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Although the 2022 European LeukemiaNet (ELN) acute myeloid leukemia (AML) risk classification reliably predicts outcomes in younger patients treated with intensive chemotherapy, it is unclear whether it applies to adults ≥60 years treated with lower-intensity treatment (LIT). We aimed to test the prognostic impact of ELN risk in patients with newly diagnosed (ND) AML aged ≥60 years given LIT and to further refine risk stratification for these patients. A total of 595 patients were included: 11% had favorable-, 11% intermediate-, and 78% had adverse-risk AML. ELN risk was prognostic for overall survival (OS) (P < .001) but did not stratify favorable- from intermediate-risk (P = .71). Within adverse-risk AML, the impact of additional molecular abnormalities was further evaluated. Multivariable analysis was performed on a training set (n = 316) and identified IDH2 mutation as an independent favorable prognostic factor, and KRAS, MLL2, and TP53 mutations as unfavorable (P < .05). A mutation score was calculated for each combination of these mutations, assigning adverse-risk patients to 2 risk groups: -1 to 0 points (Beat-AML intermediate) vs 1+ points (Beat-AML adverse). In the final refined risk classification, ELN favorable- and intermediate-risk were combined into a newly defined Beat-AML favorable-risk group, in addition to mutation scoring within the ELN adverse-risk group. This approach redefines risk for older patients with ND AML and proposes refined Beat-AML risk groups with improved discrimination for OS (2-year OS, 48% vs 33% vs 11%, respectively; P < .001), providing patients and providers additional information for treatment decision-making.

Enasidenib (ENA) is an inhibitor of isocitrate dehydrogenase 2 (IDH2) approved for the treatment of patients with IDH2-mutant relapsed/refractory acute myeloid leukemia (AML). In this phase 2/1b Beat AML substudy, we applied a risk-adapted approach to assess the efficacy of ENA monotherapy for patients aged ≥60 years with newly diagnosed IDH2-mutant AML in whom genomic profiling demonstrated that mutant IDH2 was in the dominant leukemic clone. Patients for whom ENA monotherapy did not induce a complete remission (CR) or CR with incomplete blood count recovery (CRi) enrolled in a phase 1b cohort with the addition of azacitidine. The phase 2 portion assessing the overall response to ENA alone demonstrated efficacy, with a composite complete response (cCR) rate (CR/CRi) of 46% in 60 evaluable patients. Seventeen patients subsequently transitioned to phase 1b combination therapy, with a cCR rate of 41% and 1 dose-limiting toxicity. Correlative studies highlight mechanisms of clonal elimination with differentiation therapy as well as therapeutic resistance. This study demonstrates both efficacy of ENA monotherapy in the upfront setting and feasibility and applicability of a risk-adapted approach to the upfront treatment of IDH2-mutant AML. This trial is registered at www.clinicaltrials.gov as #NCT03013998.

Based on an overview of the existing literature, this paper aims to provide a holistic and coherent conceptualisation and understanding of the complexity of educators' professional learning. First, the way in which professional development, professional learning and everyday learning have been configured in contemporary research is combined with an initial practice theory perspective. Consequently, we conceptualise professional learning as learning in and for professional practice. Subsequently, the theory of practice architectures, a practice theory developed in educational settings, is presented. Based on the authors' previous work, aspects of relatings, that is, the social space in which educators relate to each other in the mediums of power and solidarity, are highlighted. These include power, trust, recognition and agency. The paper ends by presenting a framework for understanding the complexity of learning in and for professional practice, consisting of two complementary perspectives: a site-based and time-bounded focus on professional action and an open-ended process of educators' professional and human growth. Brought together these perspectives enable an understanding of the complexity of professional learning in terms of praxis development.

This study addresses normative orientations to smartphone use in Swedish upper-secondary classrooms. We present a Nexus Analysis from a policy enactment perspective of a material comprising ethnographic interviews, classroom video observations, and smartphone screen capture, investigating how a cultural conception of the smartphone as a source of disturbance is negotiated in discursive and embodied social action. Three groups of policy actors -- head teachers, teachers, and students -- balance competing agendas such as digitalization strategies, popular media narratives, and student autonomy and peer relationship maintenance. There is a tension between orientations to the smartphone as a legitimate resource for socialization and learning in the digitalized classroom, but also as an exception to desired digitalization -- a potential threat to the social and disciplinary order of the classroom. Notably, the students display considerable awareness of such tensions, in reflective comments made in interviews and in displayed strategies for managing their smartphones in class.

Although action research has a history of bridging gaps between research and school practice, challenges emerge when aligning a scientific approach with development work in schools and in collaboration between research and school practice. In this article, we aim to deepen the knowledge on teachers' action research as social learning in collaboration with a research-based PD leader. In this study, we follow two teachers conducting action research in a Swedish upper secondary school, in collaboration with a professional development (PD) leader who is also a doctoral student. Qualitative data have been used to write value-creation stories that illustrate the learning process throughout their collaboration. Our findings show how joint work between the teachers and the PD leader functions as a boundary process where two sets of practices -- classroom and academic -- are coordinated and contribute to the learning process.

This article investigates how knowledge, competence and actions develop among teachers enrolled in a Master's degree programme in action research who have an interest in changing practices in the schools in which they teach. We draw upon the insights of seven teachers who completed the programme (part-time over four years) to examine how the Master's programme as a practice, shaped and was shaped by other practices -- in this case, each teacher's practice. We employ the theory of practice architectures to analyse the ways the programme enabled and constrained the teachers' developing knowledge, competencies and actions. We show how the teachers: a) developed perspectives on their own practice through studying literature, b) collaborated and engaged in dialogue with each other, c) actively inquired into their own practice. Second, we present distinctive stories, built on the ideas of "past" (earlier education experiences and motives for enrolling in the programme), "present" (the practice of the master's programme) and "future" (what teachers were doing after completing their master's degrees). To conclude, we claim that professional learning for teachers needs to continue over time and that important features such as structured dialogues and inquiry-based tasks are necessary to enable change in another practice.

This paper explores young people's narratives about BookTok and volitional reading. The data consist of narrative interviews with eight students (all girls) from two different classes in year 1 and year 2 of a preparatory programme for higher education, that is, students aged 17-18 years old. Using the framework of Wenger's notion of communities of practice and Bamberg's theory of narrative positioning, the findings indicate that the volitional reading practices described by the participants are strongly characterised by social, physical, and emotional dimensions that are generated and made possible by the book as an artefact. The findings also show that young people use the digital media platform TikTok and its subcommunity BookTok as a resource in constructing their own volitional reading practices and as a means to strengthen their reader identities. In view of their use of BookTok, this article contributes insights into young people's volitional reading practices and the construction of reader identities outside of school. The results also contribute to the ongoing discussion about how to support and motivate young people to read literature.

Teachers' implementation of and attitudes to school reforms and overriding pedagogical ideals have long been a topic of debate and research. In this article, we centre on teachers' descriptions of how progressive teaching was conducted as well as on the teachers' reasons for implementing such teaching in the 1940s. This study is based on written material consisting of 360 elementary school teachers' accounts of their teaching collected in 1946. The material was collected by a government investigation of how progressive teaching was conducted in Sweden. The accounts offer detailed descriptions of how pupils were activated and how elementary teachers at the time could use the community as a teaching resource. The article is inspired by a prosopography approach, in which the basic assumption is that it is possible to extend knowledge of social processes and societal development by studying the group profile of members of various institutions such as political or professional organisations. The analysis is based on John Dewey's and Larry Cuban's perspectives on progressivism. We found that, according to teaching the theme of pupils participation was frequently reported in 59% of the accounts, while student interaction (35%) and extended classroom (16%) were less reported. The teachers motivated their teaching on the basis of general ideals, as democracy. Also important were practical circumstances such as available teaching resources as well as physiological aspects as student's interest and development.

Teachers' professional learning is closely connected to and dependent on different leading practices. Teachers professional learning is regarded as a key factor in successful school development, and development leaders at different levels are assigned to provide for and support such learning. However, the connection between leading and learning needs to be further explored. In this article, we focus specifically on development leaders' leading practice when leading professional learning. Based on the theory of practice architectures, the study explores the interplay between development leaders and teacher leaders in a professional development programme, where the leading and learning practices of the different leaders meet. The findings show that development leaders' leading practice is characterised by responsiveness to ideas of successful leading, to experiences and observations of leading practices, to teacher leaders' understanding and to their own leading practices. Through these types of responsiveness, a formative aspect of leading unfolds where the interplay between development leaders' leading and teacher leaders' learning practices appears. We refer to this as "learning leading."

It is widely accepted that professional learning is a crucial aspect of the ongoing professional practice of educators. But how should this professional learning take place, and what arrangements enable and constrain practices associated with educator learning? In this article, we explore two case studies of action research projects: one undertaken with Australian Vocational Education and Training (VET) teachers, and the other undertaken with Swedish principals. Using the theory of practice architectures and the Professional Learning Framework (see text), we consider what action research team members identified that they learnt through the action research projects, and what enabled and constrained that learning. The findings highlight five key themes that enabled and constrained educator professional learning and supported educators in making positive changes in their professional practice: power and solidarity, trust, recognition, agency and time. Further, reflection and collaboration were also highlighted as important factors in supporting educator professional learning. We conclude that action research can enable educator professional learning, can support the contextualised understanding of what works, how it works and for whom it works, and can enable educators to make positive changes in their professional practices.

INTRODUCTION: Allogeneic hematopoietic cell transplantation (alloHCT) is increasingly offered to older adults, and its potential impact on cognition in this population is understudied. This work aims to evaluate the ability of cancer-specific geriatric assessments (cGA) and a global frailty index based on accumulation of deficits identified in the cGA to predict the risk of cognitive decline after alloHCT in older adults. MATERIALS AND METHODS: AlloHCT recipients aged 50 years or older completed a cGA, including a cognitive evaluation by the Blessed Orientation Memory Concentration (BOMC) test, at baseline prior to alloHCT and then at 3, 6, and 12 months after transplant. Baseline frailty was assessed using a deficit accumulation frailty index (DAFI) calculated from the cGA. A multinomial logit model was used to examine the association between predictors (individual cGA measures, DAFI) and the following three outcomes: alive with stable or improved cognition, alive with cognitive decline, and deceased. In post-hoc analyses, analysis of variance was used to compare BOMC scores at baseline, 3, 6, and 12 months across frailty categories. RESULTS: In total, 148 participants were included, with a median age of 62 (range 50-76). At baseline, 12% had cognitive impairment; at one year, 29% of survivors had improved BOMC scores, 33% had stable BOMC, and 37% had worse BOMC. Prior to transplant, 25% were pre-frail and 11% were frail. Individual baseline cGA measures were not associated with cognitive change at one year as assessed by BOMC. Adjusting for age, sex, and education, those who were frail at baseline were 7.4 times as likely to develop cognitive decline at one year than those who were non-frail, although this finding did not reach statistical significance (95% confidence interval [CI] 0.74-73.8, p = 0.09). The probability of being alive with stable/improved cognition at 12 months for the non-frail, pre-frail, and frail groups was 43%, 34%, and 8%, respectively. DISCUSSION: Baseline geriatric measures and frailty were not significantly associated with cognitive change as assessed by BOMC in adults aged 50 or older after alloHCT. However, the study was underpowered to detect clinically meaningful differences, and future work to elucidate potential associations between frailty and cognitive outcomes is warranted.

High-grade glioma is an aggressive cancer that occurs naturally in pet dogs. Canine high-grade glioma (cHGG) is treated with radiation, chemotherapy or surgery, but has no curative treatment. Within the past eight years, there have been advances in our imaging and histopathology standards as well as genetic charactereization of cHGG. However, there are only three cHGG cell lines publicly available, all of which were derived from astrocytoma and established using methods involving expansion of tumour cells in vitro on plastic dishes. In order to provide more clinically relevant cell lines for studying cHGG in vitro, the goal of this study was to establish cHGG patient-derived lines, whereby cancer cells are expanded in vivo by injecting cells into immunocompromized laboratory mice. The cells are then harvested from mice and used for in vitro studies. This method is the standard in the human field and has been shown to minimize the acquisition of genetic alterations and gene expression changes from the original tumour. Through a multi-institutional collaboration, we describe our methods for establishing two novel cHGG patient-derived lines, Boo-HA and Mo-HO, from a high-grade astrocytoma and a high-grade oligodendroglioma, respectively. We compare our novel lines to G06-A, J3T-Bg, and SDT-3G (traditional cHGG cell lines) in terms of proliferation and sensitivity to radiation. We also perform whole genome sequencing and identify an NF1 truncating mutation in Mo-HO. We report the characterization and availability of these novel patient-derived lines for use by the veterinary community.

Summary: Donor milk obtained from milk banks is a source of infant nutrition for mothers that cannot produce their own milk. Milk banks quality control the milk when donated, testing for the presence of pathogenic bacteria, protein and fat concentrations and total energy content. The macronutrient analysis allows the milk bank to decide if they need to add fortifiers to the milk and whether to continue accepting milk from a specific donor. The data registered is a large knowledge base for understanding how the macronutrient content in human milk changes with e.g. time, maternal health and gestational age. Using information from 331 donated milk samples from 74 different donors, all from Denmark, this paper looks at trends in macronutrient content relative to several parameters. Our results show that there is a statistically significant change in content over time and gestational age, but also that other parameters, not covered by the available data, can have an effect on the quality of donated human milk.

Purpose: Water freely diffuses across cell membranes, making it suitable for measuring absolute tissue perfusion. In this study, we introduce an imaging method for conducting coronary artery angiography and quantifying myocardial perfusion across the entire heart using hyperpolarized water. Methods: 1H was hyperpolarized using dissolution dynamic nuclear polarization (dDNP) with UV-generated radicals. Submillimeter resolution coronary artery images were acquired as 2D projections using a spoiled GRE (SPGRE) sequence gated on diastole. Dynamic perfusion images were obtained with a multi-slice SPGRE with diastole gating, covering the entire heart. Perfusion values were analyzed through histograms, and the most frequent estimated perfusion value (the mode of the distribution), was compared with the average values for 15O water PET from the literature. Results: A liquid state polarization of 10% at the time of the injection and a 30 s T1 in D2O TRIS buffer were measured. Both coronary artery and dynamic perfusion images exhibited good quality. The main and small coronary artery branches were well resolved. The most frequent estimated perfusion value is around 0.6 mL/g/min, which is lower than the average values obtained from the literature for 15O-water PET (around 1.1 and 1.5 mL/g/min). Conclusions: The study successfully demonstrated the feasibility of achieving high-resolution, motion-free coronary artery angiography and 3D whole-heart quantitative myocardial perfusion using hyperpolarized water.

Abstract Although patients benefit from immune checkpoint inhibition (ICI) therapy in a broad variety of tumors, resistance may arise from immune suppressive tumor microenvironments (TME), which is particularly true of hepatocellular carcinoma (HCC). Since oncolytic viruses (OV) can generate a highly immune-infiltrated, inflammatory TME, OVs could potentially restore ICI responsiveness via recruitment, priming, and activation of anti-tumor T cells. Here we find that on the contrary, an oncolytic vesicular stomatitis virus, expressing interferon-ß (VSV-IFNß), antagonizes the effect of anti-PD-L1 therapy in a partially anti-PD-L1-responsive model of HCC. Cytometry by Time of Flight shows that VSV-IFNß expands dominant anti-viral effector CD8 T cells with concomitant relative disappearance of anti-tumor T cell populations, which are the target of anti-PD-L1. However, by expressing a range of HCC tumor antigens within VSV, combination OV and anti-PD-L1 therapeutic benefit could be restored. Our data provide a cautionary message for the use of highly immunogenic viruses as tumor-specific immune-therapeutics by showing that dominant anti-viral T cell responses can inhibit sub-dominant anti-tumor T cell responses. However, through encoding tumor antigens within the virus, oncolytic virotherapy can generate anti-tumor T cell populations upon which immune checkpoint blockade can effectively work.

Hematopoietic cell transplant (HCT) recipients are at risk for thromboembolic and bleeding complications. There is limited evidence regarding the optimal approach to managing venous thromboembolism (VTE) prophylaxis in hospitalized patients undergoing HCT. In this retrospective cohort study, we evaluated the incidence of bleeding and VTE events in hospitalized HCT patients who received VTE prophylaxis per our institution's VTE Prophylaxis Protocol (VPP), with either enoxaparin 40 mg subcutaneously daily or heparin 5 000 units subcutaneously twice daily, compared to historical controls who did not receive VTE prophylaxis. The primary outcome was a composite of major bleeding events, clinically relevant non-major bleeding (CRNMB), and minor bleeding. The secondary outcome was a composite of VTE events. A total of 614 patients were evaluated, including 278 prior to and 336 after implementation of VPP. VTE prophylaxis resulted in no difference in bleeding events (15.1% in the pre-VPP group vs. 14.6% in the post-VPP group, p = 0.86) or composite of major and CRNMB events (0.72% vs. 0.30%, p = 0.59). There was a trend toward lower incidence of VTE events in the post-VPP group which did not reach statistical significance (8.6% vs. 6.0%, p = 0.20). We conclude that VTE prophylaxis does not pose additional bleeding risk in HCT patients.

BackgroundPatients with acute myeloid leukemia (AML) who have tumor protein p53 (TP53) mutations or a complex karyotype have a poor prognosis, and hypomethylating agents are often used. The authors evaluated the efficacy of entospletinib, an oral inhibitor of spleen tyrosine kinase, combined with decitabine in this patient population.MethodsThis was a multicenter, open-label, phase 2 substudy of the Beat AML Master Trial (ClinicalTrials.gov identifier NCT03013998) using a Simon two-stage design. Eligible patients aged 60 years or older who had newly diagnosed AML with mutations in TP53 with or without a complex karyotype (cohort A; n = 45) or had a complex karyotype without TP53 mutation (cohort B; n = 13) received entospletinib 400 mg twice daily with decitabine 20 mg/m2 on days 1-10 every 28 days for up to three induction cycles, followed by up to 11 consolidation cycles, in which decitabine was reduced to days 1-5. Entospletinib maintenance was given for up to 2 years. The primary end point was complete remission (CR) and CR with hematologic improvement by up to six cycles of therapy.ResultsThe composite CR rates for cohorts A and B were 13.3% (95% confidence interval, 5.1%-26.8%) and 30.8% (95% confidence interval, 9.1%-61.4%), respectively. The median duration of response was 7.6 and 8.2 months, respectively, and the median overall survival was 6.5 and 11.5 months, respectively. The study was stopped because the futility boundary was crossed in both cohorts.ConclusionsThe combination of entospletinib and decitabine demonstrated activity and was acceptably tolerated in this patient population; however, the CR rates were low, and overall survival was short. Novel treatment strategies for older patients with TP53 mutations and complex karyotype remain an urgent need.

Spontaneous coronary artery dissection (SCAD) is an understudied cause of myocardial infarction primarily affecting women. It is not known to what extent SCAD is genetically distinct from other cardiovascular diseases, including atherosclerotic coronary artery disease (CAD). Here we present a genome-wide association meta-analysis (1,917 cases and 9,292 controls) identifying 16 risk loci for SCAD. Integrative functional annotations prioritized genes that are likely to be regulated in vascular smooth muscle cells and artery fibroblasts and implicated in extracellular matrix biology. One locus containing the tissue factor gene F3, which is involved in blood coagulation cascade initiation, appears to be specific for SCAD risk. Several associated variants have diametrically opposite associations with CAD, suggesting that shared biological processes contribute to both diseases, but through different mechanisms. We also infer a causal role for high blood pressure in SCAD. Our findings provide novel pathophysiological insights involving arterial integrity and tissue-mediated coagulation in SCAD and set the stage for future specific therapeutics and preventions.

The innovative utilization of the microencapsulation technique and the antimicrobial properties of Azadirachta Indica (A.I.) and Tinospora cordifolia (T.C.) present a novel approach to producing antiseptic wipes. In this study, microcapsules with A.I. oil and T.C. extracts were synthesized and integrated into non-woven cotton fabric aiming to create disposable antiseptic medical wipes. The T.C. extract and A.I. oil were used in a 1:1 ratio and microencapsulated utilizing sodium alginate as the encapsulation material through an ionic gelation process. The optical microscope analysis of microcapsules revealed diverse microcapsule sizes, ranging from 50 μm to 180 μm in diameter and scanning electron microscopy revealed that the treated fabric has uniform distribution of microcapsules across the entire fabric surface. The antimicrobial efficacy was evaluated through disk diffusion for the extract and oil and the fabric's antimicrobial activity was assessed by measuring bacterial reduction. The treated fabric displayed substantial reductions in both Gram-positive bacteria (Staphylococcus aureus (87 %) and Bacillus cereus (99 %)) and Gram-negative bacteria (Escherichia coli (81 %) and Pseudomonas aeruginosa (99 %)). Although the treated fabric exhibited a slight decrease in whiteness (48.5–39), this alteration did not adversely affect other fabric properties. These findings underscore the potential of microencapsulated natural extracts in producing effective antimicrobial medical wipes, thereby contributing to infection control.

The transition of patients with complex needs from hospital to municipal rehabilitation following moderate and severe brain injury is challenging. This qualitative study explored the municipal service allocation processes within such transitions. The caseworkers’ comprehensive task of combining patients’ preferences and needs, healthcare providers’ recommendations and municipal guidelines and service allocation were analysed. Data comprised of patients’ health records, meeting observations and semi-structured interviews with municipal staff, patients and next of kin. Results demonstrated that the issue of most concern was the location of where the patient was to continue municipal rehabilitation. Municipal caseworkers gathered extensive information, including recommendations from healthcare providers and preferences of patients and next of kin. These were frequently in contrast to the municipal guidelines’ requirements and the services’ organisational structure. The discrepancies led to tension, which was difficult to manoeuvre. This study indicates that incorporating individually tailored services into the daily service allocation practice can be demanding and even dilemmatic. The designated focus on the transition of patients with complex rehabilitation needs gives insights into how service allocation, user involvement and coordination policies are acted out in practice and may directly influence rehabilitation trajectories.

Magnetically trapped antihydrogen atoms can be cooled by expanding the volume of the trap in which they are confined. We report a proof-of-principle experiment in which antiatoms are deliberately released from expanded and static traps. Antiatoms escape at an average trap depth of 0.08±0.01K (statistical errors only) from the expanded trap while they escape at average depths of 0.22±0.01 and 0.17±0.01K from two different static traps. (We employ temperature-equivalent energy units.) Detailed simulations qualitatively agree with the escape times measured in the experiment and show a decrease of 38% (statistical error

Background: While prevalence estimates differ by definition of metabolic syndrome (MetS), it is less clear how different definitions affect associations with alcohol consumption. Methods: We included 3051 adults aged 25–77 from the baseline examination of the Swedish INTERGENE cohort (2001–2004). Using multiple logistic regression, we investigated cross-sectional associations between ethanol intake and MetS defined according to the Adult Treatment Panel III (ATP III), the International Diabetes Federation (IDF), and the Joint Interim Statement (JIS). Alcohol exposure categories comprised abstinence, and low, medium, and high consumption defined via sex-specific tertiles of ethanol intake among current consumers. Covariates included sociodemographics, health, and lifestyle factors. Results: MetS prevalence estimates varied between 13.9 % (ATP III) and 25.3 % (JIS), with higher prevalence in men than women. Adjusted for age and sex, medium-high alcohol consumption was associated with lower odds of MetS compared to low consumption, while no difference was observed for abstainers. Only the most specific (and thus severe) definition of MetS (ATP III) showed decreasing odds for ethanol intake when adjusted for all covariates. Conclusion: Our study shows that alcohol-related associations differ by definition of MetS. The finding that individuals with the most stringently defined MetS may benefit from alcohol consumption calls for further well-controlled studies.