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Summary: Endocannabinoids, signaling through the cannabinoid CB1 receptor (CB1R), regulate several forms of neuronal plasticity. CB1Rs in the developing primary visual cortex (V1) play a key role in the maturation of inhibitory circuits. Although CB1Rs were originally thought to reside mainly on presynaptic axon terminals, several studies have highlighted an unexpected role for astrocytic CB1Rs in endocannabinoid mediated plasticity. Here, we investigate the impact of cell-type-specific removal of CB1Rs from interneurons or astrocytes on development of inhibitory synapses and network plasticity in mouse V1. We show that removing CB1Rs from astrocytes interferes with maturation of inhibitory synaptic transmission. In addition, it strongly reduces ocular dominance (OD) plasticity during the critical period. In contrast, removing interneuron CB1Rs leaves these processes intact. Our results reveal an unexpected role of astrocytic CB1Rs in critical period plasticity in V1 and highlight the involvement of glial cells in plasticity and synaptic maturation of sensory circuits.

Background: Radiation associated angiosarcoma (RAAS) of the breast is a rare malignancy with poor survival. Optimal treatment strategies remain uncertain due to a lack of data, and vary between surgery alone and a combination of surgery with (neo)adjuvant chemotherapy (NACT) and/or re-irradiation. The aim of this study was to evaluate the potential benefit of taxane based NACT. Methods: In this retrospective single center study, all patients with RAAS of the breast treated between 1994 and 2024 are included. Since 2018, NACT is considered a treatment option for this patient population in our institute. The difference in oncological outcomes of patients with and without NACT were compared. Results: Thirty-five women were included. Thirteen (37 %) received NACT of which five (39 %) also had neoadjuvant re-irradiation with hyperthermia. Eleven patients (85 %) received paclitaxel, the other two (15 %) had doxorubicine/docetaxel. Complete pathological response was found in 69 % (n = 9). Median follow up was 41 months (range 24–56) for patients with NACT and 44 (range 20–108) for patients without NACT. In the NACT group, only one patient developed a recurrence after 6.5 years. Patients with NACT had improved oncological outcomes compared to patients without NACT in terms of 3-year local recurrence free survival (100% vs. 63.9 %, p = 0.14), distant metastasis free survival (100 % vs. 47.5 %, p = 0.005), and overall survival (100% vs. 56.1 %, p = 0.016). Conclusion: In this study, neoadjuvant taxanes for RAAS of the breast leads to improved distant metastasis free survival and overal survival in patients treated with NACT compared to no NACT

Abstract The health-related quality of life (HRQoL) among long-term Adolescent and Young Adult Cancer Survivors (AYACS) and an age- and sex-matched normative population was examined. Although the HRQoL of AYACS was worse compared to the normative population before and during the COVID-19 pandemic, the scores of AYACS improved over time in contrast to the normative population. Presumably, AYACS are used to adjusting their lives to stressful life events. Furthermore, the lockdown may have been beneficial for AYACS who face difficulties fully participating in society due to the impact of cancer. AYACS who encounter HRQoL issues could benefit from support interventions to empower them and build resilience.

Introduction: Imatinib has led to a phenomenal progress in the treatment of GIST. A rare and lesser-known side effect of imatinib is pneumonitis, an uncommon multicausal interstitial lung disease. Methods: Patients registered within the Dutch GIST Registry (DGR) were reviewed. For the patients identified with an imatinib-induced pneumonitis we reported the time on imatinib to develop pneumonitis, how the pneumonitis was diagnosed, graded and managed, and how the GIST treatment was managed. Cases: Of the 1934 patients registered in the DGR, 1161 patients received imatinib at some point, of which nine patients (0.8 %) were identified with an imatinib-induced pneumonitis. At time of the pneumonitis, patients received a daily imatinib dose of 200–400 mg for a mean duration of 486 days. One patient was able to continue imatinib in a lower dose, in the other eight patients imatinib was interrupted, and six of these patients started prednisolone treatment. After management of the imatinib-induced pneumonitis, four patients stopped imatinib permanently, two patients were rechallenged with imatinib, and two patients started treatment with second-line sunitinib. Conclusion: Imatinib-induced pneumonitis is a rare side effect, which may affect GIST management considerably. After the management of imatinib-induced pneumonitis, clinicians are left with difficult treatment dilemmas.

Abstract Background Despite growing (inter)national awareness and appreciation, age‐specific care is still not always self‐evident and accepted as standard of care for adolescent and young adult (AYA) cancer patients. It is unknown whether long‐term AYA cancer survivors have missed age‐specific care, and if so, which survivors missed it and regarding which topics. Methods The Netherlands Cancer Registry (NCR) identified all long‐term AYA cancer survivors (aged 18–39 years at initial cancer diagnosis, 5–20 years past diagnosis) in the Netherlands, who were invited to participate in a population‐based, observational, cross‐sectional questionnaire study (SURVAYA study), including questions on care needs. Results In total, 3.989 AYAs participated (35.3% response rate). One‐third of them had a need for age‐specific care (33.5%), 41.2% had no need and 25.3% did not know whether they had a need. Those who had a need for age‐specific care were significantly more often female, higher educated, diagnosed at a younger age, and treated with chemotherapy, radiotherapy or hormone therapy. Most frequent topics were disease and treatment (29.7%), emotions (24.1%), friends (22.6%), family and children (15.6%), fertility and pregnancy (14.8%), work and reintegration (10.5%), care not tailored (13.8%), and overarching care and life (27.7%). Palliative care (0.0%), spirituality (0.2%), death (0.7%), complementary care (0.7%), and late effects (1.3%) were mentioned least. Conclusions A substantial proportion of long‐term AYA cancer survivors showed a need for age‐specific care, varying by sociodemographic and clinical factors, on a wide variety of topics, which could be targeted to improve current AYA care services.

Abstract In 1950, Maud Karpeles embarked on a song collecting expedition to the Appalachian Mountains with the American scholar and fieldworker Sidney Robertson Cowell. Their plan was to retrace the [...]

Background In patients after heart transplantation, systemic arterial hypertension and enhanced central aortic stiffness contribute to increased ventricular afterload, which might lead to graft dysfunction. The aim of our study was to characterize systemic arterial elastance and its impact on left ventricular function and ventriculo‐arterial coupling in a cohort of children, adolescents, and young adults after heart transplantation using invasive conductance catheter technique. Methods and Results Thirty patients who had heart transplants (age, 20.0±6.5 years, 7 female) underwent invasive cardiac catheterization including pressure‐volume loop analysis. Load‐independent parameters of systolic (ventricular elastance [Ees]) and diastolic (ventricular compliance) function as well as systemic arterial elastance (Ea, end‐systolic pressure/stroke volume) and ventriculo‐arterial coupling (Ea/Ees) were assessed at baseline level and during dobutamine infusion (10 μg/kg/min). Ees showed an appropriate increase under inotropic stimulation from 0.43 (0.11–2.52) to 1.00 (0.20–5.10) mm Hg/mL/m2 (P

Background: Participation of Adolescents and Young Adults with cancer (AYAs: 18–39 years at time of diagnosis) in patient-reported outcome studies is warranted given the limited knowledge of (long-term) physical and psychosocial health outcomes. We examined the representativeness of AYAs participating in the study, to observe the impact of various invitation methods on response rates and reasons for non-participation. Methods: A population-based, cross-sectional cohort study was performed among long-term (5–20 years) AYA cancer survivors. All participants were invited using various methods to fill in a questionnaire on their health outcomes, including enclosing a paper version of the questionnaire, and sending a reminder. Those who did not respond received a postcard in which they were asked to provide a reason for non-participation. Results: In total, 4.010 AYAs (response 36%) participated. Females, AYAs with a higher socio-economic status (SES), diagnosed more than 10 years ago, diagnosed with a central nervous system tumor, sarcoma, a lymphoid malignancy, stage III, or treated with systemic chemotherapy were more likely to participate. Including a paper questionnaire increased the response rate by 5% and sending a reminder by 13%. AYAs who did not participate were either not interested (47%) or did want to be reminded of their cancer (31%). Conclusions: Study participation was significantly lower among specific subgroups of AYA cancer survivors. Higher response rates were achieved when a paper questionnaire was included, and reminders were sent. To increase representativeness of future AYA study samples, recruitment strategies could focus on integrating patient-reported outcomes in clinical practice and involving AYA patients to promote participation in research.

This study explores the integration of Raman spectroscopy (RS) with machine learning for the early detection and subtyping of breast cancer using blood plasma samples. We performed detailed spectral analyses, identifying significant spectral patterns associated with cancer biomarkers. Our findings demonstrate the potential for classifying the four major subtypes of breast cancer at stage Ia with an average sensitivity and specificity of 90% and 95%, respectively, and a cross‐validated macro‐averaged area under the curve (AUC) of 0.98. This research highlights efforts to integrate vibrational spectroscopy with machine learning, enhancing cancer diagnostics through a non‐invasive, personalised approach for early detection and monitoring disease progression. This study is the first of its kind to utilise RS and machine learning to classify the four major breast cancer subtypes at stage Ia. [ABSTRACT FROM AUTHOR]

Purpose: To identify subgroups of patients with oesophageal cancer based on exercise intensity during prehabilitation, and to investigate whether training outcomes varied between subgroups. Materials and methods: Data from a multicentre cohort study were used, involving participants following prehabilitation before oesophagectomy. Hierarchical cluster analysis was performed using four cluster variables (intensity of aerobic exercise, the Borg score during resistance exercise, intensity of physical activity, and degree of fatigue). Aerobic capacity and muscle strength were estimated before and after prehabilitation. Results: In 64 participants, three clusters were identified based on exercise intensity. Cluster 1 (n = 23) was characterised by fatigue and physical inactivity, cluster 2 (n = 9) by a low training capacity, despite high physical activity levels, and cluster 3 (n = 32) by a high training capacity. Cluster 1 showed the greatest improvement in aerobic capacity (p = 0.37) and hand grip strength (p = 0.03) during prehabilitation compared with other clusters. Conclusions: This cluster analysis identified three subgroups with distinct patterns in exercise intensity during prehabilitation. Participants who were physically fit were able to train at high intensity. Fatigued participants trained at lower intensity but showed the greatest improvement. A small group of participants, despite being physically active, had a low training capacity and could be considered frail. IMPLICATIONS FOR REHABILITATION: Patients with oesophageal cancer show different patterns of exercise intensity during prehabilitation, resulting in three distinct subgroups. Patients with a good level of physical fitness are able to train at high intensity and may require less intensive supervision during the programme. Fatigued patients are able to perform the training programme, having more room for improvement. A small group of frail patients seem to be at risk for overtraining and may require an adjusted training intensity. [ABSTRACT FROM AUTHOR]

Surface microstructures in nature enable diverse and intriguing properties, from the iridescence of butterfly wings to the hydrophobicity of lotus leaves to the controllable adhesion of gecko toes. Many artificial analogues exist; however, there is a key characteristic of the natural materials that is largely absent from the synthetic versions-spatial variation. Here we show that exploiting spatial variation in the design of one class of synthetic microstructure, gecko-inspired adhesives, enables one-way friction, an intriguing property of natural gecko adhesive. When loaded along a surface in the preferred direction, our adhesive material supports forces 100 times larger than when loaded in the reverse direction, representing an asymmetry significantly larger than demonstrated in spatially uniform adhesives. Our study suggests that spatial variation has the potential to advance artificial microstructures, helping to close the gap between synthetic and natural materials.

This article draws on empirical research – 23 qualitative interviews and data from ethnographic observation – within the German marksmen’s club milieu. There are over one million members of these clubs in Germany, where traditional customs, sociability and shooting sports are practised. Public perceptions of marksmen’s clubs are that they are rather conservative. Marksmen’s clubs look back to centuries-old traditions and, while they can be considered as part of the political mainstream or the social centre of society (Mitte der Gesellschaft), the milieu has attracted right-wing or extreme-right actors who have sought to influence, and appropriate certain aspects of, the milieu. This makes it an important environment for social scientific study in general and for radicalisation research in particular. Rooted in the emic perspectives of the interviewed marksmen, this article explores a range of possible resources for preventing and countering radicalisation (P/CR) and facilitating non-radicalisation in the marksmen’s club milieu and society more widely. Drawing on reflections and findings in the field of criminal justice research, the moral emotion of (anticipated) shame is identified as such a potential resource alongside norms and values within the marksmen’s club and its communities. The article also discusses possible unintended, negative effects of (anticipated) shame, arguing that, if experienced as ‘stigmatising shaming’, such (anticipated) shame may also trigger or fuel radicalisation processes. The criminological concept of ‘reintegrative shaming’ is discussed as a potential way of avoiding such counterproductive ‘backfire effects’ and the notion of reintegrative dialogue – inspired by the emic perspectives of the interviewed marksmen – is explored.

Die strukturelle Durchlässigkeit in ein Hochschulstudium und Schaffung von Rahmenbedingungen für lebenslanges Lernen sind wichtige Ziele des Europäischen Hochschulraums. In den D-A-CH-Ländern sind sowohl Absolvent:innen der beruflichen Bildung ohne Matura/Abitur als auch Erwerbs- und Familientätige sowie „learners in later life“ wichtige Zielgruppen des Konstrukts „nicht-traditionelle Studierende“. Aus diversitäts- und ungleichheitstheoretischen Perspektiven untersuchen die Beiträge – auf Grundlage aktueller Daten – Regelungen des Hochschulzugangs, das Zeitbudget Studierender, die Effekte von Pflegeverantwortung sowie den Studienabbruch, u. a. während der Covid-19-Pandemie. Thematisiert werden ein Lernort auf See ebenso wie neue Wege in ein Studium zum Lehramt an beruflichen Schulen. Die Beiträge repräsentieren Tiefenbohrungen auf nach wie vor kleinem Terrain.