Early achievement of hemostasis defined by transfusion velocity: A possible mechanism for whole blood survival benefit.

Introduction: Whole blood resuscitation is associated with survival benefits in observational cohort studies. The mechanisms responsible for outcome benefits have not been adequately determined. We sought to characterize the achievement of hemostasis across patients receiving early whole blood versus component resuscitation.

Genome-wide profiling of tRNA modifications by Induro-tRNAseq reveals coordinated changes.

While all native tRNAs undergo extensive post-transcriptional modifications as a mechanism to regulate gene expression, mapping these modifications remains challenging. The critical barrier is the difficulty of readthrough of modifications by reverse transcriptases (RTs). Here we use Induro-a new group-II intron-encoded RT-to map and quantify genome-wide tRNA modifications in Induro-tRNAseq.

Protocol for the generation of HLF+ HOXA+ human hematopoietic progenitor cells from pluripotent stem cells.

Hematopoietic stem cells (HSCs) generate blood and immune cells. Here, we present a protocol to differentiate human pluripotent stem cells (hPSCs) into hematopoietic progenitors that express the signature HSC transcription factors HLF, HOXA5, HOXA7, HOXA9, and HOXA10. hPSCs are dissociated, seeded, and then sequentially differentiated into posterior primitive streak, lateral mesoderm, artery endothelium, hemogenic endothelium, and hematopoietic progenitors through the sequential addition of defined, serum-free media.

Spatial variations in urban woodland cooling between background climates.

Urban woodland composition and configuration have strong associations with land surface temperatures (LST), but the evidence is contradictory due to different spatial scales, regional climate zones, woodland types and urban contexts. In this study, we analyse associations between urban woodland and LST within and between five cities in different Köppen climate zones. Our consistent methodology is framed around local climate zones and conducted at a fine spatial scale.

Fluid flow impacts endothelial-monocyte interactions in a model of vascular inflammatory fibrosis.

The aberrant vascular response associated with tendon injury results in circulating immune cell infiltration and a chronic inflammatory feedback loop leading to poor healing outcomes. Studying this dysregulated tendon repair response in human pathophysiology has been historically challenging due to the reliance on animal models. To address this, our group developed the human tendon-on-a-chip (hToC) to model cellular interactions in the injured tendon microenvironment; however, this model lacked the key element of physiological flow in the vascular compartment.

COVID-19 Vaccine Booster Dose Fails to Enhance Antibody Response to Omicron Variant in Reinfected Healthcare Workers.

The emergence of new variants and diverse vaccination regimens have raised uncertainty about vaccine effectiveness against SARS-CoV-2. This study aims to investigate the impact of Omicron primo-/reinfection and primary vaccination schedules on the immunogenicity of an mRNA-based booster dose over a six-month period. We conducted a prospective cohort study to assess the durability and level of antibodies of 678 healthcare workers fully vaccinated against COVID-19.

Efficacy of Hearing Aids in Patients with Hearing Difficulties in Noise: Focus on Hidden Hearing Loss.

Hearing aids (HAs) have been used for standard high-frequency hearing loss and tinnitus, but their effects on speech intelligibility in noise (SIN) in people with normal hearing, including hidden hearing loss (HHL), have been little explored. We included in a prospective cohort study patients who experience poor SIN and have normal pure tone average in quiet conditions or slight HL. We used open-fit HAs.

Exploring the Link Between Renal Function Fluctuations Within the Physiological Range and Serum/CSF Levels of NfL, GFAP, tTAU, and UCHL1.

Impaired renal function can influence biomarker levels through mechanisms involving blood-brain barrier integrity and clearance pathways; however, the impact of variations within normal renal function remains unclear. The main aim of this study was to determine whether adjustment for the specific level of renal function is necessary when renal function remains within physiological levels. We studied n = 183 patients (NID n = 122; other neurological diseases n = 39; somatoform controls n = 22) who underwent lumbar puncture at University Hospital Frankfurt.

Milk Composition Is Predictive of Low Milk Supply Using Machine Learning Approaches.

The causes of low milk supply are multifactorial, including factors such as gene mutations, endocrine disorders, and infrequent milk removal. These factors affect the functional capacity of the mammary gland and, potentially, the concentrations of milk components. This study aimed to investigate the differences in milk composition between mothers with low and normal milk supply and develop predictive machine learning models for identifying low milk supply.

Unraveling complexity and leveraging opportunities in uncommon breast cancer subtypes.

Special histologic subtypes of breast cancer (BC) exhibit unique phenotypes and molecular profiles with diagnostic and therapeutic implications, often differing in behavior and clinical trajectory from common BC forms. Novel methodologies, such as artificial intelligence may improve classification. Genetic predisposition plays roles in a subset of cases.

Mcl-1 is a Gatekeeper Molecule to Regulate the Crosstalk Between Ferroptotic Agent-Induced ER Stress and TRAIL-Induced Apoptosis.

We previously reported that ferroptosis interplays with apoptosis through the integration of two independent pathways: the endoplasmic reticulum (ER) stress signaling pathway and the mitochondria-dependent apoptotic signaling pathway. In this study, we investigated a potential gatekeeper molecule, Mcl-1, between the two signal transduction pathways. Morphology studies and cell death analyses confirmed that a combination treatment of ferroptotic agent erastin (ERA) and apoptotic agent TRAIL (tumor necrosis factor-related apoptosis-inducing ligand) synergistically enhances TRAIL-induced apoptosis in human pancreatic adenocarcinoma BxPC3 and human colorectal carcinoma HCT116 cells.

Nutritional Interventions to Attenuate Quadriceps Muscle Deficits following Anterior Cruciate Ligament Injury and Reconstruction.

Following anterior cruciate ligament (ACL) injury, quadriceps muscle atrophy persists despite rehabilitation, leading to loss of lower limb strength, osteoarthritis, poor knee joint health and reduced quality of life. However, the molecular mechanisms responsible for these deficits in hypertrophic adaptations within the quadriceps muscle following ACL injury and reconstruction are poorly understood. While resistance exercise training stimulates skeletal muscle hypertrophy, attenuation of these hypertrophic pathways can hinder rehabilitation following ACL injury and reconstruction, and ultimately lead to skeletal muscle atrophy that persists beyond ACL reconstruction, similar to disuse atrophy.

Safety and Immunogenicity of the Tetravalent Recombinant COVID-19 Protein Vaccine SCTV01E in Children and Adolescents Aged 3 to 17 Years: A Randomized, Double-Blind, Placebo-Controlled Phase 2 Clinical Trial.

: SCTV01E is a tetravalent recombinant COVID-19 vaccine authorized for emergency use in China for adults 18 years and older but not for those under 18. : This Phase 2 trial assessed the safety and immunogenicity of SCTV01E in healthy children and adolescents aged 3 to 17 years, to establish immunobridging with that observed in adults from the efficacy pivotal trial (NCT05308576). : Participants were randomly assigned to receive either 30 µg of SCTV01E or a placebo.

Comparative Investigation of Vortex and Direct Plasma Discharge for Treating Titanium Surface.

Numerous studies have investigated the surface treatment of implants using various types of plasma, including atmospheric pressure plasma and vacuum plasma, to remove impurities and increase surface energy, thereby enhancing osseointegration. Most previous studies have focused on generating plasma directly on the implant surface by using the implant as an electrode for plasma discharge. However, plasmas generated under atmospheric and moderate vacuum conditions often have a limited plasma volume, meaning the shape of the electrodes significantly influences the local electric field characteristics, which in turn affects plasma behavior.

Enhanced Detection Performance of Acute Vertebral Compression Fractures Using a Hybrid Deep Learning and Traditional Quantitative Measurement Approach: Beyond the Limitations of Genant Classification.

Objective: This study evaluated the applicability of the classical method, height loss ratio (HLR), for identifying major acute compression fractures in clinical practice and compared its performance with deep learning (DL)-based VCF detection methods. Additionally, it examined whether combining the HLR with DL approaches could enhance performance, exploring the potential integration of classical and DL methodologies.

Methods: End-to-End VCF Detection (EEVD), Two-Stage VCF Detection with Segmentation and Detection (TSVD_SD), and Two-Stage VCF Detection with Detection and Classification (TSVD_DC).

Atrial Fibrillation Related Titin Truncation Is Associated With Atrial Myopathy in Patient-Derived Induced Pluripotent Stem Cell Disease Models.

Background: Protein-truncating mutations in the titin gene are associated with increased risk of atrial fibrillation. However, little is known about the underlying pathophysiology.

Methods: We identified a heterozygous titin truncating variant (TTNtv) in a patient with unexplained early onset atrial fibrillation and normal ventricular function.

Penfluridol targets septin7 to suppress endometrial cancer by septin7-Orai/IP3R-Ca-PIK3CA pathway.

Phenotypic screening of existing drugs is a good strategy to discover new drugs. Herein, 33 psychotherapeutic drugs in our drug library were screened by phenotypic screening and penfluridol (PFD) was found to exhibit excellent anti-endometrial cancer (EC) activity both and . Furthermore, the molecular target of PFD was identified as septin7, a tumor suppressor in EC.

Prolonged neurologic symptoms following immune effector cell-associated neurotoxicity syndrome in patients with large B cell lymphoma treated with chimeric antigen receptor-modified T cell therapy.

Background: While immune effector cell-associated neurotoxicity syndrome (ICANS) is a well-defined adverse effect associated with chimeric antigen receptor-modified T cell (CAR-T) therapy, some patients develop prolonged neurologic symptoms. Few studies have examined characteristics and outcomes of patients who develop such symptoms.

Objective: To provide an analysis of patients who developed ICANS in a single-center cohort of patients with large B-cell lymphoma (LBCL) who received commercial CAR-T and compare characteristics and outcomes between patients with vs.

Microbiota translocation following intestinal barrier disruption promotes Mincle-mediated training of myeloid progenitors in the bone marrow.

Impairment of the intestinal barrier allows the systemic translocation of commensal bacteria, inducing a proinflammatory state in the host. Here, we investigated innate immune responses following increased gut permeability upon administration of dextran sulfate sodium (DSS) in mice. We found that Enterococcus faecalis translocated to the bone marrow following DSS treatment and induced trained immunity (TI) hallmarks in bone-marrow-derived mouse macrophages and human monocytes.

Eye Movements and the Intraorbital Subarachnoid Space: Potential Contribution of Altered Cerebrospinal Fluid Pumping in Optic Neuropathies.

Purpose: The optic nerve (ON) is mechanically perturbed by eye movements that shift cerebrospinal fluid (CSF) within its surrounding dural sheath. This study compared changes in ON length and CSF volume within the intraorbital ON sheath caused by eye movements in healthy subjects and patients with optic neuropathies.

Methods: Twenty-one healthy controls were compared with 11 patients having primary open angle glaucoma (POAG) at normal intraocular pressure (IOP), and 11 with chronic non-arteritic anterior ischemic optic neuropathy (NA-AION).

Evolution of sleep disordered breathing in infants with achondroplasia.

Purpose: Children with achondroplasia (ACH) are at risk for sudden death in infancy due to sleep disordered breathing (SDB) and foramen magnum stenosis (FMS). Sleep studies and neuroimaging are performed in infants with ACH, but interpretation of infant studies is challenging. We sought to describe baseline data on polysomnography (PSG) indices in infants with achondroplasia as well as effects of age and surgery on these parameters.

Classifying Race in Out-of-Hospital Cardiac Arrest and Potential Disparities: A Retrospective Cohort Study.

Background: Although racial disparities have been described in resuscitation, little is known about potential bias in race classification of out-of-hospital cardiac arrest (OHCA).

Methods: We conducted a retrospective cohort study of adults treated by emergency medical services (EMS) for nontraumatic OHCA in King County, WA between January 1, 2018, and December 31, 2021. We assessed agreement using κ and evaluated patterns of missingness between EMS-assessed race versus comprehensive race classification from hospital and death records.

Heterogeneous and higher-order cortical connectivity undergirds efficient, robust, and reliable neural codes.

We hypothesized that the heterogeneous architecture of biological neural networks provides a substrate to regulate the well-known tradeoff between robustness and efficiency, thereby allowing different subpopulations of the same network to optimize for different objectives. To distinguish between subpopulations, we developed a metric based on the mathematical theory of simplicial complexes that captures the complexity of their connectivity by contrasting its higher-order structure to a random control and confirmed its relevance in several openly available connectomes. Using a biologically detailed cortical model and an electron microscopic dataset, we showed that subpopulations with low simplicial complexity exhibit efficient activity.

The Impact of Family History on Clinical Presentation and Biologic Treatment Response in Patients with Psoriasis: A Multicenter Prospective Cohort Study.

Background: Family history (FH) of psoriasis has been implicated as a risk factor for developing psoriasis. However, whether FH also carries information on clinical presentation and treatment response to biological agents in patients with psoriasis remains unclear.

Objective: This prospective, multicenter observational study aimed to analyze the clinical presentation and efficacy differences between patients with psoriasis with and without a FH.