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BACKGROUND: Low birth weight (LBW) is associated with neonatal mortality and sequelae of lifelong health problems; prioritizing the most promising antenatal interventions may guide resource allocation and improve health outcomes. OBJECTIVE: We sought to identify the most promising interventions that are not yet included in the policy recommendations of the World Health Organization (WHO) but could complement antenatal care and reduce the prevalence of LBW and related adverse birth outcomes in low- and middle-income settings. METHODS: We utilized an adapted Child Health and Nutrition Research Initiative (CHNRI) prioritization method. RESULTS: In addition to procedures already recommended by WHO for the prevention of LBW, we identified six promising antenatal interventions that are not currently recommended by WHO with an indication for LBW prevention, namely: (1) provision of multiple micronutrients; (2) low-dose aspirin; (3) high-dose calcium; (4) prophylactic cervical cerclage; (5) psychosocial support for smoking cessation; and (6) other psychosocial support for targeted populations and settings. We also identified seven interventions for further implementation research and six interventions for efficacy research. CONCLUSION: These promising interventions, coupled with increasing coverage of currently recommended antenatal care, could accelerate progress toward the global target of a 30% reduction in the number of LBW infants born in 2025 compared to 2006-10.

DNA-stabilized silver nanoclusters (AgN-DNAs) are known to have one or two DNA oligomer ligands per nanocluster. Here, we present the first evidence that AgN-DNA species can possess additional chloride ligands that lead to increased stability in biologically relevant concentrations of chloride. Mass spectrometry of five chromatographically isolated near-infrared (NIR)-emissive AgN-DNA species with previously reported X-ray crystal structures determines their molecular formulas to be (DNA)2[Ag16Cl2]8+. Chloride ligands can be exchanged for bromides, which red-shift the optical spectra of these emitters. Density functional theory (DFT) calculations of the 6-electron nanocluster show that the two newly identified chloride ligands were previously assigned as low-occupancy silvers by X-ray crystallography. DFT also confirms the stability of chloride in the crystallographic structure, yields qualitative agreement between computed and measured UV-vis absorption spectra, and provides interpretation of the 35Cl-nuclear magnetic resonance spectrum of (DNA)2[Ag16Cl2]8+. A reanalysis of the X-ray crystal structure confirms that the two previously assigned low-occupancy silvers are, in fact, chlorides, yielding (DNA)2[Ag16Cl2]8+. Using the unusual stability of (DNA)2[Ag16Cl2]8+ in biologically relevant saline solutions as a possible indicator of other chloride-containing AgN-DNAs, we identified an additional AgN-DNA with a chloride ligand by high-throughput screening. Inclusion of chlorides on AgN-DNAs presents a promising new route to expand the diversity of AgN-DNA structure-property relationships and to imbue these emitters with favorable stability for biophotonics applications.

BACKGROUND: In 2014, germline signal transducer and activator of transcription (STAT) 3 gain-of-function (GOF) mutations were first described to cause a novel multisystem disease of early-onset lymphoproliferation and autoimmunity. OBJECTIVE: This pivotal cohort study defines the scope, natural history, treatment, and overall survival of a large global cohort of patients with pathogenic STAT3 GOF variants. METHODS: We identified 191 patients from 33 countries with 72 unique mutations. Inclusion criteria included symptoms of immune dysregulation and a biochemically confirmed germline heterozygous GOF variant in STAT3. RESULTS: Overall survival was 88%, median age at onset of symptoms was 2.3 years, and median age at diagnosis was 12 years. Immune dysregulatory features were present in all patients: lymphoproliferation was the most common manifestation (73%); increased frequencies of double-negative (CD4-CD8-) T cells were found in 83% of patients tested. Autoimmune cytopenias were the second most common clinical manifestation (67%), followed by growth delay, enteropathy, skin disease, pulmonary disease, endocrinopathy, arthritis, autoimmune hepatitis, neurologic disease, vasculopathy, renal disease, and malignancy. Infections were reported in 72% of the cohort. A cellular and humoral immunodeficiency was observed in 37% and 51% of patients, respectively. Clinical symptoms dramatically improved in patients treated with JAK inhibitors, while a variety of other immunomodulatory treatment modalities were less efficacious. Thus far, 23 patients have undergone bone marrow transplantation, with a 62% survival rate. CONCLUSION: STAT3 GOF patients present with a wide array of immune-mediated disease including lymphoproliferation, autoimmune cytopenias, and multisystem autoimmunity. Patient care tends to be siloed, without a clear treatment strategy. Thus, early identification and prompt treatment implementation are lifesaving for STAT3 GOF syndrome.

Background and purpose: Changes in treatment approaches, characterised by the shift from laryngectomy to a focus on organ-preserving methods may have potentially resulted in lower survival. We aim to identify differences in survival trends for laryngeal cancer (LC) in the Nordic countries over a period of 50 years, and discuss the potential impact of factors such as changes in treatment protocols. Materials and methods: Five-year relative survival (RS) data from 1972 to 2021 were obtained from the NORDCAN database 2.0 which included 33,692 LC cases, of which 85% were diagnosed among men. In the NORDCAN database, the age-standardised RS is calculated using the Pohar Perme estimator with individual International Cancer Survival Standards weights. Joinpoint regression models were used to assess potential shifts in trend over the years in RS. Results: While Denmark and Norway demonstrated an increasing trend in 5-year RS from 1972 to 2021, in Finland and Sweden, the 5-year RS among men remained static, without any discernible significant trend. Over the 30-year period from 1992–1996 to 2017–2021, RS improved by 9, 4, 13, and 2 percentage points in Denmark, Finland, Norway, and Sweden, respectively. Among women in Sweden, a linear negative trend was observed, noticeable as a 16 percentage-point decline in 5-year RS from the earliest to the latest period. Interpretation: The underlying causes for the differences in survival trends remain unclear. Besides differences in treatment protocols, several other factors can affect RS making the interpretation of RS trends challenging.

Using a semiotically-informed material approach to the study of translation, this paper analyses an artificial intelligence (AI) system developed for automatic audio captioning (AAC), which is the automated production of written descriptions for non-lingual environmental sounds. Comparing human and AI text production processes against a semiotic framework suggests that AI uses computational methods to reach textual outcomes which humans arrive at through semiotic means. Our analysis of sound description examples produced by an AAC system makes it apparent that this distinction is useful in articulating the complex relationship between human and AI translation processes. Acknowledging the central role of semiotic meaning-construction in human text production and its arguable absence in AI computational processes allows for AI processes to be discussed under a translational framework, while still recognizing their fundamental differences from comparable human translation processes. Further, audio captioning provides a clear example of a translation task where non-lingual content must be considered on equal terms with lingual text, and our discussions illustrate how this can be achieved in computational and semiotic processes alike. Overall, this paper promotes a nuanced understanding of meaning in text production and suggests multiple fruitful points of convergence and divergence between translation theory and AI research.

This study introduces a pedagogical model: "the parallel co-inquiry cycles with performative inquiry for character related design" for higher education design studies that focus on characterization. The disciplines benefitting from cross-fertilization provided by the model include game design, fashion design, graphic design, theatre, and actor's art. Besides the model, the article discusses curriculum integration of a shared thematic denominator Commedia dell'Arte in higher education design studies. The model synthesizes progressive inquiry, drama pedagogical methodologies, and theories on theater with hands-on art workshops to create tangible and digital knowledge vessels for characterization. The research design relies on parallel co-inquiry cycles, participatory ethnography with elements from participatory design tradition. The model identifies three major components within the single 3E-inquiry cycles, namely exercise, experiment and experience. The entire process acquires complexity as each single inquiry cycle enters the next loop of Observe-Plan-Act-Reflect and more time and resources are allocated to the process. The pattern of action and reflection has an iterative cycle format in this model. Reflection has two distinguished purposes: first, to internalize reflective design and to become a reflective practitioner. Second, to see the importance of reflection as distancing oneself from the current process, to allow a reflective mind to linger on the process and learn from mistakes to turn them into assets. Reflection as a metacognitive skill has an all-encompassing purpose in both design and learning processes. The model distinguishes two types of knowledge vessels. Knowledge objects are abstractions that condense knowledge in the co-design process, whereas knowledge artifacts are concrete items, such as masks, outfits, and accessories in both digital and tangible formats. The model connects maker-culture, practice-based inquiry, and performative inquiry in the inquiry cycles. The drama method with performative inquiry acknowledges shared knowledge building in a collaborative, dialogical inquiry that fosters both argumentative and reflection skills.

Drawing on a sociocultural approach to learning, this article highlights comprehensive school pupils' perspectives on working style and classroom pedagogy based on the integrative approach to learning. Using the diamond ranking method, seven groups of 8th grade pupils ranked classroom practices according to their importance for succeeding in integrative and collaborative learning tasks. The study was conducted in the context of home economics education in Finland. Audio and video data were subjected to qualitative content analysis. The results indicate that working style to enhance interthinking and shared commitment to working was considered important, as were several practical elements such as computer use. Utilising knowledge from other school subjects was found to be challenging. The findings suggest that for the participating pupils, collaborative ways of working and the teacher's pedagogical choices in providing tools and framing the task were the keys to successful working.

Food, cooking, and eating are commonly used as contexts or legitimations to teach and communicate science. However, for teaching to have contextual credibility, the relationship between subject and context is a relevant area of study. The present contribution describes an analysis of curricula from three Nordic countries shedding light on conditions for interdisciplinarity and/or curricular integration between the subjects science/chemistry on the one side, and home economics on the other. A two-phase documentary analysis was conducted on curricula from Finland, Norway, and Sweden from 2006 to 2020, revealing substantial potential for interdisciplinary collaboration and/or curricular integration. This is seen both in common declarative knowledge content ('declarative knowledge overlap') and, more interestingly, meeting points between subject-dependent practices and ways of thinking ('transfer of practices and ways of thinking'). The second inductive phase produced 11 themes common to the subjects. Possibilities and challenges are discussed in relation to the subjects' epistemologies and ontologies, as well as practitioners' competencies, attitudes, and creativity for subject boundary-crossing. Consequently, we conceptualise teachers' roles as lying in the span between 'teacher as polymath' and 'teacher as collaborator'. The present work also provides a instrument for exploring curricular conditions for interdisciplinarity between subjects on a more general basis.

Abstract Background The Large-scale Assessment of the Key health-promoting Activities of two New mass drug administration regimens with Azithromycin (LAKANA) trial in Mali aims to evaluate the efficacy and safety of azithromycin (AZI) mass drug administration (MDA) to 1–11-month-old infants as well as the impact of the intervention on antimicrobial resistance (AMR) and mechanisms of action of azithromycin. To improve the transparency and quality of this clinical trial, we prepared this statistical analysis plan (SAP). Methods/design LAKANA is a cluster randomized trial that aims to address the mortality and health impacts of biannual and quarterly AZI MDA. AZI is given to 1–11-month-old infants in a high-mortality setting where a seasonal malaria chemoprevention (SMC) program is in place. The participating villages are randomly assigned to placebo (control), two-dose AZI (biannual azithromycin-MDA), and four-dose AZI (quarterly azithromycin-MDA) in a 3:4:2 ratio. The primary outcome of the study is mortality among the intention-to-treat population of 1–11-month-old infants. We will evaluate relative risk reduction between the study arms using a mixed-effects Poisson model with random intercepts for villages, using log link function with person-years as an offset variable. We will model outcomes related to secondary objectives of the study using generalized linear models with considerations on clustering. Conclusion The SAP written prior to data collection completion will help avoid reporting bias and data-driven analysis for the primary and secondary aims of the trial. If there are deviations from the analysis methods described here, they will be described and justified in the publications of the trial results. Trial registration ClinicalTrials.gov ID NCT04424511 . Registered on 11 June 2020.

Summary: CRISPR-Cas9 gene editing is an efficient technique to modify specific sites/regions of DNA. Delivery of the Cas9 by mRNA is particularly promising in pre-clinical genome editing applications for its transient, nonintegrating feature. However, the off-target of Cas9-gRNA still remains a concern and needs a specific monitor. Here, we present a revised protocol to edit fibroblasts by in vitro transcribed Cas9 mRNA and profile its off-target effect by the optimized GUIDE-seq method. This protocol can also be applied to other cell lines.For complete details on the use and execution of this protocol, please refer to Ganna Reint et al. (2021).1 : Publisher’s note: Undertaking any experimental protocol requires adherence to local institutional guidelines for laboratory safety and ethics.

This study builds on previous work in curriculum studies by providing insight into manifestations of the interplay between curriculum traditions, that are interested in education on a global scale and emphasized in the newest curriculum reform in Finland. This reform proposes a shift towards a competency-based curriculum, emphasizes integrative teaching and obligates to multidisciplinary teaching. Here, the suggestions are analysed from teachers' perspectives. This data-based case study uses qualitative content analysis to examine interviews conducted with five teachers from three Finnish schools. The results reveal growing diversity as a result of multiple implementations of integrative teaching in Finland. Autonomy was maintained in teaching activity and provided possibilities for professional development. That being said, some limitations and challenges for integrative teaching were identified. This study argues that the ongoing curriculum reform process, which emphasizes integrative teaching, is a fruitful starting point for expanding teacher autonomy and collaboration. Further study is needed to follow the teachers' changing perceptions of teacher autonomy.

Precision CRISPR gene editing relies on the cellular homology-directed DNA repair (HDR) to introduce custom DNA sequences to target sites. The HDR editing efficiency varies between cell types and genomic sites, and the sources of this variation are incompletely understood. Here, we have studied the effect of 450 DNA repair protein-Cas9 fusions on CRISPR genome editing outcomes. We find the majority of fusions to improve precision genome editing only modestly in a locus- and cell-type specific manner. We identify Cas9-POLD3 fusion that enhances editing by speeding up the initiation of DNA repair. We conclude that while DNA repair protein fusions to Cas9 can improve HDR CRISPR editing, most need to be optimized to the cell type and genomic site, highlighting the diversity of factors contributing to locus-specific genome editing outcomes.