Digital Commons Network^™

Benchmarking Usability Of Patient Portals In Estonia, Finland, Norway, And Sweden, Sari Kujala, Saija Simola, Bo Wang, Hedvig Soone, Josefin Hagström, Annika Bärkås, Iiris Hörhammer, Åsa Cajander, Asbjørn Johansen Fagerlund, Bridget Kane, Anna Kharko, Eli Kristiansen, Jonas Moll, Hanife Rexphepi, Maria Hägglund, Monika A. Johansen

School of Psychology

Introduction: Poor usability is a barrier to widespread adoption of electronic health records (EHR). Providing good usability is especially challenging in the health care context, as there is a wide variety of patient users. Usability benchmarking is an approach for improving usability by evaluating and comparing the strength and weaknesses of systems. The main purpose of this study is to benchmark usability of patient portals across countries. Methods: A mixed-methods survey approach was applied to benchmark the national patient portals offering patient access to EHR in Estonia, Finland, Norway, and Sweden. These Nordic countries have similar public healthcare systems, and …

Fgf5, Evelyn A Carrion, Malcolm M Moses, Richard R Behringer

Faculty, Staff and Student Publications

FGF5 functions as a negative regulator of the hair cycle in mammals. It is expressed in the outer root sheath of hair follicles during the late anagen phase of the hair cycle. It functions as a signaling molecule, mediating the transition of the anagen growth phase to catagen regression phase of the hair cycle. Spontaneous and engineered FGF5 mutations in mammalian animal models result in long hair phenotypes. In humans, inherited FGF5 mutations result in trichomegaly (long eyelashes). Knockdown of fgf5 in zebrafish embryos results in inner ear alterations. Alterations in FGF5 expression are also associated with various human pathologies.

Proton Pump Inhibitors: Rational Use And Use-Reduction - The Windsor Workshop, Hashem B El Serag, Joachim Labenz, Juan Mendive, Edoardo V Savarino, Daniel Sifrim, Mihaela Udrescu, Rena Yadlapati, A Pali Hungin

Faculty, Staff and Students Publications

BACKGROUND: Despite deprescribing initiatives to curb overutilization of proton pump inhibitors (PPIs), achieving meaningful reductions in PPI use is proving a challenge.

SUMMARY: An international group of primary care doctors and gastroenterologists examined the literature surrounding PPI use and use-reduction to clarify: (i) what constitutes rational PPI prescribing; (ii) when and in whom PPI use-reduction should be attempted; and (iii) what strategies to use when attempting PPI use-reduction.

KEY MESSAGES: Before starting a PPI for reflux-like symptoms, patients should be educated on potential causes and alternative approaches including dietary and lifestyle modification, weight loss, and relaxation strategies. When commencing a …

The Great Masquerade: Not All Coronary Artery Stenosis Are Created Equal, Veronica V Rosen, Waleed T Kayani

Faculty, Staff and Students Publications

We present the case of a 60-year-old male, with active smoking and cocaine use disorder, who reported progressive chest pain. Various anatomical and functional cardiac imaging, performed to further evaluate chest pain etiology, revealed changing severity and distribution of left main artery (LMA) stenosis, raising suspicion for vasospasm. Intracoronary nitroglycerin relieved the vasospasm, with resolution of the LMA pseudostenosis. A diagnosis of vasospastic angina (VA) led to starting appropriate medical therapy with lifestyle modification counselling. This case highlights VA, a frequently underdiagnosed etiology of angina pectoris. We discuss when to suspect VA, its appropriate work-up, and management.

Using Noninvasive Clinical Parameters To Predict Mortality And Morbidity After Cardiac Interventions In Patients With Cirrhosis: A Systematic Review, Avegail Flores, Ruben Hernaez

Faculty, Staff and Students Publications

BACKGROUND: Cardiovascular disease commonly affects advanced liver disease patients. They undergo cardiac interventions to improve cardiac outcomes. Cirrhosis increases complication risk, including bleeding, renal and respiratory failure, and further decompensation, including death, posing a clinical dilemma to proceduralists. Predicting outcomes is crucial in managing patients with cirrhosis. Our aim was to systematically review clinical parameters to assess the mortality and complication risk in patients with cirrhosis undergoing cardiac interventions.

METHODS: We searched cirrhosis and cardiovascular intervention terminology in PubMed and Excerpta Medica Database (EMBASE) from inception to January 8, 2023. We included studies reporting clinical scores (e.g. Model for End-stage …

Effects And Plasma Proteomic Analysis Of Glp-1ra Versus Cpa/Ee, In Combination With Metformin, On Overweight Pcos Women: A Randomized Controlled Trial, Ling Zhou, Liu Shi, Weixin Li, Rufei Shen, Guiliang Peng, Huan Zhao, Jiaqing Shao, Xiujie Wang, Zheng Sun, Hongting Zheng, Min Long

Faculty, Staff and Students Publications

PURPOSE: Polycystic ovary syndrome (PCOS) is characterized by reproductive dysfunctions and metabolic disorders. This study aims to compare the therapeutic effectiveness of glucagon-like peptide-1 receptor agonist (GLP-1RA) + Metformin (Met) versus cyproterone acetate/ethinylestradiol (CPA/EE) + Met in overweight PCOS women and identify potential proteomic biomarkers of disease risk in women with PCOS.

METHODS: In this prospective, open-label randomized controlled trial, we recruited 60 overweight PCOS women into two groups at a 1:1 ratio to receive CPA/EE (2 mg/day: 2 mg cyproterone acetate and 35-μg ethinylestradiol,) +Met (1500 mg/day) or GLP-1 RA (liraglutide, 1.2-1.8 mg/day) +Met (1500 mg/day) for 12 weeks. …

Research Participants' Perspectives On Precision Diagnostics For Alzheimer's Disease, Stacey Pereira, Belen Pascual, Kathleen Bradbury, Victoria Arbones, Jamie Fong, Joshua M Shulman, Amy L Mcguire, Joseph Masdeu

Faculty, Staff and Students Publications

BACKGROUND: Understanding research participants' responses to learning Alzheimer's disease (AD) risk information is important to inform clinical implementation of precision diagnostics given rapid advances in disease modifying therapies.

OBJECTIVE: We assessed participants' perspectives on the meaning of their amyloid positron emission tomography (PET) imaging results for their health, self-efficacy to understand their results, psychological impact of learning their results, experience receiving their results from the clinical team, and interest in genetic testing for AD risk.

METHODS: We surveyed individuals who were being clinically evaluated for AD and received PET imaging six weeks after the return of results. We analyzed responses …

Breast Multiparametric Mri For Prediction Of Neoadjuvant Chemotherapy Response In Breast Cancer: The Bmmr2 Challenge, Helga S Marques, Jayashree Kalpathy-Cramer, Michael A Boss, Xinzhi Teng, Jiang Zhang, Jing Cai, Despina Kontos, Eric A Cohen, Walter C Mankowski, Michael Liu, Richard Ha, Oscar J Pellicer-Valero, Klaus Maier-Hein, Simona Rabinovici-Cohen, Tal Tlusty, Michal Ozery-Flato, Vishwa S Parekh, Michael A Jacobs, Ran Yan, Kyunghyun Sung, Anum S Kazerouni, Julie C Dicarlo, Thomas E Yankeelov, Thomas L Chenevert, Nola M Hylton

Faculty, Staff and Student Publications

Purpose To describe the design, conduct, and results of the Breast Multiparametric MRI for prediction of neoadjuvant chemotherapy Response (BMMR2) challenge. Materials and Methods The BMMR2 computational challenge opened on May 28, 2021, and closed on December 21, 2021. The goal of the challenge was to identify image-based markers derived from multiparametric breast MRI, including diffusion-weighted imaging (DWI) and dynamic contrast-enhanced (DCE) MRI, along with clinical data for predicting pathologic complete response (pCR) following neoadjuvant treatment. Data included 573 breast MRI studies from 191 women (mean age [±SD], 48.9 years ± 10.56) in the I-SPY 2/American College of Radiology Imaging …

Voluntary Wheel Running Prevents Formation Of Membrane Attack Complexes And Myelin Degradation After Peripheral Nerve Injury, Suzanne M Green-Fulgham, Michael J Lacagnina, Kendal F Willcox, Jiahe Li, Michael E Harland, Igor R Correia Rocha, Renee A Dreher, Younus A Zuberi, Joseph M Dragavon, Marucia Chacur, Steven F Maier, Linda R Watkins, Peter M Grace

Faculty, Staff and Student Publications

Regular aerobic activity is associated with a reduced risk of chronic pain in humans and rodents. Our previous studies in rodents have shown that prior voluntary wheel running can normalize redox signaling at the site of peripheral nerve injury, attenuating subsequent neuropathic pain. However, the full extent of neuroprotection offered by voluntary wheel running after peripheral nerve injury is unknown. Here, we show that six weeks of voluntary wheel running prior to chronic constriction injury (CCI) reduced the terminal complement membrane attack complex (MAC) at the sciatic nerve injury site. This was associated with increased expression of the MAC inhibitor …

On The Relative Conservativeness Of Bayesian Logistic Regression Method In Oncology Dose-Finding Studies, Cheng-Han Yang, Guanghui Cheng, Ruitao Lin

Faculty, Staff and Student Publications

The Bayesian logistic regression method (BLRM) is a widely adopted and flexible design for finding the maximum tolerated dose in oncology phase I studies. However, the BLRM design has been criticized in the literature for being overly conservative due to the use of the overdose control rule. Recently, a discussion paper titled "Improving the performance of Bayesian logistic regression model with overall control in oncology dose-finding studies" in Statistics in Medicine has proposed an overall control rule to address the "excessive conservativeness" of the standard BLRM design. In this short communication, we discuss the relative conservativeness of the standard BLRM …

Pet Image Denoising Based On Denoising Diffusion Probabilistic Model, Kuang Gong, Keith Johnson, Georges El Fakhri, Quanzheng Li, Tinsu Pan

Faculty, Staff and Student Publications

Purpose: Due to various physical degradation factors and limited counts received, PET image quality needs further improvements. The denoising diffusion probabilistic model (DDPM) was a distribution learning-based model, which tried to transform a normal distribution into a specific data distribution based on iterative refinements. In this work, we proposed and evaluated different DDPM-based methods for PET image denoising.

Methods: Under the DDPM framework, one way to perform PET image denoising was to provide the PET image and/or the prior image as the input. Another way was to supply the prior image as the network input with the PET image included …

Post-Covid-19 Cognitive Symptoms In Patients Assisted By A Teleassistance Service: A Retrospective Cohort Study, Lívia Paula Freire Bonfim, Thais Rotsen Correa, Bruno Cabaleiro Cortizo Freire, Thais Marques Pedroso, Daniella Nunes Pereira, Luciane Kopittke, Antonio Lucio Teixeira, Milena Soriano Marcolino

Faculty, Staff and Student Publications

INTRODUCTION: Four years after the onset of the COVID-19 pandemic, the frequency of long-term post-COVID-19 cognitive symptoms is a matter of concern given the impact it may have on the work and quality of life of affected people.

OBJECTIVE: To evaluate the incidence of post-acute COVID-19 cognitive symptoms, as well as the associated risk factors.

METHODS: Retrospective cohort, including outpatients with laboratory-confirmed COVID-19 and who were assisted by a public telehealth service provided by the Telehealth Network of Minas Gerais (TNMG), during the acute phase of the disease, between December/2020 and March/2022. Data were collected through a structured questionnaire, applied …

Approaches To Estimate Bidirectional Causal Effects Using Mendelian Randomization With Application To Body Mass Index And Fasting Glucose, Jinhao Zou, Rajesh Talluri, Sanjay Shete

Faculty, Staff and Student Publications

Mendelian randomization (MR) is an epidemiological framework using genetic variants as instrumental variables (IVs) to examine the causal effect of exposures on outcomes. Statistical methods based on unidirectional MR (UMR) are widely used to estimate the causal effects of exposures on outcomes in observational studies. To estimate the bidirectional causal effects between two phenotypes, investigators have naively applied UMR methods separately in each direction. However, bidirectional causal effects between two phenotypes create a feedback loop that biases the estimation when UMR methods are naively applied. To overcome this limitation, we proposed two novel approaches to estimate bidirectional causal effects using …

Lysophospholipids Are Associated With Outcomes In Hospitalized Patients With Mild Traumatic Brain Injury, Sarah Hinds, Neeraj Badjatia, Georgene W Hergenroeder, Anthony N Moore, H Alex Choi, Pramod K Dash

Faculty, Staff and Student Publications

Mild traumatic brain injury (mTBI) accounts for 70-90% of all TBI cases. Lipid metabolites have important roles in plasma membrane biogenesis, function, and cell signaling. As TBI can compromise plasma membrane integrity and alter brain cell function, we sought to identify circulating phospholipid alterations after mTBI, and determine if these changes were associated with clinical outcomes. Patients with mTBI (Glasgow Coma Score [GCS] ≥13 and loss of consciousness <30 >min) were recruited. A total of 84 mTBI subjects were enrolled after admission to a level I trauma center, with the majority having evidence of traumatic intracranial hemorrhage on brain computed tomography …

Fitness Consequences Of Depressive Symptoms Vary Between Generations: Evidence From A Large Cohort Of Women Across The 20th Century, Christopher I Gurguis, Renée A Duckworth, Nicole M Bucaro, Consuelo Walss-Bass

Faculty, Staff and Student Publications

Depression has strong negative impacts on how individuals function, leading to the assumption that there is strong negative selection on this trait that should deplete genetic variation and decrease its prevalence in human populations. Yet, depressive symptoms remain common. While there has been a large body of work trying to resolve this paradox by mapping genetic variation of this complex trait, there have been few direct empirical tests of the core assumption that there is consistent negative selection on depression in human populations. Here, we use a unique long-term dataset from the National Health and Nutrition Examination Survey that spans …

A Novel Assessment Of Whole-Mount Gleason Grading In Prostate Cancer To Identify Candidates For Radical Prostatectomy: A Machine Learning-Based Multiomics Study, Jing Ning, Clemens P Spielvogel, David Haberl, Karolina Trachtova, Stefan Stoiber, Vojtech Bystry, Pascal Baltzer, Elisabeth Gurnhofer, Gerald Timelthaler, Michaela Schlederer, Laszlo Papp, Helga Schachner, Thomas Helbich, Markus Hartenbach, Bernhard Grubmüller, Shahrokh F Shariat, Marcus Hacker, Alexander Haug, Lukas Kenner

Faculty, Staff and Student Publications

Purpose: This study aims to assess whole-mount Gleason grading (GG) in prostate cancer (PCa) accurately using a multiomics machine learning (ML) model and to compare its performance with biopsy-proven GG (bxGG) assessment.

Materials and Methods: A total of 146 patients with PCa recruited in a pilot study of a prospective clinical trial (NCT02659527) were retrospectively included in the side study, all of whom underwent ⁶⁸Ga-PSMA-11 integrated positron emission tomography (PET) / magnetic resonance (MR) before radical prostatectomy (RP) between May 2014 and April 2020. To establish a multiomics ML model, we quantified PET radiomics features, pathway-level genomics …

Non-Homologous End-Joining Genotype, Mrna Expression, And Dna Repair Capacity In Childhood Acute Lymphocytic Leukemia, Chao-Chun Chen, Wen-Shin Chang, Jen-Sheng Pei, Chien-Chung Kuo, Chung-Hsing Wang, Pei-Chen Hsu, Jian Gu, Da-Tian Bau, Chia-Wen Tsai

Faculty, Staff and Student Publications

Background/aim: The capacity for non-homologous end-joining (NHEJ) repair plays a pivotal role in maintaining genome stability and in carcinogenesis. However, there is little literature on the involvement of NHEJ-related genes in childhood acute lymphocytic leukemia (ALL). Our study aimed to elucidate the impact of polymorphisms of X-ray repair cross-complementing group 4 (XRCC4) (rs6869366, rs2075685, rs2075686, rs28360071, rs3734091, rs28360317, rs1805377), XRCC5 (rs828907, rs11685387, rs9288518), XRCC6 (rs5751129, rs2267437, rs132770, rs132774), XRCC7 rs7003908, and DNA ligase IV (LIG4) rs1805388, on the odds of childhood ALL.

Materials and methods: Genotypes NHEJ-related genes of 266 cases and 266 controls were determined, and the genotype-phenotype correlation …

Incorporating Variable Rbe In Impt Optimization For Ependymoma, Hadis Moazami Goudarzi, Gino Lim, David Grosshans, Radhe Mohan, Wenhua Cao

Faculty, Staff and Student Publications

PURPOSE: To study the dosimetric impact of incorporating variable relative biological effectiveness (RBE) of protons in optimizing intensity-modulated proton therapy (IMPT) treatment plans and to compare it with conventional constant RBE optimization and linear energy transfer (LET)-based optimization.

METHODS: This study included 10 pediatric ependymoma patients with challenging anatomical features for treatment planning. Four plans were generated for each patient according to different optimization strategies: (1) constant RBE optimization (ConstRBEopt) considering standard-of-care dose requirements; (2) LET optimization (LETopt) using a composite cost function simultaneously optimizing dose-averaged LET (LET

RESULTS: We found that the LETopt plans consistently achieved increased LET in …

Double Testing With Lateral Flow Antigen Test Devices For Covid-19: Does A Second Test In Quick Succession Add Value?, Matthias E Futschik, Sarah A Tunkel, Elena Turek, David Chapman, Zareen Thorlu-Bangura, Raghavendran Kulasegaran-Shylini, Edward Blandford, Andrew Dodgson, Paul E Klapper, Malur Sudhanva, Derrick Crook, John Bell, Susan Hopkins, Tim Peto, Tom Fowler

School of Biomedical Sciences

BACKGROUND/OBJECTIVES: We investigated if performing two lateral flow device (LFD) tests, LFD2 immediately after LFD1, could improve diagnostic sensitivity or specificity for detecting severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) antigen.

STUDY DESIGN: Individuals aged ≥16 years attending UK community testing sites (February-May 2021) performed two successive LFD tests and provided a nose-and-throat sample for a polymerase chain reaction (PCR) test. Using the PCR result as the reference diagnosis, we assessed whether improvements could be achieved in sensitivity (by counting a positive result in either LFD as a positive overall test result) or specificity (by using LFD2 as confirmatory test). …

The Cost Of Providing Care By Family And Friends (Informal Care) In The Last Year Of Life: A Population Observational Study, Miriam J. Johnson, David C. Currow, Jade Chynoweth, Helen Weatherly, Gamze Keser, Ann Hutchinson, Annie Jones, Laurie Dunn, Victoria Allgar

Peninsula Medical School

Introduction: Little is known about replacement costs of care provided by informal carers during the last year of life for people dying of cancer and non-cancer diseases. Aim: To estimate informal caregiving costs and explore the relationship with carer and decedent characteristics. Design: National observational study of bereaved carers. Questions included informal end-of-life caregiving into the 2017 Health Survey for England including estimated recalled frequency, duration and intensity of care provision. We estimated replacement costs for a decedent’s last year of life valuing time at the price of a substitutable activity. Spearman rank correlations and multivariable linear regression were used …

Absolute Concentration Estimation Of Covid-19 Convalescent And Post-Vaccination Igg Antibodies, Manouchehr Hessabi, Luis Z Ostrosky-Zeichner, Kent Koster, Jeffrey D Cirillo, Dinuka Abeydeera, Steve De Lira, David D Mcpherson

Faculty, Staff and Student Publications

Soon after commencement of the SARS-CoV-2 disease outbreak of 2019 (COVID-19), it became evident that the receptor-binding domain of the viral spike protein is the target of neutralizing antibodies that comprise a critical element of protective immunity to the virus. This study addresses the relative lack of information regarding actual antibody concentrations and binding affinities in convalescent plasma (CP) samples from COVID-19 patients and extends these analyses to post-vaccination (PV) samples to estimate protective IgG antibody (Ab) levels. A direct enzyme-linked immunosorbent assay (ELISA) was used to measure IgG anti-spike protein (SP) antibodies (Abs) relative to human chimeric spike S1 …

Evolution Of Whole Blood Trauma Resuscitation In Childbearing Age Females: Practice Patterns And Trends, Alexandra Mp Brito, Mark H Yazer, Jason L Sperry, James F Luther, Stephen R Wisniewski, Frances Guyette, Ernest E Moore, Bryan A Cotton, Laura Vincent, Erin Fox, Jeremy W Cannon, Nicholas Namias, Joseph P Minei, Lee Anne Ammons, Skye Clayton, Martin Schreiber

Faculty, Staff and Student Publications

Background: The use of low titer group O whole blood (LTOWB) for resuscitation of patients with traumatic hemorrhage is becoming increasingly common. Practices regarding the administration of RhD-positive LTOWB to childbearing age females (CBAFs) vary between institutions due to concerns about RhD alloimmunization. This study examined practices related to LTOWB transfusion as they pertain to age and sex.

Methods: This was a secondary analysis of the Shock, Whole blood, and Assessment of TBI (traumatic brain injury) trial, a prospective, multicenter observational cohort study where outcomes following LTOWB transfusion were analyzed at seven level 1 trauma centers between 2018 and 2021, …

Patient-Reported Outcomes Following Severe Abdominal Trauma: A Secondary Analysis Of The Damage Control Laparotomy Trial, David E Meyer

Faculty, Staff and Student Publications

Introduction: Little is known about patient-reported outcomes (PROs) following abdominal trauma. We hypothesized that patients undergoing definitive laparotomy (DEF) would have better PROs compared to those treated with damage control laparotomy (DCL).

Methods: The DCL Trial randomized DEF versus DCL in abdominal trauma. PROs were measured using the European Quality of Life-5 Dimensions-5 Levels (EQ-5D) questionnaire at discharge and six months postdischarge (1 = perfect health, 0 = death, and < 0 = worse than death) and Posttraumatic Stress Disorder (PTSD) Checklist-Civilian. Unadjusted Bayesian analysis with a neutral prior was used to assess the posterior probability of achieving minimal clinically important difference.

Results: Of 39 randomized patients (21 DEF versus 18 DCL), 8 patients died (7 DEF versus 1 DCL). Of those who survived, 28 completed the EQ-5D at discharge (12 DEF …

Identifying Missing Is-A Relations In Snomed Ct With Fine-Tuned Pre-Trained Language Models And Non-Lattice Subgraphs, Xubing Hao, Rashmie Abeysinghe, Jay Shi, Guo-Qiang Zhang, Licong Cui

Faculty, Staff and Student Publications

Ensuring the completeness of IS-A relations in SNOMED CT is crucial for maintaining its accuracy in clinical applications. In this study, we propose a hybrid approach leveraging non-lattice subgraphs and pre-trained language models (PLMs) to identify missing IS-A relations in SNOMED CT. We fine-tuned four BERT-based models: BERT, DistillBERT, DeBERTa, and BioClinicalBERT, and four generative large language models (LLMs): BioMistral, Llama3, Gemma2, and Phi-4. Missing IS-A relations were identified through consensus predictions by all eight models. De-BERTa achieved the best performance (precision: 0.96, recall: 0.97, F1-score: 0.965) for IS-A relation prediction. Our approach identified 678 potential missing IS-A relations in …

Measurement Of 8-Hydroxy-2′-Deoxyguanosine In Serum And Cerebrospinal Fluid Of Horses With Neuroaxonal Degeneration And Other Causes Of Proprioceptive Ataxia, Mary Robinson

Faculty, Staff and Student Publications

BACKGROUND: Eight-hydroxy-2'-deoxyguanosine (8-OHdG), a biomarker of oxidative damage evaluated in human neurodegenerative disease, has potential to correlate with postmortem diagnosis of neuroaxonal dystrophy/degenerative myeloencephalopathy (NAD/DM) in horses.

HYPOTHESIS: We hypothesized that 8-OHdG will be higher in CSF and serum from NAD/DM horses compared with horses with other neurologic diseases (CVSM, EPM) and a control group of neurologically normal horses. We also hypothesized that 8-OHdG will be higher in CSF compared with serum from NAD/DM horses.

ANIMALS: Fifty client-owned horses with postmortem diagnoses: 20 NAD/DM, 10 CVSM, 10 EPM, and 10 control horses. Serum and CSF samples were obtained between November …

Measurement Of 8-Hydroxy-2′-Deoxyguanosine In Serum And Cerebrospinal Fluid Of Horses With Neuroaxonal Degeneration And Other Causes Of Proprioceptive Ataxia, Mary Robinson

Faculty, Staff and Student Publications

BACKGROUND: Eight-hydroxy-2'-deoxyguanosine (8-OHdG), a biomarker of oxidative damage evaluated in human neurodegenerative disease, has potential to correlate with postmortem diagnosis of neuroaxonal dystrophy/degenerative myeloencephalopathy (NAD/DM) in horses.

HYPOTHESIS: We hypothesized that 8-OHdG will be higher in CSF and serum from NAD/DM horses compared with horses with other neurologic diseases (CVSM, EPM) and a control group of neurologically normal horses. We also hypothesized that 8-OHdG will be higher in CSF compared with serum from NAD/DM horses.

ANIMALS: Fifty client-owned horses with postmortem diagnoses: 20 NAD/DM, 10 CVSM, 10 EPM, and 10 control horses. Serum and CSF samples were obtained between November …

Double Hit In Clear-Cell Renal Cell Carcinoma With Germline Pathogenic Atm Mutation And Somatic Vhl Mutation, Curtis Wray

Faculty, Staff and Student Publications

While renal cell carcinoma (RCC) is often linked to smoking, obesity, and hypertension, hereditary forms also account for about 3% of RCC cases. Notably, NCCN guidelines identify 7 major hereditary syndromes associated with an increased RCC risk. Inherited mutations in DNA repair genes, such as ATM, BRCA, and TP53, significantly increase the risk of various cancers. Biallelic pathogenic mutations in ATM cause Ataxia-Telangiectasia (A-T) syndrome, while heterozygous germline pathogenic ATM mutations, present in about 1% of the population, also elevate cancer risk. RCC has not traditionally been associated with germline pathogenic ATM mutations, only limited retrospective analyses have identified such …

Promising Response Of Olaparib In Patient With Germline Atm-Mutated Metastatic Gastric Cancer, Victor Yang

Faculty, Staff and Student Publications

Gastric cancer ranks as the fifth leading cause of global cancer incidences, exhibiting varied prevalence influenced by geographical, ethnic, and lifestyle factors, as well as Helicobacter pylori infection. The ATM gene on chromosome 11q22 is vital for genomic stability as an initiator of the DNA damage response, and mutations in this gene have been associated with various cancers. Poly ADP-ribose polymerase (PARP) inhibitors, such as olaparib, have shown efficacy in cancers with homologous recombination repair deficiencies, notably in those with ATM mutations. Here, we present a case of a 66-year-old patient with germline ATM-mutated metastatic gastric cancer with very high …

One-Step Production Of Fully Biotinylated And Glycosylated Human Fc Gamma Receptors

Faculty, Staff and Student Publications

Initiating and regulating humoral immunity, Fc gamma receptors (FcγRs) have been identified both as therapeutics and as drug targets, and thus production of biologically active FcγRs is highly demanded for biopharmaceutical development. Focusing on low-affinity FcγRs IIA (131H/R allotypes), IIB, and IIIA (176F/V), this study used human 293-F cells to achieve correct post-translational modifications (PTMs) including biotinylation, N-glycosylation, and disulfides. Approaches involving co-expression of FcγR-AviTag and Escherichia coli biotin ligase BirA, endoplasmic reticulum retention, stable and transient transfections, and optimization of transgene ratio were investigated. Protein electrophoresis under reducing and non-reducing conditions, enzymatic deglycosylation, streptavidin pull-down assays, and binding kinetic …

Disentangling Accelerated Cognitive Decline From The Normal Aging Process And Unraveling Its Genetic Components: A Neuroimaging-Based Deep Learning Approach, Xiaoyang Li, Nitesh Enduru, Andi Liu, Astrid M Manuel, Xiaoqian Jiang, Zhongming Zhao, Alzheimer’S Disease Neuroimaging Initiative

Faculty, Staff and Student Publications

BACKGROUND: The progressive cognitive decline, an integral component of Alzheimer's disease (AD), unfolds in tandem with the natural aging process. Neuroimaging features have demonstrated the capacity to distinguish cognitive decline changes stemming from typical brain aging and AD between different chronological points.

OBJECTIVE: To disentangle the normal aging effect from the AD-related accelerated cognitive decline and unravel its genetic components using a neuroimaging-based deep learning approach.

METHODS: We developed a deep-learning framework based on a dual-loss Siamese ResNet network to extract fine-grained information from the longitudinal structural magnetic resonance imaging (MRI) data from the Alzheimer's Disease Neuroimaging Initiative (ADNI) study. …