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The Jefferson Scale of Empathy (JSE) is a broadly used instrument developed to measure empathy in the context of health professions education and patient care. Evidence in support of psychometrics of the JSE has been reported in health professions students and practitioners with the exception of osteopathic medical students. This study was designed to examine measurement properties, underlying components, and latent variable structure of the JSE in a nationwide sample of first-year matriculants at U.S. colleges of osteopathic medicine, and to develop a national norm table for the assessment of JSE scores. A web-based survey was administered at the beginning of the 2017-2018 academic year which included the JSE, a scale to detect "good impression" responses, and demographic/background information. Usable surveys were received from 6009 students enrolled in 41 college campuses (median response rate = 92%). The JSE mean score and standard deviation for the sample were 116.54 and 10.85, respectively. Item-total score correlations were positive and statistically significant (p < 0.01), and Cronbach a = 0.82. Significant gender differences were observed on the JSE scores in favor of women. Also, significant differences were found on item scores between top and bottom third scorers on the JSE. Three factors of Perspective Taking, Compassionate Care, and Walking in Patient's Shoes emerged in an exploratory factor analysis by using half of the sample. Results of confirmatory factor analysis with another half of the sample confirmed the 3-factor model. We also developed a national norm table which is the first to assess students' JSE scores against national data.

Abstract The gut microbiome is a significant factor in the pathophysiology of ulcerative colitis (UC), prompting investigations into the use of probiotic therapies to counter gastrointestinal inflammation. However, while much attention has been given to the therapeutic potential of microbes at the species and strain level, the discovery and application of their metabolic products may offer more precise and controlled solutions in battling disease. In this work, we examined the therapeutic potential of indole lactic acid (ILA) to alleviate inflammation in a murine model of colitis. A previously constructed ILA-producing Escherichia coli Nissle 1917 strain (EcN aldh) and its isogenic non-ILA producing counterpart (EcN) were studied in a murine model of Dextran Sodium Sulfate (DSS) induced colitis. The colitic animals suffered from severe colitic symptoms, with no differentiation between the groups in body weight loss and disease activity index. However, three days after cessation of DSS treatment the EcN aldh–treated mice showed signs of reduced intestinal inflammation, as manifested by lower concentrations of fecal lipocalin-2. Additionally, expression analysis of the inflamed tissue revealed distinct effects of the EcN aldh strain on proteins associated with intestinal health, such as TFF3, occludin and IL-1β expression. These results show no impact of EcN or EcN aldh on acute DSS-induced colitis, but suggest that in particular EcN aldh may assist recovery from intestinal inflammation.

Abstract Background The prevalence of autism in Denmark has been increasing, reaching 1.65% among 10-year-old children, and similar trends are seen elsewhere. Although there are several factors associated with autism, including genetic, environmental, and prenatal factors, the molecular etiology of autism is largely unknown. Here, we use untargeted metabolomics to characterize the neonatal metabolome from dried blood spots collected shortly after birth. Methods We analyze the metabolomic profiles of a subset of a large Danish population-based cohort (iPSYCH2015) consisting of over 1400 newborns, who later are diagnosed with autism and matching controls and in two Swedish population-based cohorts comprising over 7000 adult participants. Mass spectrometry analysis was performed by a timsTOF Pro operated in QTOF mode, using data-dependent acquisition. By applying an untargeted metabolomics approach, we could reproducibly measure over 800 metabolite features. Results We detected underlying molecular perturbations across several metabolite classes that precede autism. In particular, the cyclic dipeptide cyclo-leucine-proline (FDR-adjusted p = 0.003) and the carnitine-related 5-aminovaleric acid betaine (5-AVAB) (FDR-adjusted p = 0.03), were associated with an increased probability for autism, independently of known prenatal and genetic risk factors. Analysis of genetic and dietary data in adults revealed that 5-AVAB was associated with increased habitual dietary intake of dairy (FDR-adjusted p

There are few data on Pressurized IntraPeritoneal Aerosol Chemotherapy with cisplatin and doxorubicin (PIPAC C/D) in women with primary unresectable or recurrent platinum-resistant peritoneal metastasis (PM) from ovarian cancer (OC). We evaluated survival, histological and cytological response, Quality of Life (QoL) and toxicity after PIPAC C/D in these patients.

Pressurized Intraperitoneal Aerosol Chemotherapy (PIPAC) is an experimental treatment option in peritoneal metastasis from pancreatic cancer (PM-PC). Aims were to examine mRNA profile of fibrosis due to response after systemic chemotherapy and PIPAC (Regression) compared to treatment-naïve PM-PC and chronic cholecystitis–related peritoneal fibrosis (Controls).

Malignant pleural effusion (MPE) is a common and debilitating condition seen in advanced cancer disease, and life-expectancy is short. Symptoms include pain and severe shortness of breath. Current first-line treatment options include pleural drainage using catheters as well as pleurodesis. However, these treatment modalities are often inefficient and patients need repeated procedures. Pressurized IntraThoracic Aerosol Chemotherapy (PITAC) is a minimally invasive procedure, where antineoplastic agents are nebulized under pressure into the pleural space.

Invasive plant species pose ecological threats to native ecosystems, particularly in areas adjacent to roadways, considering that roadways represent lengthy corridors through which invasive species can propagate. Traditional manual survey methods for monitoring invasive plants are labor-intensive and limited in coverage. This paper introduces a high-speed camera system, named CamAlien, designed to be mounted on vehicles for efficient invasive plant species monitoring along roadways. The camera system captures high-quality images at rapid intervals, to monitor the full roadside when following traffic speed. The system utilizes a global shutter sensor to reduce distortion and geotagging for precise localistion. The camera system makes it possible to collect extensive data sets, which can be used for a digital library of the invasive species and their locations, but also subsequent training of machine learning algorithms for automated species recognition.

Abstract The integrity of the intestinal mucus barrier is crucial for human health, as it serves as the body's first line of defense against pathogens. However, postnatal development of the mucus barrier and interactions between maturity and its ability to adapt to external challenges in neonatal infants remain unclear. In this study, we unveil a distinct developmental trajectory of the mucus barrier in preterm piglets, leading to enhanced mucus microstructure and reduced mucus diffusivity compared to term piglets. Notably, we found that necrotizing enterocolitis (NEC) is associated with increased mucus diffusivity of our large pathogen model compound, establishing a direct link between the NEC condition and the mucus barrier. Furthermore, we observed that addition of sodium decanoate had varying effects on mucus diffusivity depending on maturity and health state of the piglets. These findings demonstrate that regulatory mechanisms governing the neonatal mucosal barrier are highly complex and are influenced by age, maturity, and health conditions. Therefore, our results highlight the need for specific therapeutic strategies tailored to each neonatal period to ensure optimal gut health.

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Introduction Inflammatory bowel disease (IBD), including ulcerative colitis and Crohn’s disease, can be challenging to diagnose, and treatment outcomes are difficult to predict. In the NORDTREAT cohort study, a Nordic prospective multicentre study, we aim to identify novel molecular biomarkers of diagnostic value by assessing the diagnostic test accuracy (cross-sectionally), as well as the prognostic utility when used as prognostic markers in the long-term (cohort study). In the diagnostic test accuracy study, the primary outcome is a successful diagnosis using one or more novel index tests at baseline compared with the ECCO criteria as the reference standard. The composite outcome of the prognostic utility study is ‘severe IBD’ within 52 weeks from inclusion, defined as one or more of the following three events: IBD-related surgery, IBD-related hospitalisation or IBD-related death.Methods and analysis We aim to recruit 800 patients referred on suspicion of IBD to this longitudinal observational study, a collaboration between 11 inclusion sites in Denmark, Iceland, Norway and Sweden. Inclusion will occur from February 2022 until December 2023 with screening and baseline visits for all participants and three outcome visits at weeks 12, 26 and 52 after baseline for IBD-diagnosed patients. Biological material (blood, faeces, biopsies, urine and hair), clinical data and lifestyle information will be collected during these scheduled visits.Ethics and dissemination This study will explore novel biomarkers to improve diagnostic accuracy and prediction of disease progression, thereby improving medical therapy and the quality of life for patients with IBD.The study is approved by the Ethics Committee (DK: S-20200051, v1.4, 16.10.2021; IS: VSNb2021070006/03.01, NO: 193064; SE: DNR 2021-05090) and the Danish Data Protecting Agency (20/54594). Results will be disseminated through peer-reviewed journals, patient associations and presentations at international conferences.Clinical trial registration number NCT05414578; Pre-results.

Abstract Neutrophils play a significant role in sustaining chronic inflammation in Inflammatory Bowel Disease. The intestinal basement membrane acts as a barrier for immunological homeostasis, where the α3 and α4 chains of type IV collagen are expressed on the mucosal surface. We wanted to develop a biomarker reflecting early tissue injury, providing an opportunity for intervention. Two competitive enzyme-linked immunosorbent assays (ELISAs) quantifying human neutrophil elastase (HNE) degraded neo-epitopes of COL4A3 and COL4A4 were developed and investigated in two observational cohorts (n = 161, n = 100). A biomarker of MMP-mediated degradation of COL4A1 (C4M) was used for comparison. In Cohort 1, patients with mild endoscopic ulcerative colitis showed elevated levels of C4A3-HNE compared to those with severe disease. C4M had a strong positive correlation with disease activity. C4A3-HNE/C4M provided superior discrimination between mild and severe endoscopic disease and negatively correlated to disease activity. In Cohort 2, C4A4-HNE and C4A4-HNE/C4M showed similar trends. C4A3-HNE and C4A4-HNE possibly reflect early intestinal tissue injury. Combining the markers with a biomarker of another α-chain of the same collagen provides information on two distinct stages of mucosal damage. These biomarkers may be used to monitor disease flare-up in patients in remission, reducing the need for frequent endoscopic procedures.

Abstract Citrullinated vimentin has been linked to several chronic and autoimmune diseases, but how citrullinated vimentin is associated with disease prevalence and genetic variants in a clinical setting remains unknown. The aim of this study was to obtain a better understanding of the genetic variants and pathologies associated with citrullinated and MMP-degraded vimentin. Patient Registry data, serum samples and genotypes were collected for a total of 4369 Danish post-menopausal women enrolled in the Prospective Epidemiologic and Risk Factor study (PERF). Circulating citrullinated and MMP-degraded vimentin (VICM) was measured. Genome-wide association studies (GWAS) and phenome wide association studies (PheWAS) with levels of VICM were performed. High levels of VICM were significantly associated with the prevalence of chronic pulmonary diseases and death from respiratory and cardiovascular diseases (CVD). GWAS identified 33 single nucleotide polymorphisms (SNPs) with a significant association with VICM. These variants were in the peptidylarginine deiminase 3/4 (PADI3/PADI4) and Complement Factor H (CFH)/KCNT2 gene loci on chromosome 1. Serum levels of VICM, a marker of citrullinated and MMP-degraded vimentin, were associated with chronic pulmonary diseases and genetic variance in PADI3/PADI4 and CFH/ KCNT2. This points to the potential for VICM to be used as an activity marker of both citrullination and inflammation, identifying responders to targeted treatment and patients likely to experience disease progression.

A definition of long-term survival (LTS) in patients with peritoneal metastasis (PM) from gastric cancer (GC), pancreatic cancer (PC) or colorectal cancer (CRC) treated with systemic chemotherapy and pressurized intraperitoneal aerosol chemotherapy (PIPAC) is lacking. We aimed to define LTS and investigate characteristics and treatment response in patients who reached LTS in data from two prospective trials.

To monitor the results of PIPAC directed therapy based on data from the International Society for the Study of the Pleura and Peritoneum (ISSPP) PIPAC database.

Abstract Molecular radiotherapy combines the advantages of systemic administration of highly specific antibodies or peptides and the localized potency of ionizing radiation. A potential target for molecular radiotherapy is the cell surface antigen CD44v6, which is overexpressed in numerous cancers, with limited expression in normal tissues. The aim of the present study was to generate and characterize a panel of human anti-CD44v6 antibodies and identify a suitable candidate for future use in molecular radiotherapy of CD44v6-expressing cancers. Binders were first isolated from large synthetic phage display libraries containing human scFv and Fab antibody fragments. The antibodies were extensively analyzed through in vitro investigations of binding kinetics, affinity, off-target binding, and cell binding. Lead candidates were further subjected to in vivo biodistribution studies in mice bearing anaplastic thyroid cancer xenografts that express high levels of CD44v6. Additionally, antigen-dependent tumor uptake of the lead candidate was verified in additional xenograft models with varying levels of target expression. Interestingly, although only small differences were observed among the top antibody candidates in vitro, significant differences in tumor uptake and retention were uncovered in in vivo experiments. A high-affinity anti-CD44v6 lead drug candidate was identified, mAb UU-40, which exhibited favorable target binding properties and in vivo distribution. In conclusion, a panel of human anti-CD44v6 antibodies was successfully generated and characterized in this study. Through comprehensive evaluation, mAb UU-40 was identified as a promising lead candidate for future molecular radiotherapy of CD44v6-expressing cancers due to its high affinity, excellent target binding properties, and desirable in vivo distribution characteristics.

Invasive plant species pose ecological threats to native ecosystems, particularly in areas adjacent to roadways, considering that roadways represent lengthy corridors through which invasive species can propagate. Traditional manual survey methods for monitoring invasive plants are labor-intensive and limited in coverage. This paper introduces a high-speed camera system, named CamAlien, designed to be mounted on vehicles for efficient invasive plant species monitoring along roadways. The camera system captures high-quality images at rapid intervals, to monitor the full roadside when following traffic speed. The system utilizes a global shutter sensor to reduce distortion and geotagging for precise localistion. The camera system makes it possible to collect extensive data sets, which can be used for a digital library of the invasive species and their locations, but also subsequent training of machine learning algorithms for automated species recognition.

Summary: Adult social care services in England are struggling, and sometimes failing, to supply the quality of care deserved by the most vulnerable people in society. The Care Quality Commission (CQC) is responsible for protecting the recipients of this crucial public service. Their strongest enforcement is the ability to cancel the registration—the legal right to operate—of a health or social care provider. Using novel data from the CQC, we show that the proportion of care home closures due to CQC enforcements, relative to all closures, is increasing. Since 2011, 816 care homes (representing 19 918 registered beds) have been involuntarily closed by the CQC. Our results show that effectively all involuntary closures (804/816) occurred in for-profit care homes. This data emphasises the need for a comprehensive assessment of the impact of for-profit provision on the quality and sustainability of adult social care in England.

Background The U.S. Federal Government has supported the generation of extensive amounts of nanomaterials and related nano Environmental Health and Safety (nanoEHS) data, there is a need to make these data available to stakeholders. With recent efforts, a need for improved interoperability, translation, and sustainability of Federal nanoEHS data in the United States has been realized. The NaKnowBase (NKB) is a relational database containing experimental results generated by the EPA Office of Research and Development (ORD) regarding the actions of engineered nanomaterials on environmental and biological systems. Through the interaction of the National Nanotechnology Initiative’s Nanotechnology Environmental Health Implications (NEHI) Working Group, and the Database and Informatics Interest Group (DIIG), a U.S. Federal nanoEHS Consortium has been formed. Methods The primary goal of this consortium is to establish a “common language” for nanoEHS data that aligns with FAIR data standards. A second goal is to overcome nomenclature issues inherent to nanomaterials data, ultimately allowing data sharing and interoperability across the diverse U.S. Federal nanoEHS data compendium, but also in keeping a level of consistency that will allow interoperability with U.S. and European partners. The most recent version of the EPA NaKnowBase (NKB) has been implemented for semantic integration. Computational code has been developed to use each NKB record as input, modify and filter table data, and subsequently output each modified record to a Research Description Framework (RDF). To improve the accuracy and efficiency of this process the EPA has created the OntoSearcher tool. This tool partially automates the ontology mapping process, thereby reducing onerous manual curation. Conclusions Here we describe the efforts of the US EPA in promoting FAIR data standards for Federal nanoEHS data through semantic integration, as well as in the development of NAMs (computational tools) to facilitate these improvements for nanoEHS data at the Federal partner level.

Objectives An increased risk of stroke has been reported among patients with COVID-19 caused by SARS-CoV-2. We aimed to investigate the nationwide prevalence of SARS-CoV-2 among patients with acute ischaemic stroke and to study the impact on stroke severity, quality of care and mortality on an individual patient level.Design This was a nationwide register-based cohort study.Setting We used data from several Danish registers which were linked at an individual patient level using the unique civil registration number assigned to all Danish citizens. Patients were identified from the Danish Stroke Registry and information on SARS-CoV-2 infection status was collected from the Danish National COVID-19 Registry. Concurrent SARS-CoV-2 infection was defined as a positive PCR test within 31 days prior to, and 1 day after, stroke admission. Information on comorbidity was collected from the Danish National Patient Registry and information on vital status was collected from the Danish Civil Registration System.Participants A total of 11 502 patients admitted with acute ischaemic stroke from 10 March 2020 to 31 May 2021 were included in the study.Results Among the included patients, the majority (84.6%) were tested for SARS-CoV-2, but only 68 had a positive test. These patients were more prone to have atrial fibrillation and were more often treated with reperfusion therapy. They had a significantly increased risk of severe stroke (adjusted relative risk (aRR) 1.93, 95% CI: 1.22 to 3.04) and a significantly increased 30-day mortality risk (aRR 2.29, 95% CI: 1.19 to 4.39). There was no difference in the proportion of patients fulfilling relevant performance measures on quality of care.Conclusion In this nationwide study, only 0.6% of patients with acute ischaemic stroke were tested positive for a concurrent SARS-CoV-2 infection. The patients with SARS-CoV-2 presented with more severe strokes.

Objectives To explore the associations of long-term exposure to air pollution with onset of all human health conditions.Design Prospective phenome-wide association study.Setting Denmark.Participants All Danish residents aged ≥30 years on 1 January 2000 were included (N=3 323 612). After exclusion of individuals with missing geocoded residential addresses, 3 111 988 participants were available for the statistical analyses.Main outcome measure First registered diagnosis of every health condition according to the International Classification of Diseases, 10th revision, from 2000 to 2017.Results Long-term exposure to fine particulate matter (PM2.5) and nitrogen dioxide (NO2) were both positively associated with the onset of more than 700 health conditions (ie, >80% of the registered health conditions) after correction for multiple testing, while the remaining associations were inverse or insignificant. As regards the most common health conditions, PM2.5 and NO2 were strongest positively associated with chronic obstructive pulmonary disease (PM2.5: HR 1.06 (95% CI 1.05 to 1.07) per 1 IQR increase in exposure level; NO2: 1.14 (95% CI 1.12 to 1.15)), type 2 diabetes (PM2.5: 1.06 (95% CI 1.05 to 1.06); NO2: 1.12 (95% CI 1.10 to 1.13)) and ischaemic heart disease (PM2.5: 1.05 (95% CI 1.04 to 1.05); NO2: 1.11 (95% CI 1.09 to 1.12)). Furthermore, PM2.5 and NO2 were both positively associated with so far unexplored, but highly prevalent outcomes relevant to public health, including senile cataract, hearing loss and urinary tract infection.Conclusions The findings of this study suggest that air pollution has a more extensive impact on human health than previously known. However, as this study is the first of its kind to investigate the associations of long-term exposure to air pollution with onset of all human health conditions, further research is needed to replicate the study findings.

Abstract Thyroid cancer is the most common endocrine malignancy, affecting nearly 600,000 new patients worldwide. Treatment with the BRAF inhibitor sorafenib partially prolongs progression-free survival in thyroid cancer patients, but fails to improve overall survival. This study examines enhancing sorafenib efficacy by combination therapy with the novel HSP90 inhibitor onalespib. In vitro efficacy of sorafenib and onalespib monotherapy as well as in combination was assessed in papillary (PTC) and anaplastic (ATC) thyroid cancer cells using cell viability and colony formation assays. Migration potential was studied in wound healing assays. The in vivo efficacy of sorafenib and onalespib therapy was evaluated in mice bearing BHT-101 xenografts. Sorafenib in combination with onalespib significantly inhibited PTC and ATC cell proliferation, decreased metabolic activity and cancer cell migration. In addition, the drug combination approach significantly inhibited tumor growth in the xenograft model and prolonged the median survival. Our results suggest that combination therapy with sorafenib and onalespib could be used as a new therapeutic approach in the treatment of thyroid cancer, significantly improving the results obtained with sorafenib as monotherapy. This approach has the potential to reduce treatment adaptation while at the same time providing therapeutic anti-cancer benefits such as reducing tumor growth and metastatic potential.

Introduction: Communities who have fled torture and persecution in their home countries can find it difficult to access services in new cultural settings. Past research has shown that it is helpful to provide cultural bridging services to form a connection between locally-trained professionals and newly relocated communities. Method: This article presents, from a practitioner’s perspective, a case example of cultural bridging involving a pilot programme to train torture survivors and former refugees to become Cross-Cultural Facilitators supporting mental health services for displaced communities. Results: The Cross-Cultural Facilitator role has become an integral part of the case example agency’s services. Internal agency reviews of the Cross-Cultural Facilitators’ work shows that they have been continuing to operate successfully through challenging times, including the many societal disruptions and stressors entailed in the Covid-19 pandemic. The agency has also gathered notable anecdotal evidence that the pilot training programme has been positively impactful and supportive not only for the Cross-Cultural Facilitators but for the communities they serve. Discussion: Healthcare workers and civil society organisations have an important role to play in supporting survivors to engage in this form of cultural facilitation aimed at addressing the consequences of traumatic experiences at a community level. In doing so, they must balance efforts to empower survivors and former refugees to participate as agents of change with a duty of care not to push individuals into roles or settings that may diminish their own wellbeing.

Abstract The upper limit for partial hepatectomy (PH) in rats is 90%, which is associated with an increased risk of post-hepatectomy liver failure (PHLF), correlating with high mortality. Sixty-eight rats were randomized to 90% PH, sham operation, or no surgery. Further block randomization was performed to determine the time of euthanasia, whether 12, 24, or 48 h after surgery. A general distress score (GDS) was calculated to distinguish between rats with reversible (GDS

Abstract Background Idiopathic non-clonal cytopenia (ICUS) and clonal cytopenia (CCUS) are common in the elderly population. While these entities have similar clinical presentations with peripheral blood cytopenia and less than 10% bone marrow dysplasia, their malignant potential is different and the biological relationship between these disorders and myeloid neoplasms such as myelodysplastic syndrome (MDS) is not fully understood. Aberrant DNA methylation has previously been described to play a vital role in MDS and acute myeloid leukemia (AML) pathogenesis. In addition, obesity confers a poorer prognosis in MDS with inferior overall survival and a higher rate of AML transformation. In this study, we measured DNA methylation of the promoter for the obesity-regulated gene LEP, encoding leptin, in hematopoietic cells from ICUS, CCUS and MDS patients and healthy controls. We investigated whether LEP promoter methylation is an early event in the development of myeloid neoplasms and whether it is associated with clinical outcome. Results We found that blood cells of patients with ICUS, CCUS and MDS all have a significantly hypermethylated LEP promoter compared to healthy controls and that LEP hypermethylation is associated with anemia, increased bone marrow blast percentage, and lower plasma leptin levels. MDS patients with a high LEP promoter methylation have a higher risk of progression, shorter progression-free survival, and inferior overall survival. Furthermore, LEP promoter methylation was an independent risk factor for the progression of MDS in a multivariate Cox regression analysis. Conclusion In conclusion, hypermethylation of the LEP promoter is an early and frequent event in myeloid neoplasms and is associated with a worse prognosis.

Background Pulmonary radioaerosol mucociliary clearance (PRMC) is a reliable method for assessing in vivo whole lung mucociliary clearance and has been used at the Danish PCD Centre as a supplementary diagnostic test for primary ciliary dyskinesia (PCD) for more than two decades. This study aimed to investigate genotype-specific differences in PRMC measures and evaluate its potential as an outcome parameter. Material and methods The study was based on a retrospective analysis of PRMC tests performed over a 24-year period (1999–2022) in individuals referred for PCD work-up and included patients with genetically confirmed PCD and non-PCD controls. Patients inhaled nebulised technetium-albumin-colloid before static and dynamic imaging was obtained. Three parameters were evaluated: 1-h lung retention (LR1), tracheobronchial velocity (TBV) and cough clearance. Results The study included 69 patients from the Danish PCD cohort, representing 26 different PCD genotypes. Mucociliary clearance by PRMC was consistently absent in most PCD patients, regardless of genotype. However, a single patient with a CCDC103 mutation, preserved ciliary function and normal nasal nitric oxide levels exhibited normal LR1 and low TBV values. Voluntary cough significantly improved clearance, with a median improvement of 11% (interquartile range 4–24%). Conclusion Absent mucociliary clearance by PRMC should be expected in PCD regardless of genotype but residual ciliary function could result in measurable PRMC. This indicates a potential for PRMC to detect improvements in ciliary function if this can be restored. Addressing involuntary cough and peripheral deposition of radioaerosol is important if PRMC is to be used as an outcome measure in future clinical PCD trials.

Background: An association between diverticulitis and colon cancer has been proposed. The evidence is conflicting, and the guidelines differ regarding recommended follow-up with colonoscopy after an episode of diverticulitis. To guide regimes for follow-up, this study aimed to investigate if patients with diverticulitis have an increased risk of colon cancer. Methods: This study is reported according to the RECORD statement. We performed a cohort study with linked data from nationwide Danish registers. The inclusion period was 1997–2009, and the complete study period was 1995–2013. The primary outcome was the risk of developing colon cancer estimated using a Cox regression analysis with time-varying covariates. We performed a sensitivity analysis on a cohort of people with prior colonoscopies, comparing the risk of colon cancer between the diverticulitis group and the control group. Results: We included 29,173 adult males and females with diverticulitis and 145,865 controls matched for sex and age. The incidence proportion of colon cancer was 2.1% (95% confidence interval (CI) 1.9–2.3) in the diverticulitis group and 1.5% (95% CI 1.4–1.5) in the matched control group (hazard ratio 1.6; 95% CI 1.5–1.8). The risk of having a colon cancer diagnosis was significantly increased in the first six months after inclusion (hazard ratio 1.7; 95% CI 1.5–1.8), and hereafter there was a lower risk in the diverticulitis group compared with controls (hazard ratio 0.8; 95% CI 0.7–0.9). This protective effect lasted eight years. The increased risk of colon cancer during the first six months after diverticulitis was also found in the cohort with prior colonoscopies. Conclusions: The risk of a colon cancer diagnosis was significantly increased for patients with diverticulitis 0–6 months after the diagnosis of diverticulitis. Hereafter, we found a protective effect of diverticulitis until eight years later, possibly due to a screening effect. We recommend a follow-up colonoscopy after the first diagnosis of diverticulitis.

The objective was to develop an interdisciplinary weaning protocol (IWP) for patients with tracheostomy tubes due to acquired brain injury, and to effect evaluate implementation of the IWP on decannulation rates and weaning duration. An expert panel completed a literature review in 2018 to identify essential criteria in the weaning process. Based on consensus and availability in clinical practice, criteria for guiding the weaning process were included in the protocol. Using the IWP, dysphagia is graded as either severe, moderate, or mild. The weaning process is guided through a protocol which specified the daily duration of cuff deflation until decannulation, along with recommendations for treatment and rehabilitation interventions. Data from 337 patient records (161 before and 176 after implementation) were included for effect evaluation. Decannulation rate during hospitalization was unchanged at 91% vs. 90% before and after implementation (decannulation rate at 60 days was 68% vs. 74%). After implementation, the weaning duration had decreased compared to before implementation, hazard ratio 1.309 (95%CI: 1.013; 1.693), without any increased risk of tube-reinsertion or pneumonia. Furthermore, a tendency toward decreased length of stay was seen with median 102 days (IQR: 73–138) and median 90 days (IQR: 58–119) (p = 0.061) before and after implementation, respectively. Scientific debate on weaning protocols for tracheostomy tubes are encouraged.

Management of deep-sea fisheries in areas beyond national jurisdiction by Regional Fisheries Management Organizations/Arrangements (RFMO/As) requires identification of areas with Vulnerable Marine Ecosystems (VMEs). Currently, fisheries data, including trawl and longline bycatch data, are used by many RFMO/As to inform the identification of VMEs. However, the collection of such data creates impacts and there is a need to collect non-invasive data for VME identification and monitoring purposes. Imagery data from scientific surveys satisfies this requirement, but there currently is no established framework for identifying VMEs from images. Thus, the goal of this study was to bring together a large international team to determine current VME assessment protocols and establish preliminary global consensus guidelines for identifying VMEs from images. An initial assessment showed a lack of consistency among RFMO/A regions regarding what is considered a VME indicator taxon, and hence variability in how VMEs might be defined. In certain cases, experts agreed that a VME could be identified from a single image, most often in areas of scleractinian reefs, dense octocoral gardens, multiple VME species’ co-occurrence, and chemosynthetic ecosystems. A decision flow chart is presented that gives practical interpretation of the FAO criteria for single images. To further evaluate steps of the flow chart related to density, data were compiled to assess whether scientists perceived similar density thresholds across regions. The range of observed densities and the density values considered to be VMEs varied considerably by taxon, but in many cases, there was a statistical difference in what experts considered to be a VME compared to images not considered a VME. Further work is required to develop an areal extent index, to include a measure of confidence, and to increase our understanding of what levels of density and diversity correspond to key ecosystem functions for VME indicator taxa. Based on our results, the following recommendations are made: 1. There is a need to establish a global consensus on which taxa are VME indicators. 2. RFMO/As should consider adopting guidelines that use imagery surveys as an alternative (or complement) to using bycatch and trawl surveys for designating VMEs. 3. Imagery surveys should also be included in Impact Assessments. And 4. All industries that impact the seafloor, not just fisheries, should use imagery surveys to detect and identify VMEs.

Background Primary ciliary dyskinesia (PCD) is an inherited disorder in which dyskinetic cilia cause impaired mucociliary clearance of upper and lower airways. Airway ciliary movement can be indirectly tested in vivo after administration of a radiolabelled tracer to the lower airways for assessment of pulmonary mucociliary clearance or to the nose for assessing nasal mucociliary clearance (NMC). With this study, we investigated NMC as a quantifiable study outcome parameter in patients with PCD. Material and methods This single centre proof-of-concept study on NMC velocity investigated patients with PCD across different genotypes and nasal nitric oxide (nasal NO) levels. Healthy controls were used for comparison. NMC was determined as velocity in mm·min−1 of a nasally applied 99mTc-albumin colloid tracer. Using a gamma camera, repeated dynamic series of images each lasting 30 s were acquired during a 10-minute period and digitally stored. Results NMC velocity was investigated in seven patients with PCD (aged 9–31 years) and five adult healthy controls. Mean NMC velocity in healthy controls (8.5 mm·min−1) was significantly higher compared with people with PCD (0.00 mm·min−1, p

Introduction Persistent psychosocial problems in people with lower-limb amputation due to vascular aetiology indicate a great need for long-lasting holistic rehabilitation. An in-depth understanding of the psychosocial problems is essential for the guidance of health professionals in meeting and normalising patients’ experiences and emotions. Furthermore, identifying the psychological problems may help develop effective rehabilitation and counselling programmes. This meta-aggregation study aims to explore the psychosocial perspectives of individuals who have undergone a major lower-limb amputation due to vascular aetiology during the post-discharge rehabilitation phase.Methods and analysis A systematic meta-aggregation study will be performed to identify full-text, peer-reviewed journal articles reporting on patients’ psychosocial perspectives on major lower-limb amputation due to vascular aetiology from post-discharge to several years afterward. The databases Embase, CINAHL Ultimate, APA PsycInfo, PubMed and Scopus will be searched with no limitations regarding the publication year. Studies that satisfy the eligibility criteria will be critically appraised using an acknowledged checklist and synthesised using the Joanna Briggs Institute three-phase approach for the synthesis of meta-aggregation studies. The GRADE-CERQual (Grading of Recommendations Assessment, Development and Evaluation- Confidence in Evidence from Reviews of Qualitative research) tool will be used to determine the level of confidence in the qualitative evidence, and the PRISMA (Preferred Reporting Items for Systematic Review and Meta-Analysis) reporting guidelines will be followed throughout the review process.Ethics and dissemination Ethical approval is not required for the study, as the review is built on pre-existing available data in the literature. Findings from the review will be disseminated through publication in a peer-review journal.PROSPERO registration number CRD42022377114.

Abstract Health care expenditure in the last year of life makes up a high proportion of medical spending across the world. This is often framed as waste, but this framing is only meaningful if it is known at the time of treatment who will go on to die. We analyze the distribution of health care spending by predicted mortality for the Danish population over age 65 over the year 2016, with one-year mortality predicted by a machine learning model based on sociodemographics and use of health care services for the two years before entry into follow-up. While a reasonably good model can be built, extremely few individuals have high ex-ante probability of dying, and those with a predicted mortality of more than 50% account for only 2.8% of total health care expenditure. Decedents outspent survivors by a factor of more than ten, but compared to survivors with similar predicted mortality they spent only 2.5 times as much. Our results suggest that while spending in the last year of life is indeed high, this is nearly all spent in situations where there is a reasonable expectation that the patient can survive.

Abstract Cognitive functions of individuals with psychiatric disorders differ from that of the general population. Such cognitive differences often manifest early in life as differential school performance and have a strong genetic basis. Here we measured genetic predictors of school performance in 30,982 individuals in English, Danish and mathematics via a genome-wide association study (GWAS) and studied their relationship with risk for six major psychiatric disorders. When decomposing the school performance into math and language-specific performances, we observed phenotypically and genetically a strong negative correlation between math performance and risk for most psychiatric disorders. But language performance correlated positively with risk for certain disorders, especially schizophrenia, which we replicate in an independent sample (n = 4547). We also found that the genetic variants relating to increased risk for schizophrenia and better language performance are overrepresented in individuals involved in creative professions (n = 2953) compared to the general population (n = 164,622). The findings together suggest that language ability, creativity and psychopathology might stem from overlapping genetic roots.

Abstract Heterogeneity of COVID-19 manifestations in human population is vast, for reasons unknown. Cotton rats are a clinically relevant small animal model of human respiratory viral infections. Here, we demonstrate for the first time that SARS-CoV-2 infection in cotton rats affects multiple organs and systems, targeting species- and age-specific biological processes. Infection of S. fulviventer, which developed a neutralizing antibody response and were more susceptible to SARS-CoV-2 replication in the upper respiratory tract, was accompanied by hyperplasia of lacrimal drainage-associated lymphoid tissue (LDALT), a first known report of mucosa-associated lymphoid tissue activation at the portal of SARS-CoV-2 entry. Although less permissive to viral replication, S. hispidus showed hyperplasia of bone marrow in the facial bones and increased pulmonary thrombosis in aged males. Augmentation of these features by SARS-CoV-2 infection suggests a virus-induced breach in regulatory mechanisms which could be devastating for people of all ages with underlying conditions and in particular for elderly with a multitude of ongoing disorders.

Abstract Aspergillus terreus is well-known for lovastatin and itaconic acid production with biomedical and commercial importance. The mechanisms of metabolite formation have been extensively studied to improve their yield through genetic engineering. However, the combined repertoire of carbohydrate-active enzymes (CAZymes), cytochrome P450s (CYP) enzymes, and secondary metabolites (SMs) in the different A. terreus strains has not been well studied yet, especially with respect to the presence of biosynthetic gene clusters (BGCs). Here we present a 30 Mb whole genome sequence of A. terreus ATCC 20541 in which we predicted 10,410 protein-coding genes. We compared the CAZymes, CYPs enzyme, and SMs across eleven A. terreus strains, and the results indicate that all strains have rich pectin degradation enzyme and CYP52 families. The lovastatin BGC of lovI was linked with lovF in A. terreus ATCC 20541, and the phenomenon was not found in the other strains. A. terreus ATCC 20541 lacked a non-ribosomal peptide synthetase (AnaPS) participating in acetylaszonalenin production, which was a conserved protein in the ten other strains. Our results present a comprehensive analysis of CAZymes, CYPs enzyme, and SM diversities in A. terreus strains and will facilitate further research in the function of BGCs associated with valuable SMs.

Abstract Improvement of feed efficiency (FE) in pigs is an important milestone in order to reduce the economic and environmental impact of pig production. The goal of finding biomarkers for FE has persisted for decades. However, due to the complexity of the FE trait, these goals have still not been met. Here, we search for quantitative trait loci (QTL), candidate genes, and biological pathways associated with FE using both genotype and RNA-seq data. We obtained genotype and colon epithelium RNA-seq data for 375 and 96 pigs, respectively. In total, a genome-wide association study (GWAS) and differential expression (DE) analysis led to detection of three QTL on SSC9 and 17 DE-genes associated with FE. Possible intersection points between genes located in QTL and DE-genes were found on levels of transcription factor-target interaction. Moreover, cis-eQTL analysis revealed associations between genotype and expression levels of three DE-genes and three genes located in the GWAS QTLs, which may establish the connection between genotype and phenotype through DE. Finally, single nucleotide polymorphism calling using RNA-seq data for genes located in GWAS QTLs revealed 53 polymorphisms of which eleven were missense variants.

Abstract It remains unclear whether the rate of fetal death has changed during the COVID-19 pandemic. We assessed the impact of COVID-19 mitigation measures on fetal death in Sweden (449,347 births), Denmark (290,857 pregnancies) and Norway (261,057 pregnancies) using robust population-based registry data. We used Cox regression to assess the impact of the implementation of pandemic mitigation measures on March 12th, 2020, on miscarriage (fetal loss before gestational week 22) and stillbirth (fetal loss after gestational week 22). A total of 11% of 551,914 pregnancies in Denmark and Norway ended in miscarriage, while the proportion of stillbirths among 937,174 births across the three countries was 0.3%. There was no difference in the risk of fetal death during the year following pandemic mitigation measures. For miscarriage, the combined hazard ratio (HR) for Norway and Denmark was 1.01 (95% CI 0.98, 1.03), and for stillbirth, the combined HR for all three countries was 0.99 (95% CI 0.89, 1.09). We observed a slightly decreased risk of miscarriage during the first 4 months, with an HR of 0.94 (95% CI 0.90, 0.99) after lockdown. In conclusion, the risk of fetal death did not change after the implementation of COVID-19 pandemic mitigation measures in the three Scandinavian countries.

Abstract During the past 30 years, a mortality gap developed between Lolland-Falster (the rural-provincial southeastern part) and the rest of Denmark. A main driver was selective in-migration of Danes with a high risk of death, especially of working-ages. In the present study, we determined the role of economic status in this selective in-migration. We used individual-level data from the Central Population Register and data on income source; self- or publicly supported. The study population included people aged 30–64 and living in Denmark at any time between 1992 and 2018. Mortality rate ratios (MRR) were calculated using Poisson regression for three time-periods: 1992–1999, 2000–2009 and 2010–2018. Two in five in-migrants to Lolland-Falster were people on public support. In 2010–2018, they had an MRR of 8.71 (95% confidence interval (CI): 8.05–9.42) compared with self-supported people, and an MRR of 1.49 (95% CI: 1.38–1.61) compared with publicly supported people elsewhere in Denmark. In-migration of working-aged people on public support was a main contributor to the excess mortality in Lolland-Falster as compared with the rest of Denmark. To understand urban–rural differences in health, population movements and national income patterns are important to take into account.

Introduction Atrial fibrillation (AF) is the most common postoperative complication after surgical aortic valve replacement (SAVR) and occurs in up to 50% of the patients. Development of postoperative AF (POAF) is associated with a 2–3 fold increased risk of adverse events, including stroke, myocardial infarction and death.Several studies have implied that prophylactic Atorvastatin therapy could prevent POAF in patients undergoing coronary artery bypass graft. These studies suggest that Atorvastatin has rapid and significant pleiotropic actions that reduce the risk of POAF. However, prophylactic treatment with statins has yet to be understood in SAVR. The aim of this study is to investigate whether prophylactic administration of torvastatin reduces POAF in patients undergoing SAVR.Methods and analysis In this investigator-initiated, prospective, parallel-group, randomised, double-blind, placebo-controlled single-centre trial, 266 patients undergoing elective solitary SAVR with bioprosthetic valve, with no prior history of AF, and statin-naïve will be randomised (1:1) to treatment with Atorvastatin (80 mg once daily) or matching placebo for 1–2 weeks prior to and 30 days after surgery. The primary endpoint is POAF defined as an episode of irregular RR-intervals without a traceable p-wave of at least 30 s duration. After discharge and until day 30 after surgery, POAF will be documented by either rhythm strip or 12-lead ECG.Ethics and dissemination Protocol approval has been obtained from the Regional Scientific Ethical Committee for Southern Denmark (S-20210159), The Danish Medicines Agency (2021103821) and the Data Protection Agency (21/65621).The trial is conducted in accordance with the Declaration of Helsinki, the ICH-GCP (International Conference on Harmonisation Good Clinical Practice) guidelines and the legal regulations of Denmark. Study findings will be shared via peer-reviewed journal publication and conference presentations.Trial registration number NCT05076019.

Neutrophil activation can release neutrophil extracellular traps (NETs) in acute inflammation. NETs result in the release of human neutrophil elastase (HNE) and calprotectin, where the former can degrade the latter and generate protein fragments associated with neutrophil activity. We investigated this in chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis (IPF) using the novel neoepitope biomarker CPa9-HNE, quantifying a specific HNE-mediated fragment of calprotectin in serum. CPa9-HNE was compared to total calprotectin. Initially, CPa9-HNE was measured in healthy (n = 39), COPD (n = 67), and IPF (n = 16) serum using a neoepitope-specific competitive enzyme-linked immunosorbent assay. Then, a head-to-head comparison of CPa9-HNE and total calprotectin, a non-neoepitope, was conducted in healthy (n = 19), COPD (n = 25), and IPF (n = 19) participants. CPa9-HNE levels were significantly increased in COPD (p < 0.0001) and IPF subjects (p = 0.0001) when compared to healthy participants. Additionally, CPa9-HNE distinguished IPF (p < 0.0001) and COPD (p < 0.0001) from healthy participants more effectively than total calprotectin for IPF (p = 0.0051) and COPD (p = 0.0069). Here, CPa9-HNE also distinguished IPF from COPD (p = 0.045) participants, which was not observed for total calprotectin (p = 0.98). Neutrophil activity was significantly higher, as assessed via serum CPa9-HNE, for COPD and IPF compared to healthy participants. Additionally, CPa9-HNE exceeded the ability of non-neoepitope calprotectin serum measurements to separate healthy from lung disease and even COPD from IPF participants, indicating that neutrophil activity is essential for both COPD and IPF.

Chronic inflammation in inflammatory bowel disease (IBD) triggers significant extracellular matrix remodeling, including elastin remodeling, leading to severe clinical complications. Novel methods to assess intestinal tissue destruction may act as surrogate markers of endoscopic disease activity, relieving patients of invasive endoscopy. We explored the noninvasive blood-based biomarkers ELP-3 and ELM-12, measuring elastin degradation in IBD. In a study involving 104 Crohn’s disease (CD), 39 ulcerative colitis (UC), and 29 healthy donors, we assessed these biomarkers’ association with endoscopic and clinical disease activity using ELISA. Patients were evaluated based on the SES-CD and CDAI for CD patients and modified MES and partial Mayo for UC patients. ELP-3 and ELM-12 were elevated in patients with IBD. Discerning CD patients in endoscopic remission and mild from moderate to severe, ELP-3 provided an AUC of 0.69 and ELM-12 an AUC of 0.73. The ELP-3 biomarker was associated with UC patients and provided the highest diagnostic power of 0.87 for remission vs. active clinical disease. The data suggest an association of ELP-3 with active CD and ELM-12 with endoscopic remission in CD patients. Additionally, ELP-3 could identify UC patients with active clinical disease from patients in remission. The noninvasive biomarkers ELP-3 and ELM-12 could be potential surrogate biomarkers of elastin degradation and endoscopic and clinical disease markers.

Abstract The parasitic mite Varroa destructor is a leading cause of mortality for Western honey bee (Apis mellifera) colonies around the globe. We sought to confirm the presence and likely introduction of only one V. destructor haplotype in New Zealand, and describe the viral community within both V. destructor mites and the bees that they parasitise. A 1232 bp fragment from mitochondrial gene regions suggests the likely introduction of only one V. destructor haplotype to New Zealand. Seventeen viruses were found in bees. The most prevalent and abundant was the Deformed wing virus A (DWV-A) strain, which explained 95.0% of the variation in the viral community of bees. Black queen cell virus, Sacbrood virus, and Varroa destructor virus 2 (VDV-2) played secondary roles. DWV-B and the Israeli acute paralysis virus appeared absent from New Zealand. Ten viruses were observed in V. destructor, with > 99.9% of viral reads from DWV-A and VDV-2. Substantially more variation in viral loads was observed in bees compared to mites. Where high levels of VDV-2 occurred in mites, reduced DWV-A occurred in both the mites and the bees co-occurring within the same hive. Where there were high loads of DWV-A in mites, there were typically high viral loads in bees.

Abstract Objective To introduce salvage prostatectomy in Denmark. Prior to this, no national curative treatment for recurrent prostate cancer following radiation therapy existed in Denmark. This pilot study represent our initial experiences and the feasibility of performing salvage robot-assisted radical prostatectomy for true local, high-risk recurrence after initial therapy with external beam radiation for high-risk prostate cancer. Results Five patients underwent sRARP between April 2020 and July 2021. All patients were discharged within 48 h and no major complications were observed within 3 months. All patients had unmeasurable PSA (

Purpose The Danish Pathology Life Course (PATHOLIFE) cohort was established to facilitate epidemiological research relating histological and cytological features extracted from patient tissue specimens to the rich life course histories, including both prior and future register data, of the entire Danish population. Research results may increase quality of diagnosis, prognosis and stratification of patient subtypes, possibly identifying novel routes of treatment.Participants All Danish residents from 1 January 1986 to 31 December 2019, totalling 8 593 421 individuals.Findings to date We provide an overview of the subpopulation of Danish residents who have had a tissue specimen investigated within the Danish healthcare system, including both the primary sector and hospitals. We demonstrate heterogeneity in sociodemographic and prognostic factors between the general Danish population and the above mentioned subpopulation, and also between the general Danish population and subpopulations of patients with tissue specimens from selected anatomical sites. Results demonstrate the potential of the PATHOLIFE cohort for integrating many different factors into identification and selection of the most valuable tissue blocks for studies of specific diseases and their progression. Broadly, we find that living with a partner, having higher education and income associates with having a biopsy overall. However, this association varies across different tissue and patient types, which also display differences in time-to-death and causes of death.Future plans The PATHOLIFE cohort may be used to study specified patient groups and link health related events from several national health registries, and to sample patient groups, for which stored tissue specimens are available for further research investigations. The PATHOLIFE cohort thereby provides a unique opportunity to prospectively follow people that were characterised and sampled in the past.

The use of electronic nicotine delivery systems (ENDS) is increasing among young adults. However, there are few studies regarding predictors of ENDS initiation in tobacco-naive young adults. Identifying the risk and protective factors of ENDS initiation that are specific to tobacco-naive young adults will enable the creation of targeted policies and prevention programs. This study used machine learning (ML) to create predictive models, identify risk and protective factors for ENDS initiation for tobacco-naive young adults, and the relationship between these predictors and the prediction of ENDS initiation. We used nationally representative data of tobacco-naive young adults in the U.S drawn from the Population Assessment of Tobacco and Health (PATH) longitudinal cohort survey. Respondents were young adults (18–24 years) who had never used any tobacco products in Wave 4 and who completed Waves 4 and 5 interviews. ML techniques were used to create models and determine predictors at 1-year follow-up from Wave 4 data. Among the 2,746 tobacco-naive young adults at baseline, 309 initiated ENDS use at 1-year follow-up. The top five prospective predictors of ENDS initiation were susceptibility to ENDS, increased days of physical exercise specifically designed to strengthen muscles, frequency of social media use, marijuana use and susceptibility to cigarettes. This study identified previously unreported and emerging predictors of ENDS initiation that warrant further investigation and provided comprehensive information on the predictors of ENDS initiation. Furthermore, this study showed that ML is a promising technique that can aid ENDS monitoring and prevention programs.

Objectives To investigate the association between prestroke physical activity and depressive symptoms up to 6 months after stroke and examine if citalopram treatment modified the association.Design A secondary analysis of data from the multicentre randomised controlled trial The Efficacy of Citalopram Treatment in Acute Ischemic Stroke (TALOS).Setting and participants TALOS was conducted at multiple stroke centres in Denmark from 2013 to 2016. It enrolled 642 non-depressed patients with first-ever acute ischaemic stroke. Patients were eligible for this study if a prestroke physical activity level was assessed by the Physical Activity Scale for the Elderly (PASE).Interventions All patients were randomised to citalopram or placebo for 6 months.Outcomes Depressive symptoms 1 and 6 months after stroke measured on the Major Depression Inventory (MDI) ranging from 0 to 50.Results A total of 625 patients were included. Median (IQR) age was 69 (60–77) years, 410 (65.6%) were men, 309 (49.4 %) received citalopram and median (IQR) prestroke PASE score was 132.5 (76–197). Higher prestroke PASE quartile, compared with the lowest PASE quartile, was associated with fewer depressive symptoms both after 1 month (mean difference third quartile −2.3 (−4.2, –0.5), p=0.013, mean difference fourth quartile −2.4 (−4.3, –0.5), p=0.015) and 6 months after stroke (mean difference third quartile −3.3 (−5.5, –1.2), p=0.002, mean difference fourth quartile −2.8 (−5.2, –0.3), p=0.027). There was no interaction between citalopram treatment and prestroke PASE score on poststroke MDI scores (p=0.86).Conclusions A higher prestroke physical activity level was associated with fewer depressive symptoms 1 and 6 months after stroke. Citalopram treatment did not seem to modify this association.Trial registration numbers NCT01937182 (ClinicalTrials.gov) and 2013-002253-30 (EUDRACT).

Abstract Background Cerliponase alfa, an enzyme replacement therapy for neuronal ceroid lipofuscinosis type 2 (CLN2), is currently available in England through a managed access agreement (MAA). It is administered every 2 weeks via an intracerebroventricular device. Here we report qualitative research with families of children with CLN2 disease and healthcare professionals (HCPs) who run the MAA, to understand how access to cerliponase alfa via the MAA at Great Ormond Street Hospital (GOSH) in London, and the overall management of CLN2 disease, was affected during the coronavirus disease 2019 (COVID-19) pandemic. Methods Telephone interviews were conducted with nine families, representing 11 children with CLN2 disease, and two HCPs in November and December 2020. Results Children had received cerliponase alfa treatment for a mean (SD) of 23.1 ± 24.7 months (7.1 ± 4.6 months in the MAA). Families travelled 7–398 km for treatment (mean 210 ± 111 km). Treatment with cerliponase alfa was designated “essential” by GOSH and continued as normal during the pandemic but with extra safety precautions, and no children missed any treatments. Families were highly motivated to continue treatment, despite considerable anxiety about the risk of coronavirus infection from travelling and staying overnight but were reassured by communications from GOSH and the safety precautions put in place. Support therapy services were widely compromised, causing families concern about deterioration in their children’s condition. Families were confused about COVID-19 testing and shielding, and were unclear whether children with CLN2 disease were vulnerable to COVID-19. Conclusions Looking forward, advice for children with CLN2 disease should be specific and tailored, taking into account the family unit. Support therapies should be considered essential alongside cerliponase alfa treatment.

Large language models have received enormous attention recently with some studies demonstrating their potential clinical value, despite not being trained specifically for this domain. We aimed to investigate whether ChatGPT, a language model optimized for dialogue, can answer frequently asked questions about diabetes. We conducted a closed e-survey among employees of a large Danish diabetes center. The study design was inspired by the Turing test and non-inferiority trials. Our survey included ten questions with two answers each. One of these was written by a human expert, while the other was generated by ChatGPT. Participants had the task to identify the ChatGPT-generated answer. Data was analyzed at the question-level using logistic regression with robust variance estimation with clustering at participant level. In secondary analyses, we investigated the effect of participant characteristics on the outcome. A 55% non-inferiority margin was pre-defined based on precision simulations and had been published as part of the study protocol before data collection began. Among 311 invited individuals, 183 participated in the survey (59% response rate). 64% had heard of ChatGPT before, and 19% had tried it. Overall, participants could identify ChatGPT-generated answers 59.5% (95% CI: 57.0, 62.0) of the time, which was outside of the non-inferiority zone. Among participant characteristics, previous ChatGPT use had the strongest association with the outcome (odds ratio: 1.52 (1.16, 2.00), p = 0.003). Previous users answered 67.4% (61.7, 72.7) of the questions correctly, versus non-users' 57.6% (54.9, 60.3). Participants could distinguish between ChatGPT-generated and human-written answers somewhat better than flipping a fair coin, which was against our initial hypothesis. Rigorously planned studies are needed to elucidate the risks and benefits of integrating such technologies in routine clinical practice.

Background Spousal bereavement is a life event that affects older people differently. We investigated the impact of spousal bereavement on medical expenditures and mortality in the general population, emphasizing on age and sex. Methods Data are from a population-based, retrospective cohort study following 924,958 Danish citizens over the age of 65 years, within 2011–2016. Changes in health care expenditures in those who suffer bereavement were compared with time matched changes among those who did not. Mortality hazards were analysed with time to event analysis. Results A total of 77,722 (~8.4%) individuals experienced bereavement, 65.8% being females. Among males, bereavement was associated with increase of expenditures the year after, that was 42 Euros per week (95% CI, 36 to 48) larger than the non-bereaved group. The corresponding increase for females was 35 Euros per week (95% CI, 30 to 40). The increase of mortality hazards was highest in the first year after bereavement, higher in males than females, in young old and almost absent in the oldest old. Compared with the reference, mortality the year after spousal loss was 70% higher (HR 1.70 [95% CI 1.40 to 2.08]) for males aged 65–69 years and remained elevated for a period of six years. Mortality for females aged 65–69 years was 27% higher in the first year (HR 1.27, [1.07 to 1.52]), normalizing thereafter. Conclusion Bereavement affects older people differently with younger males being most frail with limited recovery potential.

Induced pluripotent stem cells (iPSCs) are potential cell sources for regenerative medicine. The iPSCs exhibit a preference for lineage differentiation to the donor cell type indicating the existence of memory of origin. Although the intrinsic effect of the donor cell type on differentiation of iPSCs is well recognized, whether disease-specific factors of donor cells influence the differentiation capacity of iPSC remains unknown. Using viral based reprogramming, we demonstrated the generation of iPSCs from chondrocytes isolated from healthy (AC-iPSCs) and osteoarthritis cartilage (OA-iPSCs). These reprogrammed cells acquired markers of pluripotency and differentiated into uncommitted mesenchymal-like progenitors. Interestingly, AC-iPSCs exhibited enhanced chondrogenic potential as compared OA-iPSCs and showed increased expression of chondrogenic genes. Pan-transcriptome analysis showed that chondrocytes derived from AC-iPSCs were enriched in molecular pathways related to energy metabolism and epigenetic regulation, together with distinct expression signature that distinguishes them from OA-iPSCs. Our molecular tracing data demonstrated that dysregulation of epigenetic and metabolic factors seen in OA chondrocytes relative to healthy chondrocytes persisted following iPSC reprogramming and differentiation toward mesenchymal progenitors. Our results suggest that the epigenetic and metabolic memory of disease may predispose OA-iPSCs for their reduced chondrogenic differentiation and thus regulation at epigenetic and metabolic level may be an effective strategy for controlling the chondrogenic potential of iPSCs.