Prevalence, incidence, and complications of malnutrition in severely injured patients.

Background: Severely injured patients may suffer from acute disease-related or injury-related malnutrition involving a marked inflammatory response. This study investigated the prevalence and incidence of malnutrition and its relation with complications in severely injured patients admitted to the intensive care unit (ICU).

Methods: This observational prospective cohort study included severely injured patients (Injury Severity Score ≥ 16), admitted to the ICU of five level-1 trauma centers in the Netherlands and United States.

Integrative proteogenomic analysis identifies COL6A3-derived endotrophin as a mediator of the effect of obesity on coronary artery disease.

Obesity strongly increases the risk of cardiometabolic diseases, yet the underlying mediators of this relationship are not fully understood. Given that obesity strongly influences circulating protein levels, we investigated proteins mediating the effects of obesity on coronary artery disease, stroke and type 2 diabetes. By integrating two-step proteome-wide Mendelian randomization, colocalization, epigenomics and single-cell RNA sequencing, we identified five mediators and prioritized collagen type VI α3 (COL6A3).

Transposon mediated functional genomic screening for BRAF inhibitor resistance reveals convergent Hippo and MAPK pathway activation events.

Genotype-informed anticancer therapies such as BRAF inhibitors can show remarkable clinical efficacy in BRAF-mutant melanoma; however, drug resistance poses a major hurdle to successful cancer treatment. Many resistance events to targeted therapies have been identified, suggesting a complex path to improve therapeutics. Here, we showed the utility of a piggyBac transposon activation mutagenesis screen for the efficient identification of genes that are resistant to BRAF inhibition in melanoma.

SLC25A38 is required for mitochondrial pyridoxal 5'-phosphate (PLP) accumulation.

Many essential proteins require pyridoxal 5'-phosphate, the active form of vitamin B6, as a cofactor for their activity. These include enzymes important for amino acid metabolism, one-carbon metabolism, polyamine synthesis, erythropoiesis, and neurotransmitter metabolism. A third of all mammalian pyridoxal 5'-phosphate-dependent enzymes are localized in the mitochondria; however, the molecular machinery involved in the regulation of mitochondrial pyridoxal 5'-phosphate levels in mammals remains unknown.

Using artificial intelligence to optimize anti-seizure treatment and EEG-guided decisions in severe brain injury.

Electroencephalography (EEG) is invaluable in the management of acute neurological emergencies. Characteristic EEG changes have been identified in diverse neurologic conditions including stroke, trauma, and anoxia, and the increased utilization of continuous EEG (cEEG) has identified potentially harmful activity even in patients without overt clinical signs or neurologic diagnoses. Manual annotation by expert neurophysiologists is a major resource limitation in investigating the prognostic and therapeutic implications of these EEG patterns and in expanding EEG use to a broader set of patients who are likely to benefit.

Tenzing Assisted Delivery of Aspiration (TADA) technique for thrombectomy of medium vessel occlusions using the Freeclimb 54 catheter: multicenter experience.

Background: Medium vessel occlusions (MeVOs) account for 25-40% of acute ischemic stroke. The Tenzing 5 (Route 92 Medical, San Mateo, California, USA) and FreeClimb 54 (Route 92 Medical, San Mateo, California, USA) catheter is a novel delivery-aspiration catheter combination designed to facilitate aspiration thrombectomy (AT) of MeVOs. We report our clinical experience using the Tenzing assisted delivery of aspiration (TADA) technique with FreeClimb 54 for first-line AT of MeVO.

Clinical outcomes of patients with unsuccessful mechanical thrombectomy versus best medical management of medium vessel occlusion stroke in the middle cerebral artery territory.

Background: Current randomized controlled trials are investigating the efficacy and safety of mechanical thrombectomy (MT) in patients with medium vessel occlusion (MeVO) stroke. Whether best medical management (MM) is more efficient than unsuccessful vessel recanalization during MT remains unknown.

Methods: This was a retrospective cohort study using data from 37 academic centers across North America, Asia, and Europe between September 2017 and July 2021.

Gut microbiomes are largely unchanged when exposed to their amphibian host's latitudinally variable upper thermal limit.

Climate change will increase the frequency and severity of temperature extremes. Links between host thermal physiology and their gut microbiota suggest that organisms' responses to future climates may be mediated by their microbiomes, raising the question of how the thermal environment influences the microbiome itself. Vertebrate gut microbiomes influence the physiological plasticity of their hosts via effects on immunity, metabolism, and nutrient uptake.

US children from non-English-speaking households are less likely to undergo vision testing.

Purpose: To investigate the association between primary household language and vision testing among children living in the United States from 2016 to 2020.

Methods: This analysis used data for children aged 3-17 years from the National Survey of Children's Health (NSCH), combining survey responses from 2016 to 2020. Primary household language and whether vision testing occurred were determined by survey responses.

The Efficacy and Safety of Cardiac Myosin Inhibitors Versus Placebo in Patients with Symptomatic Obstructive Hypertrophic Cardiomyopathy: A Meta-Analysis of Randomized Controlled Trials.

Introduction: Obstructive hypertrophic cardiomyopathy (oHCM) is a genetic disorder characterized by myocardial hypertrophy, which can obstruct left ventricular outflow. Cardiac myosin inhibitors (CMIs) have emerged as a novel therapeutic agent targeting cardiac muscle hypercontractility.

Objective: To compare the efficacy and safety of CMIs mavacamten and aficamten vs.

Regulation of PD-L1 glycosylation and advances in cancer immunotherapy.

Protein glycosylation plays a versatile role in regulating homeostasis, such as cell migration, protein sorting, and the immune response. Drugs aimed at targeting glycosylation have strong implications for immunity enhancement, diagnosis, and cancer regression. Programmed death-ligand 1 (PD-L1), expressed in cancer or antigen-presenting cells, binds to programmed cell death protein 1 (PD-1) and suppresses T cells.

Long term outcomes post-ICD in Chagas cardiomyopathy and non-ischemic cardiomyopathy: A comparative analysis.

Background: Chagas cardiomyopathy (CCM) is a significant cause of ventricular arrhythmias and sudden cardiac death (SCD). Although, implantable cardiac defibrillators (ICD) have been used for all forms of non-ischemic cardiomyopathy (NICM), studies on ICD efficacy in CCM are scarce.

Objective: The present study aims to compare the long-term outcomes, mortality rates, and the occurrence of tachycardia therapies after ICD implantation in patients with CCM and NICM.

Effect of one prophylactic dose of Azithromycin on Bifidobacterium infantis colonization in infants from the Mumta Trial.

Objectives: The effects of antibiotics on the microbiome remain incompletely understood. Azithromycin (AZ) has been shown to improve child survival and infant growth outcomes. This study aimed to assess the impact of AZ on B.

Therapeutic potential of siRNA PMP22-SQ nanoparticles for Charcot-Marie-Tooth 1A neuropathy in rodents and non-human primates.

Small interfering RNA (siRNA) has shown promising results for the treatment of Charcot-Marie-Tooth disease 1A (CMT1A) caused by overexpression of peripheral myelin protein (PMP22), leading to myelin dysfunction and axonal damage. Recently, we developed siRNA PMP22-squalene (SQ) nanoparticles (NPs) for intravenous use. Three consecutive injections of siRNA PMP22-SQ NPs at a cumulative dose of 1.

Causal Estimands for Analyses of Averted and Avertible Outcomes due to Infectious Disease Interventions.

During the coronavirus disease (COVID-19) pandemic, researchers attempted to estimate the number of averted and avertible outcomes due to vaccination campaigns to quantify public health impact. However, the estimands used in these analyses have not been previously formalized. It is also unclear how these analyses relate to the broader framework of direct, indirect, total, and overall causal effects under interference.

Designed mosaic nanoparticles enhance cross-reactive immune responses in mice.

Nanoparticle vaccines displaying combinations of SARS-like betacoronavirus (sarbecovirus) receptor-binding domains (RBDs) could protect against SARS-CoV-2 variants and spillover of zoonotic sarbecoviruses into humans. Using a computational approach, we designed variants of SARS-CoV-2 RBDs and selected 7 natural sarbecovirus RBDs, each predicted to fold properly and abrogate antibody responses to variable epitopes. RBDs were attached to 60-mer nanoparticles to make immunogens displaying two (mosaic-2s), five (mosaic-5), or seven (mosaic-7) different RBDs for comparisons with mosaic-8b, which elicited cross-reactive antibodies and protected animals from sarbecovirus challenges.

Necrotizing enterocolitis vs bowel ischemia of congenital heart disease: Apples and oranges.

Necrotizing enterocolitis (NEC) is a devastating illness with mortality rates approaching 26 ​%, with 4 ​% of patients with congenital heart disease (CHD) receiving this diagnosis. In this retrospective cohort study, the Pediatric Health Information System database was used to compare outcomes among patients with NEC diagnoses between 2019 and 2021 by CHD. The association of clinical factors with the outcomes of interest were compared using multivariable logistic regression.

A low-cost transhumeral prosthesis operated via an ML-assisted EEG-head gesture control system.

Objective Key challenges in upper limb prosthetics include a lack of effective control systems, the often invasive surgical requirements of brain-controlled limbs, and prohibitive costs. As a result, disuse rates remain high despite potential for increased quality of life. To address these concerns, this project developed a low cost, noninvasive transhumeral neuroprosthesis-operated via a combination of electroencephalography (EEG) signals and head gestures.

Impact of disease duration and surgical intervention on arousal networks in temporal lobe epilepsy.

Objective: Epilepsy is a common neurological disease affecting nearly 1% of the global population, and temporal lobe epilepsy (TLE) is the most common type. Patients experience recurrent seizures and chronic cognitive deficits that can impact their quality of life, ability to work, and independence. These cognitive deficits often extend beyond the temporal lobe and are not well understood.

Lewis Base-Enhanced C-H Bond Functionalization Mediated by a Diiron Imido Complex.

Herein, we investigate the effects of ligand design on the nuclearity and reactivity of metal-ligand multiply bonded (MLMB) complexes to access an exclusively bimetallic reaction pathway for C-H bond functionalization. To this end, the diiron alkoxide [Fe(Dbf)] () was treated with 3,5-bis(trifluoromethyl)phenyl azide to access the diiron imido complex [Fe(Dbf)(μ-NCHF)] () that promotes hydrogen atom abstraction (HAA) from a variety of C-H and O-H bond containing substrates. A diiron bis(amide) complex [Fe(Dbf)(μ-NHCHF)(NHCHF)] () was generated, prompting the isolation of the analogous bridging amide terminal alkoxide [Fe(Dbf)(μ-NHCHF)(OCH)] () and the asymmetric pyridine-bound diiron imido [Fe(Dbf)(μ-NCHF)(NCH)] ().

Management of Insomnia in the General Hospital.

The Psychiatric Consultation Service at Massachusetts General Hospital sees medical and surgical inpatients with comorbid psychiatric symptoms and conditions. During their twice-weekly rounds, Dr Stern and other members of the Consultation Service discuss diagnosis and management of hospitalized patients with complex medical or surgical problems who also demonstrate psychiatric symptoms or conditions. These discussions have given rise to rounds reports that will prove useful for clinicians practicing at the interface of medicine and psychiatry.

Myelin ensheathment and drug responses of oligodendrocytes are modulated by stiffness of artificial axons.

Myelination is a key biological process wherein glial cells such as oligodendrocytes wrap myelin around neuronal axons, forming an insulative sheath that accelerates signal propagation down the axon. A major obstacle to understanding myelination is the challenge of visualizing and reproducibly quantifying this inherently three-dimensional process in vitro. To this end, we previously developed artificial axons (AAs), a biocompatible platform consisting of 3D-printed hydrogel-based axon mimics designed to more closely recapitulate the micrometer-scale diameter and sub-kilopascal mechanical stiffness of biological axons.