Medicine and Health Sciences Commons^™

Differential Gait Features Across Parkinson's Disease Clinical Subtypes, Sidney T Baudendistel, Kerri S Rawson, Christina N Lessov-Schlaggar, Baijayanta Maiti, Paul T Kotzbauer, Joel S Perlmutter, Gammon M Earhart, Meghan C Campbell

2020-Current year OA Pubs

BACKGROUND: Clinical subtypes in Parkinson's disease including non-motor manifestations may be more beneficial than subtypes based upon motor manifestations alone. Inclusion of gait metrics may help identity targets for rehabilitation and potentially predict development of non-motor symptoms for individuals with Parkinson's disease. This study aims to characterize gait differences across established multi-domain subtypes.

METHODS: "Motor Only", "Psychiatric & Motor" and "Cognitive & Motor" clinical subtypes were established through motor, cognitive, and psychiatric assessment. Walking was assessed in the "OFF" medication state. Multivariate analysis of variance identified differences in gait domains across clinical subtypes.

FINDINGS: The "Motor Only" subtype exhibited the …

Sex-Specific Divergences In The Types And Timing Of Infiltrating Immune Cells During The Intervertebral Disc Acute Injury Response And Their Associations With Degeneration, Sade W Clayton, Remy E Walk, Laura Mpofu, Garrett W D Easson, Simon Y Tang

2020-Current year OA Pubs

OBJECTIVE: Inadequate repair of the intervertebral disc (IVD) contributes to low back pain. Infiltrating immune cells into damaged tissues are critical mediators of repair, yet little is known about the identities, roles, and temporal regulation following IVD injury. By analyzing transcripts of immune cell markers, histopathologic analysis, immunofluorescence, and flow cytometry, we aimed to define the temporal cascade of infiltrating immune cells and their associations with IVD degeneration.

METHODS: Caudal IVDs from 12-week-old C57BL6/J mice were injured and monitored for 42 days post-injury. Transcriptional markers identifying myeloid, B, and T immune cells, and angiogenic factors were measured from the IVDs …

Evaluating Dimensionality Reduction Of Comorbidities For Predictive Modeling In Individuals With Neurofibromatosis Type 1, Aditi Gupta, Ethan Hillis, Inez Y Oh, Stephanie M Morris, Zach Abrams, Randi E Foraker, David H Gutmann, Philip R O Payne

2020-Current year OA Pubs

OBJECTIVE: Dimensionality reduction techniques aim to enhance the performance of machine learning (ML) models by reducing noise and mitigating overfitting. We sought to compare the effect of different dimensionality reduction methods for comorbidity features extracted from electronic health records (EHRs) on the performance of ML models for predicting the development of various sub-phenotypes in children with Neurofibromatosis type 1 (NF1).

MATERIALS AND METHODS: EHR-derived data from pediatric subjects with a confirmed clinical diagnosis of NF1 were used to create 10 unique comorbidities code-derived feature sets by incorporating dimensionality reduction techniques using raw International Classification of Diseases codes, Clinical Classifications Software …

Illustrated Capsules From The Advanced Course In Platelet Research, Christian Andrea Di Buduo, Fan He, Stephen Oh, Jorge Di Paola, Et Al.

2020-Current year OA Pubs

This series of illustrated capsules summarizes the presentations made by the speakers at the first International Advanced Course in Platelet Research held in Murcia (Spain) from 27 to 28 September, 2024. This is the first course to receive a Fundamental Research Workshop Grant from the International Society on Thrombosis and Haemostasis (ISTH) and was also supported administratively and scientifically by the Spanish Society of Thrombosis and Haemostasis (SETH). This unique course focused on new methodologies applied in platelet research and how these are increasing our understanding of platelet formation, their multifunctionality in different physiological and pathological contexts, and contributing to …

Prospective Observational Study Of Fkrp-Related Limb-Girdle Muscular Dystrophy R9: A Grasp Consortium Study, Lindsay N Alfano, Stephanie Hunn, Conrad C Weihl, Et Al.

2020-Current year OA Pubs

OBJECTIVE: Limb-girdle muscular dystrophy R9 (LGMDR9, formerly known as LGMD2I), caused by variants in the fukutin-related protein (FKRP) gene leads to progressive muscle weakness of the shoulder and pelvic limb-girdles and loss of motor function over time. Clinical management and future trial design are improved by determining which standardized clinical outcome assessments (COA) of function are most appropriate to capture disease presentation and progression, informing endpoint selection and enrollment criteria. The purpose of our study was to evaluate the cross-sectional validity and reliability of clinical outcome assessments in patients with FKRP-related LGMDR9 participating in the Genetic Resolution and Assessments Solving …

Occult Ventricular Fibrillation Visualized By Echocardiogram During Cardiac Arrest: A Retrospective Observational Study From The Real-Time Evaluation And Assessment For Sonography-Outcomes Network (Reason), Romolo Gaspari, Srikar Adhikari, Timothy Gleeson, Monica Kapoor, Robert Lindsay, Vicki Noble, Jason T Nomura, Anthony Weekes, Dan Theodoro

2020-Current year OA Pubs

OBJECTIVES: Cardiac arrest patients with a shockable rhythm are more likely to survive an out-of-hospital cardiac arrest (OHCA) compared with a nonshockable rhythm. An electrocardiogram (ECG) is the most common way to identify a shockable rhythm, but it can miss patients with clinically significant ventricular fibrillation (vfib). We sought to determine the percentage of nonshockable OHCA patients that demonstrated vfib on echo.

METHODS: Secondary analysis of echo images recorded from a prior study from our group, Real-Time Evaluation and Assessment for Sonography-Outcomes Network (REASON), a multicenter, observational study of OHCA patients presenting to the emergency department with nonshockable rhythms. Using …

Assessment Of Patient Satisfaction Among Patients Treated With Intravenous Vs Subcutaneous Insulin For Diabetic Ketoacidosis, Richard T Griffey, Ryan M Schneider, Margo Girardi, Gina Larossa, Julianne Yeary, Michael Lehmkuhl, Dan Suarez, Rachel Ancona, Taylor Kaser, Paulina Cruz-Bravo

2020-Current year OA Pubs

OBJECTIVES: We previously implemented the subcutaneous (SQ) insulin in diabetic ketoacidosis (DKA) (SQuID) protocol, demonstrating safe, effective treatment of low to moderate (LTM) severity DKA in a non-intensive care unit setting. SQuID replaces intravenous (IV) insulin with SQ injections and reduces glucose checks from hourly to every 2 hours. We are not aware of any data on patient satisfaction with treatment in DKA. Our objective was to compare satisfaction in patients treated with IV insulin to that in patients treated with the SQ protocol.

METHODS: We conducted a cross-sectional study in an urban academic hospital (March 2023 to March 2024) …

Neuroimaging Findings In Nondemented Frail Individuals: A Systematic Review, Hamid Harandi, Soheil Mohammadi, Ali Jahanshahi, Mahsa Dolatshahi, Sogol Alikarami, Rasa Zafari, Cyrus A Raji

2020-Current year OA Pubs

BACKGROUND: Frailty is a chronic condition characterised by the progressive decline of multiple physiological functions. There is a critical need to investigate neuroimaging findings in nondemented frail individuals to better understand the underlying mechanisms and implications of frailty on brain health. This paper is aimed at reviewing neuroimaging studies assessing brain changes in nondemented frail individuals to understand the neuropsychological basis of frailty.

METHODS: A systematic review was conducted on studies focusing on neuroimaging modalities in frailty, including MRI, fMRI, DTI and PET. The review was based on PRISMA instructions and a two-step screening process. The studies evaluating neuroimaging findings …

Cross-Sectional Comparison Of Structural Mri Markers Of Impairment In A Diverse Cohort Of Older Adults, Julie K Wisch, Kalen Petersen, Peter R Millar, Omar Abdelmoity, Ganesh M Babulal, Karin L Meeker, Meredith N Braskie, Kristine Yaffe, Arthur W Toga, Sid O'Bryant, Beau M Ances, Habs‐Hd Study Team

2020-Current year OA Pubs

Neurodegeneration is presumed to be the pathological process measure most proximal to clinical symptom onset in Alzheimer Disease (AD). Structural MRI is routinely collected in research and clinical trial settings. Several quantitative MRI-based measures of atrophy have been proposed, but their low correspondence with each other has been previously documented. The purpose of this study was to identify which commonly used structural MRI measure (hippocampal volume, cortical thickness in AD signature regions, or brain age gap [BAG]) had the best correspondence with the Clinical Dementia Rating (CDR) in an ethno-racially diverse sample. 2870 individuals recruited by the Healthy and Aging …

Using Integrin Αvβ6-Targeted Positron Emission Tomography Imaging To Longitudinally Monitor Radiation-Induced Pulmonary Fibrosis In Vivo, William C Y Lo, Cristian W Villas Boas, Truc T Huynh, Amanda Klaas, Felicia Grogan, Lori Strong, Pamela Samson, Clifford G Robinson, Buck E Rogers, Carmen Bergom

2020-Current year OA Pubs

PURPOSE: Radiation-induced pulmonary fibrosis (RIPF) is a potentially serious and disabling late complication of radiation therapy. Monitoring RIPF progression is challenging due to the absence of early detection tools and the difficulty in distinguishing RIPF from other lung diseases using standard imaging methods. In the lungs, integrin αvβ6 is crucial in the development of RIPF, acting as a significant activator of transforming growth factor β after radiation injury. This study aimed to investigate integrin α

METHODS AND MATERIALS: We used a focal RIPF model (70 Gy delivered focally to a 3 mm spot in the lung) and a whole lung …

Cracking The Pericellular Matrix Code: Exploring How Mmp-2, -3, And -7 Influence Matrix Breakdown And Biomechanical Properties, Benjamin Tizian Baumann, Jule Nieuwstraten, Christian Konrads, Farshid Guilak, Marina Danalache

2020-Current year OA Pubs

INTRODUCTION: The intricate process of articular cartilage remodeling, pivotal for both physiological functions and osteoarthritis (OA) progression, is orchestrated through a balance of matrix synthesis and breakdown, which is mediated by matrix metalloproteinase enzymes (MMPs). At the heart of this remodeling lies the pericellular matrix (PCM), a specialized microenvironment encapsulating each chondrocyte and composed mainly of collagen type VI and perlecan. The aim of this study was to assess the impact of MMP-2, -3, and -7 on the structural integrity and biomechanical attributes of the PCM.

METHODS: Human articular cartilage explants (N = 10 patients) were incubated with activated MMP-2, …

Dataset And Analysis Of Automated And Manual Methods To Differentiate Wide Qrs Complex Tachycardias, Sarah Lococo, Anthony H Kashou, Abhishek J Deshmukh, Samuel J Asirvatham, Christopher V Desimone, Krasimira M Mikhova, Sandeep S Sodhi, Phillip S Cuculich, Rugheed Ghadban, Daniel H Cooper, Thomas M Maddox, Peter A Noseworthy, Adam M May

2020-Current year OA Pubs

The differentiation of wide complex tachycardias (WCTs) into ventricular tachycardia (VT) and supraventricular wide tachycardia (SWCT) via 12-lead ECG (electrocardiogram) interpretation is a crucial yet demanding clinical task. Decades of research have been dedicated to simplifying and improving this differentiation via manual algorithms. Despite such research, the effectiveness of such algorithms still remains limited, primarily due to reliance on user expertise. To combat this limitation, automated algorithms have been created that show promise as alternatives to manual ECG interpretation. However, direct comparison of the methods' diagnostic performances has not been undertaken. A recent publication (LoCoco et al., 2024) compared the …

Two Cardinal Features Of Als, Reduced Stmn2 And Pathogenic Tdp-43, Synergize To Accelerate Motor Decline In Mice, Kelsey L Krus, Ana Morales Benitez, Amy Strickland, Jeffrey Milbrandt, A Joseph Bloom, Aaron Diantonio

2020-Current year OA Pubs

Pathological TDP-43 loss from the nucleus and cytoplasmic aggregation occurs in almost all cases of ALS and half of frontotemporal dementia patients. Stathmin2 (Stmn2) is a key target of TDP-43 regulation and aberrantly spliced Stmn2 mRNA is found in patients with ALS, frontotemporal dementia, and Alzheimer's Disease. STMN2 participates in the axon injury response and its depletion in vivo partially replicates ALS-like symptoms including progressive motor deficits and distal NMJ denervation. The interaction between STMN2 loss and TDP-43 dysfunction has not been studied in mice because TDP-43 regulates human but not murine Stmn2 splicing. Therefore, we generated trans-heterozygous mice that …

Presentation And Surgical Outcomes Of Primary Hyperparathyroidism After Radioactive Iodine Therapy, Shaleen V Sathe, Blake Sparkman, Evan Bernard, Eileen R Smith, Kevin He, Alexander Chiu, Taylor C Brown

2020-Current year OA Pubs

BACKGROUND: Radioactive iodine (RAI) is a common treatment for various thyroid diseases. Previous studies have suggested susceptibility of parathyroid glands to the mutagenic effect of RAI and the development of primary hyperparathyroidism (PHPT). We tested the possible link between prior RAI treatment, disease presentation, and treatment outcomes.

METHODS: A retrospective analysis of 704 individuals who underwent parathyroidectomy for PHPT at a tertiary care center between the years 2015 and 2023 was performed. Preoperative and postoperative parameters, including demographic characteristics, biochemical markers, imaging data, and surgical and pathology findings were collected and analyzed to compare differences in patients who had previous …

Synthesis And In Vitro Evaluation Of Novel Compounds And Discovery Of A Promising Iodine-125 Radioligand For Purinergic P2x7 Receptor (P2x7r), Lin Qiu, Jinzhi Wang, Manju Tewari, Derek T Rensing, Terrance M Egan, Joel S Perlmutter, Zhude Tu

2020-Current year OA Pubs

The purinergic P2X ligand-gated ion channel 7 receptor (P2X7R) plays a critical role in various inflammatory processes and other diseases. Fast determination of compounds P2X7R binding potency and discovery of a promise PET radiotracer for imaging P2X7R require a P2X7R suitable radioligand for radioactive competitive binding assay. Herein, we designed and synthesized thirteen new P2X7R ligands and determined the in vitro binding potency. The fluorescence screening assay identified the iodide compound 1c with high potency and specificity toward P2X7R with an IC

The Effects Of Burst Steroid Therapy On Short-Term Decongestion In Acute Heart Failure Patients With Pro-Inflammatory Activation: A Post Hoc Analysis Of The Cortahf Randomized, Open-Label, Pilot Trial, Jan Biegus, Douglas L Mann, Et Al.

2020-Current year OA Pubs

BACKGROUND: The effect of steroids on congestion in patients with acute heart failure (AHF) is not known.

METHODS AND RESULTS: Patients with AHF, NT-proBNP levels > 1500 pg/mL and high-sensitivity C-reactive protein (hsCRP) levels > 20 mg/L were randomized to once-daily oral 40 mg prednisone for 7 days or usual care. In this post hoc analysis, congestion score was calculated on the basis of orthopnea, edema and rales (0 reflecting lack of congestion, and 9 maximal congestion) at each time point. Among 100 eligible patients randomized, those assigned to prednisone had a greater improvement in congestion score at day 31 (win odds …

Functional Or Structural Impairment Of Flow-Mediated Epicardial Vasodilation May Precede Coronary Microvascular Dysfunction, Ines Valenta, Salwa Mikhail, Ashwin Singh Parihar, Sudhir Jain, Thomas H Schindler

2020-Current year OA Pubs

BACKGROUND: The aim was to investigate whether functional and/or structural impairment of flow-mediated epicardial vasodilation (IEV) may precede coronary microvascular dysfunction (CMD) in a cardiometabolic risk population.

METHODS:

RESULTS: The prevalence of diffuse coronary artery calcification was highest in G1 with 51 %, followed by G3 with 46 % and G2 with 34 %. The extent of CCS was mild-to-moderate and did not differ significantly among groups (p = 0.222). Overall, IEV was present in 60 %, while there was a comparable prevalence of IEV between G2 and G3 (27 % and 33 %, p = 0.27). The hyperemic MBF …

Evaluating The World Health Organization's Hearts Model For Hypertension And Diabetes Management: A Pilot Implementation Study In Guatemala, Irmgardt Alicia Wellmann, Luis Fernando Ayala, Taryn M Valley, Vilma Irazola, Mark D Huffman, Michele Heisler, Peter Rohloff, Rocío Donis, Eduardo Palacios, Manuel Ramírez-Zea, David Flood

2020-Current year OA Pubs

BACKGROUND: The World Health Organization HEARTS Technical Package is a widely implemented global initiative to improve the primary care management of cardiovascular disease risk factors. The study's objective is to report outcomes from a pilot implementation trial of integrated hypertension and diabetes management based on the HEARTS model in Guatemala.

METHODS: We conducted a single-arm pilot implementation trial over six months from October 2023 to May 2024 in 11 Guatemalan Ministry of Health primary care facilities in two districts. The pilot evaluated a package of five HEARTS-aligned implementation strategies to improve the pharmacological treatment of hypertension and diabetes. The primary …

Mechanisms Of Uropathogenic E. Coli Mucosal Association In The Gastrointestinal Tract, Philippe N Azimzadeh, Nathaniel C Gualbuerto, Jerome S Pinkner, Kevin O Tamadonfar, Wandy Beatty, Thomas J Hannan, Karen W Dodson, Enid C Ibarra, Seonyoung Kim, Henry L Schreiber, James W Janetka, Andrew L Kau, Mark J Miller, Scott J Hultgren, Et Al.

2020-Current year OA Pubs

Urinary tract infections (UTIs) are highly recurrent and frequently caused by Uropathogenic

Stroma-Derived Dickkopf-1 Contributes To The Suppression Of Nk Cell Cytotoxicity In Breast Cancer, Seunghyun Lee, Biancamaria Ricci, Jennifer Tran, Emily Eul, Jiayu Ye, Qihao Ren, David Clever, Julia Wang, Pamela Wong, Michael S Haas, Sheila A Stewart, Cynthia X Ma, Todd A Fehniger, Roberta Faccio

2020-Current year OA Pubs

Mechanisms related to tumor evasion from NK cell-mediated immune surveillance remain enigmatic. Dickkopf-1 (DKK1) is a Wnt/β-catenin inhibitor, whose levels correlate with breast cancer progression. We find DKK1 to be expressed by tumor cells and cancer-associated fibroblasts (CAFs) in patient samples and orthotopic breast tumors, and in bone. By using genetic approaches, we find that bone-derived DKK1 contributes to the systemic DKK1 elevation in tumor-bearing female mice, while CAFs contribute to DKK1 at primary tumor site. Systemic and bone-specific DKK1 targeting reduce tumor growth. Intriguingly, deletion of CAF-derived DKK1 also limits breast cancer progression, without affecting its levels in circulation, …

Emotional Ecosystems: Understanding The Relationship Between Family Interactions And Anxiety Among Cancer Caregivers, Keisha White Makinde, Jacquelyn J Benson, Kyle A Pitzer, Maysara Mitchell, Debra Parker Oliver, George Demiris, Karla T Washington

2020-Current year OA Pubs

OBJECTIVES: Recent studies have challenged the assumption that families are invariable sources of support for cancer caregivers, noting that relationships with family members can have both positive and negative effects on caregiver well-being. This study expands upon prior literature to examine the relationship between cancer caregivers' perceptions of the quality of their family interactions and their symptoms of anxiety.

METHODS: We employed secondary analysis of baseline data from a multisite randomized clinical trial of an intervention for cancer caregivers conducted at 3 large academic palliative care clinics. We performed linear regression analyses to analyze the relationship between caregivers' perceptions of …

Species- And Strain-Specific Microbial Modulation Of Interferon, Innate Immunity, And Epithelial Barrier In 2d Air-Liquid Interface Respiratory Epithelial Cultures, Mian Horvath, Ruoyu Yang, Diana Cadena Castaneda, Megan Callender, Elizabeth S Aiken, Anita Y Voigt, Ryan Caldwell, José Fachi, Blanda Di Luccia, Zoe Scholar, Peter Yu, Andrew Salner, Marco Colonna, Karolina Palucka, Julia Oh

2020-Current year OA Pubs

BACKGROUND: The microbiome regulates the respiratory epithelium's immunomodulatory functions. To explore how the microbiome's biodiversity affects microbe-epithelial interactions, we screened 58 phylogenetically diverse microbes for their transcriptomic effect on human primary bronchial air-liquid interface (ALI) cell cultures.

RESULTS: We found distinct species- and strain-level differences in host innate immunity and epithelial barrier response. Strikingly, we found that host interferon, an antiviral response, was one of the most variable host processes. This variability was not driven by microbial phylogenetic diversity, bioburden, nor by the microbe's ability to stimulate other innate immunity pathways.

CONCLUSIONS: Microbial colonization differentially stimulates host gene expression with …

Propensity Score Matching: Should We Use It In Designing Observational Studies?, Fei Wan

2020-Current year OA Pubs

BACKGROUND: Propensity Score Matching (PSM) stands as a widely embraced method in comparative effectiveness research. PSM crafts matched datasets, mimicking some attributes of randomized designs, from observational data. In a valid PSM design where all baseline confounders are measured and matched, the confounders would be balanced, allowing the treatment status to be considered as if it were randomly assigned. Nevertheless, recent research has unveiled a different facet of PSM, termed "the PSM paradox". As PSM approaches exact matching by progressively pruning matched sets in order of decreasing propensity score distance, it can paradoxically lead to greater covariate imbalance, heightened model …

Robust Cluster Prediction Across Data Types Validates Association Of Sex And Therapy Response In Gbm, David L Gibbs, Gino Cioffi, Boris Aguilar, Kristin A Waite, Edward Pan, Jacob Mandel, Yoshie Umemura, Jingqin Luo, Joshua B Rubin, David Pot, Jill Barnholtz-Sloan

2020-Current year OA Pubs

BACKGROUND: Previous studies have described sex-specific patient subtyping in glioblastoma. The cluster labels associated with these "legacy data" were used to train a predictive model capable of recapitulating this clustering in contemporary contexts.

METHODS: We used robust ensemble machine learning to train a model using gene microarray data to perform multi-platform predictions including RNA-seq and potentially scRNA-seq.

RESULTS: The engineered feature set was composed of many previously reported genes that are associated with patient prognosis. Interestingly, these well-known genes formed a predictive signature only for female patients, and the application of the predictive signature to male patients produced unexpected results. …

Deficit Accumulation Frailty Index And Treatment Tolerability In Aml: Data From Calgb 11001 And 11002 (Alliance), Catherine Lai, Minji Lee, Olivia Bobek, Jennifer Le-Rademacher, Sumithra Mandrekar, Gail J Roboz, Geoffrey L Uy, Jeanne S Mandelblatt, Heidi D Klepin

2020-Current year OA Pubs

No abstract provided.

Safety And Efficacy Of Iv Onasemnogene Abeparvovec For Pediatric Patients With Spinal Muscular Atrophy: The Phase 3b Smart Study, Hugh J. Mcmillan, Craig M. Zaidman, Et Al.

2020-Current year OA Pubs

BACKGROUND AND OBJECTIVES: Safety and efficacy of IV onasemnogene abeparvovec has been demonstrated for patients with spinal muscular atrophy (SMA) weighing < 8.5 kg. SMART was the first clinical trial to evaluate onasemnogene abeparvovec for participants weighing 8.5-21 kg.

METHODS: SMART was an open-label, multicenter, phase 3b study conducted across 13 sites in 9 countries (NCT04851873). Symptomatic pediatric participants with SMA (any type; treatment-naïve or had discontinued prior treatment) were stratified into 3 weight cohorts (≥8.5-13, >13-17, and >17-21 kg), administered onasemnogene abeparvovec, and followed for 52 weeks. Corticosteroids were initiated 24 hours before infusion with dose increases in response to adverse events (AEs) and subsequent tapering at investigator discretion. The primary objective was safety. Secondary objective was …

Fate Erasure Logic Of Gene Networks Underlying Direct Neuronal Conversion Of Somatic Cells By Micrornas, Kitra Cates, Luorongxin Yuan, Yan Yang, Andrew S Yoo

2020-Current year OA Pubs

Neurogenic microRNAs 9/9

Tazemetostat, A Selective Ezh2 Inhibitor, In Combination With Pembrolizumab For Recurrent Or Metastatic Head And Neck Squamous Cell Carcinoma: A Phase 1 Trial, Peter J Oppelt, Sidharth V Puram, Jingxia Liu, Jessica C Ley, Douglas Adkins

2020-Current year OA Pubs

No abstract provided.

Ultra High Density Imaging Arrays In Diffuse Optical Tomography For Human Brain Mapping Improve Image Quality And Decoding Performance, Zachary E Markow, Jason W Trobaugh, Edward J Richter, Kalyan Tripathy, Sean M Rafferty, Alexandra M Svoboda, Mariel L Schroeder, Tracy M Burns-Yocum, Karla M Bergonzi, Mark A Chevillet, Emily M Mugler, Adam T Eggebrecht, Joseph P Culver

2020-Current year OA Pubs

Functional magnetic resonance imaging (fMRI) has dramatically advanced non-invasive human brain mapping and decoding. Functional near-infrared spectroscopy (fNIRS) and high-density diffuse optical tomography (HD-DOT) non-invasively measure blood oxygen fluctuations related to brain activity, like fMRI, at the brain surface, using more-lightweight equipment that circumvents ergonomic and logistical limitations of fMRI. HD-DOT grids have smaller inter-optode spacing (~ 13 mm) than sparse fNIRS (~ 30 mm) and therefore provide higher image quality, with spatial resolution ~ 1/2 that of fMRI, when using the several source-detector distances (13-40 mm) afforded by the HD-DOT grid. Herein, simulations indicated reducing inter-optode spacing to 6.5 …

Dna Polymerase Zeta Can Efficiently Replicate Structures Formed By At/Ta Repeat Sequences And Prevent Their Deletion, Mili Das, Suzanne E Hile, Jennifer Brewster, Jan Leendert Boer, Rachel Bezalel-Buch, Qiong Guo, Wei Yang, Peter M Burgers, Kristin A Eckert, Catherine H Freudenreich

2020-Current year OA Pubs

Long AT repeat tracts form non-B DNA structures that stall DNA replication and cause chromosomal breakage. AT repeats are abundant in human common fragile sites (CFSs), genomic regions that undergo breakage under replication stress. Using an in vivo yeast model system containing AT-rich repetitive elements from human CFS FRA16D, we find that DNA polymerase zeta (Pol ζ) is required to prevent breakage and subsequent deletions at hairpin and cruciform forming (AT/TA)n sequences, with little to no role at an (A/T)28 repeat or a control non-structure forming sequence. DNA polymerase eta is not protective for deletions at AT-rich structures, while DNA …