Digital Commons Network^™

Multimodal Brain Age Estimates Relate To Alzheimer Disease Biomarkers And Cognition In Early Stages: A Cross-Sectional Observational Study, Peter R Millar, Brian A Gordon, Patrick H Luckett, Tammie L S Benzinger, Carlos Cruchaga, Anne M Fagan, Jason J Hassenstab, Richard J Perrin, Suzanne E Schindler, Randall J Bateman, John C Morris, Beau M Ances, Et Al.

2020-Current year OA Pubs

BACKGROUND: Estimates of 'brain-predicted age' quantify apparent brain age compared to normative trajectories of neuroimaging features. The brain age gap (BAG) between predicted and chronological age is elevated in symptomatic Alzheimer disease (AD) but has not been well explored in presymptomatic AD. Prior studies have typically modeled BAG with structural MRI, but more recently other modalities, including functional connectivity (FC) and multimodal MRI, have been explored.

METHODS: We trained three models to predict age from FC, structural (S), or multimodal MRI (S+FC) in 390 amyloid-negative cognitively normal (CN/A-) participants (18-89 years old). In independent samples of 144 CN/A-, 154 CN/A+, …

Excretory/Secretory Proteome Of Females And Males Of The Hookworm Ancylostoma Ceylanicum, Samuel C Uzoechi, Bruce A Rosa, Kumar Sachin Singh, Young-Jun Choi, Bethany K Bracken, Paul J Brindley, R Reid Townsend, Robert Sprung, Bin Zhan, Maria-Elena Bottazzi, John M Hawdon, Yide Wong, Alex Loukas, Sergej Djuranovic, Makedonka Mitreva

2020-Current year OA Pubs

The dynamic host-parasite mechanisms underlying hookworm infection establishment and maintenance in mammalian hosts remain poorly understood but are primarily mediated by hookworm's excretory/secretory products (ESPs), which have a wide spectrum of biological functions. We used ultra-high performance mass spectrometry to comprehensively profile and compare female and male ESPs from the zoonotic human hookworm

Civicdb 2022: Evolution Of An Open-Access Cancer Variant Interpretation Knowledgebase, Kilannin Krysiak, Arpad M Danos, Jason Saliba, Joshua F Mcmichael, Adam C Coffman, Susanna Kiwala, Erica K Barnell, Lana Sheta, Lynzey Kujan, Shahil Pema, Nicholas C Spies, Kaitlin A Clark, Ajay C Venigalla, Avila Suda, Benjamin J Ainscough, Haolin Shen, Alex R Marr, My H Hoang, Kartik Singhal, Mariam Khanfar, Brian V Li, Katie M Campbell, Kelsy C Cotto, Zachary L Skidmore, Jason R Walker, Malachi Griffith, Obi L Griffith, Et Al.

2020-Current year OA Pubs

CIViC (Clinical Interpretation of Variants in Cancer; civicdb.org) is a crowd-sourced, public domain knowledgebase composed of literature-derived evidence characterizing the clinical utility of cancer variants. As clinical sequencing becomes more prevalent in cancer management, the need for cancer variant interpretation has grown beyond the capability of any single institution. CIViC contains peer-reviewed, published literature curated and expertly-moderated into structured data units (Evidence Items) that can be accessed globally and in real time, reducing barriers to clinical variant knowledge sharing. We have extended CIViC's functionality to support emergent variant interpretation guidelines, increase interoperability with other variant resources, and promote widespread dissemination …

Protocol For The Phase 2 Edelife Trial Investigating The Efficacy And Safety Of Intra-Amniotic Er004 Administration To Male Subjects With X-Linked Hypohidrotic Ectodermal Dysplasia, Holm Schneider, Smail Hadj-Rabia, Florian Faschingbauer, Christine Bodemer, Dorothy K Grange, Mary E Norton, Riccardo Cavalli, Gianluca Tadini, Holger Stepan, Angus Clarke, Encarna Guillén-Navarro, Sigrun Maier-Wohlfart, Athmane Bouroubi, Florence Porte

2020-Current year OA Pubs

X-linked hypohidrotic ectodermal dysplasia (XLHED) is a rare genetic disorder characte-rised by abnormal development of the skin and its appendages, such as hair and sweat glands, the teeth, and mucous glands of the airways, resulting in serious, sometimes life-threatening complications like hyperthermia or recurrent respiratory infections. It is caused by pathogenic variants of the ectodysplasin A gene (

Historic Clinical Trial External Control Arm Provides Actionable Gen-1 Efficacy Estimate Before A Randomized Trial, Xiang Yin, Ruthanna Davi, Elizabeth B Lamont, Premal H Thaker, William H Bradley, Charles A Leath 3rd, Kathleen M Moore, Khursheed Anwer, Lauren Musso, Nicholas Borys

2020-Current year OA Pubs

PURPOSE: To inform continued development of the novel immune agent GEN-1, we compared ovarian cancer patients' end points from a neoadjuvant single-arm phase IB study with those of similar historic clinical trial (HCT) patients who received standard neoadjuvant chemotherapy.

METHODS: Applying OVATION-1 trial (ClinicalTrials.gov identifier: NCT02480374) inclusion and exclusion criteria to Medidata HCT data, we identified historical trial patients for comparison. Integrating patient-level Medidata historic trial data (N = 41) from distinct neoadjuvant ovarian phase I-III trials with patient-level OVATION-1 data (N = 18), we selected Medidata patients with similar baseline characteristics as OVATION-1 patients using propensity score methods to …

Late Cardiac Events After Allogeneic Stem Cell Transplant: Incidence, Risk Factors, And Impact On Overall Survival, Christine Auberle, Daniel Lenihan, Feng Gao, Amanda Cashen

2020-Current year OA Pubs

BACKGROUND: There is limited data on the impact of cardiac disease on long term outcomes of allogeneic stem cell transplant (alloSCT). Our study aims to describe the incidence of late cardiac events after alloSCT, identify risk factors for developing a late cardiac event, and illustrate the impact of late cardiac events on overall survival.

METHODS: Patients who underwent alloSCT from 2007 to 2017 and survived more than 1 year after transplant (N = 804) were included. Gray's sub-distribution methods, while accounting for death as a competing risk, were used to calculate the cumulative incidence of late cardiac events. Univariate regression …

Methylc-Analyzer: A Comprehensive Downstream Pipeline For The Analysis Of Genome-Wide Dna Methylation, Rita Jui-Hsien Lu, Pei-Yu Lin, Ming-Ren Yen, Bing-Heng Wu, Pao-Yang Chen

2020-Current year OA Pubs

DNA methylation is a crucial epigenetic modification involved in multiple biological processes and diseases. Current approaches for measuring genome-wide DNA methylation via bisulfite sequencing (BS-seq) include whole-genome bisulfite sequencing (WGBS), reduced representation bisulfite sequencing (RRBS), and enzymatic methyl-seq (EM-seq). The computational analysis tools available for BS-seq data include customized aligners for mapping bisulfite-converted reads and computational pipelines for downstream data analysis. Current post-alignment methylation tools are specialized for the interpretation of CG methylation, which is known to dominate mammalian genomes, however, non-CG methylation (CHG and CHH, where H refers to A, C, or T) is commonly observed in plants and …

A Phase Ii Study Of Palbociclib Plus Letrozole Plus Trastuzumab As Neoadjuvant Treatment For Clinical Stages Ii And Iii Er+ Her2+ Breast Cancer (Paltan), Foluso O Ademuyiwa, Jingqin Luo, Yu Tao, Jeremy Hoog, Marie L Laury, Tracy Summa, Trish Hammerschmidt, Zhanfang Guo, Ashley Frith, Katherine Weilbaecher, Mateusz Opyrchal, Rebecca Aft, Katherine Clifton, Rama Suresh, Nusayba Bagegni, Ian S Hagemann, Michael D Iglesia, Cynthia X Ma, Et Al.

2020-Current year OA Pubs

Patients with ER+/HER2+ breast cancer (BC) are less likely to achieve pathological complete response (pCR) after chemotherapy with dual HER2 blockade than ER-/HER2+ BC. Endocrine therapy plus trastuzumab is effective in advanced ER+/HER2+ BC. Inhibition of CDK4/6 and HER2 results in synergistic cell proliferation reduction. We combined palbociclib, letrozole, and trastuzumab (PLT) as a chemotherapy-sparing regimen. We evaluated neoadjuvant PLT in early ER+/HER2+ BC. Primary endpoint was pCR after 16 weeks. Research biopsies were performed for whole exome and RNA sequencing, PAM50 subtyping, and Ki67 assessment for complete cell cycle arrest (CCCA: Ki67 ≤ 2.7%). After 26 patients, accrual stopped …

Conformational Plasticity Of Nak2k And Trek2 Potassium Channel Selectivity Filters, Marcos Matamoros, Xue Wen Ng, Joshua B Brettmann, David W Piston, Colin G Nichols

2020-Current year OA Pubs

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Intraocular Pressure And Medication Changes Associated With Xen Gel Stent: A Systematic Review Of The Literature, Joseph F Panarelli, Vanessa Vera, Arsham Sheybani, Nathan Radcliffe, Richard Fiscella, Brian A Francis, Oluwatosin U Smith, Robert J Noecker

2020-Current year OA Pubs

The Xen gel stent (Allergan Inc, an AbbVie company; Dublin, Ireland) was conceived as an option for patients requiring modest IOP reduction but for whom trabeculectomy was not yet indicated. As with any glaucoma surgery, establishing criteria for patient selection and identifying factors that contribute to a high likelihood of success are important. To help guide clinical decision-making, a systematic review of published studies on the gel stent was performed, with the goal of understanding postoperative outcomes based on clinical and patient factors. Results were organized around a series of pertinent clinical questions based on scenarios encountered in clinical practice. …

Lecanemab In Early Alzheimer's Disease, Christopher H Van Dyck, Randall J Bateman, Et Al.

2020-Current year OA Pubs

BACKGROUND: The accumulation of soluble and insoluble aggregated amyloid-beta (Aβ) may initiate or potentiate pathologic processes in Alzheimer's disease. Lecanemab, a humanized IgG1 monoclonal antibody that binds with high affinity to Aβ soluble protofibrils, is being tested in persons with early Alzheimer's disease.

METHODS: We conducted an 18-month, multicenter, double-blind, phase 3 trial involving persons 50 to 90 years of age with early Alzheimer's disease (mild cognitive impairment or mild dementia due to Alzheimer's disease) with evidence of amyloid on positron-emission tomography (PET) or by cerebrospinal fluid testing. Participants were randomly assigned in a 1:1 ratio to receive intravenous lecanemab …

Olutasidenib (Ft-2102) In Patients With Relapsed Or Refractory Idh1-Mutant Glioma: A Multicenter, Open-Label, Phase Ib/Ii Trial, Macarena I De La Fuente, Brian A Van Tine, Et Al.

2020-Current year OA Pubs

BACKGROUND: Olutasidenib (FT-2102) is a highly potent, orally bioavailable, brain-penetrant and selective inhibitor of mutant isocitrate dehydrogenase 1 (IDH1). The aim of the study was to determine the safety and clinical activity of olutasidenib in patients with relapsed/refractory gliomas harboring an IDH1R132X mutation.

METHODS: This was an open-label, multicenter, nonrandomized, phase Ib/II clinical trial. Eligible patients (≥18 years) had histologically confirmed IDH1R132X-mutated glioma that relapsed or progressed on or following standard therapy and had measurable disease. Patients received olutasidenib, 150 mg orally twice daily (BID) in continuous 28-day cycles. The primary endpoints were dose-limiting toxicities (DLTs) (cycle 1) and safety …

Alcohol Consumption And Epigenetic Age Acceleration In Young Adults, Drew R Nannini, Lei Liu, Et Al.

2020-Current year OA Pubs

Alcohol is a widely consumed substance in the United States, however its effect on aging remains understudied. In this study of young adults, we examined whether cumulative alcohol consumption, i.e., alcohol years of beer, liquor, wine, and total alcohol, and recent binge drinking, were associated with four measures of age-related epigenetic changes via blood DNA methylation. A random subset of study participants in the Coronary Artery Risk Development in Young Adults Study underwent DNA methylation profiling using the Illumina MethylationEPIC Beadchip. Participants with alcohol consumption and methylation data at examination years 15 (

Preclinical Studies In Krabbe Disease: A Model For The Investigation Of Novel Combination Therapies For Lysosomal Storage Diseases, Gregory Heller, Allison M Bradbury, Mark S Sands, Ernesto R Bongarzone

2020-Current year OA Pubs

Krabbe disease (KD) is a lysosomal storage disease (LSD) caused by mutations in the galc gene. There are over 50 monogenetic LSDs, which largely impede the normal development of children and often lead to premature death. At present, there are no cures for LSDs and the available treatments are generally insufficient, short acting, and not without co-morbidities or long-term side effects. The last 30 years have seen significant advances in our understanding of LSD pathology as well as treatment options. Two gene therapy-based clinical trials, NCT04693598 and NCT04771416, for KD were recently started based on those advances. This review will …

Individual Differences In Naturalistic Learning Link Negative Emotionality To The Development Of Anxiety, William J Villano, Noah I Kraus, Travis R Reneau, Brittany A Jaso, A Ross Otto, Aaron S Heller

2020-Current year OA Pubs

Organisms learn from prediction errors (PEs) to predict the future. Laboratory studies using small financial outcomes find that humans use PEs to update expectations and link individual differences in PE-based learning to internalizing disorders. Because of the low-stakes outcomes in most tasks, it is unclear whether PE learning emerges in naturalistic, high-stakes contexts and whether individual differences in PE learning predict psychopathology risk. Using experience sampling to assess 625 college students' expected exam grades, we found evidence of PE-based learning and a general tendency to discount negative PEs, an "optimism bias." However, individuals with elevated negative emotionality, a personality trait …

Provider Beliefs In Effectiveness And Recommendations For Primary Hpv Testing In 3 Health-Care Systems, Gina R Kruse, Jacquelyn M Lykken, Eric J Kim, Jennifer S Haas, Robin T Higashi, Steven J Atlas, Anne Marie Mccarthy, Jasmin A Tiro, Michelle I Silver, Celette S Skinner, Aruna Kamineni

2020-Current year OA Pubs

In 2018, the US Preventive Services Task Force endorsed primary human papillomavirus testing (pHPV) for cervical cancer screening. We aimed to describe providers' beliefs about pHPV testing effectiveness and which screening approach they regularly recommend. We invited providers who performed 10 or more cervical cancer screens in 2019 in 3 healthcare systems that had not adopted pHPV testing: Kaiser Permanente Washington, Mass General Brigham, and Parkland Health; 53.7% (501/933) completed the survey between October and December 2020. Response distributions varied across modalities (P < .001), with cytology alone or cotesting being more often viewed as somewhat or very effective for 30- to 65-year-olds compared with pHPV (cytology alone 94.1%, cotesting 96.1%, pHPV 66.0%). In 21- to 29-year-olds, the pattern was similar (cytology alone 92.2%, 64.7% cotesting, 50.8% pHPV). Most providers were either incorrect or unsure of the guideline-recommended screening interval for pHPV. Educational efforts are needed about the relative effectiveness and recommended use of pHPV to promote guideline-concordant care.

Large Variations In The Prices Of Urologic Procedures At Academic Medical Centers 1 Year After Implementation Of The Price Transparency Final Rule, Zeynep G Gul, Danielle R Sharbaugh, Cailey J Guercio, Daniel L Pelzman, Cameron A Jones, Emily C Hacker, Vivian I Anyaeche, Levi Bowers, Ashti M Shah, Michael G Stencel, Jonathan G Yabes, Bruce L Jacobs, Benjamin J Davies

2020-Current year OA Pubs

IMPORTANCE: Patients with urologic diseases often experience financial toxicity, defined as high levels of financial burden and concern, after receiving care. The Price Transparency Final Rule, which requires hospitals to disclose both the commercial and cash prices for at least 300 services, was implemented to facilitate price shopping, decrease price dispersion, and lower health care costs.

OBJECTIVE: To evaluate compliance with the Price Transparency Final Rule and to quantify variations in the price of urologic procedures among academic hospitals and by insurance class.

DESIGN, SETTING, AND PARTICIPANTS: This was a cross-sectional study that determined the prices of 5 common urologic …

Effect Of A Muc5ac Antibody (Npc-1c) Administered With Second-Line Gemcitabine And Nab-Paclitaxel On The Survival Of Patients With Advanced Pancreatic Ductal Adenocarcinoma: A Randomized Clinical Trial, Brandon M Huffman, Andrea Wang-Gillam, Et Al.

2020-Current year OA Pubs

IMPORTANCE: Treatment options are limited for patients with advanced pancreatic ductal adenocarcinoma (PDAC) beyond first-line 5-fluorouracil, leucovorin, irinotecan, and oxaliplatin (FOLFIRINOX), with such individuals commonly being treated with gemcitabine and nab-paclitaxel.

OBJECTIVE: To determine whether NPC-1C, an antibody directed against MUC5AC, might increase the efficacy of second-line gemcitabine and nab-paclitaxel in patients with advanced PDAC.

DESIGN, SETTING, AND PARTICIPANTS: This multicenter, randomized phase II clinical trial enrolled patients with advanced PDAC between April 2014 and March 2017 whose disease had progressed on first-line FOLFIRINOX. Eligible patients had tumors with at least 20 MUC5AC staining by centralized immunohistochemistry review. Statistical analysis …

Arginine Methylation Of The Pgc-1Α C-Terminus Is Temperature-Dependent, Meryl Mendoza, Mariel Mendoza, Tiffany Lubrino, Sidney Briski, Immaculeta Osuji, Janielle Cuala, Brendan Ly, Ivan Ocegueda, Harvey Peralta, Benjamin A. Garcia, Cecilia I. Zurita-Lopez

2020-Current year OA Pubs

We set out to determine whether the C-terminus (amino acids 481-798) of peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α, UniProt Q9UBK2), a regulatory metabolic protein involved in mitochondrial biogenesis, and respiration, is an arginine methyltransferase substrate. Arginine methylation by protein arginine methyltransferases (PRMTs) alters protein function and thus contributes to various cellular processes. In addition to confirming methylation of the C-terminus by PRMT1 as described in the literature, we have identified methylation by another member of the PRMT family, PRMT7. We performed

Association Of State Insurance Mandates For Fertility Treatment With Multiple Embryo Transfer After Preimplantation Genetic Testing For Aneuploidy, Bronwyn S Bedrick, Katelin B Nickel, Joan K Riley, Tarun Jain, Emily S Jungheim

2020-Current year OA Pubs

IMPORTANCE: Multiple gestation is one of the biggest risks after in vitro fertilization (IVF), largely due to multiple embryo transfer (MET). Single embryo transfer (SET) uptake has increased over time and has been attributed to various factors, such as mandated insurance coverage for IVF and preimplantation genetic testing for aneuploidy (PGT-A).

OBJECTIVE: To investigate whether mandates for IVF insurance coverage are associated with decreased use of MET after PGT-A.

DESIGN, SETTING, AND PARTICIPANTS: This cohort study was conducted using data on embryo transfers reported to the Society for Assisted Reproductive Technology between 2014 and 2016. Data were analyzed from January …

Magnify Is A Universal Molecular Anchoring Strategy For Expansion Microscopy, Aleksandra Klimas, Brendan R Gallagher, Piyumi Wijesekara, Sinda Fekir, Emma F Dibernardo, Zhangyu Cheng, Donna B Stolz, Franca Cambi, Simon C Watkins, Steven L Brody, Amjad Horani, Alison L Barth, Christopher I Moore, Xi Ren, Yongxin Zhao

2020-Current year OA Pubs

Expansion microscopy enables nanoimaging with conventional microscopes by physically and isotropically magnifying preserved biological specimens embedded in a crosslinked water-swellable hydrogel. Current expansion microscopy protocols require prior treatment with reactive anchoring chemicals to link specific labels and biomolecule classes to the gel. We describe a strategy called Magnify, which uses a mechanically sturdy gel that retains nucleic acids, proteins and lipids without the need for a separate anchoring step. Magnify expands biological specimens up to 11 times and facilitates imaging of cells and tissues with effectively around 25-nm resolution using a diffraction-limited objective lens of about 280 nm on conventional …

Chronic Trem2 Activation Exacerbates Aβ-Associated Tau Seeding And Spreading, Nimansha Jain, Caroline A Lewis, Jason D Ulrich, David M Holtzman

2020-Current year OA Pubs

Variants in the triggering receptor expressed on myeloid cells 2 (TREM2) gene are associated with increased risk for late-onset AD. Genetic loss of or decreased TREM2 function impairs the microglial response to amyloid-β (Aβ) plaques, resulting in more diffuse Aβ plaques and increased peri-plaque neuritic dystrophy and AD-tau seeding. Thus, microglia and TREM2 are at a critical intersection of Aβ and tau pathologies in AD. Since genetically decreasing TREM2 function increases Aβ-induced tau seeding, we hypothesized that chronically increasing TREM2 signaling would decrease amyloid-induced tau-seeding and spreading. Using a mouse model of amyloidosis in which AD-tau is injected into the …

Baricitinib With Cyclosporine Eliminates Acute Graft Rejection In Fully Mismatched Skin And Heart Transplant Models, Ramzi Abboud, Sena Kim, Karl Staser, Reyka G Jayasinghe, Sora Lim, Parmeshwar Amatya, C Corbin Frye, Benjamin Kopecky, Julie Ritchey, Feng Gao, Kory Lavine, Daniel Kreisel, John F Dipersio, Jaebok Choi

2020-Current year OA Pubs

Solid organ transplant represents a potentially lifesaving procedure for patients suffering from end-stage heart, lung, liver, and kidney failure. However, rejection remains a significant source of morbidity and immunosuppressive medications have significant toxicities. Janus kinase (JAK) inhibitors are effective immunosuppressants in autoimmune diseases and graft versus host disease after allogeneic hematopoietic cell transplantation. Here we examine the role of JAK inhibition in preclinical fully major histocompatibility mismatched skin and heart allograft models. Baricitinib combined with cyclosporine A (CsA) preserved fully major histocompatibility mismatched skin grafts for the entirety of a 111-day experimental period. In baricitinib plus CsA treated mice, circulating …

Gene-Educational Attainment Interactions In A Multi-Population Genome-Wide Meta-Analysis Identify Novel Lipid Loci, Lisa De Las Fuentes, Karen L. Schwander, Yun Ju Sung, Mary F. Feitosa, Ahn Do, C. Charles Gu, Treva K. Rice, Mary K. Wojczynski, Michael M. Province, Dabeeru C. Rao, Et Al.

2020-Current year OA Pubs

No abstract provided.

Necrotic Cardiac Myocytes Skew Macrophage Polarization Towards A Classically Activated Phenotype, Wenlong Jiang, Luigi Adamo, Kenji Lim, Scot J Matkovich, Sarah Evans, Cibele Rocha-Resende, Douglas L. Mann

2020-Current year OA Pubs

Necrotic and dying cells release damage-associated molecular patterns (DAMPs) that can initiate sterile inflammatory responses in the heart. Although macrophages are essential for myocardial repair and regeneration, the effect of DAMPs on macrophage activation remains unclear. To address this gap in knowledge we studied the effect of necrotic cardiac myocyte extracts on primary peritoneal macrophage (PPM) cultures in vitro. We first performed unbiased transcriptomic profiling with RNA-sequencing of PPMs cultured for up to 72 hours in the presence and absence of: 1) necrotic cell extracts (NCEs) from necrotic cardiac myocytes in order to mimic the release of DAMPs; 2) lipopolysaccharide …

Leveraging Health Infrastructure To Optimize Hpv Vaccination For Adolescents In Zambia: Protocol For An Implementation Study, Sam Miti, Thembekile Shato, Comfort Asante, Ana Baumann, Gershom Chongwe, Patricia M. Bobo, Michelle I. Silver, Jean M. Hunleth

2020-Current year OA Pubs

BACKGROUND: Cervical cancer is the leading cause of cancer death in Zambia, where HIV prevalence is also high (11.3%). HIV heightens the risk of developing and dying from cervical cancer. The human papillomavirus (HPV) vaccine can prevent 90% of cervical cancers, and in Zambia is recommended for adolescent girls ages 14-15 years, including those with HIV. Currently they mainly deliver HPV vaccination via school-based campaigns, which may exclude the most vulnerable adolescents-those out-of-school or who irregularly attend. Adolescents living with HIV (ALHIV) are more likely to have these vulnerabilities. Further, school-based campaigns are not tailored to the WHO-recommended HPV vaccination …

Adherence To And Experiences Of K-12 Students In Modified And Standard Home Quarantine During The Sars-Cov-2 Pandemic In Missouri, Mary Claire Worrell, Sara Malone, Patrick Dawson, Stephanie A. Fritz, Ebony Thomas, Bre Peeler, Catherine Rains, Sarah C. Tinker, John C. Neatherlin, Lisa Barrios, Jon Mooney, Katie Towns, Jason Newland, Johanna S. Salzer

2020-Current year OA Pubs

BACKGROUND: In November 2020, during the SARS-CoV-2 pandemic, Missouri allowed local public health jurisdictions the option to implement a modified quarantine policy allowing kindergarten through 12 (K-12) students with low-risk exposures to continue in-person learning. We assessed adherence to quarantine among participants in modified quarantine and standard home quarantine and the psychosocial impacts of quarantine on students and families.

METHODS: In January-March 2021, as part of an investigation of in-school transmission of SARS-CoV-2, parents of 586 participating K-12 students identified as a close contact with a person with SARS-CoV-2 were sent a survey to assess their activities and psychosocial impacts …

Glioblastoma Induces Whole-Brain Spectral Change In Resting State Fmri: Associations With Clinical Comorbidities And Overall Survival, Ki Yun Park, Abraham Z Snyder, Michael Olufawo, Gabriel Trevino, Patrick H Luckett, Bidhan Lamichhane, Tao Xie, John J Lee, Joshua S Shimony, Eric C Leuthardt

2020-Current year OA Pubs

Glioblastoma, a highly aggressive form of brain tumor, is a brain-wide disease. We evaluated the impact of tumor burden on whole brain resting-state functional magnetic resonance imaging (rs-fMRI) activity. Specifically, we analyzed rs-fMRI signals in the temporal frequency domain in terms of the power-law exponent and fractional amplitude of low-frequency fluctuations (fALFF). We contrasted 189 patients with newly-diagnosed glioblastoma versus 189 age-matched healthy reference participants from an external dataset. The patient and reference datasets were matched for age and head motion. The principal finding was markedly flatter spectra and reduced grey matter fALFF in the patients as compared to the …

Nonalcoholic Fatty Liver Disease Is A Risk Factor For Thiopurine Hepatotoxicity In Crohn's Disease, Alvin T George, Matthew Glover, Quazim Alayo, Maria Zulfiqar, Daniel R Ludwig, Matthew A Ciorba, Scott Mchenry, Parakkal Deepak

2020-Current year OA Pubs

BACKGROUND: Patients with Crohn's disease (CD) are predisposed to nonalcoholic fatty liver disease (NAFLD). CD management often includes thiopurines which can promote hepatotoxicity. We aimed to identify the role of NAFLD on the risk of developing liver injury from thiopurines in CD.

METHODS: In this prospective cohort analysis, CD patients at a single center were recruited 6/2017-5/2018. Patients with alternative liver diseases were excluded. The primary outcome was time to elevation of liver enzymes. Patients underwent MRI with assessment of proton density fat fraction (PDFF) on enrollment, where NAFLD was defined as PDFF >5.5%. Statistical analysis was performed using a …

Structural And Biophysical Characterization Of The Secreted, Β-Helical Adhesin Etpa Of Enterotoxigenic Escherichia Coli, Clifford Manyo Ntui, James M. Fleckenstein, Wolf-Dieter Schubert

2020-Current year OA Pubs

Enterotoxigenic Escherichia coli (ETEC) is a diarrhoeal pathogen associated with high morbidity and mortality especially among young children in developing countries. At present, there is no vaccine for ETEC. One candidate vaccine antigen, EtpA, is a conserved secreted adhesin that binds to the tips of flagellae to bridge ETEC to host intestinal glycans. EtpA is exported through a Gram-negative, two-partner secretion system (TPSS, type Vb) comprised of the secreted EtpA passenger (TpsA) protein and EtpB (TpsB) transporter that is integrated into the outer bacterial membrane. TpsA proteins share a conserved, N-terminal TPS domain followed by an extensive C-terminal domain with …