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Mitochondria play a significant role in numerous cellular processes through proteins encoded by both the nuclear genome (nDNA) and mito genome (mDNA), and increasing evidence shows that traits of interest might be affected by mito-nuclear interactions. Whereas the variation in nDNA is influenced by mutations and recombination of parental genomes, the variation in mDNA is solely driven by mutations. In addition, mDNA is inherited in a haploid form, from the dam. Cattle populations show substantial variation in mDNA between and within breeds. Past research suggests that variation in mDNA accounts for 1% to 5% of the phenotypic variation in dairy traits. Here we simulated a dairy cattle breeding program to assess the impact of accounting for mDNA variation in pedigree-based and genome-based genetic evaluations on the accuracy of EBVs for mDNA and nDNA components. We also examined the impact of alternative definitions of breeding values on genetic gain, including nDNA and mDNA components that both affect phenotype expression, but mDNA is inherited only maternally. We found that accounting for mDNA variation increased accuracy between +0.01 and +0.03 for different categories of animals, especially for young bulls (+0.03) and females without genotype data (between +0.01 and +0.03). Different scenarios of modeling and breeding value definition affected genetic gain. The standard approach of ignoring mDNA variation achieved competitive genetic gain. Modeling but not selecting on mDNA expectedly reduced genetic gain, whereas optimal use of mDNA variation recovered the genetic gain.

Abstract While Coronavirus disease 2019 (COVID-19) vaccines have proven to be both effective and generally safe, rare but severe adverse events following immunization (AEFIs) are described. Autoantibodies to platelet factor-4 are associated with catastrophic thrombotic AEFIs, but comprehensive investigations of other autoantibodies are lacking. We aimed to detect and describe autoantibodies targeting coagulation-related proteins in a population-wide cohort (SWEDEGENE) including AEFIs attributed to COVID-19 vaccines in Sweden. Subjects were recruited from December 2020 to October 2022 and were stratified based on diagnosis and COVID-19 exposure. Screening was carried out in two phases, with a multiplex bead-based assay in the first subset (until September 2021) and with targeted assays for the second (until October 2022). Positivity was defined based on absolute, relative, and biological/technical thresholds. Patients with coagulation-related AEFIs were older and the Vaxzevria vaccine was overrepresented in this group. Two cases had antiphospholipid antibodies but none had PF4 antibodies. We identified six positives for protein S autoantibodies. Protein S concentrations were negatively correlated with autoantibody response in patients with immunoreactivity and functional analysis revealed low protein S activity in three subjects. Our population-wide analysis reveals cases with autoantibodies against protein S which possibly underlie coagulopathic AEFIs.

Abstract COVID-19 is a severe respiratory disease affecting millions worldwide, causing significant morbidity and mortality. Adrenomedullin (bio-ADM) is a vasoactive hormone regulating the endothelial barrier and has been associated with COVID-19 mortality and other adverse events. This prospective cohort pilot study included 119 consecutive patients with verified SARS-CoV-2 infection admitted to two intensive care units (ICUs) in Southern Sweden. Bio-ADM was retrospectively analysed from plasma on ICU admission, and days 2 and 7. Information on comorbidities, adverse events and mortality was collected. The primary outcome was 90-day mortality, and secondary outcomes were markers of disease severity. The association between bio-ADM and outcomes was analysed using survival analysis and logistic regression. Bio-ADM on admission, day 2, and day 7 only moderately predicted 90-day mortality in univariate and multivariate Cox regression. The relative change in bio-ADM between sample times predicted 90-day mortality better even when adjusting for the SAPS3 score, with an HR of 1.09 (95% CI 1.04–1.15) and a C-index of 0.82 (95% CI 0.72–0.92) for relative change between day 2 and day 7. Bio-ADM had a good prediction of the need for renal replacement therapy in multivariate Cox regression adjusting for creatinine, where day 2 bio-ADM had an HR of 3.18 (95% CI 1.21–8.36) and C-index of 0.91 (95% CI 0.87–0.96). Relative changes did not perform better, possibly due to a small sample size. Admission and day 2 bio-ADM was associated with early acute kidney injury (AKI). Bio-ADM on ICU admission, day 2 and day 7 predicted 90-day mortality and dialysis needs, highlighting bio-ADM’s importance in COVID-19 pathophysiology. Bio-ADM could be used to triage patients with a risk of adverse outcomes and as a potential target for clinical interventions.

Objective This study described the experiences and perceptions of how primary health care professionals (PHCPs) support patients with venous leg ulcers (VLUs) in self-care monitoring.Design A qualitative approach with reflexive thematic analysis was used, with 24 individual qualitative open interviews.Setting Primary health care clinics and community health care in four southern regions in Sweden.Subjects Registered nurses, district nurses and nurse assistants who had experience of caring for patients with VLUs. In total, 24 interviews were conducted with PHCPs in Sweden.Results PHCPs have a vital role in promoting patient independence and responsibility, identifying needs and adapting care strategies, while also recognising unmet needs in patients with VLUs.Conclusion PHCPs actively monitor patients’ self-care and establish caring relationships. They see a need for a structured primary health care work routine for ulcer management.

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

Abstract Cerebral dopamine neurotrophic factor (CDNF) is an unconventional neurotrophic factor that is a disease-modifying drug candidate for Parkinson’s disease. CDNF has pleiotropic protective effects on stressed cells, but its mechanism of action remains incompletely understood. Here, we use state-of-the-art advanced structural techniques to resolve the structural basis of CDNF interaction with GRP78, the master regulator of the unfolded protein response (UPR) pathway. Subsequent binding studies confirm the obtained structural model of the complex, eventually revealing the interaction site of CDNF and GRP78. Finally, mutating the key residues of CDNF mediating its interaction with GRP78 not only results in impaired binding of CDNF but also abolishes the neuroprotective activity of CDNF-derived peptides in mesencephalic neuron cultures. These results suggest that the molecular interaction with GRP78 mediates the neuroprotective actions of CDNF and provide a structural basis for development of next generation CDNF-based therapeutic compounds against neurodegenerative diseases.

Abstract Introduction Patient education programmes focusing on risk factor modification and lifestyle changes are well established as part of cardiac rehabilitation in patients with coronary artery disease (CAD). As participation rates are low, digital patient education programmes (DPE) are interesting alternatives to increase access. Understanding patients’ perceptions of DPE are important in terms of successful implementation in clinical practice but are not well known. Therefore, the aim of this study was to assess patients’ perceptions of using a DPE in terms of end-user acceptance and usability, perceived significance for lifestyle changes and secondary preventive goal fulfilment in patients with CAD. Methods This was a cross-sectional survey-based study. The survey was distributed to all 1625 patients with acute coronary syndrome or chronic CAD with revascularisation, who were registered users of the DPE between 2020 and 2022 as part of cardiac rehabilitation. The survey contained 64 questions about e.g., acceptance and usability, perceived significance for making lifestyle changes and secondary preventive goal fulfilment. Patients who had never logged in to the DPE received questions about their reasons for not logging in. Data were analysed descriptively. Results A total of 366 patients (mean age: 69.1 ± 11.3 years, 20% female) completed the survey and among those 207 patients (57%) had used the DPE. Patients reported that the DPE was simple to use (80%) and improved access to healthcare (67–75%). A total of 69% of the patients were generally satisfied with the DPE, > 60% reported that the DPE increased their knowledge about secondary preventive treatment goals and approximately 60% reported having a healthy lifestyle today. On the other hand, 35% of the patients would have preferred a hospital-based education programme. Among the 159 patients (43%) who had never used the DPE, the most reported reason was a perceived need for more information about how to use the DPE (52%). Conclusions This study shows an overall high level of patient acceptance and usability of the DPE, which supports its continued development and long-term role in cardiac rehabilitation in patients with CAD. Future studies should assess associations between participation in the DPE and clinical outcomes, such as secondary preventive goal fulfilment and hospitalisation.

Summary: Variation in outcomes definitions and reporting limit the utility of clinical trial results. The Core Outcome Research Measures in Anal Cancer (CORMAC) project developed a core outcome set (COS) for chemoradiotherapy trials for anal squamous cell carcinoma (ASCC) through an international healthcare professional and patient consensus process. The CORMAC-COS comprises 19 outcomes across 4 domains (disease activity, survival, toxicity, life impact). In CORMAC-2 we have established standardised definitions for the 11 disease activity and survival outcomes in the CORMAC COS. Definitions were agreed through a 3 step process, initially identifying existing definitions through systematic review (registered with PROSPERO, CRD42016036540), using these to populate a two-round Delphi questionnaire completed by 51 experts from 13 countries, and finally ratification through an online consensus meeting. Standardising the definitions for these core outcomes facilitates real world utilisation of the CORMAC-COS, thereby increasing the quality of data available for clinical decision-making and ultimately enhancing patient care.

This study introduces a progressive methodology for examining the travel behaviour of bicyclists and pedestrians under both daylight and electric lighting conditions. By analysing data from naturalistic/undisturbed settings, we aimed to assess the representativeness of participant behaviour in an invited context compared to that of typical road users. This paper expands upon the methodological exploration initiated in the original Video Analysis of Pedestrian Movement (VAPM) study by analysing the microscopic movements of both pedestrians and bicyclists in outdoor environments under both natural and electric lighting conditions. Furthermore, the paper investigates bicyclists’ bi-directional interactions in a naturalistic setting, adding a valuable dimension to the study's comprehensive analysis. Our research introduces an effective approach to data collection through the use of drone technology to obtain microscopic data from video analysis. This method has the potential to enhance travel quality for bicyclists during the hours of twilight and darkness and increase the likelihood of short motor vehicle trips being replaced by active, sustainable forms of transport.

In an interaction between road users, the proximity and speed are two interdependent dimensions which can be captured by a type of multivariate distribution called Copula. Copula requires all marginal distribution functions to be known. However, finding the marginal distribution of the proximity dimension is challenging, as its histogram usually contains several peaks. We partition the outcome space in a way that extreme value theory can be used as a tool to approximate the target marginal distribution in the tail region. In traffic safety research, such approach has the following advantages: • The approach can approximate the distribution in the region in which the density is monotone. • Via copula and extreme value theory, it is possible to find the conditional distribution while the conditions are not present in the data set.

Background Acute respiratory distress syndrome (ARDS) is a common cause of respiratory failure in the intensive care unit (ICU). Previous studies have suggested that blood group A increases the risk of developing ARDS following sepsis and major trauma. This study investigated the association between ABO and Rh blood groups and ARDS development and mortality in ARDS.Methods Patients admitted to the ICUs at Skåne University Hospital in Lund and Malmö, Sweden, in 2016 were retrospectively screened for ARDS according to the Berlin definition. Clinical data, patient characteristics, lab results, and survival data were collected from medical records and registry data. In addition, chest radiographs were reviewed by radiologists. ARDS development and 30-day mortality were analysed using multivariable logistic regression.Results A total of 1439 ICU patients were included. Of these, 10% had ARDS. Blood group O was associated with an increased risk of having or developing ARDS compared to blood group A (odds ratio [OR] 1.79, 95% confidence interval [CI] 1.13–2.84, p = 0.014). Among ARDS patients, blood group O had decreased 30-day mortality compared to blood group A (OR 0.25, 95% CI 0.09–0.67, p = 0.007). The Rh blood group was not associated with ARDS development or mortality.Conclusion In this study of ICU patients, blood group O was associated with an increased risk of having or developing ARDS but a decreased mortality in ARDS compared to blood group A. Further studies are needed to clarify the relationship and underlying mechanisms of the ABO blood group and ARDS.

This paper presents a method for evaluating the potential for injury in any traffic scenario involving road user interactions based on trajectory data from a few hours of data of typical traffic conditions. The basic idea was to evaluate to what extent interactions at a location are limited in speed, direction, and whether the interactions happen at a safe speed. Specifically, the method works by applying an existing injury model to the highest observed values at a specific point in space. The injury model is used to estimate a worst-case scenario at that point in space. By generating a heat map, it is possible to analyse a location and evaluate the injury potential at a location. The method does not provide a complete safety analysis with exposure or risk but instead focuses specifically on the potential consequences. The method is suitable for preliminary safety analyses that focus on determining areas of particular interest for further study.

Manure application performed in autumn requires regulation due to the risk of nitrogen (N) leaching during winter. On the other hand, application of manure in spring can pose some practical problems depending on the risk for N immobilization and the difficulty in ploughing heavy clay soils during this time of year. The risk for leaching is likely to differ between different soil texture and manure characteristics. In this study, we sought to estimate the risk for nitrogen leaching depending on the carbon/nitrogen ratio (C/N) of the manure, time for manure application, and soil type. We combined 3-year lysimeter experiments with 2-year field plot experiments and laboratory soil incubations and compared results with those from an empirical model. We compared effects of manure application on two soils (silty clay and loamy sand) and solid manures with different representing C/N ratios. In incubations, only manure with a C/N-ratio below 14 contributed with significant amounts of leachable N during the first months after application. In the lysimeter study, N leaching was unaffected by the timing of the application of the manure with C/N-ratio 18. However, regarding manure with C/N-ratio 10, N leaching was elevated with 10–15 kg N per ha after manure application in October compared to November and March on both soil types. The mineral N analyses from soil profiles in the field experiments showed a similar pattern, however, the increase was higher on the loamy sand compared to the silty clay. The ammonia emissions did not differ between manure types, but were on average 24% of applied NH4-N after application in October when air temperature was on average 12°C compared to only 3% of applied NH4-N in November and March when air temperature was on average 5°C. Similar to lysimeter results, the modelled N leaching was higher the earlier the manure application occurred in autumn. However, the model also predicted increased leaching for the manure with a high C/N-ratio, and a smaller effect on leaching on clay soil. Considering this, the model calculations overestimated the leaching effects from manure with a high C/N-ratio and underestimated the leaching effects on clay soil.

ABSTRACT: Most commercial laying hens suffer from sternum (keel) bone damage including deviations and fractures. X-raying hens, followed by segmenting and assessing the keel bone, is a key to automating the monitoring of keel bone condition. The aim of the current work is to train a deep learning model to segment the keel bone out of whole-body x-ray images. We obtained full-body x-ray images of laying hens (n = 1,051) and manually drew the outline of the keel bone on each image. Using the annotated images, a U-net model was then trained to segment the keel bone. The proposed model was evaluated using 5-fold cross validation. We obtained high segmentation accuracy (Dice coefficients of 0.88–0.90) repeatably over several validation folds. In conclusion, automatic segmentation of the keel bone from full-body x-ray images is possible with good accuracy. Segmentation is a requirement for automated measurements of keel geometry and density, which can subsequently be connected to susceptibility to keel deviations and fractures.

Resilience comprises positive adaptation to stress and has been extensively studied in the context of breast cancer. Nevertheless, specific experiences of breast cancer survivors in relation to resilience are unknown. The aim of this study was to explore the diverse experiences of important resilience aspects in breast cancer survivors. We conducted semi-structured interviews with 25 breast cancer survivors residing in Sweden. We used thematic analysis to analyze the data. We identified three themes relevant for resilience, each containing several subthemes: “I will try to keep the spirits up”: Struggling with agency in the face of uncontrollability, “You know that you are not alone”: Social support and collective survivorship for better and for worse, and “I try to leave that behind me”: Conceptualizing cancer as a closed chapter or a constant. Thus, having agency in relation to one’s thoughts, feelings, treatment, health, and daily functioning, having support from others, and conceptualizing breast cancer as a closed chapter were interpreted as important aspects of resilience.