Palbociclib plus letrozole in estrogen receptor-positive advanced/recurrent endometrial cancer: Double-blind placebo-controlled randomized phase II ENGOT-EN3/PALEO trial.

Purpose: The CDK4/6 inhibitor palbociclib inhibits cyclin A, which is overexpressed in endometrial cancer. Combining palbociclib with endocrine therapy improves efficacy in hormone receptor-positive breast cancer. We investigated palbociclib combined with endocrine therapy for estrogen receptor-positive advanced/recurrent endometrial cancer.

A minimal physiologically-based pharmacokinetic modeling platform to predict intratumor exposure and receptor occupancy of an anti-LAG-3 monoclonal antibody.

In oncology drug development, measuring drug concentrations at the tumor site and at the targeted receptor remains an ongoing challenge. Positron emission tomography (PET)-imaging is a promising noninvasive method to quantify intratumor exposure of a radiolabeled drug (biodistribution data) and target saturation by treatment doses in vivo. Here, we present the development and application of a minimal physiologically-based pharmacokinetic (mPBPK) modeling approach to integrate biodistribution data in a quantitative platform to characterize and predict intratumor exposure and receptor occupancy (RO) of BI 754111, an IgG-based anti-lymphocyte-activation gene 3 (LAG-3) monoclonal antibody (mAb).

Oxygen consumption measurements at ultra-high dose rate over a wide LET range.

Background: The role of radiolytic oxygen consumption for the in-vitro "Ultra-High Dose Rate" (UHDR) sparing and in-vivo FLASH effect is subject to active debate, but data on key dependencies such as the radiation quality are lacking.

Purpose: The influence of "dose-averaged Linear Energy Transfer" (LETd) and dose rate on radiolytic oxygen consumption was investigated by monitoring the oxygen concentration during irradiation with electrons, protons, helium, carbon, and oxygen ions at UHDR and "Standard Dose Rates" (SDR).

Methods: Sealed "Bovine Serum Albumin" (BSA) 5% samples were exposed to 15 Gy of electrons and protons, and for the first time helium, carbon, and oxygen ions with LETd values of 1, 5.

Validation of the Swedish Dynamic Imaging Grade of Swallowing Toxicity for Flexible Endoscopic Evaluation of Swallowing (DIGEST-FEES).

In the head and neck cancer (HNC) population around 45% suffer from chronic swallowing difficulties after cancer treatment. Previously a measure for flexible endoscopic evaluation of swallowing (FEES) where swallowing efficiency, safety and overall ability is evaluated within the same framework has been lacking. The Dynamic Imaging Grade of Swallowing Toxicity for FEES (DIGEST-FEES) was developed in 2021 and provides such a measure for patients with HNC.

Post-race reactions: The emotional paradox of high performance and anxiety - a conventional content analysis.

Background: Studies examining post-race emotional experiences in the context of endurance races among recreational athletes are scarce. The purpose of this study was to describe how recreational athletes experience the time after completing an endurance race.

Methods: In this study, a qualitative study design was used, and data collection was carried out with semi-structured interviews.

Preventing radiation-induced dysphagia and trismus in head and neck cancer-A randomized controlled trial.

Background: Radiation-induced dysphagia and restricted mouth opening are common problems among patients with head and neck cancer. The aim of the present randomized controlled trial was to determine if an exercise protocol could prevent swallowing and mouth opening impairment.

Methods: Eighty-nine participants were randomly assigned to either an active group performing preventive swallowing and mouth opening exercises (n = 45) or to a control group (n = 44).

Long-term toxicity and efficacy of FLASH radiotherapy in dogs with superficial malignant tumors.

Introduction: FLASH radiotherapy (RT) has emerged as a promising modality, demonstrating both a normal tissue sparing effect and anticancer efficacy. We have previously reported on the safety and efficacy of single fraction FLASH RT in the treatment of oral tumors in canine cancer patients, showing tumor response but also a risk of radiation-induced severe late adverse effects (osteoradionecrosis) for doses ≥35 Gy. Accordingly, the objective in this study was to investigate if single fraction high dose FLASH RT is safe for treating non-oral tumors.

Changing diagnostic criteria for gestational diabetes (CDC4G) in Sweden: A stepped wedge cluster randomised trial.

Background: The World Health Organisation (WHO) 2013 diagnostic criteria for gestational diabetes mellitus (GDM) has been criticised due to the limited evidence of benefits on pregnancy outcomes in different populations when switching from previously higher glycemic thresholds to the lower WHO-2013 diagnostic criteria. The aim of this study was to determine whether the switch from previous Swedish (SWE-GDM) to the WHO-2013 GDM criteria in Sweden following risk factor-based screening improves pregnancy outcomes.

Methods And Findings: A stepped wedge cluster randomised trial was performed between January 1 and December 31, 2018 in 11 clusters (17 delivery units) across Sweden, including all pregnancies under care and excluding preexisting diabetes, gastric bypass surgery, or multifetal pregnancies from the analysis.

Feasibility and constraints of Bragg peak FLASH proton therapy treatment planning.

Introduction: FLASH proton therapy (FLASH-PT) requires ultra-high dose rate (≥ 40 Gy/s) protons to be delivered in a short timescale whilst conforming to a patient-specific target. This study investigates the feasibility and constraints of Bragg peak FLASH-PT treatment planning, and compares the results produced to plans for intensity modulated proton therapy (IMPT).

Materials And Method: Bragg peak FLASH-PT and IMPT treatment plans were generated for bone (n=3), brain (n=3), and lung (n=4) targets using the MIROpt research treatment planning system and the Conformal FLASH library developed by Applications SA from the open-source version of UCLouvain.

Neurobiological Causal Models of Language Processing.

The language faculty is physically realized in the neurobiological infrastructure of the human brain. Despite significant efforts, an integrated understanding of this system remains a formidable challenge. What is missing from most theoretical accounts is a specification of the neural mechanisms that implement language function.

Matrix metalloproteinase landscape in the imiquimod-induced skin inflammation mouse model.

Inflammation and autoimmunity are known as central processes in many skin diseases, including psoriasis. It is therefore important to develop pre-clinical models that describe disease-related aspects to enable testing of pharmaceutical drug candidates and formulations. A widely accepted pre-clinical model of psoriasis is the imiquimod (IMQ)-induced skin inflammation mouse model, where topically applied IMQ provokes local skin inflammation.

The AsiDNA™ decoy mimicking DSBs protects the normal tissue from radiation toxicity through a DNA-PK/p53/p21-dependent G1/S arrest.

AsiDNA™, a cholesterol-coupled oligonucleotide mimicking double-stranded DNA breaks, was developed to sensitize tumour cells to radio- and chemotherapy. This drug acts as a decoy hijacking the DNA damage response. Previous studies have demonstrated that standalone AsiDNA™ administration is well tolerated with no additional adverse effects when combined with chemo- and/or radiotherapy.

Lipid nanoparticles containing labile PEG-lipids transfect primary human skin cells more efficiently in the presence of apoE.

Nucleic acid-based therapeutics encapsulated into lipid nanoparticles (LNPs) can potentially target the root cause of genetic skin diseases. Although nanoparticles are considered impermeable to skin, research and clinical studies have shown that nanoparticles can penetrate into skin with reduced skin barrier function when administered topically. Studies have shown that epidermal keratinocytes express the low-density lipoprotein receptor (LDLR) that mediates endocytosis of apolipoprotein E (apoE)-associated nanoparticles and that dermal fibroblasts express mannose receptors.

Comparable survival in rats with intracranial glioblastoma irradiated with single-fraction conventional radiotherapy or FLASH radiotherapy.

Background: Radiotherapy increases survival in patients with glioblastoma. However, the prescribed dose is limited by unwanted side effects on normal tissue. Previous experimental studies have shown that FLASH radiotherapy (FLASH-RT) can reduce these side effects.

Reconfiguring a Plane-Parallel Transmission Ionization Chamber to Extend the Operating Range into the Ultra-High Dose-per-pulse Regime.

This study aims to investigate the feasibility of enhancing the charge collection efficiency (CCE) of a transmission chamber by reconfiguring its design and operation. The goal was to extend the range of dose-per-pulse (DPP) values with no or minimal recombination effects up to the ultra-high dose rate (UHDR) regime. The response of two transmission chambers, with electrode distance of 1 mm and 0.

Beam control system and output fine-tuning for safe and precise delivery of FLASH radiotherapy at a clinical linear accelerator.

Introduction: We have previously adapted a clinical linear accelerator (Elekta Precise, Elekta AB) for ultra-high dose rate (UHDR) electron delivery. To enhance reliability in future clinical FLASH radiotherapy trials, the aim of this study was to introduce and evaluate an upgraded beam control system and beam tuning process for safe and precise UHDR delivery.

Materials And Methods: The beam control system is designed to interrupt the beam based on 1) a preset number of monitor units (MUs) measured by a monitor detector, 2) a preset number of pulses measured by a pulse-counting diode, or 3) a preset delivery time.

Evaluation of single-fraction high dose FLASH radiotherapy in a cohort of canine oral cancer patients.

Background: FLASH radiotherapy (RT) is a novel method for delivering ionizing radiation, which has been shown in preclinical studies to have a normal tissue sparing effect and to maintain anticancer efficacy as compared to conventional RT. Treatment of head and neck tumors with conventional RT is commonly associated with severe toxicity, hence the normal tissue sparing effect of FLASH RT potentially makes it especially advantageous for treating oral tumors. In this work, the objective was to study the adverse effects of dogs with spontaneous oral tumors treated with FLASH RT.

Evaluation of intensity-modulated electron FLASH radiotherapy in a clinical setting using veterinary cases.

Purpose: The increased normal tissue tolerance for FLASH radiotherapy (FLASH-RT), as compared to conventional radiotherapy, was first observed in ultra-high dose rate electron beams. Initial clinical trials in companion animals have revealed a high risk of developing osteoradionecrosis following high-dose single-fraction electron FLASH-RT, which may be related to inhomogeneities in the dose distribution. In the current study, we aim to evaluate the possibilities of intensity-modulated electron FLASH-RT in a clinical setting to ensure a homogeneous dose distribution in future veterinary and human clinical trials.

A randomized controlled study evaluating the head-lift exercise in head and neck cancer patients with radiation-induced dysphagia: effect on swallowing function and health-related quality of life over 12 months.

Purpose: Dysphagia is common after radiotherapy for head and neck cancer (HNC) and can affect health-related quality of life (HRQL). This randomized controlled trial aimed to evaluate the effect of the head-lift exercise (HLE) over 12 months in HNC patients with radiation-induced dysphagia.

Methods: Sixty-one patients with dysphagia were randomized to intervention group (n = 30) and control group (n = 31) at 6-36 months after completion of radiotherapy for HNC.

Determining the Effects of Pelleted Cranberry Vine Grains on the Ewe and Offspring during Pregnancy and Lactation.

When creating any new anti-parasitic interventions, it is important to evaluate their effects across all life stages. This study had three objectives, which were to evaluate the effect of feeding cranberry vine pellet (CVP) on (1) ewes' body weights and BCS during late gestation and lactation; (2) ewes' milk quality during lactation; and (3) lambs' body weight and growth parameters from birth to 65 days of age. Across two years, 41 Dorset ewes were fed either a 50% CVP or a matching control pellet (CON) from 104 ± 1.

Protease-Responsive Hydrogel Microparticles for Intradermal Drug Delivery.

Protease-responsive multi-arm polyethylene glycol-based microparticles with biscysteine peptide crosslinkers (CGPGG↓LAGGC) were obtained for intradermal drug delivery through inverse suspension photopolymerization. The average size of the spherical hydrated microparticles was ∼40 μm after crosslinking, making them attractive as a skin depot and suitable for intradermal injections, as they are readily dispensable through 27G needles. The effects of exposure to matrix metalloproteinase 9 (MMP-9) on the microparticles were evaluated by scanning electron microscopy and atomic force microscopy, demonstrating partial network destruction and decrease in elastic moduli.