Digital Commons Network^™

Employment Loss And Food Insecurity - Race And Sex Disparities In The Context Of Covid-19, Jacquelyn V Coats, Sarah Humble, Kimberly J Johnson, Havisha Pedamallu, Bettina F Drake, Elvin Geng, Charles W Goss, Kia L Davis

2020-Current year OA Pubs

INTRODUCTION: Applying an intersectional framework, we examined sex and racial inequality in COVID-19-related employment loss (ie, job furlough, layoff, and reduced pay) and food insecurity (ie, quality and quantity of food eaten, food worry, and receipt of free meals or groceries) among residents in Saint Louis County, Missouri.

METHODS: We used cross-sectional data from adults aged 18 or older (N = 2,146), surveyed by using landlines or cellular phones between August 12, 2020, and October 27, 2020. We calculated survey-weighted prevalence of employment loss and food insecurity for each group (Black female, Black male, White female, White male). Odds ratios …

Defining Hierarchical Protein Interaction Networks From Spectral Analysis Of Bacterial Proteomes, Mark A Zaydman, Alexander S Little, Fidel Haro, Valeryia Aksianiuk, William J Buchser, Aaron Diantonio, Jeffrey I Gordon, Jeffrey Milbrandt, Arjun S Raman

2020-Current year OA Pubs

Cellular behaviors emerge from layers of molecular interactions: proteins interact to form complexes, pathways, and phenotypes. We show that hierarchical networks of protein interactions can be defined from the statistical pattern of proteome variation measured across thousands of diverse bacteria and that these networks reflect the emergence of complex bacterial phenotypes. Our results are validated through gene-set enrichment analysis and comparison to existing experimentally derived databases. We demonstrate the biological utility of our approach by creating a model of motility in

Sars-Cov-2 Productively Infects Primary Human Immune System Cells In Vitro And In Covid-19 Patients, Marjorie C Pontelli, Sean P J Whelan, Et Al.

2020-Current year OA Pubs

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is associated with a hyperinflammatory state and lymphocytopenia, a hallmark that appears as both signature and prognosis of disease severity outcome. Although cytokine storm and a sustained inflammatory state are commonly associated with immune cell depletion, it is still unclear whether direct SARS-CoV-2 infection of immune cells could also play a role in this scenario by harboring viral replication. We found that monocytes, as well as both B and T lymphocytes, were susceptible to SARS-CoV-2 infection in vitro, accumulating double-stranded RNA consistent with viral RNA replication and ultimately leading to expressive …

A Central Alarm System That Gates Multi-Sensory Innate Threat Cues To The Amygdala, Sukjae J Kang, Shijia Liu, Mao Ye, Dong-Il Kim, Gerald M Pao, Bryan A Copits, Benjamin Z Roberts, Kuo-Fen Lee, Michael R Bruchas, Sung Han

2020-Current year OA Pubs

Perception of threats is essential for survival. Previous findings suggest that parallel pathways independently relay innate threat signals from different sensory modalities to multiple brain areas, such as the midbrain and hypothalamus, for immediate avoidance. Yet little is known about whether and how multi-sensory innate threat cues are integrated and conveyed from each sensory modality to the amygdala, a critical brain area for threat perception and learning. Here, we report that neurons expressing calcitonin gene-related peptide (CGRP) in the parvocellular subparafascicular nucleus in the thalamus and external lateral parabrachial nucleus in the brainstem respond to multi-sensory threat cues from various …

Oropouche Orthobunyavirus Infection Is Mediated By The Cellular Host Factor Lrp1, Madeline M Schwarz, David A Price, Safder S Ganaie, Annie Feng, Nawneet Mishra, Ryan M Hoehl, Farheen Fatma, Sarah H Stubbs, Sean P J Whelan, Xiaoxia Cui, Takeshi Egawa, Daisy W Leung, Gaya K Amarasinghe, Amy L Hartman

2020-Current year OA Pubs

Oropouche orthobunyavirus (OROV;

Visualizing Molecular Interactions That Determine Assembly Of A Bullet-Shaped Vesicular Stomatitis Virus Particle, Simon Jenni, Joshua A Horwitz, Louis-Marie Bloyet, Sean P J Whelan, Stephen C Harrison

2020-Current year OA Pubs

Vesicular stomatitis virus (VSV) is a negative-strand RNA virus with a non-segmented genome, closely related to rabies virus. Both have characteristic bullet-like shapes. We report the structure of intact, infectious VSV particles determined by cryogenic electron microscopy. By compensating for polymorphism among viral particles with computational classification, we obtained a reconstruction of the shaft ("trunk") at 3.5 Å resolution, with lower resolution for the rounded tip. The ribonucleoprotein (RNP), genomic RNA complexed with nucleoprotein (N), curls into a dome-like structure with about eight gradually expanding turns before transitioning into the regular helical trunk. Two layers of matrix (M) protein link …

Precision Dynamical Mapping Using Topological Data Analysis Reveals A Hub-Like Transition State At Rest, Manish Saggar, James M Shine, Raphaël Liégeois, Nico U F Dosenbach, Damien Fair

2020-Current year OA Pubs

In the absence of external stimuli, neural activity continuously evolves from one configuration to another. Whether these transitions or explorations follow some underlying arrangement or lack a predictable ordered plan remains to be determined. Here, using fMRI data from highly sampled individuals (~5 hours of resting-state data per individual), we aimed to reveal the rules that govern transitions in brain activity at rest. Our Topological Data Analysis based Mapper approach characterized a highly visited transition state of the brain that acts as a switch between different neural configurations to organize the spontaneous brain activity. Further, while the transition state was …

Malic Enzyme 1 Absence In Synovial Sarcoma Shifts Antioxidant System Dependence And Increases Sensitivity To Ferroptosis Induction With Acxt-3102, Caitlyn B Brashears, Bethany C Prudner, Richa Rathore, Katharine E Caldwell, Sara E S Lange, Jennifer K Sehn, Dirk Spitzer, Regis O'Keefe, Jason M Held, William Hawkins, Brian A Van Tine, Carina A. Dehner, Et Al

2020-Current year OA Pubs

PURPOSE: To investigate the metabolism of synovial sarcoma (SS) and elucidate the effect of malic enzyme 1 absence on SS redox homeostasis.

EXPERIMENTAL DESIGN: ME1 expression was measured in SS clinical samples, SS cell lines, and tumors from an SS mouse model. The effect of ME1 absence on glucose metabolism was evaluated utilizing Seahorse assays, metabolomics, and C13 tracings. The impact of ME1 absence on SS redox homeostasis was evaluated by metabolomics, cell death assays with inhibitors of antioxidant systems, and measurements of intracellular reactive oxygen species (ROS). The susceptibility of ME1-null SS to ferroptosis induction was interrogated in vitro …

Plasmonic Fluor-Enhanced Antigen Arrays For High-Throughput, Serological Studies Of Sars-Cov-2, Abraham J Qavi, Chao Wu, Matthew Lloyd, Mohammad Mahabub-Uz Zaman, Jingyi Luan, Claire Ballman, Daisy W Leung, Scott L Crick, Christopher W Farnsworth, Gaya K Amarasinghe

2020-Current year OA Pubs

Serological testing for acute infection or prior exposure is critical for patient management and coordination of public health decisions during outbreaks. Current methods have several limitations, including variable performance, relatively low analytical and clinical sensitivity, and poor detection due to antigenic drift. Serological methods for SARS-CoV-2 detection for the ongoing COVID-19 pandemic suffer from several of these limitations and serves as a reminder of the critical need for new technologies. Here, we describe the use of ultrabright fluorescent reagents, Plasmonic Fluors, coupled with antigen arrays that address a subset of these limitations. We demonstrate its application using patient samples in …

Making The Rounds: Exploring The Role Of Circulating Tumor Dna (Ctdna) In Non-Small Cell Lung Cancer, Misty Dawn Shields, Kevin Chen, Giselle Dutcher, Ishika Patel, Bruna Pellini

2020-Current year OA Pubs

Advancements in the clinical practice of non-small cell lung cancer (NSCLC) are shifting treatment paradigms towards increasingly personalized approaches. Liquid biopsies using various circulating analytes provide minimally invasive methods of sampling the molecular content within tumor cells. Plasma-derived circulating tumor DNA (ctDNA), the tumor-derived component of cell-free DNA (cfDNA), is the most extensively studied analyte and has a growing list of applications in the clinical management of NSCLC. As an alternative to tumor genotyping, the assessment of oncogenic driver alterations by ctDNA has become an accepted companion diagnostic via both single-gene polymerase chain reactions (PCR) and next-generation sequencing (NGS) for …

Gawmerge Expands Gwas Sample Size And Diversity By Combining Array-Based Genotyping And Whole-Genome Sequencing, Ravi Mathur, Fang Fang, Nathan Gaddis, Dana B Hancock, Michael H Cho, John E Hokanson, Laura J Bierut, Sharon M Lutz, Kendra Young, Albert V Smith, Nhlbi Trans-Omics For Precision Medicine (Topmed) Consortium, Edwin K Silverman, Grier P Page, Eric O Johnson

2020-Current year OA Pubs

Genome-wide association studies (GWAS) have made impactful discoveries for complex diseases, often by amassing very large sample sizes. Yet, GWAS of many diseases remain underpowered, especially for non-European ancestries. One cost-effective approach to increase sample size is to combine existing cohorts, which may have limited sample size or be case-only, with public controls, but this approach is limited by the need for a large overlap in variants across genotyping arrays and the scarcity of non-European controls. We developed and validated a protocol, Genotyping Array-WGS Merge (GAWMerge), for combining genotypes from arrays and whole-genome sequencing, ensuring complete variant overlap, and allowing …

Improving Our Understanding Of Driving Changes In Preclinical And Early Symptomatic Alzheimer's Disease: The Role Of Naturalistic Driving Studies, Catherine M Roe

2020-Current year OA Pubs

Research on how preclinical and early symptomatic Alzheimer's disease (AD) impacts driving behavior is in its infancy, with several important research areas yet to be explored. This paper identifies research gaps and suggests priorities for driving studies over the next few years among those at the earliest stages of AD. These priorities include how individual differences in demographic and biomarker measures of AD pathology, as well as differences in the in-vehicle and external driving environment, affect driving behavior. Understanding these differences is important to developing future interventions to increase driving safety among those at the earliest stages of AD.

Myc Sensitises Cells To Apoptosis By Driving Energetic Demand, Joy Edwards-Hicks, Kevin Cho, Gary J Patti, Et Al

2020-Current year OA Pubs

The MYC oncogene is a potent driver of growth and proliferation but also sensitises cells to apoptosis, which limits its oncogenic potential. MYC induces several biosynthetic programmes and primary cells overexpressing MYC are highly sensitive to glutamine withdrawal suggesting that MYC-induced sensitisation to apoptosis may be due to imbalance of metabolic/energetic supply and demand. Here we show that MYC elevates global transcription and translation, even in the absence of glutamine, revealing metabolic demand without corresponding supply. Glutamine withdrawal from MRC-5 fibroblasts depletes key tricarboxylic acid (TCA) cycle metabolites and, in combination with MYC activation, leads to AMP accumulation and nucleotide …

Cross-Linked Chitosan/Gelatin Beads Loaded With Chlorella Vulgaris Microalgae/Zinc Oxide Nanoparticles For Absorbing Carcinogenic Bisphenol-A Pollutant From Water, Hazim M Ali, Omar M Ibrahim, Ahmed S M Ali, Mahmoud A Mohamed, Rehab Y Ghareeb, Elsayed E Hafez, Mohamed R El-Aassar

2020-Current year OA Pubs

Water polluted by phenolic compounds is a global threat to health and the environment; accordingly, we prepared a green novel sorbent biological system from a chitosan (CS), gelatin (GT), and

Identification Of Activity-Induced Egr3-Dependent Genes Reveals Genes Associated With Dna Damage Response And Schizophrenia, Ketan K Marballi, Khaled Alganem, Samuel J Brunwasser, Arhem Barkatullah, Kimberly T Meyers, Janet M Campbell, Annika B Ozols, Robert E Mccullumsmith, Amelia L Gallitano

2020-Current year OA Pubs

Bioinformatics and network studies have identified the immediate early gene transcription factor early growth response 3 (EGR3) as a master regulator of genes differentially expressed in the brains of patients with neuropsychiatric illnesses ranging from schizophrenia and bipolar disorder to Alzheimer's disease. However, few studies have identified and validated Egr3-dependent genes in the mammalian brain. We have previously shown that Egr3 is required for stress-responsive behavior, memory, and hippocampal long-term depression in mice. To identify Egr3-dependent genes that may regulate these processes, we conducted an expression microarray on hippocampi from wildtype (WT) and Egr3-/- mice following electroconvulsive seizure (ECS), a …

Disease-Associated Mutations Within The Yeast Dnajb6 Homolog Sis1 Slow Conformer-Specific Substrate Processing And Can Be Corrected By The Modulation Of Nucleotide Exchange Factors, Ankan K Bhadra, Michael J Rau, Jil A Daw, James A J Fitzpatrick, Conrad C Weihl, Heather L True

2020-Current year OA Pubs

Molecular chaperones, or heat shock proteins (HSPs), protect against the toxic misfolding and aggregation of proteins. As such, mutations or deficiencies within the chaperone network can lead to disease. Dominant mutations within DNAJB6 (Hsp40)-an Hsp70 co-chaperone-lead to a protein aggregation-linked myopathy termed Limb-Girdle Muscular Dystrophy Type D1 (LGMDD1). Here, we used the yeast prion model client in conjunction with in vitro chaperone activity assays to gain mechanistic insights into the molecular basis of LGMDD1. Here, we show how mutations analogous to those found in LGMDD1 affect Sis1 (a functional homolog of human DNAJB6) function by altering the structure of client …

Developmental Trajectories Of Cortical Thickness By Functional Brain Network: The Roles Of Pubertal Timing And Socioeconomic Status, Ashley F. P. Sanders, Graham L. Baum, Michael P. Harms, Sridhar Kandala, Susan Y. Bookheimer, Mirella Dapretto, Leah H. Somerville, Kathleen M. Thomas, David C. Van Essen, Essa Yacoub, Deanna M Barch

2020-Current year OA Pubs

The human cerebral cortex undergoes considerable changes during development, with cortical maturation patterns reflecting regional heterogeneity that generally progresses in a posterior-to-anterior fashion. However, the organizing principles that govern cortical development remain unclear. In the current study, we characterized age-related differences in cortical thickness (CT) as a function of sex, pubertal timing, and two dissociable indices of socioeconomic status (i.e., income-to-needs and maternal education) in the context of functional brain network organization, using a cross-sectional sample (n = 789) diverse in race, ethnicity, and socioeconomic status from the Lifespan Human Connectome Project in Development (HCP-D). We found that CT generally …

Maturation And Substrate Processing Topography Of The Plasmodium Falciparum Invasion/Egress Protease Plasmepsin X, Sumit Mukherjee, Suong Nguyen, Eashan Sharma, Daniel E Goldberg

2020-Current year OA Pubs

The malaria parasite Plasmodium invades a host erythrocyte, multiplies within a parasitophorous vacuole (PV) and then ruptures the PV and erythrocyte membranes in a process known as egress. Both egress and invasion are controlled by effector proteins discharged from specialized secretory organelles. The aspartic protease plasmepsin X (PM X) regulates activity for many of these effectors, but it is unclear how PM X accesses its diverse substrates that reside in different organelles. PM X also autoprocesses to generate different isoforms. The function of this processing is not understood. We have mapped the self-cleavage sites and have constructed parasites with cleavage …

Glycan Shield Of The Ebolavirus Envelope Glycoprotein Gp, Weiwei Peng, Vamseedhar Rayaprolu, Amar D Parvate, Matti F Pronker, Sean Hui, Diptiben Parekh, Kelly Shaffer, Xiaoying Yu, Erica O Saphire, Joost Snijder

2020-Current year OA Pubs

The envelope glycoprotein GP of the ebolaviruses is essential for host cell entry and the primary target of the host antibody response. GP is heavily glycosylated with up to 17 N-linked sites, numerous O-linked glycans in its disordered mucin-like domain (MLD), and three predicted C-linked mannosylation sites. Glycosylation is important for host cell attachment, GP stability and fusion activity, and shielding from neutralization by serum antibodies. Here, we use glycoproteomics to profile the site-specific glycosylation patterns of ebolavirus GP. We detect up to 16 unique O-linked glycosylation sites in the MLD, and two O-linked sites in the receptor-binding GP1 subunit. …

Engineering Hyaluronic Acid For The Development Of New Treatment Strategies For Osteoarthritis, Yu Seon Kim, Farshid Guilak

2020-Current year OA Pubs

Osteoarthritis (OA) is a degenerative joint disease that is characterized by inflammation of the joints, degradation of cartilage, and the remodeling of other joint tissues. Due to the absence of disease-modifying drugs for OA, current clinical treatment options are often only effective at slowing down disease progression and focus mainly on pain management. The field of tissue engineering has therefore been focusing on developing strategies that could be used not only to alleviate symptoms of OA but also to regenerate the damaged tissue. Hyaluronic acid (HA), an integral component of both the synovial fluid and articular cartilage, has gained widespread …

Left Sided Breast Cancer Is Associated With Aggressive Biology And Worse Outcomes Than Right Sided Breast Cancer, Yara Abdou, Medhavi Gupta, Mariko Asaoka, Kristopher Attwood, Opyrchal Mateusz, Shipra Gandhi, Kazuaki Takabe

2020-Current year OA Pubs

Breast cancer is more common on the left side than the right side. We aim to evaluate differences in clinicopathological and genomic characteristics based on laterality. We analyzed survival outcomes and clinical characteristics of 881,320 patients recorded by the Surveillance, Epidemiology, and End Results (SEER) program. The Cancer Genome Atlas (TCGA) was used to explore genomic and clinical features from 1,062 patients. Gene expression data was used to quantitate cytolytic activity and hallmark gene-sets were used for gene set enrichment analysis. An institutional retrospective review was conducted on 155 patients treated with neoadjuvant chemotherapy (NACT). Patient characteristics were summarized by …

Enhancing Interprofessional Collaboration And Interprofessional Education In Women's Health, Laura Baecher-Lind, Angela C Fleming, Rashmi Bhargava, Susan M Cox, Elise N Everett, David A Forstein, Shireen Madani Sims, Helen K Morgan, Christopher M Morosky, Celeste S Royce, Tammy S Sonn, Jill M Sutton, Scott C Graziano

2020-Current year OA Pubs

This article is from the 'To The Point' series from the Association of Professors of Gynecology and Obstetrics Undergraduate Medical Education Committee. The purpose of this review is to provide an understanding of the differing yet complementary nature of interprofessional collaboration and interprofessional education as well as their importance to the specialty of Obstetrics and Gynecology. We provide a historical perspective of how interprofessional collaboration and interprofessional education have become key aspects of clinical and educational programs, enhancing both patient care and learner development. Opportunities to incorporate interprofessional education within women's health educational programs across organizations are suggested. This is …

The Use Of Objective Assessments In The Evaluation Of Technical Skills In Cardiothoracic Surgery: A Systematic Review, Nabil Hussein, Jef Van Den Eynde, Connor Callahan, Alvise Guariento, Can Gollmann-Tepeköylü, Malak Elbatarny, Mahmoud Loubani

2020-Current year OA Pubs

OBJECTIVES: With reductions in training time and intraoperative exposure, there is a need for objective assessments to measure trainee progression. This systematic review focuses on the evaluation of trainee technical skill performance using objective assessments in cardiothoracic surgery and its incorporation into training curricula.

METHODS: Databases (EBSCOHOST, Scopus and Web of Science) and reference lists of relevant articles for studies that incorporated objective assessment of technical skills of trainees/residents in cardiothoracic surgery were included. Data extraction included task performed; assessment setting and tool used; number/level of assessors; study outcome and whether the assessments were incorporated into training curricula. The methodological …

Gonadal Sex Patterns P21-Induced Cellular Senescence In Mouse And Human Glioblastoma, Lauren Broestl, Nicole M Warrington, Lucia Grandison, Tamara Abou-Antoun, Olivia Tung, Saraswati Shenoy, Miranda M Tallman, Gina Rhee, Wei Yang, Jasmin Sponagel, Lihua Yang, Najla Kfoury-Beaumont, Cameron M Hill, Sulaiman A Qanni, Diane D Mao, Albert H Kim, Sheila A Stewart, Monica Venere, Jingqin Luo, Joshua B Rubin

2020-Current year OA Pubs

Males exhibit higher incidence and worse prognosis for the majority of cancers, including glioblastoma (GBM). Disparate survival may be related to sex-biased responses to treatment, including radiation. Using a mouse model of GBM, we show that female cells are more sensitive to radiation, and that senescence represents a major component of the radiation therapeutic response in both sexes. Correlation analyses revealed that the CDK inhibitor p21 and irradiation induced senescence were differentially regulated between male and female cells. Indeed, female cellular senescence was more sensitive to changes in p21 levels, a finding that was observed in wildtype and transformed murine …

Glutamine Metabolism Modulates Chondrocyte Inflammatory Response, Manoj Arra, Gaurav Swarnkar, Naga Suresh Adapala, Syeda Kanwal Naqvi, Lei Cai, Muhammad Farooq Rai, Srikanth Singamaneni, Gabriel Mbalaviele, Robert Brophy, Yousef Abu-Amer

2020-Current year OA Pubs

Osteoarthritis is the most common joint disease in the world with significant societal consequences but lacks effective disease-modifying interventions. The pathophysiology consists of a prominent inflammatory component that can be targeted to prevent cartilage degradation and structural defects. Intracellular metabolism has emerged as a culprit of the inflammatory response in chondrocytes, with both processes co-regulating each other. The role of glutamine metabolism in chondrocytes, especially in the context of inflammation, lacks a thorough understanding and is the focus of this work. We display that mouse chondrocytes utilize glutamine for energy production and anabolic processes. Furthermore, we show that glutamine deprivation …

Context-Dependent Pro- And Anti-Resection Roles Of Zkscan3 In The Regulation Of Fork Processing During Replication Stress, Zheng Yang, Delphine Sangotokun Lemacon, Shan Li, Abigael Cheruiyot, Lingzhen Kong, Ke Tan, Chen Cheng, Ecenur Turkay, Dalin He, Zhongsheng You

2020-Current year OA Pubs

Uncontrolled resection of replication forks under stress can cause genomic instability and influence cancer formation. Extensive fork resection has also been implicated in the chemosensitivity of "BReast CAncer gene" BRCA-deficient cancers. However, how fork resection is controlled in different genetic contexts and how it affects chromosomal stability and cell survival remains incompletely understood. Here, we report a novel function of the transcription repressor ZKSCAN3 in fork protection and chromosomal stability maintenance under replication stress. We show disruption of ZKSCAN3 function causes excessive resection of replication forks by the exonuclease Exo1 and homologous DNA recombination/repair protein Mre11 following fork reversal. Interestingly, …

Phase I Trial Of The Dll3/Cd3 Bispecific T-Cell Engager Bi 764532 In Dll3-Positive Small-Cell Lung Cancer And Neuroendocrine Carcinomas, Martin Wermke, Enriqueta Felip, Valentina Gambardella, Yasutoshi Kuboki, Daniel Morgensztern, Zohra Oum' Hamed, Meiruo Liu, Matus Studeny, Taofeek K Owonikoko

2020-Current year OA Pubs

Poorly differentiated neuroendocrine carcinomas such as small-cell lung cancer (SCLC) have poor survival and high relapse rates. DLL3 is found on these carcinomas and has become a target of increasing interest in recent years. The bispecific DLL3/CD3 T-cell engager BI 764532 has been shown to induce complete tumor regression in a human T cell-engrafted mouse model. Here, we describe the study design of a first-in-human, phase I, multicenter, open-label, non-randomized, dose-escalation study in patients with SCLC or other DLL3-positive neuroendocrine carcinomas. The study will determine the maximum tolerated dose and evaluate safety, tolerability, pharmacokinetics and preliminary efficacy of BI 764532 …

Snmmi/Acr/Asnc/Scmr Joint Credentialing Statement For Cardiac Pet/Mri: Endorsed By The American Heart Association, Terrence D Ruddy, Mouaz Al-Mallah, James A Arrighi, John P Bois, David A Bluemke, Marcelo F Di Carli, Vasken Dilsizian, Robert J Gropler, Hossein Jadvar, Saurabh Malhotra, Matthier Pelletier-Galarneau, Thomas H Schindler, Pamela K Woodard, Panithaya Chareonthaitawee

2020-Current year OA Pubs

No abstract provided.

Selinexor In Advanced, Metastatic Dedifferentiated Liposarcoma: A Multinational, Randomized, Double-Blind, Placebo-Controlled Trial, Mrinal M Gounder, Brian A Van Tine, Et Al

2020-Current year OA Pubs

PURPOSE: Antitumor activity in preclinical models and a phase I study of patients with dedifferentiated liposarcoma (DD-LPS) was observed with selinexor. We evaluated the clinical benefit of selinexor in patients with previously treated DD-LPS whose sarcoma progressed on approved agents.

METHODS: SEAL was a phase II-III, multicenter, randomized, double-blind, placebo-controlled study. Patients age 12 years or older with advanced DD-LPS who had received two-five lines of therapy were randomly assigned (2:1) to selinexor (60 mg) or placebo twice weekly in 6-week cycles (crossover permitted). The primary end point was progression-free survival (PFS). Patients who received at least one dose of …

Impaired Mitophagy In Sanfilippo A Mice Causes Hypertriglyceridemia And Brown Adipose Tissue Activation, Miguel Tillo, Patricia I Dickson, Et Al.

2020-Current year OA Pubs

Lysosomal storage diseases result in various developmental and physiological complications, including cachexia. To study the causes for the negative energy balance associated with cachexia, we assessed the impact of sulfamidase deficiency and heparan sulfate storage on energy homeostasis and metabolism in a mouse model of type IIIa mucopolysaccharidosis (MPS IIIa, Sanfilippo A syndrome). At 12-weeks of age, MPS IIIa mice exhibited fasting and postprandial hypertriglyceridemia compared with wildtype mice, with a reduction of white and brown adipose tissues. Partitioning of dietary [