Recognition and cleavage of human tRNA methyltransferase TRMT1 by the SARS-CoV-2 main protease.

The SARS-CoV-2 main protease (M or Nsp5) is critical for production of viral proteins during infection and, like many viral proteases, also targets host proteins to subvert their cellular functions. Here, we show that the human tRNA methyltransferase TRMT1 is recognized and cleaved by SARS-CoV-2 M. TRMT1 installs the ,-dimethylguanosine (m2,2G) modification on mammalian tRNAs, which promotes cellular protein synthesis and redox homeostasis.

Corrigendum: Inhibition of coronavirus HCoV-OC43 by targeting the eIF4F complex.

[This corrects the article DOI: 10.3389/fphar.2022.

Engineering synthetic phosphorylation signaling networks in human cells.

Protein phosphorylation signaling networks have a central role in how cells sense and respond to their environment. We engineered artificial phosphorylation networks in which reversible enzymatic phosphorylation cycles were assembled from modular protein domain parts and wired together to create synthetic phosphorylation circuits in human cells. Our design scheme enabled model-guided tuning of circuit function and the ability to make diverse network connections; synthetic phosphorylation circuits can be coupled to upstream cell surface receptors to enable fast-timescale sensing of extracellular ligands, and downstream connections can regulate gene expression.

Resolution of selective fetal growth restriction after laser surgery for twin-to-twin transfusion syndrome can be predicted by predisease growth discordance.

Objective: To determine if the resolution of fetal growth discordance after laser surgery in pregnancies with twin-to-twin transfusion syndrome (TTTS) and coexisting selective fetal growth restriction (sFGR) can be predicted by estimated fetal weight (EFW) discordance recorded prior to the development of TTTS (pre-TTTS).

Methods: This was a single-center, retrospective analysis of prospectively collected data on monochorionic twins with concurrent TTTS and sFGR that underwent laser surgery and had available growth ultrasound records from a pre-TTTS ultrasound evaluation. Maternal demographics, pregnancy characteristics and birth outcomes were compared between three outcome groups: double twin survival with resolved sFGR determined by birth weight discordance (BWD) < 20%; double twin survival with ongoing sFGR determined by BWD ≥ 20%; and single or double fetal demise after laser surgery.

Estimated Vaccine Effectiveness for Pediatric Patients With Severe Influenza, 2015-2020.

Importance: Increasing the understanding of vaccine effectiveness (VE) against levels of severe influenza in children could help increase uptake of influenza vaccination and strengthen vaccine policies globally.

Objective: To investigate VE in children by severity of influenza illness.

Design, Setting, And Participants: This case-control study with a test-negative design used data from 8 participating medical centers located in geographically different US states in the New Vaccine Surveillance Network from November 6, 2015, through April 8, 2020.

Pediatric Orbital High-Grade B-Cell Lymphoma: A Case Report and Review of the Literature.

Ocular involvement of lymphoma may present as a primary orbital or intraocular lymphoma or as a manifestation of metastatic disease. Involvement of various ocular structures may be difficult to diagnose due to its rarity and nonspecific clinical presentation. Primary high-grade B-cell lymphoma with MYC and BCL2 rearrangements of the orbit has rarely been reported in the adult population and has not previously been reported in the pediatric population.

Dataset for gastrointestinal tract segmentation on serial MRIs for abdominal tumor radiotherapy.

Purpose: Integrated MRI and linear accelerator systems (MR-Linacs) provide superior soft tissue contrast, and the capability of adapting radiotherapy plans to changes in daily anatomy. In this dataset, serial MRIs of the abdomen of patients undergoing radiotherapy were collected and the luminal gastro-intestinal tract was segmented to support an online segmentation algorithm competition. This dataset may be further utilized by radiation oncologists, medical physicists, and data scientists to further improve auto segmentation algorithms.

Design of allosteric modulators that change GPCR G protein subtype selectivity.

G protein-coupled receptors (GPCRs), the largest family of drug targets, can signal through 16 subtypes of Gα proteins. Biased compounds that selectively activate therapy-relevant pathways promise to be safer, more effective medications. The determinants of bias are poorly understood, however, and rationally-designed, G protein-subtype-selective compounds are lacking.

Effectiveness of ceftazidime-avibactam versus ceftolozane-tazobactam for multidrug-resistant Pseudomonas aeruginosa infections in the USA (CACTUS): a multicentre, retrospective, observational study.

Background: Ceftolozane-tazobactam and ceftazidime-avibactam are preferred treatment options for multidrug-resistant Pseudomonas aeruginosa infections; however, real-world comparative effectiveness studies are scarce. Pharmacokinetic and pharmacodynamic differences between the agents might affect clinical response rates. We aimed to compare the effectiveness of ceftolozane-tazobactam and ceftazidime-avibactam for treatment of invasive multidrug-resistant P aeruginosa infections.

Antiviral Use Among Children Hospitalized With Laboratory-Confirmed Influenza Illness: A Prospective, Multicenter Surveillance Study.

Background: Guidelines state that all hospitalized children with suspected or confirmed influenza receive prompt treatment with influenza-specific antivirals. We sought to determine the frequency of, and factors associated with, antiviral receipt among hospitalized children.

Methods: We conducted active surveillance of children presenting with fever or respiratory symptoms from 1 December 2016 to 31 March 2020 at 7 pediatric medical centers in the New Vaccine Surveillance Network.

Perinatal Outcomes in Appropriately Grown Monochorionic Diamniotic Twins With Intermittent Absent and Reversed End-Diastolic Umbilical Artery Flow Compared to Selective Fetal Growth Restriction Type III.

Objectives: Umbilical artery Doppler intermittent absent and reversed end-diastolic flow (iAREDF) is associated with increased perinatal morbidity and mortality in monochorionic twins with selective fetal growth restriction. The clinical significance of umbilical artery iAREDF in appropriately grown monochorionic twins is not well described.

Methods: This is a single-institution retrospective cohort study describing characteristics and outcomes of monochorionic diamniotic twins with appropriate for gestational age growth and umbilical artery iAREDF in comparison to monochorionic diamniotic twins with selective fetal growth restriction and iAREDF, or sFGR type III.

Elevated body mass index and obesity are associated with pain-associated psychological distress in patients with hip pain.

Introduction: Little research has investigated the relationship between musculoskeletal pain and body mass index (BMI) in the context of pain-associated psychological distress. This study aims to determine if independent associations exist between BMI, obesity, demographic variables, and psychological distress in patients presenting with hip pain.

Materials And Methods: Using a retrospective cross-sectional study design, 428 patients completed the Optimal Screening for Prediction of Referral and Outcome Yellow Flag (OSPRO-YF) and were categorized into pain-associated psychological distress phenotypes using latent class analysis.

Decision-making in borderline hip dysplasia and concomitant femoracetabular impingement syndrome: using a discrete choice experiment to explore patient preferences.

Decision-making regarding surgical treatment of patients showing radiographic evidence of femoroacetabular impingement syndrome (FAIS) in the setting of borderline hip dysplasia (BHD) remains a challenge as there is no consensus on treatment in current literature. When medical evidence is unclear, understanding patient preferences becomes particularly important in deciding the optimal treatment for each patient. The purpose of this study was to measure the patient-determined importance of factors surrounding surgical treatment of FAIS in BHD.

Antimicrobial prescribing practices for enteric bacterial infections in an integrated health care system, Wisconsin, 2004-2017.

Background: Few studies have evaluated antibiotic prescribing practices for bacterial enteric infections. Unnecessary antibiotics can result in adverse events and contribute to the emergence of antimicrobial resistance. We assessed treatment practices among patients with laboratory-confirmed enteric infections in a regional healthcare system in Wisconsin, USA.

Targeting eIF4G1-dependent translation in melanoma.

Elevated expression of components of eIF4F translation initiation complex has been documented in cancer, resulting in enhanced translation of mRNAs encoding pro-tumorigenic factors, including oncogenic proteins. We previously identified SBI-756, a small molecule that interferes with the eIF4F assembly and overcomes melanoma resistance to BRAF inhibitors. SBI-756 enhanced anti-tumor immunity in pancreatic cancer and was effective in the treatment of diffuse large B cell lymphoma.

Design of allosteric modulators that change GPCR G protein subtype selectivity.

G protein-coupled receptors (GPCRs), the largest family of drug targets, can signal through 16 subtypes of Gα proteins. Biased compounds that selectively activate therapy-relevant pathways promise to be safer, more effective medications. The determinants of bias are poorly understood, however, and rationally-designed, G protein-subtype-selective compounds are lacking.

Mode of injury and level of synovitis alter inflammatory chondrocyte gene expression and associated pathways.

Although various joint injuries result in post-traumatic osteoarthritis (PTOA), differences in chondrocyte response to specific injuries, such as blunt compression or fracture, are unclear. Furthermore, the role of underlying joint inflammation, or synovitis, is often not considered. We investigated how injury mechanisms and underlying synovitis affect chondrocyte gene expression using osteochondral injury models with synovial co-culture.

Revisiting Clements and Gleason: Insights from Plant Distributions on Pikes Peak, Clements's Life-Long Study Site.

AbstractHow do species' distributions respond to their environments? This question was at the heart of the Clements-Gleason controversy, ecology's most famous debate. Do species respond to the environment in concerted ways, leading to distinct and cohesive assemblages (the Clementsian paradigm), or do species respond to the environment independently (the Gleasonian paradigm)? Using plant occurrences along the elevation gradient of Pikes Peak (Colorado) as a lens through which to gain insight into Clements's perspectives on the debate, we formally test for community patterns along this gradient using a modern framework unavailable at the time of Clements and Gleason. The Pikes Peak region was Clements's study area for more than 40 years, where he established a research lab and distributed sites along the elevational gradient.

Underutilization of Influenza Antiviral Treatment Among Children and Adolescents at Higher Risk for Influenza-Associated Complications - United States, 2023-2024.

Annually, tens of thousands of U.S. children and adolescents are hospitalized with seasonal influenza virus infection.

Preventing Influenza Virus Infection and Severe Influenza Among Pregnant People and Infants.

The landscape of research on the benefits of influenza vaccines and antivirals to protect pregnant persons and infants has increased in recent years, while influenza vaccination rates and antiviral usage have declined. Pregnant people and infants <6 months of age are at increased risk of hospitalization with influenza, making protection of this population essential. Maternal influenza vaccination at any time during pregnancy is the best way to reduce the risk of influenza and severe influenza in both pregnant people and their infants <6 months of age.

An open-source, battery-powered, low-cost, and dual-channel pneumatic pulse generator for microfluidic cell-stretch assays.

Cells in the body are regularly subjected to mechanical forces that influence their biological fate in terms of morphology, gene expression, and differentiation. The current gold standard method to replicate these effects in vitro is to culture cells on devices with elastic substrates and to impart mechanical stretch using mechanical or pneumatic pull-push methods. Microfluidic device designs offer several advantages in this context for general uniform and controlled stretching.

Pediatric Clinical Influenza Disease by Type and Subtype 2015-2020: A Multicenter, Prospective Study.

Background: Previous investigations into clinical signs and symptoms associated with influenza types and subtypes have not definitively established differences in the clinical presentation or severity of influenza disease.

Methods: The study population included children 0 through 17 years old enrolled at 8 New Vaccine Surveillance Network sites between 2015 and 2020 who tested positive for influenza virus by molecular testing. Demographic and clinical data were collected for study participants via parent/guardian interview and medical chart review.

Selective degradation of phage RNAs by the Csm6 ribonuclease provides robust type III CRISPR immunity in Streptococcus thermophilus.

Type III CRISPR immune systems bind viral or plasmid RNA transcripts and activate Csm3/Cmr4 and Cas10 nucleases to uniquely cleave both invader RNA and DNA, respectively. Additionally, type III effector complexes generate cyclic oligoadenylate (cOA) signaling molecules to activate trans-acting, auxiliary Csm6/Csx1 ribonucleases, previously proposed to be non-specific in their in vivo RNA cleavage preference. Despite extensive in vitro studies, the nuclease requirements of type III systems in their native contexts remain poorly understood.