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Topological quasiparticle with higher Chern number is promising to realize large-quantized photogalvanic effect. Here, the authors observe splitting of both topological surface and bulk states in a chiral crystal PtGa, suggesting multifold fermions with a maximal Chern number of ±4.

Background: Mangrove associated fungi are the second most diverse organisms that remain less explored. Cytotoxic and antibacterial activities of foliar fungus Meyerozyma guilliermondii were investigated. Methods: Foliar fungus was isolated from the leaves of Rhizophora mucronata collected from Pichavaram mangrove forest, Tamilnadu. Extracts from liquid state culture were tested for cytotoxicity against two cancer cell lines using the MTT assay. Antibacterial activity was determined using the well diffusion method. The DNA was isolated from the fungi, and the ITS region of 5.8s RNA was sequenced. The spectral properties (GC/MS) of the purified compounds were determined. Results: The ethyl acetate extracts showed potent cytotoxicity against Hep2 and human breast adenocarcinoma (MCF-7) cell lines with IC50 values of 1.25 and 0.625 μg/ml, respectively. Antibacterial activity of the fungal extract was demonstrated against five test organisms. The fungus was found to be a new strain based on ITS sequence and database in NCBI Blast tool. Conclusion: Results indicate the potential for production of bioactive agents from mangrove foliar fungi. KEYWORDS: Marine fungi, Meyerozyma guilliermondii, Anticancer, Antibacterial

Abstract Introduction Rapid identification and treatment of stroke is crucial for the outcome of the patient. We aimed to determine the performance of glial fibrillary acidic protein (GFAP) independently and in combination with the Prehospital Stroke Score (PreSS) for identification and differentiation of acute stroke within 4.5 h after symptom onset. Patients and methods Clinical data and serum samples were collected from the Treat-Norwegian Acute Stroke Prehospital Project (Treat-NASPP). Patients with suspected stroke and symptoms lasting ≤ 4.5 h had blood samples collected and were evaluated with the National Institutes of Health Stroke Scale prospectively. In this sub study, NIHSS was retrospectively translated into PreSS and GFAP was measured using the sensitive single molecule array (SIMOA). Results A total of 299 patients with suspected stroke were recruited from Treat-NASPP and included in this study (44% acute ischemic stroke (AIS), 10% intracranial hemorrhage (ICrH), 7% transient ischemic attack (TIA), and 38% stroke mimics). ICrH was identified with a cross-fold validated area under the receiver-operating characteristic curve (AUC) of 0.73 (95% CI 0.62–0.84). A decision tree with PreSS and GFAP combined, first identified patients with a low probability of stroke. Subsequently, GFAP detected patients with ICrH with a 25.0% sensitivity (95% CI 11.5–43.4) and 100.0% specificity (95% CI 98.6–100.0). Lastly, patients with large-vessel occlusion (LVO) were detected with a 55.6% sensitivity (95% CI 35.3–74.5) and 82.4% specificity (95% CI 77.3–86.7). Conclusion In unselected patients with suspected stroke, GFAP alone identified ICrH. Combined in a decision tree, GFAP and PreSS identified subgroups with high proportions of stroke mimics, ICrH, LVO, and AIS (non-LVO strokes).

Abstract Background Osteoarthritis (OA) affects 20% of the adult Danish population, and the financial burden to society amounts to DKK 4.6 billion annually. Research suggests that up to 75% of surgical patients could have postponed an operation and managed with physical training. ERVIN.2 is an artificial intelligence (AI)-based clinical support system that addresses this problem by enhancing patient involvement in decisions concerning surgical knee and hip replacement. However, the clinical outcomes and cost-effectiveness of using such a system are scantily documented. Objective The primary objective is to investigate whether the usual care is non-inferior to ERVIN.2 supported care. The second objective is to determine if ERVIN.2 enhances clinical decision support and whether ERVIN.2 supported care is cost-effective. Methods This study used a single-centre, non-inferiority, randomised controlled in a two-arm parallel-group design. The study will be reported in compliance with CONSORT guidelines. The control group receives the usual care. As an add-on, the intervention group have access to baseline scores and predicted Oxford hip/knee scores and HRQoL for both the surgical and the non-surgical trajectory. A cost-utility analysis will be conducted alongside the trial using a hospital perspective, a 1-year time horizon and effects estimated using EQ-5D-3L. Results will be presented as cost per QALY gain. Discussion This study will bring knowledge about whether ERVIN.2 enhances clinical decision support, clinical effects, and cost-effectiveness of the AI system. The study design will not allow for the blinding of surgeons. Trial registration ClinicalTrials.gov NCT04332055 . Registered on 2 April 2020.

Abstract Background Depression and anxiety are prevalent mental disorders among the working population with potentially high personal and financial cost. The overall aim of this study was to test the applicability of an outreach collaborative model for early identification and treatment of clinical and sub-clinical mental disorders among Danish employees. This applicability was examined by I) investigating the fractions of identified and treated clinical and subclinical cases, II) describing the distribution and characteristics of cases identified and III) investigating the effect of allocated treatment. Methods A longitudinal study design with four assessments (T0-T3) over 16 months was applied. Self-reporting questionnaires probing for psychopathology were distributed to all employees in six consecutively enrolled companies at the four time points. Employees meeting the screening criteria at T1 were assessed diagnostically. Subjects diagnosed with a clinical mental disorder were allocated to outpatient psychiatric treatment, and subjects with subclinical conditions were allocated to preventive cognitive behavioural therapy. Follow-up was conducted 6 and 12 months after initiation of treatment. We used chi-squared test and F-test to compare the different groups on baseline characteristics and mixed effects linear regression to analyse the treatment effects. Results Forty (6.8%) of the 586 responders at T1 were diagnosed with a clinical mental disorder and referred to outpatient psychiatric treatment. Thirty-three (5.6%) were affected by a subclinical condition and referred to preventive treatment. Nearly two-thirds (63%) of the employees diagnosed with a clinical condition had never received treatment before. Symptom severity decreased significantly for both treated groups until follow-up. When compared to a composed control group, subclinical cases displayed a more rapid initial significant symptomatic decrease on the global symptom scale (coefs = − 0.914, 95% CI [− 1.754, − 0,075]) and anxiety sub-scale (coefs = − 1.043, 95% CI [− 2.021, − 0.066]). This did not apply to the clinical cases as no significant difference in change were identified. Conclusions The outreach collaborative model demonstrated an applicability to identify both clinical and subclinical cases, among these a high number of employees with an unmet need for treatment. We found evidence of a positive initial effect on symptomatology from the allocated preventive treatment among the subclinical cases, but not for clinical cases. Trial registration Retrospectively registered at December 18, 2018 at clinicaltrials.gov, identifier: NCT03786328.

Individuals without a protective antibody level are susceptible to measles infection. There are differences in the persistence of antibodies after vaccination and infection, while the impact of gender on this process has not been sufficiently studied. Measles Ig G antibodies were measured in 1742 employees of a large hospital facility—403 men and 1339 women aged from 25 to 67 years; 15% participants had antibody levels less than the protective threshold of ≥0.18 IU/mL. Significant differences were found in the age group 40–49, where the level of IgG antibodies to measles among men was higher than among women (1.51 IU/mL (0.41; 3.38) vs. 0.70 IU/mL (0.22;1.98) respectively, (U = 3.2, p = 0,001)); in the age group 60 and older, by contrast, the level of antibodies among women was higher compared to men (3.29 IU/mL (1.72; 4.07) vs. 2.90 IU/mL (1.46; 3.53) respectively (U = 2.2, p = 0.03)). The proportion of seronegative women in the age group 40–49 was significantly higher than of seronegative men: 22 [18–26]% and 11 [6–18]% respectively (χ2 = 7.0, p = 0.001). The revealed gender characteristics that affect persistence of measles immunity may be important in personalization of vaccinal prevention for men and women.

Abstract Background The potential for artificial intelligence (AI) to transform healthcare cannot be ignored, and the development of AI technologies has increased significantly over the past decade. Furthermore, healthcare systems are under tremendous pressure, and efficient allocation of scarce healthcare resources is vital to ensure value for money. Health economic evaluations (HEEs) can be used to obtain information about cost-effectiveness. The literature acknowledges that the conduct of such evaluations differs between medical technologies (MedTechs) and pharmaceuticals, and poor quality evaluations can provide misleading results. This systematic review seeks to map the evidence on the general methodological quality of HEEs for AI technologies to identify potential areas which can be subject to quality improvements. We used the 35-item checklist by Drummond and Jefferson and four additional checklist domains proposed by Terricone et al. to assess the methodological quality of full HEEs of interventions that include AI. Results We identified 29 studies for analysis. The included studies had higher completion scores for items related to study design than for items related to data collection and analysis and interpretation of results. However, none of the studies addressed MedTech-specific items. Conclusions There was a concerningly low number of full HEEs relative to the number of AI publications, however the trend is that the number of studies per year is increasing. Mapping the evidence of the methodological quality of HEEs of AI shows a need to improve the quality in particular the use of proxy measures as outcome, reporting, and interpretation of the ICER.

BackgroundPatients with a positive prehospital stroke severity score and underlying intracerebral hemorrhage (ICH) may be harmed by longer onset-to-admission time. We aimed to investigate the interaction between ICH severity and time from onset to admission on functional outcome.MethodsThis is an individual patient data analysis with data from two randomized prehospital stroke trials using the same prehospital stroke scale. Patients were stratified according to the presence of a positive stroke severity score. They were grouped into early arrivers (admitted ≤ 90 min from onset) and late arrivers (admitted ≥90 min after onset). The primary outcome was a shift toward a better functional outcome on the modified Rankin Scale (mRS).ResultsA total of 212 patients had ICH. A positive stroke severity score was seen in 123 of these patients. Patients with ICH and a positive prehospital stroke severity score had a significantly worse outcome if they arrived 90 min or later at the hospital (adjusted odds ratio [aOR]: 2.02, 95% CI [1.01, 4.12]). This difference was not observed in patients without a positive severity score (aOR: 0.50, 95% CI [0.22, 1.14]). Patients with a positive score also had an increased risk of death or severe dependency (mRS of 5–6) of 9.1 percentage points (95% CI [−1.6%, 19.8%]) per hour if they were diagnosed with ICH.ConclusionLonger onset-to-admission time was harmful for patients with ICH and a positive prehospital stroke severity score.

Background The optimal blood pressure management strategy in patients undergoing endovascular therapy for acute ischemic stroke is unknown. This pilot study aimed to assess the feasibility of a standard versus individualized blood pressure management strategy during endovascular therapy. Methods This randomized controlled pilot trial included adult patients with acute ischemic stroke with large‐vessel occlusion in the anterior circulation undergoing endovascular therapy. Patients were randomized to either standard (mean arterial blood pressure [MABP] targeted between 70 and 90 mm Hg) or individualized (MABP targeted ±10% of a baseline value measured in the neurointerventional suite) blood pressure targets until reperfusion or removal of groin sheath. The main outcome was the modified Rankin Scale score at 90 days. Secondary outcomes included feasibility outcomes, 90‐day dichotomized modified Rankin Scale score (0–2 versus 3–6), and reperfusion rates. Results Between April 2021 and February 2022, 60 patients (median [interquartile range] age, 76 [66–84] years) were randomly assigned to standard (n=30) or individualized (n=30) blood pressure targets. Median (interquartile range) National institutes of Health Stroke Scale score was 15 (10–18). Mean (SD) MABP, mean (SD) systolic blood pressure, and median (interquartile range) cardiac output were significantly higher in the individualized group compared with the standard group (MABP: 94 [9] versus 88 [9] mm Hg; P=0.012; systolic blood pressure: 149 [21] versus 139 [17] mm Hg; P=0.032; and cardiac output: 5.82 [4.22–7.23] versus 4.35 [3.73–5.1] L/min; P=0.02). The odds ratio for improved outcome in the individualized group was 1.37 (95% CI, 0.56–3.36). The relative risk for improved dichotomized outcome in the individualized group was 1.31 (95% CI, 0.87–1.98). Full reperfusion rates were comparable between the standard and individualized groups (90% versus 93%; P=0.64). The median percentage of time outside the MABP targets was 54.3% in the standard group versus 61.4% in the individual group (P=0.30) and did not meet the feasibility target. Recruitment rate, data completeness, and safety were within feasibility limits. Conclusions The feasibility criteria were not met in this study because of difficulties in achieving the desired blood pressure targets. These findings do not support continuing with a large trial using the current protocol.

Introduction Insomnia in depression is common and difficult to resolve. Music is commonly used as a sleep aid, and clinical trials pointing to positive effects of music as a sleep aid are increasing adding to the evidence base. There is little knowledge on the effectiveness of music for depression related insomnia. Objectives A recent RCT study conducted in psychiatry at Aalborg University Hospital examined effects of a music intervention for insomnia in depression. The intervention group listened to music at bedtime for four weeks, controls were offered music intervention post-test. Primary outcome measure was Pittsburgh Sleep Quality Index (PSQI). Secondary outcomes included Actigraphy, The Hamilton depression Rating Scale (HAMD-17) and World Health Organisation well-being questionnaires (WHO-5, WHOQOL-BREF). Methods A two-armed randomized controlled trial (n=112) and a qualitative interview study (n=4) Results The RCT study showed signficant improvements for the music intervention group in sleep quality and quality of life at four weeks according to global PSQI scores (effect size= -2.1, 95%CI -3.3; -0.9) and WHO-5 scores (effect size 8.4, 95%CI 2.7; 14.0). Actigraphy measures showed no changes and changes in depression symptoms (HAMD-17) were not detected. The interview study unfolded examples of the influences of music on sleep and relaxation. Music distracted, affected mood and arousal positively and supported formation of sleep habits. Results from the trial are discussed and merged with findings from the interview study. The results from the trial suggested moderate effects of music listening for the population while findings from the interview study showed examples of individual and highly varying outcomes. Conclusions Music is suggested as a low-cost, side-effect free and safe intervention in supplement to existing treatments improving sleep in depression. Disclosure of Interest None Declared

Background Endovascular therapy is highly effective in stroke caused by large vessel occlusion. Guidelines support treatment in case of occlusion of the intracranial internal carotid artery or the first segment of the middle cerebral artery. We aimed to examine baseline characteristics and outcome of patients who underwent endovascular therapy for tandem occlusions. Methods We conducted a retrospective study of patients who underwent endovascular therapy of tandem occlusion or occlusion of intracranial internal carotid artery/first segment of the middle cerebral artery between May 2015 and December 2019. Univariate comparisons of baseline characteristics and outcome (favorable functional outcome 90‐days after treatment and mortality) were performed. We used inverse‐probability‐of‐treatment‐weights to adjust for confounders. Results We compared 167 patients with tandem occlusion and 414 with intracranial occlusions. Patients with tandem occlusion were younger (69 years [interquartile range: 59.25–76] versus 74 [interquartile range: 64–81]; P = 0.0002), male (64.7% versus 51.4%; P = 0.004), more frequently active smokers (42.5% versus 25.6%; P = 0.0001), and less frequently subject to atrial fibrillation (18.6% versus 41.3%; P

Abstract Aims Data on socioeconomic‐related differences in heart failure (HF) care are sparse. Inequality in care may potentially contribute to a poor clinical outcome. We examined socioeconomic‐related differences in quality of HF care among patients with incident HF with reduced ejection fraction (EF) (HFrEF). Methods and results We conducted a nationwide population‐based cohort study among patients with HFrEF (EF ≤40%) registered from January 2008 to October 2015 in the Danish Heart Failure Registry, a nationwide registry of patients with a first‐time primary HF diagnosis. Associations between individual‐level socioeconomic factors (cohabitation status, education, and family income) and the quality of HF care defined by six guideline‐recommended process performance measures [New York Heart Association (NYHA) classification, treatment with angiotensin‐converting‐enzyme inhibitors (ACEI)/angiotensin receptor blockers (ARB), beta‐blockers and mineralocorticoid receptor antagonists, exercise training, and patient education] were assessed using multiple imputation and multivariable logistic regression controlling for potential confounders. Among 17 122 HFrEF patients included, 15 290 patients had data on all six process performance measures. Living alone was associated with lower odds of NYHA classification [adjusted OR (aOR) 0.81; 95% confidence interval (CI): 0.72–0.90], prescription of ACEI/ARB (aOR 0.76; 95% CI: 0.68–0.88) and beta‐blockers (aOR 0.84; 95% CI: 0.76–0.93), referral to exercise training (aOR 0.75; 95% CI: 0.69–0.81), and patient education (aOR 0.73; 95% CI: 0.67–0.80). Compared with high‐level education, low‐level education was associated with lower odds of NYHA classification (aOR 0.93; 95% CI: 0.79–1.11), treatment with ACEI/ARB (aOR 0.99; 95% CI: 0.81–1.20) and beta‐blockers (aOR 0.93; 95% CI: 0.79–1.09), referral to exercise training (aOR 0.73; 95% CI: 0.65–0.82), and patient education (aOR 0.86, 95% CI: 0.75–0.98). An income in the lowest tertile was associated with lower odds of NYHA classification (aOR 0.67; 95% CI: 0.58–0.79), prescription of ACEI/ARB (aOR 0.80, 95% CI: 0.67–0.95) and beta‐blockers (aOR 0.88, 95% CI: 0.86–1.01), referral to exercise training (aOR 0.59, 95% CI: 0.53–0.64), and patient education (aOR 0.66; 95% CI: 0.59–0.74) compared with an income in the highest tertile. Overall, no systematic differences were seen when the analyses were stratified by sex and age groups. Conclusions Living alone, low‐level education, and income in the lowest tertile were associated with reduced use of recommended processes of HF care among Danish HFrEF patients with a first‐time primary HF diagnosis. Efforts are warranted to ensure guideline‐recommended HF care to all HFrEF patients, irrespective of socioeconomic background.

Ample studies have demonstrated that internet-based cognitive behavioural therapy (iCBT) for anxiety disorders is effective and acceptable in controlled settings. Studies assessing the clinical effectiveness of iCBT for anxiety disorders among routine care populations are, however, not as numerous. The purpose of this study was to assess the effectiveness of iCBT among anxiety patients, who were on a waiting list for intensive outpatient treatment, in a specialised routine care clinic.1 Clinic for OCD and Anxiety disorders, Aarhus University Hospital, DK. A randomised controlled pilot trial was conducted. Recruited patients were on a waiting list and had a primary diagnosis of either social phobia or panic disorder. Participants were randomised into either receiving iCBT with minimal therapist contact (received access to the programme FearFighter® (FF) and received support from a clinician via telephone) or no treatment (stayed on the waiting list). The primary outcome was self-reported symptomatic change of anxiety on Beck Anxiety Inventory (BAI). The secondary outcomes were comorbid depression measured on Beck Depression Inventory (BDI-II) and quality of life measured with the EuroQol one-item visual-analogue scale (EQ-vas). All results were analysed by intention-to-treat analyses using a mixed-effects approach. N = 158 patients were assessed for eligibility of which N = 67 met all eligibility inclusion criteria, signed informed consent forms, and were randomised. Post-treatment assessment was completed by N = 47 (70%). In the intervention group, N = 11 (31%) completed all modules of FF. No significant differences of change of symptomatic levels were found between the intervention and control group for anxiety (BAI: mean diff. = 2.42; 95% CI −1.03 to 5.86; p = 0.17; d = 0.06) or for depression (BDI-II: mean diff. 1.87; 95% CI −2.25 to 6.00; p = 0.37; d = 0.02). A large and significant effect was found in self-reported quality of life in favour of the experimental group (EQ-vas: mean diff. −20.88; 95% CI −30.64 to −11.11; p