Medicine and Health Sciences Commons^™

Improved Data Quality And Statistical Power Of Trial-Level Event-Related Potentials With Bayesian Random-Shift Gaussian Processes, Dustin Pluta, Beniamino Hadj-Amar, Meng Li, Yongxiang Zhao, Francesco Versace, Marina Vannucci

Faculty, Staff and Student Publications

Studies of cognitive processes via electroencephalogram (EEG) recordings often analyze group-level event-related potentials (ERPs) averaged over multiple subjects and trials. This averaging procedure can obscure scientifically relevant variability across subjects and trials, but has been necessary due to the difficulties posed by inference of trial-level ERPs. We introduce the Bayesian Random Phase-Amplitude Gaussian Process (RPAGP) model, for inference of trial-level amplitude, latency, and ERP waveforms. We apply RPAGP to data from a study of ERP responses to emotionally arousing images. The model estimates of trial-specific signals are shown to greatly improve statistical power in detecting significant differences in experimental conditions …

High-Performance Cementitious Composites Containing Nanostructured Carbon Additives Made From Charred Coal Fines, Yuan Gao, Viet Hung Pham, Jennifer Weidman, Ki-Joong Kim, Richard E Spaulding, Congjun Wang, Christopher S Matranga

Faculty, Staff and Student Publications

Carbon-based nanomaterials, such as carbon nanoplatelets, graphene oxide, and carbon quantum dots, have many possible end-use applications due to their ability to impart unique mechanical, electrical, thermal, and optical properties to cement composites. Despite this potential, these materials are rarely used in the construction industry due to high material costs and limited data on performance and durability. In this study, domestic coal is used to fabricate low-cost carbon nanomaterials that can be used economically in cement formulations. A range of chemical and physical processing approaches are employed to control the size, morphology, and chemical functionalization of the carbon nanomaterial, which …

Tissue-Specific Atlas Of Trans-Models For Gene Regulation Elucidates Complex Regulation Patterns, Robert Dagostino, Assaf Gottlieb

Faculty, Staff and Student Publications

BACKGROUND: Deciphering gene regulation is essential for understanding the underlying mechanisms of healthy and disease states. While the regulatory networks formed by transcription factors (TFs) and their target genes has been mostly studied with relation to cis effects such as in TF binding sites, we focused on trans effects of TFs on the expression of their transcribed genes and their potential mechanisms.

RESULTS: We provide a comprehensive tissue-specific atlas, spanning 49 tissues of TF variations affecting gene expression through computational models considering two potential mechanisms, including combinatorial regulation by the expression of the TFs, and by genetic variants within the …

Brafv600e-Mutant Metastatic Nsclc: Disease Overview And Treatment Landscape, David Planchard, Rachel E Sanborn, Marcelo V Negrao, Aria Vaishnavi, Egbert F Smit

Faculty, Staff and Student Publications

In this review, we cover the current understanding of BRAF mutations and associated clinical characteristics in patients with metastatic NSCLC, approved and emerging treatment options, BRAF sequencing approaches, and unmet needs. The BRAFV600E mutation confers constitutive activity of the MAPK pathway, leading to enhanced growth, proliferation, and survival of tumor cells. Testing for BRAF mutations enables patients to be treated with therapies that directly target BRAFV600E and the MAPK pathway, but BRAF testing lags behind other oncogene testing in metastatic NSCLC. Additional therapies targeting BRAFV600E mutations provide options for patients with metastatic NSCLC. Emerging therapies and combinations under investigation could …

Revolutionizing Diabetic Foot Ulcer Care: The Senotherapeutic Approach, Guiqin Zhang, Priyadarshani Nadeeshika Samarawickrama, Li Gui, Yuan Ma, Mei Cao, Hong Zhu, Wei Li, Honglin Yang, Kecheng Li, Yang Yang, Enfang Zhu, Wen Li, Yonghan He

Faculty, Staff and Student Publications

Diabetic foot ulcers (DFUs) are a prevalent and profoundly debilitating complication that afflicts individuals with diabetes mellitus (DM). These ulcers are associated with substantial morbidity, recurrence rates, disability, and mortality, imposing substantial economic, psychological, and medical burdens. Timely detection and intervention can mitigate the morbidity and disparities linked to DFU. Nevertheless, current therapeutic approaches for DFU continue to grapple with multifaceted limitations. A growing body of evidence emphasizes the crucial role of cellular senescence in the pathogenesis of chronic wounds. Interventions that try to delay cellular senescence, eliminate senescent cells (SnCs), or suppress the senescence-associated secretory phenotype (SASP) have shown …

Self-Assembled Sting-Activating Coordination Nanoparticles For Cancer Immunotherapy And Vaccine Applications, Xiaoqi Sun, Xuehui Huang, Kyung Soo Park, Xingwu Zhou, Andrew A Kennedy, Carla D Pretto, Qi Wu, Ziye Wan, Yao Xu, Wang Gong, Jonathan Z Sexton, Andrew W Tai, Yu Leo Lei, James J Moon

Faculty, Staff and Student Publications

The cGAS-STING pathway plays a crucial role in innate immune activation against cancer and infections, and STING agonists based on cyclic dinucleotides (CDN) have garnered attention for their potential use in cancer immunotherapy and vaccines. However, the limited drug-like properties of CDN necessitate an efficient delivery system to the immune system. To address these challenges, we developed an immunostimulatory delivery system for STING agonists. Here, we have examined aqueous coordination interactions between CDN and metal ions and report that CDN mixed with Zn2+ and Mn2+ formed distinctive crystal structures. Further pharmaceutical engineering led to the development of a functional coordination …

Microbiome And Cancer Immunotherapies, Haoyan Chen, Laurence Zitvogel, Zhi Peng, Xiaochen Yin, Florencia Mcallister

Faculty, Staff and Student Publications

Here, we present 3 different perspectives on how the microbiome has impacted cancer patients, treatment, and clinical studies. We hear about the challenges of implementing microbiome analyses into the clinics, the impact these analyses might have on patients' care, and treatment in the future, specifically for gastric cancer treatment. These are a few of the many voices that are highlighting the role of the microbiome in cancer development, treatment, and clinical outcomes.

Jennifer A Wargo, Nadim J Ajami, And Carrie R Daniel-Macdougall, Jennifer A Wargo, Nadim J Ajami, Carrie R Daniel-Macdougall

Faculty, Staff and Student Publications

Dr. Jennifer A. Wargo, Dr. Nadim J. Ajami, and Dr. Carrie R. Daniel-MacDougall describe their academic and clinical work on the role of the microbiome to determine response to immunotherapies and discuss current challenges and potential needs to integrate their findings into clinical practice.

The Study On Mechanical Model Considering Optimal Self-Adaption In The Bottleneck Area, Longcheng Yang, Huajun Wang, Jun Hu, Hongyu Pan, Juan Wei, Lei You, Hao Zhang, Junxi Wang

Faculty, Staff and Student Publications

It aims to solve the problem that the evacuation state of pedestrians depicted by the traditional social force model in a crowded multiexit scenario has a relatively large difference with the actual state, especially the 'optimal path' considered by the self-driving force is the problem of shortest path, and the multiexit evacuation mode depicted by the 'herd behavior' is the local optimum problem. Through in-depth analysis of actual evacuation data of pedestrians and causes of problem, a new crowd evacuation optimization model is established in order to effectively improve the simulation accuracy of crowd evacuation in a multi-exit environment. The …

Multi-Omics Analysis Reveals Immune Features Associated With Immunotherapy Benefit In Patients With Squamous Cell Lung Cancer From Phase Iii Lung-Map S1400i Trial, Edwin Roger Parra, Jiexin Zhang, Dzifa Yawa Duose, Edgar Gonzalez-Kozlova, Mary W Redman, Hong Chen, Ganiraju C Manyam, Gayatri Kumar, Jianhua Zhang, Xingzhi Song, Rossana Lazcano, Mario L Marques-Piubelli, Caddie Laberiano-Fernandez, Frank Rojas, Baili Zhang, Len Taing, Aashna Jhaveri, Jacob Geisberg, Jennifer Altreuter, Franziska Michor, James Provencher, Joyce Yu, Ethan Cerami, Radim Moravec, Kasthuri Kannan, Rajyalakshmi Luthra, Gheath Alatrash, Hsin-Hui Huang, Hui Xie, Manishkumar Patel, Kai Nie, Jocelyn Harris, Kimberly Argueta, James Lindsay, Roshni Biswas, Stephen Van Nostrand, Seunghee Kim-Schulze, Jhanelle E Gray, Roy S Herbst, Ignacio I Wistuba, Scott Gettinger, Karen Kelly, Lyudmila Bazhenova, Sacha Gnjatic, J Jack Lee, Jianjun Zhang, Cara Haymaker

Faculty, Staff and Student Publications

PURPOSE: Identifying molecular and immune features to guide immune checkpoint inhibitor (ICI)-based regimens remains an unmet clinical need.

EXPERIMENTAL DESIGN: Tissue and longitudinal blood specimens from phase III trial S1400I in patients with metastatic squamous non-small cell carcinoma (SqNSCLC) treated with nivolumab monotherapy (nivo) or nivolumab plus ipilimumab (nivo+ipi) were subjected to multi-omics analyses including multiplex immunofluorescence (mIF), nCounter PanCancer Immune Profiling Panel, whole-exome sequencing, and Olink.

RESULTS: Higher immune scores from immune gene expression profiling or immune cell infiltration by mIF were associated with response to ICIs and improved survival, except regulatory T cells, which were associated with worse …

Safety Profile And Adverse Event Management For Futibatinib, An Irreversible Fgfr1-4 Inhibitor: Pooled Safety Analysis Of 469 Patients, Funda Meric-Bernstam, Antoine Hollebecque, Junji Furuse, Do-Youn Oh, John A Bridgewater, Masashi Shimura, Bailey Anderson, Nanae Hangai, Volker Wacheck, Lipika Goyal

Faculty, Staff and Student Publications

PURPOSE: Futibatinib, a covalently-binding inhibitor of fibroblast growth factor receptor (FGFR)1-4 gained approval for the treatment of refractory, advanced intrahepatic cholangiocarcinoma (iCCA) harboring an FGFR2 fusion/other rearrangement. An integrated analysis was performed to evaluate safety and provide guidance on the management of futibatinib-associated adverse events (AEs) in patients with unresectable/metastatic tumors, including iCCA.

PATIENTS AND METHODS: Data from three global phase I or II studies of futibatinib (NCT02052778; JapicCTI-142552) were pooled. AEs were graded per NCI CTCAE v4.03, where applicable. Safety was analyzed for patients receiving any futibatinib starting dose (overall population) and in those receiving the approved starting dose …

Sensitivity Analysis With Iterative Outlier Detection For Systematic Reviews And Meta-Analyses, Zhuo Meng, Jingshen Wang, Lifeng Lin, Chong Wu

Faculty, Staff and Student Publications

Meta-analysis is a widely used tool for synthesizing results from multiple studies. The collected studies are deemed heterogeneous when they do not share a common underlying effect size; thus, the factors attributable to the heterogeneity need to be carefully considered. A critical problem in meta-analyses and systematic reviews is that outlying studies are frequently included, which can lead to invalid conclusions and affect the robustness of decision-making. Outliers may be caused by several factors such as study selection criteria, low study quality, small-study effects, and so on. Although outlier detection is well-studied in the statistical community, limited attention has been …

Vhl Governs M6a Modification And Pik3r3 Mrna Stability In Clear Cell Renal Cell Carcinomas, Hyemin Lee, Li Zhuang, Boyi Gan

Faculty, Staff and Student Publications

N6-Methyladenosine (m6A), a prevalent posttranscriptional modification, plays an important role in cancer progression. Clear cell renal cell carcinoma (ccRCC) is chiefly associated with the loss of the von Hippel-Lindau (VHL) gene, encoding a component of the E3 ubiquitin ligase complex. In this issue of the JCI, Zhang and colleagues unveiled a function of VHL beyond its canonical role as an E3 ubiquitin ligase in regulating hypoxia-inducible factors (HIFs). It also governed m6A modification by orchestrating the assembly of m6A writer proteins METTL3 and METTL14, thereby stabilizing PIK3R3 mRNA. Mechanistically, PIK3R3 contributed to p85 ubiquitination, which restrained PI3K/AKT signaling and consequently …

Risk Assessment And Sources Apportionment Of Toxic Metals In Two Commonly Consumed Fishes From A Subtropical Estuarine Wetland System, Md Moudud Ahmed, As-Ad Ujjaman Nur, Salma Sultana, Yeasmin N Jolly, Bilal Ahamad Paray, Takaomi Arai, Jimmy Yu, Mohammad Belal Hossain

Faculty, Staff and Student Publications

The widespread occurrence of heavy metals in aquatic environments, resulting in their bioaccumulation within aquatic organisms like fish, presents potential hazards to human health. This study investigates the concentrations of five toxic heavy metals (Pb, Hg, Zn, Cu, and Cr) and their potential health implications in two economically important fish species (Otolithoides pama and Labeo bata) from a subtropical estuarine wetland system (Feni estuary, Bangladesh). Muscle and gill samples from 36 individual fish were analyzed using energy dispersive X-ray fluorescence (EDXRF). The results revealed that the average quantities of heavy metals in both fishes' muscle followed the declining …

Afamitresgene Autoleucel For Advanced Synovial Sarcoma And Myxoid Round Cell Liposarcoma (Spearhead-1): An International, Open-Label, Phase 2 Trial, Sandra P D'Angelo, Dejka M Araujo, Albiruni R Abdul Razak, Mark Agulnik, Steven Attia, Jean-Yves Blay, Irene Carrasco Garcia, John A Charlson, Edwin Choy, George D Demetri, Mihaela Druta, Edouard Forcade, Kristen N Ganjoo, John Glod, Vicki L Keedy, Axel Le Cesne, David A Liebner, Victor Moreno, Seth M Pollack, Scott M Schuetze, Gary K Schwartz, Sandra J Strauss, William D Tap, Fiona Thistlethwaite, Claudia Maria Valverde Morales, Michael J Wagner, Breelyn A Wilky, Cheryl Mcalpine, Laura Hudson, Jean-Marc Navenot, Tianjiao Wang, Jane Bai, Stavros Rafail, Ruoxi Wang, Amy Sun, Lilliam Fernandes, Erin Van Winkle, Erica Elefant, Colin Lunt, Elliot Norry, Dennis Williams, Swethajit Biswas, Brian A Van Tine

Faculty, Staff and Student Publications

Background: Afamitresgene autoleucel (afami-cel) showed acceptable safety and promising efficacy in a phase 1 trial (NCT03132922). The aim of this study was to further evaluate the efficacy of afami-cel for the treatment of patients with HLA-A*02 and MAGE-A4-expressing advanced synovial sarcoma or myxoid round cell liposarcoma.

Methods: SPEARHEAD-1 was an open-label, non-randomised, phase 2 trial done across 23 sites in Canada, the USA, and Europe. The trial included three cohorts, of which the main investigational cohort (cohort 1) is reported here. Cohort 1 included patients with HLA-A*02, aged 16-75 years, with metastatic or unresectable synovial sarcoma or myxoid …

Genome-Wide Screening Identifies Trim33 As An Essential Regulator Of Dendritic Cell Differentiation, Ioanna Tiniakou, Pei-Feng Hsu, Lorena S Lopez-Zepeda, Görkem Garipler, Eduardo Esteva, Nicholas M Adams, Geunhyo Jang, Chetna Soni, Colleen M Lau, Fan Liu, Alireza Khodadadi-Jamayran, Tori C Rodrick, Drew Jones, Aristotelis Tsirigos, Uwe Ohler, Mark T Bedford, Stephen D Nimer, Vesa Kaartinen, Esteban O Mazzoni, Boris Reizis

Faculty, Staff and Student Publications

The development of dendritic cells (DCs), including antigen-presenting conventional DCs (cDCs) and cytokine-producing plasmacytoid DCs (pDCs), is controlled by the growth factor Flt3 ligand (Flt3L) and its receptor Flt3. We genetically dissected Flt3L-driven DC differentiation using CRISPR-Cas9-based screening. Genome-wide screening identified multiple regulators of DC differentiation including subunits of TSC and GATOR1 complexes, which restricted progenitor growth but enabled DC differentiation by inhibiting mTOR signaling. An orthogonal screen identified the transcriptional repressor Trim33 (TIF-1γ) as a regulator of DC differentiation. Conditional targeting in vivo revealed an essential role of Trim33 in the development of all DCs, but not of monocytes …

Non-Traumatic Osteonecrosis Of The Femoral Head Induced By Steroid And Alcohol Exposure Is Associated With Intestinal Flora Alterations And Metabolomic Profiles, Qing-Yuan Zheng, Ye Tao, Lei Geng, Peng Ren, Ming Ni, Guo-Qiang Zhang

Faculty, Staff and Student Publications

OBJECTIVE: Osteonecrosis of the femoral head (ONFH) is a severe disease that primarily affects the middle-aged population, imposing a significant economic and social burden. Recent research has linked the progression of non-traumatic osteonecrosis of the femoral head (NONFH) to the composition of the gut microbiota. Steroids and alcohol are considered major contributing factors. However, the relationship between NONFH caused by two etiologies and the microbiota remains unclear. In this study, we examined the gut microbiota and fecal metabolic phenotypes of two groups of patients, and analyzed potential differences in the pathogenic mechanisms from both the microbial and metabolic perspectives.

METHODS: …

In Silico And In Vitro Study Of Isoquercitrin Against Kidney Cancer And Inflammation By Triggering Potential Gene Targets, Safia Iqbal, Md Rezaul Karim, Shahnawaz Mohammad, Jong Chan Ahn, Anjali Kariyarath Valappil, Ramya Mathiyalagan, Deok-Chun Yang, Dae-Hyo Jung, Hyocheol Bae, Dong Uk Yang

Faculty, Staff and Student Publications

Kidney cancer has emerged as a major medical problem in recent times. Multiple compounds are used to treat kidney cancer by triggering cancer-causing gene targets. For instance, isoquercitrin (quercetin-3-O-β-d-glucopyranoside) is frequently present in fruits, vegetables, medicinal herbs, and foods and drinks made from plants. Our previous study predicted using protein-protein interaction (PPI) and molecular docking analysis that the isoquercitrin compound can control kidney cancer and inflammation by triggering potential gene targets of IGF1R, PIK3CA, IL6, and PTGS2. So, the present study is about further in silico and in vitro validation. We performed molecular dynamic (MD) simulation, gene ontology (GO), Kyoto …

Phase 1b Study Of Intraperitoneal Ipilimumab And Nivolumab In Patients With Recurrent Gynecologic Malignancies With Peritoneal Carcinomatosis, Anne Knisely, Emily Hinchcliff, Bryan Fellman, Ann Mosley, Kathryn Lito, Sara Hull, Shannon N Westin, Anil K Sood, Kathleen M Schmeler, Jolyn S Taylor, Steven Y Huang, Rahul A Sheth, Karen H Lu, Amir A Jazaeri

Faculty, Staff and Student Publications

Background: Intravenous immune checkpoint blockade (ICB) has shown poor response rates in recurrent gynecologic malignancies. Intraperitoneal (i.p.) ICB may result in enhanced T cell activation and anti-tumor immunity.

Methods: In this phase 1b study, registered at Clinical.

Trials: gov (NCT03508570), initial cohorts received i.p. nivolumab monotherapy, and subsequent cohorts received combination i.p. nivolumab every 2 weeks and i.p. ipilimumab every 6 weeks, guided by a Bayesian design. The primary objective was determination of the recommended phase 2 dose (RP2D) of the combination. Secondary outcomes included toxicity, objective response rate (ORR), progression-free survival (PFS), and overall survival (OS).

Findings: …

Combined Deletion Of Men1, Atrx And Pten Triggers Development Of High-Grade Pancreatic Neuroendocrine Tumors In Mice, Mary Esmeralda Fuentes, Xiaoyin Lu, Natasha M Flores, Simone Hausmann, Pawel K Mazur

Faculty, Staff and Student Publications

Pancreatic neuroendocrine tumors (PanNETs) are a heterogeneous group of tumors that exhibit an unpredictable and broad spectrum of clinical presentations and biological aggressiveness. Surgical resection is still the only curative therapeutic option for localized PanNET, but the majority of patients are diagnosed at an advanced and metastatic stage with limited therapeutic options. Key factors limiting the development of new therapeutics are the extensive heterogeneity of PanNETs and the lack of appropriate clinically relevant models. In that context, genomic sequencing of human PanNETs revealed recurrent mutations and structural alterations in several tumor suppressors. Here, we demonstrated that combined loss of MEN1, …

Enhancing Nsclc Recurrence Prediction With Pet/Ct Habitat Imaging, Ctdna, And Integrative Radiogenomics-Blood Insights, Sheeba J Sujit, Muhammad Aminu, Tatiana V Karpinets, Pingjun Chen, Maliazurina B Saad, Morteza Salehjahromi, John D Boom, Mohamed Qayati, James M George, Haley Allen, Mara B Antonoff, Lingzhi Hong, Xin Hu, Simon Heeke, Hai T Tran, Xiuning Le, Yasir Y Elamin, Mehmet Altan, Natalie I Vokes, Ajay Sheshadri, Julie Lin, Jianhua Zhang, Yang Lu, Carmen Behrens, Myrna C B Godoy, Carol C Wu, Joe Y Chang, Caroline Chung, David A Jaffray, Ignacio I Wistuba, J Jack Lee, Ara A Vaporciyan, Don L Gibbons, John Heymach, Jianjun Zhang, Tina Cascone, Jia Wu

Faculty, Staff and Student Publications

While we recognize the prognostic importance of clinicopathological measures and circulating tumor DNA (ctDNA), the independent contribution of quantitative image markers to prognosis in non-small cell lung cancer (NSCLC) remains underexplored. In our multi-institutional study of 394 NSCLC patients, we utilize pre-treatment computed tomography (CT) and 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) to establish a habitat imaging framework for assessing regional heterogeneity within individual tumors. This framework identifies three PET/CT subtypes, which maintain prognostic value after adjusting for clinicopathologic risk factors including tumor volume. Additionally, these subtypes complement ctDNA in predicting disease recurrence. Radiogenomics analysis unveil the molecular underpinnings of these …

Nardilysin-Regulated Scission Mechanism Activates Polo-Like Kinase 3 To Suppress The Development Of Pancreatic Cancer, Jie Fu, Jianhua Ling, Ching-Fei Li, Chi-Lin Tsai, Wenjuan Yin, Junwei Hou, Ping Chen, Yu Cao, Ya'an Kang, Yichen Sun, Xianghou Xia, Zhou Jiang, Kenei Furukawa, Yu Lu, Min Wu, Qian Huang, Jun Yao, David H Hawke, Bih-Fang Pan, Jun Zhao, Jiaxing Huang, Huamin Wang, E I Mustapha Bahassi, Peter J Stambrook, Peng Huang, Jason B Fleming, Anirban Maitra, John A Tainer, Mien-Chie Hung, Chunru Lin, Paul J Chiao

Faculty, Staff and Student Publications

Pancreatic ductal adenocarcinoma (PDAC) develops through step-wise genetic and molecular alterations including Kras mutation and inactivation of various apoptotic pathways. Here, we find that development of apoptotic resistance and metastasis of KrasG12D-driven PDAC in mice is accelerated by deleting Plk3, explaining the often-reduced Plk3 expression in human PDAC. Importantly, a 41-kDa Plk3 (p41Plk3) that contains the entire kinase domain at the N-terminus (1-353 aa) is activated by scission of the precursor p72Plk3 at Arg354 by metalloendopeptidase nardilysin (NRDC), and the resulting p32Plk3 C-terminal Polo-box domain (PBD) is removed by proteasome degradation, preventing the inhibition of p41Plk3 by PBD. We find …

A Novel Lentiviral Vector-Based Approach To Generate Chimeric Antigen Receptor T Cells Targeting, Pappanaicken R Kumaresan, Sebastian Wurster, Karishma Bavisi, Thiago Aparecido Da Silva, Paul Hauser, Jordan Kinnitt, Nathaniel D Albert, Uddalak Bharadwaj, Sattva Neelapu, Dimitrios P Kontoyiannis

Faculty, Staff and Student Publications

Invasive aspergillosis (IA) is a common and deadly mold infection in immunocompromised patients. As morbidity and mortality of IA are primarily driven by poor immune defense, adjunct immunotherapies, such as chimeric antigen receptor (CAR) T cells, are direly needed. Here, we propose a novel approach to generate Aspergillus fumigatus (AF)-CAR T cells using the single-chain variable fragment domain of monoclonal antibody AF-269-5 and a lentiviral vector system. These cells successfully targeted mature hyphal filaments of representative clinical and reference AF isolates and elicited a potent release of cytotoxic effectors and type 1 T cell cytokines. Furthermore, AF-CAR T cells generated …

Fusobacterium Nucleatum Subsp Animalis Comes To The Spotlight In Oral Diseases, Bibek G C, Peng Zhou, Chenggang Wu

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Krieger et al.'s study in this issue of Cell Host & Microbe reveals that Fusobacterium nucleatum subsp. animalis strains, previously underestimated, are significant in disease-affected oral areas. This challenges the long-held notion of the dominance of Fusobacterium nucleatum subsp. nucleatum, reshaping our understanding of Fusobacterium distribution in the oral microbiome.

Fusobacterium Nucleatum Subsp Animalis Comes To The Spotlight In Oral Diseases, Bibek G C, Peng Zhou, Chenggang Wu

Faculty, Staff and Student Publications

Krieger et al.'s study in this issue of Cell Host & Microbe reveals that Fusobacterium nucleatum subsp. animalis strains, previously underestimated, are significant in disease-affected oral areas. This challenges the long-held notion of the dominance of Fusobacterium nucleatum subsp. nucleatum, reshaping our understanding of Fusobacterium distribution in the oral microbiome.

A Revamped Rat Reference Genome Improves The Discovery Of Genetic Diversity In Laboratory Rats, Tristan V De Jong, Yanchao Pan, Pasi Rastas, Daniel Munro, Monika Tutaj, Huda Akil, Chris Benner, Denghui Chen, Apurva S Chitre, William Chow, Vincenza Colonna, Clifton L Dalgard, Wendy M Demos, Peter A Doris, Erik Garrison, Aron M Geurts, Hakan M Gunturkun, Victor Guryev, Thibaut Hourlier, Kerstin Howe, Jun Huang, Ted Kalbfleisch, Panjun Kim, Ling Li, Spencer Mahaffey, Fergal J Martin, Pejman Mohammadi, Ayse Bilge Ozel, Oksana Polesskaya, Michal Pravenec, Pjotr Prins, Jonathan Sebat, Jennifer R Smith, Leah C Solberg Woods, Boris Tabakoff, Alan Tracey, Marcela Uliano-Silva, Flavia Villani, Hongyang Wang, Burt M Sharp, Francesca Telese, Zhihua Jiang, Laura Saba, Xusheng Wang, Terence D Murphy, Abraham A Palmer, Anne E Kwitek, Melinda R Dwinell, Robert W Williams, Jun Z Li, Hao Chen

Faculty, Staff and Student Publications

The seventh iteration of the reference genome assembly for Rattus norvegicus-mRatBN7.2-corrects numerous misplaced segments and reduces base-level errors by approximately 9-fold and increases contiguity by 290-fold compared with its predecessor. Gene annotations are now more complete, improving the mapping precision of genomic, transcriptomic, and proteomics datasets. We jointly analyzed 163 short-read whole-genome sequencing datasets representing 120 laboratory rat strains and substrains using mRatBN7.2. We defined ∼20.0 million sequence variations, of which 18,700 are predicted to potentially impact the function of 6,677 genes. We also generated a new rat genetic map from 1,893 heterogeneous stock rats and annotated transcription start sites …

Immunomodulatory Zymosan/Ι-Carrageenan/ Agarose Hydrogel For Targeting M2 To M1 Macrophages (Antitumoral), Geetha Venkatachalam, Jayant Giri, Saurav Mallik, Gandarvakottai Senthilkumar Arumugam, Manavalan Arulmani, Vimal Kumar Dewangan, Mukesh Doble, Zhongming Zhao

Faculty, Staff and Student Publications

Several studies have been performed on the immunomodulatory effects of yeast β-(1,3) glucan, but there is no proper evaluation of the thermal and immunomodulating properties of zymosan (ZM). Thermogravimetry analysis indicated a 54% weight loss of ZM at 270 °C. Circular dichroism showed absorption peaks in the region of 250 to 400 nm, suggesting a helical coil β-sheet configuration. XRD showed a broad peak at 2θ of 20.38°, indicating the crystalline nature, and the size was found to be 23 nm. ZM is biocompatible and showed no toxicity against L929 and RAW 264.7 cell lines (cell viability > 90%). Immunomodulatory …

Synovial Fibroblast Gene Expression Is Associated With Sensory Nerve Growth And Pain In Rheumatoid Arthritis, Zilong Bai, Nicholas Bartelo, Maryam Aslam, Elisabeth A Murphy, Caryn R Hale, Nathalie E Blachere, Salina Parveen, Edoardo Spolaore, Edward Dicarlo, Ellen M Gravallese, Melanie H Smith, Accelerating Medicines Partnership Ra/Sle Network, Mayu O Frank, Caroline S Jiang, Haotan Zhang, Christina Pyrgaki, Myles J Lewis, Shafaq Sikandar, Costantino Pitzalis, Joseph B Lesnak, Khadijah Mazhar, Theodore J Price, Anne-Marie Malfait, Rachel E Miller, Fan Zhang, Susan Goodman, Robert B Darnell, Fei Wang, Dana E Orange

Faculty, Staff and Student Publications

It has been presumed that rheumatoid arthritis (RA) joint pain is related to inflammation in the synovium; however, recent studies reveal that pain scores in patients do not correlate with synovial inflammation. We developed a machine-learning approach (graph-based gene expression module identification or GbGMI) to identify an 815-gene expression module associated with pain in synovial biopsy samples from patients with established RA who had limited synovial inflammation at arthroplasty. We then validated this finding in an independent cohort of synovial biopsy samples from patients who had early untreated RA with little inflammation. Single-cell RNA sequencing analyses indicated that most of …

Funcpep V20: An Updated Database Of Functional Short Peptides Translated From Non-Coding Rnas, Swati Mohapatra, Anik Banerjee, Paola Rausseo, Mihnea P Dragomir, Ganiraju C Manyam, Bradley M Broom, George A Calin

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Over the past decade, there have been reports of short novel functional peptides (less than 100 aa in length) translated from so-called non-coding RNAs (ncRNAs) that have been characterized using mass spectrometry (MS) and large-scale proteomics studies. Therefore, understanding the bivalent functions of some ncRNAs as transcripts that encode both functional RNAs and short peptides, which we named ncPEPs, will deepen our understanding of biology and disease. In 2020, we published the first database of functional peptides translated from non-coding RNAs-FuncPEP. Herein, we have performed an update including the newly published ncPEPs from the last 3 years along with the …

Nanocavity-Mediated Purcell Enhancement Of Er In Tio2 Thin Films Grown Via Atomic Layer Deposition, Cheng Ji, Michael T Solomon, Gregory D Grant, Koichi Tanaka, Muchuan Hua, Jianguo Wen, Sagar Kumar Seth, Connor P Horn, Ignas Masiulionis, Manish Kumar Singh, Sean E Sullivan, F Joseph Heremans, David D Awschalom, Supratik Guha, Alan M Dibos

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The use of trivalent erbium (Er3+), typically embedded as an atomic defect in the solid-state, has widespread adoption as a dopant in telecommunication devices and shows promise as a spin-based quantum memory for quantum communication. In particular, its natural telecom C-band optical transition and spin-photon interface make it an ideal candidate for integration into existing optical fiber networks without the need for quantum frequency conversion. However, successful scaling requires a host material with few intrinsic nuclear spins, compatibility with semiconductor foundry processes, and straightforward integration with silicon photonics. Here, we present Er-doped titanium dioxide (TiO2) thin film growth on silicon …