Digital Commons Network^™

Memorability Of Novel Words Correlates With Anterior Fusiform Activity During Reading, Oscar Woolnough, Nitin Tandon

Faculty, Staff and Student Publications

Our memory for the words we already know is best predicted by their associated meanings. However, the factors that influence whether we will remember a new word after we see it for the first time are unclear. We record memory performance for 2100 novel pseudowords across 1804 participants during a continuous recognition task. Participants show significant agreement across individuals for which novel words were memorable or forgettable, suggesting an intrinsic memorability for individual pseudowords. Pseudowords that are similar to low-frequency known words, with sparse orthographic neighbourhoods and rarely occurring letter pairs, are more memorable. Further, using intracranial recordings in 36 …

Continued Nintedanib In Patients With Systemic Sclerosis-Associated Interstitial Lung Disease: 3-Year Data From Senscis-On, Yannick Allanore, Madelon C Vonk, Oliver Distler, Arata Azuma, Maureen D Mayes, Alexandra James, Veronika Kohlbrenner, Margarida Alves, Dinesh Khanna, Kristin B Highland

Faculty, Staff and Student Publications

Objective: We assessed adverse events and changes in forced vital capacity (FVC) in patients treated with open-label nintedanib over 148 weeks of SENSCIS-ON, the extension of the SENSCIS trial.

Methods: Adverse events and changes in FVC over 148 weeks of SENSCIS-ON were assessed in patients who received nintedanib in SENSCIS and continued nintedanib in SENSCIS-ON ('continued nintedanib' group) and in patients who received placebo in SENSCIS or received nintedanib for ≤28 days in a drug-drug interaction study and then received nintedanib in SENSCIS-ON ('initiated nintedanib' group).

Results: The continued nintedanib group comprised 197 patients, and the initiated nintedanib group comprised …

Routine Evaluation Of Supracondylar Humerus Fracture Percutaneous Pin Sites Does Not Decrease Complications: A Retrospective Comparative Cohort, Alexis Aboulafia, Brendan Grant, Rohini M Vanodia, Lindsay M Crawford, Shiraz A Younas, Alfred A Mansour

Faculty, Staff and Student Publications

Background: Supracondylar humerus (SCH) fractures are the most common type of pediatric elbow fractures that require surgical intervention. Studies suggest limiting the first postoperative visit to the time of pin removal or limiting radiographs at first postoperative follow-up may not increase complication rates, but few comparative studies exist. This study aims to determine if routinely examining surgical pins sites at the first postoperative visits affects the complication rates or outcomes compared to only evaluating pin sites if a clinical indication exists.

Methods: This cohort study retrospectively reviewed patients who were surgically treated for a supracondylar humerus fracture at a Pediatric …

Primary Intrathoracic Synovial Sarcoma: An Analysis Of Outcomes Of This Rare Disease, Riddhi R Patel, Andrew J Bishop, Alexander J Lazar, Patrick P Lin, Robert S Benjamin, Shreyaskumar R Patel, Joseph Ludwig, Vinod Ravi, Ara A Vaporciyan, Dejka M Araujo

Faculty, Staff and Student Publications

No abstract provided.

Sequence Of Therapy Impact On Older Women With Comorbidities And Triple-Negative Or Her2-Positive Breast Cancer, Nina Tamirisa, Wenli Dong, Yu Shen, Heather Lin, Simona F Shaitelman, Gildy Babiera, Isabelle Bedrosian

Faculty, Staff and Student Publications

We sought to determine whether sequencing of treatment impacted outcomes in older, comorbid patients. Using the National Cancer Database(2010-2017), 2911 patients >70 with a Charleson Deyo Comorbidity(CCDM) score of 2/3 and cT1c-3/N0-3/HER2 positive or triple-negative breast cancer treated with chemotherapy,surgery,or both were included. Chi-square tests evaluated differences between groups. Multivariable models evaluated associations between overall survival and treatment. Majority 87.4%(n = 2544) underwent surgery first and 36.0%(n = 917) received adjuvant chemotherapy while 77.9%(n = 286) of chemotherapy first patients underwent surgery. Receipt of both modalities was associated with the best survival followed by surgery alone then chemotherapy alone. Additional …

Aberrant Choroid Plexus Formation Drives The Development Of Treatment-Related Brain Toxicity, Tamara Bender, Esther Schickel, Celine Schielke, Jürgen Debus, David R Grosshans, Marco Durante, Insa S Schroeder

Faculty, Staff and Student Publications

Brain tumors are commonly treated with radiotherapy, but the efficacy of the treatment is limited by its toxicity to the normal tissue including post-irradiation contrast enhanced lesions often linked to necrosis. The poorly understood mechanisms behind such brain lesions were studied using cerebral organoids. Here we show that irradiation of such organoids leads to dose-dependent growth retardation and formation of liquid-filled cavities but is not correlated with necrosis. Instead, the radiation-induced changes comprise of an enhancement of cortical hem markers, altered neuroepithelial stem cell differentiation, and an increase of ZO1+/AQP1+/CLDN3+-choroid plexus (CP)-like structures accompanied by an upregulation of IGF2 mRNA, …

The Heterogeneity Of 13q Deletions In Chronic Lymphocytic Leukemia: Diagnostic Challenges And Clinical Implications, Changqing Xia, Guang Liu, Jinglan Liu, Arash Ronaghy, Saber Tadros, Wei Wang, Hong Fang, Shanxiang Zhang, Joseph D Khoury, Zhenya Tang

Faculty, Staff and Student Publications

Chronic lymphocytic leukemia (CLL) is the most common type of adult leukemia, particularly in Western countries. CLL can present indolently or aggressively, influenced by various factors, including chromosomal alterations. Fluorescent in situ hybridization (FISH), targeting specific genes/loci frequently affected in CLL patients, has established a standard for stratifying five CLL prognostic groups: del(11q)/ATM, trisomy 12, del(13q) as a sole aberration, del(17p)/TP53, and normal CLL FISH panel results. Among these, del(13q) as a sole aberration is associated with a favorable prognosis, while the others are considered intermediate (normal CLL FISH panel result and trisomy 12) or unfavorable …

The Mutational Landscape And Functional Effects Of Noncoding Ultraconserved Elements In Human Cancers, Recep Bayraktar, Yitao Tang, Mihnea P Dragomir, Cristina Ivan, Xinxin Peng, Linda Fabris, Jianhua Zhang, Alessandro Carugo, Serena Aneli, Jintan Liu, Mei-Ju M Chen, Sanjana Srinivasan, Iman Sahnoune, Emine Bayraktar, Kadir C Akdemir, Meng Chen, Pranav Narayanan, Wilson Huang, Leonie Florence Ott, Agda Karina Eterovic, Oscar Eduardo Villarreal, Mohammad Moustaf Mohammad, Michael D Peoples, Danielle M Walsh, Jon Andrew Hernandez, Margaret B Morgan, Kenna R Shaw, Jennifer S Davis, David Menter, Constantine S Tam, Paul Yeh, Sarah-Jane Dawson, Laura Z Rassenti, Thomas J Kipps, Tanja Kunej, Zeev Estrov, Simon A Joosse, Luca Pagani, Catherine Alix-Panabières, Klaus Pantel, Alessandra Ferajoli, Andrew Futreal, Ignacio I Wistuba, Milan Radovich, Scott Kopetz, Michael J Keating, Giulio F Draetta, John S Mattick, Han Liang, George A Calin

Faculty, Staff and Student Publications

The mutational landscape of phylogenetically ultraconserved elements (UCEs), especially those in noncoding DNAs (ncUCEs), and their functional relevance in cancers remain poorly characterized. Here, we perform a systematic analysis of whole-genome and in-house targeted UCE sequencing datasets from more than 3000 patients with cancer of 13,736 UCEs and demonstrate that ncUCE somatic alterations are common. Using a multiplexed CRISPR knockout screen in colorectal cancer cells, we show that the loss of several altered ncUCEs significantly affects cell proliferation. In-depth functional studies in vitro and in vivo further reveal that specific ncUCEs can be enhancers of tumor suppressors (such as ARID1B) …

At-Home Stroke Neurorehabilitation: Early Findings With The Neuroexo Bci System, Juan José González-España, Lianne Sánchez-Rodríguez, Maxine Annel Pacheco-Ramírez, Jeff Feng, Kathryn Nedley, Shuo-Hsiu Chang, Gerard E Francisco, Jose L Contreras-Vidal

Faculty, Staff and Student Publications

Background: Democratized access to safe and effective robotic neurorehabilitation for stroke survivors requires innovative, affordable solutions that can be used not only in clinics but also at home. This requires the high usability of the devices involved to minimize costs associated with support from physical therapists or technicians.

Methods: This paper describes the early findings of the NeuroExo brain-machine interface (BMI) with an upper-limb robotic exoskeleton for stroke neurorehabilitation. This early feasibility study consisted of a six-week protocol, with an initial training and BMI calibration phase at the clinic followed by 60 sessions of neuromotor therapy at the homes of …

The Bacterial Microbiome Modulates The Initiation Of Brain Metastasis By Impacting The Gut-To-Brain Axis, Matteo Massara, Michelle Ballabio, Bastien Dolfi, Golnaz Morad, Vladimir Wischnewski, Eleni Lamprou, Joao Lourenco, Stéphanie Claudinot, Hector Gallart-Ayala, Rui Santalla Méndez, Annamaria Kauzlaric, Nadine Fournier, Ashish V Damania, Matthew C Wong, Julijana Ivanisevic, Nadim J Ajami, Jennifer A Wargo, Johanna A Joyce

Faculty, Staff and Student Publications

Brain metastases (BrMs) are the most common brain tumors in patients and are associated with poor prognosis. Investigating the systemic and environmental factors regulating BrM biology represents an important strategy to develop effective treatments. Toward this goal, we explored the contribution of the gut microbiome to BrM development by using in vivo breast-BrM models under germ-free conditions or antibiotic treatment. This revealed a detrimental role of gut microbiota in fostering BrM initiation. We thus evaluated the impact of antibiotics and BrM outgrowth on the gut-brain axis. We found the bacterial genus Alistipes was differentially present under antibiotic treatment and BrM …

Immune Checkpoint Inhibitors Plus Debulking Surgery For Patients With Metastatic Renal Cell Carcinoma: Clinical Outcomes And Immunological Correlates Of A Prospective Pilot Trial, Sangeeta Goswami, Jianjun Gao, Sreyashi Basu, Daniel D Shapiro, Jose A Karam, Rebecca Slack Tidwell, Kamran Ahrar, Matthew T Campbell, Yu Shen, Alexandro E Trevino, Aaron T Mayer, Alexsandra B Espejo, Christian Seua, Marc D Macaluso, Yulong Chen, Wenbin Liu, Zhong He, Shalini S Yadav, Ying Wang, Priya Rao, Li Zhao, Jianhua Zhang, Sonali Jindal, Nizar M Tannir, Andrew Futreal, Linghua Wang, Padmanee Sharma

Faculty, Staff and Student Publications

Surgical removal of primary tumors reverses tumor-mediated immune suppression in pre-clinical models with metastatic disease. However, how cytoreductive surgery in the metastatic setting modulates the immune responses in patients, especially in the context of immune checkpoint therapy (ICT), is not understood. We report the first prospective, pilot, non-comparative clinical trial (NCT02210117) to evaluate the feasibility, clinical benefits, and immunologic changes of combining three different ICT-containing strategies with cytoreductive surgery or biopsy for patients with metastatic clear cell renal cell carcinoma. Primary safety endpoint of this trial has been met, with 43 patients completing cytoreductive surgery, 36 patients undergoing …

Invasion And Metastasis In Cancer: Molecular Insights And Therapeutic Targets, Yongxing Li, Fengshuo Liu, Qingjin Cai, Lijun Deng, Qin Ouyang, Xiang H-F Zhang, Ji Zheng

Faculty, Staff and Students Publications

The progression of malignant tumors leads to the development of secondary tumors in various organs, including bones, the brain, liver, and lungs. This metastatic process severely impacts the prognosis of patients, significantly affecting their quality of life and survival rates. Research efforts have consistently focused on the intricate mechanisms underlying this process and the corresponding clinical management strategies. Consequently, a comprehensive understanding of the biological foundations of tumor metastasis, identification of pivotal signaling pathways, and systematic evaluation of existing and emerging therapeutic strategies are paramount to enhancing the overall diagnostic and treatment capabilities for metastatic tumors. However, current research is …

Characterization Of Rationally Designed Crispr/Cas9-Based Dna Methyltransferases With Distinct Methyltransferase And Gene Silencing Activities In Human Cell Lines And Primary Human T Cells, Rosa Selenia Guerra-Resendez, Samantha Legoff Lydon, Alex J Ma, Guy C Bedford, Daniel R Reed, Sunghwan Kim, Erik R Terán, Tomoki Nishiguchi, Mario Escobar, Andrew R Dinardo, Isaac B Hilton

Faculty, Staff and Students Publications

Nuclease-deactivated Cas (dCas) proteins can be used to recruit epigenetic effectors, and this class of epigenetic editing technologies has revolutionized the ability to synthetically control the mammalian epigenome and transcriptome. DNA methylation is one of the most important and well-characterized epigenetic modifications in mammals, and while many different forms of dCas-based DNA methyltransferases (dCas-DNMTs) have been developed for programmable DNA methylation, these tools are frequently poorly tolerated and/or lowly expressed in mammalian cell types. Further, the use of dCas-DNMTs has largely been restricted to cell lines, which limits mechanistic insights in karyotypically normal contexts and hampers translational utility in the …

Pharmacological Interventions For Negative Symptoms In Schizophrenia: A Systematic Review Of Randomised Control Trials, Lorenzo Moccia, Francesca Bardi, Maria Benedetta Anesini, Sara Barbonetti, Georgios D Kotzalidis, Sara Rossi, Romina Caso, Flavia Grisoni, Giuseppe Mandracchia, Stella Margoni, Tommaso Callovini, Delfina Janiri, Marianna Mazza, Alessio Simonetti, Silvia Montanari, Gianna Autullo, Giovanni Camardese, Maria Pepe, Marco Di Nicola, Vassilij Di Giorgio, Fabio Conti, Gabriele Sani, On Behalf Of The Gemelli Repsy Study Group

Faculty, Staff and Students Publications

Background/Objectives: While positive symptoms of schizophrenia are often satisfactorily controlled, negative symptoms are difficult to treat, persisting despite treatment. Different strategies have been devised to deal with this problem. We aimed to review drug treatment for negative symptoms of schizophrenia in controlled trials of marketed drugs.

Methods: We searched the PubMed database and the resulting records' reference lists to identify eligible trials using schizophrenia[ti] AND "negative symptom*"[ti] as a search strategy. We determined eligibility through Delphi rounds among all authors.

Results: On 11 February 2025, we identified 1485 records on PubMed and 3 more from reference lists. Eligible were 95 …

Does Adiponectin Inform Cardiovascular Risk In Older Adults?: The Aric Study, Layla A Abushamat, Xiaoming Jia, Lu Xu, Chao Cheng, Chiadi E Ndumele, Caroline Sun, B Gwen Windham, Kunihiro Matsushita, Bing Yu, Vijay Nambi, Biykem Bozkurt, Jane E B Reusch, Casey M Rebholz, Elizabeth Selvin, Christie M Ballantyne, Ron C Hoogeveen

Faculty, Staff and Student Publications

BACKGROUND: Adiponectin, an atheroprotective adipokine, is associated with adverse outcomes in older age. It is unclear whether this is due to overlapping pathophysiological pathways with N-terminal pro-B-type natriuretic peptide (NT-proBNP).

OBJECTIVES: The authors investigated adiponectin's associations with cardiovascular disease (CVD) risk in older adults.

METHODS: Among Atherosclerosis Risk in Communities prospective cohort study participants without baseline CVD at visit 5 (n = 4,729, mean age 75), adiponectin and adiponectin/NT-proBNP category associations with incident CVD events (heart failure [HF], atherosclerotic cardiovascular disease, and death during median follow-up of 5.5 years) and echocardiographic parameters were assessed. Metabolomic signatures of adiponectin/NT-proBNP categories were …

Erythritol, Erythronate, And Cardiovascular Outcomes In Older Adults In The Aric Study, Layla A Abushamat, Bing Yu, Ron C Hoogeveen, Caroline Sun, Chao Cheng, Sean M Hartig, Mark A Herman, Ashok Balasubramanyam, Jane Eb Reusch, Elizabeth Selvin, Chiadi E Ndumele, Vijay Nambi, Christie M Ballantyne

Faculty, Staff and Student Publications

BACKGROUND: Circulating erythritol, an endogenously produced metabolite and an artificial sweetener, is associated with cardiovascular outcomes.

OBJECTIVES: The authors assessed associations of erythritol and its downstream metabolite, erythronate, with cardiovascular risk factors and events in older adults in the ARIC (Atherosclerosis Risk In Communities) study (visit 5, 2011-2013).

METHODS: We included 4,006 participants without prevalent cardiovascular disease and with metabolomic profiling. Erythritol and erythronate were measured by mass spectrometry. We analyzed associations of log-transformed erythritol and erythronate with cardiovascular risk factors and events using Cox proportional hazard models.

RESULTS: Participants in the highest tertiles of erythritol or erythronate were older, …

Semaglutide And Nonarteritic Anterior Ischemic Optic Neuropathy, Cindy X Cai, Michelle Hribar, Sally Baxter, Kerry Goetz, Swarup S Swaminathan, Alexis Flowers, Eric N Brown, Brian Toy, Benjamin Xu, John Chen, Aiyin Chen, Sophia Wang, Cecilia Lee, Theodore Leng, Joshua R Ehrlich, Andrew Barkmeier, Karen R Armbrust, Michael V Boland, David Dorr, Danielle Boyce, Thamir Alshammari, Joel Swerdel, Marc A Suchard, Martijn Schuemie, Fan Bu, Anthony G Sena, George Hripcsak, Akihiko Nishimura, Paul Nagy, Thomas Falconer, Scott L Duvall, Michael Matheny, Benjamin Viernes, William O'Brien, Linying Zhang, Benjamin Martin, Erik Westlund, Nestoras Mathioudakis, Ruochong Fan, Adam Wilcox, Albert Lai, Jacqueline C Stocking, Sahar Takkouche, Lok Hin Lee, Yangyiran Xie, Izabelle Humes, David B Mccoy, Mohammad Adibuzzaman, Raymond G Areaux, William Rojas-Carabali, James Brash, David A Lee, Nicole G Weiskopf, Louise Mawn, Rupesh Agrawal, Hannah Morgan-Cooper, Priya Desai, Patrick B Ryan

Faculty, Staff and Student Publications

Importance

Semaglutide, a glucagonlike peptide-1 receptor agonist (GLP-1RA), has recently been implicated in cases of nonarteritic anterior ischemic optic neuropathy (NAION), raising safety concerns in the treatment of type 2 diabetes (T2D).

Objective

To investigate the potential association between semaglutide and NAION in the Observational Health Data Sciences and Informatics (OHDSI) network.

Design, Setting, and Participants

This was a retrospective study across 14 databases (6 administrative claims and 8 electronic health records). Included were adults with T2D taking semaglutide, other GLP-1RA (dulaglutide, exenatide), or non–GLP-1RA medications (empagliflozin, sitagliptin, glipizide) from December 1, 2017, to December 31, 2023. The incidence proportion …

A Protocol To Purify Human Mediator Complex From Freestyle 293-F Cells, Hui-Chi Tang, Kuang-Lei Tsai, Ti-Chun Chao

Faculty, Staff and Student Publications

The Mediator, a multi-subunit protein complex in all eukaryotes, comprises the core mediator (cMED) and the CDK8 kinase module (CKM). As a molecular bridge between transcription factors (TFs) and RNA polymerase II (Pol II), the Mediator plays a critical role in regulating Pol II-dependent transcription. Considering its large size and complex composition, conducting in vitro studies on the Mediator complex is challenging, especially when isolating the intact and homogeneous complex from human cells. Here, we present a method to purify the intact CKM-cMED complex from FreeStyle 293-F cells (293-F cells), which offers advantages for performing large-scale protein purification. To isolate …

Membrane Lipids Augment Cell Envelope Stress Signaling Via The Madrs System To Defend Against Antimicrobial Peptides And Antibiotics In Enterococcus Faecalis, William R Miller, April Nguyen, Kavindra V Singh, Samie Rizvi, Ayesha Khan, Sam G Erickson, Stephanie L Egge, Melissa Cruz, An Q Dinh, Lorena Diaz, Philip C Thornton, Rutan Zhang, Libin Xu, Danielle A Garsin, Yousif Shamoo, Cesar A Arias

Faculty, Staff and Student Publications

Enterococci have evolved resistance mechanisms to protect their cell envelopes against bacteriocins and host cationic antimicrobial peptides (CAMPs) produced in the gastrointestinal environment. Activation of the membrane stress response has also been tied to resistance to the lipopeptide antibiotic daptomycin. However, the actual effectors mediating resistance have not been elucidated. Here, we show that the MadRS (formerly YxdJK) membrane antimicrobial peptide defense system controls a network of genes, including a previously uncharacterized 3-gene operon (madEFG) that protects the Enterococcus faecalis cell envelope from antimicrobial peptides. Constitutive activation of the system confers protection against CAMPs and daptomycin in the absence of …

Antibiotic-Induced Loss Of Gut Microbiome Metabolic Output Correlates With Clinical Responses To Car T-Cell Therapy, Rishika Prasad, Abdur Rehman, Lubna Rehman, Faezeh Darbaniyan, Viktoria Blumenberg, Maria-Luisa Schubert, Uria Mor, Eli Zamir, Sabine Schmidt, Tomo Hayase, Chia-Chi Chang, Lauren Mcdaniel, Ivonne Flores, Paolo Strati, Ranjit Nair, Dai Chihara, Luis E Fayad, Sairah Ahmed, Swaminathan P Iyer, Michael Wang, Preetesh Jain, Loretta J Nastoupil, Jason Westin, Reetakshi Arora, Joel Turner, Fareed Khawaja, Ranran Wu, Jennifer B Dennison, Meghan Menges, Melanie Hidalgo-Vargas, Kayla Reid, Marco L Davila, Peter Dreger, Felix Korell, Anita Schmitt, Mark R Tanner, Richard E Champlin, Christopher R Flowers, Elizabeth J Shpall, Samir Hanash, Sattva S Neelapu, Michael Schmitt, Marion Subklewe, Johannes Francois-Fahrmann, C K Stein-Thoeringer, Eran Elinav, Michael D Jain, Eiko Hayase, Robert R Jenq, Neeraj Y Saini

Faculty, Staff and Student Publications

Antibiotic (ABX)–induced microbiome dysbiosis is widespread in oncology, adversely affecting outcomes and side effects of various cancer treatments, including immune checkpoint inhibitors and chimeric antigen receptor T-cell (CAR-T) therapies. In this study, we observed that prior exposure to broad-spectrum ABXs with extended anaerobic coverage such as piperacillin-tazobactam and meropenem was associated with worse anti-CD19 CAR-T therapy survival outcomes in patients with large B-cell lymphoma (N = 422) than other ABX classes. In a discovery subset of these patients (n = 67), we found that the use of these ABXs was in turn associated with substantial dysbiosis of gut microbiome function, …

Aif3 Splicing Variant Elicits Mitochondrial Malfunction Via The Concurrent Dysregulation Of Electron Transport Chain And Glutathione-Redox Homeostasis, Mi Zhou, Shuiqiao Liu, Yanan Wang, Bo Zhang, Ming Zhu, Jennifer E Wang, Veena Rajaram, Yisheng Fang, Weibo Luo, Yingfei Wang

Faculty, Staff and Student Publications

Genetic mutations in apoptosis-inducing factor (AIF) have a strong association with mitochondrial disorders; however, little is known about the aberrant splicing variants in affected patients and how these variants contribute to mitochondrial dysfunction and brain development defects. We identified pathologic AIF3/AIF3-like splicing variants in postmortem brain tissues of pediatric individuals with mitochondrial disorders. Mutations in AIFM1 exon-2/3 increase splicing risks. AIF3-splicing disrupts mitochondrial complexes, membrane potential, and respiration, causing brain development defects. Mechanistically, AIF is a mammalian NAD(P)H dehydrogenase and possesses glutathione reductase activity controlling respiratory chain functions and glutathione regeneration. Conversely, AIF3, lacking these activities, disassembles mitochondrial complexes, increases …

Oral Inflammation And Microbiome Dysbiosis Exacerbate Chronic Graft-Versus-Host Disease, Yui Kambara, Hideaki Fujiwara, Akira Yamamoto, Kazuyoshi Gotoh, Shuma Tsuji, Mari Kunihiro, Tadashi Oyama, Toshiki Terao, Ayame Sato, Takehiro Tanaka, Daniel Peltier, Keisuke Seike, Hisakazu Nishimori, Noboru Asada, Daisuke Ennishi, Keiko Fujii, Nobuharu Fujii, Ken-Ichi Matsuoka, Yoshihiko Soga, Pavan Reddy, Yoshinobu Maeda

Faculty, Staff and Students Publications

The oral microbiota, second in abundance to the gut, is implicated in chronic systemic diseases, but its specific role in graft-versus-host disease (GVHD) pathogenesis has been unclear. Our study finds that mucositis-induced oral dysbiosis in patients after hematopoietic cell transplantation (HCT) associated with increased chronic GVHD (cGVHD), even in patients receiving posttransplant cyclophosphamide. In murine HCT models, oral dysbiosis caused by bilateral molar ligatures exacerbated cGVHD and increased bacterial load in the oral cavity and gut, with Enterococcaceae significantly increasing in both organs. In this model, the migration of Enterococcaceae to cervical lymph nodes both before and after transplantation activated …

Zika Virus Ns1 Drives Tunneling Nanotube Formation For Mitochondrial Transfer And Stealth Transmission In Trophoblasts, Rafael T Michita, Long B Tran, Steven J Bark, Deepak Kumar, Shay A Toner, Joyce Jose, Indira U Mysorekar, Anoop Narayanan

Faculty, Staff and Students Publications

Zika virus (ZIKV) is unique among orthoflaviviruses in its vertical transmission capacity in humans, yet the underlying mechanisms remain incompletely understood. Here, we show that ZIKV induces tunneling nanotubes (TNTs) in placental trophoblasts which facilitate transfer of viral particles, proteins, mitochondria, and RNA to neighboring uninfected cells. TNT formation is driven exclusively via ZIKV non-structural protein 1 (NS1). Specifically, the N-terminal 1-50 amino acids of membrane-bound ZIKV NS1 are necessary for triggering TNT formation in host cells. Trophoblasts infected with TNT-deficient ZIKV

Benefits Of Equilibrium Between Microbiota- And Host-Derived Ligands Of The Aryl Hydrocarbon Receptor After Stroke In Aged Male Mice, Pedram Peesh, Maria P Blasco-Conesa, Ahmad El Hamamy, Romeesa Khan, Gary U Guzman, Parisa Honarpisheh, Eric C Mohan, Grant W Goodman, Justin N Nguyen, Anik Banerjee, Bryce E West, Kyung Ae Ko, Janelle M Korf, Chunfeng Tan, Huihui Fan, Gabriela D Colpo, Hilda Ahnstedt, Lucy Couture, Solji Roh, Julia K Kofler, Jose F Moruno-Manchon, Michael E Maniskas, Jaroslaw Aronowski, Rodney M Ritzel, Juneyoung Lee, Jun Li, Robert M Bryan, Anjali Chauhan, Venugopal Reddy Venna, Louise D Mccullough, Bhanu Priya Ganesh

Faculty, Staff and Student Publications

Recent studies have highlighted the crucial role of microglia (MG) and their interactions with the gut microbiome in post-stroke neuroinflammation. The activation of immunoregulatory pathways, including the aryl hydrocarbon receptor (AHR) pathway, is influenced by a dynamic balance of ligands derived from both the host and microbiota. This study aimed to investigate the association between stroke-induced dysbiosis and the resultant imbalance in AHR ligand sources (loss of microbiota-derived [indole-based] and increase of host-derived [kynurenine-based]) after stroke. Microbiota-derived AHR ligands decreased in human plasma and remained low for days following an ischemic stroke highlighting the translational significance. Transient-middle-cerebral-artery-occlusion was performed in …

Cardiovascular Comorbidities In Chinese Inpatients With Schizophrenia Spectrum Disorders, Zhe Dong, Gang Wu, Hongbing Liu, Song Chen, Bin Bi, Fangfang Zhang, Yi Yin, Wei Qu, Baopeng Tian, Fude Yang, Alice Kochunov, Peter Kochunov, Shengmei Ban, Yang Zhao, L Elliot Hong, Yunlong Tan

Faculty, Staff and Student Publications

Cardiovascular diseases (CVDs) are the leading cause of premature mortality in patients with schizophrenia spectrum disorders (SSDs). However, the detailed categorization of these conditions remains insufficiently explored. This study aims to identify CVDs comorbidity patterns among inpatients with SSDs and to investigate associated factors. Electronic medical records (EMRs) data from three neuropsychiatric hospitals (2015-2023) in China was conducted. Comorbidity patterns were revealed through latent class analysis (LCA), and multinomial logit analysis were utilized to evaluate the effect of factors on these patterns, calculating odds ratios (ORs) and 95% confidence intervals (CIs). Among the 2830 inpatients with SSD, four distinct comorbidity …

Early Application Value Of Flexible Laryngoscope Swallowing Function Assessment In Patients After Partial Laryngectomy, Lina Jia, Chenxu Yan, Run Liu, Pengfei He, Ailing Liu, Fei Yang, Hui Huangfu, Sen Zhang

Faculty, Staff and Student Publications

To investigate the influence of early dysphagia on quality of life in patients with partial laryngectomy, and to investigate the application value of Flexible Endoscopic Evaluation of Swallowing (FEES). This study included 30 inpatients who underwent partial laryngectomy due to laryngeal cancer. In the early postoperative period, a comprehensive assessment was conducted on each patient, encompassing Videofluoroscopic Swallowing Study (VFSS), Flexible Endoscopic Evaluation of Swallowing (FEES), and MD Anderson Dysphagia Inventory (MDADI). Each patient underwent two evaluations at different time points following the surgical procedure, all conducted on the same day. The patients' first MDADI assement score after surgery was …

Development Of A Conditional Plasmid For Gene Deletion In Non-Model Fusobacterium Nucleatum Strains, Peng Zhou, Bibek G C, Chenggang Wu

Faculty, Staff and Student Publications

Fusobacterium nucleatum is an opportunistic pathogen with four subspecies: nucleatum (FNN), vincentii (FNV), polymorphum (FNP), and animalis (FNA), each with distinct disease potentials. Research on fusobacterial pathogenesis has mainly focused on the model strain ATCC 23726 from FNN. However, this narrow focus may overlook significant behaviors of other FNN strains and those from other subspecies, given the genetic and phenotypic diversity within F. nucleatum. While ATCC 23726 is highly transformable, most other Fusobacterium strains exhibit low transformation efficiency, complicating traditional gene deletion methods that rely on non-replicating plasmids. To address this, we developed a conditional plasmid system in which …

Assessing The Contribution Of Rare Protein-Coding Germline Variants To Prostate Cancer Risk And Severity In 37,184 Cases, Jonathan Mitchell, Niedzica Camacho, Patrick Shea, Konrad H Stopsack, Vijai Joseph, Oliver S Burren, Ryan S Dhindsa, Abhishek Nag, Jacob E Berchuck, Amanda O'Neill, Ali Abbasi, Anthony W Zoghbi, Jesus Alegre-Díaz, Pablo Kuri-Morales, Jaime Berumen, Roberto Tapia-Conyer, Jonathan Emberson, Jason M Torres, Rory Collins, Quanli Wang, David Goldstein, Athena Matakidou, Carolina Haefliger, Lauren Anderson-Dring, Ruth March, Vaidehi Jobanputra, Brian Dougherty, Keren Carss, Slavé Petrovski, Philip W Kantoff, Kenneth Offit, Lorelei A Mucci, Mark Pomerantz, Margarete A Fabre

Faculty, Staff and Students Publications

To assess the contribution of rare coding germline genetic variants to prostate cancer risk and severity, we perform here a meta-analysis of 37,184 prostate cancer cases and 331,329 male controls from five cohorts with germline whole exome or genome sequencing data, and one cohort with imputed array data. At the gene level, our case-control collapsing analysis confirms associations between rare damaging variants in four genes and increased prostate cancer risk: SAMHD1, BRCA2 and ATM at the study-wide significance level (P <  1×10−8), and CHEK2 at the suggestive threshold (P <  2.6×10−6). Our case-only analysis, reveals that rare damaging variants in AOX1 are associated with more aggressive disease (OR = 2.60 [1.75–3.83], …

Deep5mc: Predicting 5-Methylcytosine (5mc) Methylation Status Using A Deep Learning Transformer Approach, Evan Kinnear, Houssemeddine Derbel, Zhongming Zhao, Qian Liu

Faculty, Staff and Student Publications

DNA methylations, such as 5-methylcytosine (5mC), are crucial in biological processes, and aberrant methylations are strongly linked to various human diseases. Genomic 5mC is not randomly distributed but exhibits a strong association with genomic sequences. Thus, various computational methods were developed to predict 5mC status based on DNA sequences. These methods generated promising achievements and overcome the limitations of experimental approaches. However, few studies have comprehensively investigated the dependency of 5mC on genomic sequences, and most existing methods focus on specific genomic regions. In this work, we introduce Deep5mC, a deep learning transformer-based method designed to predict 5mC methylations. Deep5mC …

Unveiling The Genetic Landscape Of Coronary Artery Disease Through Common And Rare Structural Variants, Kruthika R Iyer, Shoa L Clarke, Rodrigo Guarischi-Sousa, Ketrin Gjoni, Adam S Heath, Erica P Young, Nathan O Stitziel, Cecelia Laurie, Jai G Broome, Alyna T Khan, Joshua P Lewis, Huichun Xu, May E Montasser, Kellan E Ashley, Natalie R Hasbani, Eric Boerwinkle, Alanna C Morrison, Nathalie Chami, Ron Do, Ghislain Rocheleau, Donald M Lloyd-Jones, Rozenn N Lemaitre, Joshua C Bis, James S Floyd, Gregory L Kinney, Donald W Bowden, Nicholette D Palmer, Emelia J Benjamin, Matthew Nayor, Lisa R Yanek, Brian G Kral, Lewis C Becker, Sharon L R Kardia, Jennifer A Smith, Lawrence F Bielak, Arnita F Norwood, Yuan-I Min, April P Carson, Wendy S Post, Stephen S Rich, David Herrington, Xiuqing Guo, Kent D Taylor, Joann E Manson, Nora Franceschini, Katherine S Pollard, Braxton D Mitchell, Ruth J F Loos, Myriam Fornage, Lifang Hou, Bruce M Psaty, Kendra A Young, Elizabeth A Regan, Barry I Freedman, Ramachandran S Vasan, Daniel Levy, Rasika A Mathias, Patricia A Peyser, Laura M Raffield, Charles Kooperberg, Alex P Reiner, Jerome I Rotter, Goo Jun, Paul S De Vries, Themistocles L Assimes

Faculty, Staff and Student Publications

Background: Genome-wide association studies have identified several hundred susceptibility single nucleotide variants for coronary artery disease (CAD). Despite single nucleotide variant-based genome-wide association studies improving our understanding of the genetics of CAD, the contribution of structural variants (SVs) to the risk of CAD remains largely unclear.

Method and results: We leveraged SVs detected from high-coverage whole genome sequencing data in a diverse group of participants from the National Heart Lung and Blood Institute's Trans-Omics for Precision Medicine program. Single variant tests were performed on 58 706 SVs in a study sample of 11 556 CAD cases and 42 907 controls. …