The (T) thrombosis (I) in patients with (L) lower (L) limb (I) injuries (R) requiring (I) immobilisation (TILLIRI) study.

Background: Patients requiring lower limb immobilization after injury have an increased venous thromboembolism (VTE) risk. The extent of this risk in published studies varies. The Thrombosis Risk Prediction for Patients with Cast Immobilization (TRiP[cast]) model quantifies VTE risk using clinical parameters.

The Minnesota Critical Care Working Group 2: Crisis Conditions During the COVID-19 Pandemic, July 2021 through March 2022.

Background: The Minnesota Statewide Healthcare Coordination Center requested that the Minnesota Critical Care Working Group (CCWG) and Ethics Working Group (EWG), comprising interprofessional leaders from Minnesota's 9 largest health systems, plan and coordinate critical care operations during the COVID-19 pandemic, including the fall 2021 surge.

Research Question: Can a statewide working group collaboratively analyze real-time evidence to identify crisis conditions and to engage state leadership to implement care processes?

Study Design And Methods: The CCWG and EWG met via videoconferencing during the severe surge of fall 2021 to analyze evidence and plan for potential crisis care conditions. Five sources of evidence informed their actions: group consensus on operating conditions, federal teletracking data, the Medical Operations Coordination Center (MOCC) patient placement data, and 2 surveys created and distributed to hospitals and health care professionals.

Bivalent Omicron BA.1 vaccine booster increases memory B cell breadth and neutralising antibodies against emerging SARS-CoV-2 variants.

Background: Current literature informs us that bivalent vaccines will generate a broader serum neutralizing antibody response to multiple SARS-CoV-2 variants, but studies on how this breadth relates to the memory B cell (MBC) and T cell responses are sparse. This study compared breadth of neutralising antibody, and memory B and T cell responses to monovalent or a bivalent ancestral/Omicron BA.1 COVID-19 booster vaccine.

Electrophysiological Phenotype-Genotype Study of Sustained Monomorphic Ventricular Tachycardia in Inherited, High Arrhythmic Risk, Left Ventricular Cardiomyopathy.

Background: Among inherited cardiomyopathies involving the left ventricle, whether dilated or not, certain genotypes carry a well-established arrhythmic risk, notably manifested as sustained monomorphic ventricular tachycardia (SMVT). Nonetheless, the precise localization and electrophysiological profile of this substrate remain undisclosed across different genotypes.

Methods: Patients diagnosed with cardiomyopathy and left ventricle involvement due to high-risk genetic variants and SMVT treated by electrophysiological study were recruited from 18 European/US centers.

Nanopore sequencing of intact aminoacylated tRNAs.

Transfer RNAs (tRNA) are decorated during biogenesis with a variety of modifications that modulate their stability, aminoacylation, and decoding potential during translation. The complex landscape of tRNA modification presents significant analysis challenges and to date no single approach enables the simultaneous measurement of important but disparate chemical properties of individual, mature tRNA molecules. We developed a new, integrated approach to analyze the sequence, modification, and aminoacylation state of tRNA molecules in a high throughput nanopore sequencing experiment, leveraging a chemical ligation that embeds the charged amino acid in an adapted tRNA molecule.

Single-cell spatial mapping reveals alteration of cell type composition and tissue microenvironment during early colorectal cancer formation.

Colorectal cancer (CRC) is the third leading cause of cancer mortality in the United States. Familial adenomatous polyposis (FAP) is a hereditary syndrome that raises the risk of developing CRC, with total colectomy as the only effective prevention. Even though FAP is rare (0.

Impact of personalized response-directed surgery and adjuvant therapy on survival after neoadjuvant immunotherapy in stage III melanoma: Comparison of 3-year data from PRADO and OpACIN-neo.

Background: Pathologic response following neoadjuvant immune checkpoint blockade (ICB) in stage III melanoma serves as a surrogate marker for long-term outcomes. This may support more personalized, response-directed treatment strategies.

Methods: The OpACIN-neo and PRADO trials were phase 2 studies evaluating neoadjuvant treatment with ipilimumab and nivolumab in stage III melanoma.

Childhood-onset lupus nephritis is characterized by complex interactions between kidney stroma and infiltrating immune cells.

Children with systemic lupus erythematosus (SLE) are at increased risk of developing kidney disease, termed childhood-onset lupus nephritis (cLN). Single-cell transcriptomics of dissociated kidney tissue has advanced our understanding of LN pathogenesis, but loss of spatial resolution prevents interrogation of in situ cellular interactions. Using a technical advance in spatial transcriptomics, we generated a spatially resolved, single-cell resolution atlas of kidney tissue from eight patients with cLN and four control individuals.

Development and Application of High-Internal-Phase Water-in-Oil Emulsions Using Amphiphilic Nanoparticle-Based Emulsifiers.

High-internal-phase water-in-oil (W/O) emulsions generated in situ have garnered considerable attention as novel profile control systems. However, conventional emulsifiers are unreactive and poorly dispersed in water, necessitating large dosages and resulting in poor injectivity. In this study, we synthesized amphiphilic nanoparticles (SiO-NH-DAC NPs) containing amine and long-chain alkyl groups using a one-pot method and investigated the stabilized emulsion properties.

Robotic MRI/CT Guided Multiregional 'smart' Biopsy for Characterization of Tumor Heterogeneity: A Prospective Development Study.

Rationale And Objectives: Intratumoral heterogeneity means single site tumor biopsy might not be representative. Here we develop and optimize an MRI-informed robotic multiregional 'smart' biopsy technique in retroperitoneal and pelvic sarcomas (RPS). We also explore the relationship between imaging and histological biomarkers.

Real-World Study of US Adults with Paroxysmal Nocturnal Hemoglobinuria Treated with Pegcetacoplan.

: Paroxysmal nocturnal hemoglobinuria (PNH) is a rare, acquired, life-threatening disease characterized by complement-mediated hemolysis. OPERA is the first US longitudinal real-world study on C3 inhibitor therapy, known as pegcetacoplan. : OPERA enrolled US patients with PNH, age ≥18, who were prescribed pegcetacoplan, and data were collected from routine care.

A yeast-based oral therapeutic delivers immune checkpoint inhibitors to reduce intestinal tumor burden.

Engineered probiotics are an emerging platform for in situ delivery of therapeutics to the gut. Herein, we developed an orally administered, yeast-based therapeutic delivery system to deliver next-generation immune checkpoint inhibitor (ICI) proteins directly to gastrointestinal tumors. We engineered Saccharomyces cerevisiae var.

S100A1ct: A Synthetic Peptide Derived From S100A1 Protein Improves Cardiac Performance and Survival in Preclinical Heart Failure Models.

Background: The EF-hand Ca sensor protein S100A1 has been identified as a molecular regulator and enhancer of cardiac performance. The ability of S100A1 to recognize and modulate the activity of targets such as SERCA2a (sarcoplasmic reticulum Ca ATPase) and RyR2 (ryanodine receptor 2) in cardiomyocytes has mostly been ascribed to its hydrophobic C-terminal α-helix (residues 75-94). We hypothesized that a synthetic peptide consisting of residues 75 through 94 of S100A1 and an N-terminal solubilization tag (S100A1ct) could mimic the performance-enhancing effects of S100A1 and may be suitable as a peptide therapeutic to improve the function of diseased hearts.

Single-molecule states link transcription factor binding to gene expression.

The binding of multiple transcription factors (TFs) to genomic enhancers drives gene expression in mammalian cells. However, the molecular details that link enhancer sequence to TF binding, promoter state and transcription levels remain unclear. Here we applied single-molecule footprinting to measure the simultaneous occupancy of TFs, nucleosomes and other regulatory proteins on engineered enhancer-promoter constructs with variable numbers of TF binding sites for both a synthetic TF and an endogenous TF involved in the type I interferon response.

Cephalopod-inspired jetting devices for gastrointestinal drug delivery.

Needle-based injections currently enable the administration of a wide range of biomacromolecule therapies across the body, including the gastrointestinal tract, through recent developments in ingestible robotic devices. However, needles generally require training, sharps management and disposal, and pose challenges for autonomous ingestible systems. Here, inspired by the jetting systems of cephalopods, we have developed and evaluated microjet delivery systems that can deliver jets in axial and radial directions into tissue, making them suitable for tubular and globular segments of the gastrointestinal tract.

Long-Term Cognitive, Functional, and Patient-Reported Outcomes in Patients With Anti-NMDAR Encephalitis.

Background And Objectives: Anti-NMDA receptor (anti-NMDAR) encephalitis generally manifests in young adults. Although 80%-90% returns to independence, the majority experience persistent cognitive and psychosocial difficulties. Studies have demonstrated that cognitive recovery may continue for years; the temporal trajectory is largely unknown, as are factors influencing cognitive/psychosocial recovery.

Adjunctive Middle Meningeal Artery Embolization for Subdural Hematoma.

Background: Subacute and chronic subdural hematomas are common and frequently recur after surgical evacuation. The effect of adjunctive middle meningeal artery embolization on the risk of reoperation remains unclear.

Methods: In a prospective, multicenter, interventional, adaptive-design trial, we randomly assigned patients with symptomatic subacute or chronic subdural hematoma with an indication for surgical evacuation to undergo middle meningeal artery embolization plus surgery (treatment group) or surgery alone (control group).

Overuse of analgesics can affect the fertility biomarker Anti-Müllerian Hormone in females. A translational study.

Background: Medication overuse headache is a prevalent secondary headache due to the overuse of analgesics, mainly over-the-counter analgesics. Over-the-counter analgesics have been associated with disrupted male endocrinology, while the effects on female endocrinology remain nearly unknown. The aim was to understand the effect of long-term analgesic exposure in females with medication overuse headache on Anti-Müllerian hormone, a surrogate measure of female fertility.

Sodium oligomannate disrupts the adherence of Rib bacteria to gut epithelia to block SAA-triggered Th1 inflammation in 5XFAD transgenic mice.

Sodium oligomannate (GV-971), an oligosaccharide drug approved in China for treating mild-to-moderate Alzheimer's disease (AD), was previously found to recondition the gut microbiota and limit altered peripheral Th1 immunity in AD transgenic mice. As a follow-up study, we here made advances by pinpointing a Lactobacillus murinus (L.m.

Neuropsychological Outcomes After Stereo-EEG Radiofrequency Thermocoagulation.

Background And Objectives: Stereo-EEG-guided radiofrequency thermocoagulation (RFTHC) has been proposed as relatively safe from a cognitive perspective; however, there is a lack of evidence based on neuropsychological assessments supporting this. This study is the first prospective evaluation of neuropsychological outcomes associated with stereo-EEG-guided RFTHC in patients with focal drug-resistant epilepsy.

Methods: This cohort study involved prospective recruitment of consecutive patients undergoing stereo-EEG from 2 Australian centers.

Routine Spironolactone in Acute Myocardial Infarction.

Background: Mineralocorticoid receptor antagonists have been shown to reduce mortality in patients after myocardial infarction with congestive heart failure. Whether routine use of spironolactone is beneficial after myocardial infarction is uncertain.

Methods: In this multicenter trial with a 2-by-2 factorial design, we randomly assigned patients with myocardial infarction who had undergone percutaneous coronary intervention to receive either spironolactone or placebo and either colchicine or placebo.

Perception of voice cues and speech-in-speech by children with prelingual single-sided deafness and a cochlear implant.

Voice cues, such as fundamental frequency (F0) and vocal tract length (VTL), help listeners identify the speaker's gender, perceive the linguistic and emotional prosody, and segregate competing talkers. Postlingually implanted adult cochlear implant (CI) users seem to have difficulty in perceiving and making use of voice cues, especially of VTL. Early implanted child CI users, in contrast, perceive and make use of both voice cues better than CI adults, and in patterns similar to their peers with normal hearing (NH).