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Since the beginning of the 21st century, design education has been gaining momentum across disciplines as a means to equip students with skills relevant in the job market as well as to tackle wicked problems. One of the core assumptions behind integrating design education to other disciplines focuses on the need for hands-on and experiential opportunity exploration and collaborative learning, often prevalent in studio-based settings. However, as the Covid-19 pandemic has shown, physically accessing the campus or the studio is not always feasible, so how might this impact multidisciplinary design education? Acknowledging the notion that we no longer can take face-to-face learning for granted, this paper ask what aspects of design (thinking) education could be delivered in blended environments. I contribute to this body of knowledge by investigating students' perceptions of their learning about design methods and processes in a problem-based blended learning course focusing on design and multidisciplinary teamwork. Visual learning diaries of forty-seven students were analyzed to better understand how blended learning can support or hinder learning about applying design to societal issues. Data analysis revealed three aspects -- triggers for personal development, exploring ambiguity, and technology as providing structure -- that form the concept learning frame. This concept sheds light on how the students perceived blended learning elements influencing their learning about how design could be applied to societal issues. Findings contribute to further dissolving the physical-digital dichotomy in design studio and education. Pedagogical implications focus on how blended learning can promote student agency in design education across disciplines.

This study examined longitudinal associations between parental psychological distress (stress and depression) when the child was 2 to 4 years and a child's emotional and behavioural problems at ages 3 to 4, and social functioning (loneliness and social competence) at age 11 in very preterm born children. The participants were Finnish families of 172 very preterm infants (gestational age < 32 weeks and/or birth weight [less than or equal to] 1500 g). In girls, higher levels of maternal depression were associated with higher levels of social and emotional loneliness. Furthermore, higher levels of maternal stress and children's externalizing problems were associated with lower levels of experienced empathy. In boys, higher levels of paternal depression were associated with lower levels of social loneliness and impulsive behaviour. In conclusion, early parental psychological distress is associated with early socioemotional development and the later experienced social functioning in former very preterm infants. The sex of the child moderates these associations.

Abstract The performance of molecular docking can be improved by comparing the shape similarity of the flexibly sampled poses against the target proteins’ inverted binding cavities. The effectiveness of these pseudo-ligands or negative image-based models in docking rescoring is boosted further by performing enrichment-driven optimization. Here, we introduce a novel shape-focused pharmacophore modeling algorithm O-LAP that generates a new class of cavity-filling models by clumping together overlapping atomic content via pairwise distance graph clustering. Top-ranked poses of flexibly docked active ligands were used as the modeling input and multiple alternative clustering settings were benchmark-tested thoroughly with five demanding drug targets using random training/test divisions. In docking rescoring, the O-LAP modeling typically improved massively on the default docking enrichment; furthermore, the results indicate that the clustered models work well in rigid docking. The C+ +/Qt5-based algorithm O-LAP is released under the GNU General Public License v3.0 via GitHub ( https://github.com/jvlehtonen/overlap-toolkit ). Scientific contribution This study introduces O-LAP, a C++/Qt5-based graph clustering software for generating new type of shape-focused pharmacophore models. In the O-LAP modeling, the target protein cavity is filled with flexibly docked active ligands, the overlapping ligand atoms are clustered, and the shape/electrostatic potential of the resulting model is compared against the flexibly sampled molecular docking poses. The O-LAP modeling is shown to ensure high enrichment in both docking rescoring and rigid docking based on comprehensive benchmark-testing. Graphical Abstract

Abstract The incidence of brain diseases in humans is increasing as we experience a worldwide ageing of the population. Treatment for such diseases is still only symptomatic as there are almost no disease-modifying therapies available. Further, since treatment often starts when symptoms appear which is only at a late stage of pathology, we need treatments that will create new cells or restore function to still living cells. Cell transplant therapy, where neuronal progenitor cells derived from stem cells are transplanted to the brain, has seen experimental success. And though there has been some clinical progress, there is still no available therapy. While through the years brain research has focused on neurons, it is now shifting to the so-called support cells of the brain, glia. In neurodegenerative diseases and stroke, glia play roles in the pathogenesis of disease. Therefore, replacing them or enhancing their functions to ultimately save or restore neurons is a new avenue of research that has gained traction in recent years. In this review, we present the current state-of-the-art on transplantation of glia cells, feasibility of this as a therapy, and upcoming directions in the field.

As soil microbial respiration is the major component of land CO2 emissions, differences in the functional dependence of respiration on soil moisture among Earth system models (ESMs) contributes significantly to the uncertainties in their projections. Using soil organic C (SOC) stocks and CO2 data from a boreal forest–mire ecotone in Finland and Bayesian data assimilation, we revised the original precipitation-based monotonic saturation dependency of the Yasso07 soil carbon model using the non-monotonic Ricker function based on soil volumetric water content. We fit the revised functional dependency of moisture to the observed microbial respiration and SOC stocks and compared its performance against the original Yasso07 model and the version used in the JSBACH land surface model with a reduction constant for decomposition rates in wetlands. The Yasso07 soil C model coupled with the calibrated unimodal Ricker moisture function with an optimum in well-drained soils accurately reconstructed observed SOC stocks and soil CO2 emissions and clearly outperformed previous model versions on paludified organo-mineral soils in forested peatlands and water-saturated organic soils in mires. The best estimate of the posterior moisture response of decomposition used both measurements of SOC stocks and CO2 data from the full range of moisture conditions (from dry and xeric to wet and water-saturated soils). We observed unbiased residuals of SOC and CO2 data modelled with the moisture optimum in well-drained soils, suggesting that this modified function accounts more precisely for the long-term SOC change dependency according to ecosystem properties as well as the contribution of short-term CO2 responses including extreme events. The optimum moisture for decomposition in boreal forests was found in well-drained soils instead of the mid-range between dry and water-saturated conditions as is commonly assumed among soil C and ESMs. Although the unimodal moisture modifier with an optimum in well-drained soils implicitly incorporates robust biogeochemical mechanisms of SOC accumulation and CO2 emissions, it needs further evaluation with large-scale data to determine if its use in land surface models will decrease the uncertainty in projections.

Abstract Recently, various distributed energy resources are significantly integrated into the modern power systems. This introduction of distributed energy resource‐rich systems can cause various power quality issues, due to their uncertainties and capacity variations. Therefore, it is crucial to establish energy balance between generation and demand to improve power system's reliability and stability and to minimize energy costs without sacrificing customers’ comfort or utility. In this regard, power system flexibility concept is highlighted as a robust and cost‐effective energy management system, especially on the demand side, to provide consumers’ demands with an acceptable level of power quality. Accordingly, here, a comprehensive review of recent developments in the power system flexibility and demand‐side management strategies and demand response programs are provided to include mainly classifications, estimation methods, distributed energy resource modelling approaches, infrastructure requirements, and applications. In addition, current research topics for applying power system flexibility solutions and demand‐side management strategies based on modern power system operation are deliberated. Also, prominent challenges, research trends, and future perspectives are discussed. Finally, this review article aims to be an appropriate reference for comprehensive research trends in the power system flexibility concept in general and in demand‐side management strategies and demand response programs, specifically.

Abstract Photovoltaic (PV) arrays are usually installed in open areas; hence, they are vulnerable to lightning strikes that can result in cell degradation, complete damage, service disruption, and increased maintenance costs. As a result, it is imperative to develop an effective and efficient lightning protection system by evaluating the transient behaviour of PV arrays during lightning events. The aim is to evaluate the transient analysis of large‐scale PV systems when subjected to lightning strikes using the finite difference time domain (FDTD) technique. Transient overvoltages are calculated at various points within the mounting system. To optimise the FDTD method's execution time and make it more suitable for less powerful hardware, a variable cell size approach is employed. Specifically, larger cell dimensions are used in the earthing system and smaller cell dimensions are used in the mounting system. The FDTD method is utilised to calculate the temporal variation of transient overvoltages for large‐scale PV systems under different scenarios, including variations in the striking point, soil resistivity, and the presence of a metal frame. Simulation results indicate that the highest transient overvoltages occur at the striking point, and these values increase with the presence of a PV metal frame as well as with higher soil resistivity. Furthermore, a comparison is performed between the overvoltage results obtained from the FDTD approach and the partial element equivalent circuit (PEEC) method at the four corner points of the mounting systems to demonstrate the superior accuracy of the FDTD method. Besides, a laboratory experiment is conducted on a small‐scale PV system to validate the simulation results. The calculated overvoltages obtained from the FDTD and PEEC methods are compared with the measured values, yielding a mean absolute error of 5% and 11% for the FDTD and PEEC methods, respectively, thereby confirming the accuracy of the FDTD simulation model.

Abstract The increasing incidence of oropharyngeal squamous cell carcinoma (OPSCC) is primarily due to human papillomavirus, and understanding the tumor biology caused by the virus is crucial. Our goal was to investigate the proteins present in the serum of patients with OPSCC, which were not previously studied in OPSCC tissue. We examined the difference in expression of these proteins between HPV-positive and -negative tumors and their correlation with clinicopathological parameters and patient survival. The study included 157 formalin-fixed, paraffin-embedded tissue samples and clinicopathological data. Based on the protein levels in the sera of OPSCC patients, we selected 12 proteins and studied their expression in HPV-negative and HPV-positive OPSCC cell lines. LRG1, SDR16C5, PIP4K2C and MVD proteins were selected for immunohistochemical analysis in HPV-positive and -negative OPSCC tissue samples. These protein´s expression levels were compared with clinicopathological parameters and patient survival to investigate their clinical relevance. LRG1 expression was strong in HPV-negative whereas SDR16C5 expression was strong in HPV-positive tumors. Correlation was observed between LRG1, SDR16C5, and PIP4K2C expression and patient survival. High expression of PIP4K2C was found to be an independent prognostic factor for overall survival and expression correlated with HPV-positive tumor status. The data suggest the possible role of LRG1, SDR16C5 and PIP4K2C in OPSCC biology.

Abstract Key message A Soil Monitoring Law to improve soil health across all land uses has been proposed by the European Commission. As forests soils have different chemical and physical properties as well as biogeochemical dynamics compared to agricultural land, they also face different challenges in maintaining and restoring soil health. Examples are soil acidification, eutrophication by atmospheric deposition, responses to climate change, and loss of biodiversity. Therefore, we propose forest soil specific health descriptors and thresholds based on experience and knowledge from existing long-term monitoring programs.

Introduction A better understanding of the earliest stages of Alzheimer’s disease (AD) could expedite the development or administration of treatments. Large population biobanks hold the promise to identify individuals at an elevated risk of AD and related dementias based on health registry information. Here, we establish the protocol for an observational clinical recall and biomarker study called TWINGEN with the aim to identify individuals at high risk of AD by assessing cognition, health and AD-related biomarkers. Suitable candidates were identified and invited to participate in the new study among THL Biobank donors according to TWINGEN study criteria.Methods and analysis A multi-centre study (n=800) to obtain blood-based biomarkers, telephone-administered and web-based memory and cognitive parameters, questionnaire information on lifestyle, health and psychological factors, and accelerometer data for measures of physical activity, sedentary behaviour and sleep. A subcohort is being asked to participate in an in-person neuropsychological assessment (n=200) and wear an Oura ring (n=50). All participants in the TWINGEN study have genome-wide genotyping data and up to 48 years of follow-up data from the population-based older Finnish Twin Cohort (FTC) study of the University of Helsinki. The data collected in TWINGEN will be returned to THL Biobank from where it can later be requested for other biobank studies such as FinnGen that supported TWINGEN.Ethics and dissemination This recall study consists of FTC/THL Biobank/FinnGen participants whose data were acquired in accordance with the Finnish Biobank Act. The recruitment protocols followed the biobank protocols approved by Finnish Medicines Agency. The TWINGEN study plan was approved by the Ethics Committee of Hospital District of Helsinki and Uusimaa (number 16831/2022). THL Biobank approved the research plan with the permission no: THLBB2022_83.

Abstract Background Sinonasal adenocarcinoma is a rare cancer, encompassing two different entities, the intestinal-type sinonasal adenocarcinoma (ITAC) and the non-intestinal-type sinonasal adenocarcinoma (non-ITAC). Occurrence of ITAC is strongly associated with exposure to hardwood dusts. In countries with predominant exposure to softwood dust the occurrence of sinonasal adenocarcinomas is lower and the relative amount of non-ITACs to ITACs is higher. The molecular mechanisms behind the tumorigenic effects of wood dust remain largely unknown. Methods We carried out whole-genome sequencing of formalin-fixed paraffin-embedded (FFPE) samples of sinonasal adenocarcinomas from ten wood dust-exposed and six non-exposed individuals, with partial tobacco exposure data. Sequences were analyzed for the presence of mutational signatures matching COSMIC database signatures. Driver mutations and CN variant regions were characterized. Results Mutation burden was higher in samples of wood dust-exposed patients (p = 0.016). Reactive oxygen species (ROS) damage-related mutational signatures were almost exclusively identified in ITAC subtype samples (p = 0.00055). Tobacco smoke mutational signatures were observed in samples of patients with tobacco exposure or missing information, but not in samples from non-exposed patients. A tetraploidy copy number (CN) signature was enriched in ITAC subtype (p = 0.042). CN variation included recurrent gains in COSMIC Cancer Gene Census genes TERT, SDHA, RAC1, ETV1, PCM1, and MYC. Pathogenic variants were observed most frequently in TP53, NF1, CHD2, BRAF, APC, and LRP1B. Driver mutations and copy number gains did not segregate by subtype. Conclusions Our analysis identified distinct mutational characteristics in ITAC and non-ITAC. Mutational signature analysis may eventually become useful for documentation of occupation-related cancer, while the exact mechanisms behind wood dust-driven carcinogenesis remain elusive. The presence of homologous recombination deficiency signatures implies a novel opportunity for treatment, but further studies are needed.

Abstract Condition monitoring of the insulating system within power transformers has a massive importance according to the electrical utilities. Dissolved gas analysis (DGA) is frequently used for this purpose. However, DGA lacks the necessary level of accuracy to identify all equipment faults, particularly in their initial stages of degradation. Also, it does not have the capability for real‐time monitoring and relies on manual sampling and laboratory testing, causing potential delays in fault identification. Additionally, the interpretation of DGA data necessitates specialised expertise, which may pose difficulties for smaller entities that have limited access to resources. Therefore, the contribution of this research is to use infrared spectroscopy measurements as a new effective technique substituting the DGA method for fault diagnosis in insulating oil. The inception faults that were considered in this study were the electrical fault (discharges of high energy) and the thermal fault (300°C

Abstract The electrification of the transport sector to control the carbon footprint has been gaining momentum over the last decade with electric vehicles (EVs) seen as the replacement for conventional internal combustion engines. Economic incentives, subsidies, and tax exemptions are also paving the way for rising EV penetration in the power distribution networks. However, the exponential EV adoption requires careful technical and regulatory analysis of traditional networks to satisfy the network reliability constraints. Therefore, it would be vital to find EV hosting capacity (HC) limits of networks from a multifaceted approach involving various market players, mainly distribution system operators and EV owners. This review provides a systematic categorization of EV hosting capacity evaluation and improvement methods, thus enabling researchers and industry personnel to navigate the advancing landscape of EVs. This novel framework extends beyond the theoretical implication of diverse objective functions and HC improvement methods to the actual numerical values of EV HC across varying geographical settings. Therefore, this unique synthesis of varying aspects of EV HC facilitates the in‐depth understanding of the integration of sustainable energy and transport sector.

Abstract For the past few years, the addition of renewable energy sources has been on the rise, but the unregulated addition of these sources can cause severe harm to the grid. Therefore, it is necessary to have a predefined limit for a grid, beyond which no further addition of renewables should be allowed without reinforcement. That limit is called the hosting capacity (HC), which is addressed in the literature by search‐based methods with heavy computational burdens. This manuscript first presents a framework to find the HC for a grid. The same framework is then applied to 503 different simulated but realistic LV distribution feeders in Finland to find their HCs and the most effective network parameters in defining a network specific HC. Next, different machine learning models, that is, Decision Tree (DT), Random Forest (RF), Linear Regression (LR), K nearest neighbours (KNN), Logistic Regression, and Support Vector Machine (SVM) are implemented on the generated data. For the classification case, the accuracy values for logistic regression, KNN, and SVM were 0.89, 0.84, and 0.81, respectively. The findings demonstrate that the developed machine learning based technique will enable distribution network operators in finding the HC without applying any deterministic or probabilistic approaches.

While the pandemic has had a tremendous negative impact on societies, it has nonetheless provided us with a sort of living lab for investigating and exposing consolidated models of design education. The design studio, often conceptualized as a spatio-temporally inhabited milieu with translocal norms and conventions, became a blended environment where students and instructors alike had to establish new conventions and ways of knowing and inquiring. Employing Sicart's notions of play and playfulness as our theoretical lens, this paper argues how online learning has opened up a space for students and instructors to blur the boundaries of the design studio through the intersection of play and absence. Absence of things gives rise to being playful, and absence of play is required to sustain collaborative play. Through student interviews and our personal reflections, our findings reveal how play spatio-temporally fragments the design studio. In the absence of pre-existing conventions, play negotiates the boundaries of the design studio. Moreover, creating the virtual design studio can be understood as an emergent act of play; by being playful, we partly leave behind the norms and assumptions of the physical design studio to create something new. In addition, and paradoxically, creating a personalized and community-based way of being helped in seeing the immediate surroundings as the studio. Here, creating new methods for working in the studio playfully created boundaries for play. Theoretical and pedagogical implications shed light on the future of design studio and education as spaces that can be collaboratively enacted.

Background: Cardiac sarcoidosis (CS) is a rare but potentially fatal inflammatory cardiomyopathy. Objectives: The authors studied temporal changes in the incidence, characteristics, and outcome of CS. Methods: A retrospective analysis was made of a 30-year nationwide cohort of CS. Results: The cohort comprised 511 patients with a median age of 52 years and female preponderance (69%). Altogether 77, 166, and 268 cases of CS were diagnosed in years 1988 to 2009, 2010 to 2014, and 2015 to 2019, respectively; the 5-year count of 2015 to 2019 was 134-fold the count of 1990 to 1994 (268/2) and 18-fold the count of 2000 to 2004 (268/15). Prior to 2010, compared with the later periods, CS presented more often with ventricular tachycardia/fibrillation (prevalence 36% vs 19% in 2010-2014 and 11% in 2015-2019, P