Search

BACKGROUND: Preventing Loss of Independence through Exercise (PLIÉ) is a group program for people living with dementia that combines movements to support daily function with present moment body awareness and social engagement that has been found to have physical, emotional, social, and cognitive benefits. The goal of this study was to develop and refine a PLIÉ remote training program for interdisciplinary Veterans Affairs (VA) nursing home staff members also known as community living center (CLC) staff. METHODS: This pre-implementation study used iterative Plan-Do-Study-Act (PDSA) cycles. The 10-week PDSA cycles occurred from June to September 2021 at 2 VA nursing home sites. Remote training was delivered via Microsoft Teams and included 1-hour live-streamed weekly didactic sessions (nursing staff with PLIÉ instructor) focused on PLIÉ principles and 1-hour weekly live-streamed experiential sessions for staff to apply PLIÉ principles with residents. We administered weekly feedback surveys to iteratively refine the training process. RESULTS: 14 staff members participated (5 recreation therapists, 3 social workers, 2 registered nurses, 2 chaplains, 1 psychologist, and 1 speech pathologist). The experiential sessions were rated as most helpful overall. Key PDSA refinements included: (1) creating 10-minute video recording summaries to support learning, particularly for those unable to attend live training sessions due to clinical schedules; and (2) incorporating self-reflection and goal setting to support staff incorporation of PLIÉ principles into routine care and personal life. These refinements resulted in increased use of PLIÉ principles with the residents from 67 to 89% of the staff participants. 100% of regular attendees (11/11) rated their overall satisfaction with remote training as very good or excellent. CONCLUSIONS: It was feasible to train interdisciplinary CLC staff participants to deliver an integrative group movement program for residents with dementia remotely. PDSA cycles supported refinement of the training process and improved uptake. A larger study of PLIÉ remote CLC staff training is needed to assess outcomes on residents and quality of care.

BACKGROUND: The COVID-19 pandemic and shut down of in-person complementary and integrative (CIH) wellness services at the San Francisco Veterans Affairs Healthcare System (SFVAHCS) required implementation of virtual program delivery. In May 2020, VA in-person group yoga classes pivoted to virtual classes for existing attendees. In October 2020, we partnered with SFVAHCS Integrative Health and the VA Office of Rural Health to formalize the TeleYoga Program to expand yoga access to Veterans in SFVAHCS geographically dispersed area. OBJECTIVE: This pilot study evaluated Veterans experiences and self-reported health outcomes after participating in at-home tele-yoga groups during the COVID-19 pandemic. METHODS: The RE-AIM framework guided program delivery evaluation. Reach was assessed with medical record data. Adoption was assessed by the number of new facilities providing referrals to tele-yoga. Implementation, satisfaction, and patient-reported outcomes, were evaluated through structured interviews with Likert scale and open-ended responses. RESULTS: We offered 4-6 weekly livestreamed classes between October 2020-September 2021. The program reached 70 Veterans, including 40 new participants, with 1208 total unique encounters. Referrals increased from 2 to 6 SFVAHCS facilities. Fourteen participants completed structured interviews. Over half rated highly the convenience and overall experience of tele-yoga classes and reported improvement with pain, stress management, exercise, and flexibility. Open-ended responses indicated opportunities for social connection, maintaining mental health, cultivating resilience, improving function, and managing pain. Suggestions for improvement focused on technological aspects, including audiovisual quality. CONCLUSIONS: During the COVID-19 pandemic, we successfully transitioned and expanded virtual group yoga delivery to Veterans from all geographic locations within SFVAHCS. We attribute this success to existing infrastructure for telehealth and CIH services and a virtual program orientation for new participants. The results of this pilot study suggest in-person group yoga may be successfully implemented virtually, serving as a viable modality that contributes to holistic wellbeing for Veterans.

INTRODUCTION: There are few widely-available, evidence-based options to support quality of life (QOL) for people living with Alzheimers disease and related dementias. METHODS: We performed a randomized, controlled trial with a Waitlist control group to determine whether an online, livestream, mind-body, group movement program (Moving Together, 1 hour, 2 days/week, 12 weeks) improves QOL in people with cognitive impairment (PWCI) or care partners (CPs) and explore mechanisms of action. The primary outcome for both participants was self-reported QOL. Secondary outcomes and potential mediators included mobility, isolation, well-being, cognitive function, and sleep in PWCI and burden, positive emotions, caregiver self-efficacy, stress management, and sleep in CPs. Blinded assessors collected outcome data at baseline, 12, and 24 weeks. We assessed adverse events including falls through monthly check-in surveys and collected qualitative data through evaluation surveys. Intention-to-treat analyses used linear mixed models to compare mean change over time between groups and calculated standardized effect sizes (ESs). RESULTS: Ninety-seven dyads enrolled (PWCI: age 76 ± 11 years, 43% female, 80% non-Hispanic White; CPs: age 66 ± 12 years, 78% female, 71% non-Hispanic White); 15% withdrew before 12 weeks and 22% before 24 weeks. PWCI self-reported significantly better QOL from baseline to 12 weeks in the Moving Together group compared to the Waitlist group (ES = 0.474, p = 0.048) and CPs self-reported improved ability to manage stress (ES = 0.484, p = 0.021). Improvements in participant self-reported QOL were mediated by improvements in their self-reported well-being and CP-reported ability to manage stress. Results were similar when the Waitlist group participated in the program (QOL ES = 0.663, p = 0.006; stress management ES = 0.742, p = 0.002) and were supported by qualitative data. Exploratory analyses suggested possible fall reduction in PWCI. There were no study-related serious adverse events. DISCUSSION: Online programs such as Moving Together offer a scalable strategy for supporting high QOL for PWCI and helping CPs manage stress. TRIAL REGISTRATION: ClinicalTrials.gov NCT04621448. HIGHLIGHTS: The approval of new medications that slow cognitive decline in people living with Alzheimers disease and related disorders (ADRD) has raised hope and excitement. However, these medications do not appear to impact quality of life, which is often considered by patients and care partners to be the most important outcome.In this randomized clinical trial, we found that an evidence-based, online, livestream, mind-body, group movement program significantly and meaningfully improves self-rated quality of life in people with ADRD and helps care partners manage stress. Mediation analyses revealed that the key drivers of improvements in participants quality of life were improvements in their feelings of well-being and care partners ability to manage stress. Exploratory analyses also suggested a 30% reduction in falls.These results are important because they suggest that an online program, which is available now and can be performed by people from the comfort of home or other location of choice, could be recommended as a complement or alternative to new therapies to help maximize quality of life for people living with ADRD and their care partners.

Abstract Construction of minimal metabolic networks (MMNs) contributes both to our understanding of the origins of metabolism and to the efficiency of biotechnological processes by preventing the diversion of flux away from product formation. We have designed MMNs using a novel in silico synthetic biology pipeline that removes genes encoding enzymes and transporters from genome-scale metabolic models. The resulting minimal gene-set still ensures both viability and high growth rates. The composition of these MMNs has defined a new functional class of genes termed Network Efficiency Determinants (NEDs). These genes, whilst not essential, are very rarely eliminated in constructing an MMN, suggesting that it is difficult for metabolism to be re-routed to obviate the need for such genes. Moreover, the removal of NED genes from an MMN significantly reduces its global efficiency. Bioinformatic analyses of the NED genes have revealed that not only do these genes have more genetic interactions than the bulk of metabolic genes but their protein products also show more protein-protein interactions. In yeast, NED genes are predominantly single-copy and are highly conserved across evolutionarily distant organisms. These features confirm the importance of the NED genes to the metabolic network, including why they are so rarely excluded during minimisation.

Abstract Background Preventing Loss of Independence through Exercise (PLIÉ) is a group program for people living with dementia that combines movements to support daily function with present moment body awareness and social engagement that has been found to have physical, emotional, social, and cognitive benefits. The goal of this study was to develop and refine a PLIÉ remote training program for interdisciplinary Veterans Affairs (VA) nursing home staff members also known as community living center (CLC) staff. Methods This pre-implementation study used iterative Plan-Do-Study-Act (PDSA) cycles. The 10-week PDSA cycles occurred from June to September 2021 at 2 VA nursing home sites. Remote training was delivered via Microsoft Teams and included 1-hour live-streamed weekly didactic sessions (nursing staff with PLIÉ instructor) focused on PLIÉ principles and 1-hour weekly live-streamed experiential sessions for staff to apply PLIÉ principles with residents. We administered weekly feedback surveys to iteratively refine the training process. Results 14 staff members participated (5 recreation therapists, 3 social workers, 2 registered nurses, 2 chaplains, 1 psychologist, and 1 speech pathologist). The experiential sessions were rated as most helpful overall. Key PDSA refinements included: (1) creating 10-minute video recording summaries to support learning, particularly for those unable to attend live training sessions due to clinical schedules; and (2) incorporating self-reflection and goal setting to support staff incorporation of PLIÉ principles into routine care and personal life. These refinements resulted in increased use of PLIÉ principles with the residents from 67 to 89% of the staff participants. 100% of regular attendees (11/11) rated their overall satisfaction with remote training as “very good” or “excellent.” Conclusions It was feasible to train interdisciplinary CLC staff participants to deliver an integrative group movement program for residents with dementia remotely. PDSA cycles supported refinement of the training process and improved uptake. A larger study of PLIÉ remote CLC staff training is needed to assess outcomes on residents and quality of care.

Abstract We use the duality between gravitational dynamics and fluids living on dynamical surfaces carrying multiple charges, known as the blackfold approach, to perturbatively construct new asymptotically global (Anti)-de Sitter multi-spinning, non-extremal, multi-charged black holes in theories of higher-dimensional gravity minimally coupled to a dilaton and higher-form gauge fields in spacetime dimensions D ≥ 5, and new asymptotically AdS l × S m black holes in type IIB and eleven-dimensional supergravity. These solutions include the generalisation of the Kerr-Newman solution to (A)dS carrying either electric or string charge, generalisations of black rings to higher-dimensions with 𝕊 p × 𝕊 n+1 horizon topology, static de Sitter solutions carrying arbitrary q-brane charge, as well as various asymptotically AdS l × S m multi-charged and multi-spinning black hole solutions, some of which correspond to novel thermal states in N $$ \mathcal{N} $$ = 4 Super-Yang-Mills theory.

Abstract Background We retrospectively investigate feasibility and safety of whole brain radiotherapy (WBRT) including a simultaneous-integrated boost technique (WBRT-SIB) in a cohort of patients with a very poor prognosis suffering from multiple and/or large brain metastases, unfavorable primary histology, poor performance status and/or symptomatic BMs. Materials and Methods Thirty-five patients with high brain tumor burden, extracranial metastases and low life-expectancy were treated with WBRT-SIB mostly with 35-42 Gy/14 fractions. All metastases were boosted in patients with up to 12 BMs. In patients with > 12 BM, large and/or small metastases in critical brain regions were boosted up to a maximum of 12 SIB volumes. Results The median number of BM was 8 (range 2–45) and the median BM diameter was 12 mm (range 4–90 mm). Fifteen (43%) patients had ≥ 10 BMs and 25 patients presented with a Karnofski index ≤ 80%. Primary tumor histology was NSCLC (n = 13), SCLC (n = 11), breast cancer (n = 7), melanoma (n = 2), other (n = 2). The median iPFS was not reached, and 12- and 18-months iPFS were 75% and 50%, respectively. Overall, seven patients had intracranial progression: two patients within the SIB and WBRT area, one patient only within the SIB region and four patients had new BMs in the WBRT volume alone. The median iPFS for non-SCLC patients was 17 months and the 12- and 18-month iPFS were 56.8% and 28.4%, respectively. There was no significant OS difference between SCLC-group and non-SCLC patients (p = 0.38). Overall, median OS was 8.7 months and 1-year OS was 25%. The treatment was generally well-tolerated with no observed cases of radionecrosis. Conclusion Our WBRT-SIB approach involves a combination of whole brain radiotherapy and a simultaneous integrated boost to specific tumor volumes, and its effectiveness is compared with other treatment modalities in the literature. Further research, including prospective studies with larger patient cohorts, is necessary to validate and refine the findings.

Abstract Extracellular vesicles (EVs) are membrane-enclosed bio-nanoparticles secreted by cells and naturally evolved to transport various bioactive molecules between cells and even organisms. These cellular objects are considered one of the most promising bio-nanovehicles for the delivery of native and exogenous molecular cargo. However, many challenges with state-of-the-art EV-based candidates as drug carriers still exist, including issues with scalability, batch-to-batch reproducibility, and cost-sustainability of the final therapeutic formulation. Microalgal extracellular vesicles, which we named nanoalgosomes, are naturally released by various microalgal species. Here, we evaluate the innate biological properties of nanoalgosomes derived from cultures of the marine microalgae Tetraselmis chuii, using an optimized manufacturing protocol. Our investigation of nanoalgosome biocompatibility in preclinical models includes toxicological analyses, using the invertebrate model organism Caenorhabditis elegans, hematological and immunological evaluations ex vivo and in mice. We evaluate nanoalgosome cellular uptake mechanisms in C. elegans at cellular and subcellular levels, and study their biodistribution in mice with accurate space-time resolution. Further examination highlights the antioxidant and anti-inflammatory bioactivities of nanoalgosomes. This holistic approach to nanoalgosome functional characterization demonstrates that they are biocompatible and innate bioactive effectors with unique bone tropism. These findings suggest that nanoalgosomes have significant potential for future therapeutic applications.

Sex differences in glioblastoma (GBM) incidence and outcome are well recognized, and emerging evidence suggests that these extend to genetic/epigenetic and cellular differences, including immune responses. However, the mechanisms driving immunologic sex differences are not fully understood. Here, we demonstrate that T cells play a critical role in driving GBM sex differences. Male mice exhibited accelerated tumor growth, with decreased frequency and increased exhaustion of CD8+ T cells in the tumor. Furthermore, a higher frequency of progenitor exhausted T cells was found in males, with improved responsiveness to anti-PD-1 treatment. Moreover, increased T-cell exhaustion was observed in male GBM patients. Bone marrow chimera and adoptive transfer models indicated that T cell-mediated tumor control was predominantly regulated in a cell-intrinsic manner, partially mediated by the X chromosome inactivation escape gene Kdm6a. These findings demonstrate that sex-biased predetermined behavior of T cells is critical for inducing sex differences in GBM progression and immunotherapy response.SignificanceImmunotherapies in patients with GBM have been unsuccessful due to a variety of factors, including the highly immunosuppressive tumor microenvironment in GBM. This study demonstrates that sex-biased T-cell behaviors are predominantly intrinsically regulated, further suggesting sex-specific approaches can be leveraged to potentially improve the therapeutic efficacy of immunotherapy in GBM. See related commentary by Alspach, p. 1966. This article is featured in Selected Articles from This Issue, p. 1949.

One of the most robust approaches to the prediction of causal driver genes of complex diseases is to apply reverse engineering methods to infer a gene regulatory network (GRN) from gene expression profiles (GEPs). In this work, we analysed 794 GEPs of 1117 human whole-blood samples from Amyotrophic Lateral Sclerosis (ALS) patients and healthy subjects reported in the GSE112681 dataset. GRNs for ALS and healthy individuals were reconstructed by ARACNe-AP (Algorithm for the Reconstruction of Accurate Cellular Networks - Adaptive Partitioning). In order to examine phenotypic differences in the ALS population surveyed, several datasets were built by arranging GEPs according to sex, spinal or bulbar onset, and survival time. The designed reverse engineering methodology identified a significant number of potential ALS-promoting mechanisms and putative transcriptional biomarkers that were previously unknown. In particular, the characterization of ALS phenotypic networks by pathway enrichment analysis has identified a gender-specific disease signature, namely network activation related to the radiation damage response, reported in the networks of bulbar and female ALS patients. Also, focusing on a smaller interaction network, we selected some hub genes to investigate their inferred pathological and healthy subnetworks. The inferred GRNs revealed the interconnection of the four selected hub genes (TP53, SOD1, ALS2, VDAC3) with p53-mediated pathways, suggesting the potential neurovascular response to ALS neuroinflammation. In addition to being well consistent with literature data, our results provide a novel integrated view of ALS transcriptional regulators, expanding information on the possible mechanisms underlying ALS and also offering important insights for diagnostic purposes and for developing possible therapies for a disease yet incurable.

Abstract Progressive lung fibrosis is associated with poorly understood aging-related endothelial cell dysfunction. To gain insight into endothelial cell alterations in lung fibrosis we performed single cell RNA-sequencing of bleomycin-injured lungs from young and aged mice. Analysis reveals activated cell states enriched for hypoxia, glycolysis and YAP/TAZ activity in ACKR1+ venous and TrkB+ capillary endothelial cells. Endothelial cell activation is prevalent in lungs of aged mice and can also be detected in human fibrotic lungs. Longitudinal single cell RNA-sequencing combined with lineage tracing demonstrate that endothelial activation resolves in young mouse lungs but persists in aged ones, indicating a failure of the aged vasculature to return to quiescence. Genes associated with activated lung endothelial cells states in vivo can be induced in vitro by activating YAP/TAZ. YAP/TAZ also cooperate with BDNF, a TrkB ligand that is reduced in fibrotic lungs, to promote capillary morphogenesis. These findings offer insights into aging-related lung endothelial cell dysfunction that may contribute to defective lung injury repair and persistent fibrosis.

BACKGROUND: Difficulty performing basic daily activities such as bathing and dressing (functional impairment) affects more than 15% of middle-aged people, and this proportion is increasing. Little is known about the experiences and needs of individuals who develop functional impairment in middle age. OBJECTIVE: To examine the experiences and needs of adults who developed functional impairment in middle age. DESIGN: Qualitative study using semi-structured interviews. PARTICIPANTS: Forty patients aged 50-64 years who developed functional impairment in middle age, recruited from four primary care clinics in San Francisco. APPROACH: Interviews included open-ended questions about participants daily life, ability to perform activities of daily living (ADLs), and needs related to functional impairment. We analyzed interviews using qualitative thematic analysis. KEY RESULTS: Interviews revealed several themes related to the psychosocial and physical impacts of developing functional impairment in middle age. Participants noted that losses associated with functional impairment, such as loss of independence, control, and social roles, caused conflict in their sense of identity. To cope with these losses, participants used strategies including acceptance, social comparison, adjusting standards, and engaging in valued life activities. Participants reflected on the intersection of their functional impairment with the aging process, noting that their impairments seemed premature compared to the more natural aging process in older adults. In terms of physical impacts, participants described how a lack of accommodations in the built environment exacerbated their impairments. While participants used behavioral strategies to overcome these challenges, unmet needs remained, resulting in downstream physical and psychological impacts including safety risks, falls, frustration, and fear. CONCLUSIONS: Unmet psychosocial and physical needs were common among middle-aged adults with functional impairment and led to negative downstream effects. Eliciting and addressing unmet needs may help mitigate downstream health consequences for this growing population, optimizing function and quality of life.

BACKGROUND: Preventing Loss of Independence through Exercise (PLIÉ) is an in-person group mind-body movement program for people across the spectrum of cognitive decline and care partners (CPs). OBJECTIVE: This study developed and refined an online version called Moving Together and tested feasibility and satisfaction with an online delivery. METHODS: In Phase 1, we used qualitative methods to determine which elements of the in-person program were essential to retain for the online version and adaptations that would be needed to support the user experience. In Phase 2, we created a prototype of the online program and iteratively refined it based on user feedback. In Phase 3, we assessed feasibility of online delivery based on class attendance and program completion; we assessed satisfaction and participant-reported outcomes using a post-program evaluation survey with quantitative and qualitative components. RESULTS: Phase 1 findings from 27 participants (14 PLWD, 13 CPs) revealed three key considerations related to online delivery of PLIÉ: technology use, social connection as a primary motivator, and physical safety concerns. Phase 2 iterative testing among 25 participants (14 PLWD, 11 CPs) resulted in key refinements to program delivery and instructional elements; Phase 3 pilot testing included 39 participants (12 PLWD, 15 CPs, 12 MCI) who attended 75 ± 29% of 24 classes; 77% completed the 12-week program, of whom 96% rated it as excellent or good. Participant-reported outcomes included improvements in social connection, emotional well-being, physical function, cognitive function and present-centered body awareness. PLWD or MCI also reported improvements in self-concept, and CPs reported improvements in caregiving self-efficacy. The primary challenges were related to participant navigation of technology. CONCLUSION: The Moving Together online program is feasible for PLWD or MCI and CPs with participants reporting high satisfaction and positive outcomes across multiple domains. Providing individual technology support is critical for the success of livestreamed, online interventions for dementia.

Functional status, or the ability to perform activities of daily living, is central to older adults health and quality of life. However, health systems have been slow to incorporate routine measurement of function into patient care. We used multiple qualitative methods to develop a patient-centered, interprofessional intervention to improve measurement of functional status for older veterans in primary care settings. We conducted semi-structured interviews with patients, clinicians, and operations staff (n = 123) from 7 Veterans Health Administration (VHA) Medical Centers. Interviews focused on barriers and facilitators to measuring function. We used concepts from the Consolidated Framework for Implementation Science and sociotechnical analysis to inform rapid qualitative analyses and a hybrid deductive/inductive approach to thematic analysis. We mapped qualitative findings to intervention components. Barriers to measurement included time pressures, cumbersome electronic tools, and the perception that measurement would not be used to improve patient care. Facilitators included a strong interprofessional environment and flexible workflows. Findings informed the development of five intervention components, including (1) an interprofessional educational session; (2) routine, standardized functional status measurement among older patients; (3) annual screening by nurses using a standardized instrument and follow-up assessment by primary care providers; (4) electronic tools and templates to facilitate increased identification and improved management of functional impairment; and (5) tailored reports on functional status for clinicians and operations leaders. These findings show how qualitative methods can be used to develop interventions that are more responsive to real-world contexts, increasing the chances of successful implementation. Using a conceptually-grounded approach to intervention development has the potential to improve patient and clinician experience with measuring function in primary care.

BackgroundSurgery is still the standard treatment for breast lesions such as in situ ductal carcinoma (DCIS); however, its survival benefit is minimal, particularly for low-grade DCIS. Surgical complications and related depression status can adversely affect patients’ quality of life. Approximately 25% of breast cancer (BC) cases are in situ forms, with DCIS making up 90% of these. Low and intermediate-grade DCIS often grow slowly and do not always progress clinically significant diseases. Identifying non-invasive lesions could help prevent overtreatment. In this context, new diagnostic tools like vacuum-assisted excision (VAE) could enhance the management of these conditions.MethodsThe prospective VACIS study explores the role of VAE in ensuring the absence of pathology at subsequent surgery and reducing the diagnostic underestimation of breast biopsies for microcalcifications. Patients with suspicious breast microcalcifications up to 15 mm, who are candidates for stereotactic biopsy, will be enrolled and randomised into two groups. The control group will complete the biopsy with typical sampling, aiming to collect some microcalcifications from the target, while the experimental group will focus on the complete removal of the biopsy target (confirmed by mammography on the biopsy table), followed by a second sequence of cleaning samples. Radiograms will confirm lesion removal. Pathologic outcomes at surgery will be compared between the groups, and the percentage of underestimation will be assessed. The sample size is calculated to be 70 patients per group, using statistical tests and multivariate logistic models to detect a significant difference in the absence of pathology. Data collected will include patient age, lesion characteristics, and details of the biopsy, pathology and surgery.DiscussionCurrent surgical treatments for low-and sometimes intermediate-grade DCIS offer limited survival benefits and may hurt patients’ quality of life due to surgery-related complications and associated depression. These lesions often grow slowly and might not become clinically significant, suggesting a need to avoid overtreatment. Improved diagnostics procedures, such as VAE, could help distinguish non-invasive from potentially invasive lesions, reduce biopsy underestimation, enable personalised management and optimise treatment strategies. This study hypothesises that VAE could be a viable alternative to surgery, capable of removing pathology during the biopsy procedure.Clinical trial registrationClinicaltrials.gov, identifier NCT05932758.

Aims: Evaluate effectiveness and safety of multiple HyperArc courses and patterns of progression in patients affected by BMs with intracranial progression. Methods: 56 patients were treated for 702 BMs with 197 (range 2–8) HyperArc courses in case of exclusive intracranial progression. Primary end-point was the overall survival (OS), secondary end-points were intracranial progression-free survival (iPFS), toxicity, local control (LC), neurological death (ND), and whole-brain RT (WBRT)-free survival. Site of progression was evaluated against isodoses levels (0, 1, 2, 3, 5, 7, 8, 10, 13, 15, 20, and 24 Gy.). Results: The 1-year OS was 70 %, and the median was 20.8 months (17–36). At the univariate analysis (UVA) biological equivalent dose (BED) > 51.3 Gy and non-melanoma histology significantly correlated with OS. The median time to iPFS was 4.9 months, and the 1-year iPFS was 15 %. Globally, 538 new BMs occurred after the first HA cycle in patients with extracranial disease controlled. 96.4 % of them occurred within the isodoses range 0–7 Gy as follows: 26.6 % (0 Gy), 16.5 % (1 Gy), 16.5 % (2 Gy), 20.1 % (3 Gy), 13.1 % (5 Gy), 3.4 % (7 Gy) (p = 0.00). Radionecrosis occurred in 2 metastases (0.28 %). No clinical toxicity of grade 3 or higher occurred during follow-up. One- and 2-year LC was 90 % and 79 %, respectively. At the UVA BED > 70 Gy and non-melanoma histology were significant predictors of higher LC. The 2-year WBRT-free survival was 70 %. After a median follow-up of 17.4 months, 12 patients deceased by ND. Conclusion: Intracranical relapses can be safely and effectively treated with repeated HyperArc, with the aim to postpone or avoid WBRT. Diffuse dose by volumetric RT might reduce microscopic disease also at relatively low levels, potentially acting as a virtual CTV. Neurological death is not the most common cause of death in this population, which highlights the impact of extracranial disease on overall survival.

Abstract Contrast-enhanced mammography (CEM) is a relatively recent diagnostic technique increasingly being utilized in clinical practice. Until recently, there was a lack of standardized reporting for CEM findings. However, this has changed with the publication of a supplement in the Breast Imaging Reporting and Data System (BI-RADS). A comprehensive understanding of CEM is essential for further enhancing its role in both screening and managing patients with breast malignancies. CEM can also be beneficial for problem-solving, improving the management of uncertain breast findings. Practitioners in this field should become more cognizant of how and when to employ this technique and interpret the various CEM findings. This paper aims to outline the key findings in the updated version of the BI-RADS specifically dedicated to CEM. Additionally, it will present some clinical cases commonly encountered in clinical practice. Critical relevance statement Standardized reporting and a thorough understanding of CEM findings are pivotal for advancing the role of CEM in screening and managing breast cancer patients. This standardization contributes significantly to integrating CEM as an essential component of daily clinical practice. Key points • A complete knowledge and understanding of the findings outlined in the new BI-RADS CEM are necessary for accurate reporting. • BI-RADS CEM supplement is intuitive and practical to use. • Standardization of the CEM findings enables more accurate patient management. Graphical Abstract

Abstract Biochar production from woody biomass generated during forest management (slash) offers significant benefits for soil health and carbon emissions, yet its adoption remains limited in the western United States (U.S.). To address this challenge, the U.S. Department of Agriculture (U.S.D.A.) Forest Service Rocky Mountain Research Station organized two workshops focused on forest management-centric biochar production. These workshops convened a diverse group of stakeholders, including investors, land management practitioners, industry professionals, and research scientists, each with unique roles in slash-based biochar production. This article presents a synthesis of the insights and perspectives gathered from these workshops, aiming to identify barriers and propose viable pathways for overcoming them. The barriers encompass governance issues such as policy and permitting, economic challenges related to costs, funding, and market stability, technological hurdles concerning methods and equipment, and a need for further research and improved science dissemination. In response to these challenges, workshop attendees collaboratively outlined specific strategies to reduce these barriers. These strategies emphasize the expansion of operational initiatives, the development of proactive policies, the stabilization of biochar markets, and the generation of additional case studies showcasing the effects of biochar amendments across various soils and environments. Collectively, the insights gleaned from this workshop series provide a comprehensive roadmap outlining both the struggles and the necessary actions and investments required to enhance the scale of slash-based biochar production and application in the western U.S. Graphical Abstract