BIOTINYLATED AND CHELATED POLY-L-LYSINE AS EFFECTOR FOR PRETARGETING IN CANCER THERAPY AND IMAGING

Objective: The aim of this study was to synthesise and evaluate polylysine-based effectors for pretargeted radioimmunotherapy and imaging. These molecules can readily be size-modified and charge-modified to decrease the renal uptake of radioactivity, which is often a major problem for small radiolabeled molecules. Several chelators and biotin molecules (for antibody-streptavidin-binding in vivo) are also easily incorporated into one structure because of the polylysine.Methods: The effectors were synthesised using poly-L-lysine, NHS-LC-biotin, CHX-A''-DTPA or p-SCN-Bn-DOTA and succinic anhydride. They were characterised, labelled with 213Bi for targeted α therapy, 68Ga for PET and 111In for SPECT, and evaluated in vitro. A kidney uptake study was performed as well with two different-sized 213Bi-labeled effectors, to evaluate how the difference in size affects the renal filtration.Results: Radiochemical purities between 97.4±0.6 % and 99.6±0.1 % and decay-corrected yields of 80.2±2.4 % after purification were achieved with the radiolabeled molecules, as well as a specific activity of 7.6 × 103GBq/µmol. The avidin binding capacity was 94.4±1.9%. The kidney uptake study demonstrated a reduction of renal absorbed dose by 80% when modifying the molecular size and charge.Conclusion: The synthesised polylysine-based effectors show potential for further in vivo evaluation in pretargeted radioimmunotherapy and imaging

Rethinking rehabilitation after percutaneous coronary intervention: a protocol of a multicentre cohort study on continuity of care, health literacy, adherence and costs at all care levels (the CONCARD PCI )

Introduction: Percutaneous coronary intervention (PCI) aims to provide instant relief of symptoms, and improve functional capacity and prognosis in patients with coronary artery disease. Although patients may experience a quick recovery, continuity of care from hospital to home can be challenging. Within a short time span, patients must adjust their lifestyle, incorporate medications and acquire new support. Thus, CONCARDPCI will identify bottlenecks in the patient journey from a patient perspective to lay the groundwork for integrated, coherent pathways with innovative modes of healthcare delivery. The main objective of the CONCARDPCI is to investigate (1) continuity of care, (2) health literacy and self-management, (3) adherence to treatment, and (4) healthcare utilisation and costs, and to determine associations with future short and long-term health outcomes in patients after PCI. Methods and analysis: This prospective multicentre cohort study organised in four thematic projects plans to include 3000 patients. All patients undergoing PCI at seven large PCI centres based in two Nordic countries are prospectively screened for eligibility and included in a cohort with a 1-year follow-up period including data collection of patient-reported outcomes (PRO) and a further 10-year follow-up for adverse events. In addition to PROs, data are collected from patient medical records and national compulsory registries. Ethics and dissemination: Approval has been granted by the Norwegian Regional Committee for Ethics in Medical Research in Western Norway (REK 2015/57), and the Data Protection Agency in the Zealand region (REG-145-2017). Findings will be disseminated widely through peer-reviewed publications and to patients through patient organisations. Trial registration number: NCT03810612

Cruise report Hywind Tampen 13 to 28 March 2023 - Cruise no. 2023001004 G.O. Sars

Source at https://www.hi.no/hi.There is very little knowledge related to how floating windfarms effect the marine environment as this is such a new “product”. Thus, the data that we gathered on this cruise will be novel in that sense. The aim of the cruise was to look at possible effects of the windfarm on the marine environment. Based on limited cruise time and tough weather conditions around Hywind Tampen we had to be selective related to topics for this first cruise, and we choose to focus on the following: 1) Measuring noise from the turbine. This we did by deploying a hydrophone mooring within the windfarm. 2) Measuring current to track possible changes in current and wake effect. We did this by deploying ADCP’s within and around the windfarm, and by conducting CTD transects around and within the windfarm. 3) Look at possible effects on pelagic fish distribution, by conducting acoustics transects with RV G.O. Sars's multi-frequency acoustics, within and around the windfarm. As the RV G.O. Sars is not allowed closer then 500m to the turbines, we conducted acoustic transects with an acoustic kayak-drone within the 500 m range to the wind turbines. The kayak being allowed as close as 15-20m to the turbines. To able ground truthing of acoustic findings we trawled with an open trawl equipped with a camera (DeepVision) and we took eDNA samples along the transects. 4) Effect of bottom structure on the benthic fauna. This was studied by ROV transects filming fauna around 3 suction anchors and the adjacent chains connecting the turbines to the anchor. ROV control transects were conducted from the very same suction anchors, but on a line moving away from the windfarm. This cruise was conducted in collaboration with the NFR-funded WindSys project

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe

COST Action CA19114, Network for Optimized Astatine labelled Radiopharmaceuticals

Cancer is a major health concerns for European citizens. Thus, the main research aim of this Network for Optimized Astatine labeled Radiopharmaceuticals (NOAR) COST Action is to successfully demonstrate that one of the most promising radionuclides for Targeted Alpha Therapy (TAT), namely astatine-211, can become the European standard for treatment of certain cancerous pathologies. To this end, an efficient networking is essential among all European stakeholders interested in promoting astatine-211 for medical applications. NOAR COST Action brings together European and international excellence labs, astatine-211 production centers, hospitals, industry and patient associations from more than 20 countries, thus covering the whole value chain of innovation: production, chemistry, radiochemistry, biology, preclinical and clinical research and delivery of radiopharmaceuticals to patients. A European web portal will be created containing information for patients, practitioners, researchers, Industry and as a contact point for National and European patient associations. The idea is to gather forces at the European level in order to implement actions to leverage hurdles to the development of this powerful radionuclide and to identify pathologies in which it will be particularly relevant. A special emphasis will be given to train a new generation of young researchers and PhD students, promoting interdisciplinary competencies through international and inter-sectoral mobility. The long-term goal of this project is to make Astatine-211 technology available to all European citizen

Clinical Effects and Cytokine Responses from Ingestion of AndoSanTM in Patients with Ulcerative Colitis and Crohn´s Disease. A Randomized Placebo Controlled Study

Inflammatorisk tarmsykdom (IBD) er betennelsestilstander i tarmen med hovedsakelig ukjent sykdomsårsak, og består av sykdomsgruppene morbus crohn (CD) og ulcerøs kolitt (UC). Medisinsk behandling har som mål å dempe symptomer og sykdomsaktivitet, men er beheftet med varierende effekt og en del bivirkninger. Tidligere studier har vist interessante resultater for soppen Agaricus blazei Murill (AbM) på blant annet betennelse og infeksjon. Medisinsk behandling med bruk av sopp er svært vanlig i Asia, hvor for eksempel AbM brukes som behandling hos ca 500.000 mennesker i Japan. AndoSanTM er en soppekstrakt som inneholder 82% AbM, 15% Hericeum erinaceum og 3% Grifola frondosa. Dette soppekstraktet ble funnet mest potent i et utvalg av soppekstrakter i studier på blodforgiftning i mus, og ble derfor foretrukket i videre studier av vår forskningsgruppe. Stig Palm Therkelsen har i sitt doktorarbeid gjennomført studier på IBD pasienter hvor effekten av AndoSanTM ble sammenliknet med placebo. Alle pasientene hadde mild til moderat sykdomsaktivitet. Pasientene rapporterte tilbake om kliniske parametere som symptomer, livskvalitet og fatigue. Resultatene viste bedring av symptomer i AndoSanTM-gruppen sammenliknet med placebo, både for CD og UC, og i tillegg livskvalitet og fatigue for UC. Det ble også gjort analyse av signalproteiner (cytokiner) i immunforvaret fra blodprøver. Resultater fra disse undersøkelsene viste kun en marginal effekt i retning av betennelsesreduksjon, og kunne dermed ikke forklare mekanismene til at pasientene følte seg bedre. Behandling med AndoSanTM på IBD pasienter kan etter vår vurdering anbefales som et supplement til ordinær medisinsk behandling, spesielt for pasienter med UC. Det ble ikke rapportert om bivirkninger etter inntak av AndoSanTM i våre studier

Sex differences in incidence rate, and temporal changes in surgical management and adverse events after hip fracture surgery in Denmark 1997–2017: a register-based study of 153,058 hip fracture patients

Background and purpose — Extensive research and national multidisciplinary programs have striven to introduce uniform standards of treatment and mitigate mortality and adverse events after hip fracture surgery over the past decades. A large-scale overview of temporal developments in hip fracture surgery and care is warranted. Patients and methods — We studied Danish patients aged ≥ 60 years, sustaining their first ever hip fracture between 1997 and 2017. Patients were identified from the Danish National Patient Registry (DNPR). Incidence rates of first hip fracture were calculated per 1,000 patient-years and stratified by age group and sex. Information on pre-injury living settings, comorbidities, and medications were obtained from national administrative registers. Type of fracture and treatment choice were recorded, and patients were followed for 1 year to observe mortality, readmission, and surgical complications. Results — Data from 153,058 patients was analyzed. Incidence rate decreased in both sexes, but only led to a reduction in the annual number of hip fractures in the female population. Choice of surgery shifted away from sliding hip screws and parallel implants (SHS-PI), towards intramedullary nailing and hemi-/arthroplasties for trochanteric and femoral neck fractures, respectively. Pre-injury diagnosed morbidity and 1-year readmissions increased contrary to mortality. Median age remained stable around 83 (IQR 77–88) for women and 80 (IQR 73–86) for men. Interpretation — Over the past 2 decades important aspects of hip fracture management have improved. However, sex differences were observed, and men remain more vulnerable than women in terms of morbidity, mortality, and incidence rate