Effect of nirmatrelvir/ritonavir (Paxlovid) on hospitalization among adults with COVID-19: An electronic health record-based target trial emulation from N3C.

Background: Nirmatrelvir with ritonavir (Paxlovid) is indicated for patients with Coronavirus Disease 2019 (COVID-19) who are at risk for progression to severe disease due to the presence of one or more risk factors. Millions of treatment courses have been prescribed in the United States alone. Paxlovid was highly effective at preventing hospitalization and death in clinical trials.

Inhibition of the Notch signal transducer CSL by Pkc53E-mediated phosphorylation to fend off parasitic immune challenge in .

Notch signalling activity regulates hematopoiesis in and vertebrates alike. Parasitoid wasp infestation of larvae, however, requires a timely downregulation of Notch activity to allow the formation of encapsulation-active blood cells. Here, we show that the CSL transcription factor Suppressor of Hairless [Su(H)] is phosphorylated at Serine 269 in response to parasitoid wasp infestation.

Insights from an N3C RECOVER EHR-based cohort study characterizing SARS-CoV-2 reinfections and Long COVID.

Background: Although the COVID-19 pandemic has persisted for over 3 years, reinfections with SARS-CoV-2 are not well understood. We aim to characterize reinfection, understand development of Long COVID after reinfection, and compare severity of reinfection with initial infection.

Methods: We use an electronic health record study cohort of over 3 million patients from the National COVID Cohort Collaborative as part of the NIH Researching COVID to Enhance Recovery Initiative.

Novel Genome-Engineered Alleles Differentially Affect Lateral Inhibition and Cell Dichotomy Processes during Bristle Organ Development.

Hairless (H) encodes the major antagonist in the Notch signaling pathway, which governs cellular differentiation of various tissues in . By binding to the Notch signal transducer Suppressor of Hairless (Su(H)), H assembles repressor complexes onto Notch target genes. Using genome engineering, three new alleles, , and were generated and a phenotypic series was established by several parameters, reflecting the residual H-Su(H) binding capacity.

Numerous Serine/Threonine Kinases Affect Blood Cell Homeostasis in .

Blood cells in serve primarily innate immune responses. Various stressors influence blood cell homeostasis regarding both numbers and the proportion of blood cell types. The principle molecular mechanisms governing hematopoiesis are conserved amongst species and involve major signaling pathways like Notch, Toll, JNK, JAK/Stat or RTK.

Effect of Paxlovid Treatment During Acute COVID-19 on Long COVID Onset: An EHR-Based Target Trial Emulation from the N3C and RECOVER Consortia.

Preventing and treating post-acute sequelae of SARS-CoV-2 infection (PASC), commonly known as Long COVID, has become a public health priority. In this study, we examined whether treatment with Paxlovid in the acute phase of COVID-19 helps prevent the onset of PASC. We used electronic health records from the National Covid Cohort Collaborative (N3C) to define a cohort of 426,352 patients who had COVID-19 since April 1, 2022, and were eligible for Paxlovid treatment due to risk for progression to severe COVID-19.

Correction to "Manganese Catalyzed Dehydrogenative Synthesis of Urea Derivatives and Polyureas".

[This corrects the article DOI: 10.1021/acscatal.2c00850.

Long COVID risk and pre-COVID vaccination in an EHR-based cohort study from the RECOVER program.

Long COVID, or complications arising from COVID-19 weeks after infection, has become a central concern for public health experts. The United States National Institutes of Health founded the RECOVER initiative to better understand long COVID. We used electronic health records available through the National COVID Cohort Collaborative to characterize the association between SARS-CoV-2 vaccination and long COVID diagnosis.

Effect of Nirmatrelvir/Ritonavir (Paxlovid) on Hospitalization among Adults with COVID-19: an EHR-based Target Trial Emulation from N3C.

This study leverages electronic health record data in the National COVID Cohort Collaborative's (N3C) repository to investigate disparities in Paxlovid treatment and to emulate a target trial assessing its effectiveness in reducing COVID-19 hospitalization rates. From an eligible population of 632,822 COVID-19 patients seen at 33 clinical sites across the United States between December 23, 2021 and December 31, 2022, patients were matched across observed treatment groups, yielding an analytical sample of 410,642 patients. We estimate a 65% reduced odds of hospitalization among Paxlovid-treated patients within a 28-day follow-up period, and this effect did not vary by patient vaccination status.

SARS-CoV-2 Reinfection is Preceded by Unique Biomarkers and Related to Initial Infection Timing and Severity: an N3C RECOVER EHR-Based Cohort Study.

Although the COVID-19 pandemic has persisted for over 2 years, reinfections with SARS-CoV-2 are not well understood. We use the electronic health record (EHR)-based study cohort from the National COVID Cohort Collaborative (N3C) as part of the NIH Researching COVID to Enhance Recovery (RECOVER) Initiative to characterize reinfection, understand development of Long COVID after reinfection, and compare severity of reinfection with initial infection. We validate previous findings of reinfection incidence (5.

The Binding of CSL Proteins to Either Co-Activators or Co-Repressors Protects from Proteasomal Degradation Induced by MAPK-Dependent Phosphorylation.

The primary role of Notch is to specify cellular identities, whereby the cells respond to amazingly small changes in Notch signalling activity. Hence, dosage of Notch components is crucial to regulation. Central to Notch signal transduction are CSL proteins: together with respective cofactors, they mediate the activation or the silencing of Notch target genes.

Long COVID Risk and Pre-COVID Vaccination: An EHR-Based Cohort Study from the RECOVER Program.

Importance: Characterizing the effect of vaccination on long COVID allows for better healthcare recommendations.

Objective: To determine if, and to what degree, vaccination prior to COVID-19 is associated with eventual long COVID onset, among those a documented COVID-19 infection.

Design Settings And Participants: Retrospective cohort study of adults with evidence of COVID-19 between August 1, 2021 and January 31, 2022 based on electronic health records from eleven healthcare institutions taking part in the NIH Researching COVID to Enhance Recovery (RECOVER) Initiative, a project of the National Covid Cohort Collaborative (N3C).

[Bouldering: a sport with a high risk of intraarticular fractures].

Bouldering is a famous new sport with an increasing number of athletes. It became an Olympic sport in 2020. As no major sports equipment is required, everybody can take up bouldering even with little knowledge.

Dug: a semantic search engine leveraging peer-reviewed knowledge to query biomedical data repositories.

Motivation: As the number of public data resources continues to proliferate, identifying relevant datasets across heterogenous repositories is becoming critical to answering scientific questions. To help researchers navigate this data landscape, we developed Dug: a semantic search tool for biomedical datasets utilizing evidence-based relationships from curated knowledge graphs to find relevant datasets and explain why those results are returned.

Results: Developed through the National Heart, Lung and Blood Institute's (NHLBI) BioData Catalyst ecosystem, Dug has indexed more than 15 911 study variables from public datasets.

Using Named Entity Recognition to Identify Substances Used in the Self-medication of Opioid Withdrawal: Natural Language Processing Study of Reddit Data.

Background: The cessation of opioid use can cause withdrawal symptoms. People often continue opioid misuse to avoid these symptoms. Many people who use opioids self-treat withdrawal symptoms with a range of substances.

Incorporation of near-real-time hospital occupancy data to improve hospitalization forecast accuracy during the COVID-19 pandemic.

Public health decision makers rely on hospitalization forecasts to inform COVID-19 pandemic planning and resource allocation. Hospitalization forecasts are most relevant when they are accurate, made available quickly, and updated frequently. We rapidly adapted an agent-based model (ABM) to provide weekly 30-day hospitalization forecasts (i.

Can social media monitoring help identify the next EVALI? An examination of Reddit posts about vitamin E acetate and Dank Vapes.

Background: Scientists identified vitamin E acetate (VEA) and "Dank Vapes" (a fake brand of tetrahydrocannabinol [THC] vaping products) as contributors to the 2019-2020 outbreak of e-cigarette, or vaping, product use-associated lung injury (EVALI). On social media, people who post about vaping or THC discussed the causes of EVALI. We examined whether Reddit conversations may have served as early signals of the outbreak.

The Membrane-Bound Notch Regulator Mnr Supports Notch Cleavage and Signaling Activity in .

The Notch signaling pathway is pivotal to cellular differentiation. Activation of this pathway involves proteolysis of the Notch receptor and the release of the biologically active Notch intracellular domain, acting as a transcriptional co-activator of Notch target genes. While the regulation of Notch signaling dynamics at the level of ligand-receptor interaction, endocytosis, and transcriptional regulation has been well studied, little is known about factors influencing Notch cleavage.

Lessons learned from the rapid development of a statewide simulation model for predicting COVID-19's impact on healthcare resources and capacity.

The first case of COVID-19 was detected in North Carolina (NC) on March 3, 2020. By the end of April, the number of confirmed cases had soared to over 10,000. NC health systems faced intense strain to support surging intensive care unit admissions and avert hospital capacity and resource saturation.

The treatment of posterolateral knee instability with combined arthroscopic popliteus bypass and PCL reconstruction provides good-to-excellent clinical results in the mid-term follow-up.

Purpose: The purpose of this study was to evaluate the clinical outcomes of patients who were treated with an arthroscopic popliteus bypass (PB) technique, in cases of a posterolateral rotational instability (PLRI) and a concomitant posterior cruciate ligament (PCL) injury of the knee.

Methods: This was a retrospective case series in which 23 patients were clinically evaluated after a minimum of 2 years following arthroscopic PB and combined PCL reconstruction. Lysholm, Tegner and Knee Injury and Osteoarthritis Outcome scores as well as visual analog scales (VAS) for joint function and pain were evaluated.

Increases in Naloxone Administrations by Emergency Medical Services Providers During the COVID-19 Pandemic: Retrospective Time Series Study.

Background: The opioid crisis in the United States may be exacerbated by the COVID-19 pandemic. Increases in opioid use, emergency medical services (EMS) runs for opioid-related overdoses, and opioid overdose deaths have been reported. No study has examined changes in multiple naloxone administrations, an indicator of overdose severity, during the COVID-19 pandemic.

Limited Availability of General Co-Repressors Uncovered in an Overexpression Context during Wing Venation in .

Cell fate is determined by the coordinated activity of different pathways, including the conserved Notch pathway. Activation of Notch results in the transcription of Notch targets that are otherwise silenced by repressor complexes. In , the repressor complex comprises the transcription factor Suppressor of Hairless (Su(H)) bound to the Notch antagonist Hairless (H) and the general co-repressors Groucho (Gro) and C-terminal binding protein (CtBP).

DNA methylation study of Huntington's disease and motor progression in patients and in animal models.

Although Huntington's disease (HD) is a well studied Mendelian genetic disorder, less is known about its associated epigenetic changes. Here, we characterize DNA methylation levels in six different tissues from 3 species: a mouse huntingtin (Htt) gene knock-in model, a transgenic HTT sheep model, and humans. Our epigenome-wide association study (EWAS) of human blood reveals that HD mutation status is significantly (p < 10) associated with 33 CpG sites, including the HTT gene (p = 6.

The Popliteus Bypass provides superior biomechanical properties compared to the Larson technique in the reconstruction of combined posterolateral corner and posterior cruciate ligament injury.

Purpose: This study aimed to compare the biomechanical properties of the popliteus bypass against the Larson technique for the reconstruction of a combined posterolateral corner and posterior cruciate ligament injury.

Methods: In 18 human cadaver knees, the kinematics for 134 N posterior loads, 10 Nm varus loads, and 5 Nm external rotational loads in 0°, 20°, 30°, 60,° and 90° of knee flexion were measured using a robotic and optical tracking system. The (1) posterior cruciate ligament, (2) meniscofibular/-tibial fibers, (3) popliteofibular ligament (PFL), (4) popliteotibial fascicle, (5) popliteus tendon, and (6) lateral collateral ligament were cut, and the measurements were repeated.