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Abstract Postural orthostatic tachycardia syndrome (POTS) occurs in approximately 30% of people with highly symptomatic post-COVID-19 condition (PCC). It involves several symptoms that limit physical and psychological functions and cause reduced quality of life. Evidence for different treatments of POTS and PCC is limited, and this study aimed to evaluate the feasibility of individually tailored physical exercise. The secondary aim of the study was to evaluate the preliminary effectiveness of this intervention. Twenty-six participants (81% female, median age 41 years) were enrolled and performed individually tailored endurance and strength training, with progression, for twelve weeks. During the intervention period, the participants had weekly support from a physiotherapist. Feasibility was evaluated with good compliance, with 76% adherence to exercise prescription and 96% completing the study protocol. The treatment was safe, and the evaluation methods (questionnaires, physical assessments, and accelerometer monitoring) were judged to be feasible. After the intervention, improvements in symptom burden as well as in psychological and physical functions were observed. In conclusion, future randomized controlled trials can be performed with only minor adjustments and could include questionnaires, physical assessment and accelerometer monitoring, which were demonstrated as feasible by this study.

Abstract Background Myxoid liposarcoma (MLS) displays a distinctive tumor microenvironment and is characterized by the FUS::DDIT3 fusion oncogene, however, the precise functional contributions of these two elements remain enigmatic in tumor development. Methods To study the cell-free microenvironment in MLS, we developed an experimental model system based on decellularized patient-derived xenograft tumors. We characterized the cell-free scaffold using mass spectrometry. Subsequently, scaffolds were repopulated using sarcoma cells with or without FUS::DDIT3 expression that were analyzed with histology and RNA sequencing. Results Characterization of cell-free MLS scaffolds revealed intact structure and a large variation of protein types remaining after decellularization. We demonstrated an optimal culture time of 3 weeks and showed that FUS::DDIT3 expression decreased cell proliferation and scaffold invasiveness. The cell-free MLS microenvironment and FUS::DDIT3 expression both induced biological processes related to cell-to-cell and cell-to-extracellular matrix interactions, as well as chromatin remodeling, immune response, and metabolism. Data indicated that FUS::DDIT3 expression more than the microenvironment determined the pre-adipocytic phenotype that is typical for MLS. Conclusions Our experimental approach opens new means to study the tumor microenvironment in detail and our findings suggest that FUS::DDIT3-expressing tumor cells can create their own extracellular niche.

Abstract Mutation analysis is typically performed at the DNA level since most technical approaches are developed for DNA analysis. However, some applications, like transcriptional mutagenesis, RNA editing and gene expression analysis, require RNA analysis. Here, we combine reverse transcription and digital DNA sequencing to enable low error digital RNA sequencing. We evaluate yield, reproducibility, dynamic range and error correction rate for seven different reverse transcription conditions using multiplexed assays. The yield, reproducibility and error rate vary substantially between the specific conditions, where the yield differs 9.9-fold between the best and worst performing condition. Next, we show that error rates similar to DNA sequencing can be achieved for RNA using appropriate reverse transcription conditions, enabling detection of mutant allele frequencies

Here we describe the first crystal structure of a beta‐1,4‐endoglucanase from a brown‐rot fungus, Gloeophyllum trabeum GtCel45A, which belongs to subfamily C of glycoside hydrolase family 45 (GH45). GtCel45A is ~ 18 kDa in size and the crystal structure contains 179 amino acids. The structure is refined at 1.30 Å resolution and Rfree 0.18. The enzyme consists of a single catalytic module folded into a six‐stranded double‐psi beta‐barrel domain surrounded by long loops. GtCel45A is very similar in sequence (82% identity) and structure to PcCel45A from the white‐rot fungus Phanerochaete chrysosporium. Surprisingly though, initial hydrolysis of barley beta‐glucan was almost twice as fast in GtCel45A as compared to PcCel45A.

Abstract Background Most fisher-gatherer communities we know of utilized a limited number of natural resources for their livelihood. The Turkic-speaking Loptuq (exonym Loplik, Loplyk) in the Lower Tarim River basin, Taklamakan desert, Eastern Turkestan (Xinjiang), were no exception. Their habitat, the Lop Nor marsh and lake area, was surrounded by desert and very poor in plant species; the Loptuq had to make the most of a handful of available biological resources for housing, furniture, clothing and fabric, fishnets and traps, tools and other equipment. The taxa used by the Loptuq were documented by foreign explorers at the end of the nineteenth and beginning of the twentieth centuries, prior to the forced resettlement of the group in the 1950s and subsequent destruction of their language, lifestyle and culture. Methods and sources Ethnobiology explores the relationship between humans and their environment, including the use of biological resources for different purposes. In several aspects, historical ethnobiology is more challenging; it studies this relationship in the past and therefore cannot verify results with informants. As the present study discusses an extinct culture on the basis of literary and material sources, we apply a method called source pluralism. This approach allows the inclusion and combination of a wide range of data and materials, even scraps of information from various sources, with the aim to understand phenomena which are sparsely mentioned in historical records. Travel reports by Swedish, British, German, American and Russian explorers together with linguistic data provide the most important sources for understanding Loptuq interaction with the environment and its biota. Especially the large number of toponyms and phytonyms recorded by the Swedish explorer Sven Hedin and materials from his expeditions, including voucher specimens kept in Stockholm in the herbarium of the Swedish Natural History Museum, and objects of material culture in the collections of the Ethnographical Museum, are crucial for our analysis about local knowledge among the Loptuq. Illustrations and photographs provide us with additional information. Results The question of how the Loptuq managed to survive at the fringe of a desert, a marsh and a lake which changed its location, intrigued all foreign visitors to the Lop Nor. The Loptuq’s main livelihood was fishing, hunting and gathering, and their material culture provided by plants and other organic materials included their usage, consumption and trade. Only a handful of species formed the basis of the Loptuq material culture, but they had learned to use these specific plants for a variety of purposes. The most important of these were Lop hemp, Poacynum pictum (Schrenk) Baill., the riparian tree Euphrates poplar, Populus euphratica Olivier, and the aquatic common reed, Phragmites australis (Cav.) Trin. ex Steud. Several species of tamarisk were used for fuel and building fences. A few plants were also harvested for making foodstuffs such as snacks and potherbs. In addition, the Loptuq also used fur, bird skins, down, feathers, mammal bones and fish bones for their material needs. The habitat provided cultural ecological services such as motifs for their folklore, linguistic expressions and songs, and the Loptuq engaged in small-scale bartering of plant products and furs with itinerant traders, which ensured them with a supply of metal for making tools. Conclusion This article discusses the now extinct Loptuq material culture as it existed more than a hundred years ago, and how the scarce biological resources of their desert and marsh habitat were utilized. Loptuq adaptation strategies to the environment and local knowledge, transmitted over generations, which contributed to their survival and subsistence, were closely connected with the use of biological resources. For this study, a comprehensive approach has been adopted for the complex relationships between human, biota and landscape. The Loptuq are today largely ignored or deleted from history for political reasons and are seldom, if at all, mentioned in modern sources about the Lop Nor area. Their experience and knowledge, however, could be useful today, in a period of rapid climate change, for others living in or at the fringe of expanding deserts.

Abstract Aim Acyl ghrelin increases cardiac output (CO) in heart failure with reduced ejection fraction (HFrEF). This could impair the right ventricular‐pulmonary arterial coupling (RVPAC), both through an increased venous return and right ventricular afterload. We aim to investigate if acyl ghrelin increases CO with or without worsening the right‐sided haemodynamics in HFrEF assessed by RVPAC. Methods and results The Karolinska Acyl ghrelin Trial was a randomized double‐blind placebo‐controlled trial of acyl ghrelin versus placebo (120‐min intravenous infusion) in HFrEF. RVPAC was assessed echocardiographically at baseline and 120 min. ANOVA was used for difference in change between acyl ghrelin versus placebo, adjusted for baseline values. Of the 30 randomized patients, 22 had available RVPAC (acyl ghrelin n = 12, placebo n = 10). Despite a 15% increase in CO in the acyl ghrelin group (from 4.0 (3.5–4.6) to 4.6 (3.9–6.1) L/min, P = 0.003), RVPAC remained unchanged; 5.9 (5.3–7.6) to 6.3 (4.8–7.5) mm·(m/s)−1, P = 0.372, while RVPAC was reduced in the placebo group, 5.2 (4.3–6.4) to 4.8 (4.2–5.8) mm·(m/s)−1, P = 0.035. Comparing change between groups, CO increased in the acyl ghrelin group versus placebo (P = 0.036) while RVPAC and the right ventricular pressure gradient remained unchanged. Conclusion Treatment with acyl ghrelin increases CO while preserving or even improving RVPAC in HFrEF, possibly due to increased contractility, reduced PVR and/or reduced left sided filling pressures. These potential effects strengthen the role of acyl ghrelin therapy in HFrEF with right ventricular failure.

Abstract Background The tumor microenvironment clearly influences cancer progressing properties but less is known about how individual cancer microenvironments potentially moderate cancer treatment effects. By cultivating and treating cancer cell lines in patient-derived scaffolds (PDS), the impact of specific characteristics of individual cancer microenvironments can be incorporated in human-like growth modelling and cancer drug treatment testing. Methods PDSs from 78 biobanked primary breast cancer samples with known patient outcomes, were prepared and repopulated with donor breast cancer cell lines, followed by treatment with 5-fluorouracil or doxorubicin after cellular adaption to the various microenvironments. Cancer cell responses to the treatments were monitored by RNA-analyses, highlighting changes in gene sets representative for crucial tumor biological processes such as proliferation, cancer stem cell features, differentiation and epithelial-to-mesenchymal transition. Results The chemotherapy treatments induced distinct gene expression patterns in adapted cancer cells with clusters of similar treatment responses depending on the patient-derived cancer microenvironment used as growth substrate. The doxorubicin treatment displayed a favorable gene signature among surviving cancer cells with low proliferation (MKI67) and pluripotency features (NANOG, POU5F1), in comparison to 5-fluorouracil showing low proliferation but increased pluripotency. Specific gene changes monitored post-treatment were also significantly correlated with clinical data, including histological grade (NANOG), lymph node metastasis (SLUG) and disease-free patient survival (CD44). Conclusions This laboratory-based treatment study using patient-derived scaffolds repopulated with cancer cell lines, clearly illustrates that the human cancer microenvironment influences chemotherapy responses. The differences in treatment responses defined by scaffold-cultures have potential prognostic and treatment predictive values.

Black elder, Sambucus nigra, is a non-native but now partly naturalized shrub in Sweden; it has been cultivated here at least since the Middle Ages. Previously, this plant was associated with a supernatural being to whom sacrifices were made, and its fruits were used in folk medicine and wood for fuel and crafts. Traditional economic uses vanished with industrialization and urbanization and black elder was mostly planted as an ornamental shrub in urban parks. At the end of the 1970s, however, it made a sudden comeback: city dwellers started to gather flowers to make a refreshing non-alcoholic cordial. This diachronic study of Sambucus nigra spanning over a millennium reflects various attitudes and uses within the context of a changing human society. In addition to the simple but popular cordial, side dishes and desserts made of its fragrant flowers are becoming increasingly popular in modern Swedish cuisine. Globally it has also been (re)discovered and the utilization of this plant is growing: its flowers are used to add flavor to soft drinks, salads, desserts and various dishes; berries are used for medicine and in cooking, especially with meats, and its future uses seem to be limited only by human imagination.

AimsTo assess the barriers to guideline-directed medical therapy (GDMT) use in heart failure (HF), diagnostic workup and general knowledge about HF among physicians in Sweden.MethodsA survey about the management of HF was sent to 828 Swedish physicians including general practitioners (GPs) and specialists during 2021–2022. Answers were reported as percentages and comparisons were made by specialty (GPs vs. specialists).ResultsOne hundred sixty-eight physicians participated in the survey (40% females, median age 43 years; 41% GPs and 59% specialists). Electrocardiography and New York Heart Association class evaluations are mostly performed once a year by GPs (46%) and at every outpatient visit by specialists (40%). Echocardiography is mostly requested if there is clinical deterioration (60%). One-third of participants screen for iron deficiency only if there is anemia. Major obstacles to implementation of different drug classes in HF with reduced ejection fraction are related to side effects, with no significant differences between specialties. Device implantation is deemed appropriate regardless of aetiology (69%) and patient age (86%). Specialists answered correctly to knowledge questions more often than GPs. Eighty-six percent of participants think that GDMT should be implemented as much as possible. Most participants (57%) believe that regular patient assessment in nurse-led HF clinics improve adherence to GDMT.ConclusionObstacles to GDMT implementation according to physicians in Sweden mainly relate to potential side effects, lack of specialist knowledge and organizational aspects. Further efforts should be placed in educational activities and structuring of nurse-led clinics.

Objective: Experience of caries has a clearly negative impact on the quality of life in preschool children. The instrument Early Childhood Oral Health Impact Scale (ECOHIS) measures the oral health-related quality of life in preschool children (Child Impact Section) and their families (Family Impact Section). The aims of the study were to develop a Swedish version of ECOHIS and to evaluate the instrument’s reliability, validity, and internal consistency. Additionally, to analyse the oral health-related quality of life (OHRQoL) among preschool children who have experienced caries. Methods: The original ECOHIS questionnaire was translated into Swedish. Caregivers of preschool children aged 2–5 years were recruited at dental clinics in Sweden, to participate in the study and answer the Swedish version of the ECOHIS (S-ECOHIS). The internal consistency and reliability were assessed by using Cronbach’s Alpha coefficient. In order to measure the consistency of the study, the questionnaire was re-tested two weeks later for 10 of the caregivers and assessed by using intra-class correlation coefficients (ICCs). The results from S-ECOHIS were described as descriptive data and independent t-test was performed. All data were calculated using SPSS (Statistical Package for the Social Sciences). Results: S-ECOHIS was developed by translating the original English version using a double-blinded technique. A total of 274 caregivers participated in the study and completed the questionnaire. Cronbach’s Alpha was 0.84 for S-ECOHIS, 0.83 for CIS, and 0.66 for FIS. The ICCwas 0.95 for the test-retest of S-ECOHIS. Among the respondents, 117 (43%) had children diagnosed with caries, while 157 (57%) had children without caries. The children with caries reported a higher total score of 5.97 (SD 6.16) of S-ECOHIS, compared to the score of the non-caries children 0.77 (SD 1.38) (p < 0.001). Conclusion: The Swedish version of ECOHIS that was developed demonstrates good validity, test-retest reliability, and internal consistency. The findings show that the oral health-related quality of life is adversely affected in preschool children with caries, with particular vulnerability observed among children with untreated caries. These results indicate that S-ECOHISis suitable for use in future clinical and research endeavors. Abbreviations: S- ECOHIS: Swedish version of the Early Childhood Oral Health Impact Scale; OHRQoL: Oral Health-Related Quality of Life; ICC: Intraclass correlation coefficient; CIS: Children Impact Section; FIS: Family Impact Section

Abstract Post-acute COVID-19 (PACS) are associated with cardiovascular dysfunction, especially postural orthostatic tachycardia syndrome (POTS). Patients with PACS, both in the absence or presence of POTS, exhibit a wide range of persisting symptoms long after the acute infection. Some of these symptoms may stem from alterations in cardiovascular homeostasis, but the exact mechanisms are poorly understood. The aim of this study was to provide a broad molecular characterization of patients with PACS with (PACS + POTS) and without (PACS-POTS) POTS compared to healthy subjects, including a broad proteomic characterization with a focus on plasma cardiometabolic proteins, quantification of cytokines/chemokines and determination of plasma sphingolipid levels. Twenty-one healthy subjects without a prior COVID-19 infection (mean age 43 years, 95% females), 20 non-hospitalized patients with PACS + POTS (mean age 39 years, 95% females) and 22 non-hospitalized patients with PACS-POTS (mean age 44 years, 100% females) were studied. PACS patients were non-hospitalized and recruited ≈18 months after the acute infection. Cardiometabolic proteomic analyses revealed a dysregulation of ≈200 out of 700 analyzed proteins in both PACS groups vs. healthy subjects with the majority (> 90%) being upregulated. There was a large overlap (> 90%) with no major differences between the PACS groups. Gene ontology enrichment analysis revealed alterations in hemostasis/coagulation, metabolism, immune responses, and angiogenesis in PACS vs. healthy controls. Furthermore, 11 out of 33 cytokines/chemokines were significantly upregulated both in PACS + POTS and PACS-POTS vs. healthy controls and none of the cytokines were downregulated. There were no differences in between the PACS groups in the cytokine levels. Lastly, 16 and 19 out of 88 sphingolipids were significantly dysregulated in PACS + POTS and PACS-POTS, respectively, compared to controls with no differences between the groups. Collectively, these observations suggest a clear and distinct dysregulation in the proteome, cytokines/chemokines, and sphingolipid levels in PACS patients compared to healthy subjects without any clear signature associated with POTS. This enhances our understanding and might pave the way for future experimental and clinical investigations to elucidate and/or target resolution of inflammation and micro-clots and restore the hemostasis and immunity in PACS.

ABSTRACT: The most suitable light intensity for cows during nighttime has not been thoroughly investigated. Recommendations on the night-time lighting regimen on dairy farms differ between countries and range from light throughout the night to darkness to allow the animals a rest from artificial light. Commercial actors recommend red light for night-time lighting in cattle barns to facilitate livestock supervision with minimum disturbance for the animals. However, little is known about how light intensity, spectrum, and uniformity affect the ability of cows to navigate their indoor environment. Thus, in a change-over study with 12 pregnant, nonlactating dairy cows, we observed how the cows walked through an obstacle course under different light treatments. Obstacles were positioned differently for every run, to present a novel challenge for each light environment. Fourteen different light treatments were tested, involving intensity ranging from

Abstract Background Selective mutism (SM) is a childhood onset anxiety disorder, and the main symptom is not speaking in certain social situations. Knowledge about the duration and long-term outcomes of SM have been lacking and the aim of this systematic literature review was to address this gap in the literature. We investigated how long SM symptoms persisted as well as other psychiatric outcomes associated with SM in later life. Methods The PubMed, PsycInfo, Web of Science, Cochrane Library and Embase databases were initially searched from inception to 11 September 2023. Studies were included if they were published in English and had followed up subjects with clinically diagnosed SM for at least two years. The review followed the Preferred Reporting Items of Systematic Reviews and Meta-analyses guidelines and the protocol was registered with the Open Science Framework. The papers were assessed using the Quality Assessment with Diverse Studies tool. Results This review screened 2,432 papers and assessed 18 studies. Seven case series studies were excluded from discussion because of the low number of subjects and the fact that their findings could not be generalized to wider populations. In the end, nine clinical cohorts and two case control studies were reviewed. These provided a total of 292 subjects and the sample sizes ranged from 11–49. The overall quality of the studies was moderate. The review found that 190 of the 243 subjects in the studies that reported recovery rates showed moderate or total improvement from SM during follow up. Other anxiety disorders were the most common psychiatric disorders later in life, although these results should be interpreted with caution. Older age at baseline and parental psychopathology might predict greater impairment, but further studies are needed to confirm these results. Conclusions Most subjects with SM recovered from this disorder during adolescence, but anxiety disorders were common in later life. Early detection and treatment are needed to prevent symptoms from persisting and other psychiatric disorders from developing.

IntroductionEmotional awareness and emotion regulation are crucial for cognitive and socio-emotional development in children. School-based interventions on socio-emotional skills have the potential to prevent these problems and promote well-being of children. The Japanese school-based program, Universal Unified Prevention Program for Diverse Disorders (Up2-D2), has shown preventive effects on mental health of children in Japan. The aims of this protocol paper are to describe the unique process of adapting the Up2-D2 from Eastern to Western context, and to present a feasibility study of the intervention, conducted in Finland.MethodsThe cultural adaptation process started with the linguistic translation of materials, followed by the modification of language to fit the Finnish context. While the Japanese ideology was saved, some content was adapted to fit Finnish school children. Further modifications were made based on feedback from pupils and teachers. The Finnish version of the program was named “Let’s learn about emotions” and consisted of 12 sessions and targeted 8- to 12-year-old pupils. A teacher education plan was established to assist Finnish teachers with the intervention, including a workshop, teachers’ manual, brief introductory videos, and online support sessions. A feasibility study involving 512 4th graders in the City of Hyvinkää, South of Finland, was conducted. It assessed emotional and behavioral problems, classroom climate, bullying, loneliness, perception of school environment, knowledge of emotional awareness, and program acceptability.DiscussionThe originality of this study underlies in the East–West adaptation of a cognitive behavioral therapy-based program. If promising feasibility findings are replicated in Finland, it could pave the way for further research on implementing such programs in diverse contexts and cultures, promoting coping skills, awareness, social skills and early prevention of child mental health problems.EthicsThe ethical board of the University of Turku gave ethics approval for this research. The educational board of the City of Hyvinkää accepted this study.

Studies implementing a multimethod perspective in evaluating the acoustics of early childhood education and care (ECEC) spaces both quantitatively and qualitatively are still scarce. In this study the acoustic environments (noise levels and reverberation times) of seven Finnish ECEC group’s premises were examined in association with personnel’s (N = 22) and children’s (N = 71) well-being. Personnel’s well-being and vocal health and children’s well-being were assessed with questionnaires. The findings were further elaborated by documentation of the ECEC spaces and semi-structured interviews with the ECEC personnel detailing their views on the acoustic environment of the daycare buildings and how and if the acoustics should be improved. The results showed that noise exceeding 70 dB affected personnel’s vocal health negatively, whereas no associations were found regarding acoustics and children’s or personnel’s well-being. Based on the interviews, sound spreading, poor insulation, and hard surfaces add to negative experiences of noisiness. ECEC groups need spaces that can be closed and acoustically separated from each other and from other groups. The possibility to close a space supports the perceived well-being of the users and provides a more varied and individualized use of the spaces.

Abstract Wild edible plants, particularly berries, are relevant nutritional elements in the Nordic countries. In contrast to decreasing global trends, approximately 60% of the Finnish population is actively involved in (berry) foraging. We conducted 67 interviews with Finns and Karelians living in Finnish Karelia to: (a) detect the use of wild edible plants, (b) compare those results with the published data about neighbouring Russian Karelians, and (c) document the sources of local plant knowledge. The results revealed three main findings. First, we observed a similarity in wild food plant knowledge among Karelians and Finns from Karelia. Second, we detected divergences in wild food plant knowledge among Karelians living on both sides of the Finnish–Russian border. Third, the sources of local plant knowledge include vertical transmission, acquisition through literary sources, acquisition from “green” nature shops promoting healthy lifestyles, childhood foraging activities performed during the famine period following WWII, and outdoor recreational activities. We argue that the last two types of activities in particular may have influenced knowledge and connectedness with the surrounding environment and its resources at a stage of life that is crucial for shaping adult environmental behaviours. Future research should address the role of outdoor activities in maintaining (and possibly enhancing) local ecological knowledge in the Nordic countries.

Abstract Background FUS, EWS and TAF15 are structurally similar multifunctional proteins that were first discovered upon characterization of fusion oncogenes in human sarcomas and leukemias. The proteins belong to the FET (previously TET) family of RNA-binding proteins and are implicated in central cellular processes such as regulation of gene expression, maintenance of genomic integrity and mRNA/microRNA processing. In the present study, we investigated the expression and cellular localization of FET proteins in multiple human tissues and cell types. Results FUS, EWS and TAF15 were expressed in both distinct and overlapping patterns in human tissues. The three proteins showed almost ubiquitous nuclear expression and FUS and TAF15 were in addition present in the cytoplasm of most cell types. Cytoplasmic EWS was more rarely detected and seen mainly in secretory cell types. Furthermore, FET expression was downregulated in differentiating human embryonic stem cells, during induced differentiation of neuroblastoma cells and absent in terminally differentiated melanocytes and cardiac muscle cells. The FET proteins were targeted to stress granules induced by heat shock and oxidative stress and FUS required its RNA-binding domain for this translocation. Furthermore, FUS and TAF15 were detected in spreading initiation centers of adhering cells. Conclusion Our results point to cell-specific expression patterns and functions of the FET proteins rather than the housekeeping roles inferred from earlier studies. The localization of FET proteins to stress granules suggests activities in translational regulation during stress conditions. Roles in central processes such as stress response, translational control and adhesion may explain the FET proteins frequent involvement in human cancer.

Abstract Background The large sensitivity, high reproducibility and essentially unlimited dynamic range of real-time PCR to measure gene expression in complex samples provides the opportunity for powerful multivariate and multiway studies of biological phenomena. In multiway studies samples are characterized by their expression profiles to monitor changes over time, effect of treatment, drug dosage etc. Here we perform a multiway study of the temporal response of four yeast Saccharomyces cerevisiae strains with different glucose uptake rates upon altered metabolic conditions. Results We measured the expression of 18 genes as function of time after addition of glucose to four strains of yeast grown in ethanol. The data are analyzed by matrix-augmented PCA, which is a generalization of PCA for 3-way data, and the results are confirmed by hierarchical clustering and clustering by Kohonen self-organizing map. Our approach identifies gene groups that respond similarly to the change of nutrient, and genes that behave differently in mutant strains. Of particular interest is our finding that ADH4 and ADH6 show a behavior typical of glucose-induced genes, while ADH3 and ADH5 are repressed after glucose addition. Conclusion Multiway real-time PCR gene expression profiling is a powerful technique which can be utilized to characterize functions of new genes by, for example, comparing their temporal response after perturbation in different genetic variants of the studied subject. The technique also identifies genes that show perturbed expression in specific strains.

Angiosarcoma is a rare and aggressive type of soft-tissue sarcoma with high propensity to metastasize. For patients with metastatic angiosarcoma, prognosis is dismal and treatment options are limited. To improve the outcomes, identifying patients with poor treatment response at an earlier stage is imperative, enabling alternative therapy. Consequently, there is a need for improved methods and biomarkers for treatment monitoring. Quantification of circulating tumor-DNA (ctDNA) is a promising approach for patient-specific monitoring of treatment response. In this case report, we demonstrate that quantification of ctDNA using SiMSen-Seq was successfully utilized to monitor a patient with metastatic angiosarcoma. By quantifying ctDNA levels using 25 patient-specific mutations in blood plasma throughout surgery and palliative chemotherapy, we predicted the outcome and monitored the clinical response to treatment. This was accomplished despite the additional complexity of the patient having a synchronous breast cancer. The levels of ctDNA showed a superior correlation to the clinical outcome compared with the radiological evaluations. Our data propose a promising approach for personalized biomarker analysis to monitor treatment in angiosarcomas, with potential applicability to other cancers and for patients with synchronous malignancies.

Diffusion MRI uses the random displacement of water molecules to sensitize the signal to brain microstructure and to properties such as the density and shape of cells. Microstructure modeling techniques aim to estimate these properties from acquired data by separating the signal between virtual tissue ‘compartments’ such as the intra-neurite and the extra-cellular space. A key challenge is that the diffusion MRI signal is relatively featureless compared with the complexity of brain tissue. Another challenge is that the tissue microstructure is wildly different within the gray and white matter of the brain. In this review, we use results from multidimensional diffusion encoding techniques to discuss these challenges and their tentative solutions. Multidimensional encoding increases the information content of the data by varying not only the b-value and the encoding direction but also additional experimental parameters such as the shape of the b-tensor and the echo time. Three main insights have emerged from such encoding. First, multidimensional data contradict common model assumptions on diffusion and T2 relaxation, and illustrates how the use of these assumptions cause erroneous interpretations in both healthy brain and pathology. Second, many model assumptions can be dispensed with if data are acquired with multidimensional encoding. The necessary data can be easily acquired in vivo using protocols optimized to minimize Cramér-Rao lower bounds. Third, microscopic diffusion anisotropy reflects the presence of axons but not dendrites. This insight stands in contrast to current ‘neurite models’ of brain tissue, which assume that axons in white matter and dendrites in gray matter feature highly similar diffusion. Nevertheless, as an axon-based contrast, microscopic anisotropy can differentiate gray and white matter when myelin alterations confound conventional MRI contrasts.

In this prospective study we investigated a cohort after heart transplantation with a novel PCR-based approach with focus on treated rejection. Blood samples were collected coincidentally to biopsies, and both absolute levels of dd-cfDNA and donor fraction were reported using digital PCR. 52 patients (11 children and 41 adults) were enrolled (NCT03477383, clinicaltrials.gov), and 557 plasma samples were analyzed. 13 treated rejection episodes >14 days after transplantation were observed in 7 patients. Donor fraction showed a median of 0.08% in the cohort and was significantly elevated during rejection (median 0.19%, p < 0.0001), using a cut-off of 0.1%, the sensitivity/specificity were 92%/56% (AUC ROC-curve: 0.78). Absolute levels of dd-cfDNA showed a median of 8.8 copies/mL and were significantly elevated during rejection (median 23, p = 0.0001). Using a cut-off of 7.5 copies/mL, the sensitivity/specificity were 92%/43% for donor fraction (AUC ROC-curve: 0.75). The results support the feasibility of this approach in analyzing dd-cfDNA after heart transplantation. The obtained values are well aligned with results from other trials. The possibility to quantify absolute levels adds important value to the differentiation between ongoing graft damage and quiescent situations.

Abstract Background With ~ 50 million individuals suffering from post-COVID condition (PCC), low health related quality of life (HRQoL) is a vast problem. Common symptoms of PCC, that persists 3 months from the onset of COVID-19 are fatigue, shortness of breath and cognitive dysfunction. No effective treatment options have been widely adopted in clinical practice. Hyperbaric oxygen (HBO2) is a candidate drug. Methods The objective of this interim analysis is to describe our cohort and evaluate the safety of HBO2 for post covid condition. In an ongoing randomised, placebo-controlled, double blind, clinical trial, 20 previously healthy subjects with PCC were assigned to HBO2 or placebo. Primary endpoints are physical domains in RAND-36; Physical functioning (PF) and Role Physical (RP) at 13 weeks. Secondary endpoints include objective physical tests. Safety endpoints are occurrence, frequency, and seriousness of Adverse Events (AEs). An independent data safety monitoring board (DSMB) reviewed unblinded data. The trial complies with Good Clinical Practice. Safety endpoints are evaluated descriptively. Comparisons against norm data was done using t-test. Results Twenty subjects were randomised, they had very low HRQoL compared to norm data. Mean (SD) PF 31.75 (19.55) (95% Confidence interval; 22.60–40.90) vs 83.5 (23.9) p

BackgroundThere are contradictory research findings regarding whether individuals with Autism Spectrum Disorders (ASDs) are more or less likely to commit crimes. The aims of the current study were to: (1) Describe psychiatric and crime-related characteristics of a large group of offenders with ASD who had undergone a Forensic Psychiatric Investigation (FPI). (2) Identify clinical subgroups among this group of offenders. (3) Investigate associations between the identified clinical subgroups and (a) psychiatric comorbidity (b) types of crimes and (c) criminal responsibility.MethodsThe study cohort consists of all subjects (n = 831) who received an ASD-diagnosis at an FPI between 2002 and 2018 in Sweden. Descriptive and clinical, as well as crime related variables were obtained from the FPIs. Non-parametric (Pearson χ2, Fisher's exact and Mann-Whitney U-test) inferential statistics were used for analyses of between-group differences and effect sizes were reported. A Latent Class Analysis was used to identify homogeneous subgroups (or classes) from categorical characteristics.ResultsThe cohort consisted of 708 men and 123 women, aged 18 to 74 yrs. Two-thirds (66.7%) of the cohort had at least one other psychiatric diagnosis, the most prevalent was substance use disorder (SUD). A severe mental disorder, equivalent to lack of criminal responsibility, was most often reported among offenders with a comorbid diagnosis of schizophrenia spectrum disorder. The most common type of crime was violent crime. Three person-oriented clinical subgroups were identified; (1) ASD with few other diagnoses; (2) ASD and very high levels of SUDs, plus moderate levels of other externalizing disorders and psychotic psychopathology and (3) ASD and moderate to high levels of personality disorders (other than ASPD) and SUDs.ConclusionOur results highlight the importance of all parts of the CJS to be prepared to handle offenders with ASD, often with high levels of additional psychiatric problems. Traditional approaches in treatment or other psychosocial interventions for ASD may need to be adapted to at least three general clinical profiles– one with mainly neurodevelopmental problems, one with a spectrum of externalizing problems and one with complex personality related difficulties.