Preoperative intensity-modulated radiation therapy in lower extremity soft tissue sarcomas with and without dose avoidance of uninvolved skin/subcutaneous tissue.

Background: The objective of this study was to evaluate whether dosimetric sparing of uninvolved normal tissues, including skin/subcutaneous flaps, affects acute and late toxicities in preoperative image-guided intensity-modulated radiation therapy (IG-IMRT) for lower extremity soft tissue sarcomas (LE-STS).

Methods: Patients with LE-STS from a phase 2 preoperative IG-IMRT trial (flap-sparing-IMRT, 2005-2009) and a prospectively maintained institutional database (standard-IMRT, 2005-2020) were propensity matched by age, sex, tumor size, grade, location, wound closure, and interval from IG-IMRT to surgery; all received 50 Gy in 25 fractions preoperatively. The primary outcome was major wound complication (MWC).

Metastases-directed therapy in addition to standard systemic therapy in oligometastatic castration-resistant prostate cancer in Canada (GROUQ-PCS 9): a multicentre, open-label, randomised, phase 2 trial.

Background: The role of metastasis-directed therapy (MDT) in castration-resistant prostate cancer (CRPC) remains unclear. Prostate Cancer Study 9 (PCS-9) aimed to evaluate the benefits of stereotactic body radiotherapy (SBRT) in addition to standard systemic therapy in patients with oligometastatic CRPC.

Methods: This open-label, randomised, phase 2 trial was conducted across 13 Canadian academic and community oncology centres.

Feasibility of Therapist-Driven MR-Guided Adaptive Radiotherapy for Oligometastatic Disease: Geometric Accuracy and Dosimetric Impact.

Introduction: MRI-guided adaptive radiation therapy (ART) is the resource-intensive process of daily treatment plan modification. This study aims to demonstrate the feasibility of radiation therapist (RT)-led MRI-guided ART for oligometastatic disease (OMD) by comparing geometric accuracy and dosimetric differences between RT and radiation oncologist (RO) re-contouring.

Methods: Five RTs and five ROs retrospectively re-contoured gross target volumes (GTVs) and organs-at-risk (OARs) for eight OMD cases.

Comparison of online adaptation strategies for magnetic resonance guided prostate radiation therapy.

Background And Purpose: MR-guided adaptive radiation therapy allows for daily plan adaptation to account for anatomical changes. Two common strategies are adapt-to-position (ATP), involving re-optimization based on isocenter shifts, and adapt-to-shape (ATS), involving full recontouring and reoptimization. This study provides a dosimetric comparison of ATP and ATS using accumulated dose.

Lipid packing defects are necessary and sufficient for membrane binding of α-synuclein.

α-Synuclein (αSyn), an intrinsically disordered protein implicated in Parkinson's disease, is thought to initiate aggregation by binding to cellular membranes. Previous studies suggest that anionic lipids are necessary for this binding. However, these studies largely focused on unmodified αSyn, while physiological αSyn is N-terminally acetylated (NTA).

Cumulative incidence and survival outcomes of brain metastases in sarcoma: a large single center retrospective analysis.

Background: The incidence and predictors of brain metastases (BrM) from sarcoma remain poorly characterized. We aimed to determine the cumulative incidence (CuI) and risk factors for BrM.

Methods: We retrospectively analyzed data from all sarcoma patients who presented to our center (2006-2023).

The role of stereotactic body radiotherapy in oligoprogressive prostate cancer: A site-specific analysis of the prospective, phase II RADIANT trial.

Background And Purpose: Changing to next-line systemic therapy is the standard-of-care for patients with progressive metastatic castrate-resistant prostate cancer. However, to preserve systemic therapy options and minimize toxicity, stereotactic body radiation therapy (SBRT) is being increasingly considered for patients with limited disease progression ('oligoprogression'). Herein, we report clinical, toxicity and quality of life (QOL) outcomes for an oligoprogressive prostate cancer cohort from a prospective trial.

Enhanced Nonvolatile Electrochemical Random-Access Memory and Artificial Synapse Characteristics through Oxygen Ion-Exchange Engineering in an Atomic-Layer-Deposited HfO Gate Insulator and a Zinc Oxide Channel Layer.

Enhanced nonvolatile memory and artificial synapse characteristics are achieved in oxygen ion-based ECRAM consisting of a low-temperature atomic layer-deposited (ALD) oxygen-deficient hafnium oxide (HfO) ion-exchange layer and zinc oxide (ZnO) channel layer. The drain current modulation of the device reaches a few orders of magnitude upon application of positive programming and negative erasing gate bias. Also, the device exhibits nonvolatile retention of modulated current up to >10 higher than the initial value for 24 h.

Recombinant protein platform for high-throughput investigation of peptide-liposome interactions via fluorescence anisotropy depolarization.

Many cytosolic proteins critical to membrane trafficking and function contain an unstructured domain that can bind to specific membranes, with a transition into an amphipathic helix induced upon membrane association. These inducible amphipathic helices often play a critical role in organelle recognition and subsequent function by these cytosolic proteins, but the tools and techniques used to characterize affinity towards specific membranes are low-throughput and highly dependent on the solubility of the inducible amphipathic helix. Here, we introduce a modular recombinant protein platform for rapidly measuring the binding affinity of inducible amphipathic helices towards a variety of membrane compositions and curvatures using high-throughput fluorescence anisotropy measurements.

Insights into pathophysiology, biomarkers, and therapeutics in tauopathies: Proceedings of the Tau2024 Global Conference.

Recent years have seen major advances in tau-associated brain disorders through interdisciplinary research spanning molecular biology, neuroimaging, clinical trials, and therapeutic development. The Tau2024 Global Conference, hosted by the Alzheimer's Association, CurePSP, and Rainwater Charitable Foundation, showcased these efforts by bringing together researchers and experts worldwide to discuss the latest advancements in tau research. The conference aimed to attract talent and funding to study tauopathies, particularly among early-career researchers, and to foster interdisciplinary alignment and collaboration around challenges in tau research.

Survival outcomes and clinical characteristics of brain metastases from prostate cancer: A single-center analysis.

Background: Brain metastases (BrM) from prostate cancer (PC) are rare. This study sought to evaluate their prevalence, clinical features, treatment modalities, and survival outcomes.

Methods: From a database of BrM patients, we analyzed 28 cases of prostate cancer treated at our center between 2008 and 2023.

Patient-reported Quality of Life in PROFIT, a Phase 3 Randomized Clinical Trial Evaluating Moderately Hypofractionated Radiotherapy for Intermediate-risk Prostate Cancer.

Background And Objective: The PROFIT trial was designed to compare moderately hypofractionated (HF) radiotherapy versus conventional fractionation (CF) for patients with intermediate-risk prostate cancer (IR-PC). Similar efficacy and toxicity outcomes were previously reported. The aim of the current analysis was to evaluate differences in long-term patient-reported outcomes (PROs) between the HF and CF arms in PROFIT.

Predicting Maternal and Fetal Exposures of Elexacaftor-Tezacaftor-Ivacaftor during Pregnancy through Physiologically Based Pharmacokinetic Models.

The use of elexacaftor/tezacaftor/ivacaftor (ETI) has been associated with increased fertility in women with cystic fibrosis (CF) and is increasingly used during pregnancy to support both maternal and fetal health. However, little is known about the pharmacokinetics (PK) of ETI during pregnancy, which is crucial for optimizing its efficacy and safety. This study aimed to predict the PK of ETI during pregnancy and to determine the maternal dose required to achieve therapeutic concentrations in both the maternal and fetus.

Patient-Reported Quality-of-Life Outcomes After Abdominopelvic Stereotactic Body Radiation Therapy Using an MR-Linac System.

Purpose: Despite the increasing use of MR-Linac (MRL) in the management of patients with oligometastatic or upper gastrointestinal malignancies, health-related quality-of-life (HRQoL) outcomes are lacking. Currently, it is not well established whether treatments using MRL offer HRQoL advantages over CT-based treatments. In this study, we present prospectively collected HRQoL data after abdominopelvic stereotactic body radiation therapy (SBRT) on a 1.

Evaluation of Complex Drug Interactions Between Elexacaftor-Tezacaftor-Ivacaftor and Statins Using Physiologically Based Pharmacokinetic Modeling.

The increasing use of statins in people with cystic fibrosis (CF) necessitates the investigation of potential drug-drug interactions (DDI) of statins with cystic fibrosis transmembrane conductance regulator (CFTR) modulators, including elexacaftor, tezacaftor, and ivacaftor (ETI). The interactions may involve the potential inhibition of cytochrome P450 isoenzymes (CYPs), organic anion-transporting polypeptides (OATPs), and Breast Cancer Resistance Protein (BCRP) by ETI. This presents a therapeutic challenge in CF due to the potential for elevated statin levels, consequently heightening the risk of myopathy.

Pan-Canadian assessment of image guided adaptive radiation therapy and the role of the radiation therapist.

Purpose: Adaptive radiation therapy (ART) is a close-looped process where anatomic changes observed during treatment are identified, leading to plan modification prior to treatment delivery. The aim of this study was to explore the status of ART across Canada and review the impact of adaptive technologies on the roles and responsibilities of Radiation Therapists (RTTs).

Materials And Methods: Study information and a link to a 30-question survey was sent via email to the RTT manager of all cancer centres across Canada (n = 48).

An Automated Approach for Domain-Specific Knowledge Graph Generation─Graph Measures and Characterization.

In 2020, nearly 3 million scientific and engineering papers were published worldwide (White, K. Publications Output: U.S.

Lipid Packing Defects are Necessary and Sufficient for Membrane Binding of α-Synuclein.

α-Synuclein (αSyn), an intrinsically disordered protein implicated in Parkinson's disease, is thought to initiate aggregation by binding to cellular membranes. Previous studies suggest that anionic lipids are necessary for this binding. However, these studies largely focused on unmodified αSyn, while physiological αSyn is N-terminally acetylated (NTA).

Clinical Outcomes of Stage IIA/IIB Seminoma Treated With Radiation Therapy and Chemotherapy: Should Regional Therapy be Considered the Preferred Treatment Approach?

Purpose: The optimal management of patients with de novo clinical stage IIA/B (CSIIA/B) or relapsed CSIIA/B (Rel-CSIIA/B) seminoma remains debated because of a lack of randomized evidence. Here, we sought to evaluate outcomes after radiation therapy and chemotherapy in this setting.

Methods And Materials: A prospectively maintained single-institutional database was retrospectively queried for patients diagnosed between 1995 and 2016 with de novo or Rel-CSIIA/B.

Partial or focal brachytherapy for prostate cancer: a systematic review and meta-analysis.

Objectives: Recent advances in image-guided brachytherapy have allowed for treatment volume reduction in the treatment of prostate cancer, with the aim to optimize disease control and reduce toxicities. This systematic review reports on the efficacy and safety of focal brachytherapy for treatment of patients with localized prostate cancer.

Methods: Medline, Embase, Web of Science, and Cochrane were searched from inception to July 2023.

A nonequilibrium kinetic model of high-resolution vibrational energy transfer in RDX from selective IR excitation.

In this paper, we develop a model based on a second quantization-with anharmonic phonon scattering and the phonon Boltzmann transport equation-to study precise high-resolution nonequilibrium vibrational energy transfer (VET) under selective phonon excitation in cyclotrimethylene trinitramine. We simulate mid-infrared pump-probe spectroscopy and observe a prompt appearance (<1 ps) of broad-spectrum intensity, which agrees well with experimental data in the literature. The selective excitation of phonons at different frequencies reveals distinct VET pathways and the kinetic evolution of mode occupations as the system reaches a new equilibrium temperature.

Pharmacokinetics of Omadacycline in Adults with Cystic Fibrosis.

Background: Omadacycline offers a potential advancement in the management of infections in people with cystic fibrosis (CF) because of its spectrum of activity, intrapulmonary penetration, and oral bioavailability. A prospective single-dose, single-arm study was conducted to characterize the pharmacokinetic (PK) profile of omadacycline in people with CF, considering the known alterations in PK observed in this population (NCT04460586, 2020-07-01).

Methods: Plasma samples were obtained from nine adults with CF who received a single dose of intravenous omadacycline 100 mg over 0.

Identification of Malignancy in Peritumoral Edema in Soft Tissue Sarcoma: A Novel Targeted Molecular Approach.

Background: Peritumoral edema on staging magnetic resonance imaging (MRI) is associated with higher local recurrence in soft tissue sarcoma (STS). This may relate to the presence of satellite malignant cells that are difficult to distinguish from benign atypia, leading to over- or undertreatment. This study evaluated a novel targeted molecular approach to identify malignancy in STS peritumoral planes as a means to improve personalized care.