Development and validation of an LC-MS/MS method for quantification of Osimertinib and its two metabolites AZ7550 and AZ5104 in human plasma including long-time storage.

Osimertinib (AZD9291) is a widely used tyrosine kinase inhibitor for the treatment of non-small cell lung cancer patients with activating EGFR mutations. However, the correlation between dose and efficacy has been debated for several years. For this reason, there is a need for standardized methods for routine analysis, clinical studies on pharmacokinetics and dose-response relationships, and greater understanding of preanalytical conditions, such as sample storage stability.

Ethical Considerations Regarding Digital Health Services in Home-Based Palliative Care: A Subanalysis of 2 Reviews.

Historically, in-person contact between patients and nurses in home-based care has been pivotal in palliative care and hospice care. The provision of home-based palliative care services could be challenged by the projected increase in patients who need palliative care and by the expected shortage of nurses. Digital health services could constitute one measure for delivering high-quality palliative care, enabling patients to stay home.

The clinical efficacy of a novel smartphone-based salivary self-test for the prediction of pre-eclampsia, pregnancy-induced hypertension and intrauterine growth restriction: a prospective cohort study.

Introduction: This study investigated the efficacy of a digital health solution utilizing smartphone images of colorimetric test-strips for home-based salivary uric acid (sUA) measurement to predict pre-eclampsia (PE), pregnancy-induced hypertension (PIH), and intrauterine growth restriction (IUGR).

Methods: 495 pregnant women were included prospectively at Zealand University Hospital, Denmark. They performed weekly self-tests from mid-pregnancy until delivery and referred these for analysis by a smartphone-app.

Aging in (a meaningful) place - appropriateness and feasibility of Outdoor Reablement in a rural Arctic setting.

Background: As populations age in the Western world, interventions aiming for 'aging in place', such as reablement, have gained prominence. Reablement programs have focused on enabling older people to maintain independence in their home environment. However, while a growing body of research points to the considerable benefits of engaging in outdoor environments, reablement rarely addresses outdoor activities.

The proton RBE and the distal edge effect for acute and late normal tissue damage in vivo.

Background And Purpose: In proton therapy, a relative biological effectiveness (RBE) of 1.1 is used toreach an isoeffective biological response between photon and proton doses. However, the RBE varies with biological endpoints and linear energy transfer (LET), two key parameters in radiotherapy.

Automated acute skin toxicity scoring in a mouse model through deep learning.

This study presents a novel approach to skin toxicity assessment in preclinical radiotherapy trials through an advanced imaging setup and deep learning. Skin reactions, commonly associated with undesirable side effects in radiotherapy, were meticulously evaluated in 160 mice across four studies. A comprehensive dataset containing 7542 images was derived from proton/electron trials with matched manual scoring of the acute toxicity on the right hind leg, which was the target area irradiated in the trials.

Intra-Rater Reliability of Panoramic Ultrasound Imaging for Determining Quadriceps Muscle Cross-Sectional Area in Middle-Aged and Elderly Adults.

Panoramic ultrasound (US) is an extended field-of-view (EFOV) imaging technique that enables visualization of large-scale skeletal muscles. This technique has previously been found to produce valid and reliable quantifications of muscle morphology in primarily young male subjects. The purpose was to investigate the intra-rater between-session test-retest reliability of panoramic US imaging for determining vastus lateralis (VL) and rectus femoris (RF) cross-sectional area (mCSA) in healthy middle-aged to elderly adults.

Proton- compared to X-irradiation leads to more acinar atrophy and greater hyposalivation accompanied by a differential cytokine response.

Proton therapy gives less dose to healthy tissue compared to conventional X-ray therapy, but systematic comparisons of normal tissue responses are lacking. The aim of this study was to investigate late tissue responses in the salivary glands following proton- or X-irradiation of the head and neck in mice. Moreover, we aimed at investigating molecular responses by monitoring the cytokine levels in serum and saliva.

A bispecific antibody approach for the potential prophylactic treatment of inherited bleeding disorders.

Inherited bleeding disorders such as Glanzmann thrombasthenia (GT) lack prophylactic treatment options. As a result, serious bleeding episodes are treated acutely with blood product transfusions or frequent, repeated intravenous administration of recombinant activated coagulation factor VII (rFVIIa). Here we describe HMB-001, a bispecific antibody designed to bind and accumulate endogenous FVIIa and deliver it to sites of vascular injury by targeting it to the TREM (triggering receptor expressed on myeloid cells)-like transcript-1 (TLT-1) receptor that is selectively expressed on activated platelets.

Correlation between local instantaneous dose rate and oxygen pressure reduction during proton pencil beam scanning irradiation.

Background And Purpose: Oxygen dynamics may be important for the tissue-sparing effect observed at ultra-high dose rates (FLASH sparing effect). This study investigated the correlation between local instantaneous dose rate and radiation-induced oxygen pressure reduction during proton pencil beam scanning (PBS) irradiations of a sample and quantified the oxygen consumption g-value.

Materials And Methods: A 0.

Spread-out Bragg peak FLASH: quantifying normal tissue toxicity in a murine model.

Objective: A favorable effect of ultra-high dose rate (FLASH) radiation on normal tissue-sparing has been indicated in several preclinical studies. In these studies, the adverse effects of radiation damage were reduced without compromising tumor control. Most studies of proton FLASH investigate these effects within the entrance of a proton beam.

Expression of the non-coding RNA nc886 facilitates the development of tyrosine kinase inhibitor resistance in EGFR-mutated non-small-cell lung cancer cells.

Treatment of non-small-cell lung cancer (NSCLC) patients possessing EGFR-activating mutations with tyrosine kinase inhibitors (TKIs) can confer an initial promising response. However, TKI resistance inevitably arises. Numerous TKI resistance mechanisms are identified including EGFR secondary mutations, bypass receptor tyrosine kinase (RTK) signaling, and cellular transition e.

Development of an Ex Vivo Functional Assay for Prediction of Irradiation Related Toxicity in Healthy Oral Mucosa Tissue.

Radiotherapy in the head-and-neck area is one of the main curative treatment options. However, this comes at the cost of varying levels of normal tissue toxicity, affecting up to 80% of patients. Mucositis can cause pain, weight loss and treatment delays, leading to worse outcomes and a decreased quality of life.

Navigating the Critical Translational Questions for Implementing FLASH in the Clinic.

The "FLASH effect" is an increased therapeutic index, that is, reduced normal tissue toxicity for a given degree of anti-cancer efficacy, produced by ultra-rapid irradiation delivered on time scales orders of magnitude shorter than currently conventional in the clinic for the same doses. This phenomenon has been observed in numerous preclinical in vivo tumor and normal tissue models. While the underlying biological mechanism(s) remain to be elucidated, a path to clinical implementation of FLASH can be paved by addressing several critical translational questions.

The Effect of Family Nursing Conversations as an Add-on to Multidisciplinary Treatment in Patients with Chronic Non-Cancer Pain: A Quasi-Experimental Trial.

Introduction: Chronic non-cancer pain (CNCP) is a lifelong condition with radical consequences, calling for management involving patients' families. Interventions based on the family systems nursing framework by Wright and Leahey have proved beneficial in other populations but require investigation in a CNCP population. This trial assumed that family nursing conversations (FNCs) based on the family systems nursing framework would increase patients' and family members' self-efficacy concerning CNCP management.

Combination of proton- or X-irradiation with anti-PDL1 immunotherapy in two murine oral cancers.

Combining radiation therapy with immunotherapy is a strategy to improve both treatments. The purpose of this study was to compare responses for two syngeneic head and neck cancer (HNC) tumor models in mice following X-ray or proton irradiation with or without immune checkpoint inhibition (ICI). MOC1 (immunogenic) and MOC2 (less immunogenic) tumors were inoculated in the right hind leg of each mouse (C57BL/6J, n = 398).

Proton FLASH: Impact of Dose Rate and Split Dose on Acute Skin Toxicity in a Murine Model.

Purpose: Preclinical studies have shown a preferential normal tissue sparing effect of FLASH radiation therapy with ultra-high dose rates. The aim of the present study was to use a murine model of acute skin toxicity to investigate the biologic effect of varying dose rates, time structure, and introducing pauses in the dose delivery.

Methods And Materials: The right hind limbs of nonanaesthetized mice were irradiated in the entrance plateau of a pencil beam scanning proton beam with 39.

Proinflammatory polarization strongly reduces human macrophage in vitro phagocytosis of tumor cells in response to CD47 blockade.

Antibody-based CD47 blockade aims to activate macrophage phagocytosis of tumor cells. However, macrophages possess a high degree of phenotype heterogeneity that likely influences phagocytic capacity. In murine models, proinflammatory (M1) activation increases macrophage phagocytosis of tumor cells, but in human models, results have been conflicting.

Performance characteristics of a polymerase chain reaction-based assay for the detection of EGFR mutations in plasma cell-free DNA from patients with non-small cell lung cancer using cell-free DNA collection tubes.

Survival rates in non-small cell lung cancer (NSCLC) are low. Detection of circulating tumor DNA in liquid biopsy (plasma) is increasingly used to identify targeted therapies for clinically actionable mutations, including EGFR mutations in NSCLC. The cobas® EGFR Mutation Test v2 (cobas EGFR test) is FDA-approved for EGFR mutation detection in tissue or liquid biopsy from NSCLC.

Two-dimensional time-resolved scintillating sheet monitoring of proton pencil beam scanning FLASH mouse irradiations.

Background: Dosimetry in pre-clinical FLASH studies is essential for understanding the beam delivery conditions that trigger the FLASH effect. Resolving the spatial and temporal characteristics of proton pencil beam scanning (PBS) irradiations with ultra-high dose rates (UHDR) requires a detector with high spatial and temporal resolution.

Purpose: To implement a novel camera-based system for time-resolved two-dimensional (2D) monitoring and apply it in vivo during pre-clinical proton PBS mouse irradiations.

Oxygen Enhancement Ratio-Weighted Dose Quantitatively Describes Acute Skin Toxicity Variations in Mice After Pencil Beam Scanning Proton FLASH Irradiation With Changing Doses and Time Structures.

Purpose: The aim of this work was to investigate the ability of a biological oxygen enhancement ratio-weighted dose, D, to describe acute skin toxicity variations observed in mice after proton pencil beam scanning irradiations with changing doses and beam time structures.

Methods And Materials: In five independent experiments, the right hind leg of a total of 621 CDF1 mice was irradiated previously in the entrance plateau of a pencil beam scanning proton beam. The incidence of acute skin toxicity (of level 1.

ctDNA-based minimal residual disease detection in lung cancer patients treated with curative intended chemoradiotherapy using a clinically transferable approach.

Background: Reliable biomarkers are needed to identify tumor recurrence of non-small cell lung cancer (NSCLC) patients after chemoradiotherapy (CRT) with curative intent. This could improve consolidation therapy of progressing patients. However, the approach of existing studies has limited transferability to the clinic.

Evaluation of in vitro irradiation setup: Designed for the horizontal beamline at the Danish Centre for Particle Therapy.

Background: Radiobiological experimental setups are challenged by precise sample positioning along depth dose profile, scattering conditions, and practical difficulties that must be addressed in individual designs. The aim of this study was to produce cell survival curves with several irradiation modalities, by using a setup designed at the Danish Centre for Particle Therapy (DCPT) for in vitro proton irradiations using a horizontal beam line and thereby evaluating the setups use for in vitro irradiations experiments.

Materials And Methods: The setup is a water phantom suitable for in vitro research with multiple irradiation modalities, in particular the pencil scanning proton beam available from a horizontal experimental beamline.