Digital Commons Network^™

Enterococcus Faecalis-Derived Adenine Enhances Enterohaemorrhagic Escherichia Coli Type 3 Secretion System-Dependent Virulence, Fernando H Martins, Thibaut Rosay, Anubama Rajan, Hannah E Carter, Tayah Turocy, Andres Mejia, Jason M Crawford, Anthony W Maresso, Vanessa Sperandio

Faculty, Staff and Students Publications

Interactions between microbiota and enteric pathogens can promote colonization resistance or enhance pathogenesis. The pathobiont Enterococcus faecalis increases enterohaemorrhagic E. coli (EHEC) virulence by upregulating Type 3 Secretion System (T3SS) expression, effector translocation, and attaching and effacing (AE) lesion formation on enterocytes, but the mechanisms underlying this remain unknown. Using co-infection of organoids, metabolomics, supplementation experiments and bacterial genetics, here we show that co-culture of EHEC with E. faecalis increases the xanthine-hypoxanthine pathway activity and adenine biosynthesis. Adenine or E. faecalis promoted T3SS gene expression, while transcriptomics showed upregulation of adeP expression, which encodes an adenine importer. Mechanistically, adenine relieved …

Altered Extracellular Matrix-Related Pathways Accelerate The Transition From Normal To Prefibroid Myometrium In Black Women, Maria Victoria Bariani, Sandra L Grimm, Cristian Coarfa, Digna R Velez Edwards, Qiwei Yang, Cheryl L Walker, Mohamed Ali, Ayman Al-Hendy

Faculty, Staff and Students Publications

Background: Black women experience a disproportionate impact of uterine fibroids compared to White women, including earlier diagnosis, higher frequency, and more severe symptoms. The etiology underlying this racial disparity remains elusive.

Objective: The aim of this study was to evaluate the molecular differences in normal myometrium (fibroid-free uteri) and at-risk myometrium (fibroid-containing uteri) tissues in Black and White women.

Study design: We conducted whole-genome RNA-seq on normal and at-risk myometrium tissues obtained from both self-identified Black and White women (not Hispanic or Latino) to determine global gene expression profiles and to conduct enriched pathway analyses (n=3 per group). We initially …

Phylogenetically Diverse Bacterial Species Produce Histamine, Kristen A Engevik, Amber Hazzard, Brenton Puckett, Kathleen M Hoch, Sigmund J Haidacher, Anthony M Haag, Jennifer K Spinler, James Versalovic, Melinda A Engevik, Thomas D Horvath

Faculty, Staff and Students Publications

Histamine is an important biogenic amine known to impact a variety of patho-physiological processes ranging from allergic reactions, gut-mediated anti-inflammatory responses, and neurotransmitter activity. Histamine is found both endogenously within specialized host cells and exogenously in microbes. Exogenous histamine is produced through the decarboxylation of the amino acid L-histidine by bacterial-derived histidine decarboxylase enzymes. To investigate how widespread histamine production is across bacterial species, we examined 102,018 annotated genomes in the Integrated Microbial Genomes Database and identified 3,679 bacterial genomes (3.6 %) which possess the enzymatic machinery to generate histamine. These bacteria belonged to 10 phyla: Bacillota, Bacteroidota, Actinomycetota, Pseudomonadota, …

Satisfaction With Mode Of Delivery Of Genomic Sequencing Results In A Diverse National Sample Of Research Participants Through The Clinical Sequencing Evidence-Generating Research Consortium, Sarah Scollon, Jill O Robinson, Eunji Jo, Sabrina A Suckiel, Laura M Amendola, Ann Katherine M Foreman, Gail P Jarvik, Christine Rini, Tao Wang, Anne Slavotinek

Faculty, Staff and Students Publications

Purpose: Research that includes diverse patient populations is necessary to optimize implementation of telehealth.

Methods: As part of a Clinical Sequencing Evidence-Generating Research Consortium cross-site study, we assessed satisfaction with mode of return of results (RoR) delivery across a diverse sample of participants receiving genetic testing results in person vs telemedicine (TM).

Results: Ninety-eight percent of participants were satisfied with their mode of results delivery. Participants receiving results by TM were more likely to report a preference for receiving results in a different way and challenges with providers noticing difficulties with understanding. More than 90% reported satisfaction across all items …

Death-Associated Protein Kinase 3 Modulates Migration And Invasion Of Triple-Negative Breast Cancer Cells, Junkai Wang, Anh M Tran-Huynh, Beom-Jun Kim, Doug W Chan, Matthew V Holt, Diana Fandino, Xin Yu, Xiaoli Qi, Jin Wang, Weijie Zhang, Yi-Hsuan Wu, Meenakshi Anurag, Xiang H F Zhang, Bing Zhang, Chonghui Cheng, Charles E Foulds, Matthew J Ellis

Faculty, Staff and Students Publications

Sixteen patient-derived xenografts (PDXs) were analyzed using a mass spectrometry (MS)-based kinase inhibitor pull-down assay (KIPA), leading to the observation that death-associated protein kinase 3 (DAPK3) is significantly and specifically overexpressed in the triple-negative breast cancer (TNBC) models. Validation studies confirmed enrichment of DAPK3 protein, in both TNBC cell lines and tumors, independent of mRNA levels. Genomic knockout of DAPK3 in TNBC cell lines inhibited in vitro migration and invasion, along with down-regulation of an epithelial–mesenchymal transition (EMT) signature, which was confirmed in vivo. The kinase and leucine-zipper domains within DAPK3 were shown by a mutational analysis to be essential …

A Systematic Review And Expert Delphi Consensus Recommendation On The Use Of Vaccines In Patients Receiving Dupilumab: A Position Paper Of The American College Of Allergy, Asthma And Immunology, Jay A Lieberman, Derek K Chu, Tasnuva Ahmed, Timothy E Dribin, Elissa M Abrams, Aikaterini Anagnostou, Kimberly G Blumenthal, Mark Boguniewicz, Nicole M Chase, David B K Golden, Nicholas L Hartog, Jennifer R Heimall, Tina Ho, Monica G Lawrence, David A Khan, Timothy Dean Minniear, S Shahzad Mustafa, John J Oppenheimer, Elizabeth J Phillips, Allison Ramsey, Nicholas L Rider, Lynda Schneider, Marcus S Shaker, Jonathan M Spergel, Cosby A Stone, David R Stukus, Julie Wang, Matthew J Greenhawt

Faculty, Staff and Students Publications

BACKGROUND: Dupilumab is a monoclonal antibody that targets the interleukin (IL)-4 receptor alpha subunit, thus blocking the effects of IL-4 and IL-13, and has shown efficacy in treating various conditions including asthma, atopic dermatitis, eosinophilic esophagitis, and others. Because of its immune modulatory effects, clinical trials that studied dupilumab did not allow patients to receive live vaccines during the clinical trials because of an abundance of caution, and thus package inserts recommend that patients who are being treated with dupilumab should avoid live vaccines. Because dupilumab is now approved for use in patients from 6 months of age for the …

Distinct Basal Forebrain-Originated Neural Circuits Promote Homoeostatic Feeding And Suppress Hedonic Feeding In Male Mice, Hailan Liu, Jonathan C Bean, Yongxiang Li, Meng Yu, Olivia Z Ginnard, Kristine M Conde, Mengjie Wang, Xing Fang, Hesong Liu, Longlong Tu, Na Yin, Junying Han, Yongjie Yang, Qingchun Tong, Benjamin R Arenkiel, Chunmei Wang, Yang He, Yong Xu

Faculty, Staff and Students Publications

Feeding behaviour is influenced by two primary factors: homoeostatic needs driven by hunger and hedonic desires for pleasure even in the absence of hunger. While efficient homoeostatic feeding is vital for survival, excessive hedonic feeding can lead to adverse consequences such as obesity and metabolic dysregulations. However, the neurobiological mechanisms that orchestrate homoeostatic versus hedonic food consumption remain largely unknown. Here we show that GABAergic proenkephalin (Penk) neurons in the diagonal band of Broca (DBB) of male mice respond to food presentation. We further demonstrate that a subset of DBBPenk neurons that project to the paraventricular nucleus of the hypothalamus …

Neuroimaging Of The Effects Of Drug Exposure Or Self-Administration In Rodents: A Systematic Review, Gunner Drossel, Sarah R Heilbronner, Jan Zimmermann, Anna Zilverstand

Faculty, Staff and Students Publications

A systematic review of functional neuroimaging studies on drug (self-) administration in rodents is lacking. Here, we summarized effects of acute or chronic drug administration of various classes of drugs on brain function and determined consistency with human literature. We performed a systematic literature search and identified 125 studies on in vivo rodent resting-state functional magnetic resonance imaging (n = 84) or positron emission tomography (n = 41) spanning depressants (n = 27), opioids (n = 23), stimulants (n = 72), and cannabis (n = 3). Results primarily showed alterations in the striatum, consistent with the human literature. The anterior …

Pnpla3, Obesity, And Heavy Alcohol Use In Cirrhosis Patients May Exert A Synergistic Increase Hepatocellular Carcinoma Risk, Aaron P Thrift, Fasiha Kanwal, Hyeyeun Lim, Hao Duong, Yanhong Liu, Amit G Singal, Saira Khaderi, Sumeet K Asrani, Christopher I Amos, Hashem B El-Serag

Faculty, Staff and Students Publications

BACKGROUND & AIMS: In patients with cirrhosis, continued heavy alcohol consumption and obesity may increase risk of hepatocellular carcinoma (HCC). We examined whether germline susceptibility to hepatic steatosis not only independently predisposes to HCC but may also act synergistically with other risk factors.

METHODS: We analyzed data from 1911 patients in 2 multicenter prospective cohort studies in the United States. We classified patients according to alcohol consumption (current heavy vs not current heavy), obesity (body mass index ≥30 vs/m2), and PNPLA3 I148M variant status (carrier of at least one G risk allele vs noncarrier). We examined the independent and joint …

Characteristics Of Patients With Spontaneous Coronary Artery Dissection Presenting With Sudden Cardiac Arrest In The United States And The Potential Role Of Implantable Cardioverter Defibrillator Therapy, Chayakrit Krittanawong, Yusuf Kamran Qadeer, Song Peng Ang, Zhen Wang, Mahboob Alam, Samin Sharma, Hani Jneid

Faculty, Staff and Students Publications

BACKGROUND: Spontaneous coronary artery dissection (SCAD) is a disease entity that often occurs in young, healthy women and can cause life-threatening ventricular arrhythmias and sudden cardiac arrest. However, the characteristics and outcomes of SCAD with cardiac arrest are not well characterized.

METHODS: This study investigated the baseline characteristics of SCAD patients with cardiac arrest using the National Inpatient Sample (NIS) database between 2016 and 2020. In addition, we also sought to determine the potential impact that implantable cardioverter defibrillator (ICD) therapy had on morbidity and mortality in SCAD patients presenting with cardiac arrest.

RESULTS: Our findings showed that the SCAD …

A Genome-Wide Association Meta-Analysis Of All-Cause And Vascular Dementia, Mega Vascular Cognitive Impairment And Dementia (Megavcid) Consortium

Faculty, Staff and Students Publications

INTRODUCTION: Dementia is a multifactorial disease with Alzheimer's disease (AD) and vascular dementia (VaD) pathologies making the largest contributions. Yet, most genome-wide association studies (GWAS) focus on AD.

METHODS: We conducted a GWAS of all-cause dementia (ACD) and examined the genetic overlap with VaD. Our dataset includes 800,597 individuals, with 46,902 and 8702 cases of ACD and VaD, respectively. Known AD loci for ACD and VaD were replicated. Bioinformatic analyses prioritized genes that are likely functionally relevant and shared with closely related traits and risk factors.

RESULTS: For ACD, novel loci identified were associated with energy transport (SEMA4D), neuronal excitability …

The Cerebellum Modulates Thirst, Ila Mishra, Bing Feng, Bijoya Basu, Amanda M Brown, Linda H Kim, Tao Lin, Mir Abbas Raza, Amelia Moore, Abigayle Hahn, Samantha Bailey, Alaina Sharp, Juan C Bournat, Claire Poulton, Brian Kim, Amos Langsner, Aaron Sathyanesan, Roy V Sillitoe, Yanlin He, Atul R Chopra

Duncan NRI Faculty and Staff Publications

The cerebellum, a phylogenetically ancient brain region, has long been considered strictly a motor control structure. Recent studies have implicated the cerebellum in cognition, sensation, emotion and autonomic function, making it an important target for further investigation. Here, we show that cerebellar Purkinje neurons in mice are activated by the hormone asprosin, leading to enhanced thirst, and that optogenetic or chemogenetic activation of Purkinje neurons induces rapid manifestation of water drinking. Purkinje neuron-specific asprosin receptor (Ptprd) deletion results in reduced water intake without affecting food intake and abolishes asprosin's dipsogenic effect. Purkinje neuron-mediated motor learning and coordination were unaffected by …

Psychosocial Outcomes Of Pain And Pain Management In Adults With Osteogenesis Imperfecta: A Qualitative Study, Whitney S Shepherd, Andrew D Wiese, Hannah E Cho, W Conor Rork, M Usman Baig, Kristin M Kostick, Dianne Nguyen, Erin M Carter, Members Of The Bbdc, Chaya N Murali, Marie-Eve Robinson, Sophie C Schneider, Brendan Lee, V Reid Sutton, Eric A Storch

Faculty, Staff and Students Publications

Objectives

Osteogenesis imperfecta (OI) is a genetic disorder characterized by bone fragility and fractures, short stature, dental abnormalities, hearing loss, scoliosis, and chronic pain. Despite a growing literature on the functional outcomes of OI, limited research has explicitly examined the psychosocial outcomes of pain within OI.

Methods

Adults with OI (N=15) were interviewed to understand pain-related experiences through a thematic analysis of semi-structured interview data. Research team members, genetic research experts, and OI clinicians developed an interview guide focused on topics related to pain and mental health challenges. Participants’ transcripts were coded by two independent coders; codes were then merged …

Cmtm4 Inhibits Gastric Tumorigenesis And Metastasis, Xiurui Han, Weiwei Fu, Qinghua Sun, Jing Ning, Jing Zhang, Silvio Matsas, Fabrício Freire De Melo, Hejun Zhang, Xinyu Hao, Qiao Meng, Yueqing Gong, Huiling Zheng, Jing Zhang, Shigang Ding

Faculty, Staff and Student Publications

BACKGROUND: CKLF-like MARVEL transmembrane domain-containing 4 (CMTM4) is involved in immune regulation and tumor progression; however, its role in gastric cancer (GC) remains unclear. This study explored the role and mechanism of CMTM4 in GC.

METHODS: Immunohistochemistry was used to analyze CMTM4 expression in human gastric biopsied cells from patients with GC (N=23) or chronic superficial gastritis (N=23). To investigate the function of CMTM4 in GC cells, the gene

RESULTS: CMTM4 expression was more downregulated in the human GC tissues than the gastritis tissues. CMTM4 overexpression significantly inhibited the proliferation, migration, and invasion of the GC cells, whereas CMTM4 knockdown …

Single-Center Clinical Experience Of Extended Sleeve Lobectomy (Esl) Versus Standard Sleeve Lobectomy (Sl), Haoyou Wang, Wei Wang, Peng Zu, Gregor J Kocher, Mara B Antonoff, Alberto Lopez-Pastorini, Chenlei Zhang, Wei Chen, Hongxu Liu

Faculty, Staff and Student Publications

Background: Sleeve lobectomy (SL) and extended SL (ESL), which aim to preserve pulmonary function and enhance the quality of life of patients while ensuring oncological outcomes, are valuable surgical options for the treatment of centrally located non-small cell lung cancer (NSCLC). This study aimed to compare perioperative adverse events and long-term survival between SL and ESL in NSCLC patients, providing a comprehensive review of surgical outcomes, complications, and survival to assess the roles of SL and ESL in thoracic oncology.

Methods: This single-center retrospective study assessed the outcomes of NSCLC patients who underwent SL or ESL from June 2014 to …

Special Supplement Issue On Quality Assurance And Enrichment Of Biological And Biomedical Ontologies And Terminologies, Licong Cui, Ankur Agrawal

Faculty, Staff and Student Publications

Ontologies and terminologies serve as the backbone of knowledge representation in biomedical domains, facilitating data integration, interoperability, and semantic understanding across diverse applications. However, the quality assurance and enrichment of these resources remain an ongoing challenge due to the dynamic nature of biomedical knowledge. In this editorial, we provide an introductory summary of seven articles included in this special supplement issue for quality assurance and enrichment of biological and biomedical ontologies and terminologies. These articles span a spectrum of topics, such as development of automated quality assessment frameworks for Resource Description Framework (RDF) resources, identification of missing concepts in SNOMED …

Micronuclear Collapse From Oxidative Damage, Melody Di Bona, Yanyang Chen, Albert S Agustinus, Alice Mazzagatti, Mercedes A Duran, Matthew Deyell, Daniel Bronder, James Hickling, Christy Hong, Lorenzo Scipioni, Giulia Tedeschi, Sara Martin, Jun Li, Aušrinė Ruzgaitė, Nadeem Riaz, Parin Shah, Edridge K D'Souza, D Zack Brodtman, Simone Sidoli, Bill Diplas, Manisha Jalan, Nancy Y Lee, Alban Ordureau, Benjamin Izar, Ashley M Laughney, Simon Powell, Enrico Gratton, Stefano Santaguida, John Maciejowski, Peter Ly, Thomas M Jeitner, Samuel F Bakhoum

Faculty, Staff and Student Publications

Chromosome-containing micronuclei are a hallmark of aggressive cancers. Micronuclei frequently undergo irreversible collapse, exposing their enclosed chromatin to the cytosol. Micronuclear rupture catalyzes chromosomal rearrangements, epigenetic abnormalities, and inflammation, yet mechanisms safeguarding micronuclear integrity are poorly understood. In this study, we found that mitochondria-derived reactive oxygen species (ROS) disrupt micronuclei by promoting a noncanonical function of charged multivesicular body protein 7 (CHMP7), a scaffolding protein for the membrane repair complex known as endosomal sorting complex required for transport III (ESCRT-III). ROS retained CHMP7 in micronuclei while disrupting its interaction with other ESCRT-III components. ROS-induced cysteine oxidation stimulated CHMP7 oligomerization and …

Identification Of A0 Minimum Ablative Margins For Colorectal Liver Metastases: Multicentre, Retrospective Study Using Deformable Ct Registration And Artificial Intelligence-Based Autosegmentation, Iwan Paolucci, Jessica Albuquerque Marques Silva, Yuan-Mao Lin, Gregor Laimer, Valentina Cignini, Francesca Menchini, Marcio Meira, Alexander Shieh, Caleb O'Connor, Kyle A Jones, Carlo Gazzera, Paolo Fonio, Kristy K Brock, Marco Calandri, Marcos Menezes, Reto Bale, Bruno C Odisio

Faculty, Staff and Student Publications

Background: Several ablation confirmation software methods for minimum ablative margin assessment have recently been developed to improve local outcomes for patients undergoing thermal ablation of colorectal liver metastases. Previous assessments were limited to single institutions mostly at the place of development. The aim of this study was to validate the previously identified 5 mm minimum ablative margin (A0) using autosegmentation and biomechanical deformable image registration in a multi-institutional setting.

Methods: This was a multicentre, retrospective study including patients with colorectal liver metastases undergoing CT- or ultrasound-guided microwave or radiofrequency ablation during 2009-2022, reporting 3-year local disease progression (residual unablated tumour …

Inhibition Of Ulk1/2 And Kras G12c Controls Tumor Growth In Preclinical Models Of Lung Cancer, Phaedra C Ghazi, Kayla T O'Toole, Sanjana Srinivas Boggaram, Michael T Scherzer, Mark R Silvis, Yun Zhang, Madhumita Bogdan, Bryan D Smith, Guillermina Lozano, Daniel L Flynn, Eric L Snyder, Conan G Kinsey, Martin Mcmahon

Faculty, Staff and Student Publications

Mutational activation of KRAS occurs commonly in lung carcinogenesis and, with the recent U.S. Food and Drug Administration approval of covalent inhibitors of KRASG12C such as sotorasib or adagrasib, KRAS oncoproteins are important pharmacological targets in non-small cell lung cancer (NSCLC). However, not all KRASG12C-driven NSCLCs respond to these inhibitors, and the emergence of drug resistance in those patients who do respond can be rapid and pleiotropic. Hence, based on a backbone of covalent inhibition of KRASG12C, efforts are underway to develop effective combination therapies. Here, we report that the inhibition of KRASG12C signaling increases autophagy in KRASG12C-expressing lung cancer …

Persistent Mri Findings Unique To Blast And Repetitive Mild Tbi: Analysis Of The Cenc/Limbic Cohort Injury Characteristics, David F Tate, Benjamin S C Wade, Carmen S Velez, Erin D Bigler, Nicholas D Davenport, Emily L Dennis, Carrie Esopenko, Sidney R Hinds, Jacob Kean, Eamonn Kennedy, Kimbra Kenney, Andrew R Mayer, Mary R Newsome, Carissa L Philippi, Mary J Pugh, Randall S Scheibel, Brian A Taylor, Maya Troyanskaya, John K Werner, Gerald E York, William Walker, Elisabeth A Wilde

Faculty, Staff and Students Publications

Introduction: MRI represents one of the clinical tools at the forefront of research efforts aimed at identifying diagnostic and prognostic biomarkers following traumatic brain injury (TBI). Both volumetric and diffusion MRI findings in mild TBI (mTBI) are mixed, making the findings difficult to interpret. As such, additional research is needed to continue to elucidate the relationship between the clinical features of mTBI and quantitative MRI measurements.

Material and methods: Volumetric and diffusion imaging data in a sample of 976 veterans and service members from the Chronic Effects of Neurotrauma Consortium and now the Long-Term Impact of Military-Relevant Brain Injury Consortium …

Detection Of Distant Relatedness In Biobanks To Identify Undiagnosed Cases Of Mendelian Disease As Applied To Long Qt Syndrome, Megan C Lancaster, Hung-Hsin Chen, M Benjamin Shoemaker, Matthew R Fleming, Teresa L Strickland, James T Baker, Grahame F Evans, Hannah G Polikowsky, David C Samuels, Chad D Huff, Dan M Roden, Jennifer E Below

Faculty, Staff and Student Publications

Rare genetic diseases are typically studied in referral populations, resulting in underdiagnosis and biased assessment of penetrance and phenotype. To address this, we develop a generalizable method of genotype inference based on distant relatedness and deploy this to identify undiagnosed Type 5 Long QT Syndrome (LQT5) rare variant carriers in a non-referral population. We identify 9 LQT5 families referred to a single specialty clinic, each carrying p.Asp76Asn, the most common LQT5 variant. We uncover recent common ancestry and a single shared haplotype among probands. Application to a non-referral population of 69,819 BioVU biobank subjects identifies 22 additional subjects sharing this …

Feedback Inhibition By A Descending Gabaergic Neuron Regulates Timing Of Escape Behavior In Drosophila Larvae, Jiayi Zhu, Jean-Christophe Boivin, Alastair Garner, Jing Ning, Yi Q Zhao, Tomoko Ohyama

Faculty, Staff and Student Publications

Escape behaviors help animals avoid harm from predators and other threats in the environment. Successful escape relies on integrating information from multiple stimulus modalities (of external or internal origin) to compute trajectories toward safe locations, choose between actions that satisfy competing motivations, and execute other strategies that ensure survival. To this end, escape behaviors must be adaptive. When a Drosophila melanogaster larva encounters a noxious stimulus, such as the focal pressure a parasitic wasp applies to the larval cuticle via its ovipositor, it initiates a characteristic escape response. The escape sequence consists of an initial abrupt bending, lateral rolling, and …

Mechanisms And Metabolic Consequences Of Adipocyte Progenitor Replicative Senescence, Tonghui Lin, Aftab Mohammad, Mikhail G Kolonin, Kristin L Eckel-Mahan

Faculty, Staff and Student Publications

In recent decades, obesity has become a worldwide epidemic. As a result, the importance of adipose tissue (AT) as a metabolically active storage depot for lipids and a key mediator of body-wide metabolism and energy balance has been increasingly recognized. Emerging from the studies of AT in metabolic disease is a recognition of the importance of the adipocyte progenitor cell (APC) population of AT being the gatekeeper of adipocyte function. APCs have the capability to self-renew and undergo adipogenesis to propagate new adipocytes capable of lipid storage, which is important for maintaining a healthy fat pad, devoid of dysfunctional lipid …

Synergistic Effects Of Novel Penicillin-Binding Protein 1a Amino Acid Substitutions Contribute To High-Level Amoxicillin Resistance Of, Alain Cimuanga-Mukanya, Evariste Tshibangu-Kabamba, Patrick De Jesus Ngoma Kisoko, Kartika Afrida Fauzia, Fabien Mbaya Tshibangu, Antoine Tshimpi Wola, Pascal Tshiamala Kashala, Dieudonné Mumba Ngoyi, Steve Ahuka-Mundeke, Gunturu Revathi, Ghislain Disashi-Tumba, Yasutoshi Kido, Takashi Matsumoto, Junko Akada, Yoshio Yamaoka

Faculty, Staff and Students Publications

The growing resistance to amoxicillin (AMX)—one of the main antibiotics used in Helicobacter pylori eradication therapy—is an increasing health concern. Several mutations of penicillin-binding protein 1A (PBP1A) are suspected of causing AMX resistance; however, only a limited set of these mutations have been experimentally explored. This study aimed to investigate four PBP1A mutations (i.e., T558S, N562H, T593A, and G595S) carried by strain KIN76, a high-level AMX-resistant clinical H. pylori isolate with an AMX minimal inhibition concentration (MIC) of 2 µg/mL. We transformed a recipient strain 26695 with the DNA containing one to four mutation allele combinations of the pbp1 gene …

Whole Genome And Reverse Protein Phase Array Landscapes Of Patient Derived Osteosarcoma Xenograft Models, Chia-Chin Wu, Licai Huang, Zhongting Zhang, Zhenlin Ju, Xingzhi Song, E Anders Kolb, Wendong Zhang, Jonathan Gill, Min Ha, Malcolm A Smith, Peter Houghton, Christopher L Morton, Raushan Kurmasheva, John Maris, Yael Mosse, Yiling Lu, Richard Gorlick, P Andrew Futreal, Hannah C Beird

Faculty, Staff and Student Publications

Osteosarcoma is the most common primary bone malignancy in children and young adults, and it has few treatment options. As a result, there has been little improvement in survival outcomes in the past few decades. The need for models to test novel therapies is especially great in this disease since it is both rare and does not respond to most therapies. To address this, an NCI-funded consortium has characterized and utilized a panel of patient-derived xenograft models of osteosarcoma for drug testing. The exomes, transcriptomes, and copy number landscapes of these models have been presented previously. This study now adds …

Evaluating The Impact Of Laboratory-Based Eligibility Criteria By Race/Ethnicity In First-Line Clinical Trials Of Dlbcl, Arushi Khurana, Raphael Mwangi, Loretta J Nastoupil, Patrick M Reagan, Umar Farooq, Jason T Romancik, Timothy J Mcdonnell, Shaun M Riska, Lzidore S Lossos, Brad S Kahl, Peter Martin, Thomas E Witzig, James R Cerhan, Christopher R Flowers, Grzegorz S Nowakowski, Matthew J Maurer

Faculty, Staff and Student Publications

Underrepresentation of racial and ethnic subgroups in cancer clinical trials remains a persistent challenge. Restrictive clinical trial eligibility criteria have been shown to exacerbate this problem. We previously identified that up to 24% of patients treated with standard immunochemotherapy would have been excluded from recent first-line trials in diffuse large B-cell lymphoma (DLBCL) based on 5 laboratory-based criteria. These ineligible patients had worse clinical outcomes and increased deaths related to lymphoma progression, suggesting the potential exclusion of patients who could have benefited most from the novel therapies being evaluated. Using data from the prospectively enrolled Lymphoma Epidemiology Outcomes cohort study, …

Neutralization Escape, Infectivity, And Membrane Fusion Of Jn1-Derived Sars-Cov-2 Slip, Flirt, And Kp2 Variants, Pei Li, Julia N Faraone, Cheng Chih Hsu, Michelle Chamblee, Yi-Min Zheng, Claire Carlin, Joseph S Bednash, Jeffrey C Horowitz, Rama K Mallampalli, Linda J Saif, Eugene M Oltz, Daniel Jones, Jianrong Li, Richard J Gumina, Kai Xu, Shan-Lu Liu

Faculty, Staff and Student Publications

We investigate JN.1-derived subvariants SLip, FLiRT, and KP.2 for neutralization by antibodies in vaccinated individuals, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected patients, or class III monoclonal antibody S309. Compared to JN.1, SLip, KP.2, and especially FLiRT exhibit increased resistance to bivalent-vaccinated and BA.2.86/JN.1-wave convalescent human sera. XBB.1.5 monovalent-vaccinated hamster sera robustly neutralize FLiRT and KP.2 but have reduced efficiency for SLip. All subvariants are resistant to S309 and show decreased infectivity, cell-cell fusion, and spike processing relative to JN.1. Modeling reveals that L455S and F456L in SLip reduce spike binding for ACE2, while R346T in FLiRT and KP.2 strengthens …

Asthma And Hyperglycemia: Exploring The Interconnected Pathways, Dharani K Narendra, Sandhya Khurana

Faculty, Staff and Students Publications

The interplay between asthma and glucose metabolism disorders, such as hyperglycemia, has gained increasing attention due to the potential exacerbation of asthma symptoms and severity. This review explores the complex relationship between hyperglycemia and asthma, emphasizing the pathophysiological links, the impact of glucose metabolism disorders on asthma, and the effects of asthma medications on glucose levels. Hyperglycemia, often induced by asthma treatments like corticosteroids, has been associated with an increased risk of asthma exacerbations. This review delves into the pathophysiology underlying this association, highlighting the role of insulin resistance, metabolic syndrome, and obesity in both the development and management of …

Meti: Deep Profiling Of Tumor Ecosystems By Integrating Cell Morphology And Spatial Transcriptomics, Jiahui Jiang, Yunhe Liu, Jiangjiang Qin, Jianfeng Chen, Jingjing Wu, Melissa P Pizzi, Rossana Lazcano, Kohei Yamashita, Zhiyuan Xu, Guangsheng Pei, Kyung Serk Cho, Yanshuo Chu, Ansam Sinjab, Fuduan Peng, Xinmiao Yan, Guangchun Han, Ruiping Wang, Enyu Dai, Yibo Dai, Bogdan A Czerniak, Andrew Futreal, Anirban Maitra, Alexander Lazar, Humam Kadara, Amir A Jazaeri, Xiangdong Cheng, Jaffer Ajani, Jianjun Gao, Jian Hu, Linghua Wang

Faculty, Staff and Student Publications

Recent advances in spatial transcriptomics (ST) techniques provide valuable insights into cellular interactions within the tumor microenvironment (TME). However, most analytical tools lack consideration of histological features and rely on matched single-cell RNA sequencing data, limiting their effectiveness in TME studies. To address this, we introduce the Morphology-Enhanced Spatial Transcriptome Analysis Integrator (METI), an end-to-end framework that maps cancer cells and TME components, stratifies cell types and states, and analyzes cell co-localization. By integrating spatial transcriptomics, cell morphology, and curated gene signatures, METI enhances our understanding of the molecular landscape and cellular interactions within the tissue. We evaluate the performance …

Non-Coding Rnas In Peritoneal Carcinomatosis: From Bench To Bedside, Julia Bohosova, Nida Sarosh Ashraf, Ondrej Slaby, George A Calin

Faculty, Staff and Student Publications

Peritoneal carcinomatosis represents an advanced stage of tumors within the peritoneal cavity. Once considered an incurable terminal cancer metastasis, contemporary medicine is on the hunt for certain potentially curative options alongside the present day’s palliative disease management. However, for most patients, peritoneal carcinomatosis continues to pose a fatal late-stage prognosis with a grim future outlook. Over the past two decades, non-coding RNAs have garnered significant attention due to their undeniable significance in regulating cellular processes across all levels. Disruption of the intricate regulation led by non-coding RNAs has been demonstrated to have a substantial impact on various human diseases, particularly …