Maize lethal necrosis (MLN) is a devastating disease of maize caused by synergy between two viruses: maize chlorotic mottle virus (MCMV) and a potyvirus, often sugarcane mosaic virus (SCMV). Throughout the 2010s, severe MLN outbreaks occurred in East Africa including Kenya, Rwanda, and Ethiopia. Previous studies have shown extensive sequence diversity among SCMV isolates collected from this region.
View Article and Find Full Text PDFLibrary screening and selection methods can determine the binding activities of individual members of large protein libraries given a physical link between protein and nucleotide sequence, which enables identification of functional molecules by DNA sequencing. However, the solution properties of individual protein molecules cannot be probed using such approaches because they are completely altered by DNA attachment. Mass spectrometry enables parallel evaluation of protein properties amenable to physical fractionation such as solubility and oligomeric state, but current approaches are limited to libraries of 1,000 or fewer proteins.
View Article and Find Full Text PDFIntroduction: Inhaled corticosteroids (ICS) can improve clinical outcomes in patients with chronic obstructive pulmonary disease (COPD) and eosinophilic airway inflammation, but they also increase the risk of side effects like pneumonia. Blood eosinophils guide ICS use, though evidence is limited. The predictors of treatment REsponse to ICS in COPD: a randomised controlled trials (RCTs) individual participant Data re-Evaluation (ICS-RECODE) research programme will leverage data from large RCTs to identify patients who benefit most from ICS with minimal risk.
View Article and Find Full Text PDFReplication rates and virulence of pathogens are hypothesised to evolve in response to varying intensity of transmission and competition among genotypes. Under exponential growth conditions in culture, clinical isolates of the malaria parasite Plasmodium falciparum have variable intrinsic multiplication rates, but comparisons of samples from different areas are needed. To analyse parasites from an area of low endemicity, Malaysian clinical isolates cryopreserved prior to malaria elimination were studied.
View Article and Find Full Text PDFJ Neonatal Perinatal Med
November 2024
Background: Congenital diaphragmatic hernia (CDH) affects more than 1100 newborns in the United States each year. Severity of clinical presentation is highly variable. Standardized care improves outcomes by promoting consistency in decision-making and clarifying goals of treatment, but CDH management has not yet been standardized.
View Article and Find Full Text PDFImmune receptors have emerged as critical therapeutic targets for cancer immunotherapy. Designed protein binders can have high affinity, modularity, and stability and hence could be attractive components of protein therapeutics directed against these receptors, but traditional Rosetta based protein binder methods using small globular scaffolds have difficulty achieving high affinity on convex targets. Here we describe the development of helical concave scaffolds tailored to the convex target sites typically involved in immune receptor interactions.
View Article and Find Full Text PDFThe precise staging of non-small cell lung cancer (NSCLC) determines its initial treatment and provides more accurate prognostic information for patients. The aim of this cohort study was to determine pre- and post-operative mediastinal nodal staging agreement and its effect on 2-year survival. A retrospective multi-centre cohort study was performed, using prospectively collected and pre-defined data from weekly lung cancer multidisciplinary team (MDT) meetings in 11 hospitals.
View Article and Find Full Text PDFBackground: Interfacility transfer is an integral component of the modern health care system. However, there are no commonly agreed-upon standards for interfacility processes or for patient engagement and shared decision-making in transfer, and little is known about their experience. This study used qualitative methods to better understand the patient and care partner experience with interfacility emergency department (ED)-to-ED transfer.
View Article and Find Full Text PDFThe Mendelian Phenotype Search Engine (MPSE), a clinical decision support tool using Natural Language Processing and Machine Learning, helped neonatologists expedite decisions to whole genome sequencing (WGS) to diagnose patients in the neonatal intensive care unit. After the MPSE was introduced, utilization of WGS increased, time to ordering WGS decreased, and WGS diagnostic yield increased.
View Article and Find Full Text PDFBackground: Non-proliferative and proliferative diabetic retinopathy are common complications of diabetes and a major cause of sight loss. Anti-vascular endothelial growth factor drugs represent a treatment option for people with diabetic retinopathy and are routinely used to treat various other eye conditions. However, anti-vascular endothelial growth factor drugs are expensive relative to current care options, and it is unclear whether this additional cost is justified when the immediate risk of vision loss is lower compared to patients with more aggressive ophthalmological conditions.
View Article and Find Full Text PDFBackground: Emergency tracheal intubation is a common and high-risk procedure. Ketamine and etomidate are sedative medicines commonly used to induce anesthesia for emergency tracheal intubation, but whether the induction medication used affects patient outcomes is uncertain.
Research Question: Does the use of ketamine for induction of anesthesia decrease the incidence of death among adults undergoing emergency tracheal intubation, compared to the use of etomidate?
Study Design And Methods: The Randomized trial of Sedative choice for Intubation (RSI) is a pragmatic, multicenter, unblinded, parallel-group, randomized trial being conducted in 14 sites (6 emergency departments and 8 intensive care units) in the United States.
Snakebite envenoming remains a devastating and neglected tropical disease, claiming over 100,000 lives annually and causing severe complications and long-lasting disabilities for many more. Three-finger toxins (3FTx) are highly toxic components of elapid snake venoms that can cause diverse pathologies, including severe tissue damage and inhibition of nicotinic acetylcholine receptors, resulting in life-threatening neurotoxicity. At present, the only available treatments for snakebites consist of polyclonal antibodies derived from the plasma of immunized animals, which have high cost and limited efficacy against 3FTxs.
View Article and Find Full Text PDFBackground: Pediatric respiratory syncytial virus (RSV)-related acute lower respiratory tract infection (LRTI) commonly requires hospitalization. The Clinical Progression Scale Pediatrics (CPS-Ped) measures level of respiratory support and degree of hypoxia across a range of disease severity, but it has not been applied in infants hospitalized with severe RSV-LRTI.
Methods: We analyzed data from a prospective surveillance registry of infants hospitalized for RSV-related complications across 39 U.
Background: Use of long-acting, reversible contraceptives has increased over the past 20 years, but an understanding of how they could influence cancer risk is limited.
Methods: We conducted a nested case-control study among a national cohort of Australian women (n = 176 601 diagnosed with cancer between 2004 and 2013; 882 999 matched control individuals) to investigate the associations between the levonorgestrel intrauterine system, etonogestrel implants, depot-medroxyprogesterone acetate and cancer risk and compared these results with the oral contraceptive pill. We used conditional logistic regression to estimate odds ratios (OR) and 95% confidence intervals (CI).
Molecular profiling (MP), which involves testing tissue, blood, or other body fluids to identify biomarkers, has become increasingly important in cancer treatment. Genomic tumor sequencing, a specific type of MP, is commonly used to identify specific gene variants or proteins that can be targeted for treatment. Germline testing is also routinely recommended for certain cancers.
View Article and Find Full Text PDFBackground: Patients with cancer routinely undergo genomic tumor sequencing, a component of molecular profiling (MP), to better characterize their cancer and identify potential targetable alterations. Targeted treatments potentially confer higher response rates and better efficacy. With increasing complexity, patients may require detailed explanations of MP results.
View Article and Find Full Text PDFIntroduction: Vaccine mandates have been used to minimize the duty days lost and deaths attributable to infectious disease among active duty Service members (ADSMs). In response to the global COVID-19 pandemic, in August 2021, the U.S.
View Article and Find Full Text PDFBackground: To maintain standing balance, vestibular cues are processed and integrated with other sensorimotor signals to produce appropriate motor adjustments. Whole-body vestibular-driven postural responses are context-dependent and transformed based upon head and foot posture. Previous reports indicate the importance of intrinsic foot muscles during standing, but it is unclear how vestibular-driven responses of these muscles are modulated by alterations in stability and head posture.
View Article and Find Full Text PDFBackground: Blood clot formation, triggered by vascular injury, is crucial for hemostasis and thrombosis. Blood clots are composed mainly of fibrin fibers, platelets, and red blood cells (RBCs). Recent studies show that clot surfaces also develop a fibrin film, which provides protection against wound infection and retains components such as RBCs within the clot.
View Article and Find Full Text PDFThe significance of multiplication rate variation in malaria parasites needs to be determined, particularly for Plasmodium falciparum, the species that causes most virulent infections. To investigate this, parasites from cases presenting to hospital in The Gambia and from local community infections were culture-established and then tested under exponential growth conditions in a standardised six-day multiplication rate assay. The multiplication rate distribution was lower than seen previously in clinical isolates from another area in West Africa where infection is more highly endemic.
View Article and Find Full Text PDFImportance: 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.
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.
Background: Diabetic retinopathy is a major cause of sight loss in people with diabetes. The most severe form, proliferative diabetic retinopathy, carries a high risk of vision loss, vitreous haemorrhage, macular oedema and other harms. Panretinal photocoagulation is the primary treatment for proliferative diabetic retinopathy.
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