Digital Commons Network^™

Genetic Addiction Risk And Psychological Profiling Analyses For "Preaddiction" Severity Index, Kenneth Blum, Mark S Gold, Et Al.

2020-Current year OA Pubs

Since 1990, when our laboratory published the association of the

Comparison Of Metagenomic Sequencing And The Nanostring Ncounter Analysis System For The Characterization Of Bacterial And Viral Communities In Vaginal Samples, Todd N Wylie, Jane Schrimpf, Haley Gula, Brandi N Herter, Kristine M Wylie

2020-Current year OA Pubs

DNA sequencing assays have been used to characterize the vaginal microbiome and to identify associations with clinical outcomes. The purpose of this study was to evaluate the utility of the NanoString nCounter platform, a more efficient assay compared to sequencing, for the characterization of vaginal microbial communities. A panel of NanoString nCounter probes was designed to detect common vaginal bacteria and viruses with relevance to reproductive health. A defined synthetic community of microbes and 43 clinical samples were interrogated with NanoString nCounter assays and compared to known compositions or metagenomic shotgun sequencing (MSS) results. The NanoString nCounter platform and MSS …

Self-Renewal Of Macrophages: Tumor-Released Factors And Signaling Pathways, Serena Filiberti, Mariapia Russo, Silvia Lonardi, Mattia Bugatti, William Vermi, Cathy Tournier, Emanuele Giurisato

2020-Current year OA Pubs

Macrophages are the most abundant immune cells of the tumor microenvironment (TME) and have multiple important functions in cancer. During tumor growth, both tissue-resident macrophages and newly recruited monocyte-derived macrophages can give rise to tumor-associated macrophages (TAMs), which have been associated with poor prognosis in most cancers. Compelling evidence indicate that the high degree of plasticity of macrophages and their ability to self-renew majorly impact tumor progression and resistance to therapy. In addition, the microenvironmental factors largely affect the metabolism of macrophages and may have a major influence on TAMs proliferation and subsets functions. Thus, understanding the signaling pathways regulating …

Epidemiology Of Plasmid Lineages Mediating The Spread Of Extended-Spectrum Beta-Lactamases Among Clinical Escherichia Coli, Bejan Mahmud, Meghan A Wallace, Kimberly A Reske, Kelly Alvarado, Carol E Muenks, David A Rasmussen, Carey-Ann D Burnham, Cristina Lanzas, Erik R Dubberke, Gautam Dantas

2020-Current year OA Pubs

The prevalence of extended-spectrum beta-lactamases (ESBLs) among clinical isolates of Escherichia coli has been increasing, with this spread driven by ESBL-encoding plasmids. However, the epidemiology of ESBL-disseminating plasmids remains understudied, obscuring the roles of individual plasmid lineages in ESBL spread. To address this, we performed an in-depth genomic investigation of 149 clinical ESBL-like E. coli isolates from a tertiary care hospital. We obtained high-quality assemblies for 446 plasmids, revealing an extensive map of plasmid sharing that crosses time, space, and bacterial sequence type boundaries. Through a sequence-based network, we identified specific plasmid lineages that are responsible for the dissemination of …

Emergence Of Compensatory Mutations Reveals The Importance Of Electrostatic Interactions Between Hiv-1 Integrase And Genomic Rna, Christian Shema Mugisha, Tung Dinh, Abhishek Kumar, Kasyap Tenneti, Jenna E Eschbach, Keanu Davis, Robert Gifford, Mamuka Kvaratskhelia, Sebla B Kutluay

2020-Current year OA Pubs

HIV-1 integrase (IN) has a noncatalytic function in virion maturation through its binding to the viral RNA genome (gRNA). Class II IN substitutions inhibit IN-gRNA binding and result in the formation of virions with aberrant morphologies marked by mislocalization of the gRNA between the capsid lattice and the lipid envelope. These viruses are noninfectious due to a block at an early reverse transcription stage in target cells. HIV-1 IN utilizes basic residues within its C-terminal domain (CTD) to bind to the gRNA; however, the molecular nature of how these residues mediate gRNA binding and whether other regions of IN are …

Marijuana Use And Dna Methylation-Based Biological Age In Young Adults, Drew R Nannini, Yinan Zheng, Brian T Joyce, Tao Gao, Lei Liu, David R Jacobs Jr, Pamela Schreiner, Chunyu Liu, Steve Horvath, Ake T Lu, Kristine Yaffe, Stephen Sidney, Philip Greenland, Donald M Lloyd-Jones, Lifang Hou

2020-Current year OA Pubs

BACKGROUND: Marijuana is the third most commonly used drug in the USA and efforts to legalize it for medical and recreational use are growing. Despite the increase in use, marijuana's effect on aging remains understudied and understanding the effects of marijuana on molecular aging may provide novel insights into the role of marijuana in the aging process. We therefore sought to investigate the association between cumulative and recent use of marijuana with epigenetic age acceleration (EAA) as estimated from blood DNA methylation.

RESULTS: A random subset of participants from The Coronary Artery Risk Development in Young Adults (CARDIA) Study with …

Pooled Image-Base Screening Of Mitochondria With Microraft Isolation Distinguishes Pathogenic Mitofusin 2 Mutations, Alex L Yenkin, John C Bramley, Colin L Kremitzki, Jason E Waligorski, Mariel J Liebeskind, Xinyuan E Xu, Vinay D Chandrasekaran, Maria A Vakaki, Graham W Bachman, Robi D Mitra, Jeffrey D Milbrandt, William J Buchser

2020-Current year OA Pubs

Most human genetic variation is classified as variants of uncertain significance. While advances in genome editing have allowed innovation in pooled screening platforms, many screens deal with relatively simple readouts (viability, fluorescence) and cannot identify the complex cellular phenotypes that underlie most human diseases. In this paper, we present a generalizable functional genomics platform that combines high-content imaging, machine learning, and microraft isolation in a method termed "Raft-Seq". We highlight the efficacy of our platform by showing its ability to distinguish pathogenic point mutations of the mitochondrial regulator Mitofusin 2, even when the cellular phenotype is subtle. We also show …

Novel Chelating Agents For Zirconium-89-Positron Emission Tomography (Pet) Imaging: Synthesis, Dft Calculation, Radiolabeling, And In Vitro And In Vivo Complex Stability, Chi Soo Kang, Shuyuan Zhang, Haixing Wang, Yujie Liu, Siyuan Ren, Yanda Chen, Jingbai Li, Nilantha Bandara, Andrey Yu Rogachev, Buck E Rogers, Hyun-Soon Chong

2020-Current year OA Pubs

We report the synthesis and evaluation of novel chelating agents for zirconium-89 (

Human Neutrophil Development And Functionality Are Enabled In A Humanized Mouse Model, Yunjiang Zheng, Esen Sefik, John Astle, Kutay Karatepe, Hasan H Öz, Angel G Solis, Ruaidhrí Jackson, Hongbo R Luo, Emanuela M Bruscia, Stephanie Halene, Liang Shan, Richard A Flavell

2020-Current year OA Pubs

Mice with a functional human immune system serve as an invaluable tool to study the development and function of the human immune system in vivo. A major technological limitation of all current humanized mouse models is the lack of mature and functional human neutrophils in circulation and tissues. To overcome this, we generated a humanized mouse model named MISTRGGR, in which the mouse granulocyte colony-stimulating factor (G-CSF) was replaced with human G-CSF and the mouse G-CSF receptor gene was deleted in existing MISTRG mice. By targeting the G-CSF cytokine-receptor axis, we dramatically improved the reconstitution of mature circulating and tissue-infiltrating …

Ring-Fused 2-Pyridones Effective Against Multidrug-Resistant Gram-Positive Pathogens And Synergistic With Standard-Of-Care Antibiotics, Taylor M Nye, Hasan Tükenmez, Pardeep Singh, Ana L Flores-Mireles, Chloe L P Obernuefemann, Jerome S Pinkner, Souvik Sarkar, Mari Bonde, Anders E G Lindgren, Karen W Dodson, Jörgen Johansson, Fredrik Almqvist, Michael G Caparon, Scott J Hultgren

2020-Current year OA Pubs

The alarming rise of multidrug-resistant Gram-positive bacteria has precipitated a healthcare crisis, necessitating the development of new antimicrobial therapies. Here we describe a new class of antibiotics based on a ring-fused 2-pyridone backbone, which are active against vancomycin-resistant enterococci (VRE), a serious threat as classified by the Centers for Disease Control and Prevention, and other multidrug-resistant Gram-positive bacteria. Ring-fused 2-pyridone antibiotics have bacteriostatic activity against actively dividing exponential phase enterococcal cells and bactericidal activity against nondividing stationary phase enterococcal cells. The molecular mechanism of drug-induced killing of stationary phase cells mimics aspects of fratricide observed in enterococcal biofilms, where both …

Somatic Mutations In Fat Cadherin Family Members Constitute An Underrecognized Subtype Of Colorectal Adenocarcinoma With Unique Clinicopathologic Features, Liang-Li Wang, Wei Zheng, Xiu-Li Liu, Feng Yin

2020-Current year OA Pubs

BACKGROUND: The FAT cadherin family members (FAT1, FAT2, FAT3 and FAT4) are conserved tumor suppressors that are recurrently mutated in several types of human cancers, including colorectal carcinoma (CRC).

AIM: To characterize the clinicopathologic features of CRC patients with somatic mutations in FAT cadherin family members.

METHODS: We analyzed 526 CRC cases from The Cancer Genome Atlas PanCancer Atlas dataset. CRC samples were subclassified into 2 groups based on the presence or absence of somatic mutations in

RESULTS: This CRC study cohort had frequent mutations in the

CONCLUSION:

The Impact Of Tsc-1 And -2 Mutations On Response To Therapy In Malignant Pecoma: A Multicenter Retrospective Analysis, Lawrence Liu, Nikhil Grandhi, Yang Lyu, Xiao Zhang, Jingqin Luo, Mia Weiss, Brian Van Tine, Angela C Hirbe, Et Al.

2020-Current year OA Pubs

BACKGROUND: Perivascular epithelioid cell neoplasms (PEComas) are a diverse family of mesenchymal tumors with myomelanocytic differentiation that disproportionately affect women and can be associated with tuberous sclerosis (TS). Although mTOR inhibition is widely used as first-line treatment, it is unclear what genomic alterations exist in these tumors and how they influence the response to therapy.

METHODS: This was a multicenter study conducted at five sites within the US. The data were collected from 1 January 2004 to 31 January 2021. We conducted a retrospective analysis to identify PEComa patients with next-generation sequencing (NGS) data and compared outcomes based on mutations. …

Integrated Host-Microbe Plasma Metagenomics For Sepsis Diagnosis In A Prospective Cohort Of Critically Ill Adults, Katrina L Kalantar, Pratik Sinha, Et Al.

2020-Current year OA Pubs

We carried out integrated host and pathogen metagenomic RNA and DNA next generation sequencing (mNGS) of whole blood (n = 221) and plasma (n = 138) from critically ill patients following hospital admission. We assigned patients into sepsis groups on the basis of clinical and microbiological criteria. From whole-blood gene expression data, we distinguished patients with sepsis from patients with non-infectious systemic inflammatory conditions using a trained bagged support vector machine (bSVM) classifier (area under the receiver operating characteristic curve (AUC) = 0.81 in the training set; AUC = 0.82 in a held-out validation set). Plasma RNA also yielded a …

Complete Genome Sequence Of The Uropathogenic Methicillin-Resistant Staphylococcus Aureus Strain Mrsa-1369, Hasan Tükenmez, Taylor M Nye, Mari Bonde, Michael G Caparon, Fredrik Almqvist, Scott J Hultgren, Jörgen Johansson

2020-Current year OA Pubs

MRSA-1369 is a uropathogenic methicillin-resistant Staphylococcus aureus (MRSA) strain. Here, we present the complete genome sequence of MRSA-1369, which consists of one chromosome (2.87 Mb) and two plasmids (16.68 kb and 3.13 kb). This will serve as a reference genome for future Staphylococcus aureus pathogenesis and multiomic studies.

Neoplastic Cell Enrichment Of Tumor Tissues Using Coring And Laser Microdissection For Proteomic And Genomic Analyses Of Pancreatic Ductal Adenocarcinoma, Qing Kay Li, Daniel Cui Zhou, Yize Li, Rita Jui-Hsien Lu, Li Ding, Et Al.

2020-Current year OA Pubs

BACKGROUND: The identification of differentially expressed tumor-associated proteins and genomic alterations driving neoplasia is critical in the development of clinical assays to detect cancers and forms the foundation for understanding cancer biology. One of the challenges in the analysis of pancreatic ductal adenocarcinoma (PDAC) is the low neoplastic cellularity and heterogeneous composition of bulk tumors. To enrich neoplastic cells from bulk tumor tissue, coring, and laser microdissection (LMD) sampling techniques have been employed. In this study, we assessed the protein and KRAS mutation changes associated with samples obtained by these enrichment techniques and evaluated the fraction of neoplastic cells in …

Semi-Automated Assembly Of High-Quality Diploid Human Reference Genomes, Erich D Jarvis, Sarah Cody, Robert S Fulton, Lucinda L Fulton, Daofeng Li, Tina Lindsay, Nathan O Stitziel, Ting Wang, Et Al.

2020-Current year OA Pubs

The current human reference genome, GRCh38, represents over 20 years of effort to generate a high-quality assembly, which has benefitted society^1,2. However, it still has many gaps and errors, and does not represent a biological genome as it is a blend of multiple individuals^3,4. Recently, a high-quality telomere-to-telomere reference, CHM13, was generated with the latest long-read technologies, but it was derived from a hydatidiform mole cell line with a nearly homozygous genome⁵. To address these limitations, the Human Pangenome Reference Consortium formed with the goal of creating high-quality, cost-effective, diploid genome assemblies for a …

Prenatal Exposure To Maternal Social Disadvantage And Psychosocial Stress And Neonatal White Matter Connectivity At Birth, Rachel E Lean, Christopher D Smyser, Rebecca G Brady, Regina L Triplett, Sydney Kaplan, Jeanette K Kenley, Joshua S Shimony, Tara A Smyser, J Phillip Miller, Deanna M Barch, Joan L Luby, Barbara B Warner, Cynthia E Rogers

2020-Current year OA Pubs

Early life adversity (social disadvantage and psychosocial stressors) is associated with altered microstructure in fronto-limbic pathways important for socioemotional development. Understanding when these associations begin to emerge may inform the timing and design of preventative interventions. In this longitudinal study, 399 mothers were oversampled for low income and completed social background measures during pregnancy. Measures were analyzed with structural equation analysis resulting in two latent factors: social disadvantage (education, insurance status, income-to-needs ratio [INR], neighborhood deprivation, and nutrition) and psychosocial stress (depression, stress, life events, and racial discrimination). At birth, 289 healthy term-born neonates underwent a diffusion MRI (dMRI) scan. …

Il-1Β-Dependent Extravasation Of Preexisting Lung-Restricted Autoantibodies During Lung Transplantation Activates Complement And Mediates Primary Graft Dysfunction, Wenbin Yang, Daniel Kreisel, Et Al.

2020-Current year OA Pubs

Preexisting lung-restricted autoantibodies (LRAs) are associated with a higher incidence of primary graft dysfunction (PGD), although it remains unclear whether LRAs can drive its pathogenesis. In syngeneic murine left lung transplant recipients, preexisting LRAs worsened graft dysfunction, which was evident by impaired gas exchange, increased pulmonary edema, and activation of damage-associated pathways in lung epithelial cells. LRA-mediated injury was distinct from ischemia-reperfusion injury since deletion of donor nonclassical monocytes and host neutrophils could not prevent graft dysfunction in LRA-pretreated recipients. Whole LRA IgG molecules were necessary for lung injury, which was mediated by the classical and alternative complement pathways and …

Cellular Landscaping Of Covid-19 And Gynaecological Cancers: An Infrequent Correlation, Rahul Bhattacharjee, Debanjan Das, Radheka Bhadhuri, Srija Chakraborty, Tanima Dey, Rupam Buragohain, Asim Nath, Kartik Muduli, Pranjan Barman, Rohit Gundamaraju

2020-Current year OA Pubs

COVID-19 resulted in a mortality rate of 3-6% caused by SARS-CoV-2 and its variant leading to unprecedented consequences of acute respiratory distress septic shock and multiorgan failure. In such a situation, evaluation, diagnosis, treatment, and care for cancer patients are difficult tasks faced by medical staff. Moreover, patients with gynaecological cancer appear to be more prone to severe infection and mortality from COVID-19 due to immunosuppression by chemotherapy and coexisting medical disorders. To deal with such a circumtances oncologists have been obliged to reconsider the entire diagnostic, treatment, and management approach. This review will provide and discuss the molecular link …

A Quantitative Metric Of Pioneer Activity Reveals That Hnf4a Has Stronger In Vivo Pioneer Activity Than Foxa1, Jeffrey L Hansen, Barak A Cohen

2020-Current year OA Pubs

BACKGROUND: We and others have suggested that pioneer activity - a transcription factor's (TF's) ability to bind and open inaccessible loci - is not a qualitative trait limited to a select class of pioneer TFs. We hypothesize that most TFs display pioneering activity that depends on the TF concentration and the motif content at their target loci.

RESULTS: Here, we present a quantitative in vivo measure of pioneer activity that captures the relative difference in a TF's ability to bind accessible versus inaccessible DNA. The metric is based on experiments that use CUT&Tag to measure the binding of doxycycline-inducible TFs. …

Clinical And Molecular Response To Tebentafusp In Previously Treated Patients With Metastatic Uveal Melanoma: A Phase 2 Trial, Richard D Carvajal, Leonel Hernandez-Aya, Et Al.

2020-Current year OA Pubs

In patients with previously treated metastatic uveal melanoma, the historical 1 year overall survival rate is 37% with a median overall survival of 7.8 months. We conducted a multicenter, single-arm, open-label phase 2 study of tebentafusp, a soluble T cell receptor bispecific (gp100×CD3), in 127 patients with treatment-refractory metastatic uveal melanoma (NCT02570308). The primary endpoint was the estimation of objective response rate based on RECIST (Response Evaluation Criteria in Solid Tumours) v1.1. Secondary objectives included safety, overall survival, progression-free survival and disease control rate. All patients had at least one treatment-related adverse event, with rash (87%), pyrexia (80%) and pruritus …

Personalized Structural Biology Reveals The Molecular Mechanisms Underlying Heterogeneous Epileptic Phenotypes Caused By De Novo Kcnc2 Variants, Souhrid Mukherjee, Jonathan H Sheehan, Et Al.

2020-Current year OA Pubs

Whole-exome sequencing (WES) in the clinic has identified several rare monogenic developmental and epileptic encephalopathies (DEE) caused by ion channel variants. However, WES often fails to provide actionable insight for rare diseases, such as DEEs, due to the challenges of interpreting variants of unknown significance (VUS). Here, we describe a "personalized structural biology" (PSB) approach that leverages recent innovations in the analysis of protein 3D structures to address this challenge. We illustrate this approach in an Undiagnosed Diseases Network (UDN) individual with DEE symptoms and a

Whole Genome Sequence Analysis Of Blood Lipid Levels In >66,000 Individuals, Margaret Sunitha Selvaraj, Lisa De Las Fuentes, Susan K. Dutcher, Et Al.

2020-Current year OA Pubs

No abstract provided.

Mesoscale Structure-Function Relationships In Mitochondrial Transcriptional Condensates, Marina Feric, Azadeh Sarfallah, Furqan Dar, Dmitry Temiakov, Rohit V Pappu, Tom Misteli

2020-Current year OA Pubs

In live cells, phase separation is thought to organize macromolecules into membraneless structures known as biomolecular condensates. Here, we reconstituted transcription in condensates from purified mitochondrial components using optimized in vitro reaction conditions to probe the structure-function relationships of biomolecular condensates. We find that the core components of the mt-transcription machinery form multiphasic, viscoelastic condensates in vitro. Strikingly, the rates of condensate-mediated transcription are substantially lower than in solution. The condensate-mediated decrease in transcriptional rates is associated with the formation of vesicle-like structures that are driven by the production and accumulation of RNA during transcription. The generation of RNA alters …

Amyloid Β, Lipid Metabolism, Basal Cholinergic System, And Therapeutics In Alzheimer's Disease, Victoria Campos-Peña, Pavel Pichardo-Rojas, Talía Sánchez-Barbosa, Emma Ortíz-Islas, Citlali Ekaterina Rodríguez-Pérez, Pedro Montes, Gerardo Ramos-Palacios, Daniela Silva-Adaya, Rafael Valencia-Quintana, Jorge Francisco Cerna-Cortes, Danira Toral-Rios

2020-Current year OA Pubs

The presence of insoluble aggregates of amyloid β (Aβ) in the form of neuritic plaques (NPs) is one of the main features that define Alzheimer's disease. Studies have suggested that the accumulation of these peptides in the brain significantly contributes to extensive neuronal loss. Furthermore, the content and distribution of cholesterol in the membrane have been shown to have an important effect on the production and subsequent accumulation of Aβ peptides in the plasma membrane, contributing to dysfunction and neuronal death. The monomeric forms of these membrane-bound peptides undergo several conformational changes, ranging from oligomeric forms to beta-sheet structures, each …

Occupational Characteristics Associated With Sars-Cov-2 Infection In The Uk Biobank During August-November 2020: A Cohort Study, Elizabeth L Yanik, Bradley A Evanoff, Ann Marie Dale, Yinjiao Ma, Karen E Walker-Bone

2020-Current year OA Pubs

BACKGROUND: Occupational exposures may play a key role in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection risk. We used a job-exposure matrix linked to the UK Biobank to measure occupational characteristics and estimate associations with a positive SARS-CoV-2 test.

METHODS: People reporting job titles at their baseline interview in England who were < 65 years of age in 2020 were included. Healthcare workers were excluded because of differential access to testing. Jobs were linked to the US Occupational Information Network (O*NET) job exposure matrix. O*NET-based scores were examined for occupational physical proximity, exposure to diseases/infection, working outdoors exposed to weather, and working outdoors under cover (score range = 1-5). Jobs were classified as remote work using two algorithms. SARS-CoV-2 test results were evaluated between August 5th-November 10th, 2020, when the UK was released from lockdown. Cox regression was used to calculate adjusted hazard ratios (aHRs), accounting for age, sex, race, education, neighborhood deprivation, assessment center, household size, and income.

RESULTS: We included 115,451 people with job titles, of whom 1746 tested positive for SARS-CoV-2. A one-point increase in physical proximity score was associated with 1.14 times higher risk of SARS-CoV-2 (95%CI = 1.05-1.24). A one-point increase in the exposure to diseases/infections score was associated with 1.09 …

Cellular Sources And Neuroprotective Roles Of Interleukin-10 In The Facial Motor Nucleus After Axotomy, Elizabeth M Runge, Deborah O Setter, Abhirami K Iyer, Eric J Regele, Felicia M Kennedy, Virginia M Sanders, Kathryn J Jones

2020-Current year OA Pubs

Facial motoneuron (FMN) survival is mediated by CD4+ T cells in an interleukin-10 (IL-10)-dependent manner after facial nerve axotomy (FNA), but CD4+ T cells themselves are not the source of this neuroprotective IL-10. The aims of this study were to (1) identify the temporal and cell-specific induction of IL-10 expression in the facial motor nucleus and (2) elucidate the neuroprotective capacity of this expression after axotomy. Immunohistochemistry revealed that FMN constitutively produced IL-10, whereas astrocytes were induced to make IL-10 after FNA.

A Bioresorbable Peripheral Nerve Stimulator For Electronic Pain Block, Geumbee Lee, Emily Ray, Sabrina Genovese, Ying Yan, Arman Odabas, Umang Khandpur, Wilson Z Ray, Matthew R Macewan, Et Al.

2020-Current year OA Pubs

Local electrical stimulation of peripheral nerves can block the propagation of action potentials, as an attractive alternative to pharmacological agents for the treatment of acute pain. Traditional hardware for such purposes, however, involves interfaces that can damage nerve tissue and, when used for temporary pain relief, that impose costs and risks due to requirements for surgical extraction after a period of need. Here, we introduce a bioresorbable nerve stimulator that enables electrical nerve block and associated pain mitigation without these drawbacks. This platform combines a collection of bioresorbable materials in architectures that support stable blocking with minimal adverse mechanical, electrical, …

Continuous Npwt Regulates Fibrosis In Murine Diabetic Wound Healing, Mengfan Wu, Dany Y Matar, Zhen Yu, Ziyu Chen, Samuel Knoedler, Brian Ng, Oliver A Darwish, Sadaf Sohrabi, Leigh Friedman, Valentin Haug, George F Murphy, Yuval Rinkevich, Dennis P Orgill, Adriana C Panayi

2020-Current year OA Pubs

Scarring is associated with significant morbidity. The mechanical signaling factor yes-associated protein (YAP) has been linked to Engrailed-1 (En1)-lineage positive fibroblasts (EPFs), a pro-scarring fibroblast lineage, establishing a connection between mechanotransduction and fibrosis. In this study, we investigate the impact of micromechanical forces exerted through negative pressure wound therapy (NPWT) on the pathophysiology of fibrosis. Full-thickness excisional dorsal skin wounds were created on diabetic (db/db) mice which were treated with occlusive covering (control) or NPWT (continuous, -125 mmHg, 7 days; NPWT). Analysis was performed on tissue harvested 10 days after wounding. NPWT was associated with increased YAP (

Antidepressant Use And Its Association With 28-Day Mortality In Inpatients With Sars-Cov-2: Support For The Fiasma Model Against Covid-19, Nicolas Hoertel, Angela M Reiersen, Eric J Lenze, Bradley A Fritz, Et Al.

2020-Current year OA Pubs

To reduce Coronavirus Disease 2019 (COVID-19)-related mortality and morbidity, widely available oral COVID-19 treatments are urgently needed. Certain antidepressants, such as fluvoxamine or fluoxetine, may be beneficial against COVID-19. We included 388,945 adult inpatients who tested positive for SARS-CoV-2 at 36 AP-HP (Assistance Publique-Hôpitaux de Paris) hospitals from 2 May 2020 to 2 November 2021. We compared the prevalence of antidepressant use at admission in a 1:1 ratio matched analytic sample with and without COVID-19 (N = 82,586), and assessed its association with 28-day all-cause mortality in a 1:1 ratio matched analytic sample of COVID-19 inpatients with and without antidepressant …