Digital Commons Network^™

Standardized Radiomics Analysis Of Clinical Myocardial Perfusion Stress Spect Images To Identify Coronary Artery Calcification, Saeed Ashrafinia, Pejman Dalaie, Thomas H. Schindler, Martin G. Pomper, Arman Rahmim

2020-Current year OA Pubs

PURPOSE: Myocardial perfusion (MP) stress single-photon emission computed tomography (SPECT) is an established diagnostic test for patients suspected of coronary artery disease (CAD). Meanwhile, coronary artery calcification (CAC) scoring obtained from diagnostic CT is a highly sensitive test, offering incremental diagnostic information in identifying patients with significant CAD yet normal MP stress SPECT (MPSS) scans. However, after decades of wide utilization of MPSS, CAC is not commonly reimbursed (e.g. by the CMS), nor widely deployed in community settings. We studied the potential of complementary information deduced from the radiomics analysis of normal MPSS scans in predicting the CAC score.

METHODS: …

Alcohol Consumption Among Adults With A Cancer Diagnosis In The All Of Us Research Program, Mengyao Shi, Chongliang Luo, Oluseye K Oduyale, Xiaoyu Zong, Noelle K Loconte, Yin Cao

2020-Current year OA Pubs

IMPORTANCE: Alcohol consumption is associated with adverse oncologic and treatment outcomes among individuals with a diagnosis of cancer. As a key modifiable behavioral factor, alcohol consumption patterns among cancer survivors, especially during treatment, remain underexplored in the United States.

OBJECTIVE: To comprehensively characterize alcohol consumption patterns among US cancer survivors.

DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study used data from May 6, 2018, to January 1, 2022, from the National Institutes of Health All of Us Research Program, a diverse US cohort with electronic health record (EHR) linkage, and included 15 199 participants who reported a cancer diagnosis and 1839 …

Changing Faces: Factors Associated With The Intention To Pursue Plastic Surgery And Practice In Underserved Areas, Mytien Nguyen, Annette Kaminaka, Nicholas N. Brutus, Luis A. Gonzalez, Amit Ratanpal, Michael Alperovich, Donna B. Jeffe, Ashar Ata, Hyacinth R. C. Mason, Paris D. Butler

2020-Current year OA Pubs

UNLABELLED: Improving the number of plastic and reconstructive surgeons who provide care to patients in underserved communities is critical to achieving health equity. We aimed to identify factors associated with graduating medical students' intentions to pursue plastic surgery and practice in underserved areas.

METHODS: De-identified data for US medical school graduates were obtained from the Association of American Medical Colleges for students who matriculated in academic years 2007-2008 and 2011-2012. Data collected included self-reported demographic and future practice intentions. Multivariate analysis was conducted to determine indicators of students' interest in plastic surgery, and their intention to practice in underserved areas. …

Framework For Quality Assurance Of Ultrahigh Dose Rate Clinical Trials Investigating Flash Effects And Current Technology Gaps, Wei Zou, Tianyu Zhao, Walter R Bosch, Et Al.

2020-Current year OA Pubs

FLASH radiation therapy (FLASH-RT), delivered with ultrahigh dose rate (UHDR), may allow patients to be treated with less normal tissue toxicity for a given tumor dose compared with currently used conventional dose rate. Clinical trials are being carried out and are needed to test whether this improved therapeutic ratio can be achieved clinically. During the clinical trials, quality assurance and credentialing of equipment and participating sites, particularly pertaining to UHDR-specific aspects, will be crucial for the validity of the outcomes of such trials. This report represents an initial framework proposed by the NRG Oncology Center for Innovation in Radiation Oncology …

Striatal Mglu5-Mediated Synaptic Plasticity Is Independently Regulated By Location-Specific Receptor Pools And Divergent Signaling Pathways, Yuh-Jiin I Jong, Yukitoshi Izumi, Steven K Harmon, Charles F Zorumski, Karen L Ómalley

2020-Current year OA Pubs

Metabotropic glutamate receptor 5 (mGlu

Location Of Pathogenic Variants In Psen1 Impacts Progression Of Cognitive, Clinical, And Neurodegenerative Measures In Autosomal-Dominant Alzheimer's Disease, Stephanie A Schultz, Eric Mcdade, Nicolas R Barthelemy, Nelly Joseph-Mathurin, Carlos Cruchaga, Charles D Chen, Tammie L S Benzinger, Anne M Fagan, Brian A Gordon, Jason J Hassenstab, Celeste M Karch, John C Morris, Richard J Perrin, Chengjie Xiong, Randall J Bateman, Et Al.

2020-Current year OA Pubs

Although pathogenic variants in PSEN1 leading to autosomal-dominant Alzheimer disease (ADAD) are highly penetrant, substantial interindividual variability in the rates of cognitive decline and biomarker change are observed in ADAD. We hypothesized that this interindividual variability may be associated with the location of the pathogenic variant within PSEN1. PSEN1 pathogenic variant carriers participating in the Dominantly Inherited Alzheimer Network (DIAN) observational study were grouped based on whether the underlying variant affects a transmembrane (TM) or cytoplasmic (CY) protein domain within PSEN1. CY and TM carriers and variant non-carriers (NC) who completed clinical evaluation, multimodal neuroimaging, and lumbar puncture for collection …

Sars-Cov-2 Uses Cd4 To Infect T Helper Lymphocytes, Natalia S Brunetti, Louis-Marie Bloyet, Spencer Stumpf, Marjorie C Pontelli, Sean Whelan, Alessandro S Farias, Et Al.

2020-Current year OA Pubs

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the agent of a major global outbreak of respiratory tract disease known as Coronavirus Disease 2019 (COVID-19). SARS-CoV-2 infects mainly lungs and may cause several immune-related complications, such as lymphocytopenia and cytokine storm, which are associated with the severity of the disease and predict mortality. The mechanism by which SARS-CoV-2 infection may result in immune system dysfunction is still not fully understood. Here, we show that SARS-CoV-2 infects human CD4

Subunit Gating Resulting From Individual Protonation Events In Kir2 Channels, Grigory Maksaev, Michael Bründl-Jirout, Anna Stary-Weinzinger, Eva-Maria Zangerl-Plessl, Sun-Joo Lee, Colin G Nichols

2020-Current year OA Pubs

Inwardly rectifying potassium (Kir) channels open at the 'helix bundle crossing' (HBC), formed by the M2 helices at the cytoplasmic end of the transmembrane pore. Introduced negative charges at the HBC (G178D) in Kir2.2 channels forces opening, allowing pore wetting and free movement of permeant ions between the cytoplasm and the inner cavity. Single-channel recordings reveal striking, pH-dependent, subconductance behaviors in G178D (or G178E and equivalent Kir2.1[G177E]) mutant channels, with well-resolved non-cooperative subconductance levels. Decreasing cytoplasmic pH shifts the probability towards lower conductance levels. Molecular dynamics simulations show how protonation of Kir2.2[G178D], or the D173 pore-lining residues, changes solvation, K

Emerging Therapies For Antibody-Mediated Rejection In Kidney Transplantation, Farah Abuazzam, Casey Dubrawka, Tarek Abdulhadi, Gwendolyn Amurao, Louai Alrata, Dema Yaseen Alsabbagh, Omar Alomar, Tarek Alhamad

2020-Current year OA Pubs

Despite the advances in immunosuppressive medications, antibody-mediated rejection (AMR) continues to be a major cause of kidney allograft failure and remains a barrier to improving long-term allograft survival. Recently, there have been significant advances in the understanding of the pathophysiological process of AMR, along with the development of new therapeutic options. Additionally, surveillance protocols with donor-derived cell-free DNA and gene profile testing have been established, leading to the early detection of AMR. A multitude of clinical trials are ongoing, opening numerous opportunities for improving outcome in kidney transplant recipients. In this brief review, we discuss the emerging therapies for managing …

Membrane Stretch As The Mechanism Of Activation Of Piezo1 Ion Channels In Chondrocytes, Alireza Savadipour, Robert J Nims, Neda Rashidi, Jaquelin M Garcia-Castorena, Ruhang Tang, Gabrielle K Marushack, Sara J Oswald, Wolfgang B Liedtke, Farshid Guilak

2020-Current year OA Pubs

Osteoarthritis is a chronic disease that can be initiated by altered joint loading or injury of the cartilage. The mechanically sensitive PIEZO ion channels have been shown to transduce injurious levels of biomechanical strain in articular chondrocytes and mediate cell death. However, the mechanisms of channel gating in response to high cellular deformation and the strain thresholds for activating PIEZO channels remain unclear. We coupled studies of single-cell compression using atomic force microscopy (AFM) with finite element modeling (FEM) to identify the biophysical mechanisms of PIEZO-mediated calcium (Ca

Phase Ii, Open-Label Study Of Encorafenib Plus Binimetinib In Patients With Brafv600-Mutant Metastatic Non-Small-Cell Lung Cancer, Gregory J Riely, Daniel Morgensztern, Et Al.

2020-Current year OA Pubs

PURPOSE: The combination of encorafenib (BRAF inhibitor) plus binimetinib (MEK inhibitor) has demonstrated clinical efficacy with an acceptable safety profile in patients with

METHODS: In this ongoing, open-label, single-arm, phase II study, patients with

RESULTS: At data cutoff, 98 patients (59 treatment-naïve and 39 previously treated) with

CONCLUSION: For patients with treatment-naïve and previously treated

Engineered Reporter Phages For Detection Of Escherichia Coli, Enterococcus, And Klebsiella In Urine, Susanne Meile, Jonas Marschall, Et Al.

2020-Current year OA Pubs

The rapid detection and species-level differentiation of bacterial pathogens facilitates antibiotic stewardship and improves disease management. Here, we develop a rapid bacteriophage-based diagnostic assay to detect the most prevalent pathogens causing urinary tract infections: Escherichia coli, Enterococcus spp., and Klebsiella spp. For each uropathogen, two virulent phages were genetically engineered to express a nanoluciferase reporter gene upon host infection. Using 206 patient urine samples, reporter phage-induced bioluminescence was quantified to identify bacteriuria and the assay was benchmarked against conventional urinalysis. Overall, E. coli, Enterococcus spp., and Klebsiella spp. were each detected with high sensitivity (68%, 78%, 87%), specificity (99%, 99%, …

Loss Of Function Mutation In Ank Causes Aberrant Mineralization And Acquisition Of Osteoblast-Like-Phenotype By The Cells Of The Intervertebral Disc, Takashi Ohnishi, Victoria Tran, Kimheak Sao, Pranay Ramteke, William Querido, Ruteja A Barve, Koen Van De Wetering, Makarand V Risbud

2020-Current year OA Pubs

Pathological mineralization of intervertebral disc is debilitating and painful and linked to disc degeneration in a subset of human patients. An adenosine triphosphate efflux transporter, progressive ankylosis (ANK) is a regulator of extracellular inorganic pyrophosphate levels and plays an important role in tissue mineralization. However, the function of ANK in intervertebral disc has not been fully explored. Herein we analyzed the spinal phenotype of Ank mutant mice (ank/ank) with attenuated ANK function. Micro-computed tomography and histological analysis showed that loss of ANK function results in the aberrant annulus fibrosus mineralization and peripheral disc fusions with cranial to caudal progression in …

Segmentation Of Human Functional Tissue Units In Support Of A Human Reference Atlas, Yashvardhan Jain, Leah L Godwin, Yingnan Ju, Naveksha Sood, Ellen M Quardokus, Andreas Bueckle, Teri Longacre, Aaron Horning, Yiing Lin, Edward D Esplin, John W Hickey, Michael P Snyder, Nathan Heath Patterson, Jeffrey M Spraggins, Katy Börner

2020-Current year OA Pubs

The Human BioMolecular Atlas Program (HuBMAP) aims to compile a Human Reference Atlas (HRA) for the healthy adult body at the cellular level. Functional tissue units (FTUs), relevant for HRA construction, are of pathobiological significance. Manual segmentation of FTUs does not scale; highly accurate and performant, open-source machine-learning algorithms are needed. We designed and hosted a Kaggle competition that focused on development of such algorithms and 1200 teams from 60 countries participated. We present the competition outcomes and an expanded analysis of the winning algorithms on additional kidney and colon tissue data, and conduct a pilot study to understand spatial …

A Spatially Anchored Transcriptomic Atlas Of The Human Kidney Papilla Identifies Significant Immune Injury In Patients With Stone Disease, Victor Hugo Canela, Joseph P Gaut, Sanjay Jain, Et Al.

2020-Current year OA Pubs

Kidney stone disease causes significant morbidity and increases health care utilization. In this work, we decipher the cellular and molecular niche of the human renal papilla in patients with calcium oxalate (CaOx) stone disease and healthy subjects. In addition to identifying cell types important in papillary physiology, we characterize collecting duct cell subtypes and an undifferentiated epithelial cell type that was more prevalent in stone patients. Despite the focal nature of mineral deposition in nephrolithiasis, we uncover a global injury signature characterized by immune activation, oxidative stress and extracellular matrix remodeling. We also identify the association of MMP7 and MMP9 …

Isoflurane Conditioning-Induced Delayed Cerebral Ischemia Protection In Subarachnoid Hemorrhage-Role Of Inducible Nitric Oxide Synthase, Meizi Liu, Keshav Jayaraman, Aaron J Norris, Ahmed Hussein, James W Nelson, Jogender Mehla, Deepti Diwan, Ananth Vellimana, Yousef Abu-Amer, Gregory J Zipfel, Umeshkumar Athiraman

2020-Current year OA Pubs

Background Recent evidence implicates inflammation as a key driver in delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage (SAH). Inducible nitric oxide synthase (iNOS) is one of the known major mediators of inflammation. We previously showed that an inhalational anesthetic, isoflurane, provides strong protection against delayed cerebral ischemia after SAH. Our current study aims to define the role of iNOS in isoflurane conditioning-induced protection against delayed cerebral ischemia in a mouse model of SAH. Methods and Results The experiments used 10- to 14-week-old male wild-type (C57BL/6) and iNOS global knockout mice. Anesthetic conditioning was initiated 1 hour after SAH with isoflurane …

Apoe-Ε4 Synergizes With Sleep Disruption To Accelerate Aβ Deposition And Aβ-Associated Tau Seeding And Spreading, Chanung Wang, Aishwarya Nambiar, Michael R. Strickland, Choonghee Lee, Samira Parhizkar, Alec C. Moore, Erik S. Musiek, Jason D. Ulrich, David M. Holtzman

2020-Current year OA Pubs

Alzheimer's disease (AD) is the most common cause of dementia. The APOE-ε4 allele of the apolipoprotein E (APOE) gene is the strongest genetic risk factor for late-onset AD. The APOE genotype modulates the effect of sleep disruption on AD risk, suggesting a possible link between apoE and sleep in AD pathogenesis, which is relatively unexplored. We hypothesized that apoE modifies Aβ deposition and Aβ plaque-associated tau seeding and spreading in the form of neuritic plaque-tau (NP-tau) pathology in response to chronic sleep deprivation (SD) in an apoE isoform-dependent fashion. To test this hypothesis, we used APPPS1 mice expressing human APOE-ε3 …

Deletion Of Taf1 And Taf5 In Zebrafish Capitulate Cardiac And Craniofacial Abnormalities Associated With Tafopathies Through Perturbations In Metabolism, Jamison Leid, Ryan Gray, Peter Rakita, Andrew L Koenig, Rohan Tripathy, James A J Fitzpatrick, Charles Kaufman, Lilianna Solnica-Krezel, Kory J Lavine

2020-Current year OA Pubs

Intellectual disability is a neurodevelopmental disorder that affects 2-3% of the general population. Syndromic forms of intellectual disability frequently have a genetic basis and are often accompanied by additional developmental anomalies. Pathogenic variants in components of TATA-binding protein associated factors (TAFs) have recently been identified in a subset of patients with intellectual disability, craniofacial hypoplasia, and congenital heart disease. This syndrome has been termed as a TAFopathy and includes mutations in TATA binding protein (TBP), TAF1, TAF2, and TAF6. The underlying mechanism by which TAFopathies give rise to neurodevelopmental, craniofacial, and cardiac abnormalities remains to be defined. Through a forward …

Lrp1 Is Essential For Lethal Rift Valley Fever Hepatic Disease In Mice, Madeline M Schwarz, Safder S Ganaie, Annie Feng, Griffin Brown, Tenzin Yangdon, J Michael White, Ryan M Hoehl, Cynthia M Mcmillen, Rachael E Rush, Kaleigh A Connors, Xiaoxia Cui, Daisy W Leung, Takeshi Egawa, Gaya K Amarasinghe, Amy L Hartman

2020-Current year OA Pubs

Rift Valley fever virus (RVFV) is an emerging arbovirus found in Africa. While RVFV is pantropic and infects many cells and tissues, viral replication and necrosis within the liver play a critical role in mediating severe disease. The low-density lipoprotein receptor-related protein 1 (Lrp1) is a recently identified host factor for cellular entry and infection by RVFV. The biological significance of Lrp1, including its role in hepatic disease in vivo, however, remains to be determined. Because Lrp1 has a high expression level in hepatocytes, we developed a mouse model in which Lrp1 is specifically deleted in hepatocytes to test how …

Survival With Axicabtagene Ciloleucel In Large B-Cell Lymphoma, Jason R Westin, Armin Ghobadi, Et Al.

2020-Current year OA Pubs

BACKGROUND: In an analysis of the primary outcome of this phase 3 trial, patients with early relapsed or refractory large B-cell lymphoma who received axicabtagene ciloleucel (axi-cel), an autologous anti-CD19 chimeric antigen receptor T-cell therapy, as second-line treatment had significantly longer event-free survival than those who received standard care. Data were needed on longer-term outcomes.

METHODS: In this trial, we randomly assigned patients with early relapsed or refractory large B-cell lymphoma in a 1:1 ratio to receive either axi-cel or standard care (two to three cycles of chemoimmunotherapy followed by high-dose chemotherapy with autologous stem-cell transplantation in patients who had …

Effects Of Nalcn-Encoded Na+ Leak Currents On The Repetitive Firing Properties Of Scn Neurons Depend On K+-Driven Rhythmic Changes In Input Resistance, Nien-Du Yang, Rebecca L Mellor, Tracey O Hermanstyne, Jeanne M Nerbonne

2020-Current year OA Pubs

Neurons in the suprachiasmatic nucleus (SCN) generate circadian changes in the rates of spontaneous action potential firing that regulate and synchronize daily rhythms in physiology and behavior. Considerable evidence suggests that daily rhythms in the repetitive firing rates (higher during the day than at night) of SCN neurons are mediated by changes in subthreshold potassium (K

Real-Time Environmental Surveillance Of Sars-Cov-2 Aerosols, Joseph V Puthussery, Kevin R Mcbrearty, Brookelyn M Doherty, Woodrow D Gardiner, Jordan P Magrecki, Traci L Bricker, Adrianus C M Boon, Carla M Yuede, John R Cirrito, Et Al.

2020-Current year OA Pubs

Real-time surveillance of airborne SARS-CoV-2 virus is a technological gap that has eluded the scientific community since the beginning of the COVID-19 pandemic. Offline air sampling techniques for SARS-CoV-2 detection suffer from longer turnaround times and require skilled labor. Here, we present a proof-of-concept pathogen Air Quality (pAQ) monitor for real-time (5 min time resolution) direct detection of SARS-CoV-2 aerosols. The system synergistically integrates a high flow (~1000 lpm) wet cyclone air sampler and a nanobody-based ultrasensitive micro-immunoelectrode biosensor. The wet cyclone showed comparable or better virus sampling performance than commercially available samplers. Laboratory experiments demonstrate a device sensitivity of …

Thermosensitive And Antioxidant Wound Dressings Capable Of Adaptively Regulating Tgfβ Pathways Promote Diabetic Wound Healing, Hong Niu, Ya Guan, Ting Zhong, Liang Ma, Mohamed Zayed, Jianjun Guan

2020-Current year OA Pubs

Various therapies have been utilized for treating diabetic wounds, yet current regiments do not simultaneously address the key intrinsic causes of slow wound healing, i.e., abnormal skin cell functions (particularly migration), delayed angiogenesis, and chronic inflammation. To address this clinical gap, we develop a wound dressing that contains a peptide-based TGFβ receptor II inhibitor (PTβR2I), and a thermosensitive and reactive oxygen species (ROS)-scavenging hydrogel. The wound dressing can quickly solidify on the diabetic wounds following administration. The released PTβR2I inhibits the TGFβ1/p38 pathway, leading to improved cell migration and angiogenesis, and decreased inflammation. Meanwhile, the PTβR2I does not interfere with …

Proteome Wide Association Studies Of Lrrk2 Variants Identify Novel Causal And Druggable Proteins For Parkinson's Disease, Bridget Phillips, Daniel Western, Lihua Wang, Jigyasha Timsina, Yichen Sun, Priyanka Gorijala, Chengran Yang, Anh Do, Niko-Petteri Nykänen, John C Morris, Suzanne E Schindler, Anne M Fagan, Joel S Perlmutter, Laura Ibanez, Richard J Perrin, Yun Ju Sung, Carlos Cruchaga, Et Al.

2020-Current year OA Pubs

Common and rare variants in the LRRK2 locus are associated with Parkinson's disease (PD) risk, but the downstream effects of these variants on protein levels remain unknown. We performed comprehensive proteogenomic analyses using the largest aptamer-based CSF proteomics study to date (7006 aptamers (6138 unique proteins) in 3107 individuals). The dataset comprised six different and independent cohorts (five using the SomaScan7K (ADNI, DIAN, MAP, Barcelona-1 (Pau), and Fundació ACE (Ruiz)) and the PPMI cohort using the SomaScan5K panel). We identified eleven independent SNPs in the LRRK2 locus associated with the levels of 25 proteins as well as PD risk. Of …

Endothelial Cell Cd36 Regulates Membrane Ceramide Formation, Exosome Fatty Acid Transfer And Circulating Fatty Acid Levels, V S Peche, T A Pietka, M Jacome-Sosa, D Samovski, H Palacios, G Chatterjee-Basu, A C Dudley, W Beatty, G A Meyer, I J Goldberg, N A Abumrad

2020-Current year OA Pubs

Endothelial cell (EC) CD36 controls tissue fatty acid (FA) uptake. Here we examine how ECs transfer FAs. FA interaction with apical membrane CD36 induces Src phosphorylation of caveolin-1 tyrosine-14 (Cav-1Y14) and ceramide generation in caveolae. Ensuing fission of caveolae yields vesicles containing FAs, CD36 and ceramide that are secreted basolaterally as small (80-100 nm) exosome-like extracellular vesicles (sEVs). We visualize in transwells EC transfer of FAs in sEVs to underlying myotubes. In mice with EC-expression of the exosome marker emeraldGFP-CD63, muscle fibers accumulate circulating FAs in emGFP-labeled puncta. The FA-sEV pathway is mapped through its suppression by CD36 depletion, blocking …

High Dynamic Range 3d Motion Tracking Using Circular Scans With Optical Coherence Tomography, Senyue Hao, Marcello Magri Amaral, Chao Zhou

2020-Current year OA Pubs

Motion artifacts, from such sources as heartbeats, respiration, or peristalsis, often degrade microscopic images or videos of live subjects. We have developed a method using circular optical coherence tomography (OCT) scans to track the transverse and axial motion of biological samples at speeds ranging from several micrometers per second to several centimeters per second. We achieve fast and high-precision measurements of the magnitude and direction of the sample's motion by adaptively controlling the circular scan pattern settings and applying interframe and intraframe analyses. These measurements are the basis of active motion compensation via feedback control for future

Rad51 Foci As A Biomarker Predictive Of Platinum Chemotherapy Response In Ovarian Cancer, Amanda J Compadre, Lillian N Van Biljon, Mark C Valentine, Emily Graham, Bisiayo Fashemi, Emilee N Kotnik, Isaac Cooper, Lindsay M Kuroki, Carolyn K Mccourt, Andrea R Hagemann, Premal H Thaker, David G Mutch, Matthew A Powell, Lulu Sun, Nima Mosammaparast, Peinan Zhao, Elena Lomonosova, Dineo Khabele, Mary M Mullen, Et Al.

2020-Current year OA Pubs

PURPOSE: To determine the ability of RAD51 foci to predict platinum chemotherapy response in high-grade serous ovarian cancer (HGSOC) patient-derived samples.

EXPERIMENTAL DESIGN: RAD51 and γH2AX nuclear foci were evaluated by immunofluorescence in HGSOC patient-derived cell lines (n = 5), organoids (n = 11), and formalin-fixed, paraffin-embedded tumor samples (discovery n = 31, validation n = 148). Samples were defined as RAD51-High if >10% of geminin-positive cells had ≥5 RAD51 foci. Associations between RAD51 scores, platinum chemotherapy response, and survival were evaluated.

RESULTS: RAD51 scores correlated with in vitro response to platinum chemotherapy in established and primary ovarian cancer cell …

An Immunostimulatory Glycolipid That Blocks Sars-Cov-2, Rsv, And Influenza Infections In Vivo, Moriya Tsuji, Zhenlu Chong, Tamarand L Darling, Kuljeet Seehra, Adrianus C M Boon, Michael S Diamond, Et Al.

2020-Current year OA Pubs

Prophylactic vaccines for SARS-CoV-2 have lowered the incidence of severe COVID-19, but emergence of viral variants that are antigenically distinct from the vaccine strains are of concern and additional, broadly acting preventive approaches are desirable. Here, we report on a glycolipid termed 7DW8-5 that exploits the host innate immune system to enable rapid control of viral infections in vivo. This glycolipid binds to CD1d on antigen-presenting cells and thereby stimulates NKT cells to release a cascade of cytokines and chemokines. The intranasal administration of 7DW8-5 prior to virus exposure significantly blocked infection by three different authentic variants of SARS-CoV-2, as …

Metabolic Signatures Of Cardiac Dysfunction, Multimorbidity, And Post-Transcatheter Aortic Valve Implantation Death, Andrew S Perry, Nishath Quader, Alan Zajarias, Et Al.

2020-Current year OA Pubs

Background Studies in mice and small patient subsets implicate metabolic dysfunction in cardiac remodeling in aortic stenosis, but no large comprehensive studies of human metabolism in aortic stenosis with long-term follow-up and characterization currently exist. Methods and Results Within a multicenter prospective cohort study, we used principal components analysis to summarize 12 echocardiographic measures of left ventricular structure and function pre-transcatheter aortic valve implantation in 519 subjects (derivation). We used least absolute shrinkage and selection operator regression across 221 metabolites to define metabolic signatures for each structural pattern and measured their relation to death and multimorbidity in the original cohort …

Human Gut Bacteria Tailor Extracellular Vesicle Cargo For The Breakdown Of Diet- And Host-Derived Glycans, Mariana G Sartorio, Evan J Pardue, Nichollas E Scott, Mario F Feldman

2020-Current year OA Pubs

Extracellular vesicles are produced in all three domains of life, and their biogenesis has common ancient origins in eukaryotes and archaea. Although bacterial vesicles were discovered several decades ago and multiple roles have been attributed to them, no mechanism has been established for vesicles biogenesis in bacteria. For this reason, there is a significant level of skepticism about the biological relevance of bacterial vesicles.