Digital Commons Network^™

The Role Of Epigenetic Mechanisms In The Long-Term Effects Of Early-Life Adversity And Mother-Infant Relationship On Physiology And Behavior Of Offspring In Laboratory Rats And Mice, Olga V Burenkova, Elena L Grigorenko

Faculty, Staff and Students Publications

Maternal care during the early postnatal period of altricial mammals is a key factor in the survival and adaptation of offspring to environmental conditions. Natural variations in maternal care and experimental manipulations with maternal-child relationships modeling early-life adversity (ELA) in laboratory rats and mice have a strong long-term influence on the physiology and behavior of offspring in rats and mice. This literature review is devoted to the latest research on the role of epigenetic mechanisms in these effects of ELA and mother-infant relationship, with a focus on the regulation of hypothalamic-pituitary-adrenal axis and brain-derived neurotrophic factor. An important part of …

Sensory Experiences Questionnaire Unravels Differences In Sensory Profiles Between Mecp2-Related Disorders, Bernhard Suter, Davut Pehlivan, Muharrem Ak, Holly K Harris, Ariel M Lyons-Warren

Faculty, Staff and Students Publications

The methyl CpG-binding protein-2 (MECP2) gene is located on the Xq28 region. Loss of function mutations or increased copies of MECP2 result in Rett syndrome (RTT) and MECP2 duplication syndrome (MDS), respectively. Individuals with both disorders exhibit overlapping autism symptoms, yet few studies have dissected the differences between these gene dosage sensitive disorders. Further, research examining sensory processing patterns in persons with RTT and MDS is largely absent. Thus, the goal of this study was to analyze and compare sensory processing patterns in persons with RTT and MDS. Towards this goal, caregivers of 50 female individuals with RTT and 122 …

Single-Center Outcomes After Liver Transplantation With Sars-Cov-2-Positive Donors: An Argument For Increased Utilization, Ashton A Connor, Max W Adelman, Constance M Mobley, Mozhgon Moaddab, Alexandra J Erhardt, David E Hsu, Elizabeth W Brombosz, Mansi Sanghvi, Yee Lee Cheah, Caroline J Simon, Mark J Hobeika, Ashish S Saharia, David W Victor, Sudha Kodali, Tamneet Basra, Edward A Graviss, Duc T Nguyen, Ahmed Elsaiey, Linda W Moore, Masayuki Nigo, Ashley L Drews, Kevin A Grimes, Cesar A Arias, Xian C Li, A Osama Gaber, R Mark Ghobrial

Faculty, Staff and Students Publications

Background: The COVID-19 pandemic has led to an increase in SARS-CoV-2-test positive potential organ donors. The benefits of life-saving liver transplantation (LT) must be balanced against the potential risk of donor-derived viral transmission. Although emerging evidence suggests that the use of COVID-19-positive donor organs may be safe, granular series thoroughly evaluating safety are still needed. Results of 29 consecutive LTs from COVID-19-positive donors at a single center are presented here.

Methods: A retrospective cohort study of LT recipients between April 2020 and December 2022 was conducted. Differences between recipients of COVID-19-positive (n = 29 total; 25 index, 4 redo) and …

A Scoping Review Of Artificial Intelligence In Medical Education: Beme Guide No 84, Morris Gordon, Michelle Daniel, Aderonke Ajiboye, Hussein Uraiby, Nicole Y Xu, Rangana Bartlett, Janice Hanson, Mary Haas, Maxwell Spadafore, Ciaran Grafton-Clarke, Rayhan Yousef Gasiea, Colin Michie, Janet Corral, Brian Kwan, Diana Dolmans, Satid Thammasitboon

Faculty, Staff and Students Publications

Background: Artificial Intelligence (AI) is rapidly transforming healthcare, and there is a critical need for a nuanced understanding of how AI is reshaping teaching, learning, and educational practice in medical education. This review aimed to map the literature regarding AI applications in medical education, core areas of findings, potential candidates for formal systematic review and gaps for future research.

Methods: This rapid scoping review, conducted over 16 weeks, employed Arksey and O'Malley's framework and adhered to STORIES and BEME guidelines. A systematic and comprehensive search across PubMed/MEDLINE, EMBASE, and MedEdPublish was conducted without date or language restrictions. Publications included in …

Using Starling Murmuration As A Model For Creating A Global Health Community Of Practice To Advance Equity In Scholarship, Diane Nguyen, Rogers N Ssebunya, Kajal Hirani, Anna Mandalakas, Jennifer Benjamin, B Lee Ligon, Satid Thammasitboon

Faculty, Staff and Students Publications

Background: Disparities in scholarship exist between authors in low- or middle-income countries (LMIC) and high-income countries. Recognizing these disparities in our global network providing pediatric, adolescent, and maternal healthcare to vulnerable populations in LMIC, we sought to improve access and provide resources to address educational needs and ultimately impact the broader scholarship disparity.

Methods: We created a virtual community of practice (CoP) program underpinned by principles from starling murmuration to promote interdisciplinary scholarship. We developed guiding principles- autonomy, mastery and purpose- to direct the Global Health Scholarship Community of Practice Program. Program components included a continuing professional development (CPD) program, …

Association Of Hematological And Biochemical Parameters And Hla-Drb1 Alleles With Anti-Cyclic Citrullinated Peptide Autoantibodies In Sudanese Rheumatic Patients, Khalid E Khalid

Faculty, Staff and Student Publications

Introduction

Anti-citrullinated protein/peptide antibodies (ACPA) are crucial for the diagnosis and prognosis of rheumatoid arthritis (RA) and are associated with class II HLA-DRB1 alleles.

The study’s goal was to determine how DRB1 alleles and hematological and biochemical parameters affect ACPA production in RA patients from Sudan.

Methods

The study analyzed the hematological and biochemical parameters and the frequency of HLA-DRB1 alleles in 120 RA patients and 100 controls. Automated analyzers, ELISA, the latex agglutination test, and the Westergren method were utilized for hematological and biochemical testing. HLA class II alleles were genotyped using polymerase chain reaction-sequence-specific primers (PCR-SSP). The student’s …

Sprint Performance Following Plyometric Conditioning Activity In Elite Sprinters, Kinga Huminska-Lisowska, Aleksandra Strońska-Pluta, Aleksandra Suchanecka, Myosotis Massidda, Grzegorz Trybek, Carla Maria Calò, Agata Rzeszutko-Bełzowska, Remigiusz Recław, Anna Grzywacz

Baltic Journal of Health and Physical Activity

Introduction: This study investigates an association between the human dopamine receptor 2 gene DRD2 Taq1D rs1800498 polymorphism and personality traits among athletes, exploring the genetic underpinnings of sports performance and psychological characteristics. It aims to understand how genetic factors related to dopamine reception influence athletic predispositions and behaviors. Materials and Methods: An association study was conducted with 391 male participants, comparing 159 sports subjects with 232 non-trained controls. Personality traits were assessed using the NEO Five-Factor Inventory, while the DRD2 Taq1D rs1800498 polymorphism was genotyped through real-time PCR. Results: Significant differences in the DRD2 Taq1D rs1800498 genotype and allele frequencies …

Proteoglycan Dysfunction: A Common Link Between Intervertebral Disc Degeneration And Skeletal Dysplasia, Kimheak Sao, Makarand V. Risbud

Department of Orthopaedic Surgery Faculty Papers

Proteoglycans through their sulfated glycosaminoglycans regulate cell-matrix signaling during tissue development, regeneration, and degeneration processes. Large extracellular proteoglycans such as aggrecan, versican, and perlecan are especially important for the structural integrity of the intervertebral disc and cartilage during development. In these tissues, proteoglycans are responsible for hydration, joint flexibility, and the absorption of mechanical loads. Loss or reduction of these molecules can lead to disc degeneration and skeletal dysplasia, evident from loss of disc height or defects in skeletal development respectively. In this review, we discuss the common proteoglycans found in the disc and cartilage and elaborate on various murine …

The Impact Of Kangaroo Care On The Weight Gain Of Premature Infants, Heather Vincequere

SACAD: Scholarly Activities

Premature birth remains a global health concern, affecting approximately 15 million infants annually (WHO, 2023). Kangaroo Care (KC), involving skin-to-skin contact between caregivers and infants, was developed as a promising intervention to mitigate the adverse effects of prematurity. This study aimed to investigate the impact of KC on weight gain among preterm infants in the neonatal intensive care unit (NICU) at Doctors Hospital of Augusta (DHOA). A quasi-experimental quantitative posttest-only design was employed, with eight preterm infants (< 37 weeks gestation) participating in KC for at least 30 minutes daily. Daily weight measurements were collected over a four-week period and compared to the expected weight gain for infants receiving traditional incubator care. Results revealed a statistically significant increase in weight gain among infants receiving KC compared to the historical average for infants in traditional incubator care (t (7) = 2.443, p = 0.022). A large effect size (Cohen's d = 0.864) further supported the significance of these findings. Despite limitations such as a small sample size and convenience sampling, this study emphasizes that KC enhances weight gain in preterm infants, thus improving overall health outcomes. Implementation of KC requires ongoing support from nurse leaders to ensure proper education and successful integration into routine care practices. Nonetheless, continued research with larger samples and improved randomization is warranted to fully understand the long-term benefits of KC in neonatal care settings.

Tgf-Β1 And Tgf-Βr1 Variants Are Associated With Clinical Outcomes In Smoking-Related Head And Neck Cancer Patients Treated With Chemoradiation Through Modulating Microrna-Mediated Regulation, Zihao Niu, Peng Sun, Mark E Zafereo, Hongliang Liu, Peng Wei, Jia Wu, Neil D Gross, Sanjay Shete, Qingyi Wei, Guibin Zheng, Andy G Sikora, George A Calin, Guojun Li

Faculty, Staff and Student Publications

TGF-β1 and TGF-βR1 play important roles in immune and inflammatory responses. Genetic variants of TGF-β1 rs1800470 and TGF-βR1 rs334348 have emerged as potentially prognostic biomarkers for HPV-related head and neck cancer, while their prognostic effect on survival of smoking-related head and neck cancer remains unknown. This study included 1403 patients with smoking-related head and neck cancer, and all these patients were genotyped for TGF-β1 rs1800470 and TGF-βR1 rs334348. Both univariate and multivariate analyses were performed to evaluate associations between the two functional genetic variants in microRNA binding sites of TGF-β1 and TGF-βR1 and survivals. Patients with TGF-β1 rs1800470 CT or …

The Effect Of Cervical Pessary On Increasing Gestational Age At Delivery In Twin Pregnancies With Asymptomatic Short Cervix: A Systematic Review And Meta-Analysis Of Randomized Controlled Trials, Amir Hossein Norooznezhad, Nikan Zargarzadeh, Ali Javinani, Seyedeh Maedeh Nabavian, Shohra Qaderi, Shayan Mostafaei, Vincenzo Berghella, Yinka Oyelese, Alireza A. Shamshirsaz

Department of Obstetrics and Gynecology Faculty Papers

OBJECTIVE: The incidence of preterm delivery is much higher in twin pregnancies than in singletons and even higher if a short cervical length is detected in the second trimester. Studies are contradictory regarding the efficacy of a cervical pessary to decrease preterm birth in twin pregnancies and short cervical length. To conduct a systematic review and meta-analysis investigating the efficacy of cervical pessary in prolonging gestation, preventing preterm birth, and reducing adverse neonatal outcomes in twin pregnancies with an asymptomatic short cervix.

DATA SOURCES: PubMed, Scopus, Web of Science, and ClinicalTrials.org were searched for randomized controlled trials from inception to …

Myeloid-Derived Suppressor Cell Mitochondrial Fitness Governs Chemotherapeutic Efficacy In Hematologic Malignancies, Saeed Daneshmandi, Jee Eun Choi, Qi Yan, Cameron R. Macdonald, Manu Pandey, Mounika Goruganthu, Nathan Roberts, Prashant K. Singh, Richard M. Higashi, Andrew N. Lane, Teresa W-M Fan, Jianmin Wang, Philip L. Mccarthy, Elizabeth A. Repasky, Hemn Mohammadpour

Markey Cancer Center Faculty Publications

Myeloid derived suppressor cells (MDSCs) are key regulators of immune responses and correlate with poor outcomes in hematologic malignancies. Here, we identify that MDSC mitochondrial fitness controls the efficacy of doxorubicin chemotherapy in a preclinical lymphoma model. Mechanistically, we show that triggering STAT3 signaling via β2-adrenergic receptor (β2-AR) activation leads to improved MDSC function through metabolic reprogram- ing, marked by sustained mitochondrial respiration and higher ATP generation which reduces AMPK signaling, altering energy metabolism. Furthermore, induced STAT3 signaling in MDSCs enhances glutamine consumption via the TCA cycle. Metabolized glutamine generates itaconate which downregulates mitochondrial reactive oxygen species via regulation of …

Real World Clinical Experience Using Daily Intelligence-Assisted Online Adaptive Radiotherapy For Head And Neck Cancer, Philip Blumenfeld, Eduard Arbit, Robert Den, Ayman Salhab, Tal Falick Michaeli, Marc Wygoda, Yair Hillman, Raphael Pfeffer, Marcel Fang, Yael Misrati, Noam Weizman, Jon Feldman, Aron Popovtzer

Department of Radiation Oncology Faculty Papers

Background

Adaptive radiation therapy (ART) offers a dynamic approach to address structural and spatial changes that occur during radiotherapy (RT) for locally advanced head and neck cancers. The integration of daily ART with Cone-Beam CT (CBCT) imaging presents a solution to enhance the therapeutic ratio by addressing inter-fractional changes.

Methods

We evaluated the initial clinical experience of daily ART for patients with head and neck cancer using an online adaptive platform with intelligence-assisted workflows on daily CBCT. Treatment included auto-contour and structure deformation of Organs at Risk (OARs) and target structures, with adjustments by the treating physician. Two plans were …

Transcriptional Responses Of Different Brain Cell Types To Oxygen Decline, Camille Ravel-Godreuil, Ethan R Roy, Srinivas N Puttapaka, Sanming Li, Yanyu Wang, Xiaoyi Yuan, Holger K Eltzschig, Wei Cao

Faculty, Staff and Student Publications

Brain hypoxia is associated with a wide range of physiological and clinical conditions. Although oxygen is an essential constituent of maintaining brain functions, our understanding of how specific brain cell types globally respond and adapt to decreasing oxygen conditions is incomplete. In this study, we exposed mouse primary neurons, astrocytes, and microglia to normoxia and two hypoxic conditions and obtained genome-wide transcriptional profiles of the treated cells. Analysis of differentially expressed genes under conditions of reduced oxygen revealed a canonical hypoxic response shared among different brain cell types. In addition, we observed a higher sensitivity of neurons to oxygen decline, …

Activation Of Endogenous Retroviruses And Induction Of Viral Mimicry By Mek1/2 Inhibition In Pancreatic Cancer, Alice Cortesi, Francesco Gandolfi, Fabiana Arco, Pierluigi Di Chiaro, Emanuele Valli, Sara Polletti, Roberta Noberini, Francesco Gualdrini, Sergio Attanasio, Francesca Citron, I-Lin Ho, Rutvi Shah, Er-Yen Yen, Mara Cetty Spinella, Simona Ronzoni, Simona Rodighiero, Nico Mitro, Tiziana Bonaldi, Serena Ghisletti, Silvia Monticelli, Andrea Viale, Giuseppe Riccardo Diaferia, Gioacchino Natoli

Faculty, Staff and Student Publications

While pancreatic ductal adenocarcinomas (PDACs) are addicted to KRAS-activating mutations, inhibitors of downstream KRAS effectors, such as the MEK1/2 kinase inhibitor trametinib, are devoid of therapeutic effects. However, the extensive rewiring of regulatory circuits driven by the attenuation of the KRAS pathway may induce vulnerabilities of therapeutic relevance. An in-depth molecular analysis of the transcriptional and epigenomic alterations occurring in PDAC cells in the initial hours after MEK1/2 inhibition by trametinib unveiled the induction of endogenous retroviruses (ERVs) escaping epigenetic silencing, leading to the production of double-stranded RNAs and the increased expression of interferon (IFN) genes. We tracked ERV activation …

Admix-Kit: An Integrated Toolkit And Pipeline For Genetic Analyses Of Admixed Populations, Kangcheng Hou, Stephanie Gogarten, Joohyun Kim, Xing Hua, Julie-Alexia Dias, Quan Sun, Ying Wang, Taotao Tan, Elizabeth G Atkinson, Alicia Martin, Jonathan Shortt, Jibril Hirbo, Yun Li, Bogdan Pasaniuc, Haoyu Zhang

Faculty, Staff and Students Publications

SUMMARY: Admixed populations, with their unique and diverse genetic backgrounds, are often underrepresented in genetic studies. This oversight not only limits our understanding but also exacerbates existing health disparities. One major barrier has been the lack of efficient tools tailored for the special challenges of genetic studies of admixed populations. Here, we present admix-kit, an integrated toolkit and pipeline for genetic analyses of admixed populations. Admix-kit implements a suite of methods to facilitate genotype and phenotype simulation, association testing, genetic architecture inference, and polygenic scoring in admixed populations.

AVAILABILITY AND IMPLEMENTATION: Admix-kit package is open-source and available at https://github.com/KangchengHou/admix-kit. …

Non-Thermal Plasma Reduces Hsv-1 Infection Of And Replication In Hacat Keratinocytes In Vitro, Julia Sutter, Jascha Brettschneider, Brian Wigdahl, Peter Bruggeman, Fred Krebs, Vandana Miller

Kimmel Cancer Center Faculty Papers

Herpes simplex virus type 1 (HSV-1) is a lifelong pathogen characterized by asymptomatic latent infection in the trigeminal ganglia (TG), with periodic outbreaks of cold sores caused by virus reactivation in the TG and subsequent replication in the oral mucosa. While antiviral therapies can provide relief from cold sores, they are unable to eliminate HSV-1. We provide experimental results that highlight non-thermal plasma (NTP) as a new alternative therapy for HSV-1 infection that would resolve cold sores faster and reduce the establishment of latent infection in the TG. Additionally, this study is the first to explore the use of NTP …

Visual Analysis Of Bone Malignancies Immunotherapy: A Bibliometric Analysis From 2010 To 2023, Kaiyu Shen, Liu Yang, Shuaiyi Ke, Wencang Gao

Faculty, Staff and Student Publications

Background: Bone malignancies (BM), including osteosarcoma, Ewing's sarcoma, chondrosarcoma, and chordoma, are characterized by high rates of recurrence and mortality, despite the availability of diverse treatment approaches. Immunotherapy has gained increasing importance in cancer treatment. However, there is a lack of comprehensive studies that utilize bibliometric analysis to explore immunotherapy for BM.

Methods: A literature search of English studies on BM and immunotherapy from 2010 to 2023 was conducted in the Web of Science Core Collection database. Bibliometric analysis tools such as VOSviewer, CiteSpace, and R Studio were utilized to examine global trends and research hotspots in this field.

Results: …

Ndrgs In Breast Cancer: A Review And In Silico Analysis, Emilly S Villodre, Anh P N Nguyen, Bisrat G Debeb

Faculty, Staff and Student Publications

Simple Summary

Breast cancer is the most common cancer in women and one of the deadliest. While survival rates for patients with breast cancer have seen notable improvements in recent decades, current treatment strategies still face significant limitations, especially for patients with aggressive, therapy-resistant, and metastatic breast cancers. For this reason, it is important to identify new targets in order to develop more effective therapeutic strategies. The N-myc downstream regulated gene family (NDRGs), comprising NDRG1, NDRG2, NDRG3, and NDRG4, has been previously described as tumor suppressors. However, recent findings challenge this perception, particularly for NDRG1, …

Regional Analysis To Delineate Intrasample Heterogeneity With Regionalst, Yue Lyu, Chong Wu, Wei Sun, Ziyi Li

Faculty, Staff and Student Publications

MOTIVATION: Spatial transcriptomics has greatly contributed to our understanding of spatial and intra-sample heterogeneity, which could be crucial for deciphering the molecular basis of human diseases. Intra-tumor heterogeneity, e.g. may be associated with cancer treatment responses. However, the lack of computational tools for exploiting cross-regional information and the limited spatial resolution of current technologies present major obstacles to elucidating tissue heterogeneity.

RESULTS: To address these challenges, we introduce RegionalST, an efficient computational method that enables users to quantify cell type mixture and interactions, identify sub-regions of interest, and perform cross-region cell type-specific differential analysis for the first time. Our simulations …

Dissection, Histological Processing, And Gene Expression Analysis Of Murine Supraclavicular Brown Adipose Tissuejove: Peer Reviewed Scientific Video Journal Article Protocols, Mark G Waterstraat, Ziyi Wang, Mari Kogiso, Rommel Caballero-Juarez, Miao-Hsueh Chen

Faculty, Staff and Students Publications

Brown adipose tissue (BAT)-mediated thermogenesis plays an important role in the regulation of metabolism, and its morphology and function can be greatly impacted by environmental stimuli in mice and humans. Currently, murine interscapular BAT (iBAT), which is located between two scapulae in the upper dorsal flank of mice, is the main BAT depot used by research laboratories to study BAT function. Recently, a few previously unknown BAT depots were identified in mice, including one analogous to human supraclavicular brown adipose tissue. Unlike iBAT, murine supraclavicular brown adipose tissue (scBAT) is situated in the intermediate layer of the neck and thus …

Challenges And Considerations Of Preclinical Development For Ipsc-Based Myogenic Cell Therapy, Congshan Sun, Carlo Serra, Brianna Harley Kalicharan, Jeffrey Harding, Mahendra Rao

Faculty, Staff and Students Publications

Cell therapies derived from induced pluripotent stem cells (iPSCs) offer a promising avenue in the field of regenerative medicine due to iPSCs' expandability, immune compatibility, and pluripotent potential. An increasing number of preclinical and clinical trials have been carried out, exploring the application of iPSC-based therapies for challenging diseases, such as muscular dystrophies. The unique syncytial nature of skeletal muscle allows stem/progenitor cells to integrate, forming new myonuclei and restoring the expression of genes affected by myopathies. This characteristic makes genome-editing techniques especially attractive in these therapies. With genetic modification and iPSC lineage specification methodologies, immune-compatible healthy iPSC-derived muscle cells …

Gut Microbiota And Blood Metabolites Related To Fiber Intake And Type 2 Diabetes, Zheng Wang, Brandilyn A Peters, Bing Yu, Megan L Grove, Tao Wang, Xiaonan Xue, Bharat Thyagarajan, Martha L Daviglus, Eric Boerwinkle, Gang Hu, Yasmin Mossavar-Rahmani, Carmen R Isasi, Rob Knight, Robert D Burk, Robert C Kaplan, Qibin Qi

Faculty, Staff and Student Publications

BACKGROUND: Consistent evidence suggests diabetes-protective effects of dietary fiber intake. However, the underlying mechanisms, particularly the role of gut microbiota and host circulating metabolites, are not fully understood. We aimed to investigate gut microbiota and circulating metabolites associated with dietary fiber intake and their relationships with type 2 diabetes (T2D).

METHODS: This study included up to 11 394 participants from the HCHS/SOL (Hispanic Community Health Study/Study of Latinos). Diet was assessed with two 24-hour dietary recalls at baseline. We examined associations of dietary fiber intake with gut microbiome measured by shotgun metagenomics (350 species/85 genera and 1958 enzymes; n=2992 at …

Cancer Biomarkers: Emerging Trends And Clinical Implications For Personalized Treatment, Antonio Passaro, Maise Al Bakir, Emily G Hamilton, Maximilian Diehn, Fabrice André, Sinchita Roy-Chowdhuri, Giannis Mountzios, Ignacio I Wistuba, Charles Swanton, Solange Peters

Faculty, Staff and Student Publications

The integration of cancer biomarkers into oncology has revolutionized cancer treatment, yielding remarkable advancements in cancer therapeutics and the prognosis of cancer patients. The development of personalized medicine represents a turning point and a new paradigm in cancer management, as biomarkers enable oncologists to tailor treatments based on the unique molecular profile of each patient's tumor. In this review, we discuss the scientific milestones of cancer biomarkers and explore future possibilities to improve the management of patients with solid tumors. This progress is primarily attributed to the biological characterization of cancers, advancements in testing methodologies, elucidation of the immune microenvironment, …

The Hagfish Genome And The Evolution Of Vertebrates, Ferdinand Marlétaz, Nataliya Timoshevskaya, Vladimir A. Timoshevskiy, Elise Parey, Oleg Simakov, Daria Gavriouchkina, Masakazu Suzuki, Kaoru Kubokawa, Sydney Brenner, Jeramiah James Smith, Daniel S. Rokhsar

Markey Cancer Center Faculty Publications

As the only surviving lineages of jawless fishes, hagfishes and lampreys provide a crucial window into early vertebrate evolution1–3 . Here we investigate the complex history, timing and functional role of genome-wide duplications4–7 and programmed DNA elimination8,9 in vertebrates in the light of a chromosome-scale genome sequence for the brown hagfish Eptatretus atami. Combining evidence from syntenic and phylogenetic analyses, we establish a comprehensive picture of vertebrate genome evolution, including an auto-tetraploidization (1RV) that predates the early Cambrian cyclostome–gnathostome split, followed by a mid–late Cambrian allo-tetraploidization (2RJV) in gnathostomes and a prolonged Cambrian–Ordovician hexaploidization (2RCY) in cyclostomes. Subsequently, hagfishes underwent …

Embracing Cancer Complexity: Hallmarks Of Systemic Disease, Charles Swanton, Elsa Bernard, Chris Abbosh, Fabrice André, Johan Auwerx, Allan Balmain, Dafna Bar-Sagi, René Bernards, Susan Bullman, James Degregori, Catherine Elliott, Ayelet Erez, Gerard Evan, Mark A Febbraio, Andrés Hidalgo, Mariam Jamal-Hanjani, Johanna A Joyce, Matthew Kaiser, Katja Lamia, Jason W Locasale, Sherene Loi, Ilaria Malanchi, Miriam Merad, Kathryn Musgrave, Ketan J Patel, Sergio Quezada, Jennifer A Wargo, Ashani Weeraratna, Eileen White, Frank Winkler, John N Wood, Karen H Vousden, Douglas Hanahan

Faculty, Staff and Student Publications

The last 50 years have witnessed extraordinary developments in understanding mechanisms of carcinogenesis, synthesized as the hallmarks of cancer. Despite this logical framework, our understanding of the molecular basis of systemic manifestations and the underlying causes of cancer-related death remains incomplete. Looking forward, elucidating how tumors interact with distant organs and how multifaceted environmental and physiological parameters impinge on tumors and their hosts will be crucial for advances in preventing and more effectively treating human cancers. In this perspective, we discuss complexities of cancer as a systemic disease, including tumor initiation and promotion, tumor micro- and immune macro-environments, aging, metabolism …

The Remission Status Of Aml Patients After Allo-Hct Is Associated With A Distinct Single-Cell Bone Marrow T-Cell Signature, Anna Mathioudaki, Xizhe Wang, David Sedloev, Richard Huth, Aryan Kamal, Michael Hundemer, Yi Liu, Spyridoula Vasileiou, Premal Lulla, Carsten Müller-Tidow, Peter Dreger, Thomas Luft, Tim Sauer, Michael Schmitt, Judith B Zaugg, Caroline Pabst

Faculty, Staff and Students Publications

Acute myeloid leukemia (AML) is a hematologic malignancy for which allogeneic hematopoietic cell transplantation (allo-HCT) often remains the only curative therapeutic approach. However, incapability of T cells to recognize and eliminate residual leukemia stem cells might lead to an insufficient graft-versus-leukemia (GVL) effect and relapse. Here, we performed single-cell RNA-sequencing (scRNA-seq) on bone marrow (BM) T lymphocytes and CD34+ cells of 6 patients with AML 100 days after allo-HCT to identify T-cell signatures associated with either imminent relapse (REL) or durable complete remission (CR). We observed a higher frequency of cytotoxic CD8+ effector and gamma delta (γδ) T cells in …

S100a8/A9 As A Prognostic Biomarker With Causal Effects For Post-Acute Myocardial Infarction Heart Failure, Jie Ma, Yang Li, Ping Li, Xinying Yang, Shuolin Zhu, Ke Ma, Fei Gao, Hai Gao, Hui Zhang, Xin-Liang Ma, Jie Du, Yulin Li

Department of Emergency Medicine Faculty Papers

Heart failure is the prevalent complication of acute myocardial infarction. We aim to identify a biomarker for heart failure post-acute myocardial infarction. This observational study includes 1062 and 1043 patients with acute myocardial infarction in the discovery and validation cohorts, respectively. The outcomes are in-hospital and long-term heart failure events. S100A8/A9 is screened out through proteomic analysis, and elevated circulating S100A8/A9 is independently associated with heart failure in discovery and validation cohorts. Furthermore, the predictive value of S100A8/A9 is superior to the traditional biomarkers, and the addition of S100A8/A9 improves the risk estimation using traditional risk factors. We finally report …

High-Density Glass Scintillators For Proton Radiography-Relative Luminosity, Proton Response, And Spatial Resolution, Ethan Stolen, Ryan Fullarton, Rain Hein, Robin L Conner, Luiz G Jacobsohn, Charles-Antoine Collins-Fekete, Sam Beddar, Ugur Akgun, Daniel Robertson

Faculty, Staff and Student Publications

Proton radiography is a promising development in proton therapy, and researchers are currently exploring optimal detector materials to construct proton radiography detector arrays. High-density glass scintillators may improve integrating-mode proton radiography detectors by increasing spatial resolution and decreasing detector thickness. We evaluated several new scintillators, activated with europium or terbium, with proton response measurements and Monte Carlo simulations, characterizing relative luminosity, ionization quenching, and proton radiograph spatial resolution. We applied a correction based on Birks's analytical model for ionization quenching. The data demonstrate increased relative luminosity with increased activation element concentration, and higher relative luminosity for samples activated with europium. …

Advancing Access To Genome Sequencing For Rare Genetic Disorders: Recent Progress And Call To Action, Vaidehi Jobanputra, Brock Schroeder, Heidi L Rehm, Wei Shen, Elizabeth Spiteri, Ghunwa Nakouzi, Stacie Taylor, Christian R Marshall, Linyan Meng, Stephen F Kingsmore, Katarzyna Ellsworth, Euan Ashley, Ryan J Taft, Medical Genome Initiative

Faculty, Staff and Students Publications

No abstract provided.