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A child's vocabulary ability may be influenced by many different factors in their home environment. The present study focused on supportive aspects in home environments and the relation to children's vocabulary size through an online study where 166 parents of children aged 47.63 months (range 33.7-59.9 months) responded. Children's home literacy environments were positively associated with children's vocabulary size. Aspects of the home environment such as the parents engaging in teaching colors, and letters and talking about daily activities showed a positive association with vocabulary size. Print book reading was important, but the number of books the parents read did not seem to be associated with vocabulary size, rather whether the parent was engaging in dialogical reading and discussing the books, explaining the content, and relating the content to the life of the child mattered. Digital media (screen media and digital games) did not show a positive association with vocabulary, regardless of content or parents' joint media engagement. Watching screen media showed a negative association with developing vocabulary. This association was, however, ameliorated when positive influences and activities in the home literacy environment were present.

This article comprises two international studies. Study 1 aimed to develop a scale to measure the frequency of learners' voluntary, informal, out-of-school engagement with English, so-called Extramural English (EE) activities. It involved three stages -- pilot study, exploratory factor analysis, and confirmatory factor analysis -- followed by measuring the test-retest reliability and known-groups validity of the scale. L2 English learners (N = 907; mean age: 17) from Scandinavia (Denmark, Norway, and Sweden) and Turkey participated. The analyses led to a 32-item EE Scale that loaded onto eight factors: "EE Digital Creativity," "Gaming," "Internalized," "Music," "Niche Activities," "Reading" and "Listening," "Social Interaction," and "Viewing." Study 2, in which the scale was implemented, aimed to explore the frequency of EE activities and examined whether EE predicts learners' perceived speaking ability in different settings. Learners from Scandinavia (N = 197) and Asia (N = 125; China and Turkey) participated. Data analyses showed that both samples engaged most frequently in "EE Music," "Viewing" and "Reading and Listening." Ordinal regression analysis revealed that EE predicts perceived speaking ability in both contexts, but differently so. Thus, EE seems to play different roles for learning English in the different settings. Implications are discussed regarding the context-specific nature of EE.

Liver metabolism is central to human physiology and influences the pathogenesis of common metabolic diseases. Yet, our understanding of human liver metabolism remains incomplete, with much of current knowledge based on animal or cell culture models that do not fully recapitulate human physiology. Here, we perform in-depth measurement of metabolism in intact human liver tissue ex vivo using global 13C tracing, non-targeted mass spectrometry and model-based metabolic flux analysis. Isotope tracing allowed qualitative assessment of a wide range of metabolic pathways within a single experiment, confirming well-known features of liver metabolism but also revealing unexpected metabolic activities such as de novo creatine synthesis and branched-chain amino acid transamination, where human liver appears to differ from rodent models. Glucose production ex vivo correlated with donor plasma glucose, suggesting that cultured liver tissue retains individual metabolic phenotypes, and could be suppressed by postprandial levels of nutrients and insulin, and also by pharmacological inhibition of glycogen utilization. Isotope tracing ex vivo allows measuring human liver metabolism with great depth and resolution in an experimentally tractable system.

Horses revolutionized human history with fast mobility1. However, the timeline between their domestication and their widespread integration as a means of transport remains contentious2-4. Here we assemble a collection of 475 ancient horse genomes to assess the period when these animals were first reshaped by human agency in Eurasia. We find that reproductive control of the modern domestic lineage emerged around 2200 BCE, through close-kin mating and shortened generation times. Reproductive control emerged following a severe domestication bottleneck starting no earlier than approximately 2700 BCE, and coincided with a sudden expansion across Eurasia that ultimately resulted in the replacement of nearly every local horse lineage. This expansion marked the rise of widespread horse-based mobility in human history, which refutes the commonly held narrative of large horse herds accompanying the massive migration of steppe peoples across Europe around 3000 BCE and earlier3,5. Finally, we detect significantly shortened generation times at Botai around 3500 BCE, a settlement from central Asia associated with corrals and a subsistence economy centred on horses6,7. This supports local horse husbandry before the rise of modern domestic bloodlines.

Abstract Background p63 is a transcription factor with intrinsic pioneer factor activity and pleiotropic functions. Transforming growth factor β (TGFβ) signaling via activation and cooperative action of canonical, SMAD, and non-canonical, MAP-kinase (MAPK) pathways, elicits both anti- and pro-tumorigenic properties, including cell stemness and invasiveness. TGFβ activates the ΔNp63 transcriptional program in cancer cells; however, the link between TGFβ and p63 in unmasking the epigenetic landscape during tumor progression allowing chromatin accessibility and gene transcription, is not yet reported. Methods Small molecule inhibitors, including protein kinase inhibitors and RNA-silencing, provided loss of function analyses. Sphere formation assays in cancer cells, chromatin immunoprecipitation and mRNA expression assays were utilized in order to gain mechanistic evidence. Mass spectrometry analysis coupled to co-immunoprecipitation assays revealed novel p63 interactors and their involvement in p63-dependent transcription. Results The sphere-forming capacity of breast cancer cells was enhanced upon TGFβ stimulation and significantly decreased upon ΔNp63 depletion. Activation of TGFβ signaling via p38 MAPK signaling induced ΔNp63 phosphorylation at Ser 66/68 resulting in stabilized ΔNp63 protein with enhanced DNA binding properties. TGFβ stimulation altered the ratio of H3K27ac and H3K27me3 histone modification marks, pointing towards higher H3K27ac and increased p300 acetyltransferase recruitment to chromatin. By silencing the expression of ΔNp63, the TGFβ effect on chromatin remodeling was abrogated. Inhibition of H3K27me3, revealed the important role of TGFβ as the upstream signal for guiding ΔNp63 to the TGFβ/SMAD gene loci, as well as the indispensable role of ΔNp63 in recruiting histone modifying enzymes, such as p300, to these genomic regions, regulating chromatin accessibility and gene transcription. Mechanistically, TGFβ through SMAD activation induced dissociation of ΔNp63 from NURD or NCOR/SMRT histone deacetylation complexes, while promoted the assembly of ΔNp63-p300 complexes, affecting the levels of histone acetylation and the outcome of ΔNp63-dependent transcription. Conclusions ΔNp63, phosphorylated and recruited by TGFβ to the TGFβ/SMAD/ΔNp63 gene loci, promotes chromatin accessibility and transcription of target genes related to stemness and cell invasion.

Echocardiography is recommended as a first-line diagnostic tool in patients with premature ventricular contractions (PVCs). However, standard echocardiography is not always able to identify early signs of myocardial dysfunction and cardiac magnetic resonance (CMR) may offer additional information. Since CMR has lower accessibility and higher cost compared to echocardiography, we wanted to evaluate how additional echocardiographic parameters, not included in routine examinations, perform compared to CMR in detecting signs of cardiomyopathy in PVC patients with normal findings at a standard echocardiogram. We compared CMR findings and results from an extended echocardiographic examination in thirty-nine patients who had a high PVC burden. The additional echocardiographic parameters were global longitudinal strain, mechanical dispersion, ventricular–arterial coupling, integrated backscatter and left atrial activation time. Eleven patients had pathological findings at CMR. The additional echocardiographic parameters did not significantly differ between patients with or without CMR findings. However, several patients with normal CMR findings showed signs of ventricular dysfunction when evaluated with the additional echocardiographic parameters, which suggests that these could possibly offer supplementary information in the assessment of PVC patients.

Co-teaching has been brought forth as an inclusive teaching approach in research and in the Finnish core curriculum. The realisation of co-teaching at the school level puts great demands on teachers, but also on school leaders (SLs) who are expected to lead educational change. The aim of the study was to examine how SLs in Finnish schools were co-teaching has been realised experience their own and co-teachers' roles in leading the realisation of co-teaching as an inclusive approach. Data were collected through semi-structured interviews with nine SLs in Finland. Inductive thematic analysis was used and revealed two overarching themes: SLs as facilitators of co-teaching and teachers as driving forces of co-teaching. The need for a more active and goal-oriented SL role focused on involving the whole school community in developing co-teaching rather than delegating the responsibility to single teachers is discussed through the lens of distributed leadership and earlier research.

This study examined how Finnish primary school students perceive teachers' roles and responsibilities, their own learning and participation, and the social climate during co-taught lessons. Data were collected through a web-based questionnaire among primary school students (N = 242) from grades four to six from Finnish schools where Swedish is the medium of instruction and co-teaching has been initiated. Students with and without special educational needs participated in the study. Students without special educational needs were more positive to co-teaching the more co-taught lessons they received per week, while students with special educational needs were most positive when they received four to five lessons weekly. Students also perceived that mostly the general education teacher is responsible for lesson planning and instruction but that both teachers contribute to the students' learning. In earlier research, the students' perceptions have seldom been in focus and there is an obvious need for more research on students' perspectives to develop and realise co-teaching as a teaching approach that promotes learning and participation for all students in a general classroom.

IntroductionOvarian cancer is a lethal disease with low survival rates for women diagnosed in advanced stages. Current cancer immunotherapies are not efficient in ovarian cancer, and there is therefore a significant need for novel treatment options. The β-galactoside-binding lectin, Galectin-3, is involved in different immune processes and has been associated with poor outcome in various cancer diagnoses. Here, we investigated how Galectin-3 affects the interaction between natural killer (NK) cells and neutrophils in the tumor microenvironment of ovarian cancer.MethodAscites from the metastatic tumor microenvironment and cyst fluid from the primary tumor site were collected from patients with high-grade serous carcinoma (HGSC) together with peripheral blood samples. Galectin-3 concentration was measured in ascites, cyst fluid and serum or plasma. Neutrophils isolated from HGSC ascites and autologous blood were analyzed to evaluate priming status and production of reactive oxygen species. In vitro co-culture assays with NK cells, neutrophils and K562 target cells (cancer cell line) were conducted to evaluate NK cell viability, degranulation and cytotoxicity.ResultsHigh levels of Galectin-3 were observed in cyst fluid and ascites from patients with HGSC. Neutrophils present in HGSC ascites showed signs of priming; however, the priming status varied greatly among the patient samples. Galectin-3 induced production of reactive oxygen species in ascites neutrophils, but only from a fraction of the patient samples, which is in line with the heterogenous priming status of the ascites neutrophils. In co-cultures with NK cells and K562 target cells, we observed that Galectin-3-induced production of reactive oxygen species in neutrophils resulted in decreased NK cell viability and lowered anti-tumor responses.ConclusionTaken together, our results demonstrate high levels of Galectin-3 in the tumormicroenvironment of HGSC. High levels of Galectin-3 may induce production of reactiveoxygen species in ascites neutrophils in some patients. In turn, reactive oxygen species produced by neutrophils may modulate the NK cell anti-tumor immunity. Together, this study suggests further investigation to evaluate if a Galectin-3-targeting therapy may be used in ovarian cancer.

Large gaps exist in the literature on COVID-19 pandemic-related mental health outcomes and after-effects specific to adolescents and young adults. The aim was to explore adolescents’ and young adults’ experiences of well-being, health and loneliness during the COVID-19 pandemic. A qualitative exploratory design with qualitative content analysis was used. Twenty-three participants (aged 19–27; four men and 19 women) were interviewed in Finland in 2021. Four main categories emerged: Changed social networks – fewer and closer contacts, Changed mental and physical health, Increased isolation and social loneliness, and Well-being, internal growth and need for support. Adolescents’ and young adults’ experiences of well-being, health and loneliness are subtle and complex. Participants experienced changed social networks, mental and physical health, and well-being. Internal growth, need for support and increased loneliness were also seen. Clear information on how to seek help and support from professionals should be made available.

The comorbidity between problem gambling and substance use/abuse is high in many populations previously studied. However, the occurrence of problem gambling among individuals with substance abuse has not been thoroughly studied, which is especially true for individuals in inpatient or compulsory care. The present early-stage study explored the presence of gambling and problem gambling among inpatients in compulsory care in Sweden who has been court-ordered to treatment for their substance abuse (alcohol and/or drugs). The study furthermore investigates the use of preventive measures and treatment seeking. The most effective strategy to recruit participants (no incentive, incentive and incentive and face-to-face recruitment) was also explored. Twenty-one participants were recruited and seven of them had at-risk or problem gambling and none of them had accessed treatment. The best way of recruiting was to offer a gift certificate and inform about the study face-to-face. The implications are that individuals in compulsory care for substance abuse need to be screened for problem gambling, that recruitment for studies in this population is best carried out by offering incentives and educational efforts and that it might be beneficial for the clients in compulsory care to be offered gambling treatment.

Transitions can be described as passage/movement from one life phase, condition, or status to another, where people learn to adapt to the change through inner reorientation, adaptation, and/or transformation. The aim was to explore whether educational transitions during adolescence and emerging adulthood relate to loneliness and mental health. A systematic review was conducted. A total of 32 articles were included. Educational transitions were associated with both positive and negative outcomes. Individual variables might impact how a transition is experienced. To alleviate negative outcomes for young people, social support and targeted interventions should be developed, and support made available and accessible. Interventions should focus on preventing disruptions in social networks and increasing connections and collaborations between support networks across each educational stage. Future research should examine how interventions can support individuals who are negatively affected by educational transitions.

Educational transitions can influence loneliness and increase mental health issues for young people transitioning between educational stages. The aim was to explore the link between educational transitions and emerging adults’ loneliness and mental health and how they perceive they can alleviate and/or improve these issues. Semi-structured qualitative interviews with a total of 12 emerging adults, 10 females and two males aged 18–29 (mean age, 22.91) were conducted. Data were analysed using qualitative content analysis. Emerging adults’ loneliness and mental health across educational transitions could be influenced by changes to their sense of security, for example concurrent transitions, increased academic demands, changed social network, insufficient attachment, lack of community, or changed physical environment. Transitions can be associated with positive expectations and self-development but also worry, emotional turmoil, loneliness, and mental health issues. A better transition experience can be enabled by increasing resources and activities and promoting a secure environment.

BackgroundPsychoeducation is a recommended first-line intervention for transition-aged autistic youth, but it has not been previously evaluated in an internet-delivered format. SCOPE (Spectrum Computerized Psychoeducation) is an 8-week individual, internet-delivered, therapist-supported psychoeducative intervention. ObjectiveThis study aimed to investigate the effectiveness of SCOPE through a 3-armed randomized controlled trial. The intervention aims to increase participants’ understanding of autism and, in doing so, increase their quality of life (QoL). MethodsSCOPE was codeveloped with clinicians and autistic young adults. It contains 8 autism-related modules, each with (1) text describing the module topic, (2) four video vignettes with recurring characters who describe their lives and perspectives on the module topic, (3) a list of neurotypical characteristics related to the module’s topic, and (4) self-reflection using 3 or 4 questions about the module topic, answered by multiple-choice bullets and voluntary open-ended written comments. Participants were randomized (2:1:1) to SCOPE, an active control (web-based self-study), or treatment as usual (TAU). The primary outcome was participants’ autism knowledge, assessed using the Autism Spectrum Disorder Quiz, and secondary outcomes included acceptance of diagnosis, QoL, and symptoms of mental health problems. All outcomes were assessed at the baseline, postintervention, and 3-month follow-up time points, using mixed-effects models to assess change in outcome measures across time points. ResultsBetween 2014 and 2020, a total of 141 participants were randomized to 1 of the 3 treatment arms. The SCOPE participants had significantly greater autism knowledge gains at the posttreatment time point compared to TAU participants with a moderate effect size (d=0.47; P=.05); gains were maintained at the 3-month follow-up (d=0.46; P=.05). The self-study participants also had increased knowledge gains compared to TAU participants at the posttreatment time point with a moderate effect size (d=0.60; P=.03) but did not maintain these gains at the 3-month follow-up, and their autism knowledge scores returned to baseline (mean change score: –0.13, 95% CI –1.20 to 0.94; P=.81). In addition, SCOPE participants reported improved QoL at the postintervention (d=0.37, P=.02) and 3-month follow-up time points (d=0.60; P=.001), compared to the combined controls. The gained autism knowledge was not mirrored by changes in symptoms of anxiety or depression. ConclusionsEffective internet-delivered interventions may facilitate first-line service access to individuals who are unable or unwilling to use traditional health care interventions or who live in geographically remote locations. Additionally, an intervention such as SCOPE could impart and sustain the knowledge gained through psychoeducation in transition-aged autistic youth. For future research, qualitative studies could further our understanding of the lived experiences of intervention participation and outcomes after internet-delivered psychoeducation. Trial RegistrationClinicalTrials.gov NCT03665363; https://clinicaltrials.gov/study/NCT03665363

Tidigare forskning visar att blivande och verksamma förskollärare ofta har negativa attityder och lågt självförtroende i matematik. Dessa attityder påverkar deras undervisning och barns möjligheter att lära sig. Förskollärarutbildningen behöver adressera studenternas attityder och främja positiva attityder gentemot matematik. Denna studie syftar till att undersöka blivande förskollärares attityder mot matematik, hur dessa förändras under utbildningen och vilka faktorer i utbildningen som påverkar förändringarna. Studenter i tre stadier av programmet deltar – i termin 1, termin 3 och termin 5. En tvådimensionell definition av attityd anammas och en kortversion av Attitudes Towards Mathematics Inventory (ATMI) används tillsammans med öppna frågor och intervjuer. Resultaten visar att studenternas attityder är negativa i den affektiva komponenten men neutrala till positiva i den kognitiva komponenten. De flesta studenterna i termin 5 upplever en positiv förändring i attityd under utbildningen på grund av positiva och tillgängliga lärare, ökad kunskap om matematik i förskolan samt utvecklad ämneskunskap vilket de får ”kvitto” på när de klarat ämnestentamen. ENGLISH ABSTRACT Important but Not Fun – Prospective Teachers’ Attitudes Towards Mathematics Previous research shows that many prospective and early childhood teachers have negative attitudes and low self-confidence in mathematics. These negative attitudes affect their teaching and children’s opportunities to learn mathematics. It is crucial that early childhood teacher education (ECTE) address students’ attitudes and work to promote positive attitudes towards mathematics. The aim of this study is to investigate prospective teachers’ attitudes towards mathematics, whether and how their attitudes change during ECTE and what might cause the changes. Students in three stages of the program participate – in semester 1, semester 3 and semester 5. A two-dimensional definition of attitude is adopted and a short version of the Attitudes Towards Mathematics Inventory (ATMI) is used together with open-ended questions and interviews. The results show that the students’ attitudes are negative within the affective component and neutral to positive within the cognitive component. Most of the students in semester 5 experience a positive change in attitude during education due to positive and accessible teachers, increased knowledge of what mathematics in preschool can be and developed subject knowledge.

Abstract Secondary tropical forests are at the forefront of deforestation pressures. They store large amounts of carbon, which, if compensated for to avoid net emissions associated with conversion to non-forest uses, may help advance tropical forest conservation. We measured above- and below-ground carbon stocks down to 1 m soil depth across a secondary forest and in oil palm plantations in Malaysia. We calculated net carbon losses when converting secondary forests to oil palm plantations and estimated payments to avoid net emissions arising from land conversion to a 22-year oil palm rotation, based on land opportunity costs per hectare. We explored how estimates would vary between forests by also extracting carbon stock data for primary forest from the literature. When tree and soil carbon was accounted for, payments of US$18–51 tCO2 –1 for secondary forests and US$14–40 tCO2 –1 for primary forest would equal opportunity costs associated with oil palm plantations per hectare. If detailed assessments of soil carbon were not accounted for, payments to offset opportunity costs would need to be considerably higher for secondary forests (US$28–80 tCO2 –1). These results show that assessment of carbon stocks down to 1 m soil depth in tropical forests can substantially influence the estimated value of avoided-emission payments.

Purpose: We aimed to characterize genomic alterations with potential prognostic or predictive significance in patients with metastatic triple-negative breast cancer (mTNBC) treated with chemotherapy in a real-world setting. Patients and methods: Next-generation sequencing with FoundationOne® CDx was conducted primarily on primary tumor tissue from 112 consecutive patients with mTNBC. Genomic alterations were subdivided into canonical oncogenic pathways and noted for their involvement in homologous recombination deficiency (HRD). Altered genes and pathways were correlated with overall survival (OS) and evaluated regarding their association with real-world progression-free survival (rwPFS) in patients treated with different chemotherapy agents. Occurrence of alterations were compared between patients with exceptional response and rapid progression to chemotherapy. Results: After exclusion due to insufficient tumor tissue or clinical data, material from 97 patients was analyzed. The most frequently altered genes were TP53 (82 %), RAD21 (25 %) and PIK3CA (23 %). Altogether, 26 % of patients had an alteration leading to HRD. None of the analyzed alterations were associated with OS. Variants leading to HRD were associated with a prolonged rwPFS in patients treated with platinum-based chemotherapy in the first line setting (hazard ratio [HR], 0.31 [95 % CI: 0.12–0.84]). Exceptional responders more often exhibited alterations in the MYC and RAS/RTK pathways compared to rapid progressors. Conclusions: Patients with tumor alterations in HRD-related genes seem to define subgroups that respond favorably to platinum-based chemotherapy. Further research into the genomic landscape of tumors from patients with rapid progression or exceptional response to different treatment strategies can provide insights into mechanisms of resistance and identify predictive biomarkers.

Vocabulary experts recommend first language (L1) translation equivalents for establishing form-meaning mappings for new second language (L2) words, especially for lower proficiency learners. Empirical evidence to date speaks in favor of L1 translation equivalents over L2 meaning definitions, but most studies have investigated bi- rather than multilingual learners. In our study, we investigated instructed English vocabulary learning through an intervention study in six language-diverse secondary school English classrooms in Sweden (N = 74) involving three conditions for presentation of word meanings: (a) definitions in the L2 (English), (b) translation equivalents in the shared school and majority language (Swedish), and (c) translation equivalents in the shared school and majority language plus other prior languages among the learners (Swedish and other). Based on overall weighted mean effect sizes and mixed-effects modeling, the results showed that conditions that involved L1 translation equivalents yielded higher scores than did target language definitions in immediate posttests with a small effect size but no differences in delayed posttests.