Digital Commons Network^™

Pre-Left Ventricular Assist Device Endoscopic Evaluation Does Not Reduce The Risk Of Later Gastrointestinal Bleeding: A Multicenter Study, Jiahao Peng, Samanthika Devalaraju, Mohamed Azab, William T Cates, Molly Stone, Jonathan Reichstein, Sneha Shaha, Subhasis Chatterjee, Andrew B Civitello, Mourad H Senussi, B Joseph Elmunzer, Michael Volk, Wasseem Skef

Faculty, Staff and Students Publications

BACKGROUND: Gastrointestinal bleeding (GIB) is a common complication after placement of a left ventricular assist device (LVAD). Some institutions attempt to mitigate post-LVAD GIB using preoperative endoscopy. Our study evaluated whether preoperative endoscopy was associated with a lower risk of post-LVAD GIB.

METHODS: This was a multicenter cohort study of patients who underwent LVAD insertion from 2010-2019 at 3 academic sites. A total of 398 study participants were categorized based on whether they underwent preoperative endoscopy or not. The follow-up period was 1 year and the primary outcome was GIB. Secondary outcomes were severe bleeding and intraprocedural complications.

RESULTS: A …

Scientific Impact Of The National Birth Defects Prevention Network Multistate Collaborative Publications, Jacqueline T Bascom, Sara B Stephens, Philip J Lupo, Mark A Canfield, Russell S Kirby, Eirini Nestoridi, Jason L Salemi, Cara T Mai, Wendy N Nembhard, Nina E Forestieri, Paul A Romitti, Amanda M St Louis, A J Agopian

Faculty, Staff and Students Publications

BACKGROUND: Given the lack of a national, population-based birth defects surveillance program in the United States, the National Birth Defects Prevention Network (NBDPN) has facilitated important studies on surveillance, research, and prevention of major birth defects. We sought to summarize NBDPN peer-reviewed publications and their impact.

METHODS: We obtained and reviewed a curated list of 49 NBDPN multistate collaborative publications during 2000-2022, as of December 31, 2022. Each publication was reviewed and classified by type (e.g., risk factor association analysis). Key characteristics of study populations and analytic approaches used, along with publication impact (e.g., number of citations), were tabulated.

RESULTS: …

Scan-Less Microscopy Based On Acousto-Optic Encoded Illumination, Andrea Marchese, Pietro Ricci, Peter Saggau, Martí Duocastella

Faculty, Staff and Students Publications

Several optical microscopy methods are now available for characterizing scientific and industrial processes at sub-micron resolution. However, they are often ill-suited for imaging rapid events. Limited by the trade-off between camera frame-rate and sensitivity, or the need for mechanical scanning, current microscopes are optimized for imaging at hundreds of frames-per-second (fps), well-below what is needed in processes such as neuronal signaling or moving parts in manufacturing lines. Here, we present a scan-less technology that allows sub-micrometric imaging at thousands of fps. It is based on combining a single-pixel camera with parallelized encoded illumination. We use two acousto-optic deflectors (AODs) placed …

Inference Of Phylogenetic Trees Directly From Raw Sequencing Reads Using Read2tree, David Dylus, Adrian Altenhoff, Sina Majidian, Fritz J Sedlazeck, Christophe Dessimoz

Faculty, Staff and Students Publications

Current methods for inference of phylogenetic trees require running complex pipelines at substantial computational and labor costs, with additional constraints in sequencing coverage, assembly and annotation quality, especially for large datasets. To overcome these challenges, we present Read2Tree, which directly processes raw sequencing reads into groups of corresponding genes and bypasses traditional steps in phylogeny inference, such as genome assembly, annotation and all-versus-all sequence comparisons, while retaining accuracy. In a benchmark encompassing a broad variety of datasets, Read2Tree is 10-100 times faster than assembly-based approaches and in most cases more accurate-the exception being when sequencing coverage is high and reference …

Idppub: Illuminating The Dark Phosphoproteome Through Pubmed Mining, Sara R Savage, Yaoyun Zhang, Eric J Jaehnig, Yuxing Liao, Zhiao Shi, Huy Anh Pham, Hua Xu, Bing Zhang

Faculty, Staff and Students Publications

Global phosphoproteomics experiments quantify tens of thousands of phosphorylation sites. However, data interpretation is hampered by our limited knowledge on functions, biological contexts, or precipitating enzymes of the phosphosites. This study establishes a repository of phosphosites with associated evidence in biomedical abstracts, using deep learning-based natural language processing techniques. Our model for illuminating the dark phosphoproteome through PubMed mining (IDPpub) was generated by fine-tuning BioBERT, a deep learning tool for biomedical text mining. Trained using sentences containing protein substrates and phosphorylation site positions from 3000 abstracts, the IDPpub model was then used to extract phosphorylation sites from all MEDLINE abstracts. …

Age-Associated Temporal Decline In Butyrate-Producing Bacteria Plays A Key Pathogenic Role In The Onset And Progression Of Neuropathology And Memory Deficits In 3×Tg-Ad Mice, Paula M Chilton, Smita S Ghare, Benjamin T Charpentier, Scott A Myers, Aakarsha V Rao, Joseph F Petrosino, Kristi L Hoffman, John C Greenwell, Neetu Tyagi, Jyotirmaya Behera, Yali Wang, Lucy J Sloan, Jingwen Zhang, Christopher B Shields, Gregory E Cooper, Leila Gobejishvili, Scott R Whittemore, Craig J Mcclain, Shirish S Barve

Faculty, Staff and Students Publications

Alterations in the gut-microbiome-brain axis are increasingly being recognized to be involved in Alzheimer's disease (AD) pathogenesis. However, the functional consequences of enteric dysbiosis linking gut microbiota and brain pathology in AD progression remain largely undetermined. The present work investigated the causal role of age-associated temporal decline in butyrate-producing bacteria and butyrate in the etiopathogenesis of AD. Longitudinal metagenomics, neuropathological, and memory analyses were performed in the 3×Tg-AD mouse model. Metataxonomic analyses showed a significant temporal decline in the alpha diversity marked by a decrease in butyrate-producing bacterial communities and a concurrent reduction in cecal butyrate production. Inferred metagenomics analysis …

Inter And Intra-Host Diversity Of Rsv In Hematopoietic Stem Cell Transplant Adults With Normal And Delayed Viral Clearance, Vasanthi Avadhanula, Daniel Paiva Agustinho, Vipin Kumar Menon, Roy F Chemaly, Dimpy P Shah, Xiang Qin, Anil Surathu, Harshavardhan Doddapaneni, Donna M Muzny, Ginger A Metcalf, Sara Javornik Cregeen, Richard A Gibbs, Joseph F Petrosino, Fritz J Sedlazeck, Pedro A Piedra

Faculty, Staff and Students Publications

Respiratory syncytial virus (RSV) infection in immunocompromised individuals often leads to prolonged illness, progression to severe lower respiratory tract infection, and even death. How the host immune environment of the hematopoietic stem cell transplant (HCT) adults can affect viral genetic variation during an acute infection is not understood well. In the present study, we performed whole genome sequencing of RSV/A or RSV/B from samples collected longitudinally from HCT adults with normal (<14 >days) and delayed (≥14 days) RSV clearance who were enrolled in a ribavirin trial. We determined the inter-host and intra-host genetic variation of RSV and the effect of …

Comparison Of Four Protocols For In Vitro Differentiation Of Human Embryonic Stem Cells Into Trophoblast Lineages By Bmp4 And Dual Inhibition Of Activin/Nodal And Fgf2 Signaling, Zahra Anvar, Imen Chakchouk, Momal Sharif, Sangeetha Mahadevan, Li Su, Swathi Anikar, Fatemeh Alavi Naini, Alloysius Budi Utama, Ignatia B Van Den Veyver

Faculty, Staff and Students Publications

Human embryonic stem cells (hESCs) cultured in media containing bone morphogenic protein 4 (BMP4; B) differentiate into trophoblast-like cells. Supplementing media with inhibitors of activin/nodal signaling (A83-01) and of fibroblast growth factor 2 (PD173074) suppresses mesoderm and endoderm formation and improves specification of trophoblast-like lineages, but with variable effectiveness. We compared differentiation in four BMP4-containing media: mTeSR1-BMP4 only, mTeSR1-BAP, basal medium with BAP (basal-BAP), and a newly defined medium, E7-BAP. These media variably drive early differentiation towards trophoblast-like lineages with upregulation of early trophoblast markers CDX2 and KRT7 and downregulation of pluripotency markers (OCT4 and NANOG). As expected, based on …

The Uterine Secretome Initiates Growth Of Gynecologic Tissues In Ectopic Locations, Jan Sunde, Morgan Wasickanin, Tiffany A Katz, Laurel Gillette, Sanam Bidadi, Derek O'Neil, Ramya Masand, Richard O Burney, Kathleen A Pennington

Faculty, Staff and Students Publications

Endosalpingiosis (ES) and endometriosis (EM) refer to the growth of tubal and endometrial epithelium respectively, outside of their site of origin. We hypothesize that uterine secretome factors drive ectopic growth. To test this, we developed a mouse model of ES and EM using tdTomato (tdT) transgenic fluorescent mice as donors. To block implantation factors, progesterone knockout (PKO) tdT mice were created. Fluorescent lesions were present after oviduct implantation with and without WT endometrium. Implantation was increased (p<0.05) when tdt oviductal tissue was implanted with endometrium compared to oviductal tissue alone. Implantation was reduced (p<0.0005) in animals implanted with minced tdT oviductal tissue with PKO tdT endometrium compared to WT endometrium. Finally, oviductal tissues was incubated with and without a known implantation factor, leukemia inhibitory factor (LIF) prior to and during implantation. LIF promoted lesion implantation. In conclusion, endometrial derived implantation factors, such as LIF, are necessary to initiate ectopic tissue growth. We have developed an animal model of ectopic growth of gynecologic tissues in a WT mouse which will potentially allow for development of new prevention and treatment modalities.

Tremor In Cervical Dystonia, Sinem Balta Beylergil, Krishna Nikhil Mukunda, Mohamed Elkasaby, Joel S Perlmutter, Stewart Factor, Tobias Bäumer, Jeanne Feurestein, Erika Shelton, Steven Bellows, Joseph Jankovic, Abhimanyu Mahajan, Tila Wamer-Rosen, Stephen G Reich, Aparna Wagle Shukla, Irene Malaty, Alberto Espay, Kevin Duque, Mark S Ledoux, Rachel Saunders-Pullman, Katherine Leaver, Samuel Frank, Alexander Pantelyat, Victor Fung, Sarah Pirio Richardson, Brian Berman, Natividad Stover, Andres Deik, William Ondo, Christopher Groth, Hyder A Jinnah, Aasef G Shaikh

Faculty, Staff and Students Publications

BACKGROUND: Cervical dystonia (CD) is the most common form of focal dystonia encountered in the clinic. Approximately one-third of CD patients have co-existing tremor in the head and hands. Assessment of tremor as regular or irregular in context of its oscillation trajectory, frequency, and amplitude is a major clinical challenge and can confound the diagnosis of CD. The misdiagnosis may lead to therapeutic failures, poor quality of life, and poor utilization of medical and financial resources.

METHODS: We analyzed the largest cohort of CD patients (

RESULTS: Out of 3,117 CD patients, 1,367 had neck tremor. The neck tremor was …

Adipose Tissue Lymphocytes And Obesity, Feng Gao, Benjamin Litchfield, Huaizhu Wu

Faculty, Staff and Students Publications

Obesity is associated with chronic inflammation in adipose tissue (AT), mainly evidenced by infiltration and phenotypic changes of various types of immune cells. Macrophages are the major innate immune cells and represent the predominant immune cell population within AT. Lymphocytes, including T cells and B cells, are adaptive immune cells and constitute another important immune cell population in AT. In obesity, CD8+ effector memory T cells, CD4+ Th1 cells, and B2 cells are increased in AT and promote AT inflammation, while regulatory T cells and Th2 cells, which usually function as immune regulatory or type 2 inflammatory cells, are reduced …

The Impact Of Race On Pancreatic Cancer Treatment And Survival In The Nationwide Veterans Affairs Healthcare System, Natalia Khalaf, Ann Xu, Theresa Nguyen Wenker, Jennifer R Kramer, Yan Liu, Hardeep Singh, Hashem B El-Serag, Fasiha Kanwal

Faculty, Staff and Students Publications

OBJECTIVES: Among patients with pancreatic cancer, studies show racial disparities at multiple steps of the cancer care pathway. Access to healthcare is a frequently cited cause of these disparities. It remains unclear if racial disparities exist in an integrated, equal access public system such as the Veterans Affairs healthcare system.

METHODS: We identified all patients diagnosed with pancreatic adenocarcinoma in the national Veterans Affairs Central Cancer Registry from January 2010 to December 2018. We examined the independent association between race and 3 endpoints: stage at diagnosis, receipt of treatment, and survival while adjusting for sociodemographic factors and medical comorbidities.

RESULTS: …

The Challenges And Opportunities Of Offering And Integrating Training In Clinical Molecular Genetics And Clinical Cytogenetics: A Survey Of Lgg Fellowship Program Directors, Joshua L Deignan, Vimla Aggarwal, Allen E Bale, Daniel B Bellissimo, Jessica K Booker, Yang Cao, Kristy R Crooks, Kristen L Deak, Daniela Del Gaudio, Birgit Funke, Nicole L Hoppman, Vanessa Horner, Robert B Hufnagel, Colleen Jackson-Cook, Prasad Koduru, Marco L Leung, Shibo Li, Pengfei Liu, Minjie Luo, Rong Mao, Heather Mason-Suares, Fady M Mikhail, Stephen R Moore, Rizwan C Naeem, Laura M Pollard, Elena A Repnikova, Lina Shao, Brandon M Shaw, Shashirekha Shetty, Teresa A Smolarek, Elizabeth Spiteri, Jessica Van Ziffle, Gail H Vance, Cindy L Vnencak-Jones, Eli S Williams

Faculty, Staff and Students Publications

PURPOSE: The specialty of Laboratory Genetics and Genomics (LGG) was created in 2017 in an effort to reflect the increasing convergence in technologies and approaches between clinical molecular genetics and clinical cytogenetics. However, there has not yet been any formal evaluation of the merging of these disciplines and the challenges faced by Program Directors (PDs) tasked with ensuring the successful training of laboratory geneticists under the new model.

METHODS: An electronic multi-question Qualtrics survey was created and was sent to the PD for each of the Accreditation Council for Graduate Medical Education-accredited LGG fellowship programs at the time. The data …

Continuing Education And Professional Development: Unifying Opportunities For Genetic Counselors Globally, Kathleen D Valverde, Tiffiney R Hartman, Sara L Reichert, Robin L Bennett, Martha Dudek, Debra Duquette, Daniel Riconda, Nancy J Cox, Gail P Jarvik, Sarah H Elsea, Elizabeth M Mcnally, Kim C Worley, Daniel J Rader

Faculty, Staff and Students Publications

No abstract provided.

Fam20a: A Potential Diagnostic Biomarker For Lung Squamous Cell Carcinoma, Yalin Zhang, Qin Sun, Yangbo Liang, Xian Yang, Hailian Wang, Siyuan Song, Yi Wang, Yong Feng

Faculty, Staff and Students Publications

Background: Lung squamous cell carcinoma (LUSC) ranks among the carcinomas with the highest incidence and dismal survival rates, suffering from a lack of effective therapeutic strategies. Consequently, biomarkers facilitating early diagnosis of LUSC could significantly enhance patient survival. This study aims to identify novel biomarkers for LUSC.

Methods: Utilizing the TCGA, GTEx, and CGGA databases, we focused on the gene encoding Family with Sequence Similarity 20, Member A (FAM20A) across various cancers. We then corroborated these bioinformatic predictions with clinical samples. A range of analytical tools, including Kaplan-Meier, MethSurv database, Wilcoxon rank-sum, Kruskal-Wallis tests, Gene Set Enrichment Analysis, …

Bivalirudin Stability In Citrated Plasma And Citrated Whole Blood, Karen Bruzdoski, Vadim Kostousov, Jun Teruya

Faculty, Staff and Students Publications

No abstract provided.

Advances In Nanoprobes For Molecular Mri Of Alzheimer’S Disease, Parag Parekh, Andrew A Badachhape, Eric A Tanifum, Ananth V Annapragada, Ketan B Ghaghada

Faculty, Staff and Students Publications

Alzheimer's disease is the most common cause of dementia and a leading cause of mortality in the elderly population. Diagnosis of Alzheimer's disease has traditionally relied on evaluation of clinical symptoms for cognitive impairment with a definitive diagnosis requiring post-mortem demonstration of neuropathology. However, advances in disease pathogenesis have revealed that patients exhibit Alzheimer's disease pathology several decades before the manifestation of clinical symptoms. Magnetic resonance imaging (MRI) plays an important role in the management of patients with Alzheimer's disease. The clinical availability of molecular MRI (mMRI) contrast agents can revolutionize the diagnosis of Alzheimer's disease. In this article, we …

Moving From Conventional To Adaptive Risk Stratification For Oropharyngeal Cancer, Vlad C Sandulache, R Parker Kirby, Stephen Y Lai

Faculty, Staff and Students Publications

Oropharyngeal cancer (OPC) poses a complex therapeutic dilemma for patients and oncologists alike, made worse by the epidemic increase in new cases associated with the oncogenic human papillomavirus (HPV). In a counterintuitive manner, the very thing which gives patients hope, the high response rate of HPV-associated OPC to conventional chemo-radiation strategies, has become one of the biggest challenges for the field as a whole. It has now become clear that for ~30-40% of patients, treatment intensity could be reduced without losing therapeutic efficacy, yet substantially diminishing the acute and lifelong morbidity resulting from conventional chemotherapy and radiation. At the same …

Co-Expression Of Prepulse Inhibition And Schizophrenia Genes In The Mouse And Human Brain, Lillian Garrett, Dietrich Trümbach, Donghyung Lee, Silvia Mandillo, Rodney Samaco, Ann M Flenniken, Michelle Stewart, Impc Consortium, Jacqueline K White, Colin Mckerlie, Lauryl M J Nutter, Igor Vukobradovic, Surabi Veeraragavan, Lisa Yuva, Jason D Heaney, Mary E Dickinson, Hamid Meziane, Yann Hérault, Sara Wells, K C Kent Lloyd, Lynette Bower, Louise Lanoue, Dave Clary, Annemarie Zimprich, Valerie Gailus-Durner, Helmut Fuchs, Steve D M Brown, Elissa J Chesler, Wolfgang Wurst, Martin Hrabě De Angelis, Sabine M Hölter

Faculty, Staff and Students Publications

Schizophrenia is a complex psychiatric disorder with genetic and phenotypic heterogeneity. Accumulating rare and genome-wide association study (GWAS) common risk variant information has yet to yield robust mechanistic insight. Leveraging large-scale gene deletion mouse phenomic data thus has potential to functionally interrogate and prioritize human disease genes. To this end, we applied a cross-species network-based approach to parse an extensive mouse gene set (188 genes) associated with disrupted prepulse inhibition (PPI), a Schizophrenia endophenotype. Integrating PPI genes with high-resolution mouse and human brain transcriptomic data, we identified functional and disease coherent co-expression modules through hierarchical clustering and weighted gene co-expression …

Editorial: Symmetry As A Guiding Principle In Artificial And Brain Neural Networks, Volume Ii, Fabio Anselmi, Ankit B Patel

Faculty, Staff and Students Publications

No abstract provided.

Fluoxetine And Sertraline Inhibit Height Growth And Growth Hormone Signaling During Puberty, Chadi Calarge, Chima Amushie, Stephanie Dinh, James A Mills, Sridevi Devaraj, Griselda Barba-Villalobos, Jacqueline Nguyen, Jose M Garcia, Stephanie Sisley, Fida Bacha, Babette Zemel

Faculty, Staff and Students Publications

Purpose: The aim of this study was to examine the effect of fluoxetine and sertraline on height growth and insulin-like growth factor-1 (IGF-1) during puberty.

Methods: In this 6-month cohort study, electronic medical records were used to identify 8- to 15-year-old participants, within 1 month of starting fluoxetine (n = 39) or sertraline (n = 27), and sexual maturation stages 2 to 4 were confirmed. Conditions that interfere with height growth led to exclusion. Participants underwent anthropometric assessments and phlebotomy. Healthy, unmedicated children (n = 36) also provided anthropometric data.

Results: After the baseline height Z-score, sex, Tanner stage, daily …

High-Fat Diets Promote Peritoneal Inflammation And Augment Endometriosis-Associated Abdominal Hyperalgesia, Tristin Herup-Wheeler, Mingxin Shi, Madeleine E Harvey, Chandni Talwar, Ramakrishna Kommagani, James A Maclean, Kanako Hayashi

Faculty, Staff and Students Publications

Immune dysfunction is one of the central components in the development and progression of endometriosis by establishing a chronic inflammatory environment. Western-style high-fat diets (HFD) have been linked to greater systemic inflammation to cause metabolic and chronic inflammatory diseases, and are also considered an environmental risk factor for gynecologic diseases. Here, we aimed to examine how HFD cause an inflammatory environment in endometriosis and discern their contribution to endometriotic-associated hyperalgesia. Our results showed that HFD-induced obesity enhanced abdominal hyperalgesia that was induced by endometriotic lesions. Peritoneal inflammatory macrophages and cytokine levels increased by lesion induction were elevated by chronic exposure …

Pharmacological Inhibition Of The Map2k7 Kinase In Human Disease, H Daniel Lacorazza

Faculty, Staff and Students Publications

The MAP2K7 signaling pathway activates the c-Jun NH2-terminal protein kinase (JNK) in response to stress signals, such as inflammatory cytokines, osmotic stress, or genomic damage. While there has been interest in inhibiting JNK due to its involvement in inflammatory processes and cancer, there is increasing focus on developing MAP2K7 inhibitors to enhance specificity when MAP2K7 activation is associated with disease progression. Despite some progress, further research is needed to fully comprehend the role of MAP2K7 in cancer and assess the potential use of kinase inhibitors in cancer therapy. This review examines the role of MAP2K7 in cancer and the development …

Genetic Variation Between Small Bowel And Colon-Predominant Crohn's Disease, Halee Patel, R Alan Harris, Justin H Qian, Numan Oezguen, Ashleigh Watson, Reka G Szigeti, Stanley Cho, Wenly Ruan, Savini Britto, Antone Opekun, Geoffrey Preidis, Richard Kellermayer

Faculty, Staff and Students Publications

No abstract provided.

Safety And Efficacy Of Intravenous Sotalol Following Congenital Heart Surgery, Ellis Rochelson, Maria Gutierrez, Santiago O Valdés, Katherine Lemming, Taylor S Howard, Tam Dan N Pham, Christina Y Miyake, Vicken Asadourian, Raajen Patel, Jeffrey J Kim

Faculty, Staff and Students Publications

No abstract provided.

Anemia, Iron Deficiency, And Cause-Specific Mortality: The Atherosclerosis Risk In Communities Study, Ethan J Cannon, Jeffrey R Misialek, Leo F Buckley, Iman A F Aboelsaad, Christie M Ballantyne, John Leister, James S Pankow, Pamela L Lutsey

Faculty, Staff and Students Publications

Introduction: Anemia is a risk factor for all-cause mortality in older adults. Iron deficiency may also be associated with adverse outcomes, independent of its role in causing anemia. This study tested the hypotheses that anemia, and low ferritin among non-anemic participants, were associated with all-cause and cause-specific mortality in a community-based cohort of older adults.

Methods: Fasting blood was obtained from 5,070 ARIC participants (median age: 75 years) in 2011-2013. Anemia was defined by hemoglobin concentrations < 12 g/dL in women and < 13 g/dL in men. We classified 4,020 non-anemic participants by quartiles of plasma ferritin, measured by the SomaScan proteomics platform. Cox proportional hazards regression was used. Mortality was ascertained via phone calls with proxies as part of twice-yearly cohort follow-up, surveillance of local hospital discharge indexes, state death records, and linkage to the National Death Index.

Results: Of the total participants, 21% had anemia at baseline. Over a median of 7.5 years, there were 1,147 deaths, including 357 due to …

Generation And Characterization Of In Vitro Transcribed Mrna, Cristina Poveda, Yi-Lin Chen, Ulrich Strych

Faculty, Staff and Students Publications

Here we describe the in vitro preparation of mRNA from DNA templates, including setting up the transcription reaction, mRNA capping, and mRNA labeling. We then describe methods used for mRNA characterization, including UV and fluorescence spectrophotometry, as well as gel electrophoresis. Moreover, characterization of the in vitro transcribed RNA using the Bioanalyzer instrument is described, allowing a higher resolution analysis of the target molecules. For the in vitro testing of the mRNA molecules, we include protocols for the transfection of various primary cell cultures and the confirmation of translation by intracellular staining and western blotting.

Functional Genomics And Small Molecules In Mitochondrial Neurodevelopmental Disorders, Daniel G Calame, Lisa T Emrick

Faculty, Staff and Students Publications

Mitochondria are critical for brain development and homeostasis. Therefore, pathogenic variation in the mitochondrial or nuclear genome which disrupts mitochondrial function frequently results in developmental disorders and neurodegeneration at the organismal level. Large-scale application of genome-wide technologies to individuals with mitochondrial diseases has dramatically accelerated identification of mitochondrial disease-gene associations in humans. Multi-omic and high-throughput studies involving transcriptomics, proteomics, metabolomics, and saturation genome editing are providing deeper insights into the functional consequence of mitochondrial genomic variation. Integration of deep phenotypic and genomic data through allelic series continues to uncover novel mitochondrial functions and permit mitochondrial gene function dissection on an …

Diagnostic Value Of Soluble Urokinase-Type Plasminogen Activator Receptor In Patients With Acute Coronary Syndrome: A Systematic Review And Meta-Analysis, Michal Pruc, Iwona Jannasz, Damian Swieczkowski, Grzegorz Procyk, Aleksandra Gasecka, Zubaid Rafique, Francesco Chirico, Nicola Luigi Bragazzi, Milosz J Jaguszewski, Jaroslaw Wysocki, Lukasz Szarpak

Faculty, Staff and Students Publications

BACKGROUND: In contemporary clinical practice, there is an increasing need for new clinically relevant biomarkers potentially optimizing management strategies in patients with suspected acute coronary syndrome (ACS). This study aimed to determine the diagnostic utility of soluble urokinase-type plasminogen activator receptor (suPAR) levels in individuals with suspected ACS.

METHODS: A literature search was performed in Web of Science, PubMed, Scopus, and the Cochrane Central Register of Controlled Trials databases, for studies comparing suPAR levels among patients with and without ACS groups. The methodological quality of the included papers was assessed using the Newcastle-Ottawa Scale (NOS). A fixed-effects model was used …

Bi-Allelic Variants In Cep295 Cause Seckel-Like Syndrome Presenting With Primary Microcephaly, Developmental Delay, Intellectual Disability, Short Stature, Craniofacial And Digital Abnormalities, Niu Li, Yufei Xu, Hongzhu Chen, Jingqi Lin, Lama Alabdi, Mir Reza Bekheirnia, Guoqiang Li, Yoel Gofin, Nasim Bekheirnia, Eissa Faqeih, Lina Chen, Guoying Chang, Jie Tang, Ruen Yao, Tingting Yu, Xiumin Wang, Wei Fu, Qihua Fu, Yiping Shen, Fowzan S Alkuraya, Keren Machol, Jian Wang

Faculty, Staff and Students Publications

BACKGROUND: Pathogenic variants in the centrosome protein (CEP) family have been implicated in primary microcephaly, Seckel syndrome, and classical ciliopathies. However, most CEP genes remain unlinked to specific Mendelian genetic diseases in humans. We sought to explore the roles of CEP295 in human pathology.

METHODS: Whole-exome sequencing was performed to screen for pathogenic variants in patients with severe microcephaly. Patient-derived fibroblasts and CEP295-depleted U2OS and RPE1 cells were used to clarify the underlying pathomechanisms, including centriole/centrosome development, cell cycle and proliferation changes, and ciliogenesis. Complementary experiments using CEP295 mRNA were performed to determine the pathogenicity of the identified missense variant. …