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Honey is a sweet, syrup-like substance that bees (Apis sp.) produce from the nectar of flowering plants. The aim of this study was to examine the physicochemical properties and antioxidant activities of multifloral honey (Apis dorsata forest honey) and (Apis cerana cultivated honey) from Kerinci, Jambi. The analysis consist of the intensity of colour, pH, viscosity, water content, ash content, sugar content, HMF content, acidity and antioxidant activity. The results showed that forest honey had light amber colour while cultivated honey had extra light amber colour. The pH, viscosity, water content, sugar content, HMF content, and acidity in forest honey were still in compliance with SNI standard, but the ash content was higher than the SNI standard. Cultivated honey had pH, sugar content, and HMF content in the range of SNI standar. However, the viscosity, water content, ash content, and acidity in cultivated honey were not in compliance with SNI standar. Forest honey and cultivated honey had antioxidant capacities about 16,74 mgVCE/g and 16,60 mgVCE/g, respectively. Meanwhile the antioxidant activity were 63,80% and 63,28%, respectively. Forest honey had more physicochemical aspects  that were still in compliance with SNI standards compared to cultivated honey. The antioxidant activities of Kerinci honey, both forest honey and cultivated honey, were higher than the results of previous honey studies in other location.

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.

Kjell Torén,1 Jenny Vikgren,2 Anna-Carin Olin,1 Annika Rosengren,3 Göran Bergström,3 John Brandberg2 1Section of Occupational and Environmental Medicine, Institute of Medicine, Sahlgrenska Academy, 2Department of Radiology, Institute of Clinical Sciences, 3Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden Background: The aim of this study was to estimate the occupational burden of airflow limitation, chronic airflow limitation, COPD, and emphysema.Materials and methods: Subjects aged 50–64 years (n=1,050) were investigated with forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC). Airflow limitation was defined as FEV1/FVC

Kjell Torén,1,2 Nicola Murgia,1,2 Anna-Carin Olin,1 Jan Hedner,3 John Brandberg,4 Annika Rosengren,5 Göran Bergström51Section of Occupational and Environmental Medicine, Sahlgrenska Academy, University of Gothenburg, Sweden; 2Section of Occupational Medicine, Respiratory Diseases and Toxicology, University of Perugia, Italy; 3Department of Medicine/Lung Medicine, Sahlgrenska Academy, University of Gothenburg, 4Department of Radiology, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, 5Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Sweden Background: In epidemiological studies, items about physician-diagnosed COPD are often used. There is a lack of validation and standardization of these items.Materials and methods: In a general population-based study, 1,050 subjects completed a questionnaire and performed spirometry, including forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC) after inhalation of 400 µg of salbutamol. COPD was defined as the ratio of FEV1/FVC

K Torén,1 B Bake,1 A-C Olin,1 G Engström,2 A Blomberg,3 J Vikgren,4 J Hedner,5 J Brandberg,4 HL Persson,6,7 CM Sköld,8 A Rosengren,9 G Bergström,9 C Janson10 1Section of Occupational and Environmental Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, 2Department of Clinical Science, Lund University, Malmö, 3Division of Medicine/Respiratory Medicine, Department of Public Health and Clinical Medicine, Umeå University, Umeå, 4Department of Radiology, Institute of Clinical Sciences, 5Department of Internal Medicine/Lung Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, 6Department of Respiratory Medicine, 7Department of Medicine and Health Sciences, Linköping University, Linköping, 8Respiratory Medicine Unit, Department of Medicine Solna, Centre for Molecular Medicine, Karolinska Institutet, Stockholm, 9Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, 10Department of Medical Sciences, Clinical Physiology and Lung, Allergy and Sleep Research, Uppsala University, Uppsala, Sweden Background: Data are lacking from general population studies on how to define changes in lung function after bronchodilation. This study aimed to analyze different measures of bronchodilator response of forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC) and slow vital capacity (SVC). Materials and methods: Data were derived from the Swedish Cardiopulmonary Bioimage Study (SCAPIS) Pilot study. This analysis comprised 1,050 participants aged 50–64 years from the general population. Participants were investigated using a questionnaire, and FEV1, FVC and SVC were recorded before and 15 minutes after inhalation of 400 µg of salbutamol. A bronchodilator response was defined as the relative change from baseline value expressed as the difference in units of percent predicted normal. Predictors of bronchodilator responses were assessed using multiple linear regression models. Airway obstruction was defined as FEV1/FVC ratio below lower limit of normal (LLN) before bronchodilation, and COPD was defined as an FEV1/FVC ratio below LLN after bronchodilation. Physician-diagnosed asthma was defined as an affirmative answer to “Have you ever had asthma diagnosed by a physician?”. Asymptomatic never-smokers were defined as those not reporting physician-diagnosed asthma, physician-diagnosed COPD or emphysema, current wheeze or chronic bronchitis and being a lifelong never-smoker.Results: Among all subjects, the greatest bronchodilator responses (FEV1, FVC and SVC) were found in subjects with asthma or COPD. The upper 95th percentile of bronchodilator responses in asymptomatic never-smokers was 8.7% for FEV1, 4.2% for FVC and 5.0% for SVC. The bronchodilator responses were similar between men and women. In a multiple linear regression model comprising all asymptomatic never-smokers, the bronchodilator response of FEV1 was significantly associated with airway obstruction and height. Conclusion: When the bronchodilator response in asymptomatic never-smokers is reported as the difference in units of predicted normal, significant reversibility of FEV1, FVC and SVC to bronchodilators is ~9%, 4% and 5%, respectively. Keywords: spirometry, reversibility, COPD, epidemiology

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.

Joel Bergqvist,1 Anders Andersson,2 Anna-Carin Olin,3 Nicola Murgia,3,4 Linus Schiöler,3 Mogens Bove,5 Johan Hellgren1 1Department of Otorhinolaryngology, Head and Neck Surgery, Institute of Clinical Sciences, 2Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, 3Department of Occupational and Environmental Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; 4Department of Medicine, Section of Occupational Medicine, Respiratory Diseases and Toxicology, University of Perugia, Perugia, Italy; 5Department of ENT and Oral Maxillofacial Surgery, NU Hospital Group, Trollhättan, Sweden Background: The aim of this population-based study was to investigate the risk of developing noninfectious rhinitis (NIR) in subjects with chronic obstructive pulmonary disease (COPD). Materials and methods: This is a longitudinal population-based study comprising 3,612 randomly selected subjects from Gothenburg, Sweden, aged 25–75 years. Lung function was measured at baseline with spirometry and the included subjects answered a questionnaire on respiratory symptoms. At follow-up, the subjects answered a questionnaire with a response rate of 87%. NIR was defined as symptoms of nasal obstruction, nasal secretion, and/or sneezing attacks without having a cold, during the last 5 years. COPD was defined as a spirometry ratio of forced expiratory volume in 1 second divided by forced vital capacity (FEV1/FVC) 40 years. Smoking, atopy, and occupational exposure to gas, fumes, or dust were also associated with new-onset NIR. COPD, smoking, and atopy remained individual risk factors for new-onset NIR in the logistic regression analysis. Conclusions: This longitudinal population-based study of a large cohort showed that COPD is a risk factor for developing NIR. Smoking and atopy are also risk factors for NIR. The results indicate that there is a link present between upper and lower respiratory inflammation in NIR and COPD. Keywords: COPD, rhinitis, smoking, epidemiology, spirometry

Kjell Torén,1 Anna-Carin Olin,1 Anne Lindberg,2 Jenny Vikgren,3 Linus Schiöler,1 John Brandberg,3 Åse Johnsson,3 Gunnar Engström,4 H Lennart Persson,5 Magnus Sköld,6 Jan Hedner,7 Eva Lindberg,8 Andrei Malinovschi,8 Eeva Piitulainen,9 Per Wollmer,9 Annika Rosengren,10 Christer Janson,8 Anders Blomberg,2 Göran Bergström10 1Section of Occupational and Environmental Medicine, Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, 2Department of Public Health and Clinical Medicine, Division of Medicine/Respiratory Medicine, Umeå University, Umeå, 3Department of Radiology, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, 4Department of Clinical Science, Malmö, Lund University, Lund, 5Department of Respiratory Medicine and Department of Medicine and Health Sciences, Linköping University, Linköping, 6Respiratory Medicine Unit, Department of Medicine Solna, Center for Molecular Medicine, Karolinska Institutet, Stockholm, 7Department of Internal Medicine/Lung Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, 8Department of Medical Sciences, Clinical Physiology and Respiratory, Allergy and Sleep Research, Uppsala University, Uppsala, 9Department of Translational Medicine, Lund University, Malmö, 10Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden Background: Spirometric diagnosis of chronic obstructive pulmonary disease (COPD) is based on the ratio of forced expiratory volume in 1 second (FEV1)/vital capacity (VC), either as a fixed value

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.

Many American kestrel (Falco sparverius) populations are declining across North America. Potential causes include mortality from reduction in food availability, a changing climate, habitat degradation, an increase in avian predators, disease, and toxins. We analyzed American kestrel count and banding data from seven raptor migration sites throughout North America with at least 20 years of migration data. We used count data to determine the year at which the kestrel population began a significant decline and then used banding records to determine whether body mass and wing chord declined after this point. We found reductions in kestrel body mass at three sites and reductions in kestrel wing chord at five sites. Our results indicate declines in body size at the majority of sites are consistent with the hypotheses that food availability, impacts of a changing climate, or predation risk may be contributing to population declines. Keywords: Body size, Falcon, Mass, Population decline, Raptor, Wing chord

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.

BACKGROUND:Climate change produces extremes in both temperature and precipitation causing increased drought severity and increased reliance on groundwater resources. Agricultural practices, which rely on groundwater, are sensitive to but also sources of contaminants, including nitrate. How agricultural contamination drives groundwater geochemistry through microbial metabolism is poorly understood. METHODS:On an active cow dairy in the Central Valley of California, we sampled groundwater from three wells at depths of 4.3 m (two wells) and 100 m (one well) below ground surface (bgs) as well as an effluent surface water lagoon that fertilizes surrounding corn fields. We analyzed the samples for concentrations of solutes, heavy metals, and USDA pathogenic bacteria of the Escherichia coli and Enterococcus groups as part of a long term groundwater monitoring study. Whole metagenome shotgun sequencing and assembly revealed taxonomic composition and metabolic potential of the community. RESULTS:Elevated nitrate and dissolved organic carbon occurred at 4.3m but not at 100m bgs. Metagenomics confirmed chemical observations and revealed several Planctomycete genomes, including a new Brocadiaceae lineage and a likely Planctomycetes OM190, as well novel diversity and high abundance of nano-prokaryotes from the Candidate Phyla Radiation (CPR), the Diapherotrites, Parvarchaeota, Aenigmarchaeota, Nanoarchaeota, Nanohaloarchaea (DPANN) and the Thaumarchaeota, Aigarchaeota, Crenarchaeota, Korarchaeota (TACK) superphyla. Pathway analysis suggests community interactions based on complimentary primary metabolic pathways and abundant secondary metabolite operons encoding antimicrobials and quorum sensing systems. CONCLUSIONS:The metagenomes show strong resemblance to activated sludge communities from a nitrogen removal reactor at a wastewater treatment plant, suggesting that natural bioremediation occurs through microbial metabolism. Elevated nitrate and rich secondary metabolite biosynthetic capacity suggest incomplete remediation and the potential for novel pharmacologically active compounds.

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.

Abstract The McDonald Islands, together with Heard Island and the Kerguelen Archipelago, are volcanic islands on the mostly submerged Kerguelen Plateau, and the products of the long‐lived Kerguelen mantle plume (at least 130 Myr; Coffin et al., 2002, https://doi.org/10.25919/jw5f‐ad35). The first multibeam bathymetry data acquired around the Heard and McDonald islands reveal > 70 sea knolls surrounding the McDonald Islands and three sea knolls north of Heard Island. Rocks dredged from McDonald Islands sea knolls include fresh vesicular phonolitic lavas, phonolitic obsidian, phonolitic pillow fragments, and one basanite. These are the first phonolites sampled from the seafloor on the Kerguelen Plateau. Dredging of one sea knoll north of Heard Island recovered basaltic lavas. Lavas from the sea knolls are young, returning 40Ar/39Ar plateau ages of 73.7 ± 15.1 ka to 7.0 ± 2.7 ka for McDonald Islands sea knoll phonolites and 9.0 ± 1.3 ka for the Heard Island sea knoll. We define a new magma series, the McDonald Series, characterized by low εHf (−3.9 to −4.4) and lower Δ207Pb/204Pb (4.5–4.8) and Δ208Pb/204Pb (79–85) than all other lavas on the Kerguelen Plateau. This newly defined series is the product of a relatively young (Pleistocene‐Holocene) phase of volcanism produced by a distinct component of the Kerguelen mantle plume. We propose that McDonald Series phonolites together with 53.4 Ma lavas previously dredged from Ninetyeast Ridge provide evidence for zonation of the Kerguelen mantle plume.

For decades prior to NCAA v. Board of Regents, the brand of college athletics, even at the highest level, was amateurism. However, the last three decades of surging revenues and costs, as well as the current wave of litigation challenging amateurism, force decision makers in major college athletics to contemplate a future in which amateurism is banished or in retreat. In sum, the brand has outgrown amateurism. Major college athletics can survive a paradigm shift by selling the action in its games, the game day experience, and the traditions of the institutions.