Digital Commons Network^™

Dfcp1 Is A Regulator Of Starvation-Driven Atgl-Mediated Lipid Droplet Lipolysis, Victoria A Ismail, Meg Schuetz, Zak N Baker, Jean A Castillo-Badillo, Teri V Naismith, David J Pagliarini, David J Kast

2020-Current year OA Pubs

Lipid droplets (LDs) are transient lipid storage organelles that can be readily tapped to resupply cells with energy or lipid building blocks, and therefore play a central role in cellular metabolism. Double FYVE Domain Containing Protein 1 (DFCP1/ZFYVE1) has emerged as a key regulator of LD metabolism, where the nucleotide-dependent accumulation of DFCP1 on LDs influences their size, number, and dynamics. Here we show that DFCP1 regulates lipid metabolism by directly modulating the activity of Adipose Triglyceride Lipase (ATGL/PNPLA2), the rate-limiting lipase driving the catabolism of LDs. We show through pharmacological inhibition of key enzymes associated with LD metabolism that …

The Cross-Sectional Association Between State-Level Public Health Funding Per Capita And Physical Health Among Adults In The United States, Stephen Hunter, Sze Y. Liu, Daniel M. Cook, Kia L. Davis, Brendan T. Smith, Roman Pabayo

2020-Current year OA Pubs

OBJECTIVES: This study examined the association between state-level public health funding per capita and the odds of poor physical health.

STUDY DESIGN: Cross-sectional.

METHODS: Data from the 2018 Behavioral Risk Factor Surveillance System (BRFSS) were used. Participants' self-reported physical health was reported using the CDC Healthy Days Core Module. State-level public health funding per capita was obtained from the State Health Access Data Assistance Center website. Multilevel logistic regression was used to adjust for self-reported individual-level characteristics and state-level characteristics from the 2018 American Community Survey. We also tested whether household income or education attainment moderated any observed associations.

RESULTS: …

Viral Kinetics Among Persons Living With Hiv (Plwh) On Dolutegravir-Based Antiretroviral Regimen: A Retrospective And Prospective Analysis From Selected Hiv Clinics In Ghana, Samuel Badu Nyarko, Joel Adu Twum, Aikins Sarpong Obeng, Helena Dede Djangba, Oksana Ryabinina, Foster Kyei, George Boateng Kyei, Nicholas Ekow Thomford

2020-Current year OA Pubs

BACKGROUND: Dolutegravir (DTG)-based antiretroviral therapy has demonstrated superior efficacy, tolerability, and durability when compared to other HIV treatment regimens. However, monitoring viral kinetics is critical for determining treatment efficacy and making sound judgments. The purpose of this study was to assess viral kinetics in people living with HIV (PLWH) on DTG-based ART and identify characteristics related to virologic response in the Cape Coast Metropolis, Ghana.

METHODS: Among people living with HIV (PLWH) attending HIV clinics between January 2020 and December 2023, a prospective and retrospective analysis of viral kinetics and clinical data were carried out. Data on viral loads, clinical …

The Role Of Telehealth In Sepsis Care In Rural Emergency Departments: A Qualitative Study Of Emergency Department Sepsis Telehealth User Perspectives, Nicholas M. Mohr, Kimberly A. S. Merchant, Brian M. Fuller, Brett Faine, Luke Mack, Amanda Bell, Katie Dejong, Edith A. Parker, Keith Mueller, Elizabeth Chrischilles, Christopher R. Carpenter, Michael P. Jones, Steven Q. Simpson, Marcia M. Ward

2020-Current year OA Pubs

PURPOSE: Sepsis is a leading cause of hospitalization and death in the United States, and rural patients are at particularly high risk. Telehealth has been proposed as one strategy to narrow rural-urban disparities. The objective of this study was to understand why rural emergency department (ED) staff use provider-to-provider telehealth (tele-ED) and how tele-ED care changes the care for rural patients with sepsis.

METHODS: We conducted a qualitative interview study between February 15, 2022, and May 22, 2023, with participants from upper Midwest rural EDs and tele-ED hub physicians in a single tele-ED network that delivers provider-to-provider consultation for sepsis …

Multisensory Naturalistic Decoding With High-Density Diffuse Optical Tomography, Kalyan Tripathy, Zachary E Markow, Morgan Fogarty, Mariel L Schroeder, Alexa M Svoboda, Adam T Eggebrecht, Bradley L Schlaggar, Jason W Trobaugh, Joseph P Culver

2020-Current year OA Pubs

SIGNIFICANCE: Decoding naturalistic content from brain activity has important neuroscience and clinical implications. Information about visual scenes and intelligible speech has been decoded from cortical activity using functional magnetic resonance imaging (fMRI) and electrocorticography, but widespread applications are limited by the logistics of these technologies.

AIM: High-density diffuse optical tomography (HD-DOT) offers image quality approaching that of fMRI but with the silent, open scanning environment afforded by optical methods, thus opening the door to more naturalistic research and applications. Although early visual decoding studies with HD-DOT have been promising, decoding of naturalistic auditory and multisensory stimulus information from HD-DOT data …

Zika Virus Encephalitis Causes Transient Reduction Of Functional Cortical Connectivity, Shannon C Agner, Lindsey M Brier, Jeremy D Hill, Ethan Y Liu, Annie Bice, Rachel M Rahn, Shengxuan Chen, Joseph P Culver, Robyn S Klein

2020-Current year OA Pubs

SIGNIFICANCE: Determining the long-term cognitive impact of infections is clinically challenging. Using functional cortical connectivity, we demonstrate that interhemispheric cortical connectivity is decreased in individuals with acute Zika virus (ZIKV) encephalitis. This correlates with decreased presynaptic terminals in the somatosensory cortex. During recovery from ZIKV infection, presynaptic terminals recover, which is associated with recovered interhemispheric connectivity. This supports the contribution of synapses in the cortex to functional networks in the brain, which can be detected by widefield optical imaging. Although myeloid cell and astrocyte numbers are still increased during recovery, RNA transcription of multiple proinflammatory cytokines that increase during acute …

Clinical Trials For Wolfram Syndrome Neurodegeneration: Novel Design, Endpoints, And Analysis Models, Guoqiao Wang, Zhaolong Adrian Li, Ling Chen, Heather Lugar, Tamara Hershey

2020-Current year OA Pubs

OBJECTIVE: Wolfram syndrome, an ultra-rare condition, currently lacks effective treatment options. The rarity of this disease presents significant challenges in conducting clinical trials, particularly in achieving sufficient statistical power (e.g., 80%). The objective of this study is to propose a novel clinical trial design based on real-world data to reduce the sample size required for conducting clinical trials for Wolfram syndrome.

METHODS: We propose a novel clinical trial design with three key features aimed at reducing sample size and improve efficiency: (i) Pooling historical/external controls from a longitudinal observational study conducted by the Washington University Wolfram Research Clinic. (ii) Utilizing …

Examining And Classifying Reasons For Missing Viral Loads Among Adults Living With Hiv: An Extended Outcome Investigation And Ascertainment Approach In Western Kenya, Harriet Fridah Adhiambo, Jayne Lewis-Kulzer, Edwin Nyagesoa, Sarah Gimbel, Eliud Akama, Dorothy Mangale, Lina Montonya, Ingrid Eshun-Wilson, Sarah Iguna, Everlyne Nyandieka, Elizabeth Bukusi, Lisa Abuogi, Thomas Odeny, Maya L. Petersen, Elvin H. Geng

2020-Current year OA Pubs

Gaps in HIV RNA monitoring persist globally impeding the ability to determine clinical progress and outcomes. This study systematically evaluated provider (e.g., guideline non-adherence), system (e.g., laboratory error) and participant-level (e.g., refusal) drivers of missed viral load (VL) monitoring measurements among people with HIV in Kenya. Adults aged 18-65 years were followed across five health facilities in Kenya as part of a clinical trial (NCT#02338739) where HIV RNA monitoring was done routinely. Instances of missed VL despite being indicated per Kenyan guidelines were identified. An algorithm for assessing root causes of missing HIV RNA was developed and generalized linear models …

Rethinking Immune Check Point Inhibitors Use In Liver Transplantation: Implications And Resistance, Vivian Ortiz, Emilien Loeuillard

2020-Current year OA Pubs

Immune checkpoint inhibitors (ICIs) have revolutionized cancer therapy, including the two most common liver tumors, hepatocellular carcinoma and cholangiocarcinoma, but their use in the peri-transplantation period is controversial. ICI therapy aims to heighten cytotoxic T lymphocytes response against tumors. However, tumor recurrence is common owing to tumor immune response escape involving ablation of CTL response by interfering with antigen presentation, triggering CLT apoptosis and inducing epigenetic changes that promote ICI therapy resistance. ICI can also affect tissue resident memory T cell population, impact tolerance in the post-transplant period, and induce acute inflammation risking graft survival post-transplant. Their interaction with immunosuppression …

Poor Sleep Is Common In Treatment-Resistant Late-Life Depression And Associated With Poorer Antidepressant Response: Findings From The Optimum Clinical Trial, Michael S B Mak, Marie Anne Gebara, Eric J Lenze, Daniel M Blumberger, Patrick J Brown, Pilar Cristancho, Alastair J Flint, Jordan F Karp, Helen Lavretsky, J Philip Miller, Charles F Reynolds 3rd, Steven P Roose, Benoit H Mulsant, Sarah T Stahl

2020-Current year OA Pubs

BACKGROUND: Adults with treatment-resistant late-life depression (TRLLD) have high rates of sleep problems; however, little is known about the occurrence and change in sleep during pharmacotherapy of TRLLD. This analysis examined: (1) the occurrence of insufficient sleep among adults with TRLLD; (2) how sleep changed during pharmacotherapy; and (3) whether treatment outcomes differed among participants with persistent insufficient sleep, worsened sleep, improved sleep, or persistent sufficient sleep.

METHODS: Secondary analysis of data from 634 participants age 60+ years in the OPTIMUM clinical trial for TRLLD. Sleep was assessed using the sleep item from the Montgomery-Asberg Depression Rating Scale at the …

Molecular Regulation And Therapeutic Targeting Of Vldl Production In Cardiometabolic Disease, Kendall H Burks, Nathan O Stitziel, Nicholas O Davidson

2020-Current year OA Pubs

There exists a complex relationship between steatotic liver disease (SLD) and atherosclerotic cardiovascular disease (CVD). CVD is a leading cause of morbidity and mortality among individuals with SLD, particularly those with metabolic dysfunction-associated SLD (MASLD), a significant proportion of whom also exhibit features of insulin resistance. Recent evidence supports an expanded role of very low-density lipoprotein (VLDL) in the pathogenesis of CVD in patients, both with and without associated metabolic dysfunction. VLDL represents the major vehicle for exporting neutral lipid from hepatocytes, with each particle containing one molecule of apolipoproteinB100 (APOB100). VLDL production becomes dysregulated under conditions characteristic of MASLD …

Reliability Of Wrist Arthroscopy In The Diagnosis And Treatment Of Triangular Fibrocartilage Complex Tears, Elizabeth A Graesser, Lindley B Wall, Sanjeev Kakar, Jeffrey Yao, Marc J Richard, R Glenn Gaston, Charles A Goldfarb

2020-Current year OA Pubs

PURPOSE: Wrist arthroscopy is considered the gold standard for diagnosis of intra-articular wrist conditions including triangular fibrocartilage complex (TFCC) tears; however, the ability to reliably diagnose TFCC pathology during wrist arthroscopy is unclear. The purpose of this study was to assess the reliability of the diagnosis of TFCC tears on wrist arthroscopy videos.

METHODS: Five hand surgeons reviewed 43 cases on a secure web-based platform at two time points separated by 4-6 weeks. Each case included a deidentified clinical vignette and wrist radiographs with ulnar variance measurements and an arthroscopy video of ulnar wrist pathology, averaging 42 seconds. Surgeons were …

Costs Of Non-Metastatic Prostate Cancer Treatment Among Privately Insured Men In The United States, Ashley J. Housten, Su-Hsin Chang, Hannah E. Rice, Allison J. L'Hotta, Eric H. Kim, Bettina F. Drake, Joanna L. Buss, Mary C. Politi

2020-Current year OA Pubs

BACKGROUND: Our objective was to quantify the cumulative total and out-of-pocket (OOP) costs for 3 non-metastatic prostate cancer treatment modalities: radiation, surgery, and conservative management at intervals of 1-, 3-, and 5-years post-diagnosis. We predicted these cumulative costs for a typical patient to improve cost transparency, facilitate conversations about potential costs, and to help advance non-metastatic prostate cancer cost evaluation.

METHODS: We used Merative™ MarketScan® Commercial Database data from 2007-2020. The cumulative total costs evaluated from the healthcare sector perspective were patient, clinician, and system/facility costs. We used descriptive statistics to summarize the sociodemographic characteristics of the cohort and a …

First Successful Ovarian Cortex Allotransplant To A Turner Syndrome Patient Requiring Immunosuppression: Wide Implications, Sherman J Silber, Sierra Goldsmith, Benjamin Rubinoff, Eduardo Kelly, Rowena Delos Santos, Anibal Melo, Daniel Brennan

2020-Current year OA Pubs

OBJECTIVE: To determine whether we can safely and successfully transplant an ovary tissue allograft from a nonidentical donor to her Turner syndrome sister.

DESIGN: Transplantation of cryopreserved ovary tissue, as well as fresh transplantation of ovarian tissue between identical twins, is now well established with numerous reported successful cases. However, there have not yet been any ovary transplants between nonidentical women requiring immunosuppression (ovary allotransplant). This could be a much more common indication for ovary tissue transplantation if safe and reliable immunosuppression were available.

PATIENT(S): A 20-year-old amenorrheic woman with nonmosaic 45-XO Turner syndrome requested ovary tissue transplantation from her …

A Holistic Ecosystem Model To Diversify The Physician Workforce And Enhance Health, Erik J Porfeli, Sunny Nakae, Leila Amiri, Leila E Harrison, Will Ross

2020-Current year OA Pubs

IMPORTANCE: The U.S. medical education system attracts and trains the next generation of physicians to advance the health care needs of a growing and increasingly diverse nation. This system can be credited for supplying a physician workforce achieving remarkable growth and innovation, yielding one of the world's most technologically advanced health care systems on the planet. This system, unfortunately, also contributes to educational, workforce, and health disparities.

OBSERVATIONS: The successes and challenges of the medical education and health care system align with broader economic, health, and educational patterns in the United States. An ecological model can be employed to unite …

Concomitant Traumatic Brain Injury Exacerbates Endotheliopathy In Patients With Spinal Cord Injury, Shahab Hafezi, Miguel A. Ruiz-Cardozo, Sarbani Ghosh, Sravanthi Bandla, Matthew N. Montoya Rush, Anand Dharmarajan, Mark H. Hoofnagle, Isaiah R. Turnbull, Camilo A. Molina, Grace M. Niziolek

2020-Current year OA Pubs

No abstract provided.

Baseline Clinical Characterization Of Participants In The Accelerating Medicines Partnership Schizophrenia Program, Jean Addington, Daniel Mamah, Et Al.

2020-Current year OA Pubs

BACKGROUND: This paper focuses on the baseline clinical characterization of the participants in the Accelerating Medicines Partnership Schizophrenia (AMP SCZ) program. The AMP SCZ program is designed to investigate a wide array of clinical variables and biomarkers in a total of 2040 clinical high-risk (CHR) participants and 652 community control (CC) participants.

METHODS: The dataset analyzed includes 1642 individuals at clinical high risk for psychosis and 519 CCs. Key measures include the Positive Symptoms and Diagnostic Criteria for the Comprehensive Assessment of At-Risk Mental States Harmonized with the Structured Interview for Psychosis-Risk Syndromes, which determined CHR criteria and the severity …

Sample Ascertainment And Recruitment Sources In The Accelerating Medicines Partnership Schizophrenia Program, Jean Addington, Daniel Mamah, Et Al.

2020-Current year OA Pubs

BACKGROUND: This paper presents the recruitment sources of clinical high-risk (CHR) and community controls (CC) from the Accelerating Medicines Partnership Schizophrenia (AMP SCZ) program, which aims to study various clinical variables and biomarkers in 2040 CHR and 652 CC participants.

METHODS: A total of 1640 CHR and 514 CC had recruitment source data. The Positive Symptoms and Diagnostic Criteria for the Comprehensive Assessment of At-Risk Mental States Harmonized with the SIPS was utilized to assess CHR criteria and severity of attenuated psychotic symptoms (APSs), and the Global Functioning: Social Scale was used for social functioning. Participants were recruited through various …

An Explainable Ai Approach For Mapping Multivariate Regional Brain Age And Clinical Severity Patterns In Alzheimer's Disease, Gauri Darekar, Taslim Murad, Hui-Yuan Miao, Deepa S Thakuri, Alzheimer’S Disease Neuroimaging Initiative, Ganesh B Chand

2020-Current year OA Pubs

Age is a significant risk factor for mild cognitive impairment (MCI) and Alzheimer's disease (AD) and identifying brain age patterns is critical for comprehending the normal aging and MCI/AD processes. Prior studies have widely established the univariate relationships between brain regions and age, while multivariate associations remain largely unexplored. Herein, various artificial intelligence (AI) models were used to perform brain age prediction using an MRI dataset (

Phase I Study Of Nt-I7, A Long-Acting Interleukin-7, In Severe Treatment-Related Lymphopenia Following Standard Radiation And Temozolomide For High-Grade Glioma, Jian L Campian, Milan G Chheda, John F Dipersio, Et Al.

2020-Current year OA Pubs

BACKGROUND: High-grade gliomas (HGG) have a poor prognosis despite aggressive treatment. Severe, persistent lymphopenia occurring in HGG patients after concurrent chemoradiation is associated with worse survival. NT-I7, a long-acting interleukin-7 analog, has been shown to increase CD4 and CD8 counts in healthy, septic, and HIV-positive adults. This multi-institutional, NCI-funded dose-escalation trial is the first to evaluate NT-I7 safety and activity in HGG patients with severe treatment-related lymphopenia (TRL) and the effect of co-administered glucocorticoids.

METHODS: Eligible HGG patients had CD4 counts < 300 cells/mm

RESULTS: NT-I7 was well tolerated in all 12 patients (median age 64; median CD4 count 161 cells/mm³) before the …

Recombinant Human Alpha-N-Acetylglucosamine-6-Sulfatase Delivered To Sanfilippo D Mice With Repeated Intracerebroventricular Injections Corrects Cns Pathology, Grant L. Austin, Feng Wang, Steven Q. Le, Alexander Sorensen, Shan Li, Lai C. Foong, Srikanth Singamsetty, Jill Wood, Tsui-Fen Chou, Patricia I. Dickson

2020-Current year OA Pubs

Mucopolysaccharidosis type IIID (MPS IIID; Sanfilippo D) is caused by biallelic pathogenic variants in N-acetylglucosamine-6-sulfatase (GNS), which participates in catabolism of heparan sulfate (HS) glycosaminoglycans. Characterization of MPS IIID disease at a cellular level has not been robustly achieved. We used unbiased quantitative proteomics to establish a cellular phenotype for MPS IIID mice. Recombinant human GNS (rhGNS), a variant of which previously demonstrated single dose efficacy in MPS IIID human fibroblasts and in MPS IIID neonatal mice, was used to establish a repeat dosing schedule to treat MPS IIID mice. Adult Gns KO mice or heterozygous carriers were treated via …

Thalamic And Visual Network Dysfunction Relates To Tremor Response In Thalamic Deep Brain Stimulation, Aimee E Morris, Babatunde Adeyemo, Meghan C Campbell, Abraham Z Snyder, Joel S Perlmutter, Jonathan W Mink, Scott A Norris

2020-Current year OA Pubs

BACKGROUND: Essential tremor (ET) is the most common movement disorder in adults, but its pathogenesis is incompletely understood. Deep brain stimulation of the ventral intermediate thalamic nucleus (VIM DBS) provides effective treatment for medically-refractory cases. We aimed to determine how pre-surgical resting-state functional connectivity (FC) in medically-refractory ET relates to VIM DBS clinical response.

METHODS: We analyzed resting-state FC MRI in 21 participants with medically-refractory ET who subsequently underwent VIM DBS and 34 matched controls. We applied rigorous quality assurance to minimize motion artifact. Whole-brain correlation matrices were computed across 300 cortical, subcortical, and cerebellar regions and compared across groups …

Pediatric Cervical Spine Clearance: A 10-Year Evaluation Of X-Ray In Evaluable Patients At A Level 1 Pediatric Trauma Center, William Starr, Stephanie Iantorno, Jing Wang, Richard Eldredge, Rajiv Iyer, Karch Smith, Natalya Mcnamara, Kezlyn Larsen, Stephen Fenton, Robert Swendiman, Katie Russell

2020-Current year OA Pubs

OBJECTIVES: Cervical spine (c-spine) X-ray (XR) remains an important tool for pediatric trauma patients. XR is a low radiation alternative to multidetector CT (MDCT). Our primary aims were to analyze the sensitivity of a negative c-spine XR and to analyze what factors lead to additional imaging after a negative c-spine XR.

METHODS: A retrospective cohort study was conducted at a level 1 pediatric trauma center from 2012 to 2021. We compared the group with negative c-spine XR and no additional imaging to the group with negative c-spine XR followed by additional c-spine MDCT and/or MRI.

RESULTS: There were 2,081 negative …

Development Of A High-Throughput Platform For Quantitation Of Histone Modifications On A New Qtof Instrument, Emily Zahn, Yixuan Xie, Xingyu Liu, Rashmi Karki, Richard M Searfoss, Francisca N De Luna Vitorino, Joanna K Lempiäinen, Joanna Gongora, Zongtao Lin, Chenfeng Zhao, Zuo-Fei Yuan, Benjamin A Garcia

2020-Current year OA Pubs

Histone post-translational modifications (PTMs) regulate gene expression patterns through epigenetic mechanisms. The five histone proteins (H1, H2A, H2B, H3, and H4) are extensively modified, with over 75 distinct modification types spanning more than 200 sites. Despite strong advances in mass spectrometry (MS)-based approaches, identification and quantification of modified histone peptides remains challenging because of factors, such as isobaric peptides, pseudo-isobaric PTMs, and low stoichiometry of certain marks. Here, we describe the development of a new high-throughput method to identify and quantify over 150 modified histone peptides by LC-MS. Fast gradient microflow liquid chromatography and variable window sequential windows acquisition of …

Caregiver Worry About Covid-19 As A Predictor Of Social Mitigation Behaviours And Sars-Cov-2 Infection In A 12-City U.S. Surveillance Study Of Households With Children, Steven M Brunwasser, Katherine Rivera-Spoljaric, Et Al.

2020-Current year OA Pubs

OBJECTIVE: Understanding compliance with COVID-19 mitigation recommendations is critical for informing efforts to contain future infectious disease outbreaks. This study tested the hypothesis that higher levels of worry about COVID-19 illness among household caregivers would predict lower (a) levels of overall and discretionary social exposure activities and (b) rates of household SARS-CoV-2 infections.

METHODS: Data were drawn from a surveillance study of households with children (

RESULTS: Caregivers with high enrollment levels of worry about COVID-19 illness were more likely to reduce direct social contact outside the household, particularly during the U.S.'s most deadly pandemic wave. Households of caregivers with …

Disclosing Disabilities: Barriers For Medical School Applicants, Sarah Leah Solomon, Aitan E. Magence, Harry Haran, Fern R. Juster, Kristina H. Petersen

2020-Current year OA Pubs

This study investigated the availability of accommodation request procedures for medical school admissions interviews and the accessibility of Technical Standards (TS) for candidates with disabilities (CWD) across Liaison Committee on Medical Education (LCME)-accredited institutions in the United States and Canada. Utilizing a cross-sectional study methodology, surveys were distributed to Deans of Admissions and Disabilities Resource Professionals (DRP) at all LCME-accredited US and Canadian MD programs. Surveys gathered data about interview formats, interview accommodation procedures, and TS accessibility during the 2018-2019 academic year. We received responses from 71 institutions (41.3%), with 56.3% survey completion rate (n = 40). Among respondents, interview …

Comparison And Clinical Applicability Analysis Of All-Posterior, Combined Anterior-Posterior, And Combined Lateral-Posterior Approaches In Adult Spinal Deformities: A Narrative Review, Garrison P. Bentz, Christopher Diaz, Nicholas A. Pollatta, Mark J. Lambrechts

2020-Current year OA Pubs

No abstract provided.

Efficacy And Safety Of Dostarlimab In Combination With Chemotherapy In Patients With Dmmr/Msi-H Primary Advanced Or Recurrent Endometrial Cancer In A Phase 3, Randomized, Placebo-Controlled Trial (Engot-En6-Nsgo/Gog-3031/Ruby), Matthew A Powell, Carolyn Mccourt, Et Al.

2020-Current year OA Pubs

OBJECTIVES: Part 1 of the RUBY trial (NCT03981796) demonstrated improved survival in patients with primary advanced or recurrent endometrial cancer (EC) treated with dostarlimab plus carboplatin-paclitaxel versus placebo plus carboplatin-paclitaxel. Here, we examine additional efficacy and safety data from patients with mismatch repair deficient/microsatellite instability-high (dMMR/MSI-H) EC in the RUBY trial.

METHODS: Patients were randomized 1:1 to dostarlimab 500 mg or placebo plus carboplatin-paclitaxel every 3 weeks for 6 cycles followed by dostarlimab or placebo every 6 weeks for up to 3 years. In the dMMR/MSI-H population of RUBY Part 1, analysis of progression-free survival by investigator assessment compared with …

Early Changes In Spatiotemporal Dynamics Of Remapped Circuits And Global Networks Predict Functional Recovery After Stroke In Mice, Ryan M Bowen, Jake Lee, Brendon Wang, Keith R Lohse, Hanyang Miao, Jonah A Padawer-Curry, Asher J Albertson, Eric C Landsness, Adam Q Bauer, Jin-Moo Lee

2020-Current year OA Pubs

SIGNIFICANCE: Stroke is the leading cause of chronic disability in the United States. How stroke size affects post-stroke repair and recovery is poorly understood.

AIM: We aim to investigate the effects of stroke size on early repair patterns and determine how early changes in neuronal circuits and networks predict functional outcomes after stroke.

APPROACH: We used wide-field optical imaging, photothrombosis, and the cylinder-rearing assay to examine changes in neuronal circuit and network activity in the context of functional recovery after stroke.

RESULTS: Larger strokes ablating

CONCLUSIONS: These results suggest that diffuse patterns of remapping, and desynchronization and hyperconnectivity of cortical …

Piezo1-Mediated Calcium Influx Transiently Alters Nuclear Mechanical Properties Via Actin Remodeling In Chondrocytes, Jaquelin M Garcia-Castorena, Rosa Riester, Miranda Gamino-Ornelas, Nikitha Ada, Farshid Guilak, Marina Danalache

2020-Current year OA Pubs

Mechanosensation allows cells to generate intracellular signals in response to mechanical cues from their environment. Previous research has demonstrated that mechanical stress can alter the mechanical properties of the nucleus, affecting gene transcription, chromatin methylation, and nuclear mechanoprotection during mechanical loading. PIEZO1, a mechanically gated Ca