Efgartigimod efficacy and safety in refractory myasthenia gravis: UK's first real-world experience.

Background: We report our experience of patients with generalised myasthenia gravis (gMG) treated with efgartigimod, an neonatal Fc receptor antagonist, under the Early Access to Medicine Scheme (EAMS) in the UK.

Methods: Data from all UK patients treated with efgartigimod under the EAMS July 2022 to July 2023 were collected retrospectively. Efgartigimod was administered as per the ADAPT protocol (consisting of a treatment cycle of four infusions at weekly intervals with further cycles given according to clinical need).

Hemophagocytic Lymphohistiocytosis Due to Ehrlichiosis: A Case Series.

Background: Hemophagocytic lymphohistiocytosis (HLH) is an immunologic syndrome characterized by excessive inflammation and tissue injury due to uncontrolled activation of the phagocytic system. The underlying mechanism is a lack of downregulation of activated macrophages and lymphocytes by natural killer and T cells. Unfortunately, the diagnosis is often delayed or missed due to the rarity of the disease, decreased awareness, and clinical picture variability.

Compulsive exercise and disordered eating in college men: Body shame as a mediator for appearance pressures, a mixed methods study.

The present mixed-method study aims to understand the association between sociocultural pressures, disordered eating, and compulsive exercise in men, with body shame as a mediator. We surveyed 263 U.S.

Contact X-ray Brachytherapy as a Boost Therapy After Neoadjuvant (Chemo)Radiation in High-Risk Locally Advanced Rectal Cancer.

Purpose: Radical surgery following neoadjuvant therapy is the standard of care for locally advanced rectal cancer. A contact x-ray brachytherapy (CXB) boost can alternatively be used to treat residual disease postneoadjuvant (chemo)radiation, especially in patients who are not suitable for or do not wish to have surgery. Its role has mostly been studied to date in low- to intermediate-risk patients.

Central control of dynamic gene circuits governs T cell rest and activation.

The ability of cells to maintain distinct identities and respond to transient environmental signals requires tightly controlled regulation of gene networks. These dynamic regulatory circuits that respond to extracellular cues in primary human cells remain poorly defined. The need for context-dependent regulation is prominent in T cells, where distinct lineages must respond to diverse signals to mount effective immune responses and maintain homeostasis.

Diagnosis of in a fledgling kererū ().

In early summer, a wild fledgling kererū () was admitted to a wildlife hospital in Dunedin after falling from its nest and being found on the ground. The bird was underweight, weighing only 391 g (expected weight > 450 g), and determined to be in poor body condition based on palpation of pectoral muscle mass. There was bilateral periorbital swelling and ocular discharge with caseous material blocking the choana.

How speech and language therapists and parents work together in the therapeutic process for children with speech sound disorder: A scoping review.

Background: Speech sound disorders (SSDs) are broadly defined as difficulty producing speech sounds in childhood. Reported prevalence of SSD varies from 2.3% to 24.

Endoplasmic Reticulum Stress in Bronchopulmonary Dysplasia: Contributor or Consequence?

Bronchopulmonary dysplasia (BPD) is the most common complication of prematurity. Oxidative stress (OS) and inflammation are the major contributors to BPD. Despite aggressive treatments, BPD prevalence remains unchanged, which underscores the urgent need to explore more potential therapies.

Expanding the Molecular and Clinical Phenotype of Patients With De Novo Variants in KIF5C: A Six Patient Case Series.

Heterozygous de novo loss of function variants in the motor domain of KIF5C are associated with a neurodevelopmental disorder characterized by infantile-onset epilepsy, frontal cortical dysplasia, and developmental delays including motor and speech impairments. Previously, only three missense variants in KIF5C were known to be pathogenic. We identified an additional six patients with significant developmental delays with heterozygous de novo variants in the KIF5C gene (Glu237Val, Thr93Ile, Thr93Asn, Ser90del, Lys92Arg, and Glu237Lys), of which four variants have not been reported before.

Probing photochemical dynamics using electronic vs vibrational sum-frequency spectroscopy: The case of the hydrated electron at the water/air interface.

Photo-dynamics can proceed differently at the water/air interface compared to in the respective bulk phases. Second-order non-linear spectroscopy is capable of selectively probing the dynamics of species in such an environment. However, certain conclusions drawn from vibrational and electronic sum-frequency generation spectroscopies do not agree as is the case for the formation and structure of hydrated electrons at the interface.

QCManyBody: A flexible implementation of the many-body expansion.

While the many-body expansion (MBE) and counterpoise treatments are commonly used to mitigate the high scaling of accurate ab initio methods, researchers may need to piece together tools and scripts if their primary chosen software does not support targeted features. To further modular software in quantum chemistry, the arbitrary-order, multiple-model-chemistry, counterpoise-enabled MBE implementation from Psi4 has been extracted into an independent, lightweight, and open-source Python module, QCManyBody, with new schema underpinning, application programming interface, and software integrations. The package caters to direct users by facilitating single-point and geometry optimization MBE calculations backed by popular quantum chemistry codes through the QCEngine runner and by defining a schema for requesting and reporting many-body computations.

Gene regulatory network inference from CRISPR perturbations in primary CD4 T cells elucidates the genomic basis of immune disease.

The effects of genetic variation on complex traits act mainly through changes in gene regulation. Although many genetic variants have been linked to target genes in cis, the trans-regulatory cascade mediating their effects remains largely uncharacterized. Mapping trans-regulators based on natural genetic variation has been challenging due to small effects, but experimental perturbations offer a complementary approach.

Improvements in Clinical Cancer Care Associated with Integration of Personalized Medicine.

Background: While adoption of personalized medicine (PM) continues to increase in clinical oncology, there is limited data connecting the level of PM adoption at a given institution to improved clinical outcomes for patients. The purpose of this study was to analyze the correlation between health care providers' scores on a previously described PM integration framework and two outcome measures: the use of targeted therapy and clinical trial enrollment.

Methods: This study was conducted using real-world data (RWD) from the Syapse Learning Health Network (LHN).

Temporal Dynamics of Oxidative Stress and Inflammation in Bronchopulmonary Dysplasia.

Bronchopulmonary dysplasia (BPD) is the most common lung complication of prematurity. Despite extensive research, our understanding of its pathophysiology remains limited, as reflected by the stable prevalence of BPD. Prematurity is the primary risk factor for BPD, with oxidative stress (OS) and inflammation playing significant roles and being closely linked to premature birth.

Nutmeg and SPICE: Models and Data for Biomolecular Machine Learning.

We describe version 2 of the SPICE data set, a collection of quantum chemistry calculations for training machine learning potentials. It expands on the original data set by adding much more sampling of chemical space and more data on noncovalent interactions. We train a set of potential energy functions called Nutmeg on it.

A molecular switch from tumor suppressor to oncogene in ER+ve breast cancer: Role of androgen receptor, JAK-STAT, and lineage plasticity.

Cancers develop resistance to inhibitors of oncogenes mainly due to target-centric mechanisms such as mutations and splicing. While inhibitors or antagonists force targets to unnatural conformation contributing to protein instability and resistance, activating tumor suppressors may maintain the protein in an agonistic conformation to elicit sustainable growth inhibition. Due to the lack of tumor suppressor agonists, this hypothesis and the mechanisms underlying resistance are not understood.

Imaging and Pharmacokinetics of Percutaneously Injected Ultrasound and X-ray Imageable Thermosensitive Hydrogel loaded with Doxorubicin versus Free Drug in Swine.

Intratumoral injections often lack visibility, leading to unpredictable outcomes such as incomplete tumor coverage, off-target drug delivery and systemic toxicities. This study investigated an ultrasound (US) and x-ray imageable thermosensitive hydrogel based on poloxamer 407 (POL) percutaneously delivered in a healthy swine model. The primary objective was to assess the 2D and 3D distribution of the hydrogel within tissue across three different needle devices and injection sites: liver, kidney, and intercostal muscle region.

Discovery and Development of Highly Potent and Orally Bioavailable Nonpeptidic αβ Integrin Inhibitors.

A series of 3-aryl(()-3-fluoropyrrolidin-1-yl)butanoic acids were developed as potent orally bioavailable αβ integrin inhibitors. Starting from a zwitterionic peptidomimetic series optimized for inhaled administration, the balancing of potency and passive permeability to achieve suitable oral agents through modification and exploration of aryl substituents and p of the central cyclic amine is described. ()-4-(()-3-Fluoro-3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)pyrrolidin-1-yl)-3-(3-(2-methoxyethoxy)phenyl)butanoic acid was found to have highly desirable oral pharmacokinetic profiles in rat, dog, and minipig, with low to moderate clearance (26%, 7%, and 18% liver blood flow, respectively), moderate volumes of distribution (3.