Digital Commons Network^™

A Systematic Review On The Techniques, Long-Term Outcomes, And Complications Of Partial Breast Irradiation After Breast-Conserving Surgery For Early-Stage Breast Cancer, Jing Ning, Guanghui Cheng, Ning Wu

Faculty, Staff and Student Publications

To evaluate the efficacy and safety of four techniques of partial breast irradiation (PBI) including interstitial brachytherapy (ISBT), balloon-based brachytherapy (BBT), Intraoperative radiotherapy (IORT) and three-dimensional conformal radiotherapy (3DCRT) in the treatment for early-stage breast cancer patients after breast-conserving surgery. A systematic search was performed according to the Preferred Reporting Items of Systematic Reviews and Meta-analyses (PRISMA) guidelines using the PubMed, Embase, Cochrane Library and Web of Science databases. The inclusion criteria were clinical trials and observational studies that reported on outcome measures of principal PBI techniques. The methodological quality of the included research data was assessed using bias risk …

Crinophagic Granules In Pancreatic Β Cells Contribute To Mouse Autoimmune Diabetes By Diversifying Pathogenic Epitope Repertoire, Hao Hu, Anthony N Vomund, Orion J Peterson, Neetu Srivastava, Tiandao Li, Lisa Kain, Wandy L Beatty, Bo Zhang, Chyi-Song Hsieh, Luc Teyton, Cheryl F Lichti, Emil R Unanue, Xiaoxiao Wan

2020-Current year OA Pubs

Autoimmune attack toward pancreatic β cells causes permanent loss of glucose homeostasis in type 1 diabetes (T1D). Insulin secretory granules store and secrete insulin but are also thought to be tissue messengers for T1D. Here, we show that the crinophagic granules (crinosome), a minor set of vesicles formed by fusing lysosomes with the conventional insulin dense-core granules (DCG), are pathogenic in T1D development in mouse models. Pharmacological inhibition of crinosome formation in β cells delays T1D progression without affecting the dominant DCGs. Mechanistically, crinophagy inhibition diminishes the epitope repertoire in pancreatic islets, including cryptic, modified and disease-relevant epitopes derived from …

Nur77 Protects The Bladder Urothelium From Intracellular Bacterial Infection, Christina A Collins, Chevaughn Waller, Ekaterina Batourina, Lokesh Kumar, Cathy L Mendelsohn, Nicole M Gilbert

2020-Current year OA Pubs

Intracellular infections by Gram-negative bacteria are a significant global health threat. The nuclear receptor Nur77 (also called TR3, NGFI-B, or NR4A1) was recently shown to sense cytosolic bacterial lipopolysaccharide (LPS). However, the potential role for Nur77 in controlling intracellular bacterial infection has not been examined. Here we show that Nur77 protects against intracellular infection in the bladder by uropathogenic Escherichia coli (UPEC), the leading cause of urinary tract infections (UTI). Nur77 deficiency in mice promotes the formation of UPEC intracellular bacterial communities (IBCs) in the cells lining the bladder lumen, leading to persistent infection in bladder tissue. Conversely, treatment with …

An Approach To Analyze Spatiotemporal Patterns Of Gene Expression At Single-Cell Resolution In Candida Albicans-Infected Mouse Tongues, Elena Lindemann-Perez, Diana L Rodríguez, J Christian Pérez

Faculty, Staff and Student Publications

Microbial gene expression measurements derived from infected organs are invaluable to understand pathogenesis. However, current methods are limited to "bulk" analyses that neglect microbial cell heterogeneity and the lesion's spatial architecture. Here, we report the use of hybridization chain reaction RNA fluorescence in situ hybridization (HCR RNA-FISH) to visualize and quantify Candida albicans transcripts at single-cell resolution in tongues of infected mice. The method is compatible with fixed-frozen and formalin-fixed paraffin-embedded tissues. We document cell-to-cell variation and intriguing spatiotemporal expression patterns for C. albicans mRNAs that encode products implicated in oral candidiasis. The approach provides a spatial dimension to gene …

B Cells Drive Neuropathic Pain-Related Behaviors In Mice Through Igg-Fc Gamma Receptor Signaling, Michael J Lacagnina, Kendal F Willcox, Nabila Boukelmoune, Alexis Bavencoffe, Ishwarya Sankaranarayanan, Daniel T Barratt, Younus A Zuberi, Dorsa Dayani, Melissa V Chavez, Jonathan T Lu, Alex Bersellini Farinotti, Stephanie Shiers, Allison M Barry, Juliet M Mwirigi, Diana Tavares-Ferreira, Geoffrey A Funk, Anna M Cervantes, Camilla I Svensson, Edgar T Walters, Mark R Hutchinson, Cobi J Heijnen, Theodore J Price, Nathan T Fiore, Peter M Grace

Faculty, Staff and Student Publications

Neuroimmune interactions are essential for the development of neuropathic pain, yet the contributions of distinct immune cell populations have not been fully unraveled. Here, we demonstrate the critical role of B cells in promoting mechanical hypersensitivity (allodynia) after peripheral nerve injury in male and female mice. Depletion of B cells with a single injection of anti-CD20 monoclonal antibody at the time of injury prevented the development of allodynia. B cell-deficient (muMT) mice were similarly spared from allodynia. Nerve injury was associated with increased immunoglobulin G (IgG) accumulation in ipsilateral lumbar dorsal root ganglia (DRGs) and dorsal spinal cords. IgG was …

Dense And Persistent Odor Representations In The Olfactory Bulb Of Awake Mice, Delaram Pirhayati, Cameron L Smith, Ryan Kroeger, Saket Navlakha, Paul Pfaffinger, Jacob Reimer, Benjamin R Arenkiel, Ankit Patel, Elizabeth H Moss

Children’s Nutrition Research Center Staff Publications

Recording and analysis of neural activity are often biased toward detecting sparse subsets of highly active neurons, masking important signals carried in low-magnitude and variable responses. To investigate the contribution of seemingly noisy activity to odor encoding, we used mesoscale calcium imaging from mice of both sexes to record odor responses from the dorsal surface of bilateral olfactory bulbs (OBs). The outer layer of the mouse OB is comprised of dendrites organized into discrete "glomeruli," which are defined by odor receptor-specific sensory neuron input. We extracted activity from a large population of glomeruli and used logistic regression to classify odors …

In Vivo Crispr Screens Identify Mga As An Immunotherapy Target In Triple-Negative Breast Cancer, Xu Feng, Chang Yang, Yuanjian Huang, Dan Su, Chao Wang, Lori Lyn Wilson, Ling Yin, Mengfan Tang, Siting Li, Zhen Chen, Dandan Zhu, Shimin Wang, Shengzhe Zhang, Jie Zhang, Huimin Zhang, Litong Nie, Min Huang, Jae-Il Park, Traver Hart, Dadi Jiang, Kuirong Jiang, Junjie Chen

Faculty, Staff and Student Publications

Understanding the mechanisms underlying immune evasion is crucial for developing novel anticancer modalities. To systematically uncover tumor-intrinsic genetic modulators involved in immune escape in tumor microenvironment, we performed genome-scale in vivo CRISPR screens in two syngeneic models and later expanded up to seven syngeneic models with a focused validation library. These data help us better understand tumor immune evasion and pave the way for developing effective therapeutics. Importantly, we uncovered that Mga depletion elicited an antitumor immune response and inhibited tumor growth in triple-negative breast cancer. Our findings suggest that Mga may play a role in modulating the tumor immune …

Conformational Ensembles In Klebsiella Pneumoniae Fimh Impact Uropathogenesis, Edward D B Lopatto, Jerome S Pinkner, Denise A Sanick, Robert F Potter, Lily X Liu, Jesús Bazán Villicaña, Kevin O Tamadonfar, Yijun Ye, Maxwell I Zimmerman, Nathaniel C Gualberto, Karen W Dodson, James W Janetka, David A Hunstad, Scott J Hultgren

2020-Current year OA Pubs

No abstract provided.

Mta-Cooperative Prmt5 Inhibitors Enhance T Cell-Mediated Antitumor Activity In Mtap-Loss Tumors, Si Chen, Jiakai Hou, Roshni Jaffery, Ashley Guerrero, Rongjie Fu, Leilei Shi, Ningbo Zheng, Ritu Bohat, Nicholas A Egan, Chengtai Yu, Sana Sharif, Yue Lu, Wei He, Shuyue Wang, Donjeta Gjuka, Everett M Stone, Pooja Anil Shah, Jordi Rodon Ahnert, Taiping Chen, Xinli Liu, Mark T Bedford, Han Xu, Weiyi Peng

Faculty, Staff and Student Publications

BACKGROUND: Hyperactivated protein arginine methyltransferases (PRMTs) are implicated in human cancers. Inhibiting tumor intrinsic PRMT5 was reported to potentiate antitumor immune responses, highlighting the possibility of combining PRMT5 inhibitors (PRMT5i) with cancer immunotherapy. However, global suppression of PRMT5 activity impairs the effector functions of immune cells. Here, we sought to identify strategies to specifically inhibit PRMT5 activity in tumor tissues and develop effective PRMT5i-based immuno-oncology (IO) combinations for cancer treatment, particularly for methylthioadenosine phosphorylase (MTAP)-loss cancer.

METHODS: Isogeneic tumor lines with and without MTAP loss were generated by CRISPR/Cas9 knockout. The effects of two PRMT5 inhibitors (GSK3326595 and MRTX1719) were …

Strategic Stabilization Of Arousal Boosts Sustained Attention, Jan Willem De Gee, Zakir Mridha, Marisa Hudson, Yanchen Shi, Hannah Ramsaywak, Spencer Smith, Nishad Karediya, Matthew Thompson, Kit Jaspe, Hong Jiang, Wenhao Zhang, Matthew J Mcginley

Duncan NRI Faculty and Staff Publications

Arousal and motivation interact to profoundly influence behavior. For example, experience tells us that we have some capacity to control our arousal when appropriately motivated, such as staying awake while driving a motor vehicle. However, little is known about how arousal and motivation jointly influence decision computations, including if and how animals, such as rodents, adapt their arousal state to their needs. Here, we developed and show results from an auditory, feature-based, sustained-attention task with intermittently shifting task utility. We use pupil size to estimate arousal across a wide range of states and apply tailored signal detection theoretic, hazard function …

Ablation Of The Integrin Cd11b Mac-1 Limits Deleterious Responses To Traumatic Spinal Cord Injury And Improves Functional Recovery In Mice, Yun Li, Zhuofan Lei, Rodney M Ritzel, Junyun He, Simon Liu, Li Zhang, Junfang Wu

Faculty, Staff and Student Publications

Spinal cord injury (SCI) triggers microglial/monocytes activation with distinct pro-inflammatory or inflammation-resolving phenotypes, which potentiate tissue damage or facilitate functional repair, respectively. The major integrin Mac-1 (CD11b/CD18), a heterodimer consisting of CD11b and CD18 chains, is expressed in multiple immune cells of the myeloid lineage. Here, we examined the effects of CD11b gene ablation in neuroinflammation and functional outcomes after SCI. qPCR analysis of C57BL/6 female mice showed upregulation of

Pelage Variation And Morphometrics Of Closely Related Callithrix Marmoset Species And Their Hybrids, Joanna Malukiewicz, Kerryn Warren, Vanner Boere, Illaira L C Bandeira, Nelson H A Curi, Fabio T Das Dores, Lilian S Fitorra, Haroldo R Furuya, Claudia S Igayara, Liliane Milanelo, Silvia B Moreira, Camila V Molina, Marcello S Nardi, Patricia A Nicola, Marcelo Passamani, Valeria S Pedro, Luiz C M Pereira, Bruno Petri, Alcides Pissinatti, Adriana Alves Quirino, Jeffrey Rogers, Carlos R Ruiz-Miranda, Daniel L Silva, Ita O Silva, Monique O M Silva, Juliana L Summa, Ticiana Zwarg, Rebecca R Ackermann

Faculty, Staff and Students Publications

BACKGROUND: Hybrids are expected to show greater phenotypic variation than their parental species, yet how hybrid phenotype expression varies with genetic distances in closely-related parental species remains surprisingly understudied. Here, we investigate pelage and morphometric trait variation in anthropogenic hybrids between four species of Brazilian Callithrix marmosets, a relatively recent primate radiation. Marmoset species are distinguishable by pelage phenotype and morphological specializations for eating tree exudates. In this work, we (1) describe qualitative phenotypic pelage differences between parental species and hybrids; (2) test whether significant quantitative differences exist between parental and hybrid morphometric phenotypes; and (3) determine which hybrid morphometic …

Protocol For Continuous Intravenous Drug Delivery With Implantable Iprecio Pump In Free-Moving Rats And Mice, Tusar Giri, Arvind Palanisamy

2020-Current year OA Pubs

Variable-rate delivery of intravenous drugs is difficult to achieve with a tethered infusion system in a freely moving animal. Here, we present a protocol for continuous intravenous delivery of oxytocin in pregnant rats and mice. We describe steps for using an implantable, preprogrammed, microprocessor-controlled infusion pump connected to the jugular vein to induce labor. This protocol can be adapted to a variety of experimental paradigms in non-pregnant animals where precise intravenous pharmacological manipulation is desired. For complete details on the use and execution of this protocol, please refer to Giri et al.

Cyp1b1-Rmdn2 Alzheimer's Disease Endophenotype Locus Identified For Cerebral Tau Pet, Kwangsik Nho, Muhammad Ali, Tammie Benzinger, Carlos Cruchaga, Diana Hobbs, Et Al.

2020-Current year OA Pubs

Determining the genetic architecture of Alzheimer's disease pathologies can enhance mechanistic understanding and inform precision medicine strategies. Here, we perform a genome-wide association study of cortical tau quantified by positron emission tomography in 3046 participants from 12 independent studies. The CYP1B1-RMDN2 locus is associated with tau deposition. The most significant signal is at rs2113389, explaining 4.3% of the variation in cortical tau, while APOE4 rs429358 accounts for 3.6%. rs2113389 is associated with higher tau and faster cognitive decline. Additive effects, but no interactions, are observed between rs2113389 and diagnosis, APOE4, and amyloid beta positivity. CYP1B1 expression is upregulated in AD. …

Lamina Cribrosa Microstructure In Nonhuman Primates With Naturally Occurring Peripapillary Retinal Nerve Fiber Layer Thinning, Palaiologos Alexopoulos, Arthur G Fernandes, Zeinab Ghassabi, Ronald Zambrano, Anse Vellappally, Eitan Shemuelian, Tingfang Lee, Jiyuan Hu, Armando Burgos-Rodriguez, Melween I Martinez, Joel S. Schuman, Amanda D Melin, James P Higham, John Danias, Gadi Wollstein

Wills Eye Hospital Papers

PURPOSE: The lamina cribrosa (LC) is hypothesized to be the site of initial axonal damage in glaucoma with the circumpapillary retinal nerve fiber layer thickness (RNFL-T) widely used as a standard metric for quantifying the glaucomatous damage. The purpose of this study was to determine in vivo, 3-dimensional (3D) differences in the microstructure of the LC in eyes of nonhuman primates (NHPs) with naturally occurring glaucoma.

METHODS: Spectral-domain optical coherence tomography (OCT) scans (Leica, Chicago, IL, USA) of the optic nerve head were acquired from a colony of 50 adult rhesus monkeys suspected of having high prevalence of glaucoma. The …

Influences Of Quality Of Maternal Care And Environmental Enrichment On Associative Memory Function In Rats With Early Life Lead Exposure, Jay S. Schneider, Courtney Williams, Shamaila Zafar, Jaehyun Joo, Blanca E. Himes

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

INTRODUCTION: Children in low socioeconomic status (SES) communities are at higher risk of exposure to lead (Pb) and potentially more severe adverse outcomes from Pb exposures. While the factors encompassing SES are complex, low SES households often have less enriching home environments and parent-child interactions. This study investigated the extent to which environmental/behavioral factors (quality of maternal care and richness of the postnatal environment) may modify adverse effects from Pb exposure.

METHODS: Long-Evans female rats were randomly assigned to Control (no Pb), Early Postnatal (EPN: birth through weaning), or Perinatal (PERI: 14 days pre-mating through weaning) Pb exposure groups. From …

Generalized Encoding Of The Relative Subjective Value Of Cognitive Effort In The Dorsal Acc, Jennifer L Crawford, Rachel E Brough, Sarah A Eisenstein, Jonathan E Peelle, Todd S Braver

2020-Current year OA Pubs

Making choices about whether and when to engage cognitive effort are a common feature of everyday experience, with important consequences for academic, career, and health outcomes. Yet, despite their hypothesized importance, very little is understood about the underlying mechanisms that support this form of human cost-benefit decision-making. To investigate these mechanisms, we used the Cognitive Effort Discounting Paradigm (Cog-ED) during fMRI scanning to precisely quantify the neural encoding of varying cognitive effort demands relative to reward outcomes, within two distinct cognitive domains (working memory, speech comprehension). The findings provide strong evidence that the dorsal anterior cingulate cortex (dACC) plays a …

Single-Cell Analysis Identifies Distinct Macrophage Phenotypes Associated With Prodisease And Proresolving Functions In The Endometriotic Niche., Yasmin Henlon, Kavita Panir, Iona Mcintyre, Chloe Hogg, Priya Dhami, Antonia O Cuff, Anna Senior, Niky Moolchandani-Adwani, Elise T Courtois, Andrew W Horne, Matthew Rosser, Sascha Ott, Erin Greaves

Faculty Research 2024

Endometriosis negatively impacts the health-related quality of life of 190 million women worldwide. Novel advances in nonhormonal treatments for this debilitating condition are desperately needed. Macrophages play a vital role in the pathophysi- ology of endometriosis and represent a promising therapeutic target. In the current study, we revealed the full transcriptomic complexity of endometriosis-associated macrophage subpopulations using single-cell analyses in a preclinical mouse model of experimental endometriosis. We have identified two key lesion-resident populations that resemble i) tumor-associated macrophages (characterized by expression of Folr2, Mrc1, Gas6, and Ccl8+) that promoted expression of Col1a1 and Tgfb1 in human endometrial stromal cells …

Gut Phageome In Mexican Americans: A Population At High Risk For Metabolic Dysfunction-Associated Steatotic Liver Disease And Diabetes, Suet-Ying Kwan, Caroline M Sabotta, Lorenzo R Cruz, Matthew C Wong, Nadim J Ajami, Joseph B Mccormick, Susan P Fisher-Hoch, Laura Beretta

Faculty, Staff and Student Publications

Mexican Americans are disproportionally affected by metabolic dysfunction-associated steatotic liver disease (MASLD), which often co-occurs with diabetes. Despite extensive evidence on the causative role of the gut microbiome in MASLD, studies determining the involvement of the gut phageome are scarce. In this cross-sectional study, we characterized the gut phageome in Mexican Americans of South Texas by stool shotgun metagenomic sequencing of 340 subjects, concurrently screened for liver steatosis by transient elastography. Inter-individual variations in the phageome were associated with gender, country of birth, diabetes, and liver steatosis. The phage signatures for diabetes and liver steatosis were subsequently determined. Enrichment of …

Creb-Binding Protein/P300 Bromodomain Inhibition Reduces Neutrophil Accumulation And Activates Antitumor Immunity In Triple-Negative Breast Cancer, Xueying Yuan, Xiaoxin Hao, Hilda L Chan, Na Zhao, Diego A Pedroza, Fengshuo Liu, Kang Le, Alex J Smith, Sebastian J Calderon, Nadia Lieu, Michael J Soth, Philip Jones, Xiang Hf Zhang, Jeffrey M Rosen

Faculty, Staff and Students Publications

Tumor-associated neutrophils (TANs) have been shown to promote immunosuppression and tumor progression, and a high TAN frequency predicts poor prognosis in triple-negative breast cancer (TNBC). Dysregulation of CREB-binding protein (CBP)/P300 function has been observed with multiple cancer types. The bromodomain (BRD) of CBP/P300 has been shown to regulate its activity. In this study, we found that IACS-70654, a selective CBP/P300 BRD inhibitor, reduced TANs and inhibited the growth of neutrophil-enriched TNBC models. In the bone marrow, CBP/P300 BRD inhibition reduced the tumor-driven abnormal differentiation and proliferation of neutrophil progenitors. Inhibition of CBP/P300 BRD also stimulated the immune response by inducing …

Vglut2-Based Glutamatergic Signaling In Central Noradrenergic Neurons Is Dispensable For Normal Breathing And Chemosensory Reflexes, Yuan Chang, Savannah Lusk, Andersen Chang, Christopher S Ward, Russell S Ray

Faculty, Staff and Students Publications

Central noradrenergic (NA) neurons are key constituents of the respiratory homeostatic network. NA dysfunction is implicated in several developmental respiratory disorders including Congenital Central Hyperventilation Syndrome (CCHS), Sudden Infant Death Syndrome (SIDS), and Rett Syndrome. The current unchallenged paradigm in the field, supported by multiple studies, is that glutamate co-transmission in subsets of central NA neurons plays a role in breathing control. If true, NA-glutamate co-transmission may also be mechanistically important in respiratory disorders. However, the requirement of NA-derived glutamate in breathing has not been directly tested and the extent of glutamate co-transmission in the central NA system remains uncharacterized. …

Procedural Justice In Prison: Examining Female Inmates’ Experiences, Perceptions, And Interactions With Correctional Officers, Michael E. Antonio, Selena R. Price, Cassandra L. Reyes

Qualitative Criminology (QC)

"Correctional staff behavior can impact inmates’ perceptions of procedural justice and facilitate incidents of prison misconduct and violence. This analysis showed findings gathered from 136 female inmates incarcerated in a state correctional system. This exploratory analysis examined inmates’ self-reported responses about direct experiences, perceptions, and interactions with correctional officers. Findings from 19 Likert-scale items highlighted inmates’ encounters with correctional officers, however, results shown here focused on findings uncovered from a content analysis performed on inmates’ written comments to an open-ended item. The emerging themes portrayed correctional officers as disrespectful, indifferent, misusing authority, and dehumanizing."

A Novel Non-Invasive Murine Model Of Neonatal Hypoxic-Ischemic Encephalopathy Demonstrates Developmental Delay And Motor Deficits With Activation Of Inflammatory Pathways In Monocytes, Elise A Lemanski, Bailey A Collins, Andrew T Ebenezer, Sudha Anilkumar, Victoria A Langdon, Qi Zheng, Shanshan Ding, Karl Royden Franke, Jaclyn M Schwarz, Elizabeth Wright-Jin

Department of Medicine Faculty Papers

Neonatal hypoxic-ischemic encephalopathy (HIE) occurs in 1.5 per 1000 live births, leaving affected children with long-term motor and cognitive deficits. Few animal models of HIE incorporate maternal immune activation (MIA) despite the significant risk MIA poses to HIE incidence and diagnosis. Our non-invasive model of HIE pairs late gestation MIA with postnatal hypoxia. HIE pups exhibited a trend toward smaller overall brain size and delays in the ontogeny of several developmental milestones. In adulthood, HIE animals had reduced strength and gait deficits, but no difference in speed. Surprisingly, HIE animals performed better on the rotarod, an assessment of motor coordination. …

Hif-2Α-Dependent Induction Of Mir-29a Restrains Th1 Activity During T Cell Dependent Colitis, Agnieszka K Czopik, Eóin N Mcnamee, Victoria Vaughn, Xiangsheng Huang, In Hyuk Bang, Trent Clark, Yanyu Wang, Wei Ruan, Tom Nguyen, Joanne C Masterson, Eunyoung Tak, Sandra Frank, Colm B Collins, Howard Li, Cristian Rodriguez-Aguayo, Gabriel Lopez-Berestein, Mark E Gerich, Glenn T Furuta, Xiaoyi Yuan, Anil K Sood, Edwin F De Zoeten, Holger K Eltzschig

Faculty, Staff and Student Publications

Metabolic imbalance leading to inflammatory hypoxia and stabilization of hypoxia-inducible transcription factors (HIFs) is a hallmark of inflammatory bowel diseases. We hypothesize that HIF could be stabilized in CD4+ T cells during intestinal inflammation and alter the functional responses of T cells via regulation of microRNAs. Our assays reveal markedly increased T cell-intrinsic hypoxia and stabilization of HIF protein during experimental colitis. microRNA screen in primary CD4+ T cells points us towards miR-29a and our subsequent studies identify a selective role for HIF-2α in CD4-cell-intrinsic induction of miR-29a during hypoxia. Mice with T cell-intrinsic HIF-2α deletion display elevated T-bet (target …

The Impact Of Hypertension On Clinical Outcomes In Moyamoya Disease: A Multicenter, Propensity Score-Matched Analysis, Basel Musmar, Joanna Roy, Hammam Abdalrazeq, Elias Atallah, Kareem El Naamani, Ching-Jen Chen, Roland Jabre, Hassan Saad, Jonathan Grossberg, Adam Dmytriw, Aman Patel, Mirhojjat Khorasanizadeh, Christopher Ogilvy, Ajith Thomas, Andre Monteiro, Adnan Siddiqui, Gustavo Cortez, Ricardo Hanel, Guilherme Porto, Alejandro Spiotta, Anthony Piscopo, David Hasan, Mohammad Ghorbani, Joshua Weinberg, Shahid Nimjee, Kimon Bekelis, Mohamed Salem, Jan-Karl Burkhardt, Akli Zetchi, Charles Matouk, Brian Howard, Rosalind Lai, Rose Du, Rawad Abbas, Georgios Sioutas, Abdelaziz Amllay, Alfredo Munoz, Nabeel Herial, Stavropoula Tjoumakaris, Michael Gooch, Robert Rosenwasswer, Pascal Jabbour

Department of Neurosurgery Faculty Papers

BACKGROUND: Moyamoya disease (MMD) is a rare cerebrovascular disorder characterized by progressive steno-occlusive changes in the internal carotid arteries, leading to an abnormal vascular network. Hypertension is prevalent among MMD patients, raising concerns about its impact on disease outcomes. This study aims to compare the clinical characteristics and outcomes of MMD patients with and without hypertension.

METHODS: We conducted a multicenter, retrospective study involving 598 MMD patients who underwent surgical revascularization across 13 academic institutions in North America. Patients were categorized into hypertensive (n=292) and non-hypertensive (n=306) cohorts. Propensity score matching (PSM) was performed to adjust for baseline differences.

RESULTS: …

Effect Of Cemented Vs Uncemented On Outcomes For Hemiarthroplasty In The Elderly: A Meta-Analysis Of Randomized Clinical Trials, Yuning Feng, Jun Wan, Haidong Deng, Lvlin Chen, Yangchun Xiao, Tiangui Li, Jialing He, Peng Wang, Weelic Chong, Yang Hai, Lu Jia, Yu Zhang

Department of Medical Oncology Faculty Papers

PURPOSE: In patients undergoing hemiarthroplasty in the elderly, the choice of the cemented method remains controversial. This meta-analysis was undertaken to compare the impact of cemented vs uncemented on outcomes for hemiarthroplasty in the elderly.

METHODS: This study included randomized controlled trials comparing the postoperative effects of cemented vs uncemented in patients with hemiarthroplasty. With no language restrictions, we searched Medline (Ovid), Embase (Ovid), Cochrane Central Register of Controlled Trials (Cochrane Collaboration), Clinical Trials.gov, the ISRCTN registry, as well as gray literature with no language restrictions from January 1966 to April 2023. Data were quantitatively summarized using a random-effects model. …

Expanding The Crispr Base Editing Toolbox In Drosophila Melanogaster, Michael Clark, Christina Nguyen, Hung Nguyen, Aidan Tay, Samuel J Beach, Maciej Maselko, Víctor López Del Amo

Faculty, Staff and Student Publications

CRISPR base editors can introduce point mutations into DNA precisely, and cytosine base editors (CBEs) catalyze C to T transitions. While CBEs have been thoroughly explored in cell culture and organisms such as mice, little is known about DNA base editing in insects. In this study, we evaluated germline editing rates of three different CBEs expressed under actin (ubiquitous) or nanos (germline) promoters utilizing Drosophila melanogaster. The original Rattus norvegicus-derived cytosine deaminase APOBEC1 (rAPO-1) displayed high base editing rates (~99%) with undetectable indel formation. Additionally, we show that base editors can be used for generating male sterility and female lethality. …

Context-Aware Single-Cell Multiomics Approach Identifies Cell-Type-Specific Lung Cancer Susceptibility Genes, Erping Long, Jinhu Yin, Ju Hye Shin, Yuyan Li, Bolun Li, Alexander Kane, Harsh Patel, Xinti Sun, Cong Wang, Thong Luong, Jun Xia, Younghun Han, Jinyoung Byun, Tongwu Zhang, Wei Zhao, Maria Teresa Landi, Nathaniel Rothman, Qing Lan, Yoon Soo Chang, Fulong Yu, Christopher I Amos, Jianxin Shi, Jin Gu Lee, Eun Young Kim, Jiyeon Choi

Faculty, Staff and Students Publications

Genome-wide association studies (GWAS) identified over fifty loci associated with lung cancer risk. However, underlying mechanisms and target genes are largely unknown, as most risk-associated variants might regulate gene expression in a context-specific manner. Here, we generate a barcode-shared transcriptome and chromatin accessibility map of 117,911 human lung cells from age/sex-matched ever- and never-smokers to profile context-specific gene regulation. Identified candidate cis-regulatory elements (cCREs) are largely cell type-specific, with 37% detected in one cell type. Colocalization of lung cancer candidate causal variants (CCVs) with these cCREs combined with transcription factor footprinting prioritize the variants for 68% of the GWAS loci. …

Bacteroides Ovatus Alleviates Dysbiotic Microbiota-Induced Graft-Versus-Host Disease, Eiko Hayase, Tomo Hayase, Akash Mukherjee, Stuart C Stinson, Mohamed A Jamal, Miriam R Ortega, Christopher A Sanchez, Saira S Ahmed, Jennifer L Karmouch, Chia-Chi Chang, Ivonne I Flores, Lauren K Mcdaniel, Alexandria N Brown, Rawan K El-Himri, Valerie A Chapa, Lin Tan, Bao Q Tran, Yao Xiao, Christopher Fan, Dung Pham, Taylor M Halsey, Yimei Jin, Wen-Bin Tsai, Rishika Prasad, Israel K Glover, Altai Enkhbayar, Aqsa Mohammed, Maren Schmiester, Katherine Y King, Robert A Britton, Pavan Reddy, Matthew C Wong, Nadim J Ajami, Jennifer A Wargo, Samuel Shelburne, Pablo C Okhuysen, Chen Liu, Stephanie W Fowler, Margaret E Conner, Zoe Katsamakis, Natalie Smith, Marina Burgos Da Silva, Doris M Ponce, Jonathan U Peled, Marcel R M Van Den Brink, Christine B Peterson, Gabriela Rondon, Jeffrey J Molldrem, Richard E Champlin, Elizabeth J Shpall, Philip L Lorenzi, Rohtesh S Mehta, Eric C Martens, Amin M Alousi, Robert R Jenq

Faculty, Staff and Student Publications

Acute lower gastrointestinal GVHD (aLGI-GVHD) is a serious complication of allogeneic hematopoietic stem cell transplantation. Although the intestinal microbiota is associated with the incidence of aLGI-GVHD, how the intestinal microbiota impacts treatment responses in aLGI-GVHD has not been thoroughly studied. In a cohort of patients with aLGI-GVHD (n = 37), we found that non-response to standard therapy with corticosteroids was associated with prior treatment with carbapenem antibiotics and a disrupted fecal microbiome characterized by reduced abundances of Bacteroides ovatus. In a murine GVHD model aggravated by carbapenem antibiotics, introducing B. ovatus reduced GVHD severity and improved survival. These beneficial effects …

The Roles Of Cd4+ T Cell Help, Sex, And Dose In The Induction Of Protective Cd8+ T Cells Against A Lethal Poxvirus By Mrna-Lnp Vaccines, Samita Kafle, Brian Montoya, Lingjuan Tang, Ying Tam, Hiromi Muramatsu, Norbert Pardi, Luis Sigal

Department of Microbiology and Immunology Faculty Papers

The role of CD4⁺ T cells in the induction of protective CD8⁺ T cells by mRNA lipid nanoparticle (LNP) vaccines is unknown. We used B6 or Tlr9^−/− mice depleted or not of CD4⁺ T cells and LNP vaccines loaded with mRNAs encoding the ectromelia virus (ECTV) MHC class I H-2 K^b-restricted immunodominant CD8⁺ T cell epitope TSYKFESV (TSYKFESV mRNA-LNPs) or the ECTV EVM158 protein, which contains TSYKFESV (EVM-158 mRNA-LNPs). Following prime and boost with 10 μg of either vaccine, K^b-TSYKFESV-specific CD8⁺ T cells fully protected male and female mice from …