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Increasing pressure on arable land related to climate change mitigation and adaptation within recent policy frameworks has generated widespread interest in the effect of sustainable agricultural management practices on soil organic carbon (SOC) storage. Current frameworks point to soil microorganisms and their functioning as the key drivers of SOC accrual. This study provides a comprehensive on-farm assessment of changes in SOC formation pathways (physico-chemical and microbial) and the underlying drivers comparing three soil use systems: conservation and conventional farming systems as well as permanently vegetated adjacent reference soils (i.e., field margins) without agricultural land-use.Overall, our results indicated substantial increases in extractable organic carbon (+22 %), microbial biomass carbon (+29 %) and necromass carbon stocks (+11 %) in soils of conservation farming systems as compared to conventional farming systems. Differences between all three soil use systems were strongly pronounced in the surface soil (0–5 cm) and declined in deeper soil layers. Structural equation modelling revealed a varying influence of SOC storage pathways among soil use systems, with microbial-mediated (‘in-vivo’) turnover and direct sorption being the most dominant pathways. Moreover, diversity of crop rotation and tillage intensity were identified as the most important factors influencing extractable organic carbon and carbon-liberating enzyme activity within conservation farming management. Our on-farm approach demonstrates that enhanced bioavailable carbon inputs and reduced soil disturbance are the key drivers for microbially-controlled SOC accrual in arable soils and that conservation farming systems with extended plant coverage and increased crop diversity can substantially advance the restoration of soil health.

Background: Allergic rhinitis (AR) is a highly prevalent disease. We aimed to assess the symptoms that physicians who see patients with AR perceive as the most bothersome in their patients. Methods: We performed a cross-sectional study based on an online questionnaire sent to all members of the Allergic Rhinitis and its Impact on Asthma (ARIA) initiative. The survey included questions on the physicians' perceptions of patients’ AR symptoms as well as of their own AR symptoms. Results: Among 401 respondents, 155 (38.7%) reported having AR. ARIA members reported nasal symptoms to be the most frequent (89.7%) and bothersome (80.0%) symptoms experienced by themselves. Likewise, nasal symptoms were reported by ARIA members as the most frequent (94.8% in members with AR vs 96.0% in members without AR) and bothersome (57.0% in members with AR vs 67.9% in members without AR) in their patients. We found a significant association (p = 0.001) between physicians’ own symptoms and those perceived as the most bothersome in their patients. Conclusion: Physicians perceive nasal symptoms to be the most frequent and the most bothersome symptoms in AR patients. The physicians' personal experiences with AR may influence their perception of patients’ symptoms.

Background: The risk of cardiovascular disease in atopic dermatitis (AD) is not well established. Objectives: Our aims were to evaluate the incidence rate (IR) of venous thromboembolism (VTE) in patients with AD in a population-based cohort study and to assess atherosclerotic cardiovascular disease (ASCVD) risk factors and incidence of malignancies, major adverse cardiovascular events (MACE), and VTE in patients with AD and rheumatoid arthritis (RA) in a nested cohort analysis. Methods: Data from individuals age 12 years or older (nested cohort age ≥ 18 years) from January 1, 2000, to December 31, 2018, were extracted from the Danish National Patient Registry. Patients with AD were age- and sex-matched with 10 healthy controls. ASCVD risk factors included age 65 years or older and history of smoking, coronary artery disease, stroke, deep vein thrombosis (DVT), pulmonary embolism (PE), and malignancy. Results: The population-based cohort comprised 190,751 patients (17,341 patients with AD and 173,410 healthy controls). The IRs per 100 patient-years were comparable between the AD cohort and healthy controls for VTE (0.14 [95% CI = 0.12-0.16] vs 0.11 [95% CI = 0.11-0.12]), DVT (0.08 [95% CI = 0.06-0.09] vs 0.06 [95% CI = 0.06-0.07]), and PE (0.06 [95% CI = 0.05-0.08] vs 0.05 [95% CI = 0.05-0.05]). The IR for VTE was higher in the AD cohort age 65 years or older (0.71 [95% CI = 0.56-0.90]) than in the age-matched controls (0.50 [95% CI = 0.46-0.54]). ASCVD risk factors were more frequent in the patients with RA than in the patients with AD. The IRs for malignancies and MACE were higher with specific ASCVD risk factors. Conclusions: The IRs of cardiovascular events were comparable between the AD cohort and general population. The risk of VTE, malignancy, or MACE was higher with specific ASCVD risk factors, underscoring the need for patient monitoring.

Abstract Over the past decades, there has been a growing interest in long‐term heart rate records, especially from free‐living animals. Largely, this increase is because most of the metabolic activity of tissues is based on oxygen delivery by the heart. Therefore, heart rate has served as a proxy for energy expenditure in animals. However, heart rates or other physiological variables recorded in humans and animals using loggers often contain noise. False measurements are sometimes eliminated by hand or by filters that reject variables based on the shape or frequency of the signal. Occasionally, outliers are rejected because they occur a long distance from genuine data. We introduce an R package, boxfilter, which enables users to eliminate noise based on counting the number of close neighbours inside a gliding window. Depending on the cut‐off value chosen, a focal point with a low proportion of neighbours will be rejected as noise. All three parameters, namely window width and height, as well as the cut‐off value, can be computed automatically. The choice of the clip‐off value beyond which data points are discarded is crucial. The package boxfilter cannot, of course, solve problems caused by completely erroneous measurements. Like the human eye, this filter prefers points that are part of a pattern, such as a dense band, and rejects isolated values. The boxfilter may also be applied to other measures than heart rate that do not change instantaneously, such as body temperature, blood pressure or sleep parameters.

In recent years, we have been observing the phenomenon of an emerging scientific field: "digital transformation research" (DTR). Due to the diversity and complexity of its object of research digital, transformation is not effectively researchable if confined to the boundaries of individual disciplines. In the light of Scientific/Intellectual Movement theory (Frickel and Gross 2005), we wonder how interdisciplinarity could and should be mobilized to further advance the development of the field of DTR. To answer this question, we (a) need to understand how interdisciplinarity is conceived and (b) how it is considered in research practice by researchers in the emerging field. This is important, as scientists' application of interdisciplinarity will highly influence an emerging field, shape its growth, consolidation as well as its academic establishment. We conducted six group discussions with 26 researchers from different disciplines and career levels (PhD students, postdocs, professors). The discussions were studied with a structuring qualitative content analysis. The results reflect the vagueness of the concept of interdisciplinarity. Interdisciplinarity is largely conceived as multidisciplinarity. Further, the interviewees mentioned more challenges than opportunities when it comes to interdisciplinary DTR. The present study widens the scientific understanding about how researchers of different career levels perceive, learn, and practice interdisciplinarity in DTR. It further provides valuable indications of how interdisciplinary research in an emerging field can be profitably shaped for practice.

ObjectiveThe quality of the relationship between persons with dementia and family carers influences health and quality-of-life outcomes. Little is known regarding those at higher risk of experiencing a decline in relationship quality, who could potentially benefit the most from interventions. We aimed to identify these risk profiles and explore the underlying factors.MethodsWe applied a latent profile analysis to relationship quality data from a 1-year follow-up of 350 dyads of persons with dementia and their informal carers from the Actifcare cohort in eight European countries. Assessments included sociodemographic, clinical, functional, psychosocial and quality-of-life measures. Relationship quality was assessed with the Positive Affect Index. A discriminant analysis explored factors influencing the risk profiles.ResultsThere were two relationship quality profiles among persons with dementia (gradually decreasing, 74.0%; low but improving, 26%) and two among carers (steadily poor, 57.7%; consistently positive, 42.3%). The ‘gradually decreasing’ profile (persons with dementia) was related to their levels of dependence and unmet needs, along with carers’ social distress and negative feelings, lower baseline RQ and sense of coherence. The ‘steadily poor’ profile (carers) was influenced by their social distress and negative feelings, lower sense of coherence and perceived social support. These two predominant profiles showed significant decreases in quality-of-life over one year.ConclusionsSpecific profiles of persons with dementia and their carers are at risk of worse relationship quality trajectories. By considering modifiable related factors (e.g., carers’ stress), our findings can help develop tailored, effective interventions.

The assessment of soil health and the determination of carbon stability in soils are current challenges that have gained momentum through initiatives at national as well as international scales. However, inferring universally valid soil health parameters that are directly linked to carbon permanence remains challenging. Our aim was to evaluate the potential of simultaneous thermal analysis (STA) for an improved monitoring of soil health advances in the context of carbon farming strategies. For this purpose, an on-farm comparison of soil health in ten conservation agricultural systems with adjacent conventional farms was performed based on STA and thermal measures were related to key biological and physical indicators for monitoring soil functions. Using an autocorrelation-based approach, we identified independent thermal indicators, revealing that carbon farming efforts predominantly increased labile soil organic matter fractions in the range of 300–400 °C, while thermally more recalcitrant fractions did not respond to farming system transformation. Similarly, most soil health indicators revealed highest correlation with temperature ranges of mass loss of labile organic matter fractions. The relation of STA with commonly used soil health indicators was highest for soil organic carbon (SOC, r=0.971) and total nitrogen (TN, r=0.981). However, also inference on microbial activity parameters such as dimethylsulfoxid reduction, microbial biomass carbon and substrate-induced respiration could be demonstrated with r>0.663. The results thus highlight key temperature ranges of organic matter stability for future soil monitoring tasks of climate change mitigation potentials of carbon farming and related advances in soil health.

Introduction Due to the increasing number of persons with dementia, the need for family and professional support is growing. Counselling services aim to support family dementia caregivers and the use of information and communication technology may improve accessibility to counselling. The effectiveness of technology-based counselling in dementia remains unclear so far. Few randomised controlled trials have been conducted assessing heterogeneous outcomes. Theoretical underpinnings for the development and evaluation of these complex interventions were lacking in most cases. We therefore aim to formulate an initial programme theory of a technology-assisted counselling intervention for family dementia caregivers and to create the data basis for the consensus process of a core outcome set.Methods and analysis The methodological approaches for developing a programme theory and a core outcome set will be integrated. In a scoping review, data on the characteristics, theoretical foundations of counselling interventions and outcomes of clinical studies will be collected. The lifeworld perception of relevant stakeholders on the importance of counselling in family caregiving will be explored in a phenomenological substudy using semistructured interviews. The synthesis of data from the literature review and the qualitative substudy will be performed by developing a logic model. Mechanisms of action and assumed causal relationships are explicated in the elements of programme theory (theory of change, outcomes chain and theory of action). An initial programme theory is then formulated. In addition, a ‘long list’ of outcomes and assessment instruments will be compiled.Ethics and dissemination The ethics committee of the Medical Faculty of the Martin Luther University Halle-Wittenberg approved the study protocol (no. 2023–093).Findings will be reported to participants and the funding organisation and disseminated in peer-reviewed journals and at national and international conferences.Trial registration number The ProCOS (Development and evaluation of a technology-assissted counselling intervention for family caregivers of persons with dementia - Programme theory and preparation of a core outcome set) project is registered with the Core Outcome Measures in Effectiveness Trials initiative (https://www.comet-initiative.org/Studies/Details/2884).

Background: Vagal atrophy is a hallmark of Parkinson’s disease (PD) and has been found to be associated with autonomic dysfunction, while analyses of the vagus nerve (VN) in atypical Parkinsonian syndromes (APS) have not yet been performed. We here investigate the characteristics of the VN in multiple system atrophy (MSA) and progressive supranuclear palsy (PSP) and, in a second step, its potential as a possible biomarker for orthostatic dysregulation. Objectives: The aim was to compare the VN pathology in MSA and PSP with healthy individuals and patients with PD as a differentiating factor and to further analyse the correlation of the VN with clinical parameters and cardiovascular response. Design: We conducted a monocentric, cross-sectional cohort study in 41 APS patients and compared nerve ultrasound (NUS) parameters with 90 PD patients and 39 healthy controls. Methods: In addition to a detailed neurological history and examination, several clinical severity and motor scores were obtained. Autonomic symptoms were reported in the Scales for Outcomes in Parkinson’s Disease – Autonomic questionnaire. Further scores were used to detect other non-motor symptoms, quality of life and cognition. Additionally, we performed a head up tilt test (HUTT) and NUS of the VN. We conducted correlation analyses of the VN cross-sectional area (CSA) with clinical scores and the heart rate and blood pressure variability parameters of the HUTT. Results: The examination demonstrated a high prevalence of abnormal autonomic response in both MSA (90%) and PSP (80%). The VN CSA correlated with spectral parameters of the HUTT, which are associated with sympatho-vagal imbalance. In addition, the CSA of the VN in patients with PD and PSP were significantly smaller than in healthy controls. In MSA, however, there was no marked vagal atrophy in comparison. Conclusion: The occurrence of autonomic dysfunction was high in MSA and PSP, which underlines its impact on these syndromes. Our findings indicate a connection between vagal pathology and autonomic dysfunction and might contribute to a better comprehension of APS. To further evaluate the clinical relevance and the VN as a possible marker of autonomic dysfunction in APS, prospective longitudinal observations are necessary.

Author(s): Dagmar Wilsmann-Theis (corresponding author) [1]; Rhena Funk [1]; Rotraut Mössner [2]; Thomas Bieber [1]; Jörg Wenzel [1] Introduction Psoriasis vulgaris (PV), a chronic inflammatory skin disease, is accompanied by [...], Background: Methotrexate (MTX) in the therapy of psoriasis vulgaris (PV) is a well and long-established treatment option. Aims: To assess the long-term experience of individual patients in the real world with regard to the efficacy and safety of MTX in PV therapy. Patients and Methods: In a retrospective study, MTX as a weekly used monotherapy in PV was examined. Clinical data including the Psoriasis Area Severity Index (PASI), prevalence of psoriatic-arthritis (PsA), Investigator Global Assessment (IGA), laboratory parameters, occurrence of adverse events (AEs), dosing of MTX and characteristics of patients treated for at least 24 months were collected. Results: A total of 55 patients with 247 patient-years under MTX therapy were included. The mean PASI reduction was 51.2 with a significant (P < 0.001) improvement in the skin condition in the first 6 months of treatment, remaining stable thereafter. The mean MTX dose increased from 11.8 ± 3.7 mg to 12.9 ± 3.8 mg in the first year of therapy, with a constant mean dose in the following years. In 247 patient-years, no serious AE was documented. Gastrointestinal side effects or fatigue were commonly detected. The liver parameter alanine aminotransferase/ glutamate-pyruvate transaminase (ALT/GPT) (baseline 35.8 ± 22.0 U/L) increased after 3 years of therapy (42.0 ± 22.4 U/L; P = 0.013) without clinical significance. Conclusion: In this patient collective, MTX in low doses was effective and safe in long-term therapy. The improved skin condition was steady and reached by an unvarying dose. New data showed a better efficacy of MTX in higher doses; however, additional data must be collected on the long-term efficacy and safety of MTX with a higher dose regime. Keywords: Long-term treatment, methotrexate, psoriasis therapy

This paper outlines a method enabling the quick and accurate calculation of semiconductor conduction and switching losses of multilevel voltage-sourced converters. The proposed method needs only the equations defining the voltages and currents of the converter’s stacks of submodules and director switch valves to calculate the overall converter semiconductor losses, thereby accelerating the design cycle of novel converter topologies. For any defined operating point, the method quickly returns the semiconductor losses, making it straightforward to sweep across a converter’s range of operation, enabling quick comparison with other well-known, state-of-the-art converters. The method is derived for any generic multilevel converter, while examples of its application to the hybrid three-level converter, which is composed of both stacks and director switches, validate its accuracy. The method is further applied to the extended-overlap alternate-arm converter, also composed of stacks and director switches, providing further evidence of the method’s consistency. To validate the results, the semiconductor losses obtained from detailed simulations of a 600kV, 1GVA VSC-HVDC converter test system are compared against the proposed method, which demonstrate exceptional agreement. The relative errors in overall semiconductor losses between the simulation and the proposed method for the H3LC and EO-AAC are 0.76% and 0.94%, respectively.

(1) Background: Autoimmune pancreatitis (AIP) is mainly treated with steroids. Using an AIP mouse model, we investigated two potential alternatives, the transforming growth factor-β-activated kinase 1 inhibitor, takinib, and the Janus kinase inhibitor, tofacitinib. (2) Methods: In a multicenter preclinical study, MRL/MpJ mice were injected with polyinosinic/polycytidylic acid (poly I:C) for two weeks to induce AIP. They were then treated for four weeks with either takinib (25, 50, or 75 mg/kg body weight), tofacitinib (5, 10 or 15 mg/kg), dexamethasone (1 mg/kg), or solvent, while the poly I:C injections were continued. The severity of AIP was assessed histopathologically. Flow cytometry was used to examine lymphocyte subtypes in the spleen and mesenteric lymph nodes. The pancreatic gene expression profiles were analyzed by RNA sequencing. (3) Results: Poly I:C-treated mice developed severe AIP with inflammation, destruction of acinar tissue, and fibrosis. Dexamethasone significantly attenuated the disease, while takinib or tofacitinib had no effects. Dexamethasone also antagonized the effects of poly I:C on the relative frequencies of the AIP-associated lymphocyte subtypes CD4/CD69, CD8/CD44high, and CD4/CD25/FoxP3 in the spleen. In the principal component analysis of pancreatic transcriptomics, poly I:C-injected mice treated with tofacitinib, takinib, or solvent clustered together, while untreated and dexamethasone-treated mice formed separate, unique clusters. (4) Conclusions: Dexamethasone effectively reduced AIP severity, while takinib and tofacitinib were ineffective. The unique gene expression profile in dexamethasone-treated mice may provide a basis for identifying new drug targets for AIP treatment.

Cancer persister cells are able to survive otherwise lethal doses of drugs through nongenetic mechanisms, which can lead to cancer regrowth and drug resistance. The broad spectrum of molecular differences observed between persisters and their treatment-naïve counterparts makes it challenging to identify causal mechanisms underlying persistence. Here, we modulate environmental signals to identify cellular mechanisms that promote the emergence of persisters and to pinpoint actionable vulnerabilities that eliminate them. We found that interferon-γ (IFNγ) can induce a pro-persistence signal that can be specifically eliminated by inhibition of type I protein arginine methyltransferase (PRMT) (PRMTi). Mechanistic investigation revealed that signal transducer and activator of transcription 1 (STAT1) is a key component connecting IFNγ's pro-persistence and PRMTi's antipersistence effects, suggesting a previously unknown application of PRMTi to target persisters in settings with high STAT1 expression. Modulating environmental signals can accelerate the identification of mechanisms that promote and eliminate cancer persistence.

Gastrointestinal toxicity is a major concern in the development of drugs. Here, we establish the ability to use murine small and large intestine-derived monolayers to screen drugs for toxicity. As a proof-of-concept, we applied this system to assess gastrointestinal toxicity of ~50 clinically used oncology drugs, encompassing diverse mechanisms of action. Nearly all tested drugs had a deleterious effect on the gut, with increased sensitivity in the small intestine. The identification of differential toxicity between the small and large intestine enabled us to pinpoint differences in drug uptake (antifolates), drug metabolism (cyclophosphamide) and cell signaling (EGFR inhibitors) across the gut. These results highlight an under-appreciated distinction between small and large intestine toxicity and suggest distinct tissue properties important for modulating drug-induced gastrointestinal toxicity. The ability to accurately predict where and how drugs affect the murine gut will accelerate preclinical drug development.

Organic matter can initiate heterogeneous ice nucleation in supercooled water droplets, thereby influencing atmospheric cloud glaciation. Predicting the ice nucleation ability of organic matter-containing cloud droplets is challenging due to the unknown mechanism for templating ice. Here, we observed the presence of nanoparticles in aqueous samples of known ice-nucleating biopolymers cellulose and lignin, as well as in newly identified ice-nucleating biopolymers xylan and laminarin. Using our drop Freezing Ice Nuclei Counter (FINC), we measured the median ice nucleation temperature (T50) of xylan and of laminarin droplets of 2 μl to be −14.2 and −20.0 °C, respectively. Next, we characterized these samples using nanoparticle tracking analysis, and we detected and quantified nanoparticles with mean diameters between 132 and 267 nm. Xylan contained the largest nanoparticles and froze at higher temperatures. Xylan also dictated the freezing in a 1:1:1:1 mixture with cellulose, lignin, laminarin, and xylan. Filtration experiments down to 300 kDa with the xylan sample indicated that the presence of nanoparticles triggered freezing. Overall, only samples with mean diameters above 150 nm froze above −20 °C. Furthermore, we determined the ice-active site densities normalized to particle concentrations, surface area, and mass of the nanoparticles to show that the samples' nucleation site densities are similar to sea spray aerosols and nanometer-sized dust. The identification and characterization of xylan and laminarin as nanometer-sized ice-nucleating substances expands the growing list of organic matter capable of impacting cloud formation and thus climate. [ABSTRACT FROM AUTHOR]

BackgroundAssistive technologies can help people living with dementia maintain their everyday activities. Nevertheless, there is a gap between the potential and use of these materials. Involving future users may help close this gap, but the impact on people with dementia is unclear. ObjectiveWe aimed to determine if user-centered development of smartwatch-based interventions together with people with dementia is feasible. In addition, we evaluated the extent to which user feedback is plausible and therefore helpful for technological improvements. MethodsWe examined the interactions between smartwatches and people with dementia or people with mild cognitive impairment. All participants were prompted to complete 2 tasks (drinking water and a specific cognitive task). Prompts were triggered using a smartphone as a remote control and were repeated up to 3 times if participants failed to complete a task. Overall, 50% (20/40) of the participants received regular prompts, and 50% (20/40) received intensive audiovisual prompts to perform everyday tasks. Participants’ reactions were observed remotely via cameras. User feedback was captured via questionnaires, which included topics like usability, design, usefulness, and concerns. The internal consistency of the subscales was calculated. Plausibility was also checked using qualitative approaches. ResultsParticipants noted their preferences for particular functions and improvements. Patients struggled with rating using the Likert scale; therefore, we assisted them with completing the questionnaire. Usability (mean 78 out of 100, SD 15.22) and usefulness (mean 9 out of 12) were rated high. The smartwatch design was appealing to most participants (31/40, 76%). Only a few participants (6/40, 15%) were concerned about using the watch. Better usability was associated with better cognition. The observed success and self-rated task comprehension were in agreement for most participants (32/40, 80%). In different qualitative analyses, participants’ responses were, in most cases, plausible. Only 8% (3/40) of the participants were completely unaware of their irregular task performance. ConclusionsPeople with dementia can have positive experiences with smartwatches. Most people with dementia provided valuable information. Developing assistive technologies together with people with dementia can help to prioritize the future development of functional and nonfunctional features.