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Background/Purpose: Organized events with environmental and outdoor education (EOE) components have the potential to change participant environmental behaviors. This study further investigates emergent outcomes, meanings, and effect on behavior that an organized, community-based, multigenerational river canoeing and kayaking event may have for its participants and considers these intersections of pro-environmental behavior, sense of place, and multigenerational community involvement. Methodology/Approach: Research participants experienced a multi-day canoeing and kayaking event and were invited to participate in semi-structured interviews (n = 13). Participants ranged from teen-age to older adults. This research uses a qualitative methodology and a data collection procedure which employs semi-structured interviews conducted on the water, in-situ, during the program. Interviews were recorded and transcribed. Findings: Emergent themes and sub-themes including experiential learning's effect on knowledge acquisition, changes in attitude and environmental behavior, the value of rivers, and sense of place and socio-cultural outcomes related to such EOE programs. Implications: These results support experientially based EOE programs effectiveness for the continued development of pro-environmental behavior in the citizenry. This research aims to add to the current EOE literature on diverse and inclusive socially supported, community engagement EOE programs through a diverse sample (i.e., age, gender, race/ethnicity, etc.).

BACKGROUNDAndrogen receptor signaling inhibitors (ARSIs) have improved outcomes for patients with metastatic castration-resistant prostate cancer (mCRPC), but their clinical benefit is limited by treatment resistance.METHODSTo investigate the mechanisms of ARSI resistance, we analyzed the whole-genome (n = 45) and transcriptome (n = 31) sequencing data generated from paired metastatic biopsies obtained before initiation of first-line ARSI therapy for mCRPC and after radiographic disease progression. We investigated the effects of genetic and pharmacologic modulation of SSTR1 in 22Rv1 cells, a representative mCRPC cell line.RESULTSWe confirmed the predominant role of tumor genetic alterations converging on augmenting androgen receptor (AR) signaling and the increased transcriptional heterogeneity and lineage plasticity during the emergence of ARSI resistance. We further identified amplifications involving a putative enhancer downstream of the AR and transcriptional downregulation of SSTR1, encoding somatostatin receptor 1, in ARSI-resistant tumors. We found that patients with SSTR1-low mCRPC tumors derived less benefit from subsequent ARSI therapy in a retrospective cohort. We showed that SSTR1 was antiproliferative in 22Rv1 cells and that the FDA-approved drug pasireotide suppressed 22Rv1 cell proliferation.CONCLUSIONOur findings expand the knowledge of ARSI resistance and point out actionable next steps, exemplified by potentially targeting SSTR1, to improve patient outcomes.FUNDINGNational Cancer Institute (NCI), NIH; Prostate Cancer Foundation; Conquer Cancer, American Society of Clinical Oncology Foundation; UCSF Benioff Initiative for Prostate Cancer Research; Netherlands Cancer Institute.

The impact of variations in the three-dimensional structure of the genome has been recognized, but solid cancer tissue studies are limited. Here, we performed integrated deep Hi-C sequencing with matched whole-genome sequencing, whole-genome bisulfite sequencing, 5-hydroxymethylcytosine (5hmC) sequencing and RNA sequencing across a cohort of 80 biopsy samples from patients with metastatic castration-resistant prostate cancer. Dramatic differences were present in gene expression, 5-methylcytosine/5hmC methylation and in structural variation versus mutation rate between A and B (open and closed) chromatin compartments. A subset of tumors exhibited depleted regional chromatin contacts at the AR locus, linked to extrachromosomal circular DNA (ecDNA) and worse response to AR signaling inhibitors. We also identified topological subtypes associated with stark differences in methylation structure, gene expression and prognosis. Our data suggested that DNA interactions may predispose to structural variant formation, exemplified by the recurrent TMPRSS2-ERG fusion. This comprehensive integrated sequencing effort represents a unique clinical tumor resource.

BackgroundRadiation delivery with ultra-high dose rate (FLASH) radiotherapy (RT) holds promise for improving treatment outcomes and reducing side effects but poses challenges in radiation delivery accuracy due to its ultra-high dose rates. This necessitates the development of novel imaging and verification technologies tailored to these conditions.PurposeOur study explores the effectiveness of proton-induced acoustic imaging (PAI) in tracking the Bragg peak in three dimensions and in real time during FLASH proton irradiations, offering a method for volumetric beam imaging at both conventional and FLASH dose rates.MethodsWe developed a three-dimensional (3D) PAI technique using a 256-element ultrasound detector array for FLASH dose rate proton beams. In the study, we tested protoacoustic signal with a beamline of a FLASH-capable synchrocyclotron, setting the distal 90% of the Bragg peak around 35 mm away from the ultrasound array. This configuration allowed us to assess various total proton radiation doses, maintaining a consistent beam output of 21 pC/pulse. We also explored a spectrum of dose rates, from 15 Gy/s up to a FLASH rate of 48 Gy/s, by administering a set number of pulses. Furthermore, we implemented a three-dot scanning beam approach to observe the distinct movements of individual Bragg peaks using PAI. All these procedures utilized a proton beam energy of 180 MeV to achieve the maximum possible dose rate.ResultsOur findings indicate a strong linear relationship between protoacoustic signal amplitudes and delivered doses (R2 = 0.9997), with a consistent fit across different dose rates. The technique successfully provided 3D renderings of Bragg peaks at FLASH rates, validated through absolute Gamma index values.ConclusionsThe protoacoustic system demonstrates effectiveness in 3D visualization and tracking of the Bragg peak during FLASH proton therapy, representing a notable advancement in proton therapy quality assurance. This method promises enhancements in protoacoustic image guidance and real-time dosimetry, paving the way for more accurate and effective treatments in ultra-high dose rate therapy environments.

DLSIA (Deep Learning for Scientific Image Analysis) is a Python-based machine learning library that empowers scientists and researchers across diverse scientific domains with a range of customizable convolutional neural network (CNN) architectures for a wide variety of tasks in image analysis to be used in downstream data processing. DLSIA features easy-to-use architectures, such as autoencoders, tunable U-Nets and parameter-lean mixed-scale dense networks (MSDNets). Additionally, this article introduces sparse mixed-scale networks (SMSNets), generated using random graphs, sparse connections and dilated convolutions connecting different length scales. For verification, several DLSIA-instantiated networks and training scripts are employed in multiple applications, including inpainting for X-ray scattering data using U-Nets and MSDNets, segmenting 3D fibers in X-ray tomographic reconstructions of concrete using an ensemble of SMSNets, and leveraging autoencoder latent spaces for data compression and clustering. As experimental data continue to grow in scale and complexity, DLSIA provides accessible CNN construction and abstracts CNN complexities, allowing scientists to tailor their machine learning approaches, accelerate discoveries, foster interdisciplinary collaboration and advance research in scientific image analysis.

Abstract Background Public health emergencies, such as the Covid-19 pandemic, put great pressure on healthcare workers (HCW) across the world, possibly increasing the risk of experiencing ethically challenging situations (ECS). Whereas experiencing ECS as a HCW in such situations is likely unavoidable, mitigation of their adverse effects (e.g., moral distress) is necessary to reduce the risk of long-term negative consequences. One possible route of mitigation of these effects is via work environmental factors. Objectives The current study aimed to examine: [1] risk factors associated with ECS among HCW [2], intensity of moral distress associated with ECS across various occupational factors (i.e., profession, degree of exposure to patients with Covid-19), and [3] the impact of work environmental factors on this association, in a sample of HCW during the pandemic. Methods We employed multiple logistic and linear regression to self-report data from 977 HCWs at four Norwegian hospitals responding to a survey at the fourth wave of the pandemic. Results About half of HCW in this study had experienced ECS during the pandemic, and levels of moral distress associated with such were higher than in previous studies using similar assessment methods. Younger age, female sex, geographical work area (mid-north of Norway), and profession (nurse) were all associated with higher odds (range of OR: 1.30–2.59) of experiencing ECS, as were direct contact with patients with Covid-19. Among those participants who reported that they had experienced ECS during the pandemic, moral distress levels when recalling those situations were moderate (Mean 5.7 on a 0–10 scale). Men reported somewhat lower intensity of moral distress (partial eta squared; ηp2 = 0.02). Reporting a manageable workload (ηp2 = 0.02), and greater opportunity to work according to best practice (ηp2 = 0.02), were associated with lower levels of moral distress. Conclusions Our findings suggest that moral distress could potentially be mitigated on an organizational level, particularly by focusing on ensuring a manageable workload, and an ability to work according to best practice. To build sustainable healthcare systems robust enough to withstand future public health emergencies, healthcare organizations should implement measures to facilitate these aspects of HCWs’ work environment.

Abstract Background Measuring the swallowing muscle mass with volume measurements is complex and time intensive; therefore, it is not used in clinical practice. However, it can be clinically relevant, for instance, in the case of sarcopenic dysphagia. The aim of the study was to develop a feasible and clinically applicable method to measure swallowing muscle mass. Methods Data from 10 head and neck cancer patients were collected from the Oncological Life Study data‐biobank of the University Medical Center Groningen. The pharyngeal constrictor, genioglossus, mylohyoid and geniohyoid complex muscles, as well as the tongue complex muscles, were delineated manually on routinely performed head and neck computed tomography scans. Axial and sagittal planes were used for volume and area measurements, respectively. Muscle density measurements were performed with and without Hounsfield unit thresholding. Correlations were assessed by Pearson correlation coefficients, and interobserver reliability was measured using intra‐class correlation coefficients (ICCs). Results Significant differences were observed between sagittal area measurements with and without Hounsfield unit thresholds for pharyngeal constrictor, tongue complex and the sum of the swallowing muscles (t > 6; P‐value

Abstract Background Numerous studies have examined associations between overweight and obesity and risk of low back pain (LBP), but the exact magnitude of these associations is not yet clear. The purpose of this work was to assess such sex-specific associations in a community-based setting in Norway, taking into account potential relationships with other risk factors. Methods A cohort study was conducted combining data from two waves of the Trøndelag Health Study, HUNT3 (2006–2008) and HUNT4 (2017–2019). Separate analyses were performed of risk of chronic LBP in HUNT4 among 14,775 individuals without chronic LBP in HUNT3, and of recurrence or persistence in HUNT4 among 5034 individuals with chronic LBP in HUNT3. Relative risks were estimated in generalised linear models for overweight and obesity compared to normal weight. Body size classification was based on values of BMI computed from measurements of height and weight. Chronic LBP was defined as LBP persisting at least 3 months during last year. Results After adjustment for age, smoking, physical activity in leisure time and work activity, analysis of risk among women produced relative risks 1.11 (95% CI 1.00–1.23) for overweight, 1.36 (95% CI 1.20–1.54) for obesity class I and 1.68 (95% CI 1.42–2.00) for obesity classes II-III. Relative risks among men were 1.10 (95% CI 0.94–1.28) for overweight, 1.36 (95% CI 1.13–1.63) for obesity class I and 1.02 (95% CI 0.70–1.50) for obesity classes II-III, the last estimate being based on relatively few individuals. Analyses of recurrence or persistence indicated similar relationships but with smaller magnitude of relative risks and no drop in risk among obesity classes II-III in men. The change in BMI from HUNT3 to HUNT4 hardly differed between individuals with and without chronic LBP in HUNT3. Conclusions Risk of chronic LBP increases with higher values of BMI in both sexes, although it is uncertain whether this applies to very obese men. Very obese women carry a particularly large risk. Probabilities of recurrence or persistence of chronic LBP among those already afflicted also increase with higher values of BMI. Adjustment for other factors does not influence relationships with overweight and obesity to any major extent.

Abstract Citizen science can be a powerful approach to foster the successful implementation of technological innovations in health, care or well-being. Involving experience experts as co-researchers or co-designers of technological innovations facilitates mutual learning, community building, and empowerment. By utilizing the expert knowledge of the intended users, innovations have a better chance to get adopted and solve complex health-related problems. As citizen science is still a relatively new practice for health and well-being, little is known about effective methods and guidelines for successful collaboration. This scoping review aims to provide insight in (1) the levels of citizen involvement in current research on technological innovations for health, care or well-being, (2) the used participatory methodologies, and (3) lesson’s learned by the researchers. A scoping review was conducted and reported in accordance with the PRISMA-ScR guidelines. The search was performed in SCOPUS in January 2021 and included peer-reviewed journal and conference papers published between 2016 and 2020. The final selection (N = 83) was limited to empirical studies that had a clear focus on technological innovations for health, care or well-being and involved citizens at the level of collaboration or higher. Our results show a growing interest in citizens science as an inclusive research approach. Citizens are predominantly involved in the design phase of innovations and less in the preparation, data-analyses or reporting phase. Eight records had citizens in the lead in one of the research phases. Researcher use different terms to describe their methodological approach including participatory design, co-design, community based participatory research, co-creation, public and patient involvement, partcipatory action research, user-centred design and citizen science. Our selection of cases shows that succesful citizen science projects develop a structural and longitudinal partnership with their collaborators, use a situated and adaptive research approach, and have researchers that are willing to abandon traditional power dynamics and engage in a mutual learning experience.

Over the past several decades outdoor adventure recreation programs (OARPs) have seen an increase in popularity on university campuses across the country. This study used the Leisure Motivation Scale (LMS) developed, to measure motives for participation; that is, the study investigated college students' motivations to participate in OARPs. Specifically, we sought to build a model for predicting interest in water or land-based activities based on experience levels and year in school. Using a sample of 152 participants from an OARP at a Midwestern University, results indicated significant differences in motivations based on stimulus avoidance. The findings from this study will help researchers and practitioners understand motivations for participation in OARPs and provide direction for more attractive and impactful outdoor programming.

Abstract Background The genetic background of cancer remains complex and challenging to integrate. Many somatic mutations within genes are known to cause and drive cancer, while genome-wide association studies (GWAS) of cancer have revealed many germline risk factors associated with cancer. However, the overlap between known somatic driver genes and positional candidate genes from GWAS loci is surprisingly small. We hypothesised that genes from multiple independent cancer GWAS loci should show tissue-specific co-regulation patterns that converge on cancer-specific driver genes. Results We studied recent well-powered GWAS of breast, prostate, colorectal and skin cancer by estimating co-expression between genes and subsequently prioritising genes that show significant co-expression with genes mapping within susceptibility loci from cancer GWAS. We observed that the prioritised genes were strongly enriched for cancer drivers defined by COSMIC, IntOGen and Dietlein et al. The enrichment of known cancer driver genes was most significant when using co-expression networks derived from non-cancer samples of the relevant tissue of origin. Conclusion We show how genes within risk loci identified by cancer GWAS can be linked to known cancer driver genes through tissue-specific co-expression networks. This provides an important explanation for why seemingly unrelated sets of genes that harbour either germline risk factors or somatic mutations can eventually cause the same type of disease.

Abstract Continued exploration of the androgen receptor (AR) is crucial, as it plays pivotal roles in diverse diseases such as prostate cancer (PCa), serving as a significant therapeutic focus. Therefore, the Department of Urology Dresden hosted an international meeting for scientists and clinical oncologists to discuss the newest advances in AR research. The 2nd International Androgen Receptor Symposium was held in Dresden, Saxony, Germany, from 26–27.04.2024, organised by Dr. Holger H.H. Erb. Following the format of the first meeting, more than 35 scientists from 8 countries attended the event to discuss recent developments, research challenges, and identification of venues in AR research. An important new feature was the involvement of PhD students and young investigators, acknowledging the high scientific quality of their work. The symposium included three covers: new advances from clinical research, basic and translational research, and novel strategies to target AR. Moreover, based on its increasing clinical relevance, a PSMA theranostic mini-symposium was added at the end of the AR symposium to allow the audience to discuss the newest advances in PSMA theranostic. This report focuses on the highlights and discussions of the meeting.

Abstract Cytokine release syndrome (CRS) was associated with teclistamab treatment in the phase I/II MajesTEC‐1 study. Cytokines, especially interleukin (IL)‐6, are known suppressors of cytochrome P450 (CYP) enzymes' activity. A physiologically based pharmacokinetic model evaluated the impact of IL‐6 serum levels on exposure of substrates of various CYP enzymes (1A2, 2C9, 2C19, 3A4, 3A5). Two IL‐6 kinetics profiles were assessed, the mean IL‐6 profile with a maximum concentration (Cmax) of IL‐6 (21 pg/mL) and the IL‐6 profile of the patient presenting the highest IL‐6 Cmax (288 pg/mL) among patients receiving the recommended phase II dose of teclistamab in MajesTEC‐1. For the mean IL‐6 kinetics profile, teclistamab was predicted to result in a limited change in exposure of CYP substrates (area under the curve [AUC] mean ratio 0.87–1.20). For the maximum IL‐6 kinetics profile, the impact on omeprazole, simvastatin, midazolam, and cyclosporine exposure was weak to moderate (mean AUC ratios 1.90–2.23), and minimal for caffeine and s‐warfarin (mean AUC ratios 0.82–1.25). Maximum change in exposure for these substrates occurred 3–4 days after step‐up dosing in cycle 1. These results suggest that after cycle 1, drug interaction from IL‐6 effect has no meaningful impact on CYP activities, with minimal or moderate impact on CYP substrates. The highest risk of drug interaction is expected to occur during step‐up dosing up to 7 days after the first treatment dose (1.5 mg/kg subcutaneously) and during and after CRS.

Abstract It is now widely recognised that the environment in space activates a diverse set of genes involved in regulating fundamental cellular pathways. This includes the activation of genes associated with blood homeostasis and erythropoiesis, with a particular emphasis on those involved in globin chain production. Haemoglobin biology provides an intriguing model for studying space omics, as it has been extensively explored at multiple -omic levels, spanning DNA, RNA, and protein analyses, in both experimental and clinical contexts. In this study, we examined the developmental expression of haemoglobin over time and space using a unique suite of multi-omic datasets available on NASA GeneLab, from the NASA Twins Study, the JAXA CFE study, and the Inspiration4 mission. Our findings reveal significant variations in globin gene expression corresponding to the distinct spatiotemporal characteristics of the collected samples. This study sheds light on the dynamic nature of globin gene regulation in response to the space environment and provides valuable insights into the broader implications of space omics research.