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Abstract Background Healthcare policy implemented during the COVID-19 pandemic may have impacted the health of patients with heart failure. Australian data provide a unique opportunity to examine service disruption independent of significant COVID-19 burden. This study aimed to examine heart failure care during the pandemic in New South Wales (NSW). Methods Analysis of hospital utilisation among patients aged ≥ 18 years with a primary diagnosis of heart failure conducted using linked administrative health records from hospital admission, emergency department, non-admitted services, and mortality data collections. Health service utilisation and outcomes were compared “Pre-pandemic” (PP): 16th March 2018 – 28th August 2019 and “During pandemic” (DP): 16th March 2020 – 28th August 2021. Mortality data were available until December 2021. Results Heart failure-related ED presentations and hospital admissions were similar between the periods (PP = 15,324 vs DP = 15,023 ED presentations, PP = 24,072 vs DP = 23,145 hospital admissions), though rates of admission from ED were lower DP (PP = 12,783/15,324 (83.4% [95% CI 82.8-84.0]) vs DP = 12,230/15,023 (81.4% [95% CI 80.8-82.0%]). There was no difference according to age, sex, rurality, or socioeconomic status. Outpatient volume reduced DP (PP = 44,447 vs DP = 35,801 occasions of service), but telehealth visits increased nearly threefold (PP = 5,978/44,447 (13.4% [95% CI 13.1-13.8%]) vs DP = 15,901/35,801 (44.4% [95% CI 43.9-44.9%]) with highest uptake among the wealthy and those in major cities. Time to heart failure-related ED presentation, hospitalisation or all-cause mortality following index admission was longer DP (PP = 273 [IQR 259, 290] days, DP = 323 [IQR 300, 342] days, HR 0.91 [95% CI 0.88, 0.95]). Conclusions Policies implemented DP had minimal impact on volumes of inpatient heart failure care in NSW hospitals, but there were fewer admissions from ED and reduced volumes of publicly funded outpatient care. A rapid shift from patient-facing to remotely delivered care enabled compliance with restrictions and was associated with increased time to heart failure-related adverse events, but access was not afforded equally across the socio-demographic spectrum.

Abstract In multicentric studies, data sharing between institutions might negatively impact patient privacy or data security. An alternative is federated analysis by secure multiparty computation. This pilot study demonstrates an architecture and implementation addressing both technical challenges and legal difficulties in the particularly demanding setting of clinical research on cancer patients within the strict European regulation on patient privacy and data protection: 24 patients from LMU University Hospital in Munich, Germany, and 24 patients from Policlinico Universitario Fondazione Agostino Gemelli, Rome, Italy, were treated for adrenal gland metastasis with typically 40 Gy in 3 or 5 fractions of online-adaptive radiotherapy guided by real-time MR. High local control (21% complete remission, 27% partial remission, 40% stable disease) and low toxicity (73% reporting no toxicity) were observed. Median overall survival was 19 months. Federated analysis was found to improve clinical science through privacy-friendly evaluation of patient data in the European health data space.

Abstract This study investigated the effects of corn cob biochar (CCB) and rice husk biochar (RHB) additions (at 0%, 5%, and 10% w/w) on nitrogen and carbon dynamics during co-composting with poultry litter, rice straw, and domestic bio-waste. The study further assessed the temperature, moisture, pH, and nutrient contents of the mature biochar co-composts, and their potential phytotoxicity effects on amaranth, cucumber, cowpea, and tomato. Biochar additions decreased NH4 +-N and NO3- contents, but bacteria and fungi populations increased during the composting process. The mature biochar co-composts showed higher pH (9.0–9.7), and increased total carbon (24.7–37.6%), nitrogen (1.8–2.4%), phosphorus (6.5–8.1 g kg−1), potassium (26.8–42.5 g kg−1), calcium (25.1–49.5 g kg−1), and magnesium (4.8–7.2 g kg−1) contents compared to the compost without biochar. Germination indices (GI) recorded in all the plants tested with the different composts were greater than 60%. Regardless of the biochar additions, all composts treatments showed no or very minimal phytotoxic effects on cucumber, amaranth and cowpea seeds. We conclude that rice husk and corn cob biochar co-composts are nutrient-rich and safe soil amendment for crop production.

Abstract Generative deep learning models enable data-driven de novo design of molecules with tailored features. Chemical language models (CLM) trained on string representations of molecules such as SMILES have been successfully employed to design new chemical entities with experimentally confirmed activity on intended targets. Here, we probe the application of CLM to generate multi-target ligands for designed polypharmacology. We capitalize on the ability of CLM to learn from small fine-tuning sets of molecules and successfully bias the model towards designing drug-like molecules with similarity to known ligands of target pairs of interest. Designs obtained from CLM after pooled fine-tuning are predicted active on both proteins of interest and comprise pharmacophore elements of ligands for both targets in one molecule. Synthesis and testing of twelve computationally favored CLM designs for six target pairs reveals modulation of at least one intended protein by all selected designs with up to double-digit nanomolar potency and confirms seven compounds as designed dual ligands. These results corroborate CLM for multi-target de novo design as source of innovation in drug discovery.

Abstract Purpose/objective Currently, there are few prospective data on the tolerability of combining targeted therapies (TT) with radiation therapy (RT). The objective of this prospective study was to assess the feasibility and toxicity of pairing RT with concurrent TT in cancer patients. The aim was to enhance the existing evidence base for the simultaneous administration of targeted substances together with radiotherapy. Methods Prospective study enrollment was conducted at a single institution between March 1, 2020, and December 31, 2021, for all patients diagnosed with histologically confirmed cancer who underwent external beam radiotherapy in combination with targeted therapy. The study, known as the “targeted RT study,” was registered in the German Clinical Trials Register under DRKS00026193. Systematic documentation of the toxicity profiles of different targeted therapies was performed, and the assessment of acute toxicity followed the guidelines of the National Cancer Institute Common Terminology Criteria for Adverse Events Version v5.0. Results A total of 334 patients underwent 683 radiation therapy series. During the course of RT, 51 different TT substances were concurrently administered. External beam radiotherapy was employed for various anatomical sites. The combination of RT and concurrent TT administration was generally well tolerated, with no instances of severe acute toxicity observed. The most commonly reported toxicity was fatigue, ranging from mild to moderate Common Terminology Criteria for Adverse Events (CTCAE) °I-°III. Other frequently observed toxicities included dermatitis, dyspnea, dysphagia, and dry cough. No toxicity greater than moderate severity was recorded at any point. In only 32 patients (4.7% of evaluated RT series), the concurrent substance administration was discontinued due to side effects. However, these side effects did not exceed mild severity according to CTCAE, suggesting that discontinuation was a precautionary measure. Only one patient receiving Imatinib treatment experienced a severe CTCAE °III side effect, leading to discontinuation of the concurrent substance due to the sudden occurrence of melaena during RT. Conclusion In conclusion, the current study did not demonstrate a significant increase or additional toxicity when combining radiotherapy and concurrent targeted therapy. However, additional research is required to explore the specific toxicity profiles of the various substances that can be utilized in this context. Trial registration number DRKS00026193. Date of registration 12/27/2022 (retrospectively registered).

There is emerging evidence to suggest that diet and dietary interventions can have an impact on heart failure (HF) outcomes. Currently, the restriction of salt intake is the only dietary advice that is consistently guideline-recommended for the management of HF despite conflicting evidence for its efficacy. Dietary components that have been investigated in people with HF include middle-chain triglyceride (MCT) oil, beta-hydroxybutyrate (BHB) salts, ketone esters and coenzyme Q10 (CoQ10). Supplementation with these components is thought to be cardioprotective possibly due to an increase in myocardial energy production. There have been research studies on the effectiveness of The Dietary Approaches to Stop Hypertension (DASH) diet and the Mediterranean Diet (MedDiet) in the treatment of HF, but with conflicting results. The ketogenic diet (KD) has come to the forefront of interest due to evidence indicating its effectiveness in addressing the metabolic shift that occurs in HF. However, there is a lack of randomised controlled trials (RCT) centred around the KD. In any dietary intervention, factors such as adherence and compliance affect the validity of the results. Malnutrition, sarcopenia and/or cardiac cachexia can be present in the more advanced stages of heart failure. Nutritional screening, assessment and support/intervention are important aspects of treatment in the advanced stages of heart failure. Furthermore, HF management through dietary intervention is further complicated by the presence of comorbidities, such as diabetes mellitus (DM) and coronary artery disease (CAD). Long-term studies on the use of dietary modifications in people with HF are warranted to ascertain their efficacy, safety and side effects.

Background Protein biomarkers that reflect different pathophysiological pathways have been associated with the risk of adverse cardiovascular events. However, it is uncertain whether these associations are sustained with increasing years after the biomarkers are measured. Methods and Results In this cohort study, 7745 patients with coronary heart disease who participated in the LIPID (Long‐Term Intervention With Pravastatin in Ischemic Disease) trial, BNP (B‐type natriuretic peptide), troponin I, cystatin‐C, C‐reactive protein, d‐dimer and midregional proadrenomedullin were measured at baseline and after 1 year. Discrimination of plasma biomarker concentrations for cardiovascular death were evaluated in landmark analyses from 1 year for the next 5 years of the randomized trial, and for 10 additional years after trial completion. All 6 biomarkers were associated with risk of cardiovascular death (n=1903) both during and after the clinical trial (each P

Objective To examine the feasibility of implementing remote atrial fibrillation (AF) self-screening among older people supported by a remote central monitoring system.Design Process evaluation of the Mass AF randomised clinical trial (ACTRN12621000184875) with one-to-one semistructured interviews using interview guides underpinned by the Critical Realism approach and coded using the UK Medical Research Council Guidance of Process Evaluation Framework.Setting and participants Community-dwelling people aged ≥75 years from both genders (ratio 1:1) and urban/rural (ratio 2:1) in Australia.Interventions Participants were provided handheld single-lead electrocardiogram (ECG) devices and trained to self-record ECGs once daily on weekdays for at least 6 months. A remote central team notified participants and general practitioners (GPs) of AF.Primary feasibility outcomes The strengths, weaknesses, opportunities and threats (SWOT) analysis examined enablers (ie, strengths and opportunities) and barriers (ie, weaknesses and threats).Results Overall, 200 participants; 98.5% completed the 6-month programme, 96% reported being satisfied with screening and 48 were interviewed: mean age 79 years, 54% male and 71% urban. 11 GPs were interviewed: 55% female and 64% urban. Programme participants trusted the remote monitoring system that supported the screening programme and provided follow-up pathways where required. GPs saw opportunities to introduce this self-screening programme to at-risk patients and improve patients’ risk profiles. Programme participants reported that after being trained to use the device, they felt empowered to do self-screening and found it convenient. GPs saw empowerment could enhance the doctor–patient relationship. Programme participants and GPs valued screening in diagnosing AF that would otherwise be missed in usual care, but the uncertainty of effective screening duration could be a barrier.Conclusions This screening programme was feasible with the reinforcement of the underpinning enablers. Several implementation strategies were identified using SWOT analysis, including leveraging the opportunity for GPs to introduce this screening programme to at-risk patients.Trial registration number ACTRN12621000184875.

Esophageal lichen planus is an underrecognized manifestation of lichen planus. It is typically diagnosed based on characteristic endoscopic findings, such as hyperkeratosis, trachealization, denudation and/or stenosis, along with the presence of a lichenoid infiltrate in histopathological examination. In cases where no other manifestation of lichen planus are found and direct immunofluorescence for fibrinogen along the basement membrane is negative, the term “lichenoid esophagitis” should be preferred. This distinction is critical, as it prompts a thorough evaluation for underlying diseases, including autoimmune conditions and viral infections. We report a case of a 69-year-old male with stenosing esophagitis resembling esophageal lichen planus on endoscopic evaluation. The condition was refractory to multiple dilation procedures and high-dose proton pump inhibitor therapy. Histopathological analysis revealed a dense lymphocytic infiltrate extending into the epithelial layer, while direct immunofluorescence microscopy for fibrinogen was negative. There were no other signs of lichen planus on the skin or mucous membranes. The patient’s medical history included recurrent transient ischemic attack (non-cardiac), penile cancer and recurrent mucosal candidiasis. Laboratory findings revealed Epstein–Barr virus viremia and IgG hypergammaglobulinemia, raising suspicion of immunodeficiency. Further testing confirmed an active HIV infection, classified as category C3, and antiretroviral therapy was initiated. Following the initiation of antiretroviral therapy, the patient experienced rapid clinical and histopathological improvement of the lichenoid esophageal inflammation, although the esophageal stenosis persisted. Subsequent follow-up endoscopies confirmed resolution of the inflammatory component, underscoring the positive impact of addressing the underlying HIV infection on the esophagus. This case report highlights the importance of recognizing lichenoid esophagitis as a potential diagnosis in cases of unexplained chronic esophagitis, especially when standard treatments are ineffective. The presence of lichenoid inflammation without other manifestations of lichen planus should trigger an investigation into underlying conditions.

Abstract The neuroprotective transcription factor nuclear receptor-related 1 (Nurr1) has shown great promise as a therapeutic target in Parkinson’s and Alzheimer’s disease as well as multiple sclerosis but high-quality chemical tools for pharmacological target validation of Nurr1 are rare. We have employed the weak Nurr1 modulator amodiaquine (AQ) and AQ-derived fragments as templates to design a new Nurr1 agonist chemotype by scaffold hopping and fragment growing strategies. Systematic structural optimization of this scaffold yielded Nurr1 agonists with nanomolar potency and binding affinity. Comprehensive in vitro profiling revealed efficient cellular target engagement and compliance with the highest probe criteria. In human midbrain organoids bearing a Parkinson-driving LRRK2 mutation, a novel Nurr1 agonist rescued tyrosine hydroxylase expression highlighting the potential of the new Nurr1 modulator chemotype as lead and as a chemical tool for biological studies.

Abstract Nuclear receptors (NRs) regulate transcription in response to ligand binding and NR modulation allows pharmacological control of gene expression. Although some NRs are relevant as drug targets, the NR1 family, which comprises 19 NRs binding to hormones, vitamins, and lipid metabolites, has only been partially explored from a translational perspective. To enable systematic target identification and validation for this protein family in phenotypic settings, we present an NR1 chemogenomic (CG) compound set optimized for complementary activity/selectivity profiles and chemical diversity. Based on broad profiling of candidates for specificity, toxicity, and off-target liabilities, sixty-nine comprehensively annotated NR1 agonists, antagonists and inverse agonists covering all members of the NR1 family and meeting potency and selectivity standards are included in the final NR1 CG set. Proof-of-concept application of this set reveals effects of NR1 members in autophagy, neuroinflammation and cancer cell death, and confirms the suitability of the set for target identification and validation.

Purpose – The purpose of this study is to analyze how sentiment affects economic activity in Brazil. Design/methodology/approach – Based on a nonlinear autoregressive distributed lag (NARDL) model, this study examines in detail the short-term and long-term asymmetric impacts between the variables during the period from January 2007 to December 2020. Findings – There are three main results of this study. First, sentiment is an important factor for economic activity in Brazil, and its effect possibly occurs through the channels of consumption and investment, which are the two main components of economic growth. Second, sentiment affects economic activity in different ways in the short and the long term: in Brazil, although in the short-term, immediate shocks of sentiment may be confusing, the negative shocks from previous periods have a negative impact on economic activity. Third, the effect of shocks of optimism and pessimism on economic activity is asymmetric, and in the long run, only shocks of optimism have a significant and positive impact. Originality/value – The relationship between sentiment and economic activity is still a controversial issue in the literature and this study seeks to advance its understanding in Brazil.

Abstract Head and Neck Squamous Cell Carcinoma (HNSCC) is a heterogeneous malignancy that remains a significant challenge in clinical management due to frequent treatment failures and pronounced therapy resistance. While metabolic dysregulation appears to be a critical factor in this scenario, comprehensive analyses of the metabolic HNSCC landscape and its impact on clinical outcomes are lacking. This study utilized transcriptomic data from four independent clinical cohorts to investigate metabolic heterogeneity in HNSCC and define metabolic pathway-based subtypes (MPS). In HPV-negative HNSCCs, MPS1 and MPS2 were identified, while MPS3 was enriched in HPV-positive cases. MPS classification was associated with clinical outcome post adjuvant radio(chemo)therapy, with MPS1 consistently exhibiting the highest risk of therapeutic failure. MPS1 was uniquely characterized by upregulation of glycan (particularly chondroitin/dermatan sulfate) metabolism genes. Immunohistochemistry and pilot mass spectrometry imaging analyses confirmed this at metabolite level. The histological context and single-cell RNA sequencing data identified the malignant cells as key contributors. Globally, MPS1 was distinguished by a unique transcriptomic landscape associated with increased disease aggressiveness, featuring motifs related to epithelial-mesenchymal transition, immune signaling, cancer stemness, tumor microenvironment assembly, and oncogenic signaling. This translated into a distinct histological appearance marked by extensive extracellular matrix remodeling, abundant spindle-shaped cancer-associated fibroblasts, and intimately intertwined populations of malignant and stromal cells. Proof-of-concept data from orthotopic xenotransplants replicated the MPS phenotypes on the histological and transcriptome levels. In summary, this study introduces a metabolic pathway-based classification of HNSCC, pinpointing glycan metabolism-enriched MPS1 as the most challenging subgroup that necessitates alternative therapeutic strategies.

Abstract This article aimed to determine how rational and irrational investor sentiments impact the return and volatility of the Brazilian market. The role of sentiment in financial markets is still a recent, controversial and limited subject, and this study explores this relationship in the Brazilian market. The evidence from this research adds to the limited number of studies on investor sentiment in emerging markets and extends the evidence already documented in Brazil. Our results are expected to have an impact on investors, policymakers and monetary authorities. Investors must be aware of economic fundamentals when formulating their investment strategies and also when choosing the stocks that will make up their portfolios. Policymakers and monetary authorities should take sentiment into account when formulating political, economic and monetary strategies, as economic changes can affect investor psychology and be reflected in their stock market trading. Consumer and business confidence indexes were used as proxies for investor sentiment and were regressed against a set of economic fundamentals to isolate their rational and irrational components. Then, autoregressive vector models were estimated and impulse response functions and variance decompositions were generated to verify the impact of sentiment on the return and volatility of the Ibovespa. There are three main results. First, investor sentiment impacts both returns and volatility in the Brazilian market. Second, economic fundamentals were important determinants of returns and volatility in the Brazilian market, indicating that fundamental trading induced by rational sentiment had a greater effect than trading induced by irrational sentiment. Third, in terms of magnitude, consumer-based sentiment had a greater impact than business-based sentiment.

Snow distribution has been altered over the past decades under global warming, with a significant reduction in duration and extent of snow cover and an increase in unprecedented snowstorms across large areas in cold regions. The altered snow conditions are likely to have immediate (in winter) and carry-over or legacy (which an extended effect might continue in the following spring, summer and autumn) impacts on soil processes and functioning, but a quantification of the legacy effect of snow coverage alternation is still lacking. Furthermore, studies investigating the effect of snow cover changes on soil respiration, soil carbon pools and microbial activity are increasing, but contrasting results of different studies makes it difficult to assess the overall effect of snow cover changes and the underlying mechanisms, thus a systematic and comprehensive meta-analysis is required. In this study, we synthesized the results from 60 papers based on field snow manipulation experiments and conducted a meta-analysis to evaluate immediate and prolonged effects on eight variables related to soil carbon dynamics and microbial activity to snow coverage alternation. Results showed that snow removal had no significant effect on soil respiration, but increased dissolved organic carbon (DOC) (11.5%) and fungal abundance (32.0%). By contrast, snow addition significantly increased soil respiration (16.3%) and microbial biomass carbon (MBC) (6.6%). Snow addition had immediate and prolonged impacts on soil carbon dynamics and microbial activity lasting from winter to the following autumn, whereas an effect of snow removal on total organic carbon (TOC) and DOC was detectable only in the following spring. Snow depth, ecosystem and soil types determined the extent of the impact of snow treatments on soil respiration, DOC, MBC and microbial biomass nitrogen (MBN). Our findings provide critical insights into understanding how changes in snow coverage affect soil respiration and microbial activity. We suggest future field-based experiments to enhance our understanding the effect of climate change on soil processes and functioning in the winter and the following seasons.

The reactions of 2,4-di-tert-butyl-6-(diphenylphosphino)phenol and various Michael acceptors (acrylonitrile, acrylamide, methyl vinyl ketone, several acrylates, methyl vinyl sulfone) yield the respective phosphonium phenolate zwitterions at room temperature. Nine different zwitterions were synthesized and fully characterized. Zwitterions with the poor Michael acceptors methyl methacrylate and methyl crotonate formed, but could not be isolated in pure form. The solid-state structures of two phosphonium phenolate molecules were determined by single-crystal X-ray crystallography. The bonding situation in the solid state together with NMR data suggests an important contribution of an ylidic resonance structure in these molecules. The phosphonium phenolates are characterized by UV–vis absorptions peaking around 360 nm and exhibit a negative solvatochromism. An analysis of the kinetics of the zwitterion formation was performed for three Michael acceptors (acrylonitrile, methyl acrylate, and acrylamide) in two different solvents (chloroform and methanol). The results revealed the proton transfer step necessary to stabilize the initially formed carbanion as the rate-determining step. A preorganization of the carbonyl bearing Michael acceptors allowed for reasonable fast direct proton transfer from the phenol in aprotic solvents. In contrast, acrylonitrile, not capable of forming a similar preorganization, is hardly reactive in chloroform solution, while in methanol the corresponding phosphonium phenolate is formed.

Ameliorating soil acidity using a combination of lime and organic amendments (OAs) can be an alternative to lime alone, but determining the appropriate OA rates can be difficult. We developed a new method for calculating the combined application rate of lime and OAs (wheat straw, faba bean straw, blended poultry litter, biochar, and compost) that is based on the titratable alkalinity of OAs and the equilibrium lime buffer capacity (LBCeq) of acidic soils. The effect of calculated soil amendment rates on soil pH was validated at soil water contents of 60 %, 100 %, and 150 % of field capacity (FC). The soil used to develop and validate the method was a sandy loam with a soil pH in deionised water (pHW) of 4.84 and a soil pH in 0.01 M CaCl2 solution (pHCa) of 4.21. The LBCeq of the soil was 1657 mg CaCO3 kg−1 pH−1 (where “CaCO3 kg−1 pH−1” denotes the amount of lime required to raise the pH of 1 kg of soil by one unit). The titratable alkalinity of the OAs ranged from 11.7 cmol Heq+ kg−1 for wheat straw to 357 cmol Heq+ kg−1 for compost. At 60 % FC, faba bean and wheat straw amendment increased the soil pHW to 6.48 and 6.42, respectively, but lower pH values were reached in soil amended with less biodegradable or resistant OAs (ROAs) (i.e. blended poultry litter, biochar, and compost). At 150 % FC, the two straws increased the soil pHW to only 5.93 and 5.75, respectively, possibly due to slower decomposition under submerged conditions, resulting in limited alkalinity production, whereas amendment with ROAs produced pHW values close to 6.5. With an increasing lime-equivalent value (LEV) of the OA, from 5.8 g CaCO3 kg−1 (wheat straw) to 179 g CaCO3 kg−1 (compost), the lime requirement to reach pHW 6.5 in lime–OA combinations decreased from 2.72 to 0.09 g CaCO3 kg−1. The developed method was shown to be effective in determining the appropriate rates of OAs (with or without additional lime) for the management of acidic sandy loam soils in this study and highlights the importance of the soil water content with respect to its acid-neutralising effect.

Background Transcatheter renal denervation (RDN) has had inconsistent efficacy and concerns for durability of denervation. We aimed to investigate long‐term safety and efficacy of transcatheter microwave RDN in vivo in normotensive sheep in comparison to conventional radiofrequency ablation. Methods and Results Sheep underwent bilateral RDN, receiving 1 to 2 microwave ablations (maximum power of 80–120 W for 240 s–480 s) and 12 to 16 radiofrequency ablations (180 s–240 s) in the main renal artery in a paired fashion, alternating the side of treatment, euthanized at 2 weeks (acute N=15) or 5.5 months (chronic N=15), and compared with undenervated controls (N=4). Microwave RDN produced substantial circumferential perivascular injury compared with radiofrequency at both 2 weeks [area 239.8 (interquartile range [IQR] 152.0–343.4) mm2 versus 50.1 (IQR, 32.0–74.6) mm2, P

Purpose: Stereotactic body radiotherapy (SBRT) is an effective treatment for adrenal gland metastases, but it is technically challenging and there are concerns about toxicity. We performed a multi-institutional pooled retrospective analysis to study clinical outcomes and toxicities after MR-guided SBRT (MRgSBRT) using for adrenal gland metastases. Methods and Materials: Clinical and dosimetric data of patients treated with MRgSBRT on a 0.35 T MR-Linac at 11 institutions between 2016 and 2022 were analyzed. Local control (LC), local progression-free survival (LPFS), distant progression-free survival (DPFS) and overall survival (OS) were estimated using Kaplan-Meier method and log-rank test. Results: A total of 255 patients (269 adrenal metastases) were included. Metastatic pattern was solitary in 25.9 % and oligometastatic in 58.0 % of patients. Median total dose was 45 Gy (range, 16–60 Gy) in a median of 5 fractions, and the median BED10 was 100 Gy (range, 37.5–132.0 Gy). Adaptation was done in 87.4 % of delivered fractions based on the individual clinicians' judgement. The 1- and 2- year LPFS rates were 94.0 % (95 % CI: 90.7–97.3 %) and 88.3 % (95 % CI: 82.4–94.2 %), respectively and only 2 patients (0.8 %) experienced grade 3 + toxicity. No local recurrences were observed after treatment to a total dose of BED10 > 100 Gy, with single fraction or fractional dose of > 10 Gy. Conclusions: This is a large retrospective multi-institutional study to evaluate the treatment outcomes and toxicities with MRgSBRT in over 250 patients, demonstrating the need for frequent adaptation in 87.4 % of delivered fractions to achieve a 1- year LPFS rate of 94 % and less than 1 % rate of grade 3 + toxicity. Outcomes analysis in 269 adrenal lesions revealed improved outcomes with delivery of a BED10 > 100 Gy, use of single fraction SBRT and with fraction doses > 10 Gy, providing benchmarks for future clinical trials.

This study investigated the efficacy of a 10-session nature-based therapeutic intervention for people with post-concussion symptoms. The intervention involved physical and vestibular exercises, sensory training, relaxation, and psychoeducation, all of which were integrated with the natural environment in a forest therapy garden. This study was designed with a passive control period followed by the intervention (n = 30). The Mental Fatigue Scale (MFS) was the primary outcome measure. The secondary outcome measures were the Warwick–Edinburg Mental Wellbeing Scale and the short version of the Quality of Life after Brain Injury. A Likert scale was used to examine the mental strain of the sessions themselves. The MFS (primary outcome) exhibited a significant decrease with a medium-sized effect from before to after the intervention. The secondary outcomes exhibited significant increases from the beginning to the end of the intervention. All outcomes were sustained at follow-up ten weeks later. No significant difference was found from the control period. This study indicates that the described nature-based intervention is a feasible treatment for reducing prolonged post-concussion symptoms. However, it should be studied more in-depth to understand the impact of the natural environment and to validate the results on a larger representative population.

Abstract Background and purpose Magnetic resonance imaging guided radiotherapy (MRgRT) offers treatment plan adaptation to the anatomy of the day. In the current MRgRT workflow, this requires the time consuming and repetitive task of manual delineation of organs-at-risk (OARs), which is also prone to inter- and intra-observer variability. Therefore, deep learning autosegmentation (DLAS) is becoming increasingly attractive. No investigation of its application to OARs in thoracic magnetic resonance images (MRIs) from MRgRT has been done so far. This study aimed to fill this gap. Materials and methods 122 planning MRIs from patients treated at a 0.35 T MR-Linac were retrospectively collected. Using an 80/19/23 (training/validation/test) split, individual 3D U-Nets for segmentation of the left lung, right lung, heart, aorta, spinal canal and esophagus were trained. These were compared to the clinically used contours based on Dice similarity coefficient (DSC) and Hausdorff distance (HD). They were also graded on their clinical usability by a radiation oncologist. Results Median DSC was 0.96, 0.96, 0.94, 0.90, 0.88 and 0.78 for left lung, right lung, heart, aorta, spinal canal and esophagus, respectively. Median 95th percentile values of the HD were 3.9, 5.3, 5.8, 3.0, 2.6 and 3.5 mm, respectively. The physician preferred the network generated contours over the clinical contours, deeming 85 out of 129 to not require any correction, 25 immediately usable for treatment planning, 15 requiring minor and 4 requiring major corrections. Conclusions We trained 3D U-Nets on clinical MRI planning data which produced accurate delineations in the thoracic region. DLAS contours were preferred over the clinical contours.