Heat stable and intrinsically sterile liquid protein formulations.

Over 80% of biologic drugs, and 90% of vaccines, require temperature-controlled conditions throughout the supply chain to minimize thermal inactivation and contamination. This cold chain is costly, requires stringent oversight, and is impractical in remote environments. Here, we report chemical dispersants that non-covalently solvate proteins within fluorous liquids to alter their thermodynamic equilibrium and reduce conformational flexibility.

Orthogonal and multiplexable genetic perturbations with an engineered prime editor and a diverse RNA array.

Programmable and modular systems capable of orthogonal genomic and transcriptomic perturbations are crucial for biological research and treating human genetic diseases. Here, we present the minimal versatile genetic perturbation technology (mvGPT), a flexible toolkit designed for simultaneous and orthogonal gene editing, activation, and repression in human cells. The mvGPT combines an engineered compact prime editor (PE), a fusion activator MS2-p65-HSF1 (MPH), and a drive-and-process multiplex array that produces RNAs tailored to different types of genetic perturbation.

Higher skeletal muscle mitochondrial oxidative capacity is associated with preserved brain structure up to over a decade.

Impaired muscle mitochondrial oxidative capacity is associated with future cognitive impairment, and higher levels of PET and blood biomarkers of Alzheimer's disease and neurodegeneration. Here, we examine its associations with up to over a decade-long changes in brain atrophy and microstructure. Higher in vivo skeletal muscle oxidative capacity via MR spectroscopy (post-exercise recovery rate, k) is associated with less ventricular enlargement and brain aging progression, and less atrophy in specific regions, notably primary sensorimotor cortex, temporal white and gray matter, thalamus, occipital areas, cingulate cortex, and cerebellum white matter.

PSCA-targeted BPX-601 CAR T cells with pharmacological activation by rimiducid in metastatic pancreatic and prostate cancer: a phase 1 dose escalation trial.

Here we report results of a phase 1 multi-institutional, open-label, dose-escalation trial (NCT02744287) of BPX-601, an investigational autologous PSCA-directed GoCAR-T® cell product containing an inducible MyD88/CD40 ON-switch responsive to the activating dimerizer rimiducid, in patients with metastatic pancreatic (mPDAC) or castration-resistant prostate cancer (mCRPC). Primary objectives were to evaluate safety and tolerability and determine the recommended phase 2 dose/schedule (RP2D). Secondary objectives included the assessment of efficacy and characterization of the pharmacokinetics of rimiducid.

Hydronium Ions Are Less Excluded from Hydrophobic Polymer-Water Interfaces than Hydroxide Ions.

The cloud point temperatures of aqueous poly(-isopropylacrylamide) (PNIPAM) and poly(ethylene) oxide (PEO) solutions were measured from pH 1.0 to pH 13.0 at a constant ionic strength of 100 mM.

Geriatric Nutritional Risk Index and Postoperative Outcomes Following Head and Neck Cancer Surgery.

Background: The geriatric nutritional risk index (GNRI) is a tool to assess preoperative nutritional status that can be calculated simply based on height, weight, and serum albumin. This study assesses the utility of GNRI in predicting postoperative complications in patients undergoing major head and neck cancer (HNC) surgery.

Methods: Retrospective review of the 2016-2020 National Surgical Quality Improvement Program database.

A Natural Disaster Exacerbates and Redistributes Disease Risk Among Free-Ranging Macaques by Altering Social Structure.

Climate change is intensifying extreme weather events, with severe implications for ecosystem dynamics. A key behavioural mechanism whereby animals may cope with such events is by altering their social structure, which in turn could influence epidemic risk. However, how and to what extent natural disasters affect disease risk via changes in sociality remains unexplored in animal populations.

Future Applications of Central Neuromodulation and Neurophysiological Testing in Cyclic Vomiting Syndrome.

Background: Cyclic vomiting syndrome (CVS) is defined by its episodic patterning. Furthermore, CVS is associated with other episodic disorders such as migraine and epilepsy. Indeed, many of the medications that are known to be useful for prophylaxis and abortive therapy in CVS are also effective in preventing and aborting migraines and seizures.

Symptom Patterns in Adults With Cyclic Vomiting Syndrome: A 6-Month Prospective Observational Study.

Background: Data are limited on the natural history and symptom patterns of cyclic vomiting syndrome (CVS), a disorder of gut-brain interaction characterized by recurrent stereotypical vomiting, retching, and nausea episodes.

Methods: A 6-month, observational, remote study prospectively assessed symptom patterns in adults with CVS using an electronic daily diary. Patients recorded their disease experience, including CVS symptoms and associated severity, in the daily diary.

Expanding the phenotype and genotype spectrum of TAOK1 neurodevelopmental disorder and delineating TAOK2 neurodevelopmental disorder.

Purpose: The TAOK proteins are a group of serine/threonine-protein kinases involved in signalling pathways, cytoskeleton regulation, and neuronal development. TAOK1 variants are associated with a neurodevelopmental disorder (NDD) characterized by distinctive facial features, hypotonia and feeding difficulties. TAOK2 variants have been reported to be associated with autism and early-onset obesity.

A phase I study using bortezomib (Velcade), cladribine, and rituximab in treating patients over 50 years old with mantle cell lymphoma.

Unlabelled: Cladribine indirectly downregulates methylation of DNA, RNA, and histones by blocking the transfer of methyl groups from -adenosyl-methionine. The cladribine and rituximab combination showed a synergetic effect in treating B-cell lymphomas. Bortezomib (Velcade) is a Food and Drug Administration (FDA)-approved proteasome inhibitor for treating mantle cell lymphoma (MCL).

Standardized protocol for labor induction: a type I hybrid effectiveness-implementation trial.

Background: Cesarean delivery remains the most common obstetrical procedure with more than 250,000 patients in the US undergoing cesarean following labor induction annually. Here, we evaluated the impact of prospectively implementing a standardized labor induction protocol on cesarean delivery rates.

Methods: This multi-site type I hybrid effectiveness-implementation study compared 2 years before (PRE) and 2 years after (POST) implementation of a standardized labor induction protocol at two hospitals within the University of Pennsylvania Health System (2018-2022).

Use of intrauterine dextrose as an alternative to systemic antibiotics for treatment of clinical metritis in dairy cattle: a microbiome perspective.

Introduction: Clinical metritis (CM) has significant costs to dairy producers. Current treatment strategy involves systemic antibiotics; however, there is increasing concern about judicious antibiotic use. The study objective was to evaluate the effects of a non-antibiotic treatment vs.

Anti-IL-4Ra therapy is superior to other biologic classes in treating allergic bronchopulmonary aspergillosis.

Background: Allergic bronchopulmonary aspergillosis (ABPA) is a disease resulting from an overactive type 2 response to . Initial studies suggest that asthma biologics can effectively treat ABPA, but it is unclear which biologic class is superior.

Objective: We sought to compare the effectiveness of asthma biologics in the treatment of ABPA.

Predicting kidney graft function and failure among kidney transplant recipients.

Background: Graft loss is a major health concern for kidney transplant (KTx) recipients. It is of clinical interest to develop a prognostic model for both graft function, quantified by estimated glomerular filtration rate (eGFR), and the risk of graft failure. Additionally, the model should be dynamic in the sense that it adapts to accumulating longitudinal information, including time-varying at-risk population, predictor-outcome association, and clinical history.

The Spatial Ventricular Gradient Is Associated with Pacing-Induced Cardiomyopathy.

Background: Pacing-induced cardiomyopathy (PICM) is a frequent complication of right ventricular pacing that often requires re-operation for biventricular or conduction system pacing. Better methods for predicting PICM may inform initial pacing strategy and follow-up monitoring.

Objective: To determine if the spatial ventricular gradient (SVG), a vectorcardiographic marker of ventricular electrical and mechanical heterogeneity, is associated with subsequent development of PICM.

Factors Associated with Pediatric Drowning-Associated Lung Injury.

Objective: To identify risk factors for clinically-important drowning-associated lung injury (ciDALI) in children.

Study Design: This was a cross-sectional study of children (0 through18 years) who presented to 32 pediatric emergency departments (EDs) from 2010 through 2017. We reviewed demographics, comorbidities, prehospital data, chest radiographs reports, and ED course from emergency medical services, medical, and fatality records.