Levels In Radiation Therapy For Lung Cancer, Xinru Chen, Xiaodong Zhang, Ting Xu, Radhe Mohan, Ruitao Lin, Mei Chen, Rachel C Maguire, Yao Zhao, Efstratios Koutroumpakis, Nicolas L Palaskas, Anita Deswal, Ali Ajdari, Joshua S Niedzielski, Sanjay S Shete, Laurence E Court, Jinzhong Yang, Zhongxing Liao
Faculty, Staff and Student Publications
Purpose: Cardiotoxicity is a major concern for patients undergoing thoracic radiation therapy. This study compared the predictive power of radiation dose-volume histogram (DVH) parameters and radiomic/dosiomic features of the whole heart (WH) and cardiac substructures for elevated circulating high-sensitivity cardiac troponin T (hs-cTnT), a biomarker for early detection of cardiac adverse events.
Methods and materials: A retrospective cohort of 160 patients with non-small cell lung cancer (NSCLC) from a completed prospective trial and a prospective cohort of 57 patients with NSCLC enrolled in an ongoing trial were analyzed. The endpoint was hs-cTnT elevation, indicated by an increase of ≥5 ng/L …
High Dietary Fiber Is Associated With Improved Outcomes In Patients With Melanoma And Sarcoma Treated With Immunotherapy Regardless Of Gut Microbiome Dysbiosis And Social Vulnerability, Brittany C Fields, Raymond S Traweek, Kai Jiang, Russell G Witt, Ashish Damania, Yi-Ju Chiang, Nadim Ajami, Elise Nassif-Haddad, Emily Z Keung, Manoj Chelvanambi, Xiaotao Zhang, Christine B Peterson, Jennifer A Wargo, Carrie R Daniel, Christina L Roland, Ashley M Holder
High Dietary Fiber Is Associated With Improved Outcomes In Patients With Melanoma And Sarcoma Treated With Immunotherapy Regardless Of Gut Microbiome Dysbiosis And Social Vulnerability, Brittany C Fields, Raymond S Traweek, Kai Jiang, Russell G Witt, Ashish Damania, Yi-Ju Chiang, Nadim Ajami, Elise Nassif-Haddad, Emily Z Keung, Manoj Chelvanambi, Xiaotao Zhang, Christine B Peterson, Jennifer A Wargo, Carrie R Daniel, Christina L Roland, Ashley M Holder
Faculty, Staff and Student Publications
Background: Social vulnerability, dietary fiber, and the gut microbiome have been individually implicated in clinical outcomes for melanoma and sarcoma patients. This study hypothesized that increasing social vulnerability is associated with insufficient dietary fiber intake and negatively associated with microbiome composition and clinical outcomes.
Methods: Clinicopathologic data, baseline fiber intake, and gut microbiome profiles were assessed in 153 patients with melanoma or sarcoma treated with immune checkpoint blockade (ICB) and prospectively followed. Patients' social vulnerability index (SVI) and fiber intake were evaluated for associations with microbiome composition, treatment response, and overall survival (OS).
Results: SVI percentile was 0.4 (interquartile ratio …
Beyond The Brain: How Does Alzheimer’S Disease Affect The Body?, Ye-Jin Park, Hongjie Li
Beyond The Brain: How Does Alzheimer’S Disease Affect The Body?, Ye-Jin Park, Hongjie Li
Center on Aging Staff Publications
No abstract provided.
Uncovering Hidden Prognostic Patterns In Colorectal Cancer Histology Using Unsupervised Learning: A Computational Pathology Study, Wen-Tong Zhou, Yong Liu, Gang Yu, Kuan-Song Wang, Chao Xu, Jonathan Greenbaum, Chong Wu, Lin-Dong Jiang, Christopher J Papasian, Hong-Mei Xiao, Hong-Wen Deng
Uncovering Hidden Prognostic Patterns In Colorectal Cancer Histology Using Unsupervised Learning: A Computational Pathology Study, Wen-Tong Zhou, Yong Liu, Gang Yu, Kuan-Song Wang, Chao Xu, Jonathan Greenbaum, Chong Wu, Lin-Dong Jiang, Christopher J Papasian, Hong-Mei Xiao, Hong-Wen Deng
Faculty, Staff and Student Publications
Colorectal cancer (CRC) remains a leading cause of cancer mortality globally, yet current histopathological diagnostics capture only limited features. This study aimed to discover subtle, prognostically significant histomorphological patterns in CRC tissues using unsupervised deep learning. We developed a framework integrating convolutional neural networks with deep clustering, trained on 23,341 image patches from 493 patients. We identified 30 distinct histomorphological clusters from CRC tissue images. Through univariate and multivariate survival analyses, three clusters (Cluster13, Cluster19, and Cluster24) were consistently associated with patient prognosis. These clusters were integrated with clinical factors (T stage, N stage, and differentiation degree) to construct a …
Telemedicine As A Gateway To Early-Phase Oncology Trials: Lessons From 14,000 Patients And Future Directions For Global Access And Equity, Carlos Torrado, Clark R Andersen, Lei Kang, Amanda L Brink, Taiwo Adesoye, Hung Le, Clover J Patterson, Anna Poullard, Jessica A Osburn, Harold N Tan, Mohamed A Gouda, Sheena Charles, Gabriele E Urschel, Tin-Yun Tang, David S Hong, Stephane Champiat, Aung Naing, Apostolia M Tsimberidou, Ecaterina E Dumbrava, Sarina A Piha-Paul, Jordi Rodon, Timothy A Yap, Paula R Pohlmann, Funda Meric-Bernstam, Siqing Fu
Telemedicine As A Gateway To Early-Phase Oncology Trials: Lessons From 14,000 Patients And Future Directions For Global Access And Equity, Carlos Torrado, Clark R Andersen, Lei Kang, Amanda L Brink, Taiwo Adesoye, Hung Le, Clover J Patterson, Anna Poullard, Jessica A Osburn, Harold N Tan, Mohamed A Gouda, Sheena Charles, Gabriele E Urschel, Tin-Yun Tang, David S Hong, Stephane Champiat, Aung Naing, Apostolia M Tsimberidou, Ecaterina E Dumbrava, Sarina A Piha-Paul, Jordi Rodon, Timothy A Yap, Paula R Pohlmann, Funda Meric-Bernstam, Siqing Fu
Faculty, Staff and Student Publications
Background: Telemedicine expanded rapidly during the COVID-19 pandemic, but its role in early-phase oncology trials remains uncertain. We evaluated its impact on recruitment, enrollment, equity, and access in a large phase I program.
Patients and methods: We retrospectively analyzed patients seen for first consultation in the MD Anderson Phase I Program (2016-2023). Recruitment (consent) and enrollment (treatment initiation) were compared by visit type, race/ethnicity, and geography across pre-pandemic (2016-2019), pandemic (2020-March 11, 2023), and post-public health emergency (PHE; March-December 2023) periods. A chart review of 400 patients validated findings.
Results: Of 14,085 patients, 7,247 were evaluated post-pandemic, with 36% (n …
Pan-Cancer Evolution Signatures Link Clonal Expansion To Dynamic Changes In The Tumor Immune Microenvironment, Xinyu Yang, Wei Liu, Geoff Macintyre, Peter Van Loo, Florian Markowetz, Peter Bailey, Ke Yuan
Pan-Cancer Evolution Signatures Link Clonal Expansion To Dynamic Changes In The Tumor Immune Microenvironment, Xinyu Yang, Wei Liu, Geoff Macintyre, Peter Van Loo, Florian Markowetz, Peter Bailey, Ke Yuan
Faculty, Staff and Student Publications
Cancer is an evolutionary process characterized by profound intratumor heterogeneity (ITH), which can be quantified using in silico estimates of cancer cell fractions (CCFs) of tumor-specific somatic mutations. We demonstrate a data-driven approach based on CCF distributions to identify 4 robust pan-cancer evolutionary signatures from 4,146 tumors across 17 cancer types in The Cancer Genome Atlas (TCGA). These signatures define a continuum of cancer cell fractions reflecting neutral evolution, clonal expansion, and clonal fixation. Correlating evolutionary signatures with mutational and biological programs reveals that tumors enriched for clonal expansion and fixation are associated with immune evasion and distinct changes in …
Energetic Heterogeneity In Retinal Ganglion Cells: Role Of Neuronal Activity And Implications For Resilience, Zelun Wang
Energetic Heterogeneity In Retinal Ganglion Cells: Role Of Neuronal Activity And Implications For Resilience, Zelun Wang
Arts & Sciences Graduate Student Theses and Dissertations
Retinal ganglion cells (RGCs) form the only connection between the eye and the brain via their axons in the optic nerve. In diseases such as glaucoma, RGCs undergo irreversible neurodegeneration leading to vision loss. RGCs consist of multiple types differing in morphology, gene expression, and signaling properties. Moreover, these types exhibit differential survival after axon injury. What cellular properties vary between RGC types that could underlie their heterogeneous response to neurodegeneration? Given that energy metabolism is tightly optimized for the homeostatic and active functions of different neurons, physiologically distinct RGC types likely exhibit divergent energetic characteristics. Furthermore, energy metabolism is …
In Vivo Hsc Gene Therapy Enables Sustained Ecd4-Ig Expression For Siv Prevention, Chang Li, Anna K Anderson, Anne-Sophie Kuhlmann, Veronica Nelson, Audrey Germond, Hongjie Wang, Aphrodite Georgakopoulou, Sucheol Gil, Jasmin Martinez-Reyes, Andrew Riker, Shruthi Shankar Raman, Jiho Kim, Philip Ng, Donna Palmer, Michael D Alpert, Nickolas Skamangas, Charles Bailey, Tianling Ou, Christine M Fennessey, Michael Farzan, Keith R Jerome, Brandon F Keele, Hans-Peter Kiem, André Lieber, John K Bui
In Vivo Hsc Gene Therapy Enables Sustained Ecd4-Ig Expression For Siv Prevention, Chang Li, Anna K Anderson, Anne-Sophie Kuhlmann, Veronica Nelson, Audrey Germond, Hongjie Wang, Aphrodite Georgakopoulou, Sucheol Gil, Jasmin Martinez-Reyes, Andrew Riker, Shruthi Shankar Raman, Jiho Kim, Philip Ng, Donna Palmer, Michael D Alpert, Nickolas Skamangas, Charles Bailey, Tianling Ou, Christine M Fennessey, Michael Farzan, Keith R Jerome, Brandon F Keele, Hans-Peter Kiem, André Lieber, John K Bui
Faculty, Staff and Students Publications
We aim to develop an in vivo hematopoietic stem cell (HSC) gene therapy approach for the prevention and control of HIV-1 infection. Toward this goal, we engineered helper-dependent adenovirus (HDAd) 6/3+ vectors to directly transduce HSCs in vivo, enabling progeny cells to secrete eCD4-Ig, a decoy protein that broadly neutralizes HIV/simian immunodeficiency virus (SIV) isolates by mimicking the primary viral receptor CD4 and coreceptors such as CCR5. In rhesus macaques, the HDAd 6/3+ platform achieved long-term expression of an enhanced eCD4-Ig variant (“eCD4-Ig-Emm06”) that retained potent neutralization efficacy in vivo. Transduced HSCs differentiated into lymphoid and myeloid lineages …
Investigating Corollaries Between Streptococcus Gallolyticus Subsp. Gallolyticus Virulence And Colorectal Cancer, Tyler G. Myers
Investigating Corollaries Between Streptococcus Gallolyticus Subsp. Gallolyticus Virulence And Colorectal Cancer, Tyler G. Myers
Pursuit - The Journal of Undergraduate Research at The University of Tennessee
Streptococcus gallolyticus subsp. gallolyticus (Sgg) is a gram-positive, non-beta-hemolytic bacterium that belongs to the Lancefield group D of streptococcal pathogens. For the past several decades, associations between Sgg bacteremia and colorectal cancer (CRC) have been apparent, with gastroenterologists routinely recommending colonoscopies for positive cases of Sgg in either blood or stool samples. However, current research has not wholly established whether Sgg acts as a causative agent of CRC or if pre-existing cancers make the lumen of the colon more hospitable to its colonization. Regardless, Sgg has been implicated in the modulation of host inflammatory pathways and subsequent remodeling …
Brain-Engrafted Monocyte-Derived Macrophages From Blood And Skull-Bone Marrow Exhibit Distinct Properties, Siling Du, Feiya Ou, Antoine Drieu, Eric Z Xu, Yumeng Cheng, Steffen E Storck, Tornike Mamuladze, Jay Cao, Nora Abduljawad, Bishan Bhattarai, Justin Rustenhoven, Niall Mortimer, Simone Brioschi, Khai Nguyen, Patrick Fernandes Rodrigues, Igor Smirnov, Daniel Gibson, J Michael White, Wandy Beatty, David Denardo, Qingyun Li, Michael Meers, Claudia Z Han, Na Sun, Florent Ginhoux, Marina Cella, Marco Colonna, Jonathan Kipnis
Brain-Engrafted Monocyte-Derived Macrophages From Blood And Skull-Bone Marrow Exhibit Distinct Properties, Siling Du, Feiya Ou, Antoine Drieu, Eric Z Xu, Yumeng Cheng, Steffen E Storck, Tornike Mamuladze, Jay Cao, Nora Abduljawad, Bishan Bhattarai, Justin Rustenhoven, Niall Mortimer, Simone Brioschi, Khai Nguyen, Patrick Fernandes Rodrigues, Igor Smirnov, Daniel Gibson, J Michael White, Wandy Beatty, David Denardo, Qingyun Li, Michael Meers, Claudia Z Han, Na Sun, Florent Ginhoux, Marina Cella, Marco Colonna, Jonathan Kipnis
The Brown Foundation: Institute of Molecular Medicine
Microglia arise from yolk sac progenitors and are thought to persist throughout life with minimal input from adult hematopoiesis. However, whether brain-engrafted monocyte-derived macrophages (MDMs) exist at homeostasis and during turnover and how they function relative to yolk-sac-derived microglia (YSMs) remain unsettled. Here, we combine lineage tracing, pharmacological microglia depletion, and multi-omics profiling to define the ontogeny, identity, and function of brain parenchymal macrophages. Despite sharing the parenchymal milieu, MDMs display transcriptional and epigenetic landscapes distinct from YSMs. Fate-mapping reveals that brain-engrafted MDMs transiently express CD206, echoing a developmental stage of microglial precursors. MDM engraftment and polarization are modulated by …
Quality Of Life In Patients With P16+ Oropharyngeal Cancer Receiving Accelerated Radiation Therapy With Either Cisplatin Or Cetuximab In The Nrg/Rtog 1016 Randomized Controlled Trial, Jolie Ringash, Pedro A Torres-Saavedra, Maura L Gillison, Jimmy J Caudell, David J Adelstein, Paul M Harari, Erich M Sturgis, Ethan Basch, Shlomo A Koyfman, Greg A Krempl, Dukagjin M Blakaj, James Edward Bates, Thomas J Galloway, Christopher U Jones, Beth M Beadle, Jonathan Harris, Quynh-Thu Le, Sue S Yom, Benjamin Movsas
Quality Of Life In Patients With P16+ Oropharyngeal Cancer Receiving Accelerated Radiation Therapy With Either Cisplatin Or Cetuximab In The Nrg/Rtog 1016 Randomized Controlled Trial, Jolie Ringash, Pedro A Torres-Saavedra, Maura L Gillison, Jimmy J Caudell, David J Adelstein, Paul M Harari, Erich M Sturgis, Ethan Basch, Shlomo A Koyfman, Greg A Krempl, Dukagjin M Blakaj, James Edward Bates, Thomas J Galloway, Christopher U Jones, Beth M Beadle, Jonathan Harris, Quynh-Thu Le, Sue S Yom, Benjamin Movsas
Faculty, Staff and Students Publications
Purpose: NRG/RTOG 1016 was a phase III randomized noninferiority de-escalation trial comparing cetuximab versus cisplatin, concurrent with accelerated radiation 70 Gy/6 weeks, in p16+ oropharyngeal cancer. Quality of life (QOL) was a secondary endpoint.
Methods and materials: Eligible/consenting patients among the first 400 entered completed the EORTC QLQ-C30/H&N35 at baseline, end of treatment, 3, 6, and 12 months posttreatment, to provide 90% power to detect an effect size of 0.5 in the between-arm change in QOL scores from baseline to 6 months. We report completion, responsiveness, and patterns over time across domains between arms, considering a difference of >10 points …
International Consensus-Driven Recommendations For Patient-Reported Outcome Research Objectives In Early Phase Dose-Finding Oncology Trials: Optimise-Ror, Emily Alger, Olalekan Lee Aiyegbusi, Amylou C Dueck, Anna Minchom, Madeline Pe, John D Peipert, Claire Snyder, Stefan N Symeonides, Roger Wilson, Ethan Basch, Yu Qiao, Susan E Bates, Helen Bulbeck, Lizzie Dean, Massimo Di Maio, Aaron R Hansen, Olga Kholmanskikh, Ken Kobayashi, Dónal Landers, Christophe Le Tourneau, J Jack Lee, Brigette B Y Ma, Lynley V Marshall, Sheetal Patel, Joan Petrie, Gregory R Pond, Kieran Prior, Khadija R Rantell, John F Reeve, Olga Solovyeva, Nolan A Wages, Harald A Weber, Melanie J Calvert, Christina Yap
International Consensus-Driven Recommendations For Patient-Reported Outcome Research Objectives In Early Phase Dose-Finding Oncology Trials: Optimise-Ror, Emily Alger, Olalekan Lee Aiyegbusi, Amylou C Dueck, Anna Minchom, Madeline Pe, John D Peipert, Claire Snyder, Stefan N Symeonides, Roger Wilson, Ethan Basch, Yu Qiao, Susan E Bates, Helen Bulbeck, Lizzie Dean, Massimo Di Maio, Aaron R Hansen, Olga Kholmanskikh, Ken Kobayashi, Dónal Landers, Christophe Le Tourneau, J Jack Lee, Brigette B Y Ma, Lynley V Marshall, Sheetal Patel, Joan Petrie, Gregory R Pond, Kieran Prior, Khadija R Rantell, John F Reeve, Olga Solovyeva, Nolan A Wages, Harald A Weber, Melanie J Calvert, Christina Yap
Faculty, Staff and Student Publications
Purpose: There is growing scientific interest in incorporating patient-reported outcomes (PROs) in early phase dose-finding oncology trials (DFOTs) to assess tolerability, inform dose selection, and guide later stage trial design. However, research indicates that PRO objectives in DFOTs are often unclear. The Incorporating Patient-Reported Outcomes in Dose-Finding Trials-Research Objectives Recommendations (OPTIMISE-ROR) project was established to support trialists to effectively incorporate PROs into DFOTs.
Methods: Using the Enhancing Quality and Transparency of Health Research (EQUATOR) Network's methodological framework, guideline development included the following: (1) a methodological review of published DFOTs incorporating PROs; (2) candidate item generation, refined through expert consultation; (3) …
Underexplored Maternal Microbiomes: Immune, Metabolic, And Microbial Pathways Shaping Pregnancy Outcomes, Rafael Tomoya Michita, Nicole Jimenez, Melissa M Herbst-Kralovetz, Indira U Mysorekar
Underexplored Maternal Microbiomes: Immune, Metabolic, And Microbial Pathways Shaping Pregnancy Outcomes, Rafael Tomoya Michita, Nicole Jimenez, Melissa M Herbst-Kralovetz, Indira U Mysorekar
Faculty, Staff and Students Publications
Maternal microbial ecosystems play critical roles in shaping reproductive physiology and pregnancy outcomes. During the pre-conception and prenatal periods, these communities modulate maternal physiology by regulating immune tolerance, nutrient metabolism, and susceptibility to pregnancy complications such as preterm birth, hypertensive disorders, and gestational diabetes. While the gut microbiota has been extensively studied, the roles of cervicovaginal, urinary, respiratory, oral, and upper reproductive tract microbiomes remain less clear. In this minireview, we synthesize current knowledge on these underexplored maternal microbiomes, with an emphasis on the cervicovaginal and urinary microbiota and their interactions with the placenta and fetus. We discuss cross-niche microbial …
Dual Phagocytosis-Checkpoint Blockade Revitalizes Immune Surveillance In Mouse Models Of Glioblastoma, Jonghoon Ha, Yifan Wang, Yifan Ma, Annette Wu, Shiyan Dong, Seong Dong Jeong, Jared L Edwards, Mengyu Chang, Yen-Tzu Chang, Xiaotian Wang, Maurice Dufilho, Michelle Najarro Torres, Shannon Mccabe, Weiye Deng, Adam J Grippin, Jeffrey S Weinberg, Shaan M Raza, Franco Demonte, Ian E Mccutcheon, Sujit Prabhu, Sherise D Ferguson, Chibawanye I Ene, Kadir Akdemir, Sreyashi Basu, Sonali Jindal, Benjamin R Schrank, Jian Hu, Sangeeta Goswami, Vinay K Puduvalli, Frederick F Lang, Kristin Huntoon, Padmanee Sharma, Betty Y S Kim, Wen Jiang
Dual Phagocytosis-Checkpoint Blockade Revitalizes Immune Surveillance In Mouse Models Of Glioblastoma, Jonghoon Ha, Yifan Wang, Yifan Ma, Annette Wu, Shiyan Dong, Seong Dong Jeong, Jared L Edwards, Mengyu Chang, Yen-Tzu Chang, Xiaotian Wang, Maurice Dufilho, Michelle Najarro Torres, Shannon Mccabe, Weiye Deng, Adam J Grippin, Jeffrey S Weinberg, Shaan M Raza, Franco Demonte, Ian E Mccutcheon, Sujit Prabhu, Sherise D Ferguson, Chibawanye I Ene, Kadir Akdemir, Sreyashi Basu, Sonali Jindal, Benjamin R Schrank, Jian Hu, Sangeeta Goswami, Vinay K Puduvalli, Frederick F Lang, Kristin Huntoon, Padmanee Sharma, Betty Y S Kim, Wen Jiang
Faculty, Staff and Student Publications
Macrophage-mediated phagocytosis of tumor cells elicits potent antitumor immunity. Nonetheless, sole-blockade of the anti-phagocytosis molecule CD47 has yielded insufficient therapeutic outcomes. Here, we report that glioblastoma (GBM) cells expressed abundant levels of phagocytosis checkpoint CD24. We further show that dual blockade of CD24 and CD47 synergistically enhances the pro-phagocytic activity of macrophages, thereby improving tumor antigen cross-presentation and activating the cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) pathway. This innate immune activation facilitates T cell infiltration into tumors and sensitizes tumors to anti-PD1 therapy, improving survival outcomes in murine GBM models, including immunosuppressive tumors reflecting human GBM-like features. Thus, our …
Microrna-625-3p Increases Chemosensitivity In Ovarian Cancer Cells Through Decreasing Ssx2ip-Mediated Cisplatin Export In Extracellular Vesicles, Chi-Lam Au-Yeung, Tetsushi Tsuruga, Marina A Talor, Yadira J Pacheco, Guangan He, Zahid H Siddik, Byeong J Cha, Suet-Ying Kwan, Kwong-Kwok Wong, Kay-Pong Yip, Samuel C Mok
Microrna-625-3p Increases Chemosensitivity In Ovarian Cancer Cells Through Decreasing Ssx2ip-Mediated Cisplatin Export In Extracellular Vesicles, Chi-Lam Au-Yeung, Tetsushi Tsuruga, Marina A Talor, Yadira J Pacheco, Guangan He, Zahid H Siddik, Byeong J Cha, Suet-Ying Kwan, Kwong-Kwok Wong, Kay-Pong Yip, Samuel C Mok
Faculty, Staff and Student Publications
Introduction: Advanced-stage high-grade serous ovarian cancer (HGSC) is a disease that is difficult to manage due to its heterogeneous clinical behavior. No reliable prediction of response to chemotherapy is currently available and the overall survival rate remains poor. Herein, we sought to determine the molecular mechanisms by which microRNAs (miRNAs) confer chemoresistance in ovarian cancer and demonstrate the efficacy of targeting miRNAs to sensitize HGSC to cisplatin treatment.
Methods: Next-generation miRNA sequencing was performed using microdissected HGSC specimens to identify an miRNA signature for intrinsic chemoresistance, and miR-625-3p was selected for further study. The effects of miR-625-3p on cisplatin sensitivity …
Early Camp Signaling Orchestrates Single-Cell Synchronicity Throughout Dictyostelium Development, Mariko Katoh-Kurasawa, Lena Trnovec, Peter Lehmann, Rui Chen, Yumei Li, Blaž Zupan, Gad Shaulsky
Early Camp Signaling Orchestrates Single-Cell Synchronicity Throughout Dictyostelium Development, Mariko Katoh-Kurasawa, Lena Trnovec, Peter Lehmann, Rui Chen, Yumei Li, Blaž Zupan, Gad Shaulsky
Faculty, Staff and Students Publications
Synchronicity is observed in many biological systems, including development, as seen in vertebrate body axis formation, fly eye development, and development of the social amoeba D. discoideum. Despite its prevalence, quantitative analyses of synchronicity at the single-cell level remain rare. Here we show that synchronicity in D. discoideum is mediated by early cAMP signaling. Using single-cell RNA sequencing (scRNA-seq), we quantify transcriptome similarities between individual cells during development. We show that synchronicity first declines upon starvation but then increases with the onset of cAMP-pulse signaling. Synchronicity remains stable throughout development and differs between prespore and prestalk cells. Genetic perturbations of …
Differences Between Sexual Orientations Regarding Perceived Knowledge Of And Attitudes Toward Lgbtia+ Persons Among Athletic Trainers, Julianne Goza, S. Andrew Cage, Meredith Decker, Brandon J. Warner
Differences Between Sexual Orientations Regarding Perceived Knowledge Of And Attitudes Toward Lgbtia+ Persons Among Athletic Trainers, Julianne Goza, S. Andrew Cage, Meredith Decker, Brandon J. Warner
Clinical Practice in Athletic Training
Context: LGBTQIA+ athletic trainers and patients encounter difficulties in their workplaces and sport communities. Several medical professional associations have produced statements claiming their commitment to fostering an patient-centered environment for healthcare for LGBTQIA+ patients. To date, there has been little research on the factors that impact perceived knowledge of and attitudes toward the LGBTQIA+ community among healthcare providers. With more information on what factors impact perceived knowledge of and attitudes toward the LGBTQIA+ community, better interventions for improving perceived knowledge and attitudes toward the LGBTQIA+ community could be created. The purpose of this study was to determine differences between sexual …
Differences Between Genders Related To Perceived Knowledge Of And Attitudes Toward Lgbtia+ Persons Among Athletic Trainers, Brandon J. Warner, Julianne Goza, Meredith Decker, S. Andrew Cage
Differences Between Genders Related To Perceived Knowledge Of And Attitudes Toward Lgbtia+ Persons Among Athletic Trainers, Brandon J. Warner, Julianne Goza, Meredith Decker, S. Andrew Cage
Clinical Practice in Athletic Training
Context: Previous literature reports that healthcare providers and student-athletes identifying as LGBTQIA+ encounter difficulties in their respective communities. A number medical professional associations have published statements affirming their commitment to providing access to patient-centered healthcare for LGBTQIA+ patients. Unfortunately, there is a lack of research related to the factors that influence perceived knowledge of and attitudes toward the LGBTQIA+ community among healthcare providers. More information on what factors impact perceived knowledge of and attitudes toward the LGBTQIA+ community would assist with creating interventions that improve perceived knowledge and attitudes toward the LGBTQIA+ community. The purpose of this study was to …
Awareness Of Native American Living Conditions Among Athletic Trainers, Laurel Trail, Brandon Warner, Rebecca Peebles, Robert French, Lynzi Warner, S. Andrew Cage
Awareness Of Native American Living Conditions Among Athletic Trainers, Laurel Trail, Brandon Warner, Rebecca Peebles, Robert French, Lynzi Warner, S. Andrew Cage
Clinical Practice in Athletic Training
Context: Native Americans and First Nations People have dealt with healthcare disparities that have been documented in previous studies. One factor that appears to have played a role in these disparities was the Indian Removal Act of 1851 which established the first Native American reservations. The foundation of these reservations led to many Native Americans being displaced from areas where the United States was establishing new population centers. This has led many individuals not understanding the conditions that Native Americans live in. Lack of knowledge of the conditions patients live in may negatively affect clinicians’ ability to provide optimal healthcare. …
Sleep And Stress Experienced By Collegiate Baseball Players During A Fall Season, Andrew R. Gallucci, Katie M. Lee, Eric Rash, Jeremy A. Bigalke, Jason R. Carter
Sleep And Stress Experienced By Collegiate Baseball Players During A Fall Season, Andrew R. Gallucci, Katie M. Lee, Eric Rash, Jeremy A. Bigalke, Jason R. Carter
Clinical Practice in Athletic Training
Introduction: College students are notoriously poor sleepers due to academic and social demands. Collegiate athletes have additional athletic responsibilities that can also affect sleep. During a season, baseball players experience prolonged bouts of high intensity activity that increase the need for recovery and sleep. Athletes can also experience higher perceived stress levels, a factor also known to impact sleep. Reduced sleep quality and quantity during a competitive season can impede recovery and decrease performance. The present study sought to determine the relationships between sleep [Total Sleep Time (TST), Sleep Efficiency (SE), Sleep Onset Latency (SOL), Awakenings] and stress over a …