Digital Commons Network^™

Relationship Between Mri Brain-Age Heterogeneity, Cognition, Genetics And Alzheimer's Disease Neuropathology, Mathilde Antoniades, Pamela Lamontagne, Tammie Benzinger, Daniel S Marcus, John C Morris, Et Al.

2020-Current year OA Pubs

BACKGROUND: Brain ageing is highly heterogeneous, as it is driven by a variety of normal and neuropathological processes. These processes may differentially affect structural and functional brain ageing across individuals, with more pronounced ageing (older brain age) during midlife being indicative of later development of dementia. Here, we examined whether brain-ageing heterogeneity in unimpaired older adults related to neurodegeneration, different cognitive trajectories, genetic and amyloid-beta (Aβ) profiles, and to predicted progression to Alzheimer's disease (AD).

METHODS: Functional and structural brain age measures were obtained for resting-state functional MRI and structural MRI, respectively, in 3460 cognitively normal individuals across an age …

Attention-Based Cnn-Bilstm For Sleep State Classification Of Spatiotemporal Wide-Field Calcium Imaging Data, Xiaohui Zhang, Eric C Landsness, Hanyang Miao, Wei Chen, Michelle J Tang, Lindsey M Brier, Joseph P Culver, Jin-Moo Lee, Mark A Anastasio

2020-Current year OA Pubs

BACKGROUND: Wide-field calcium imaging (WFCI) with genetically encoded calcium indicators allows for spatiotemporal recordings of neuronal activity in mice. When applied to the study of sleep, WFCI data are manually scored into the sleep states of wakefulness, non-REM (NREM) and REM by use of adjunct EEG and EMG recordings. However, this process is time-consuming, invasive and often suffers from low inter- and intra-rater reliability. Therefore, an automated sleep state classification method that operates on spatiotemporal WFCI data is desired.

NEW METHOD: A hybrid network architecture consisting of a convolutional neural network (CNN) to extract spatial features of image frames and …

Adjuvant Trastuzumab Emtansine Versus Paclitaxel Plus Trastuzumab For Stage I Human Epidermal Growth Factor Receptor 2-Positive Breast Cancer: 5-Year Results And Correlative Analyses From Atempt, Paolo Tarantino, Ron Bose, Et Al.

2020-Current year OA Pubs

PURPOSE: Long-term outcomes of patients with stage I human epidermal growth factor receptor 2 (HER2)-positive breast cancer receiving adjuvant trastuzumab emtansine (T-DM1) remain undefined, and prognostic predictors represent an unmet need.

METHODS: In the ATEMPT phase II trial, patients with stage I centrally confirmed HER2-positive breast cancer were randomly assigned 3:1 to adjuvant T-DM1 for 1 year or paclitaxel plus trastuzumab (TH). Coprimary objectives were to compare the incidence of clinically relevant toxicities between arms and to evaluate invasive disease-free survival (iDFS) with T-DM1. Correlative analyses included the HER2DX genomic tool, multiomic evaluations of HER2 heterogeneity, and predictors of thrombocytopenia. …

Clinical Validation Of A Cell-Free Dna Fragmentome Assay For Augmentation Of Lung Cancer Early Detection, Peter J Mazzone, David Gierada, Et Al.

2020-Current year OA Pubs

Lung cancer screening via annual low-dose computed tomography has poor adoption. We conducted a prospective case-control study among 958 individuals eligible for lung cancer screening to develop a blood-based lung cancer detection test that when positive is followed by a low-dose computed tomography. Changes in genome-wide cell-free DNA fragmentation profiles (fragmentomes) in peripheral blood reflected genomic and chromatin characteristics of lung cancer. We applied machine learning to fragmentome features to identify individuals who were more or less likely to have lung cancer. We trained the classifier using 576 cases and controls from study samples and validated it in a held-out …

Distinct Patterns Of Smooth Muscle Phenotypic Modulation In Thoracic And Abdominal Aortic Aneurysms, Chien-Jung Lin, Campbell Keating, Robyn Roth, Yasar Caliskan, Mustafa Nazzal, Vernat Exil, Richard Dipaolo, Divya Ratan Verma, Kishore Harjai, Mohamed Zayed, Chieh-Yu Lin, Robert P Mecham, Ajay K Jain

2020-Current year OA Pubs

Thoracic and abdominal aortic aneurysms (TAAs and AAAs, respectively) share morphological features but have distinct clinical and hereditary characteristics. Studies using bulk RNA comparisons revealed distinct patterns of gene expression in human TAA and AAA tissues. However, given the summative nature of bulk RNA studies, these findings represent the totality of gene expression without regards to the differences in cellular composition. Single-cell RNA sequencing provides an opportunity to interrogate cell-type-specific transcriptomes. Single cell RNA sequencing datasets from mouse TAA (GSE153534) and AAA (GSE164678 and GSE152583) with respective controls were obtained from the Gene Expression Omnibus. Bioinformatic analysis was performed with …

A Phase 1 First-In-Human Study Of The Mcl-1 Inhibitor Azd5991 In Patients With Relapsed/Refractory Hematologic Malignancies, Pinkal Desai, Amanda Cashen, Et Al.

2020-Current year OA Pubs

PURPOSE: AZD5991, a human MCL-1 inhibitor, was assessed for safety, tolerability, pharmacokinetics, and antitumor activity as monotherapy and in combination with venetoclax in patients with relapsed or refractory hematologic malignancies.

PATIENTS AND METHODS: In the monotherapy cohort (n = 61), patients with hematologic malignancies received AZD5991 intravenously in escalating doses either once or twice weekly, following intrapatient dose escalation, during a 3-week cycle. In the combination cohort (n = 17), patients with acute myeloid leukemia and myelodysplastic syndrome received escalating doses of AZD5991 and venetoclax during either a 3- or 4-week cycle. Primary objectives were safety and maximum tolerated dose; …

Il-10r Inhibition Reprograms Tumor-Associated Macrophages And Reverses Drug Resistance In Multiple Myeloma, Jennifer Sun, Monica Shokeen, Barbara Muz, Kinan Alhallak, Chaelee Park, Berit Lubben, Yixuan Chen, Ola Adebayo, Hannah Bash, Sarah Kelley, Mark Fiala, Diane E Bender, Ravi Vij, Abdel Kareem Azab, Et Al.

2020-Current year OA Pubs

Multiple myeloma (MM) is the cancer of plasma cells within the bone marrow and remains incurable. Tumor-associated macrophages (TAMs) within the tumor microenvironment often display a pro-tumor phenotype and correlate with tumor proliferation, survival, and therapy resistance. IL-10 is a key immunosuppressive cytokine that leads to recruitment and development of TAMs. In this study, we investigated the role of IL-10 in MM TAM development as well as the therapeutic application of IL-10/IL-10R/STAT3 signaling inhibition. We demonstrated that IL-10 is overexpressed in MM BM and mediates M2-like polarization of TAMs in patient BM, 3D co-cultures in vitro, and mouse models. In …

Multiomic Profiling Identifies Predictors Of Survival In African American Patients With Acute Myeloid Leukemia, Andrew Stiff, Geoffrey L Uy, Et Al.

2020-Current year OA Pubs

Genomic profiles and prognostic biomarkers in patients with acute myeloid leukemia (AML) from ancestry-diverse populations are underexplored. We analyzed the exomes and transcriptomes of 100 patients with AML with genomically confirmed African ancestry (Black; Alliance) and compared their somatic mutation frequencies with those of 323 self-reported white patients with AML, 55% of whom had genomically confirmed European ancestry (white; BeatAML). Here we find that 73% of 162 gene mutations recurrent in Black patients, including a hitherto unreported PHIP alteration detected in 7% of patients, were found in one white patient or not detected. Black patients with myelodysplasia-related AML were younger …

Limitations And Potential Of Κor Biased Agonists For Pain And Itch Management, Amal El Daibani, Manish K Madasu, Ream Al-Hasani, Tao Che

2020-Current year OA Pubs

The concept of ligand bias is based on the premise that different agonists can elicit distinct responses by selectively activating the same receptor. These responses often determine whether an agonist has therapeutic or undesirable effects. Therefore, it would be highly advantageous to have agonists that specifically trigger the therapeutic response. The last two decades have seen a growing trend towards the consideration of ligand bias in the development of ligands to target the κ-opioid receptor (κOR). Most of these ligands selectively favor G-protein signaling over β-arrestin signaling to potentially provide effective pain and itch relief without adverse side effects associated …

Transmembrane Protein 53 Craniotubular Dysplasia (Omim # 619727): The Skeletal Disease And Consequent Blindness Of This New Disorder, Michael P Whyte, Robert S Weinstein, Paul H Phillips, William H Mcalister, Raghuhr H Ramakrishnaiah, G Bradley Schaefer, Rongsheng Cai, Michele R Hutchison, Shenghui Duan, Gary S Gottesman, Steven Mumm

2020-Current year OA Pubs

Craniotubular dysplasia, Ikegawa type (OMIM #619727) denotes the autosomal recessive skeletal disease identified in 2021 featuring blindness acquired in childhood. Five young members of four Indian families harbored a homozygous indel within TMEM53 (OMIM *619722), the gene that encodes transmembrane protein 53 (TMEM53). When intact, TMEM53 spans the nuclear envelope of osteoprogenitor cells, dampens BMP-SMAD signaling, and thereby slows bone formation. Consequently, defective TMEM53 accelerates osteogenesis. Herein, an American boy is compound heterozygous for a novel deletion and a novel missense mutation within TMEM53. His vision and sensorineural hearing became impaired. Radiographic survey revealed diploic thickening of his skull, broad …

Iglon5 Frequency In Idiopathic Rem Sleep Behavior Disorder: A Multicenter Study, Ronald Postuma, Jennifer Mcleland, Albert A. Davis, Yo-El S. Ju, Et Al.

2020-Current year OA Pubs

BACKGROUND AND OBJECTIVES: Idiopathic/isolated REM sleep behavior disorder (iRBD) has been strongly linked to neurodegenerative synucleinopathies such as Parkinson disease, dementia with Lewy bodies, and multiple system atrophy. However, there have been increasing reports of RBD as a presenting feature of serious and treatable autoimmune syndromes, particularly IGLON5. This study's objective was to investigate the frequency of autoantibodies in a large cohort of participants with iRBD.

METHODS: Participants were enrolled in the North American Prodromal Synucleinopathy cohort with polysomnography-confirmed iRBD, free of parkinsonism and dementia. Plasma samples were systematically screened for the autoantibodies IGLON5, DPPX, LGI1, and CASPR2 using plasma …

Current Best Practices And Future Opportunities For Reproducible Findings Using Large-Scale Neuroimaging In Psychiatry, Neda Jahanshad, Petra Lenzini, Janine Bijsterbosch

2020-Current year OA Pubs

Research into the brain basis of psychopathology is challenging due to the heterogeneity of psychiatric disorders, extensive comorbidities, underdiagnosis or overdiagnosis, multifaceted interactions with genetics and life experiences, and the highly multivariate nature of neural correlates. Therefore, increasingly larger datasets that measure more variables in larger cohorts are needed to gain insights. In this review, we present current "best practice" approaches for using existing databases, collecting and sharing new repositories for big data analyses, and future directions for big data in neuroimaging and psychiatry with an emphasis on contributing to collaborative efforts and the challenges of multi-study data analysis.

Tocilizumab Prophylaxis Following Axicabtagene Ciloleucel In Relapsed Or Refractory Large B-Cell Lymphoma, Frederick L Locke, Nancy L Bartlett, Et Al.

2020-Current year OA Pubs

Axicabtagene ciloleucel (axi-cel) is an autologous anti-CD19 chimeric antigen receptor (CAR) T-cell therapy approved in patients with relapsed/refractory (R/R) large B-cell lymphoma (LBCL). Most patients treated with axi-cel experience cytokine release syndrome (CRS) and/or adverse neurologic events (NEs). To explore potential approaches for reducing CAR T-cell-related toxicities with axi-cel, several safety expansion cohorts were added to the pivotal ZUMA-1 trial. ZUMA-1 Cohort 3 was an exploratory safety cohort that investigated the use of the IL-6 receptor-blocking antibody tocilizumab and anticonvulsant levetiracetam as prophylaxis against CRS and NEs in patients treated with axi-cel. Patients with R/R LBCL were enrolled in Cohort …

Psychiatric Neuroimaging Designs For Individualised, Cohort, And Population Studies, Martin Gell, Stephanie Noble, Timothy O Laumann, Steven M Nelson, Brenden Tervo-Clemmens

2020-Current year OA Pubs

Psychiatric neuroimaging faces challenges to rigour and reproducibility that prompt reconsideration of the relative strengths and limitations of study designs. Owing to high resource demands and varying inferential goals, current designs differentially emphasise sample size, measurement breadth, and longitudinal assessments. In this overview and perspective, we provide a guide to the current landscape of psychiatric neuroimaging study designs with respect to this balance of scientific goals and resource constraints. Through a heuristic data cube contrasting key design features, we discuss a resulting trade-off among small sample, precision longitudinal studies (e.g., individualised studies and cohorts) and large sample, minimally longitudinal, population …

Differential Chromatin Accessibility And Transcriptional Dynamics Define Breast Cancer Subtypes And Their Lineages, Michael D Iglesia, Reyka G Jayasinghe, Siqi Chen, Nadezhda V Terekhanova, John M Herndon, Erik Storrs, Alla Karpova, Daniel Cui Zhou, Nataly Naser Al Deen, Andrew T Shinkle, Rita Jui-Hsien Lu, Wagma Caravan, Andrew Houston, Yanyan Zhao, Kazuhito Sato, Preet Lal, Cherease Street, Fernanda Martins Rodrigues, Austin N Southard-Smith, André Luiz N Targino Da Costa, Houxiang Zhu, Chia-Kuei Mo, Lisa Crowson, Robert S Fulton, Matthew A Wyczalkowski, Catrina C Fronick, Lucinda A Fulton, Hua Sun, Sherri R Davies, Elizabeth L Appelbaum, Sara E Chasnoff, Madelyn Carmody, Candace Brooks, Ruiyang Liu, Michael C Wendl, Clara Oh, Diane Bender, Carlos Cruchaga, Oscar Harari, Andrea Bredemeyer, Kory Lavine, Ron Bose, Julie Margenthaler, Jason M Held, Samuel Achilefu, Foluso Ademuyiwa, Rebecca Aft, Cynthia Ma, Graham A Colditz, Stephen T Oh, James Fitzpatrick, Kooresh I Shoghi, Milan G Chheda, Deborah J Veis, Feng Chen, Ryan C Fields, William E Gillanders, Li Ding, Et Al.

2020-Current year OA Pubs

Breast cancer (BC) is defined by distinct molecular subtypes with different cells of origin. The transcriptional networks that characterize the subtype-specific tumor-normal lineages are not established. In this work, we applied bulk, single-cell and single-nucleus multi-omic techniques as well as spatial transcriptomics and multiplex imaging on 61 samples from 37 patients with BC to show characteristic links in gene expression and chromatin accessibility between BC subtypes and their putative cells of origin. Regulatory network analysis of transcription factors underscored the importance of BHLHE40 in luminal BC and luminal mature cells and KLF5 in basal-like tumors and luminal progenitor cells. Furthermore, …

Posttreatment Surveillance Intensity And Overall Survival In Prostate Cancer Survivors (Aft-30), Ronald C Chen, Ramsankar Basak, Stacie Dusetzina, Deborah S Usinger, Zahed Mohammed, Aaron D Falchook, Jessica R Schumacher, Amanda B Francescatti, Amanda Cuddy, George J Chang, Benjamin D Kozower, Caprice C Greenberg, Anne K Barber, Aaron J Katz

2020-Current year OA Pubs

BACKGROUND: Posttreatment surveillance affects millions of cancer survivors, but empiric data to guide clinical practice are lacking. This study assessed whether the intensity of surveillance testing after radical prostatectomy or radiation therapy for localized prostate cancer is associated with overall survival.

METHODS: Men diagnosed with localized prostate cancer between 2005 and 2010 who underwent radical prostatectomy or radiation therapy at a Commission on Cancer-accredited facility were randomly sampled. Primary data collected from 10 147 patients sampled across 1007 facilities were linked with existing data from the National Cancer Database. Analysis examined whether intensity of surveillance measured as the number of …

Determining The N-Glycan And Collagen/Extracellular Matrix Protein Compositions In A Novel Outcome Cohort Of Prostate Cancer Tissue Microarrays Using Maldi-Msi, Jordan P Hartig, Joseph E Ippolito, Et Al.

2020-Current year OA Pubs

Using matrix-assisted laser desorption/ionization mass spectrometry imaging techniques on a unique cohort of prostate cancer tissues, we highlighted several molecular characteristics of matrix that have potential to act as early predictors of prostate cancer metastasis.

The Post-Transplant Lymphoproliferative Disorders-Metagenomic Shotgun Microbial Sequencing (Ptld-Msms) Study Methods And Protocol, Vikas R. Dharnidharka, Kristine M. Wylie, Todd N. Wylie, Marianna B. Ruzinova, Charles W. Goss, Gregory A. Storch, Neha Mehta-Shah, Derek Byers, Leslie Walther, Lujain Jaza, Hongjie Gu, Mansi Agarwal, Et Al.

2020-Current year OA Pubs

Post-transplant lymphoproliferative disorders (PTLDs) remain a feared complication of transplantation, with significant morbidity and mortality. The oncogenic Epstein-Barr virus (EBV) is a key pathogenic driver in 50%-80% of cases. Numerous prognostic indices, comprising multiple clinical, epidemiological and tumor characteristics, including EBV tumor positivity, do not consistently associate with worse patient survival, suggesting a potential role for EBV genome variants in determining outcome. However, the precision medicine tools for determining if a viral genome variant is pathogenic are very limited compared with human genome variants. Further, targeted studies have not implicated a specific viral etiological agent in EBV-negative PTLD. Using novel …

Diclofenac Sensitizes Multi-Drug Resistant Acinetobacter Baumannii To Colistin, Fabiana Bisaro, Clay D. Jackson-Litteken, Jenna C. Mcguffey, Anna J. Hooppaw, Sophie Bodrog, Leila Jebeli, Manon Janet-Maitre, Juan C. Ortiz-Marquez, Tim Van Opijnen, Nichollas E. Scott, Gisela Di Venanzio, Mario F. Feldman

2020-Current year OA Pubs

Acinetobacter baumannii causes life-threatening infections that are becoming difficult to treat due to increasing rates of multi-drug resistance (MDR) among clinical isolates. This has led the World Health Organization and the CDC to categorize MDR A. baumannii as a top priority for the research and development of new antibiotics. Colistin is the last-resort antibiotic to treat carbapenem-resistant A. baumannii. Not surprisingly, reintroduction of colistin has resulted in the emergence of colistin-resistant strains. Diclofenac is a non-steroidal anti-inflammatory drug used to treat pain and inflammation associated with arthritis. In this work, we show that diclofenac sensitizes colistin-resistant A. baumannii clinical strains …

Evidence Of Human Bourbon Virus Infections, North Carolina, Usa, Diana L Zychowski, Gayan Bamunuarachchi, Scott P Commins, Ross M Boyce, Adrianus C M Boon

2020-Current year OA Pubs

Bourbon virus is a tickborne virus that can cause human disease. Cases have been reported in Kansas, Oklahoma, and Missouri, USA. We identified Bourbon virus-specific neutralizing antibodies in patients from North Carolina. Bourbon virus infections are likely more common than previously thought, highlighting the need for improved diagnostics and surveillance.

A Case Report Of An Unprovoked Neonatal Pulmonary Embolism: Management Strategies And Cardiopulmonary Complications, Aashana Dhruva Cowan, Ezinwanne Rosemary Emelue, George Spyropoulos, Mehul Thakkar, Jorge Di Paola, Andrew Glatz, Edon J Rabinowitz

2020-Current year OA Pubs

BACKGROUND: Neonatal pulmonary embolism is a rare occurrence, especially when idiopathic, instead occurring in patients with identifiable risk factors including severe dehydration, presence or history of a central venous line, or identifiable genetic causes. Given the rarity of paediatric and neonatal pulmonary emboli, few guidelines exist to support the clinician in both the initial resuscitation and ongoing management of the critically ill patient with pulmonary emboli.

CASE SUMMARY: We present a 5-day-old female with unprovoked massive pulmonary embolism and associated haemodynamic compromise. She presented with central cyanosis and weak respiratory effort with hypoxaemia, persistent tachycardia, and hypotension despite initial fluid …

Pdgf-Bb Overexpression In P53 Null Oligodendrocyte Progenitors Increases H3k27me3 And Induces Transcriptional Changes Which Favor Proliferation, Dennis Huang, Angeliki Mela, Natarajan V Bhanu, Benjamin A Garcia, Peter Canoll, Patrizia Casaccia

2020-Current year OA Pubs

Proneural gliomas are brain tumors characterized by enrichment of oligodendrocyte progenitor cell (OPC) transcripts and genetic alterations. In this study we sought to identify transcriptional and epigenetic differences between OPCs with Trp53 deletion and PDGF-BB overexpression (BB-p53n) and those carrying only p53 deletion (p53n). In culture, the BB-p53n OPCs display growth characteristics more similar to glioma cells than p53n OPCs. When injected in mouse brains, BB-p53n OPC form tumors, while the p53n OPCs do not. Unbiased histone proteomics and transcriptomic analysis on these OPC populations identified higher levels of the histone H3K27me3 mark and lower levels of the histone H4K20me3. …

Cohort Expansion And Genotype-Phenotype Analysis Of Rab11a-Associated Neurodevelopmental Disorder, Maria Carla Borroto, Jorge L Granadillo, Et Al.

2020-Current year OA Pubs

BACKGROUND: GTPases of the Rab family are important orchestrators of membrane trafficking, and their dysregulation has been linked to a variety of neuropathologies. In 2017, we established a causal link between RAB11A variants and developmental and epileptic encephalopathy. In this study, we expand the phenotype of RAB11A-associated neurodevelopmental disorder and explore genotype-phenotype correlations.

METHODS: We assessed 16 patients with pathogenic or likely pathogenic RAB11A variants, generally de novo, heterozygous missense variants. One individual had a homozygous nonsense variant, although concomitant with a pathogenic LAMA2 variant, which made their respective contributions to the phenotype difficult to discriminate.

RESULTS: We reinforce the …

Comprehensive Clinical Implementation, Workflow, And Fmea Of Bespoke Silicone Bolus Cast From 3d Printed Molds Using Open-Source Resources, Dean Hobbis, Michael D Armstrong, Samir H Patel, Riley C Tegtmeier, Brady S Laughlin, Shadi Chitsazzadeh, Edward L Clouser, Jennifer L Smetanick, Justin Pettit, Justin D Gagneur, Joshua B Stoker, Yi Rong, Courtney R Buckey

2020-Current year OA Pubs

BACKGROUND: Bolus materials have been used for decades in radiotherapy. Most frequently, these materials are utilized to bring dose closer to the skin surface to cover superficial targets optimally. While cavity filling, such as nasal cavities, is desirable, traditional commercial bolus is lacking, requiring other solutions. Recently, investigators have worked on utilizing 3D printing technology, including commercially available solutions, which can overcome some challenges with traditional bolus.

PURPOSE: To utilize failure modes and effects analysis (FMEA) to successfully implement a comprehensive 3D printed bolus solution to replace commercial bolus in our clinic using a series of open-source (or free) software …

Effectiveness Of Original Monovalent And Bivalent Covid-19 Vaccines Against Covid-19-Associated Hospitalization And Severe In-Hospital Outcomes Among Adults In The United States, September 2022-August 2023, Jennifer Decuir, Jennie H Kwon, Et Al.

2020-Current year OA Pubs

BACKGROUND: Assessments of COVID-19 vaccine effectiveness are needed to monitor the protection provided by updated vaccines against severe COVID-19. We evaluated the effectiveness of original monovalent and bivalent (ancestral strain and Omicron BA.4/5) COVID-19 vaccination against COVID-19-associated hospitalization and severe in-hospital outcomes.

METHODS: During September 8, 2022 to August 31, 2023, adults aged ≥ 18 years hospitalized with COVID-19-like illness were enrolled at 26 hospitals in 20 US states. Using a test-negative case-control design, we estimated vaccine effectiveness (VE) with multivariable logistic regression adjusted for age, sex, race/ethnicity, admission date, and geographic region.

RESULTS: Among 7028 patients, 2924 (41.6%) were …

Clinical Trials For Lennox-Gastaut Syndrome: Challenges And Priorities, Juliet K Knowles, Aaron E L Warren, Ismail S Mohamed, Carl E Stafstrom, Hyun Yong Koh, Debopam Samanta, Renée A Shellhaas, Gita Gupta, Tracy Dixon-Salazar, Linh Tran, Sonal Bhatia, Jane M Mccabe, Anup D Patel, Zachary M Grinspan

2020-Current year OA Pubs

OBJECTIVE: Lennox-Gastaut syndrome (LGS) is a severe, childhood-onset epilepsy that is typically refractory to treatment. We surveyed the current landscape of LGS treatment, aiming to identify challenges to the development of efficacious therapies, and to articulate corresponding priorities toward clinical trials that improve outcomes.

METHODS: The LGS Special Interest Group of the Pediatric Epilepsy Research Consortium integrated evidence from the literature and expert opinion, into a narrative review.

RESULTS: We provide an overview of approved and emerging medical, dietary, surgical and neuromodulation approaches for LGS. We note that quality of care could be improved by standardizing LGS treatment based on …

A Finite Element Model For Biomechanical Characterization Of Ex Vivo Peripheral Nerve Dysfunction During Stretch, Nicholas C Vasas, Adam M Forrest, Nathaniel A Meyers, Michael B Christensen, Jenny L Pierce, Sidney M Kaufmann, Kimberly B Lanaghen, Randal C Paniello, Julie M Barkmeier-Kraemer, Jonathan P Vande Geest

2020-Current year OA Pubs

Peripheral nerve damage can cause debilitating symptoms ranging from numbness and pain to sensory loss and atrophy. To uncover the underlying mechanisms of peripheral nerve injury, our research aims to develop a relationship between biomechanical peripheral nerve damage and function through finite element modeling. A noncontact, ex vivo electrophysiology chamber, capable of axially stretching explanted nerves while recording electrical signals, was used to investigate peripheral nerve injury. Successive stretch trials were run on eight sciatic nerves (four females and four males) excised from Sprague-Dawley rats. Nerves were stretched until 50% compound action potential (CAP) amplitude reduction was obtained. A constitutive …

Impact Of Self-Reported Race On Villalta Scale Postthrombotic Syndrome Scores And Correlation With Venous Disease-Specific Quality Of Life: An Exploratory Analysis Of The Acute Venous Thrombosis: Thrombus Removal With Adjunctive Catheter-Directed Thrombolysis Trial, James Shih, Chu-Shu Gu, Suresh Vedantham, John Kaufman, Susan R Kahn

2020-Current year OA Pubs

BACKGROUND: The Villalta Scale (VS) to diagnose postthrombotic syndrome (PTS) consists of 5 patient-reported leg symptoms and 6 clinician-rated leg signs. It is unknown how the scale performs across racial groups.

OBJECTIVES: Our study explored if there were differences in VS scores, particularly clinician-rated signs components, according to self-reported race.

METHODS: Exploratory analysis of the ATTRACT trial, a randomized controlled trial conducted at 56 US sites that investigated pharmacomechanical catheter-directed thrombolysis to prevent PTS after proximal deep vein thrombosis (DVT). At the 6-month visit after randomization, we compared self-reported Black (n = 123) and White (n = 541) participants for …

Fusobacterium Nucleatum Abundance Is Associated With Cachexia In Colorectal Cancer Patients: The Colocare Study, Mmadili N Ilozumba, Adetunji T Toriola, Et Al.

2020-Current year OA Pubs

BACKGROUND: Cachexia accounts for about 20% of all cancer-related deaths and indicates poor prognosis. The impact of Fusobacterium nucleatum (Fn), a microbial risk factor for colorectal cancer (CRC), on the development of cachexia in CRC has not been established.

METHODS: We evaluated the association between Fn abundance in pre-surgical stool samples and onset of cachexia at 6 months post-surgery in n = 87 patients with stages I-III CRC in the ColoCare Study.

RESULTS: High fecal Fn abundance compared to negative/low fecal Fn abundance was associated with 4-fold increased risk of cachexia onset at 6 months post-surgery (OR = 4.82, 95% …

A Site-Wise Reliability Analysis Of The Abcd Diffusion Fractional Anisotropy And Cortical Thickness: Impact Of Scanner Platforms, Yezhi Pan, L Elliot Hong, Ashley Acheson, Paul M Thompson, Neda Jahanshad, Alyssa H Zhu, Jiaao Yu, Chixiang Chen, Tianzhou Ma, Ho-Ling Liu, Jelle Veraart, Els Fieremans, Nicole R Karcher, Peter Kochunov, Shuo Chen

2020-Current year OA Pubs

The Adolescent Brain and Cognitive Development (ABCD) project is the largest study of adolescent brain development. ABCD longitudinally tracks 11,868 participants aged 9-10 years from 21 sites using standardized protocols for multi-site MRI data collection and analysis. While the multi-site and multi-scanner study design enhances the robustness and generalizability of analysis results, it may also introduce nonbiological variances including scanner-related variations, subject motion, and deviations from protocols. ABCD imaging data were collected biennially within a period of ongoing maturation in cortical thickness and integrity of cerebral white matter. These changes can bias the classical test-retest methodologies, such as intraclass correlation …