Digital Commons Network^™

A Precision Functional Atlas Of Personalized Network Topography And Probabilities, Robert J M Hermosillo, Ally Dworetsky, Babatunde Adeyemo, Caterina Gratton, Steven Petersen, Nico U F Dosenbach, Et Al.

2020-Current year OA Pubs

Although the general location of functional neural networks is similar across individuals, there is vast person-to-person topographic variability. To capture this, we implemented precision brain mapping functional magnetic resonance imaging methods to establish an open-source, method-flexible set of precision functional network atlases-the Masonic Institute for the Developing Brain (MIDB) Precision Brain Atlas. This atlas is an evolving resource comprising 53,273 individual-specific network maps, from more than 9,900 individuals, across ages and cohorts, including the Adolescent Brain Cognitive Development study, the Developmental Human Connectome Project and others. We also generated probabilistic network maps across multiple ages and integration zones (using a …

Disease Staging Of Alzheimer's Disease Using A Csf-Based Biomarker Model, Gemma Salvadó, Kanta Horie, Nicolas R Barthélemy, Charles D Chen, Andrew J Aschenbrenner, Brian A Gordon, Tammie L S Benzinger, David M Holtzman, John C Morris, Suzanne E Schindler, Randall J Bateman, Et Al.

2020-Current year OA Pubs

Biological staging of individuals with Alzheimer's disease (AD) may improve diagnostic and prognostic workup of dementia in clinical practice and the design of clinical trials. In this study, we used the Subtype and Stage Inference (SuStaIn) algorithm to establish a robust biological staging model for AD using cerebrospinal fluid (CSF) biomarkers. Our analysis involved 426 participants from BioFINDER-2 and was validated in 222 participants from the Knight Alzheimer Disease Research Center cohort. SuStaIn identified a singular biomarker sequence and revealed that five CSF biomarkers effectively constituted a reliable staging model (ordered: Aβ42/40, pT217/T217, pT205/T205, MTBR-tau243 and non-phosphorylated mid-region tau). The …

Single-Nucleotide Variant Calling In Single-Cell Sequencing Data With Monopogen, Jinzhuang Dou, Li Ding, Et Al.

2020-Current year OA Pubs

Single-cell omics technologies enable molecular characterization of diverse cell types and states, but how the resulting transcriptional and epigenetic profiles depend on the cell's genetic background remains understudied. We describe Monopogen, a computational tool to detect single-nucleotide variants (SNVs) from single-cell sequencing data. Monopogen leverages linkage disequilibrium from external reference panels to identify germline SNVs and detects putative somatic SNVs using allele cosegregating patterns at the cell population level. It can identify 100 K to 3 M germline SNVs achieving a genotyping accuracy of 95%, together with hundreds of putative somatic SNVs. Monopogen-derived genotypes enable global and local ancestry inference …

Genetic Complexities Of Cerebral Small Vessel Disease, Blood Pressure, And Dementia, Muralidharan Sargurupremraj, Chia-Ling Phuah, Carlos Cruchaga, Et Al.

2020-Current year OA Pubs

IMPORTANCE: Vascular disease is a treatable contributor to dementia risk, but the role of specific markers remains unclear, making prevention strategies uncertain.

OBJECTIVE: To investigate the causal association between white matter hyperintensity (WMH) burden, clinical stroke, blood pressure (BP), and dementia risk, while accounting for potential epidemiologic biases.

DESIGN, SETTING, AND PARTICIPANTS: This study first examined the association of genetically determined WMH burden, stroke, and BP levels with Alzheimer disease (AD) in a 2-sample mendelian randomization (2SMR) framework. Second, using population-based studies (1979-2018) with prospective dementia surveillance, the genetic association of WMH, stroke, and BP with incident all-cause dementia was …

Red Flag Signs And Symptoms For Patients With Early-Onset Colorectal Cancer: A Systematic Review And Meta-Analysis, Joshua Demb, Cassandra D L Fritz, Yin Cao, Et Al.

2020-Current year OA Pubs

IMPORTANCE: Early-onset colorectal cancer (EOCRC), defined as a diagnosis at younger than age 50 years, is increasing, and so-called red flag signs and symptoms among these individuals are often missed, leading to diagnostic delays. Improved recognition of presenting signs and symptoms associated with EOCRC could facilitate more timely diagnosis and impact clinical outcomes.

OBJECTIVE: To report the frequency of presenting red flag signs and symptoms among individuals with EOCRC, to examine their association with EOCRC risk, and to measure variation in time to diagnosis from sign or symptom presentation.

DATA SOURCES: PubMed/MEDLINE, Embase, CINAHL, and Web of Science were searched …

Spatial Mapping Of Hematopoietic Clones In Human Bone Marrow, Andrew L Young, Hannah C Davis, Maggie J Cox, Tyler M Parsons, Samantha C Burkart, Diane E Bender, Lulu Sun, Stephen T Oh, Grant A Challen

2020-Current year OA Pubs

UNLABELLED: Clonal hematopoiesis (CH) is the expansion of somatically mutated cells in the hematopoietic compartment of individuals without hematopoietic dysfunction. Large CH clones (i.e., >2% variant allele fraction) predispose to hematologic malignancy, but CH is detected at lower levels in nearly all middle-aged individuals. Prior work has extensively characterized CH in peripheral blood, but the spatial distribution of hematopoietic clones in human bone marrow is largely undescribed. To understand CH at this level, we developed a method for spatially aware somatic mutation profiling and characterized the bone marrow of a patient with polycythemia vera. We identified the complex clonal distribution …

Population Pharmacokinetic Analysis Of Atomoxetine And Its Metabolites In Children And Adolescents With Attention-Deficit/Hyperactivity Disorder., Shen Cheng, Mahmoud Al-Kofahi, J Steven Leeder, Jacob T. Brown

Manuscripts, Articles, Book Chapters and Other Papers

Atomoxetine (ATX) is a non-stimulant used to treat attention-deficit/hyperactivity disorder (ADHD) and systemic exposure is highly variable due to polymorphic cytochrome P450 2D6 (CYP2D6) activity. The objective of this study was to characterize the time course of ATX and metabolites (4-hydroxyatomoxetine (4-OH); N-desmethylatomoxetine (NDA); and 2-carboxymethylatomoxetine (2-COOH)) exposure following oral ATX dosing in children with ADHD to support individualized dosing. A nonlinear mixed-effect modeling approach was used to analyze ATX, 4-OH, and NDA plasma and urine, and 2-COOH urine profiles obtained over 24-72 hours from children with ADHD (n = 23) following a single oral ATX dose. Demographics and CYP2D6 …

Image Quality Characterization Of An Ultra-High-Speed Kilovoltage Cone-Beam Computed Tomography Imaging System On An O-Ring Linear Accelerator, Euidam Kim, Yang Kyun Park, Tianyu Zhao, Eric Laugeman, Xiaodong Neo Zhao, Yao Hao, Yoonsun Chung, Hugh Lee

2020-Current year OA Pubs

PURPOSE: The quality of on-board imaging systems, including cone-beam computed tomography (CBCT), plays a vital role in image-guided radiation therapy (IGRT) and adaptive radiotherapy. Recently, there has been an upgrade of the CBCT systems fused in the O-ring linear accelerators called HyperSight, featuring a high imaging performance. As the characterization of a new imaging system is essential, we evaluated the image quality of the HyperSight system by comparing it with Halcyon 3.0 CBCT and providing benchmark data for routine imaging quality assurance.

METHODS: The HyperSight features ultra-fast scan time, a larger kilovoltage (kV) detector, a more substantial kV tube, and …

Contemporary Management Of Aneurysmal Subarachnoid Haemorrhage. An Update For The Intensivist, Chiara Robba, Katharina M Busl, Jan Claassen, Michael N Diringer, Raimund Helbok, Soojin Park, Alejandro Rabinstein, Miriam Treggiari, Mervyn D I Vergouwen, Giuseppe Citerio

2020-Current year OA Pubs

Aneurysmal subarachnoid haemorrhage (aSAH) is a rare yet profoundly debilitating condition associated with high global case fatality and morbidity rates. The key determinants of functional outcome include early brain injury, rebleeding of the ruptured aneurysm and delayed cerebral ischaemia. The only effective way to reduce the risk of rebleeding is to secure the ruptured aneurysm quickly. Prompt diagnosis, transfer to specialized centers, and meticulous management in the intensive care unit (ICU) significantly improved the prognosis of aSAH. Recently, multimodality monitoring with specific interventions to correct pathophysiological imbalances has been proposed. Vigilance extends beyond intracranial concerns to encompass systemic respiratory and …

My Anesthesia Choice-Hf: Development And Preliminary Testing Of A Tool To Facilitate Conversations About Anesthesia For Hip Fracture Surgery, Mark D Neuman, Glyn Elwyn, Veena Graff, Viktoria Schmitz, Mary C Politi

2020-Current year OA Pubs

BACKGROUND: Patients often desire involvement in anesthesia decisions, yet clinicians rarely explain anesthesia options or elicit preferences. We developed My Anesthesia Choice-Hip Fracture, a conversation aid about anesthesia options for hip fracture surgery and tested its preliminary efficacy and acceptability.

METHODS: We developed a 1-page, tabular format, plain-language conversation aid with feedback from anesthesiologists, decision scientists, and community advisors. We conducted an online survey of English-speaking adults aged 50 and older. Participants imagined choosing between spinal and general anesthesia for hip fracture surgery. Before and after viewing the aid, participants answered a series of questions regarding key outcomes, including decisional …

Cooking With Liquefied Petroleum Gas Or Biomass And Fetal Growth Outcomes: A Multi-Country Randomised Controlled Trial, William Checkley, Victor G Dávila-Román, Lisa De Las Fuentes, Et Al.

2020-Current year OA Pubs

BACKGROUND: Household air pollution might lead to fetal growth restriction during pregnancy. We aimed to investigate whether a liquefied petroleum gas (LPG) intervention to reduce personal exposures to household air pollution during pregnancy would alter fetal growth.

METHODS: The Household Air Pollution Intervention Network (HAPIN) trial was an open-label randomised controlled trial conducted in ten resource-limited settings across Guatemala, India, Peru, and Rwanda. Pregnant women aged 18-34 years (9-19 weeks of gestation) were randomly assigned in a 1:1 ratio to receive an LPG stove, continuous fuel delivery, and behavioural messaging or to continue usual cooking with biomass for 18 months. …

Key Variants Via The Alzheimer's Disease Sequencing Project Whole Genome Sequence Data, Yanbing Wang, Chloé Sarnowski, Honghuang Lin, Achilleas N Pitsillides, Nancy L Heard-Costa, Seung Hoan Choi, Dongyu Wang, Joshua C Bis, Elizabeth E Blue, Eric Boerwinkle, Philip L De Jager, Myriam Fornage, Ellen M Wijsman, Sudha Seshadri, Josée Dupuis, Gina M Peloso, Anita L Destefano

Faculty, Staff and Student Publications

INTRODUCTION: Genome-wide association studies (GWAS) have identified loci associated with Alzheimer's disease (AD) but did not identify specific causal genes or variants within those loci. Analysis of whole genome sequence (WGS) data, which interrogates the entire genome and captures rare variations, may identify causal variants within GWAS loci.

METHODS: We performed single common variant association analysis and rare variant aggregate analyses in the pooled population (N cases = 2184, N controls = 2383) and targeted analyses in subpopulations using WGS data from the Alzheimer's Disease Sequencing Project (ADSP). The analyses were restricted to variants within 100 kb of 83 previously …

Retinal Dystrophies Associated With Peripherin-2: Genetic Spectrum And Novel Clinical Observations In 241 Patients, Rachael C. Heath Jeffery, Jennifer A. Thompson, Johnny Lo, Enid S. Chelva, Sean Armstrong, Jose S. Pulido, Rebecca Procopio, Andrea L. Vincent, Lorenzo Bianco, Maurizio Battaglia Parodi, Lucia Ziccardi, Giulio Antonelli, Lucilla Barbano, João P. Marques, Sara Geada, Ana L. Carvalho, Wei C. Tang, Choi M. Chan, Camiel J. F. Boon, Jonathan Hensman, Ta-Ching Chen, Chien-Yu Lin, Pei-Lung Chen, Ajoy Vincent, Anupreet Tumber, Elise Heon, John R. Grigg, Robyn V. Jamieson, Elisa E. Cornish, Benjamin M. Nash, Shyamanga Borooah, Lauren N. Ayton, Alexis Ceecee Britten-Jones, Thomas L. Edwards, Jonathan B. Ruddle, Abhishek Sharma, Rowan G. Porter, Tina M. Lamey, Terri L. Mclaren, Samuel Mclenachan, Danial Roshandel, Fred K. Chen

Wills Eye Hospital Papers

PURPOSE: To describe the clinical, electrophysiological and genetic spectrum of inherited retinal diseases associated with variants in the PRPH2 gene.

METHODS: A total of 241 patients from 168 families across 15 sites in 9 countries with pathogenic or likely pathogenic variants in PRPH2 were included. Records were reviewed for age at symptom onset, visual acuity, full-field ERG, fundus colour photography, fundus autofluorescence (FAF), and SD-OCT. Images were graded into six phenotypes. Statistical analyses were performed to determine genotype-phenotype correlations.

RESULTS: The median age at symptom onset was 40 years (range, 4-78 years). FAF phenotypes included normal (5%), butterfly pattern dystrophy, …

Outcomes Of Infectious Panuveitis Associated With Simultaneous Multi-Positive Ocular Fluid Polymerase Chain Reaction, Viet Q. Chau, John W. Hinkle, Chris Y. Wu, Parastou Pakravan, Vincent Volante, Jesse D. Sengillo, Patrick C. Staropoli, Darlene Miller, Nicolas A. Yannuzzi, Thomas A. Albini

Wills Eye Hospital Papers

PURPOSE: To evaluate features of infectious panuveitis associated with multiple pathogens detected by ocular fluid sampling.

METHODS: Single-center, retrospective, consecutive case series of patients with aqueous/vitreous polymerase chain reaction testing with >1 positive result in a single sample from 2001 to 2021.

RESULTS: Of 1,588 polymerase chain reaction samples, 28 (1.76%) were positive for two pathogens. Most common pathogens were cytomegalovirus (n = 16, 57.1%) and Epstein-Barr virus (n = 13, 46.4%), followed by varicella zoster virus (n = 8, 28.6%), Toxoplasma gondii (n = 6, 21.4%), herpes simplex virus 2 (n = 6, 21.4%), herpes simplex virus 1 (n …

Travel-Time Disparities In Access To Proton Beam Therapy For Cancer Treatment, Todd Burus, Alexander Vanhelene, Michael Rooney, Krystle Lang Kuhs, W. Jay Christian, Christopher Mcnair, Sanjay Mishra, Arnold Paulino, Grace Smith, Steven Frank, Jeremy Warner

Department of Pharmacology, Physiology, and Cancer Biology Faculty Papers

IMPORTANCE: Proton beam therapy is an emerging radiotherapy treatment for patients with cancer that may produce similar outcomes as traditional photon-based therapy for many cancers while delivering lower amounts of toxic radiation to surrounding tissue. Geographic proximity to a proton facility is a critical component of ensuring equitable access both for indicated diagnoses and ongoing clinical trials.

OBJECTIVE: To characterize the distribution of proton facilities in the US, quantify drive-time access for the population, and investigate the likelihood of long commutes for certain population subgroups.

DESIGN, SETTING, AND PARTICIPANTS: This population-based cross-sectional study analyzed travel times to proton facilities in …

Patterns Of Undertreatment And Overtreatment In Adjuvant Radiotherapy For Early-Stage Endometrial Cancer Based On Molecular Classification, Otilia Ciobanu, Yixuan He, Alicia R Martin, Jill S Remick, Joseph W Shelton, Tony Y Eng, David C Qian

Faculty, Staff and Student Publications

The quality improvement study examines the use of risk-adaptive adjuvant radiotherapy in women with non–mismatch repair deficiency endometrial cancer.

Abnormality Of Early White Matter Development In Tuberous Sclerosis Complex And Autism Spectrum Disorder: Longitudinal Analysis Of Diffusion Tensor Imaging Measures, Siddharth Srivastava, Fanghan Yang, Anna K Prohl, Peter E Davis, Jamie K Capal, Rajna Filip-Dhima, E Martina Bebin, Darcy A Krueger, Hope Northrup, Joyce Y Wu, Simon K Warfield, Mustafa Sahin, Bo Zhang, Tacern Study Group

Faculty, Staff and Student Publications

Background:

Abnormalities in white matter development may influence development of autism spectrum disorder in tuberous sclerosis complex (TSC). Our goals for this study were as follows: (1) use data from a longitudinal neuroimaging study of tuberous sclerosis complex (TACERN) to develop optimized linear mixed effects models for analyzing longitudinal, repeated diffusion tensor imaging metrics (fractional anisotropy, mean diffusivity) pertaining to select white matter tracts, in relation to positive Autism Diagnostic Observation Schedule–Second Edition classification at 36 months, and (2) perform an exploratory analysis using optimized models applied to all white matter tracts from these data.

Methods:

Eligible participants (3-12 months) …

Ictal Central Apnea Is Predictive Of Mesial Temporal Seizure Onset: An Intracranial Investigation, Nuria Lacuey, Blanca Talavera, Oman Magana-Tellez, Oscar Mancera-Páez, Norma Hupp, Xi Luo, Johnson P Hampson, Jaison Hampson, M R Sandhya Rani, Manuela Ochoa-Urrea, Omar A Alamoudi, Stephen Melius, Sandipan Pati, Jay Gavvala, Nitin Tandon, John C Mosher, Samden D Lhatoo

Faculty, Staff and Student Publications

Objective: Ictal central apnea (ICA) is a semiological sign of focal epilepsy, associated with temporal and frontal lobe seizures. In this study, using qualitative and quantitative approaches, we aimed to assess the localizational value of ICA. We also aimed to compare ICA clinical utility in relation to other seizure semiological features of focal epilepsy.

Methods: We analyzed seizures in patients with medically refractory focal epilepsy undergoing intracranial stereotactic electroencephalographic (SEEG) evaluations with simultaneous multimodal cardiorespiratory monitoring. A total of 179 seizures in 72 patients with reliable artifact-free respiratory signal were analyzed.

Results: ICA was seen in 55 of 179 (30.7%) …

Association Of Minor Electrocardiographic (Ecg) Abnormalities With Epilepsy Duration In Children: A Manifestation Of The Epileptic Heart?, Brittnie Bartlett-Lee, Leslie Dervan, Christina Miyake, R Scott Watson, See Wai Chan, Anne E Anderson, Yi-Chen Lai

Faculty, Staff and Students Publications

Purpose: Cardiac abnormalities resulting from chronic epilepsy ("the epileptic heart") constitute a well-recognized comorbidity. However, the association of cardiac alterations with epilepsy duration remains understudied. We sought to evaluate this association using electrocardiogram (ECG).

Methods: We prospectively enrolled children between 1 months and 18 years of age without known cardiac conditions or ion channelopathies during routine clinic visits. ECGs were categorized as abnormal if there were alterations in rhythm; PR, QRS, or corrected QT interval; QRS axis or morphology; ST segment or T wave. An independent association between ECG abnormalities and epilepsy duration was evaluated using multivariable logistic regression modeling. …

Longitudinal Natural History Studies Based On Real-World Data In Rare Diseases: Opportunity And A Novel Approach, Laura Ann Adang, Anjana Sevagamoorthy, Omar Sherbini, Jamie L Fraser, Joshua L Bonkowsky, Francesco Gavazzi, Russel D'Aiello, Nicholson B Modesti, Emily Yu, Sylvia Mutua, Emma Kotes, Justine Shults, Ariel Vincent, Lisa T Emrick, Stephanie Keller, Keith P Van Haren, Sarah Woidill, Isabella Barcelos, Amy Pizzino, Johanna L Schmidt, Florian Eichler, Ali Fatemi, Adeline Vanderver

Faculty, Staff and Students Publications

Growing interest in therapeutic development for rare diseases necessitate a systematic approach to the collection and curation of natural history data that can be applied consistently across this group of heterogenous rare diseases. In this study, we discuss the challenges facing natural history studies for leukodystrophies and detail a novel standardized approach to creating a longitudinal natural history study using existing medical records.

Prospective studies are uniquely challenging for rare diseases. Delays in diagnosis and overall rarity limit the timely collection of natural history data. When feasible, prospective studies are often cross-sectional rather than longitudinal and are unlikely to capture …

Robotic-Assisted Single-Site Abdominal Cerclage In The Bicornuate Uterus Patient With Cervical Insufficiency, Nurul Farhanah Binte Abdul Latif, Zhenkun Guan, Sylvia Asare, Xiaoming Guan

Faculty, Staff and Students Publications

Objective: To demonstrate the surgical techniques for improving safety in robotic-assisted abdominal cerclage in patients with bicornuate uteri complicated by recurrent pregnancy loss and cervical insufficiency.

Design: Stepwise demonstration with narrated video footage.

Setting: An academic tertiary care hospital.

Patients: Our patient is a 22-year-old G2P0020 with a history of recurrent pregnancy loss. During her first pregnancy, she was asymptomatic until 19 weeks and delivered because of a preterm premature rupture of membranes. A transvaginal cerclage was performed for her second pregnancy at 14 weeks, which ended at 16 weeks because of preterm premature rupture of membranes. The final magnetic …

Rna Sequencing For Solid Tumor Fusion Gene Detection: Proficiency Testing Practice And Performance Comparison, Julia A Bridge, Kevin C Halling, Joel T Moncur, Rhona J Souers, Meera R Hameed, Helen Fernandes, Angshumoy Roy, Lea Surrey, Laura J Tafe, Patricia Vasalos, Dolores H Lopez-Terrada

Faculty, Staff and Students Publications

Context: Next-generation sequencing-based approaches using RNA have increasingly been used by clinical laboratories for the detection of fusion genes, intragenic rearrangements, and exon-skipping events. Correspondingly, the College of American Pathologists (CAP) has advanced RNA sequencing proficiency testing (PT) to ensure optimal performance of these assays.

Objective: To report on laboratory performance and practices of RNA sequencing for the detection of fusion genes, intragenic rearrangements, and exon-skipping events using CAP PT data from 8 mailings (2018-A through 2021-B).

Design: CAP PT RNA sequencing program results from 153 laboratories across 24 proficiency test specimens, interrogating 22 distinct engineered fusion transcripts, were analyzed …

Immune Cell Pair Ratio Captured By Imaging Mass Cytometry Has Superior Predictive Value For Prognosis Of Non-Small Cell Lung Cancer Than Cell Fraction And Density, Jian-Rong Li, Chao Cheng

Faculty, Staff and Students Publications

No abstract provided.

Using Workplace-Based Assessments In Undergraduate Medical Education, Arindam Sarkar

Faculty, Staff and Students Publications

No abstract provided.

Proteomic Biomarkers Of Quantitative Interstitial Abnormalities In Copdgene And Cardia Lung Study, Bina Choi, Gabrielle Y Liu, Quanhu Sheng, Kaushik Amancherla, Andrew Perry, Xiaoning Huang, Ruben San José Estépar, Samuel Y Ash, Weihua Guan, David R Jacobs, Fernando J Martinez, Ivan O Rosas, Russell P Bowler, Jonathan A Kropski, Nicholas E Banovich, Sadiya S Khan, Raúl San José Estépar, Ravi Shah, Bharat Thyagarajan, Ravi Kalhan, George R Washko

Faculty, Staff and Students Publications

Rationale: Quantitative interstitial abnormalities (QIAs) are early measures of lung injury automatically detected on chest computed tomography scans. QIAs are associated with impaired respiratory health and share features with advanced lung diseases, but their biological underpinnings are not well understood. Objectives: To identify novel protein biomarkers of QIAs using high-throughput plasma proteomic panels within two multicenter cohorts.

Methods: We measured the plasma proteomics of 4,383 participants in an older, ever-smoker cohort (COPDGene [Genetic Epidemiology of Chronic Obstructive Pulmonary Disease]) and 2,925 participants in a younger population cohort (CARDIA [Coronary Artery Disease Risk in Young Adults]) using the SomaLogic SomaScan assays. …

Targeting C-Myc Transactivation By Lmna Inhibits Trna Processing Essential For Malate-Aspartate Shuttle And Tumour Progression, Jianqun Wang, Mei Hong, Yang Cheng, Xiaojing Wang, Dan Li, Guo Chen, Banghe Bao, Jiyu Song, Xinyi Du, Chunhui Yang, Liduan Zheng, Qiangsong Tong

Faculty, Staff and Students Publications

Background: A series of studies have demonstrated the emerging involvement of transfer RNA (tRNA) processing during the progression of tumours. Nevertheless, the roles and regulating mechanisms of tRNA processing genes in neuroblastoma (NB), the prevalent malignant tumour outside the brain in children, are yet unknown.

Methods: Analysis of multi-omics results was conducted to identify crucial regulators of downstream tRNA processing genes. Co-immunoprecipitation and mass spectrometry methods were utilised to measure interaction between proteins. The impact of transcriptional regulators on expression of downstream genes was measured by dual-luciferase reporter, chromatin immunoprecipitation, western blotting and real-time quantitative reverse transcription-polymerase chain reaction (RT-PCR) …

Neurodevelopment And Metabolism In The Maternal-Placental-Fetal Unit, Mariana Parenti, Rebecca J Schmidt, Daniel J Tancredi, Irva Hertz-Picciotto, Cheryl K Walker, Carolyn M Slupsky

Faculty, Staff and Students Publications

Importance: Disturbances in maternal, placental, and fetal metabolism are associated with developmental outcomes. Associations of maternal, placental, and fetal metabolism with subsequent neurodevelopmental outcomes in the child are understudied.

Objective: To investigate the metabolic associations within the maternal-placental-fetal unit and subsequent neurodevelopmental outcomes in younger siblings of children with autism spectrum disorder (ASD).

Design, setting, and participants: This cohort study was conducted within a subset of the Markers of Autism Risk in Babies, Learning Early Signs (MARBLES) cohort. MARBLES is a prospective birth cohort of younger siblings of children with ASD assessed for neurodevelopmental outcomes at approximately age 36 months. …

Virtual Scribes And Physician Time Spent On Electronic Health Records, Lisa Rotenstein, Edward R Melnick, Christine Iannaccone, Jianyi Zhang, Aqsa Mugal, Stuart R Lipsitz, Michael J Healey, Christopher Holland, Richard Snyder, Christine A Sinsky, David Ting, David W Bates

Faculty, Staff and Students Publications

Importance: Time on the electronic health record (EHR) is associated with burnout among physicians. Newer virtual scribe models, which enable support from either a real-time or asynchronous scribe, have the potential to reduce the burden of the EHR and EHR-related documentation.

Objective: To characterize the association of use of virtual scribes with changes in physicians' EHR time and note and order composition and to identify the physician, scribe, and scribe response factors associated with changes in EHR time upon virtual scribe use.

Design, setting, and participants: Retrospective, pre-post quality improvement study of 144 physicians across specialties who had used a …

Looking Beyond Mortality Prediction: Primary Care Physician Views Of Patients' Palliative Care Needs Predicted By A Machine Learning Tool, Lisa Rotenstein, Liqin Wang, Sophia N Zupanc, Akhila Penumarthy, John Laurentiev, Jan Lamey, Subrina Farah, Stuart Lipsitz, Nina Jain, David W Bates, Li Zhou, Joshua R Lakin

Faculty, Staff and Students Publications

Objectives: To assess primary care physicians' (PCPs) perception of the need for serious illness conversations (SIC) or other palliative care interventions in patients flagged by a machine learning tool for high 1-year mortality risk.

Methods: We surveyed PCPs from four Brigham and Women's Hospital primary care practice sites. Multiple mortality prediction algorithms were ensembled to assess adult patients of these PCPs who were either enrolled in the hospital's integrated care management program or had one of several chronic conditions. The patients were classified as high or low risk of 1-year mortality. A blinded survey had PCPs evaluate these patients for …

Single-Tube Four-Target Lateral Flow Assay Detects Human Papillomavirus Types Associated With Majority Of Cervical Cancers, Maria Barra, Megan Chang, Mila P Salcedo, Kathleen Schmeler, Michael Scheurer, Mauricio Maza, Leticia Lopez, Karla Alfaro, Rebecca Richards-Kortum

Faculty, Staff and Students Publications

Isothermal nucleic acid amplification methods have many advantages for use at the point of care. However, there is a lack of multiplexed isothermal amplification tests to detect multiple targets in a single reaction, which would be valuable for many diseases, such as infection with high-risk human papillomavirus (hrHPV). In this study, we developed a multiplexed loop-mediated isothermal amplification (LAMP) reaction to detect the three most common hrHPV types that cause cervical cancer (HPV16, HPV18, and HPV45) and a cellular control for sample adequacy. First, we characterized the assay limit of detection (LOD) in a real-time reaction with fluorescence readout; after …