Digital Commons Network^™

Proteolysis Of The Pericellular Matrix: Pinpointing The Role And Involvement Of Matrix Metalloproteinases In Early Osteoarthritic Remodeling, Marina Danalache, Felix Umrath, Rosa Riester, Maik Schwitalle, Farshid Guilak, Ulf Krister Hoffmann

2020-Current year OA Pubs

The pericellular matrix (PCM) serves a critical role in signal transduction and mechanoprotection in chondrocytes. Osteoarthritis (OA) leads to a gradual deterioration of the cartilage, marked by a shift in the spatial arrangement of chondrocytes from initially isolated strands to large cell clusters in end-stage degeneration. These changes coincide with progressive enzymatic breakdown of the PCM. This study aims to assess the role and involvement of specific matrix metalloproteinases (MMPs) in PCM degradation during OA. We selected cartilage samples from 148 OA patients based on the predominant spatial chondrocyte patterns. The presence of various MMPs (-1,-2,-3,-7,-8,-9,-10,-12,-13) was identified by multiplexed …

Use Of A Blood Biomarker Test Improves Economic Utility In The Evaluation Of Older Patients Presenting With Cognitive Impairment, William J Canestaro, Randall J Bateman, David M Holtzman, Mark Monane, Joel B Braunstein

2020-Current year OA Pubs

More than 16 million Americans living with cognitive impairment warrant a diagnostic evaluation to determine the cause of this disorder. The recent availability of disease-modifying therapies for Alzheimer's disease (AD) is expected to significantly drive demand for such diagnostic testing. Accurate, accessible, and affordable methods are needed. Blood biomarkers (BBMs) offer advantages over usual care amyloid positron emission tomography (PET) and cerebrospinal fluid (CSF) biomarkers in these regards. This study used a budget impact model to assess the economic utility of the PrecivityAD

Genetic Loci Regulate Sarbecovirus Pathogenesis: A Comparison Across Mice And Humans, Alexandra Schäfer, Laura A Vanblargan, Larissa B Thackray, Michael S Diamond, Et Al.

2020-Current year OA Pubs

Coronavirus (CoV) cause considerable morbidity and mortality in humans and other mammals, as evidenced by the emergence of Severe Acute Respiratory CoV (SARS-CoV) in 2003, Middle East Respiratory CoV (MERS-CoV) in 2012, and SARS-CoV-2 in 2019. Although poorly characterized, natural genetic variation in human and other mammals modulate virus pathogenesis, as reflected by the spectrum of clinical outcomes ranging from asymptomatic infections to lethal disease. Using multiple human epidemic and zoonotic Sarbecoviruses, coupled with murine Collaborative Cross genetic reference populations, we identify several dozen quantitative trait loci that regulate SARS-like group-2B CoV pathogenesis and replication. Under a Chr4 QTL, we …

Infectious Diseases Physician Management Of Cryptococcal Meningitis In North America-Is Single High-Dose Liposomal Amphotericin B Being Used?, Nathan C Bahr, Susan E Beekmann, Philip M Polgreen, Jeremey B Walker, Andrej Spec, David R Boulware, John W Baddley

2020-Current year OA Pubs

BACKGROUND: Several recent randomized trials have been conducted in resource-limited settings for cryptococcal meningitis that have rapidly innovated international guidelines. The 2010 Infectious Diseases Society of America (IDSA) cryptococcal meningitis guideline has not been updated with recent trials. The 2022 AMBITION-cm trial found that a single 10-mg/kg dose of liposomal amphotericin B plus daily flucytosine and fluconazole for 2 weeks was noninferior to 1 week of amphotericin B deoxycholate with flucytosine. It is unknown whether physicians in high-resource settings are using this regimen or more traditional regimens.

METHODS: We developed an electronic survey in June 2023 to better understand whether …

Migraine Headache In Patients With Spontaneous Coronary Artery Dissection: A Report Of The Iscad Registry, Bryan J Wells, Kathryn Lindley, Et Al.

2020-Current year OA Pubs

INTRODUCTION: Spontaneous coronary artery dissection (SCAD) is a nonatherosclerotic cause of myocardial infarction. Migraine headache has been reported to be common among patients with SCAD, but the degree of migraine-related disability has not been quantified.

METHODS: Clinical data and headache variables were obtained from the baseline assessment of the prospective, multicenter iSCAD Registry. Migraine-related disability was quantified using the self-reported Migraine Disability Assessment (MIDAS). Demographic, clinical, psychosocial, and medical characteristics from data entry forms were compared between patients with and without migraine.

RESULTS: Of the 773 patients with available data, 46% reported previous or current migraines. Those with migraines were …

The First Reported Case Of Treating The Ultra-Central Thorax With Cone Beam Computed Tomography-Guided Stereotactic Adaptive Radiotherapy (Ct-Star), Stephanie Zhao, Robbie Beckert, Xiaodong Zhao, Eric Laugeman, Clifford G. Robinson, Gregory Vlacich, Pamela P. Samson, Joshua P. Schiff

2020-Current year OA Pubs

Stereotactic body radiotherapy (SBRT) to the central and ultra-central thorax is associated with infrequent but potentially serious adverse events. Adaptive SBRT, which provides more precise treatment planning and inter-fraction motion management, may allow the delivery of ablative doses to ultra-central tumors with effective local control and improved toxicity profiles. Herein, we describe the first reported case of cone beam computed tomography (CBCT)-guided stereotactic adaptive radiotherapy (CT-STAR) in the treatment of ultra-central non-small cell lung cancer (NSCLC) in a prospective clinical trial (NCT05785845). An 80-year-old man with radiographically diagnosed early-stage NSCLC presented for definitive management of an enlarging ultra-central lung nodule. …

Skeletal Abnormalities In Mice With Dnmt3a Missense Mutations, Austin Bell-Hensley, Diana C Beard, Kathryn Feeney, Hongjun Zheng, Yunhao Jiang, Xiyun Zhang, Jin Liu, Harrison Gabel, Audrey Mcalinden

2020-Current year OA Pubs

Overgrowth and intellectual disability disorders in humans are typified by length/height and/or head circumference ≥ 2 standard deviations above the mean as well as intellectual disability and behavioral comorbidities, including autism and anxiety. Tatton-Brown-Rahman Syndrome is one type of overgrowth and intellectual disability disorder caused by heterozygous missense mutations in the DNA methyltransferase 3A (DNMT3A) gene. Numerous DNMT3A mutations have been identified in Tatton-Brown-Rahman Syndrome patients and may be associated with varying phenotype severities of clinical presentation. Two such mutations are the R882H and P904L mutations which result in severe and mild phenotypes, respectively. Mice with paralogous mutations (Dnmt3a

Symptom Characteristics, Perceived Causal Attributions, And Contextual Factors Influencing Self-Care Behaviors: An Ecological Daily Assessment Study Of Adults With Chronic Illness, Barbara Riegel, Shayleigh Dickson Page, Subhash Aryal, Christopher S Lee, Andrew Belfiglio, Kenneth E Freedland, Anna Stromberg, Ercole Vellone, Heleen Westland, Michelle M Van Rijn, Sara Pettersson, Douglas J Wiebe, Tiny Jaarsma

2020-Current year OA Pubs

OBJECTIVE: Insights into how symptoms influence self-care can guide patient education and improve symptom control. This study examined symptom characteristics, causal attributions, and contextual factors influencing self-care of adults with arthritis, asthma, chronic obstructive pulmonary disease, diabetes, or heart failure.

METHODS: Adults (n = 81) with a symptomatic chronic illness participated in a longitudinal observational study. Using Ecological Daily Assessment, participants described one symptom twice daily for two weeks, rating its frequency, severity, bothersomeness, duration, causes, and self-care.

RESULTS: The most frequent symptoms were fatigue and shortness of breath. Pain, fatigue, and joint stiffness were the most severe and bothersome. …

A Microbiota-Directed Complementary Food Intervention In 12-18-Month-Old Bangladeshi Children Improves Linear Growth, Ishita Mostafa, Matthew C Hibberd, Steven J Hartman, Md Hasan Hafizur Rahman, Mustafa Mahfuz, S M Tafsir Hasan, Per Ashorn, Michael J Barratt, Tahmeed Ahmed, Jeffrey I Gordon

2020-Current year OA Pubs

BACKGROUND: Globally, stunting affects ∼150 million children under five, while wasting affects nearly 50 million. Current interventions have had limited effectiveness in ameliorating long-term sequelae of undernutrition including stunting, cognitive deficits and immune dysfunction. Disrupted development of the gut microbiota has been linked to the pathogenesis of undernutrition, providing potentially new treatment approaches.

METHODS: 124 Bangladeshi children with moderate acute malnutrition (MAM) enrolled (at 12-18 months) in a previously reported 3-month RCT of a microbiota-directed complementary food (MDCF-2) were followed for two years. Weight and length were monitored by anthropometry, the abundances of bacterial strains were assessed by quantifying metagenome-assembled …

Aeeg In The First 3 Days After Extremely Preterm Delivery Relates To Neurodevelopmental Outcomes, Roberta Pineda, Zachary Vesoulis, Nathalie El Ters, Amit Mathur

2020-Current year OA Pubs

OBJECTIVES: Investigate relationships between aEEG in the first 72 h in extremely preterm infants with 1) infant, medical, and environmental factors, and 2) infant feeding and neurobehavioral outcomes at term and school-age.

METHODS: Sixty-four preterm infants (≤28 weeks gestation) were enrolled within the first 24-hours of life and had two-channel aEEG until 72 h of life. Standardized neurobehavioral and feeding assessments were conducted at term, and parent-reported outcomes were documented at 5-7 years.

RESULTS: Lower aEEG Burdjalov scores (adjusted for gestational age) were related to vaginal delivery (p = 0.04), cerebral injury (p = 0.01), Black race (p < 0.01) and having unmarried parents (p = 0.02). Lower Burdjalov scores related to less NICU Network Neurobehavioral Scale arousal (p = 0.002) at term and poorer BRIEF global executive function (p = 0.004), inhibition (p = 0.007), working memory (p = 0.02), material organization (p = 0.0008), metacognition (p = 0.01), and behavioral regulation (p = 0.02) at 5-7 years. We did not observe relationships of early aEEG to feeding outcomes or sensory processing measures.

CONCLUSION: Early …

Efficacy And Safety Of A Four-Drug, Quarter-Dose Treatment For Hypertension: The Quartet Usa Randomized Trial, Mark D Huffman, Et Al.

2020-Current year OA Pubs

New approaches are needed to lower blood pressure (BP) given persistently low control rates. QUARTET USA sought to evaluate the effect of four-drug, quarter-dose BP lowering combination in patients with hypertension. QUARTET USA was a randomized (1:1), double-blinded trial conducted in federally qualified health centers among adults with hypertension. Participants received either a quadpill of candesartan 2 mg, amlodipine 1.25 mg, indapamide 0.625 mg, and bisoprolol 2.5 mg or candesartan 8 mg for 12 weeks. If BP was >130/>80 mm Hg at 6 weeks in either arm, then participants received open label add-on amlodipine 5 mg. The primary outcome …

Ascc1 Structures And Bioinformatics Reveal A Novel Helix-Clasp-Helix Rna-Binding Motif Linked To A Two-Histidine Phosphodiesterase, Naga Babu Chinnam, Jennifer M Soll, Nima Mosammaparast, Et Al.

2020-Current year OA Pubs

Activating signal co-integrator complex 1 (ASCC1) acts with ASCC-ALKBH3 complex in alkylation damage responses. ASCC1 uniquely combines two evolutionarily ancient domains: nucleotide-binding K-Homology (KH) (associated with regulating splicing, transcriptional, and translation) and two-histidine phosphodiesterase (PDE; associated with hydrolysis of cyclic nucleotide phosphate bonds). Germline mutations link loss of ASCC1 function to spinal muscular atrophy with congenital bone fractures 2 (SMABF2). Herein analysis of The Cancer Genome Atlas (TCGA) suggests ASCC1 RNA overexpression in certain tumors correlates with poor survival, Signatures 29 and 3 mutations, and genetic instability markers. We determined crystal structures of Alvinella pompejana (Ap) ASCC1 and Human (Hs) …

Changes In Online Marketing And Sales Practices Among Non-Medical Cannabis Retailers In 5 Us Cities, 2022 To 2023, Yuxian Cui, Zongshuan Duan, Cassidy R Loparco, Katie Vinson, Katelyn F Romm, Yan Wang, Patricia A Cavazos-Rehg, Erin Kasson, Y Tony Yang, Carla J Berg

2020-Current year OA Pubs

OBJECTIVES: Given the evolving cannabis marketplace (e.g., products, marketing strategies), this study examined online cannabis marketing practices over time.

METHODS: In 2022 and 2023, researchers assessed website content (e.g., age verification, sales, delivery, warnings, ad content, promotional strategies) among 175 randomly-selected cannabis retailers' websites across 5 US cities (Denver, Colorado; Seattle, Washington; Portland, Oregon; Las Vegas, Nevada; Los Angeles [LA], California, n=∼35/city). Analyses compared data from 2022 vs. 2023 and considered regulatory factors across cities.

RESULTS: Similar to 2022, in 2023, 76.6 % required age verification for site entry, 85.1 % used social media promotion, and 90.9 % offered online …

Co-Aggregation With Apolipoprotein E Modulates The Function Of Amyloid-Β In Alzheimer's Disease, Zengjie Xia, Michael R Strickland, Hong Jiang, David M Holtzman, Et Al.

2020-Current year OA Pubs

Which isoforms of apolipoprotein E (apoE) we inherit determine our risk of developing late-onset Alzheimer's Disease (AD), but the mechanism underlying this link is poorly understood. In particular, the relevance of direct interactions between apoE and amyloid-β (Aβ) remains controversial. Here, single-molecule imaging shows that all isoforms of apoE associate with Aβ in the early stages of aggregation and then fall away as fibrillation happens. ApoE-Aβ co-aggregates account for ~50% of the mass of diffusible Aβ aggregates detected in the frontal cortices of homozygotes with the higher-risk APOE4 gene. We show how dynamic interactions between apoE and Aβ tune disease-related …

The Impact Of An Advanced Practice Radiation Therapist Contouring For A Cbct-Based Adaptive Radiotherapy Program, Robbie Beckert, Joshua P Schiff, Eric Morris, Pamela Samson, Hyun Kim, Eric Laugeman

2020-Current year OA Pubs

We successfully implemented an APRT specializing in CBCT-guided online adaptive contouring. These data show statistical improvements in contouring time with APRT-led vs non-APRT led ART contouring, suggesting that an APRT specifically trained to manage the ART process may reduce physician workload and patient treatment time.

Metastasectomy For Extracalvarial Renal Cell Carcinoma, Rahim Abo Kasem, Karan Joseph, Adnan Shaik, Angela Downes, M Burhan Janjua

2020-Current year OA Pubs

KEY CLINICAL MESSAGE: Palliative surgical resection of extra-calvarial metastatic lesions from renal cell tumors is crucial for controlling metastatic spread, improving quality of life, and preventing associated morbidity. Careful surgical planning, including selective preoperative embolization and controlled resection around critical structures such as the sagittal sinus, is essential for successful outcomes. Cranioplasty with Titanium mesh and bone cement post-resection can provide symptomatic relief, better cosmesis, and overall improved quality of life.

ABSTRACT: Renal cell carcinomas are aggressive tumors with distant systemic disease. The calvarium appears to be an unusual and rare site for distant metastasis. The treatment modalities are challenging …

Retrospective Multicenter Cohort Study On Safety And Electroencephalographic Response To Lacosamide For Neonatal Seizures, Moninder Kaur, Rejean M Guerriero, Renée A Shellhaas, Et Al.

2020-Current year OA Pubs

BACKGROUND: There is growing evidence supporting the safety and effectiveness of lacosamide in older children. However, minimal data are available for neonates. We aimed to determine the incidence of adverse events associated with lacosamide use and explore the electroencephalographic seizure response to lacosamide in neonates.

METHODS: A retrospective cohort study was conducted using data from seven pediatric hospitals from January 2009 to February 2020. For safety outcomes, neonates were followed for ≤30 days from index date. Electroencephalographic response of lacosamide was evaluated based on electroencephalographic reports for ≤3 days.

RESULTS: Among 47 neonates, 98% received the first lacosamide dose in …

Genome-Wide Association Studies And Mendelian Randomization Analyses Provide Insights Into The Causes Of Early-Onset Colorectal Cancer, R S Laskar, Y Cao, Et Al.

2020-Current year OA Pubs

BACKGROUND: The incidence of early-onset colorectal cancer (EOCRC; diagnosed < 50 years of age) is rising globally; however, the causes underlying this trend are largely unknown. CRC has strong genetic and environmental determinants, yet common genetic variants and causal modifiable risk factors underlying EOCRC are unknown. We conducted the first EOCRC-specific genome-wide association study (GWAS) and Mendelian randomization (MR) analyses to explore germline genetic and causal modifiable risk factors associated with EOCRC.

PATIENTS AND METHODS: We conducted a GWAS meta-analysis of 6176 EOCRC cases and 65 829 controls from the Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO), the Colorectal Transdisciplinary Study (CORECT), the Colon Cancer Family Registry (CCFR), and the UK Biobank. We then used the EOCRC GWAS to investigate 28 modifiable risk factors using two-sample MR.

RESULTS: We found two novel risk loci for EOCRC at 1p34.1 and 4p15.33, which were not previously associated with CRC risk. We identified a deleterious coding variant (rs36053993, G396D) at polyposis-associated DNA repair gene MUTYH …

Late-Season Influenza Vaccine Effectiveness Against Medically Attended Outpatient Illness, United States, December 2022-April 2023, Jessie R Chung, Stacey L House, Tara Curley, Et Al.

2020-Current year OA Pubs

BACKGROUND: The 2022-23 US influenza season peaked early in fall 2022.

METHODS: Late-season influenza vaccine effectiveness (VE) against outpatient, laboratory-confirmed influenza was calculated among participants of the US Influenza VE Network using a test-negative design.

RESULTS: Of 2561 participants enrolled from December 12, 2022 to April 30, 2023, 91 laboratory-confirmed influenza cases primarily had A(H1N1)pdm09 (6B.1A.5a.2a.1) or A(H3N2) (3C.2a1b.2a.2b). Overall, VE was 30% (95% confidence interval -9%, 54%); low late-season activity precluded estimation for most subgroups.

CONCLUSIONS: 2022-23 late-season outpatient influenza VE was not statistically significant. Genomic characterization may improve the identification of influenza viruses that circulate postinfluenza peak.

Takotsubo Syndrome In Patients With Covid-19: A Systematic Review, Xiaojia Lu, Catherine Teng, Peng Cai, Jing Liang, Yanxuan Wang, Hawa Abu, Yuan Jia Wang, John E Madias, Kan Liu, Qi Liu, Pengyang Li

2020-Current year OA Pubs

BACKGROUND: Respiratory conditions are major physical triggers of takotsubo syndrome (TTS) and portend worse outcomes. However, data on TTS in patients with coronavirus disease-2019 infection (COVID-19) are limited.

METHODS: We searched PubMed, Embase, and Cochrane Library databases for case reports for the period 2019-2022 describing TTS in patients with COVID-19 pneumonia (TTS-COVID). We summarized the clinical data and outcomes and compared them to those in patients with TTS with an acute respiratory disease other than COVID-19 as a trigger (TTS-acute respiratory disease) and those with TTS with no respiratory disease (TTS-no respiratory disease).

RESULTS: The mortality rate was higher in …

Validated Clinical Score To Predict Gastroesophageal Reflux In Patients With Chronic Laryngeal Symptoms: Cough Reflux, Amanda J Krause, Alexander M Kaizer, Dustin A Carlson, Walter W Chan, Chien-Lin Chen, C Prakash Gyawali, Andrew Jenkins, John E Pandolfino, Vinathi Polamraju, Ming-Wun Wong, Madeline Greytak, Rena Yadlapati

2020-Current year OA Pubs

BACKGROUND & AIMS: Discerning whether laryngeal symptoms result from gastroesophageal reflux is clinically challenging and a reliable tool to stratify patients is needed. We aimed to develop and validate a model to predict the likelihood of gastroesophageal reflux disease (GERD) among patients with chronic laryngeal symptoms.

METHODS: This multicenter international study collected data from adults with chronic laryngeal symptoms who underwent objective testing (upper gastrointestinal endoscopy and/or ambulatory reflux monitoring) between March 2018 and May 2023. The training phase identified a model with optimal receiver operating characteristic curves, and β coefficients informed a weighted model. The validation phase assessed performance …

Paracrine Signaling By Pancreatic Islet Cilia, Samantha E Adamson, Jing W Hughes

2020-Current year OA Pubs

The primary cilium is a sensory and signaling organelle present on most pancreatic islet endocrine cells, where it receives and interprets a wide range of intra-islet chemical cues including hormones, peptides, and neurotransmitters. The ciliary membrane possesses a molecular composition distinct from the plasma membrane, with enrichment of signaling mediators including G protein-coupled receptors (GPCRs), tyrosine kinase family receptors, membrane transporters and others. When activated, these membrane proteins interact with ion channels and adenylyl cyclases to trigger local Ca

Bcar4 Expression As A Predictive Biomarker For Endocrine Therapy Resistance In Breast Cancer, Muheng Liao, Jace Webster, Emily M Coonrod, Katherine N Weilbaecher, Christopher A Maher, Nicole M White

2020-Current year OA Pubs

BACKGROUND: Breast cancer, particularly the estrogen receptor positive (ER+) subtype, remains a leading cause of cancer-related death among women. Endocrine therapy is the most effective treatment for ER+ breast cancer; however, the development of resistance presents a significant challenge. This study explored the role of the breast cancer antiestrogen resistance 4 (BCAR4) gene as a potential driver of resistance and a pivotal biomarker in breast cancer.

PATIENTS AND METHODS: The researchers undertook a comprehensive analysis of 1743 patients spanning 6 independent cohorts. They examined the association of BCAR4 expression with patient outcomes across all breast cancer types and the PAM50 …

Inherited C-Terminal Trex1 Variants Disrupt Homology-Directed Repair To Cause Senescence And Dna Damage Phenotypes In Drosophila, Mice, And Humans, Samuel D Chauvin, Fang R Zhao, W Alexander Stinson, Wei Qian, Prabhakar S Andhey, Maxim N Artyomov, Elisha D O Roberson, Jonathan J Miner, Et Al.

2020-Current year OA Pubs

Age-related microangiopathy, also known as small vessel disease (SVD), causes damage to the brain, retina, liver, and kidney. Based on the DNA damage theory of aging, we reasoned that genomic instability may underlie an SVD caused by dominant C-terminal variants in TREX1, the most abundant 3'-5' DNA exonuclease in mammals. C-terminal TREX1 variants cause an adult-onset SVD known as retinal vasculopathy with cerebral leukoencephalopathy (RVCL or RVCL-S). In RVCL, an aberrant, C-terminally truncated TREX1 mislocalizes to the nucleus due to deletion of its ER-anchoring domain. Since RVCL pathology mimics that of radiation injury, we reasoned that nuclear TREX1 would cause …

Safety Of Non-Cuffed Tunneled Central Venous Catheters In Adults With Cystic Fibrosis, Arshan Dehbozorgi, Badr Jandali, Robert Turner, Aaron Rohr, Brandon Custer, Kate Young, Carissa Walter, Lauren Clark, Yanming Li, Deepika Polineni, Joel Mermis

2020-Current year OA Pubs

BACKGROUND: Peripherally inserted central catheters (PICCs) are the most common route of intravenous (I.V.) access for treatment of cystic fibrosis (CF) pulmonary exacerbations, but repeated PICC placement can result in upper extremity peripheral venous stenosis. Once peripheral stenosis develops, a non-cuffed tunneled central venous catheter (NcTCVC) is an alternative route for IV access. While these are regularly used at some CF centers, the safety and complication rate compared to PICCs in adults with CF has not been reported. This study aims to describe the safety of NcTCVCs in adults with CF.

METHODS: A retrospective cohort study was performed at a …

Predictors Of Non-Variceal Hemorrhage In A National Cohort Of Patients With Chronic Liver Disease, Amber Afzal, Preethi Kesavan, Luo Suhong, Brian F Gage, Kevin Korenblat, Martin Schoen, Kristen Sanfilippo

2020-Current year OA Pubs

BACKGROUND: Non-variceal hemorrhage in patients with chronic liver disease (CLD) increases morbidity, mortality, and healthcare costs. There are limited data on risk factors for non-variceal hemorrhage in the CLD population. The aim of this study was to assess the predictive value of various clinical and laboratory parameters for non-variceal hemorrhage in CLD patients.

METHODS: We conducted a retrospective cohort study of US veterans diagnosed with CLD between 2002 and 2018 within the Veterans Health Administration database. We derived candidate variables from existing risk prediction models for hemorrhage, risk calculators for severity of liver disease, Charlson index of prognostic comorbidities, and …

Three-Year Outcomes Of Post-Acute Sequelae Of Covid-19, Miao Cai, Yan Xie, Eric J Topol, Ziyad Al-Aly

2020-Current year OA Pubs

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection causes post-acute sequelae of coronavirus disease 2019 (COVID-19) (PASC) in many organ systems. Risks of these sequelae have been characterized up to 2 years after infection, but longer-term follow-up is limited. Here we built a cohort of 135,161 people with SARS-CoV-2 infection and 5,206,835 controls from the US Department of Veterans Affairs who were followed for 3 years to estimate risks of death and PASC. Among non-hospitalized individuals, the increased risk of death was no longer present after the first year of infection, and risk of incident PASC declined over the 3 …

Plasma Extracellular Vesicle Tau And Tdp-43 As Diagnostic Biomarkers In Ftd And Als, Madhurima Chatterjee, Nicolas R Barthélemy, Randall J Bateman, Et Al.

2020-Current year OA Pubs

Minimally invasive biomarkers are urgently needed to detect molecular pathology in frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS). Here, we show that plasma extracellular vesicles (EVs) contain quantifiable amounts of TDP-43 and full-length tau, which allow the quantification of 3-repeat (3R) and 4-repeat (4R) tau isoforms. Plasma EV TDP-43 levels and EV 3R/4R tau ratios were determined in a cohort of 704 patients, including 37 genetically and 31 neuropathologically proven cases. Diagnostic groups comprised patients with TDP-43 proteinopathy ALS, 4R tauopathy progressive supranuclear palsy, behavior variant FTD (bvFTD) as a group with either tau or TDP-43 pathology, and healthy …

Scmr Expert Consensus Statement For Cardiovascular Magnetic Resonance Of Patients With A Cardiac Implantable Electronic Device, Daniel Kim, Pamela K Woodard, Et Al.

2020-Current year OA Pubs

Cardiovascular magnetic resonance (CMR) is a proven imaging modality for informing diagnosis and prognosis, guiding therapeutic decisions, and risk stratifying surgical intervention. Patients with a cardiac implantable electronic device (CIED) would be expected to derive particular benefit from CMR given high prevalence of cardiomyopathy and arrhythmia. While several guidelines have been published over the last 16 years, it is important to recognize that both the CIED and CMR technologies, as well as our knowledge in MR safety, have evolved rapidly during that period. Given increasing utilization of CIED over the past decades, there is an unmet need to establish a …

Single-Cell Lineage Capture Across Genomic Modalities With Celltag-Multi Reveals Fate-Specific Gene Regulatory Changes, Kunal Jindal, Mohd Tayyab Adil, Naoto Yamaguchi, Xue Yang, Helen C Wang, Kenji Kamimoto, Guillermo C Rivera-Gonzalez, Samantha A Morris

2020-Current year OA Pubs

Complex gene regulatory mechanisms underlie differentiation and reprogramming. Contemporary single-cell lineage-tracing (scLT) methods use expressed, heritable DNA barcodes to combine cell lineage readout with single-cell transcriptomics. However, reliance on transcriptional profiling limits adaptation to other single-cell assays. With CellTag-multi, we present an approach that enables direct capture of heritable random barcodes expressed as polyadenylated transcripts, in both single-cell RNA sequencing and single-cell Assay for Transposase Accessible Chromatin using sequencing assays, allowing for independent clonal tracking of transcriptional and epigenomic cell states. We validate CellTag-multi to characterize progenitor cell lineage priming during mouse hematopoiesis. Additionally, in direct reprogramming of fibroblasts to …