Digital Commons Network^™

Airy-Beam Holographic Sonogenetics For Advancing Neuromodulation Precision And Flexibility, Zhongtao Hu, Yaoheng Yang, Leqi Yang, Yan Gong, Chinwendu Chukwu, Dezhuang Ye, Yimei Yue, Jinyun Yuan, Alexxai V Kravitz, Hong Chen

2020-Current year OA Pubs

Advancing our understanding of brain function and developing treatments for neurological diseases hinge on the ability to modulate neuronal groups in specific brain areas without invasive techniques. Here, we introduce Airy-beam holographic sonogenetics (AhSonogenetics) as an implant-free, cell type-specific, spatially precise, and flexible neuromodulation approach in freely moving mice. AhSonogenetics utilizes wearable ultrasound devices manufactured using 3D-printed Airy-beam holographic metasurfaces. These devices are designed to manipulate neurons genetically engineered to express ultrasound-sensitive ion channels, enabling precise modulation of specific neuronal populations. By dynamically steering the focus of Airy beams through ultrasound frequency tuning, AhSonogenetics is capable of modulating neuronal populations …

Effectiveness Of An Online Text-Based Stress Management Program For Employees Who Work In Micro- And Small-Sized Enterprises: A Randomized Controlled Trial, Natsu Sasaki, Sayaka Ogawa, Utako Sawada, Taichi Shimazu, Byron J Powell, Hajime Takeno, Akizumi Tsutsumi, Kotaro Imamura

2020-Current year OA Pubs

BACKGROUND: Internet psychoeducational interventions improve employees' mental health. However, implementing them for employees in micro- and small-sized enterprises (MSEs) is challenging.

OBJECTIVES: This randomized controlled trial examined the effectiveness of a fully automated text-based stress management program, "WellBe-LINE," in improving mental health and job-related outcomes for employees in workplaces with fewer than 50 employees.

METHODS: The program was developed based on stakeholder interviews and surveys of 1000 employees at MSEs. Adult full-time employees at an enterprise with fewer than 50 employees were recruited from registered members of a web survey company in Japan. Participants were randomly allocated to the intervention …

The Vaginal Immunoproteome For The Prediction Of Spontaneous Preterm Birth: A Retrospective Longitudinal Study, Zachary Shaffer, Roberto Romero, Adi L Tarca, Jose Galaz, Marcia Arenas-Hernandez, Dereje W Gudicha, Tinnakorn Chaiworapongsa, Eunjung Jung, Manaphat Suksai, Kevin R Theis, Nardhy Gomez-Lopez

2020-Current year OA Pubs

BACKGROUND: Preterm birth is the leading cause of neonatal morbidity and mortality worldwide. Most cases of preterm birth occur spontaneously and result from preterm labor with intact (spontaneous preterm labor [sPTL]) or ruptured (preterm prelabor rupture of membranes [PPROM]) membranes. The prediction of spontaneous preterm birth (sPTB) remains underpowered due to its syndromic nature and the dearth of independent analyses of the vaginal host immune response. Thus, we conducted the largest longitudinal investigation targeting vaginal immune mediators, referred to herein as the immunoproteome, in a population at high risk for sPTB.

METHODS: Vaginal swabs were collected across gestation from pregnant …

Harmonized Cross-Species Cell Atlases Of Trigeminal And Dorsal Root Ganglia, Shamsuddin A Bhuiyan, Lite Yang, Lisa A Mcilvried, Bryan A Copits, Zachariah Bertels, John S Del Rosario, Allie J Widman, Richard A Slivicki, Jiwon Yi, Robert W Gereau Iv, Et Al.

2020-Current year OA Pubs

Sensory neurons in the dorsal root ganglion (DRG) and trigeminal ganglion (TG) are specialized to detect and transduce diverse environmental stimuli to the central nervous system. Single-cell RNA sequencing has provided insights into the diversity of sensory ganglia cell types in rodents, nonhuman primates, and humans, but it remains difficult to compare cell types across studies and species. We thus constructed harmonized atlases of the DRG and TG that describe and facilitate comparison of 18 neuronal and 11 non-neuronal cell types across six species and 31 datasets. We then performed single-cell/nucleus RNA sequencing of DRG from both human and the …

Clinical Prediction For Surgical Versus Nonsurgical Interventions In Patients With Vertebral Osteomyelitis And Discitis, Jennifer Lee, Miguel A. Ruiz-Cardozo, Rujvee P. Patel, Saad Javeed, Raj Swaroop Lavadi, Catherine Newsom-Stewart, Anton Alyakin, Camilo A. Molina, Nitin Agarwal, Wilson Z. Ray, Michele Santacatterina, Brenton H. Pennicooke

2020-Current year OA Pubs

BACKGROUND: Vertebral osteomyelitis and discitis (VOD), an infection of intervertebral discs, often requires spine surgical intervention and timely management to prevent adverse outcomes. Our study aims to develop a machine learning (ML) model to predict the indication for surgical intervention (during the same hospital stay) versus nonsurgical management in patients with VOD.

METHODS: This retrospective study included adult patients (≥18 years) with VOD (ICD-10 diagnosis codes M46.2,3,4,5) treated at a single institution between 01/01/2015 and 12/31/2019. The primary outcome studied was surgery. Candidate predictors were age, sex, race, Elixhauser comorbidity index, first-recorded lab values, first-recorded vital signs, and admit diagnosis. …

Defining Cis-Regulatory Elements And Transcription Factors That Control Human Cortical Interneuron Development, Gareth Chapman, Julianna Determan, Haley Jetter, Komal Kaushik, Ramachandran Prakasam, Kristen L Kroll

2020-Current year OA Pubs

Although human cortical interneurons (cINs) are a minority population in the cerebral cortex, disruption of interneuron development is a frequent contributor to neurodevelopmental disorders. Here, we utilized a model for deriving cINs from human embryonic stem cells to profile chromatin state changes and generate an atlas of

Noninvasive Assessment Of The Lung Inflammation-Fibrosis Axis By Targeted Imaging Of Cmklr1, Philip Z Mannes, Taylor S Adams, Samaneh Farsijani, Clayton E Barnes, Joseph D Latoche, Kathryn E Day, Jessie R Nedrow, Farida Ahangari, Naftali Kaminski, Janet S Lee, Sina Tavakoli

2020-Current year OA Pubs

Precision management of fibrotic lung diseases is challenging due to their diverse clinical trajectories and lack of reliable biomarkers for risk stratification and therapeutic monitoring. Here, we validated the accuracy of CMKLR1 as an imaging biomarker of the lung inflammation-fibrosis axis. By analyzing single-cell RNA sequencing datasets, we demonstrated

Improving Emergency Medicine Resident Pediatric Lumbar Puncture Procedural Performance Through A Brief Just-In-Time Video Intervention, Sarayna S Mcguire, Alexander S Finch, Jenna M Thomas, Octavio Lazaro, Sara A Hevesi, Aidan F Mullan, Jim L Homme

2020-Current year OA Pubs

BACKGROUND: Emergency medicine (EM) trainee comfort level with lumbar puncture (LP) has decreased over time due to changing practice guidelines, particularly amongst pediatric patients. We implemented a "just in time" (JIT) brief educational video based on a previously published LP Performance Scoring Checklist to improve trainee efficiency and competence in LP performance.

METHODS: Our pilot quasi-experimental study took place January-June 2022 within a large, academic Midwestern emergency department (ED) with an established 3-year EM residency program. All 9 interns performed a timed diagnostic LP on an infant LP model in January, scored according to the LP Performance Scoring Checklist. In …

Advanced Hiv Disease And Associated Factors Among Young People Aged 15-24 Years At A Tertiary Hospital In Sierra Leone: A Cross-Sectional Study, Mamadu Baldeh, Samuel Kizito, Sulaiman Lakoh, Daniel Sesay, Samuel Adeyemi Williams, Umu Barrie, Frida Dennis, Dimbintsoa Rakotomalala Robinson, Franck Lamontagne, Franck Amahowe, Patrick Turay, Ozge Sensoy Bahar, Elvin Geng, Fred M Ssewamala

2020-Current year OA Pubs

BACKGROUND: Advanced HIV disease (AHD) in young people living with HIV (PLHIV) is an increasingly pressing public health issue in sub-Saharan Africa. Despite global progress in early HIV testing and reducing HIV-related deaths, many youths experience increased rates of HIV disease progression in sub-Saharan Africa. This study describes the burden, clinical manifestations, and factors for disease progression among young PLHIV aged 15 - 24 years seeking medical services at a major public hospital in Sierra Leone.

METHODS: We performed a cross-sectional analysis of routinely collected data for PLHIV patients aged 15 to 24 seen at Connaught Hospital in Sierra Leone …

Enabling Tobacco Treatment For Gastroenterology Patients Via A Novel Low-Burden Point-Of-Care Model, Suha Abushamma, Li-Shiun Chen, Jingling Chen, Nina Smock, Giang Pham, Chien-Huan Chen

2020-Current year OA Pubs

BACKGROUND & AIM: Smoking is a major risk factor for multiple gastrointestinal cancers, and adversely affects peptic ulcer disease, gastroesophageal reflux, pancreatitis and Crohn's disease. Despite key recommendations for diagnosing and treating tobacco use disorder in healthcare settings, the degree to which this is implemented in Gastroenterology (GI) clinics is unknown. We aimed to assess our providers' practices, identify barriers for implementing evidence-based smoking cessation treatments, and address these barriers by implementing a novel low-burden point of care Electronic health record-enabled evidence-based tobacco treatment (ELEVATE), in GI clinics.

METHODS: An online survey was distributed to clinic gastroenterologists. ELEVATE module training …

Impact Of Cognitive Impairment On Driving Behaviour And Route Choices Of Older Drivers: A Real-World Driving Study, Reihaneh Derafshi, Ganesh M Babulal, Sayeh Bayat

2020-Current year OA Pubs

Maintaining driving independence is important for older adults. However, cognitive decline, a common issue in older populations, can impair older adults' driving abilities and overall safety on the roads. This study explores how cognitive impairment influences driving patterns and driving choices among older adults. We analyzed real-world driving patterns of 246 older adults using GPS dataloggers. Our sample included 230 cognitively normal older adults (CN; Clinical Dementia Rating

Antibiotic Dispensing Practices Among Informal Healthcare Providers In Low-Income And Middle-Income Countries: A Scoping Review Protocol, Meera Tandan, Poshan Thapa, Buna Bhandari, Sumanth Gandra, Diwash Timalsina, Shweta Bohora, Swostika Thapaliya, Anupama Bhusal, Genevieve C Gore, Surbhi Sheokand, Prachi Shukla, Chandrashekhar Joshi, Nitin Mudgal, Madhukar Pai, Giorgia Sulis

2020-Current year OA Pubs

INTRODUCTION: The rise of antimicrobial resistance represents a critical threat to global health, exacerbated by the excessive and inappropriate dispensing and use of antimicrobial drugs, notably antibiotics, which specifically target bacterial infections. The surge in antibiotic consumption globally is particularly concerning in low-income and middle-income countries (LMICs), where informal healthcare providers (IPs) play a vital role in the healthcare landscape. Often the initial point of contact for healthcare-seeking individuals, IPs play a crucial role in delivering primary care services in these regions. Despite the prevalent dispensing of antibiotics by IPs in many LMICs, as highlighted by existing research, there remains …

Incidence And Risk Factors For New And Recurrent Infarcts In Adults With Sickle Cell Disease, Lori C Jordan, Allison A King, Andria L Ford, Taniya E Varughese, Lisa Garrett, Et Al.

2020-Current year OA Pubs

BACKGROUND: Most adults with sickle cell disease will experience a silent cerebral infarction (SCI) or overt stroke. Identifying patient subgroups with increased stroke incidence is important for future clinical trials focused on stroke prevention. Our 3-center prospective cohort study tested the primary hypothesis that adults with sickle cell disease and SCIs have a greater incidence of new stroke or SCI compared with those without SCI. A secondary aim focused on identifying additional risk factors for progressive infarcts, particularly traditional risk factors for stroke in adults.

METHODS AND RESULTS: This observational study included adults with sickle cell disease and no history …

Structural Basis For Hyperpolarization-Dependent Opening Of Human Hcn1 Channel, Verena Burtscher, Jonathan Mount, Jian Huang, John Cowgill, Yongchang Chang, Kathleen Bickel, Jianhan Chen, Peng Yuan, Baron Chanda

2020-Current year OA Pubs

Hyperpolarization and cyclic nucleotide (HCN) activated ion channels are critical for the automaticity of action potentials in pacemaking and rhythmic electrical circuits in the human body. Unlike most voltage-gated ion channels, the HCN and related plant ion channels activate upon membrane hyperpolarization. Although functional studies have identified residues in the interface between the voltage-sensing and pore domain as crucial for inverted electromechanical coupling, the structural mechanisms for this unusual voltage-dependence remain unclear. Here, we present cryo-electron microscopy structures of human HCN1 corresponding to Closed, Open, and a putative Intermediate state. Our structures reveal that the downward motion of the gating …

Protein Restriction Slows The Development And Progression Of Pathology In A Mouse Model Of Alzheimer's Disease, Reji Babygirija, Natalie M Niemi, Et Al.

2020-Current year OA Pubs

Dietary protein is a critical regulator of metabolic health and aging. Low protein diets are associated with healthy aging in humans, and dietary protein restriction extends the lifespan and healthspan of mice. In this study, we examined the effect of protein restriction (PR) on metabolic health and the development and progression of Alzheimer's disease (AD) in the 3xTg mouse model of AD. Here, we show that PR promotes leanness and glycemic control in 3xTg mice, specifically rescuing the glucose intolerance of 3xTg females. PR induces sex-specific alterations in circulating and brain metabolites, downregulating sphingolipid subclasses in 3xTg females. PR also …

Seeding Activity Of Human Superoxide Dismutase 1 Aggregates In Familial And Sporadic Amyotrophic Lateral Sclerosis Postmortem Neural Tissues By Real-Time Quaking-Induced Conversion, Justin K Mielke, Mikael Klingeborn, Eric P Schultz, Erin L Markham, Emily D Reese, Parvez Alam, Ian R Mackenzie, Cindy V Ly, Byron Caughey, Neil R Cashman, Moses J Leavens

2020-Current year OA Pubs

Amyotrophic lateral sclerosis (ALS) is a rapidly progressive neurodegenerative disease with average lifespan of 2-5 years after diagnosis. The identification of novel prognostic and pharmacodynamic biomarkers are needed to facilitate therapeutic development. Metalloprotein human superoxide dismutase 1 (SOD1) is known to accumulate and form aggregates in patient neural tissue with familial ALS linked to mutations in their SOD1 gene. Aggregates of SOD1 have also been detected in other forms of ALS, including the sporadic form and the most common familial form linked to abnormal hexanucleotide repeat expansions in the Chromosome 9 open reading frame 72 (C9ORF72) gene. Here, we report …

Development Of A Method For Making Optimal Decisions For Intervention Flexibility During Implementation (Modifi): A Modified Delphi Study, Stephanie K Brewer, Catherine M Corbin, Ana A Baumann, Shannon Wiltsey Stirman, Janine M Jones, Michael D Pullmann, Aaron R Lyon, Modifi Expert Panel

2020-Current year OA Pubs

BACKGROUND: Intervention adaptation is often necessary to improve the fit between evidence-based practices/programs and implementation contexts. Existing frameworks describe intervention adaptation processes but do not provide detailed steps for prospectively designing adaptations, are designed for researchers, and require substantial time and resources to complete. A pragmatic approach to guide implementers through developing and assessing adaptations in local contexts is needed. The goal of this project was to develop Making Optimal Decisions for Intervention Flexibility during Implementation (MODIFI), a method for intervention adaptation that leverages human centered design methods and is tailored to the needs of intervention implementers working in applied …

Cancer-Associated Histone H3 N-Terminal Arginine Mutations Disrupt Prc2 Activity And Impair Differentiation, Benjamin A Nacev, Benjamin A Garcia, Et Al.

2020-Current year OA Pubs

Dysregulated epigenetic states are a hallmark of cancer and often arise from genetic alterations in epigenetic regulators. This includes missense mutations in histones, which, together with associated DNA, form nucleosome core particles. However, the oncogenic mechanisms of most histone mutations are unknown. Here, we demonstrate that cancer-associated histone mutations at arginines in the histone H3 N-terminal tail disrupt repressive chromatin domains, alter gene regulation, and dysregulate differentiation. We find that histone H3R2C and R26C mutants reduce transcriptionally repressive H3K27me3. While H3K27me3 depletion in cells expressing these mutants is exclusively observed on the minor fraction of histone tails harboring the mutations, …

Structural Characterization Of Ligand Binding And Ph-Specific Enzymatic Activity Of Mouse Acidic Mammalian Chitinase, Roberto Efraín Díaz, Andrew K Ecker, Galen J Correy, Pooja Asthana, Iris D Young, Bryan Faust, Michael C Thompson, Ian B Seiple, Steven Van Dyken, Richard M Locksley, James S Fraser

2020-Current year OA Pubs

Chitin is an abundant biopolymer and pathogen-associated molecular pattern that stimulates a host innate immune response. Mammals express chitin-binding and chitin-degrading proteins to remove chitin from the body. One of these proteins, Acidic Mammalian Chitinase (AMCase), is an enzyme known for its ability to function under acidic conditions in the stomach but is also active in tissues with more neutral pHs, such as the lung. Here, we used a combination of biochemical, structural, and computational modeling approaches to examine how the mouse homolog (mAMCase) can act in both acidic and neutral environments. We measured kinetic properties of mAMCase activity across …

A Longitudinal Mri And Tspo Pet-Based Investigation Of Brain Region-Specific Neuroprotection By Diazepam Versus Midazolam Following Organophosphate-Induced Seizures, Brad A Hobson, Douglas J Rowland, Yimeng Dou, Naomi Saito, Zachary T Harmany, Donald A Bruun, Danielle J Harvey, Abhijit J Chaudhari, Joel R Garbow, Pamela J Lein

2020-Current year OA Pubs

Acute poisoning with organophosphorus cholinesterase inhibitors (OPs), such as OP nerve agents and pesticides, can cause life threatening cholinergic crisis and status epilepticus (SE). Survivors often experience significant morbidity, including brain injury, acquired epilepsy, and cognitive deficits. Current medical countermeasures for acute OP poisoning include a benzodiazepine to mitigate seizures. Diazepam was long the benzodiazepine included in autoinjectors used to treat OP-induced seizures, but it is now being replaced in many guidelines by midazolam, which terminates seizures more quickly, particularly when administered intramuscularly. While a direct correlation between seizure duration and the extent of brain injury has been widely reported, …

Prevalence Of Anti-Myelin Oligodendrocyte Glycoprotein Antibodies Across Neuroinflammatory And Neurodegenerative Diseases, Ritu R Trivedi, Angela S Archambault, Clarice Pavlak, Matteo Gastaldi, Claudia Cantoni, Laura Ghezzi, Anne H Cross, Timothy M Miller, Gregory F Wu

2020-Current year OA Pubs

Inflammatory central nervous system (CNS) diseases, such as multiple sclerosis (MS) and myelin oligodendrocyte glycoprotein (MOG) antibody-associated disease (MOGAD), are characterized by humoral immune abnormalities. Anti-MOG antibodies are not specific to MOGAD, with their presence described in MS. Autoantibodies may also be present and play a role in various neurodegenerative diseases. Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease driven by motor neuron dysfunction. While immune involvement in ALS has been recognized, the presence of antibodies targeting CNS myelin antigens has not been established. We aimed to establish a live cell-based assay for quantification of serum anti-MOG IgG1 in …

A Randomized, Double-Blind, Phase 3 Safety And Efficacy Study Of Ridinilazole Versus Vancomycin For Treatment Of Clostridioides Difficile Infection: Clinical Outcomes With Microbiome And Metabolome Correlates Of Response, Pablo C Okhuysen, Erik R Dubberke, Et Al.

2020-Current year OA Pubs

BACKGROUND: Exposure to antibiotics predisposes to dysbiosis and Clostridioides difficile infection (CDI) that can be severe, recurrent (rCDI), and life-threatening. Nonselective drugs that treat CDI and perpetuate dysbiosis are associated with rCDI, in part due to loss of microbiome-derived secondary bile acid (SBA) production. Ridinilazole is a highly selective drug designed to treat CDI and prevent rCDI.

METHODS: In this phase 3 superiority trial, adults with CDI, confirmed with a stool toxin test, were randomized to receive 10 days of ridinilazole (200 mg twice daily) or vancomycin (125 mg 4 times daily). The primary endpoint was sustained clinical response (SCR), …

Through The Cat-Map Gateway: A Brief History Of Cataract Genetics, Alan Shiels

2020-Current year OA Pubs

Clouding of the transparent eye lens, or cataract(s), is a leading cause of visual impairment that requires surgical replacement with a synthetic intraocular lens to effectively restore clear vision. Most frequently, cataract is acquired with aging as a multifactorial or complex trait. Cataract may also be inherited as a classic Mendelian trait-often with an early or pediatric onset-with or without other ocular and/or systemic features. Since the early 1990s, over 85 genes and loci have been genetically associated with inherited and/or age-related forms of cataract. While many of these underlying genes-including those for lens crystallins, connexins, and transcription factors-recapitulate signature …

Identifying Mage-A4-Positive Tumors For Tcr T Cell Therapies In Hla-A∗02-Eligible Patients, Tianjiao Wang, Ramaswamy Govindan, Et Al.

2020-Current year OA Pubs

T cell receptor (TCR) T cell therapies target tumor antigens in a human leukocyte antigen (HLA)-restricted manner. Biomarker-defined therapies require validation of assays suitable for determination of patient eligibility. For clinical trials evaluating TCR T cell therapies targeting melanoma-associated antigen A4 (MAGE-A4), screening in studies NCT02636855 and NCT04044768 assesses patient eligibility based on: (1) high-resolution HLA typing and (2) tumor MAGE-A4 testing via an immunohistochemical assay in HLA-eligible patients. The HLA/MAGE-A4 assays validation, biomarker data, and their relationship to covariates (demographics, cancer type, histopathology, tissue location) are reported here. HLA-A∗02 eligibility was 44.8% (2,959/6,606) in patients from 43 sites across …

Comorbid Neurotrauma Increases Neurodegenerative-Relevant Cognitive, Motor, And Autonomic Dysfunction In Patients With Rapid Eye Movement Sleep Behavior Disorder: A Substudy Of The North American Prodromal Synucleinopathy Consortium, Jonathan E Elliott, Jennifer Mcleland, Yo-El S Ju, Et Al.

2020-Current year OA Pubs

STUDY OBJECTIVES: Rapid eye movement sleep behavior disorder (RBD) is strongly associated with phenoconversion to an overt synucleinopathy, e.g. Parkinson's disease (PD), Lewy body dementia, and related disorders. Comorbid traumatic brain injury (TBI) and posttraumatic stress disorder (PTSD)-henceforth "neurotrauma" (NT)-increase the odds of RBD by ~2.5-fold and are associated with an increased rate of service-connected PD in Veterans. Thus, RBD and NT are both independently associated with PD; however, it is unclear how NT influences neurological function in patients with RBD.

METHODS: Participants ≥18 years with overnight polysomnogram-confirmed RBD were enrolled between 8/2018 to 4/2021 through the North American Prodromal …

Scaling Up A Brief Alcohol Intervention To Prevent Hiv Infection In Vietnam: A Cluster Randomized, Implementation Trial, Sophia M Bartels, Byron J Powell, Et Al.

2020-Current year OA Pubs

BACKGROUND: Evidence-based interventions (EBIs) often address normative behaviors. If a behavior is also common among clinicians, they may be skeptical about the necessity or effectiveness of an EBI. Alternatively, clinicians' attitudes and behaviors may be misaligned, or they may lack the knowledge and self-efficacy to deliver the EBI. Several EBIs address unhealthy alcohol use, a common and often culturally acceptable behavior. But unhealthy alcohol use may be particularly harmful to people with HIV (PWH). Here, we present an implementation trial using an experiential implementation strategy to address clinicians' knowledge, attitudes, and behaviors. Clinicians receive the experiential intervention before they begin …

A Systematic Review And Meta-Analysis, Investigating Dose And Time Of Fluvoxamine Treatment Efficacy For Covid-19 Clinical Deterioration, Death, And Long-Covid Complications, Mani Iyer Prasanth, Dhammika Leshan Wannigama, Angela Michelle Reiersen, Premrutai Thitilertdecha, Anchalee Prasansuklab, Tewin Tencomnao, Sirikalaya Brimson, James Michael Brimson

2020-Current year OA Pubs

There have been 774,075,242 cases of COVID-19 and 7,012,986 deaths worldwide as of January 2024. In the early stages of the pandemic, there was an urgent need to reduce the severity of the disease and prevent the need for hospitalization to avoid stress on healthcare systems worldwide. The repurposing of drugs to prevent clinical deterioration of COVID-19 patients was trialed in many studies using many different drugs. Fluvoxamine (an SSRI and sigma-1 receptor agonist) was initially identified to potentially provide beneficial effects in COVID-19-infected patients, preventing clinical deterioration and the need for hospitalization. Fourteen clinical studies have been carried out …

Inhibitory Roles Of Apolipoprotein E Christchurch Astrocytes In Curbing Tau Propagation Using Human Pluripotent Stem Cell-Derived Models, Rei Murakami, Hirotaka Watanabe, Hideko Hashimoto, Mayu Kashiwagi-Hakozaki, Tadafumi Hashimoto, Celeste M. Karch, Takeshi Iwatsubo, Hideyuki Okano, Dominantly Inherited Alzheimer Network (Dian)

2020-Current year OA Pubs

Genetic variants in the

Tenovin-1, A Selective Sirt1/2 Inhibitor, Attenuates High-Fat Diet-Induced Hepatic Fibrosis Via Inhibition Of Hsc Activation In Zdf Rats, Swati Sharma, Sreevarsha Gali, Amit Kundu, Jae Hyeon Park, Jae-Sung Kim, Hyung Sik Kim

2020-Current year OA Pubs

Type 2 diabetes mellitus (T2DM) increases the risk of non-alcoholic fatty liver disease (NAFLD) progression to advanced stages, especially upon high-fat diet (HFD). HFD-induced hepatic fibrosis can be marked by oxidative stress, inflammation, and activation of hepatic stellate cells. Sirtuin 1/2 (SIRT1/2), NAD-dependent class III histone deacetylases, are involved in attenuation of fibrosis. In our conducted research, TGF-β1-activated LX-2 cells, free fatty acid (FFA)-treated simultaneous co-culture (SCC) cells, and HFD-induced hepatic fibrosis in Zucker diabetic fatty (ZDF) rats, a widely used animal model in the study of metabolic syndromes, were used to evaluate the protective effect of Tenovin-1, a SIRT1/2 …

Outcomes Of Subsequent Antilymphoma Therapies After Second-Line Axicabtagene Ciloleucel Or Standard Of Care In Zuma-7, Armin Ghobadi, Et Al.

2020-Current year OA Pubs

The optimal management of patients with relapsed/refractory large B-cell lymphoma (LBCL) after disease progression or lack of response to second-line (2L) therapy remains unclear. Here, we report outcomes among patients who received subsequent antilymphoma therapy per investigator discretion separately by their randomized 2L arm in ZUMA-7, namely axicabtagene ciloleucel (axi-cel) vs standard of care (SOC). Progression-free survival (PFS) and overall survival (OS) were calculated from 3L therapy initiation. In the SOC arm, 127 of 179 randomized patients (71%) received 3L therapy. Median PFS among those who received 3L cellular immunotherapy (n = 68) vs those who did not (n = …