Medicine and Health Sciences Commons^™

Surgical Repair Of An Atypical Midsubstance Distal Biceps Tendon Partial Tear: A Case Report, Michael M. Valenzuela, Genoveffa R. Morway, Christopher M. Jones

Department of Orthopaedic Surgery Faculty Papers

No abstract provided.

Author Correction: Orthogonal And Multiplexable Genetic Perturbations With An Engineered Prime Editor And A Diverse Rna Array, Qichen Yuan, Hongzhi Zeng, Tyler C Daniel, Qingzhuo Liu, Yongjie Yang, Emmanuel C Osikpa, Qiaochu Yang, Advaith Peddi, Liliana M Abramson, Boyang Zhang, Yong Xu, Xue Gao

Faculty, Staff and Students Publications

Correction to: Nature Communications 10.1038/s41467-024-55134-9, published online 30 December 2024

In the version of the article initially published, there were errors in Fig. 3d, where in the x-axis labels now reading “GPP-shRNA1, GPP-shRNA2, GPP-shRNA3…,” the second and third labels were duplicates of the first. The figure is amended in the HTML and PDF versions of the article.

Intensive Lifestyle Intervention, Cardiac Biomarkers, And Cardiovascular Outcomes In Diabetes: Look Ahead Cardiac Biomarker Ancillary Study, Kershaw V Patel, Zainali Chunawala, Subodh Verma, Matthew W Segar, Katelyn R Garcia, Chiadi E Ndumele, Thomas J Wang, James L Januzzi, Antoni Bayes-Genis, Javed Butler, Carolyn S P Lam, Christie M Ballantyne, James A De Lemos, Alain G Bertoni, Mark Espeland, Ambarish Pandey

Faculty, Staff and Students Publications

Background: N-terminal pro-B-type natriuretic peptide (NT-proBNP) and high-sensitivity cardiac troponin T (hs-cTnT) are associated with cardiovascular outcomes and are recommended for measurement in type 2 diabetes (T2D). However, the effects of an intensive lifestyle intervention (ILI) targeting weight loss on cardiac biomarkers and the prognostic association of changes in these biomarkers with risk of adverse cardiovascular outcomes in T2D are not well-established.

Objectives: This study sought to evaluate the effects of an ILI on cardiac biomarkers and the association of changes in cardiac biomarkers with risk of cardiovascular outcomes in T2D.

Methods: Participants of the Look AHEAD (Action for Health …

Complete Genome Sequence Of A Penicillin-Resistant Fusobacterium Necrophorum Subsp Funduliforme Isolate From A Tonsillitis Patient, Bibek G C, Anders Jensen, Chenggang Wu

Faculty, Staff and Student Publications

We report the complete genome sequence of a penicillin-resistant Fusobacterium necrophorum subsp. funduliforme isolate, AJ79, from a tonsillitis patient. The AJ79 genome consists of a chromosome (2,440,359 bp) and plasmid (9,887 bp), providing insights into the genetic basis of penicillin resistance in F. necrophorum and its implications for treating tonsillitis.

Nprl2 Gene Therapy Induces Effective Antitumor Immunity In Kras/Stk11 Mutant Anti-Pd1 Resistant Metastatic Non-Small Cell Lung Cancer (Nsclc) In A Humanized Mouse Model, Ismail M Meraz, Mourad Majidi, Renduo Song, Feng Meng, Lihui Gao, Qi Wang, Jing Wang, Elizabeth J Shpall, Jack A Roth

Faculty, Staff and Student Publications

Expression of NPRL2/TUSC4, a tumor-suppressor gene, is reduced in many cancers including NSCLC. Restoration of NPRL2 induces DNA damage, apoptosis, and cell-cycle arrest. We investigated NPRL2 antitumor immune responses in aPD1R/KRAS/STK11^mt NSCLC in humanized-mice. Humanized-mice were generated by transplanting fresh human cord blood-derived CD34 stem cells into sub-lethally irradiated NSG mice. Lung-metastases were developed from KRAS/STK11^mt/aPD1R A549 cells and treated with NPRL2 w/wo pembrolizumab. NPRL2-treatment reduced lung metastases significantly, whereas pembrolizumab was ineffective. Antitumor effect was greater in humanized than non-humanized-mice. NPRL2 + pembrolizumab was not synergistic in KRAS/STK11^mt/aPD1R tumors but was …

Otolaryngology Practitioner Attitudes Toward Human Papillomavirus Vaccination In Academic Otolaryngology Clinics, Dante J. Merlino, Katelyn S. Rourk, George B. Sankar, Adam J. Luginbuhl, Brian J. Boyce, Michelle M. Chen, Eric M. Dowling, Michael C. Topf, Raymond L. Chai, Karthik Rajasekaran, Eric J. Moore, Daniel L. Price, George Saieed, Kathryn M. Van Abel

Department of Otolaryngology - Head and Neck Surgery Faculty Papers

Despite the existence of a highly effective and safe vaccine against human papillomavirus (HPV) infection, vaccination rates remain low. The most prevalent HPV-associated malignancy in the United States is oropharyngeal cancer, but otolaryngology practitioners do not offer the HPV vaccine, and their feelings around offering HPV vaccination have not been evaluated. A 43-question survey, including a twelve-question knowledge quiz, was sent to otolaryngology practitioners at seven academic institutions. Twelve questions comprised a knowledge quiz testing practitioner understanding of HPV, while the remainder of the questions evaluated comfort with and likelihood of recommending vaccination. Of the 442 practitioners who were sent …

Repeat Expansion In A Fragile X Model Is Independent Of Double Strand Break Repair Mediated By Pol Θ, Rad52, Rad54 Or Rad54b, Bruce E Hayward, Geum-Yi Kim, Carson J Miller, Cai Mccann, Megan G Lowery, Richard D Wood, Karen Usdin

Faculty, Staff and Student Publications

Microsatellite instability is responsible for the human repeat expansion diseases (REDs). The mutagenic process differs from classical cancer-associated microsatellite instability (MSI) in that it requires the mismatch repair proteins that normally protect against MSI. LIG4, an enzyme essential for non-homologous end-joining (NHEJ), the major pathway for double-strand break repair (DSBR) in mammalian cells, protects against expansion in mouse models. Thus, NHEJ may compete with the expansion pathway for access to a common intermediate. This raises the possibility that expansion involves an NHEJ-independent form of DSBR. Pol θ, a polymerase involved in the theta-mediated end joining (TMEJ) DSBR pathway, has been …

Engineered Immunomodulatory Extracellular Vesicles From Epithelial Cells With The Capacity For Stimulation Of Innate And Adaptive Immunity In Cancer And Autoimmunity, Xin Luo, Fernanda G Kugeratski, Dara P Dowlatshahi, Hikaru Sugimoto, Kent A Arian, Yibo Fan, Li Huang, Danielle Wills, Sergio Lilla, Kelly Hodge, Sara R Zanivan, Valerie S Lebleu, Kathleen M Mcandrews, Raghu Kalluri

Faculty, Staff and Student Publications

Extracellular vesicles (EVs) are generated by all cells. Systemic administration of allogenic EVs derived from epithelial and mesenchymal cells have been shown to be safe, despite carrying an array of functional molecules, including thousands of proteins. To address whether epithelial cells derived EVs can be modified to acquire the capacity to induce immune response, we engineered 293T EVs to harbor the immunomodulatory molecules CD80, OX40L and PD-L1. We demonstrated abundant levels of these proteins on the engineered cells and EVs. Functionally, the engineered EVs efficiently elicited positive and negative co-stimulation of human and murine T cells. In the setting of …

Regression Modeling Of Cumulative Incidence Function For Left-Truncated Right-Censored Competing Risks Data: A Modified Pseudo-Observation Approach, Rong Rong, Jing Ning, Hong Zhu

Faculty, Staff and Student Publications

Statistical methods have been developed for regression modeling of the cumulative incidence function (CIF) given left-truncated right-censored competing risks data. Nevertheless, existing methods typically involve complicated weighted estimating equations or nonparametric conditional likelihood function and often require a restrictive assumption that censoring and/or truncation times are independent of failure time. The pseudo-observation (PO) approach has been used in regression modeling of CIF for right-censored competing risks data under covariate-independent censoring or covariate-dependent censoring. We extend this approach to left-truncated right-censored competing risks data and propose to directly model the CIF based on POs, under general truncation and censoring mechanisms. We …

Bbox1 Restrains Tbk1-Mtorc1 Oncogenic Signaling In Clear Cell Renal Cell Carcinoma, Chengheng Liao, Lianxin Hu, Liwei Jia, Jin Zhou, Tao Wang, Kangsan Kim, Hua Zhong, Hongwei Yao, Lei Dong, Lei Guo, Qian Liang, Cheng Zhang, Fangzhou Zhao, Jun Fang, Hongyi Liu, Shina Li, Lin Xu, Jeremy M Simon, Srinivas Malladi, Payal Kapur, James Brugarolas, Ralph J Deberardinis, Qing Zhang

Faculty, Staff and Student Publications

Clear cell renal cell carcinoma (ccRCC), a metabolic disease originating from renal proximal convoluted tubule (PCT) epithelial cells, remains incompletely understood in terms of its initiating signaling events. Here, we identify γ-butyrobetaine hydroxylase 1 (BBOX1), a key enzyme in carnitine synthesis predominantly expressed in PCT cells, as a tumor suppressor in ccRCC. BBOX1 expression is lost during ccRCC malignant transformation, and its restoration reduces cell viability in physiological medium and inhibits xenograft tumor growth. Transcriptomic analyses reveal that BBOX1 suppresses critical metabolic pathways including mTORC1 signaling and glycolysis in ccRCC. Further, we identify TANK-binding kinase 1 (TBK1) as an essential …

Mbnl Overexpression Rescues Cardiac Phenotypes In A Myotonic Dystrophy Type 1 Heart Mouse Model, Rong-Chi Hu, Yi Zhang, Larissa Nitschke, Sara J Johnson, Ayrea E Hurley, William R Lagor, Zheng Xia, Thomas A Cooper

Faculty, Staff and Students Publications

Myotonic dystrophy type 1 (DM1) is an autosomal dominant disease caused by a CTG repeat expansion in the dystrophia myotonica protein kinase (DMPK) gene. The expanded CUG repeat RNA (CUGexp RNA) transcribed from the mutant allele sequesters the muscleblind-like (MBNL) family of RNA-binding proteins, causing their loss of function and disrupting regulated pre-mRNA processing. We used a DM1 heart mouse model that inducibly expresses CUGexp RNA to test the contribution of MBNL loss to DM1 cardiac abnormalities and explored MBNL restoration as a potential therapy. AAV9-mediated overexpression of MBNL1 and/or MBNL2 significantly rescued DM1 cardiac phenotypes including conduction delays, contractile …

Investigating The Impact Of Tirzepatide Treatment On Alcohol And Cigarette Consumption, Yvannia Gray, Benjamin Latey, Hayden Mcaffee, Karissa Mccown, Seth Maki, Victoria Nguyen, Andrew Payne

Annual Research Symposium

No abstract provided.

Transcranial Magnetic Stimulation As A Treatment Modality For Functional Bowel Disorder And Irritable Bowel Syndrome And Possible Correlations With The Gut-Brain Axis: A Review, Lauren Draper, Devin Pfister, Ethan Zaugg

Annual Research Symposium

Functional Bowel Disorders (FBD), including Irritable Bowel Syndrome (IBS), are highly prevalent gastrointestinal conditions classified as Disorders of Gut-Brain Interactions (DGBIs) under the Rome IV criteria. These conditions, marked by abdominal pain, altered bowel habits, and significant psychological comorbidities, present substantial challenges in both diagnosis and treatment. Conventional therapies primarily target gut-centric mechanisms but often yield limited efficacy, underscoring the need for approaches that account for the complex interplay of the gut-brain axis in DGBI pathophysiology.

Anesthesia And Pain Management In Conflict-Affected Regions: Addressing Global Health Barriers To Access And Quality Of Care​, Naeel Uddin, Sierra Brown, Maria Easler, Ayanda Mkhize, Marwa Hamdam, Chandu Goli, Lauren Draper

Annual Research Symposium

This poster examines how to deliver safe, effective anesthesia and pain control in areas with limited resources and ongoing security threats. Focusing on portable technology, ketamine-based protocols, and telemedicine, we highlight ethical considerations, training needs, and global collaborations. Our findings outline a pathway to reduce suffering and improve surgical outcomes in vulnerable populations by addressing challenges unique to conflict settings.

Use Of Synthetic Water-Soluble Kcc2 To Modulate Chloride Homeostasis In Cultured Dopamine-Neuron-Like Cells, Mason Terry, Andrew Payne, Dario Mizrachi

Annual Research Symposium

No abstract provided.

Unraveling Physiologic Mechanisms In Passive And Active Mechanoreceptor Stimulation, Halah Khan, Braden Ashcraft

Annual Research Symposium

No abstract provided.

Effects Of Hvla On Shoulder Mobilization And Baseball Pitch Velocity With Dari Motion Capture, Drew T. Mortensen, James Barber, Jordyn Huecker, Garret Phillips, Jayne Stuter, Braden Ashcraft, Isabella Termini, Victoria Oyeniyi, Christina Small, Kyle Bills

Annual Research Symposium

No abstract provided.

A Galleria Mellonella Study: Protective Effects Of Sulforaphane On Immune Function In Binge Alcohol Exposure, Robert Kento Darby, Braydon Black, Vincent Tran, Dallen James, Scott Quimby

Annual Research Symposium

Alcohol is associated with increased mortality and morbidity. Pulmonary infections with opportunistic pathogens can occur in healthy humans; however, hazardous alcohol exposure like binge alcohol intoxication (≥ 0.08% BAC) is a major risk factor. We’ve previously investigated the efficacy of Sulforaphane (SFN) prophylaxis in protecting human and murine alveolar macrophage function against opportunistic infections when exposed to binge alcohol conditions in vitro. However, an in vivo model investigating SFN and hazardous alcohol exposure in the context of infection is not well understood. The aim of this study is to 1) establish a G. mellonella larvae model by determining the LD50 …

A Targeted Gene Expression Biomarker Predicts Clinic Low-Risk Meningioma Recurrence, Minh P Nguyen, Ramin A Morshed, Mark W Youngblood, Haley K Perlow, Calixto-Hope G Lucas, Akash J Patel, Joshua D Palmer, Craig M Horbinski, Stephen T Magill, William C Chen, David R Raleigh

Duncan NRI Faculty and Staff Publications

Background: Despite reassuring clinical and histological features, low-grade meningiomas can recur after surgery. Targeted gene expression profiling improves risk stratification of meningiomas, but the utility of this approach for clinical low-risk meningiomas is incompletely understood.

Methods: This was a multicenter retrospective cohort study of meningiomas from patients who were treated at 4 institutions from 1992 to 2023. Adult patients with newly diagnosed or recurrent World Health Organization (WHO) grade 1 meningiomas that were treated with gross total resection (GTR) or subtotal resection (STR), or newly diagnosed WHO grade 2 meningiomas that were treated with GTR, were included. A 34-gene expression …

Red Meat Consumption And Hypertension: An Updated Review, Tara S Allen, Michael Najem, Alexis C Wood, Danielle J Lee, Lorena S Pacheco, Lori B Daniels, Matthew A Allison

Faculty, Staff and Students Publications

PURPOSE OF REVIEW: Hypertension (HTN) is a major risk factor for cardiovascular diseases (CVD). The global prevalence of HTN and related CVD mortality continues to rise. The development of HTN is influenced by genetic predisposition and modifiable risk factors, including diet. One area of ongoing debate is the relationship between red meat consumption and risk of HTN.

RECENT FINDINGS: Processed red meat has become increasingly implicated in the pathogenesis and morbidity of HTN, though randomized control trials comparing HTN-related outcomes associated with red meat subtypes have yielded heterogenous results. This review summarizes the existing relevant literature and highlights the methodological …

Characteristics And Outcomes Of Adults Hospitalized With Respiratory Syncytial Virus, Brian S. Shaw, Cara Slaton, Ian P. Murphy, Michael Mcalister, Daniel Egan, Kwabena Ayesu

The University of Louisville Journal of Respiratory Infections

Background: Respiratory syncytial virus (RSV) is a negative sense single-stranded RNA virus (ssRNA) that primarily causes respiratory infections in both children and older adults. We examined clinical characteristics and outcomes of hospitalized adult patients who tested positive for RSV.

Methods: This was a multicenter, retrospective, descriptive study that examined adult patients admitted with a positive RSV test over two years across eight hospitals in Orlando, Florida.

Results: A total of 120 patients were included, of which 88 (73%) were 60 years old and older. Overall, patients with RSV infection were caucasian (62%) with a median age of 70 years and …

Glucagon-Like Peptide-1 Receptor Agonists Improve Metabolic Dysfunction-Associated Steatotic Liver Disease Outcomes, Brandon Havranek, Rebecca Loh, Beatriz Torre, Rachel Redfield, Dina Halegoua-De Marzio

Division of Gastroenterology and Hepatology Faculty Papers

Metabolic dysfunction-associated steatotic liver disease (MASLD) is the leading cause of chronic liver disease and is associated with significant cardiovascular morbidity and mortality. This study aims to investigate the association of glucagon-like peptide-1 (GLP-1) agonists with major cardiovascular events, clinically significant portal hypertension events, and all-cause mortality in patients with MASLD. A large, population-based retrospective cohort study was conducted using the TriNetX platform, which provided real-time access to electronic health records of 634,265 adult patients with MASLD/MASH. Propensity score matching (PSM) was employed to create two cohorts: A GLP-1 agonists group and a control group without GLP-1 agonists usage. Hazard …

A Deep Learning-Based System For Automatic Detection Of Emesis With High Accuracy In Suncus Murinus, Zengbing Lu, Yimeng Qiao, Xiaofei Huang, Dexuan Cui, Julia Y H Liu, Man Piu Ngan, Luping Liu, Zhixin Huang, Zi-Tong Li, Lingqing Yang, Aleena Khalid, Yingyi Deng, Sze Wa Chan, Longlong Tu, John A Rudd

Children’s Nutrition Research Center Staff Publications

Quantifying emesis in Suncus murinus (S. murinus) has traditionally relied on direct observation or reviewing recorded behaviour, which are laborious, time-consuming processes that are susceptible to operator error. With rapid advancements in deep learning, automated animal behaviour quantification tools with high accuracy have emerged. In this study, we pioneere the use of both three-dimensional convolutional neural networks and self-attention mechanisms to develop the Automatic Emesis Detection (AED) tool for the quantification of emesis in S. murinus, achieving an overall accuracy of 98.92%. Specifically, we use motion-induced emesis videos as training datasets, with validation results demonstrating an accuracy of 99.42% for …

Contrast-Enhanced Magnetic Resonance Imaging Based Calf Muscle Perfusion And Machine Learning In Peripheral Artery Disease, Bijen Khagi, Tatiana Belousova, Christina M Short, Addison A Taylor, Jean Bismuth, Dipan J Shah, Gerd Brunner

Faculty, Staff and Students Publications

Peripheral artery disease (PAD) remains underdiagnosed and undertreated and is associated with an increased risk for adverse cardiovascular outcomes. Imaging provides an approach to identifying patients with PAD. However, the role of integrating imaging with machine learning to identify PAD patients and potentially assess disease severity remains understudied. A total of 56 participants, including 36 PAD patients with intermittent claudication and 20 matched controls, underwent contrast-enhanced magnetic resonance imaging (CE-MRI) calf muscle perfusion scanning. CE-MRI-derived dynamic muscle perfusion maps were developed to quantify alterations of the microvascular circulation in the calf muscles based on voxel contrast enhancement. These dynamic muscle …

Classification Of Non-Tcga Cancer Samples To Tcga Molecular Subtypes Using Compact Feature Sets, Kyle Ellrott, Christopher K Wong, Christina Yau, Mauro A A Castro, Jordan A Lee, Brian J Karlberg, Jasleen K Grewal, Vincenzo Lagani, Bahar Tercan, Verena Friedl, Toshinori Hinoue, Vladislav Uzunangelov, Lindsay Westlake, Xavier Loinaz, Ina Felau, Peggy I Wang, Anab Kemal, Samantha J Caesar-Johnson, Ilya Shmulevich, Alexander J Lazar, Ioannis Tsamardinos, Katherine A Hoadley, Cancer Genome Atlas Analysis Network, A Gordon Robertson, Theo A Knijnenburg, Christopher C Benz, Joshua M Stuart, Jean C Zenklusen, Andrew D Cherniack, Peter W Laird

Faculty, Staff and Student Publications

Molecular subtypes, such as defined by The Cancer Genome Atlas (TCGA), delineate a cancer's underlying biology, bringing hope to inform a patient's prognosis and treatment plan. However, most approaches used in the discovery of subtypes are not suitable for assigning subtype labels to new cancer specimens from other studies or clinical trials. Here, we address this barrier by applying five different machine learning approaches to multi-omic data from 8,791 TCGA tumor samples comprising 106 subtypes from 26 different cancer cohorts to build models based upon small numbers of features that can classify new samples into previously defined TCGA molecular subtypes-a …

Sex And Outcomes Of Patients With Microsatellite Instability-High And Braf V600e Mutated Metastatic Colorectal Cancer Receiving Immune Checkpoint Inhibitors, Vincenzo Nasca, Joseph Zhao, Javier Ros, Sara Lonardi, Koen Zwart, Romain Cohen, Marwan Fakih, Priya Jayachandran, Jeanine M L Roodhart, Jeroen Derksen, Rossana Intini, Francesca Bergamo, Giacomo Mazzoli, Filippo Ghelardi, Marta Ligero, Jitendra Jonnagaddala, Nicholas Hawkins, Robyn L Ward, Durgesh Wankhede, Hermann Brenner, Michael Hoffmeister, Marco Vitellaro, Lisa Salvatore, Claire Gallois, Pierre Laurent-Puig, Chiara Cremolini, Michael J Overman, Julien Taieb, David Tougeron, Thierry Andre, Jakob Nikolas Kather, Raghav Sundar, Javier Carmona, Elena Elez, Miriam Koopman, Filippo Pietrantonio

Faculty, Staff and Student Publications

Background: Immune checkpoint inhibitors (ICIs) are the gold standard therapy in patients with deficient mismatch repair (dMMR)/microsatellite instability-high (MSI-H) metastatic colorectal cancer (mCRC). A significant proportion of patients show resistance, making the identification of determinants of response crucial. Growing evidence supports the role of sex in determining susceptibility to anticancer therapies, but data is lacking for patients with MSI-H CRC.

Methods: In this real-world cohort comprising 624 patients with MSI-H mCRC receiving ICIs, we investigated the impact of sex on patients' outcomes, overall and according to RAS-BRAF mutational status or type of treatment (anti-PD-(L)1 with or without anti-CTLA-4 agents). We …

Tigit Inhibitor M6223 As Monotherapy Or In Combination With Bintrafusp Alfa In Patients With Advanced Solid Tumors: A First-In-Human, Phase 1, Dose-Escalation Trial, Aung Naing, Meredith Mckean, Anthony Tolcher, Anja Victor, Ping Hu, Wei Gao, Marco A F Nogueira Filho, Thomas Kitzing, Stephan Gleicher, Daniel Holland, Emilia Richter, Keyvan Tadjalli-Mehr, Lillian L Siu

Faculty, Staff and Student Publications

Background: M6223 is an intravenous (IV), Fc-competent, fully human, antagonistic, anti-T cell immunoreceptor with immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domains (TIGIT) antibody. Bintrafusp alfa (BA) is a bifunctional fusion protein that simultaneously blocks nonredundant immunosuppressive TGF-β and PD-(L)1 pathways.

Methods: This first-in-human, dose-escalation study in patients with advanced solid tumors (N=58; aged ≥18 years, ECOG PS≤1) evaluated M6223 alone (Part 1A, n=40; M6223 10-2400 mg every 2 weeks, n=32; M6223 2400 mg every 3 weeks, n=8) or with BA (Part 1B, n=18; M6223 300-1600 mg with BA 1200 mg; both every 2 weeks, intravenous). Primary objectives were safety, tolerability, …

Long-Read Sequencing Of 945 Han Individuals Identifies Structural Variants Associated With Phenotypic Diversity And Disease Susceptibility, Jiao Gong, Huiru Sun, Kaiyuan Wang, Yanhui Zhao, Yechao Huang, Qinsheng Chen, Hui Qiao, Yang Gao, Jialin Zhao, Yunchao Ling, Ruifang Cao, Jingze Tan, Qi Wang, Yanyun Ma, Jing Li, Jingchun Luo, Sijia Wang, Jiucun Wang, Guoqing Zhang, Shuhua Xu, Feng Qian, Fang Zhou, Huiru Tang, Dali Li, Chinese Pangenome Consortium (Cpc), Fritz J Sedlazeck, Li Jin, Yuting Guan, Shaohua Fan

Faculty, Staff and Students Publications

Genomic structural variants (SVs) are a major source of genetic diversity in humans. Here, through long-read sequencing of 945 Han Chinese genomes, we identify 111,288 SVs, including 24.56% unreported variants, many with predicted functional importance. By integrating human population-level phenotypic and multi-omics data as well as two humanized mouse models, we demonstrate the causal roles of two SVs: one SV that emerges at the common ancestor of modern humans, Neanderthals, and Denisovans in GSDMD for bone mineral density and one modern-human-specific SV in WWP2 impacting height, weight, fat, craniofacial phenotypes and immunity. Our results suggest that the GSDMD SV could …

Hidradenitis Suppurativa Is Associated With An Increased Risk Of Adverse Cardiac Events And All-Cause Mortality, Thomas Z. Rohan, Ramsay Hafer, Teresa Duong, Rishob Dasgupta, Sherry Yang

Department of Dermatology and Cutaneous Biology Faculty Papers

Background: Hidradenitis suppurativa (HS) has been previously associated with greater rates of major adverse cardiac events (MACEs) compared to the general population. This study aims to better elucidate the association between HS, MACEs, and other cardiovascular diseases. Methods: We utilized TriNetX, a global database of electronic health records, to conduct a retrospective cohort study. HS patients were matched on demographic and cardiovascular disease risk factors to both healthy and psoriasis groups as controls. Results: After adjusting for cardiovascular disease risk factors, HS patients had a relative risk (RR) (95% CI) of 2.06 (1.83-2.32) for myocardial infarction, 1.62 …

Neuronal Network Activation Induced By Forniceal Deep Brain Stimulation In Mice, Bin Tang, Zhenyu Wu, Qi Wang, Jianrong Tang

Faculty, Staff and Students Publications

Background: The fimbria-fornix is a nerve fiber bundle that connects various structures of the limbic system in the brain and plays a key role in cognition. It has become a major target of deep brain stimulation (DBS) to treat memory impairment in both dementia patients and animal models of neurological diseases. Previously, we have reported the beneficial memory effects of chronic forniceal DBS in mouse models of intellectual disability disorders. In Rett syndrome and CDKL5 deficiency disorder models, DBS strengthens hippocampal synaptic plasticity, reduces dentate inhibitory transmission or increases adult hippocampal neurogenesis that aids memory. However, the underlying neuronal circuitry …