Medical Specialties Commons^™

Hape (High-Altitude Pulmonary Edema) - Hiking Trip From Texas To Colorado Turns Into Nightmare, Eunbee Cho, Jessica Marcela Daza, Shakirat Ganiyu

Research Symposium

Introduction: High-altitude pulmonary edema (HAPE) is a non-cardiogenic pulmonary edema that typically occurs in lowlanders who ascend rapidly to altitudes greater than 2,500 meters to 3,000 meters (8,200 feet to 10,000 feet) above sea level. Risk factors for developing HAPE include a history of high altitude illness, rapid ascent without acclimatization, and comorbidities that impair ventilation or respiration. The southern part of Texas is one of the regions with the lowest altitude in the United States. It has proximity to Colorado, well known for its Rocky Mountain National Park, with elevations from 7,890 feet to 14,259 feet. This case presents …

Comparing Cognitive Tests And Smartphone-Based Assessment In 2 Us Community-Based Cohorts., Ileana De Anda-Duran, Preeti Sunderaraman, Edward Searls, Shirine Moukaled, Xuanyi Jin, Zachary Popp, Cody Karjadi, Phillip H Hwang, Huitong Ding, Sherral Devine, Ludy C Shih, Spencer Low, Honghuang Lin, Vijaya B Kolachalama, Lydia Bazzano, David J Libon, Rhoda Au

Rowan-Virtua School of Osteopathic Medicine Departmental Research

BACKGROUND: Smartphone-based cognitive assessments have emerged as promising tools, bridging gaps in accessibility and reducing bias in Alzheimer disease and related dementia research. However, their congruence with traditional neuropsychological tests and usefulness in diverse cohorts remain underexplored.

METHODS AND RESULTS: A total of 406 FHS (Framingham Heart Study) and 59 BHS (Bogalusa Heart Study) participants with traditional neuropsychological tests and digital assessments using the Defense Automated Neurocognitive Assessment (DANA) smartphone protocol were included. Regression models investigated associations between DANA task digital measures and a neuropsychological global cognitive

CONCLUSIONS: Our findings demonstrate that smartphone-based cognitive assessments exhibit concurrent validity with a …

Classification Of Colorectal Cancer Using Resnet And Efficientnet Models, Abhishek Ranjan, Priyanshu Srivastva, B Prabadevi, R Sivakumar, Rahul Soangra, Shamala K. Subramaniam

Physical Therapy Faculty Articles and Research

Introduction:

Cancer is one of the most prevalent diseases from children to elderly adults. This will be deadly if not detected at an earlier stage of the cancerous cell formation, thereby increasing the mortality rate. One such cancer is colorectal cancer, caused due to abnormal growth in the rectum or colon. Early screening of colorectal cancer helps to identify these abnormal growth and can exterminate them before they turn into cancerous cells.

Aim:

Therefore, this study aims to develop a robust and efficient classification system for colorectal cancer through Convolutional Neural Networks (CNNs) on histological images.

Methods:

Despite challenges in …

The Respiratory Enzyme Complex Rnf Is Vital For Metabolic Adaptation And Virulence In Fusobacterium Nucleatum, Timmie A Britton, Chenggang Wu, Yi-Wei Chen, Dana Franklin, Yimin Chen, Martha I Camacho, Truc T Luong, Asis Das, Hung Ton-That

Faculty, Staff and Student Publications

The Gram-negative oral pathobiont Fusobacterium nucleatum can traverse to extra-oral sites such as placenta and colon, promoting adverse pregnancy outcomes and colorectal cancer, respectively. How this anaerobe sustains many metabolically changing environments enabling its virulence potential remains unclear. Informed by our genome-wide transposon mutagenesis, we report here that the highly conserved Rhodobacter nitrogen-fixation (Rnf) complex, encoded by the rnfCDGEAB gene cluster, is key to fusobacterial metabolic adaptation and virulence. Genetic disruption of the Rnf complex via non-polar, in-frame deletion of rnfC (ΔrnfC) abrogates polymicrobial interaction (or coaggregation) associated with adhesin RadD and biofilm formation. The defect in coaggregation …

Development And Validation Of A Nomogram For Predicting Pulmonary Infection In Patients Receiving Immunosuppressive Drugs, Chuxuan Luo, Yue Zhang, Jiajie Zhang, Chen Jin, Xiaolan Ye, Yan Ren, Huajuan Shen, Maosheng Chen, Yiwen Li, Qiang He, Guangbiao Xu, Lina Shao

Faculty, Staff and Student Publications

Objective: Pulmonary infection (PI), a severe complication of immunosuppressive therapy, affects patients' prognosis. As part of this study, we aimed to construct a pulmonary infection prediction (PIP) model and validate it in patients receiving immunosuppressive drugs (ISDs). Methods: Totally, 7,977 patients being treated with ISDs were randomised 7:3 to the developing (n = 5,583) versus validation datasets (n = 2,394). Our predictive nomogram was established using the least absolute shrinkage and selection operator (LASSO) and multivariate COX regression analyses. With the use of the concordance index (C-index) and calibration curve, the prediction performance of the final model was …

Analysis Of Breast Cancer Mortality In The Us-1975 To 2019, Jennifer L Caswell-Jin, Liyang P Sun, Diego Munoz, Ying Lu, Yisheng Li, Hui Huang, John M Hampton, Juhee Song, Jinani Jayasekera, Clyde Schechter, Oguzhan Alagoz, Natasha K Stout, Amy Trentham-Dietz, Sandra J Lee, Xuelin Huang, Jeanne S Mandelblatt, Donald A Berry, Allison W Kurian, Sylvia K Plevritis

Faculty, Staff and Student Publications

IMPORTANCE: Breast cancer mortality in the US declined between 1975 and 2019. The association of changes in metastatic breast cancer treatment with improved breast cancer mortality is unclear.

OBJECTIVE: To simulate the relative associations of breast cancer screening, treatment of stage I to III breast cancer, and treatment of metastatic breast cancer with improved breast cancer mortality.

DESIGN, SETTING, AND PARTICIPANTS: Using aggregated observational and clinical trial data on the dissemination and effects of screening and treatment, 4 Cancer Intervention and Surveillance Modeling Network (CISNET) models simulated US breast cancer mortality rates. Death due to breast cancer, overall and by …

Expanded T Lymphocytes In The Cerebrospinal Fluid Of Multiple Sclerosis Patients Are Specific For Epstein-Barr-Virus-Infected B Cells, Assaf Gottlieb, H Phuong T Pham, Jerome G Saltarrelli, J William Lindsey

Faculty, Staff and Student Publications

Epstein-Barr virus (EBV) infection has long been associated with multiple sclerosis (MS), but the role of EBV in the pathogenesis of MS is not clear. Our hypothesis is that a major fraction of the expanded clones of T lymphocytes in the cerebrospinal fluid (CSF) are specific for autologous EBV-infected B cells. We obtained blood and CSF samples from eight relapsing-remitting patients in the process of diagnosis. We stimulated cells from the blood with autologous EBV-infected lymphoblastoid cell lines (LCL), EBV, varicella zoster virus, influenza, and candida and sorted the responding cells with flow cytometry after 6 d. We sequenced the …

In-Patient Evolution Of A High-Persister Escherichia Coli Strain With Reduced In Vivo Antibiotic Susceptibility, Joshua B Parsons, Ashelyn E Sidders, Amanda Z Velez, Blake M Hanson, Michelle Angeles-Solano, Felicia Ruffin, Sarah E Rowe, Cesar A Arias, Vance G Fowler, Joshua T Thaden, Brian P Conlon

Faculty, Staff and Student Publications

Gram-negative bacterial bloodstream infections (GNB-BSI) are common and frequently lethal. Despite appropriate antibiotic treatment, relapse of GNB-BSI with the same bacterial strain is common and associated with poor clinical outcomes and high healthcare costs. The role of persister cells, which are sub-populations of bacteria that survive for prolonged periods in the presence of bactericidal antibiotics, in relapse of GNB-BSI is unclear. Using a cohort of patients with relapsed GNB-BSI, we aimed to determine how the pathogen evolves within the patient between the initial and subsequent episodes of GNB-BSI and how these changes impact persistence. Using

Perioperative Toripalimab Plus Chemotherapy For Patients With Resectable Non-Small Cell Lung Cancer: The Neotorch Randomized Clinical Trial, Shun Lu, Wei Zhang, Lin Wu, Wenxiang Wang, Peng Zhang, Wentao Fang, Wenqun Xing, Qixun Chen, Lin Yang, Jiandong Mei, Lijie Tan, Xiaohong Sun, Shidong Xu, Xiaohua Hu, Guohua Yu, Dongliang Yu, Nong Yang, Yuping Chen, Jinlu Shan, Ligang Xing, Hui Tian, Xun Zhang, Ming Zhou, Haohui Fang, Guowu Wu, Yunpeng Liu, Minhua Ye, Lejie Cao, Jie Jiang, Xingya Li, Liangming Zhu, Danqing Li, Mingqiang Kang, Aihong Zhong, Keneng Chen, Nan Wu, Qian Sun, Haitao Ma, Kaican Cai, Changli Wang, Gen Lin, Kunshou Zhu, Yu Zhang, Xiaochun Zhang, Hong Hu, Wengang Zhang, Jun Chen, Zhixiong Yang, Xiaosheng Hang, Jian Hu, Yunchao Huang, Zhiye Zhang, Lumin Zhang, Liwei Zhang, Lunxu Liu, Dongmei Lin, Jie Zhang, Gang Chen, Yuan Li, Lei Zhu, Weihua Wang, Wenbo Yu, Dezhen Cao, Patricia Keegan, Sheng Yao

Faculty, Staff and Student Publications

IMPORTANCE: Adjuvant and neoadjuvant immunotherapy have improved clinical outcomes for patients with early-stage non-small cell lung cancer (NSCLC). However, the optimal combination of checkpoint inhibition with chemotherapy remains unknown.

OBJECTIVE: To determine whether toripalimab in combination with platinum-based chemotherapy will improve event-free survival and major pathological response in patients with stage II or III resectable NSCLC compared with chemotherapy alone.

DESIGN, SETTING, AND PARTICIPANTS: This randomized clinical trial enrolled patients with stage II or III resectable NSCLC (without EGFR or ALK alterations for nonsquamous NSCLC) from March 12, 2020, to June 19, 2023, at 50 participating hospitals in China. The …

Hidradenitis Suppurativa Disease Severity And Outcomes Among Black Patients From Low-Income Neighborhoods At A Tertiary Care Hospital: A Retrospective Review, Anna M. Catinis, Olivia A. Gioe, Caroline Savoie, Erika Rosen, Deborah Hilton

School of Medicine Faculty Publications

Hidradenitis suppurativa (HS) is a debilitating, inflammatory condition of apocrine sweat glands. Black patients are disproportionately affected, a finding largely attributed to lower socioeconomic status (SES) in the literature; yet, most HS studies include majority White cohorts. We present, to our knowledge, the first retrospective review of an entirely Black patient population living in low-income neighborhoods diagnosed with hidradenitis suppurativa (HS) to identify potentially modifiable factors related to disease severity and outcomes. We reviewed charts of Black patients with an encounter for HS from 2010-2020 in the New Orleans University Medical Center database. Hurley stage III (HSt III) disease was …

Overnight 1-Mg Dst Serum Cortisol In Various Stages Of Chronic Kidney Disease-Normative Data And Underlying Mechanisms, Robin Garg, Saba Samad Memon, Anurag Lila, Vijaya Sarathi, Priyanka Patil, Tukaram Jamale, Sreyashi Bose, Manjiri Karlekar, Virendra Patil, Nalini Shah, Tushar Bandgar

Faculty, Staff and Student Publications

CONTEXT: Data on the overnight 1 mg-dexamethasone suppression test (ONDST) in renal dysfunction are limited.

OBJECTIVE: We aim to determine the normative range of ONDST cortisol across chronic kidney disease (CKD) stages and reasons for its alteration.

METHODS: Prospectively, 180 CKD (30 each in G2-G5/5D) patients and 30 healthy controls underwent ONDST 8 Am serum cortisol (chemiluminescent immunoassay [CLIA]). In an exploratory cohort, 45 (15 each: G3b/G4, G5/G5D, and healthy controls) individuals' blood biochemistry for basal (8 Am) cortisol and adrenocorticotropin (ACTH), post-ONDST 8 Am dexamethasone, ACTH, cortisol (CLIA and liquid chromatography-tandem mass spectrometry), and 4 Pm cortisol was collected. …

Novel Pan-Err Agonists Ameliorate Heart Failure Through Enhancing Cardiac Fatty Acid Metabolism And Mitochondrial Function, Weiyi Xu, Cyrielle Billon, Hui Li, Andrea Wilderman, Lei Qi, Andrea Graves, Jernie Rae Dela Cruz Rideb, Yuanbiao Zhao, Matthew Hayes, Keyang Yu, Mckenna Losby, Carissa S Hampton, Christiana M Adeyemi, Seok Jae Hong, Eleni Nasiotis, Chen Fu, Tae Gyu Oh, Weiwei Fan, Michael Downes, Ryan D Welch, Ronald M Evans, Aleksandar Milosavljevic, John K Walker, Brian C Jensen, Liming Pei, Thomas Burris, Lilei Zhang

Faculty, Staff and Students Publications

BACKGROUND: Cardiac metabolic dysfunction is a hallmark of heart failure (HF). Estrogen-related receptors ERRα and ERRγ are essential regulators of cardiac metabolism. Therefore, activation of ERR could be a potential therapeutic intervention for HF. However, in vivo studies demonstrating the potential usefulness of ERR agonist for HF treatment are lacking, because compounds with pharmacokinetics appropriate for in vivo use have not been available.

METHODS: Using a structure-based design approach, we designed and synthesized 2 structurally distinct pan-ERR agonists, SLU-PP-332 and SLU-PP-915. We investigated the effect of ERR agonist on cardiac function in a pressure overload-induced HF model in vivo. We …

Kinase Inhibitor Pulldown Assay (Kip) For Clinical Proteomics, Alexander B Saltzman, Doug W Chan, Matthew V Holt, Junkai Wang, Eric J Jaehnig, Meenakshi Anurag, Purba Singh, Anna Malovannaya, Beom-Jun Kim, Matthew J Ellis

Faculty, Staff and Students Publications

Protein kinases are frequently dysregulated and/or mutated in cancer and represent essential targets for therapy. Accurate quantification is essential. For breast cancer treatment, the identification and quantification of the protein kinase ERBB2 is critical for therapeutic decisions. While immunohistochemistry (IHC) is the current clinical diagnostic approach, it is only semiquantitative. Mass spectrometry-based proteomics offers quantitative assays that, unlike IHC, can be used to accurately evaluate hundreds of kinases simultaneously. The enrichment of less abundant kinase targets for quantification, along with depletion of interfering proteins, improves sensitivity and thus promotes more effective downstream analyses. Multiple kinase inhibitors were therefore deployed as …

Gad65abs Are Not Associated With Beta-Cell Dysfunction In Patients With T2d In The Grade Study, Christiane S Hampe, Ali Shojaie, Barbara Brooks-Worrell, Sepideh Dibay, Kristina Utzschneider, Steven E Kahn, Mary E Larkin, Mary L Johnson, Naji Younes, Neda Rasouli, Cyrus Desouza, Robert M Cohen, Jean Y Park, Hermes J Florez, Willy Marcos Valencia, Robert Stempel, Jerry P Palmer, Ashok Balasubramanyam

Faculty, Staff and Students Publications

CONTEXT: Autoantibodies directed against the 65-kilodalton isoform of glutamic acid decarboxylase (GAD65Abs) are markers of autoimmune type 1 diabetes (T1D) but are also present in patients with Latent Autoimmune Diabetes of Adults and autoimmune neuromuscular diseases, and also in healthy individuals. Phenotypic differences between these conditions are reflected in epitope-specific GAD65Abs and anti-idiotypic antibodies (anti-Id) against GAD65Abs. We previously reported that 7.8% of T2D patients in the GRADE study have GAD65Abs but found that GAD65Ab positivity was not correlated with beta-cell function, glycated hemoglobin (HbA1c), or fasting glucose levels.

CONTEXT: In this study, we aimed to better characterize islet autoantibodies …

The Pan-Microbiome Profiling System Taxa4meta Identifies Clinical Dysbiotic Features And Classifies Diarrheal Disease, Qinglong Wu, Shyam Badu, Sik Yu So, Todd J Treangen, Tor C Savidge

Faculty, Staff and Students Publications

Targeted metagenomic sequencing is an emerging strategy to survey disease-specific microbiome biomarkers for clinical diagnosis and prognosis. However, this approach often yields inconsistent or conflicting results owing to inadequate study power and sequencing bias. We introduce Taxa4Meta, a bioinformatics pipeline explicitly designed to compensate for technical and demographic bias. We designed and validated Taxa4Meta for accurate taxonomic profiling of 16S rRNA amplicon data acquired from different sequencing strategies. Taxa4Meta offers significant potential in identifying clinical dysbiotic features that can reliably predict human disease, validated comprehensively via reanalysis of individual patient 16S data sets. We leveraged the power of Taxa4Meta's pan-microbiome …

Metabolomic Rewiring Promotes Endocrine Therapy Resistance In Breast Cancer, Songyeon Ahn, Jun Hyoung Park, Sandra L Grimm, Danthasinghe Waduge Badrajee Piyarathna, Tagari Samanta, Vasanta Putluri, Dereck Mezquita, Suzanne A W Fuqua, Nagireddy Putluri, Cristian Coarfa, Benny Abraham Kaipparettu

Faculty, Staff and Students Publications

Approximately one-third of endocrine-treated women with estrogen receptor-alpha positive (ER+) breast cancers (BC) are at risk of recurrence due to intrinsic or acquired resistance. Thus, it is vital to understand the mechanisms underlying endocrine therapy resistance in ER+ BC to improve patient treatment. Mitochondrial fatty acid β-oxidation (FAO) has been shown to be a major metabolic pathway in triple-negative BC (TNBC) that can activate Src signaling. Here, we found metabolic reprogramming that increases FAO in ER+ BC as a mechanism of resistance to endocrine therapy. A metabolically relevant, integrated gene signature was derived from transcriptomic, metabolomic, and lipidomic analyses in …

Novel Species Of Triatoma (Hemiptera: Reduviidae) Identified In A Case Of Vectorial Transmission Of Chagas Disease In Northern Belize, Sarah M Gunter, Alisa Nelson, Alexander R Kneubehl, Silvia A Justi, Russell Manzanero, Emily Zielinski-Gutierrez, Claudia Herrera, Julie Thompson, Rajendra Mandage, Hans Desale, Adrianna Maliga, Kim Bautista, Shannon E Ronca, Francis Morey, Rafael Chacon Fuentes, Beatriz Lopez, Eric Dumonteil, Gerhaldine H Morazan, Kristy O Murray

Faculty, Staff and Students Publications

Chagas disease is a leading cause of non-ischemic cardiomyopathy in endemic regions of Central and South America. In Belize, Triatoma dimidiata sensu lato has been identified as the predominate taxon but vectorial transmission of Chagas disease is considered to be rare in the country. We recently identified an acute case of vector-borne Chagas disease in the northern region of Belize. Here we present a subsequent investigation of triatomines collected around the case-patient's home. We identified yet undescribed species, closely related to Triatoma huehuetenanguensis vector by molecular systematics methods occurring in the peridomestic environment. The identification of a T. cruzi-positive, novel …

Associations Of Galectin-3 Levels With Measures Of Vascular Disease In Patients With Rheumatoid Arthritis, Amanda Nussdorf, Elizabeth Park, Isabelle Amigues, Laura Geraldino-Pardilla, Sabahat Bokhari, Jon T. Giles, Joan M. Bathon

Division of Rheumatology Faculty Papers

OBJECTIVES: Galectin-3 is a beta-galactoside-binding lectin and is a marker of cardiovascular disease (CVD) in the general population. It may also play a role in joint inflammation. We asked whether serum galectin-3 is a useful marker of subclinical vascular disease in patients with rheumatoid arthritis (RA).

METHODS: RA patients without clinical CVD underwent assessment of coronary artery calcium (CAC) score, aortic inflammation (using 18Fluorodeoxyglucose positron emission-computed tomography [FDG PET/CT]), and myocardial flow reserve (MFR). Aorta FDG uptake was measured as standardized uptake values (SUV). Generalized linear models were constructed to explore the associations of galectin-3 levels with CAC score, aortic …

Qiditangshen Granules Alleviates Diabetic Nephropathy Podocyte Injury: A Network Pharmacology Study And Experimental Validation In Vivo And Vitro, Fei Gao, Ying Zhou, Borui Yu, Huidi Xie, Yang Shi, Xianhui Zhang, Hongfang Liu

Faculty, Staff and Student Publications

BACKGROUND: QiDiTangShen granules (QDTS), a traditional Chinese medicine (TCM) compound prescription, have remarkable efficacy in diabetic nephropathy (DN) patients, and their pharmacological mechanism needs further exploration.

METHODS: According to the active ingredients and targets of the QDTS in the TCMSP database, the network pharmacology of QDTS was investigated. The potential active ingredients were chosen based on the oral bioavailability and the drug similarity index. At the same time, targets for DN-related disease were obtained from GeneCards, OMIM, PharmGKB, TTD, and DrugBank. The TCM-component-target network and the protein-protein interaction (PPI) network were constructed with the Cytoscape and STRING platforms, respectively, and …

Modeling The Health Impact And Cost-Effectiveness Of A Combined Schoolgirl Hpv Vaccination And Cervical Cancer Screening Program In Guangdong Province, China, Yating Huang, Dantao Zhang, Lihua Yin, Jianguo Zhao, Zhifeng Li, Jing Lu, Xiaoming Zhang, Chenggang Wu, Wei Wu

Faculty, Staff and Student Publications

Low human papillomavirus (HPV) vaccine uptake is a key barrier to cervical cancer elimination. We aimed to evaluate the health impact and cost-effectiveness of introducing different HPV vaccines into immunization programs and scaling up the screening program in Guangdong. We used a dynamic compartmental model to estimate the impact of intervention strategies during 2023-2100. We implemented the incremental cost-effectiveness ratio (ICER) in costs per averted disability-adjusted life year (DALY) as an indicator to assess the effectiveness of the intervention. We used an age-standardized incidence of 4 cases per 100,000 women as the threshold for the elimination of cervical cancer. Compared …

Beyond The Global Brain Differences: Intraindividual Variability Differences In 1q211 Distal And 15q112 Bp1-Bp2 Deletion Carriers, Rune Boen, Tobias Kaufmann, Dennis Van Der Meer, Oleksandr Frei, Ingrid Agartz, David Ames, Micael Andersson, Nicola J Armstrong, Eric Artiges, Joshua R Atkins, Jochen Bauer, Francesco Benedetti, Dorret I Boomsma, Henry Brodaty, Katharina Brosch, Randy L Buckner, Murray J Cairns, Vince Calhoun, Svenja Caspers, Sven Cichon, Aiden P Corvin, Benedicto Crespo-Facorro, Udo Dannlowski, Friederike S David, Eco J C De Geus, Greig I De Zubicaray, Sylvane Desrivières, Joanne L Doherty, Gary Donohoe, Stefan Ehrlich, Else Eising, Thomas Espeseth, Simon E Fisher, Andreas J Forstner, Lidia Fortaner-Uyà, Vincent Frouin, Masaki Fukunaga, Tian Ge, David C Glahn, Janik Goltermann, Hans J Grabe, Melissa J Green, Nynke A Groenewold, Dominik Grotegerd, Gøril Rolfseng Grøntvedt, Tim Hahn, Ryota Hashimoto, Jayne Y Hehir-Kwa, Frans A Henskens, Avram J Holmes, Asta K Håberg, Jan Haavik, Sebastien Jacquemont, Andreas Jansen, Christiane Jockwitz, Erik G Jönsson, Masataka Kikuchi, Tilo Kircher, Kuldeep Kumar, Stephanie Le Hellard, Costin Leu, David E Linden, Jingyu Liu, Robert Loughnan, Karen A Mather, Katie L Mcmahon, Allan F Mcrae, Sarah E Medland, Susanne Meinert, Clara A Moreau, Derek W Morris, Bryan J Mowry, Thomas W Mühleisen, Igor Nenadić, Markus M Nöthen, Lars Nyberg, Roel A Ophoff, Michael J Owen, Christos Pantelis, Marco Paolini, Tomas Paus, Zdenka Pausova, Karin Persson, Yann Quidé, Tiago Reis Marques, Perminder S Sachdev, Sigrid B Sando, Ulrich Schall, Rodney J Scott, Geir Selbæk, Elena Shumskaya, Ana I Silva, Sanjay M Sisodiya, Frederike Stein, Dan J Stein, Benjamin Straube, Fabian Streit, Lachlan T Strike, Alexander Teumer, Lea Teutenberg, Anbupalam Thalamuthu, Paul A Tooney, Diana Tordesillas-Gutierrez, Julian N Trollor, Dennis Van 'T Ent, Marianne B M Van Den Bree, Neeltje E M Van Haren, Javier Vázquez-Bourgon, Henry Völzke, Wei Wen, Katharina Wittfeld, Christopher R K Ching, Lars T Westlye, Paul M Thompson, Carrie E Bearden, Kaja K Selmer, Dag Alnæs, Ole A Andreassen, Ida E Sønderby, Enigma-Cnv Working Group

Faculty, Staff and Student Publications

Background: Carriers of the 1q21.1 distal and 15q11.2 BP1-BP2 copy number variants exhibit regional and global brain differences compared with noncarriers. However, interpreting regional differences is challenging if a global difference drives the regional brain differences. Intraindividual variability measures can be used to test for regional differences beyond global differences in brain structure.

Methods: Magnetic resonance imaging data were used to obtain regional brain values for 1q21.1 distal deletion (n = 30) and duplication (n = 27) and 15q11.2 BP1-BP2 deletion (n = 170) and duplication (n = 243) carriers and matched noncarriers (n = 2350). Regional intra-deviation scores, i.e., …

Armc5 Controls The Degradation Of Most Pol Ii Subunits, And Armc5 Mutation Increases Neural Tube Defect Risks In Mice And Humans, Hongyu Luo, Linjiang Lao, Kit Sing Au, Hope Northrup, Xiao He, Diane Forget, Marie-Soleil Gauthier, Benoit Coulombe, Isabelle Bourdeau, Wei Shi, Lucia Gagliardi, Maria Candida Barisson Villares Fragoso, Junzheng Peng, Jiangping Wu

Faculty, Staff and Student Publications

BACKGROUND: Neural tube defects (NTDs) are caused by genetic and environmental factors. ARMC5 is part of a novel ubiquitin ligase specific for POLR2A, the largest subunit of RNA polymerase II (Pol II).

RESULTS: We find that ARMC5 knockout mice have increased incidence of NTDs, such as spina bifida and exencephaly. Surprisingly, the absence of ARMC5 causes the accumulation of not only POLR2A but also most of the other 11 Pol II subunits, indicating that the degradation of the whole Pol II complex is compromised. The enlarged Pol II pool does not lead to generalized Pol II stalling or a generalized …

Small Needle-Knife Versus Extracorporeal Shock Wave Therapy For The Treatment Of Plantar Fasciitis: A Systematic Review And Meta-Analysis, Chaoqun Feng, Junjie Yao, Yizhou Xie, Min Zhao, Youpeng Hu, Ziang Hu, Ruoyan Li, Haoyang Wu, Yuanxin Ge, Fei Yang, Xiaohong Fan

Faculty, Staff and Student Publications

BACKGROUND: Plantar fasciitis (PF) is the most common cause of chronic heel pain among adults. Extracorporeal shock wave therapy (ESWT) is the recommended in the current guidelines, and the small needle-knife yields acceptable clinical effects for musculoskeletal pain.

OBJECTIVE: To systematically compare the efficacy of the small needle-knife versus ESWT for the treatment of PF.

METHODS: The present review was registered in the International Prospective Register of Systematic Reviews (i.e., "PROSPERO", CRD42023448813). Two of the authors searched electronic databases for randomized controlled trials (RCTs) comparing the small needle-knife versus ESWT for the treatment of PF, and collected outcomes including curative …

Large Scale Plasma Proteomics Identifies Novel Proteins And Protein Networks Associated With Heart Failure Development, Amil M Shah, Peder L Myhre, Victoria Arthur, Pranav Dorbala, Humaira Rasheed, Leo F Buckley, Brian Claggett, Guning Liu, Jianzhong Ma, Ngoc Quynh Nguyen, Kunihiro Matsushita, Chiadi Ndumele, Adrienne Tin, Kristian Hveem, Christian Jonasson, Håvard Dalen, Eric Boerwinkle, Ron C Hoogeveen, Christie Ballantyne, Josef Coresh, Torbjørn Omland, Bing Yu

Faculty, Staff and Student Publications

Heart failure (HF) causes substantial morbidity and mortality but its pathobiology is incompletely understood. The proteome is a promising intermediate phenotype for discovery of novel mechanisms. We measured 4877 plasma proteins in 13,900 HF-free individuals across three analysis sets with diverse age, geography, and HF ascertainment to identify circulating proteins and protein networks associated with HF development. Parallel analyses in Atherosclerosis Risk in Communities study participants in mid-life and late-life and in Trøndelag Health Study participants identified 37 proteins consistently associated with incident HF independent of traditional risk factors. Mendelian randomization supported causal effects of 10 on HF, HF risk …

Increased Iron Uptake By Splenic Hematopoietic Stem Cells Promotes Tet2-Dependent Erythroid Regeneration, Yu-Jung Tseng, Yuki Kageyama, Rebecca L Murdaugh, Ayumi Kitano, Jong Hwan Kim, Kevin A Hoegenauer, Jonathan Tiessen, Mackenzie H Smith, Hidetaka Uryu, Koichi Takahashi, James F Martin, Md Abul Hassan Samee, Daisuke Nakada

Faculty, Staff and Student Publications

Hematopoietic stem cells (HSCs) are capable of regenerating the blood system, but the instructive cues that direct HSCs to regenerate particular lineages lost to the injury remain elusive. Here, we show that iron is increasingly taken up by HSCs during anemia and induces erythroid gene expression and regeneration in a Tet2-dependent manner. Lineage tracing of HSCs reveals that HSCs respond to hemolytic anemia by increasing erythroid output. The number of HSCs in the spleen, but not bone marrow, increases upon anemia and these HSCs exhibit enhanced proliferation, erythroid differentiation, iron uptake, and TET2 protein expression. Increased iron in HSCs promotes …

Portable Air Purifiers To Mitigate The Harms Of Wildfire Smoke For People With Asthma, Tianshi David Wu

Faculty, Staff and Students Publications

No abstract provided.

A Novel Erβ High Throughput Microscopy Platform For Testing Endocrine Disrupting Chemicals, Derek A Abbott, Maureen G Mancini, Michael J Bolt, Adam T Szafran, Kaley A Neugebauer, Fabio Stossi, Daniel A Gorelick, Michael A Mancini

Faculty, Staff and Students Publications

In this study we present an inducible biosensor model for the Estrogen Receptor Beta (ERβ), GFP-ERβ:PRL-HeLa, a single-cell-based high throughput (HT) in vitro assay that allows direct visualization and measurement of GFP-tagged ERβ binding to ER-specific DNA response elements (EREs), ERβ-induced chromatin remodeling, and monitor transcriptional alterations via mRNA fluorescence in situ hybridization for a prolactin (PRL)-dsRED2 reporter gene. The model was used to accurately (Z' = 0.58-0.8) differentiate ERβ-selective ligands from ERα ligands when treated with a panel of selective agonists and antagonists. Next, we tested an Environmental Protection Agency (EPA)-provided set of 45 estrogenic reference chemicals with known …

Impact Of Transcatheter Heart Valve Type On Outcomes Of Surgical Explantation After Failed Transcatheter Aortic Valve Replacement: The Explant-Tavr International Registry, Syed Zaid, Neal S Kleiman, Sachin S Goel, Molly I Szerlip, Michael J Mack, Mateo Marin-Cuartas, Siamak Mohammadi, Tamim M Nazif, Axel Unbehaun, Martin Andreas, Derek R Brinster, Newell B Robinson, Lin Wang, Basel Ramlawi, Lenard Conradi, Nimesh D Desai, John K Forrest, Rodrigo Bagur, Tom C Nguyen, Ron Waksman, Lionel Leroux, Eric Van Belle, Kendra J Grubb, Hasan A Ahmad, Paolo Denti, Thomas Modine, Vinayak N Bapat, Tsuyoshi Kaneko, Michael J Reardon, Gilbert H L Tang, On Behalf Of The Explant-Tavr Registry Investigators

Faculty, Staff and Students Publications

Background: There are limited data on the impact of transcatheter heart valve (THV) type on the outcomes of surgical explantation after THV failure.

Aims: We sought to determine the outcomes of transcatheter aortic valve replacement (TAVR) explantation for failed balloon-expandable valves (BEV) versus self-expanding valves (SEV).

Methods: From November 2009 to February 2022, 401 patients across 42 centres in the EXPLANT-TAVR registry underwent TAVR explantation during a separate admission from the initial TAVR. Mechanically expandable valves (N=10, 2.5%) were excluded. The outcomes of TAVR explantation were compared for 202 (51.7%) failed BEV and 189 (48.3%) failed SEV.

Results: Among 391 …

Coagulopathy In Severe Covid-19 Patients: Causes, Concerns And Current Treatment Regimen, Tanusree Sengupta, Arun Luiz, Chennakesavan Suganthi, Samarpan Majumder

School of Graduate Studies Faculty Publications

Elevated D-dimer and fibrinogen level, mild thrombocytopenia, modest prolongation of prothrombin time, and activated partial thromboplastin time, are key indicators of coagulopathy, and have been consistently reported in severely ill COVID-19 patients. Coronavirus disease 2019 (COVID-19)-induced coagulopathy can develop serious venous and arterial thromboembolic complications. Endothelial dysfunction and hypercoagulability, triggered mostly by overproduction of inflammatory cytokines as an immune response to the infection, are the pivotal factors responsible for the above-mentioned coagulation disorder. Thus, low-molecular-weight heparin (LMWH), which has both anticoagulant and anti-inflammatory properties, has been reported to improve disease prognosis. However, there have been increasing reports of venous thromboembolic …

Exploring The Role Of Information And Communication Technologies In Allergic Rhinitis In Specialist Centers: Patient Perspectives On Usefulness, Value, And Impact On Healthcare, Ivan Cherrez Ojeda, Jean Bousquet, Zouina Sarfraz, Azza Sarfraz, Monica Rodriguez Gonzales, Anna Bedbrook, Nelson Rosario, Benjamin Zepeda Ortega, Guillermo Guidos, Ulbio Alcivar Molina

Department of Paediatrics and Child Health

Introduction: Information and communication technologies (ICTs) improve patient-centered care and are routinely used in Allergic Rhinitis (AR), but patients' preferences and attitudes are unexplored. This study examines AR-related information preferences and ICT use by AR patients.
Methods: A survey-based cross-sectional study was carried out in Ecuador from July to September 2019 in seven centers of reference for allergic disease. Participants were 18 years or older, diagnosed with AR and had access to ICT and the Internet. Descriptive and binomial logistic regressions were performed. A value of less than 0.05 was considered statistically significant.
Results: 217 patients were included. 47% (n …