Recommendations for reporting and evaluating proton therapy beyond dose and constant relative biological effectiveness.

Background And Purpose: In proton therapy, a relative biological effectiveness (RBE) of 1.1 is used to convert proton dose into an equivalent photon dose. However, RBE varies with tissue type, fraction dose, and beam quality parameters beyond dose such as linear energy transfer (LET) raising concerns about increased local effectiveness and potential toxicity.

Multi-target gene therapy AUP1602-C to improve healing and quality of life for diabetic foot ulcer patients: a phase I, open-label, dose-finding study.

Background: Diabetic foot ulcer (DFU) is a common and highly morbid complication of diabetes with high unmet medical needs. AUP1602-C, a topical four-in-one gene therapy medicinal product (GTMP), consisting of a strain that produces fibroblast growth factor-2, interleukin-4, and colony-stimulating factor-1, is a promising novel treatment for DFU.

Objectives: The aim of this first-in-human study was to investigate whether AUP1602-C is safe and effective in improving wound healing and quality of life (QoL) in patients with non-healing DFU (nhDFU), and to determine the recommended phase II dose.

Towards a unified approach in managing resistance to vaccines, drugs, and pesticides.

Everywhere, pests and pathogens evolve resistance to our control efforts, impairing human health and welfare. Developing sustainable solutions to this problem requires working with evolved immune and ecological systems, rather than against these evolutionary forces. We advocate a transdisciplinary approach to resistance based on an evolutionary foundation informed by the concepts of integrated pest management and One Health.

Changes in Muscle Activation and Joint Motion During Walking After Transtibial Amputation with Sensory Feedback from Spinal Cord Stimulation: A Case Study.

Background: The goal of this study was to examine the effects of spinal cord stimulation (SCS) on muscle activity during walking after lower-limb amputation. Amputation results in a loss of sensory feedback and alterations in gait biomechanics, including co-contractions of antagonist muscles about the knee and ankle, and reduced pelvic obliquity range-of-motion and pelvic drop. SCS can restore sensation in the missing limb, but its effects on muscle activation and gait biomechanics have not been studied in people with lower-limb amputation.

Incidence of idiopathic syrinx in pediatric patients diagnosed with VACTERL association.

Objective: While the association of a syrinx with a tethered spinal cord in the context of VACTERL (vertebral defects [V], imperforate anus or anal atresia [A], cardiac malformations [C], tracheoesophageal defects [T] with or without esophageal atresia [E], renal anomalies [R], and limb defects [L]) association is known, the incidence of idiopathic syrinxes among these patients has not previously been reported. The authors aimed to characterize the incidence of syrinxes and the pattern of congenital anomalies in pediatric patients with VACTERL association, with a specific focus on the presence of idiopathic syrinxes in this population.

Methods: An institutional database was retrospectively queried for all pediatric patients with VACTERL association.

Revisiting the role of education in attitudes toward immigration in different contexts in Europe.

Unlabelled: Among the individual determinants of attitudes toward immigration, the liberalising role of education is well known-those with higher levels of education tend to be more in favour of immigration. However, recent socioeconomic changes and idiosyncratic differences between European countries prompt us to reassess the role of education, given these contextual differences. Does it still apply, and is it universal? Moreover, does this relationship apply to both cultural and economic attitudes toward immigration? Using data from the European Social Survey, we analyse the role of education and socioeconomic changes in shaping economic and cultural attitudes toward immigration in 15 European countries over 16 years using a hierarchical model with cross-classified random effects.

Transcriptomic resources for Bagrada hilaris (Burmeister), a widespread invasive pest of Brassicales.

The bagrada bug, Bagrada hilaris (Burmeister), is an emerging agricultural pest in the Americas, threatening agricultural production in the southwestern United States, Mexico and Chile, as well as in the Old World (including Africa, South Asia and, more recently, Mediterranean areas of Europe). Substantive transcriptomic sequence resources for this damaging species would be beneficial towards understanding its capacity for developing insecticide resistance, identifying viruses that may be present throughout its population and identifying genes differentially expressed across life stages that could be exploited for biomolecular pesticide formulations. This study establishes B.

Detection of Putative Ligand Dissociation Pathways in Proteins Using Site-Identification by Ligand Competitive Saturation.

Drug efficacy often correlates better with dissociation kinetics than binding affinity alone. To study binding kinetics computationally, it is necessary to identify all of the possible ligand dissociation pathways. The site identification by ligand competitive saturation (SILCS) method involves the precomputation of a set of maps (FragMaps), which describe the free energy landscapes of typical chemical functionalities in and around a target protein or RNA.

Letter to the editor in response to Duan X, et al, CYP4A22 loss-of-function causes a new type of vitamin D-dependent rickets (VDDR1C).

Duan X, et al, report that CYP4A22 loss-of-function causes a new form of vitamin D-dependent rickets. Here we describe the basis for our rejection of their proposal and provide evidence that the CYP4A22 variant that they have identified (c.901del, p.

An expert consensus statement on biomarkers of ageing for use in intervention studies.

Biomarkers of ageing serve as important outcome measures in longevity-promoting interventions. However, there is limited consensus on which specific biomarkers are most appropriate for human intervention studies. This work aimed to address this need by establishing an expert consensus on biomarkers of ageing for use in intervention studies via the Delphi method.

Improving localization and measurements of M-waves using high-density surface electromyography.

Surface electromyography (sEMG) is useful for studying muscle function and controlling prosthetics, but cross talk from nearby muscles often limits its effectiveness. High-density surface EMG (HD-sEMG) improves spatial resolution, allowing for the isolation of M-waves in the densely packed forearm muscles. This study assessed HD-sEMG for localizing M-waves and evaluated the impact of spatial filters on cross talk reduction.

Analysis of polaron pair lifetime dynamics and secondary processes in exciplex driven TADF OLEDs using organic magnetic field effects.

Magnetic field effects (MFEs) in thermally activated delayed fluorescence (TADF) materials have been shown to influence the reverse intersystem crossing (RISC) and to impact on electroluminescence (EL) and conductivity. Here, we present a novel model combining Cole-Cole and Lorentzian functions to describe low and high magnetic field effects originating from hyperfine coupling, the Δg mechanism, and triplet processes. We applied this approach to organic light-emitting devices of third generation based on tris(4-carbazoyl-9-ylphenyl)amine (TCTA) and 2,2',2″-(1,3,5-benzinetriyl)-tris(1-phenyl-1-H-benzimidazole) (TPBi), exhibiting blue emission, to unravel their loss mechanisms.

Unusual variants implicate uncommon genetic mechanisms for X-linked hypophosphatemic rickets.

X-linked hypophosphatemic rickets (XLH), the most common form of hereditary rickets, is characterized by renal phosphate wasting and abnormal vitamin D metabolism due to elevated circulating levels of the phosphatonin fibroblast growth factor 23 (FGF23). Dominant inactivating variants of the phosphate regulating endopeptidase homolog, X-linked (), gene are present in patients with XLH, and more than half of affected patients carry de novo variants. We report on 3 families in whom affected members had highly unusual pathogenic variants.

Mitophagosomes induced during EV-D68 infection promote viral nonlytic release.

Enterovirus-D68 (EV-D68) is a plus-strand RNA virus that primarily causes infant respiratory infections. In rare pediatric cases, infection with EV-D68 has been associated with acute flaccid myelitis, a polio-like paralytic disease. We have previously demonstrated that EV-D68 induces nonselective autophagy for its benefit.

A Rollercoaster of Grades Versus Growth in the Clerkship Year: A Phenomenological Study of Medical Student Experience with Competency Development.

Purpose: As competency-based medical education (CBME) continues to advance in undergraduate medical education, students are expected to simultaneously pursue their competency development while also discriminating themselves for residency selection. During the foundational clerkship year, it is important to understand how these seemingly competing goals are navigated.

Methods: In this phenomenological qualitative study, the authors describe the experience of 15 clerkship students taking part in a pilot pathway seeking to implement CBME principles.

Palmitic acid and eicosapentaenoic acid supplementation in 3T3 adipocytes: impact on lipid storage and oxidative stress.

Objectives: Obesity is a worldwide public health problem, predisposing individuals to serious cardiovascular and metabolic complications such as type 2 diabetes mellitus. White adipose tissue serves as an important regulator of energy balance, and its expansion in obesity can trigger inflammatory reactions and oxidative stress, which can also lead to insulin resistance. Adipocytes, with a key role in regulating metabolic homeostasis, respond to increased calorie intake and altered fatty acid composition with hypertrophy or hyperplasia.

Overcoming immunosuppression in cancer: how ketogenic diets boost immune checkpoint blockade.

Immune checkpoint blockade (ICB) is now part of the standard of care in the treatment of many forms of cancer, yet it lacks efficacy in some patients, necessitating adjunct therapies to support the anti-tumor immune response. Ketogenic diets (KDs), i.e.

A Free-Standing Boron-Doped Diamond Grid Electrode for Fundamental Spectroelectrochemistry.

Spectroelectrochemistry (SEC) is a powerful technique that enables a variety of redox properties to be studied, including formal potential (), thermodynamic values (Δ, Δ, Δ), diffusion coefficient (), electron transfer stoichiometry (), and others. SEC requires an electrode which light can pass through while maintaining sufficient electrical conductivity. This has been traditionally composed of metal or metal oxide films atop transparent substrates like glass, quartz, or metallic mesh.

Evaluation of Automated Object-Detection Algorithms for Koala Detection in Infrared Aerial Imagery.

Effective detection techniques are important for wildlife monitoring and conservation applications and are especially helpful for species that live in complex environments, such as arboreal animals like koalas (). The implementation of infrared cameras and drones has demonstrated encouraging outcomes, regardless of whether the detection was performed by human observers or automated algorithms. In the case of koala detection in eucalyptus plantations, there is a risk to spotters during forestry operations.

Temporal evolution and inter-patient heterogeneity in primary and recurrent head and neck squamous cell carcinoma.

Background: Head and neck squamous cell carcinomas (HNSCCs) are heterogeneous in terms of origin and aetiology. In addition, there is uncertainty about the genetic evolution from initial diagnosis to recurrence after primary treatments and further disease progression following systemic treatment. Changes in the genetic profile have implications on the selection of appropriate treatments for patients, especially in the era of targeted therapies and immunotherapies.