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Teachers' ability to critically reflect classroom situations in relation to their own actions constitutes an important prerequisite to improve teaching performance and professional behavior. This study investigated electroencephalogram activity in the alpha band during a reflection task before and after training in a sample of preservice teachers. Reflection was associated with stable brain activity patterns over two separate time points of assessment. Increased alpha power during reflection of pedagogically relevant scenarios was found at occipital sites, especially in participants with higher reflection competence. This is consistent with prior studies that showed increased alpha power during mental imagery among other tasks. Training of reflection competence, administered in a subsample of participants, was accompanied by increased reflection performance, while no intervention-related effects were found at the neurophysiological level. The findings of this study provide first preliminary evidence of increased alpha power at occipital sites as a neurophysiological indicator of reflections of pedagogically relevant educational scenarios.

Abstract Escalations in wildfire activity are of significant global concern, particularly within vulnerable wetland ecosystems integral to natural carbon sequestration and climate change mitigation. Our understanding and management of future wildfire activity may be better contextualised through the study of historic and ancient fire records, independent of human influence. Methods of study include ‘geothermometry’ - approximating ancient fire intensity from temperature-dependent changes in the chemistry of fossil charcoal. Though well established in their relation to experimental charcoalification, these methods still fail to quantify the true intensity of ancient fires, as a measure of energy release. As a result, their applicability, and contributions to the characterisation of modern fire activity, remain uncertain. Here, we present a novel measure of wildfire energy release, as a proxy for true intensity, through the co-application of cone calorimetry and Raman spectroscopy of charcoal. By applying a range of wildfire heat fluxes to variable peatland fuel mixes, this research demonstrates the complexity in correlating fire behaviour and charcoal microstructure. Further statistical analyses suggest a correlation between spectroscopic results, measures of CO and CO2 release, and fire severity. This offers a principal measure of ancient wildfire intensity, consistent with modern practices in wildfire modelling, monitoring, and management.

Abstract Lipoprotein (a) [Lp(a)] is suspected to have antifibrinolytic effects, however, its relevance for the severity of venous thromboembolic events remains unclear. We studied the association of Lp(a) levels with thrombus load in pulmonary embolism (PE). 90 patients (40% female, median age 70 [56–79] years) at our tertiary care hospital with a diagnosis of acute PE, available Lp(a) levels and CT pulmonary angiography (CT-PA) performed between April 2017 and December 2019 were included. All CT-PA scans were reanalyzed and thrombus load was determined via Qanadli CT obstruction index (CTOI) and most proximal thrombus location. Median Lp(a) levels were 11.4 [9.3–29.1] mg/dL, median D-dimer levels were 4.6 [2.1–9.8] mg/L, median CTOI was 23 [8–50], central PE was present in 27 (30%) patients. Lp(a) did not correlate with CTOI (r = 0.02, p = 0.922) and was not associated with thrombus location (p = 0.369). CTOI significantly correlated with D-dimer (r = 0.43, p

Abstract It never rains in standard lab-confinements; thus we have limited understanding of animal reactions to water and wetness. To address this issue, we sprayed water on different body parts of rats and measured drying and fur temperature by thermal imaging while manipulating behavior, sensory cues and fur. Spraying water on rats resulted in fur changes (hair clumping, apex formation), grooming, shaking, and scratching. Anesthesia abolished behavioral responses, interfered with fur changes, and slowed drying. Spraying water on different body parts resulted in differential behavioral drying responses. Spraying the head resulted in grooming and shaking responses; water evaporated from the head twice as fast as water sprayed on the animal’s back or belly. We observed no effect of whisker removal on post-water-spraying behavior. In contrast, local anesthesia of dorsal facial skin reduced post-water-spraying behavioral responses. Shaving of head fur drastically enhanced post-water-spraying behaviors, but reduced water loss during drying; indicating that fur promotes evaporation, acting in tandem with behavior to mediate drying. Excised wet fur patches dried and cooled faster than shaved excised wet skin. Water was sucked into distal hair tips, where it evaporated. We propose the wet-fur-heat-pump-hypothesis; fur might extract heat required for drying by cooling ambient air.

The Electro Cardio Gram is a very valuable clinical tool to access the electric function of the heart. It provides insight into the different phases of the heart beat and various kinds of disorders which may affect them. In the past decades various algorithms to detect and delineate ECG beats have been developed. The complex-lead based algorithms compute a virtual-lead by averaging the samples of an arbitrary number of channels. In this study exponential weighted moving powers based estimates for the skewness, kurtosis and signal to noise ratio are used to select the channels which are included in the resulting complex lead signal. According to these parameters the channels are labelled bad, poor, scaled and good. A weighted average is used to to compute the next sample of the complex lead from the channels labelled good and scaled. The 75 30minutes records of the ”St.-Petersburg Institute of Cardiological Technics 12-lead Arrhythmia Database” are used to evaluate the proposed approach. The average sensitivity increases to 99.61% and to 99.63% in total compared to 99.57% and 99.59% for the standard approach. The average and overall specificity increases to 99.65% and the F1 and F-M scores to 0.9964. This shows that the estimates provide sufficient information about the quality, to successfully reduce the distortion of the complex-lead signal by artefacts and strong muscle signals while avoiding the additional time delay imposed by standard window based methods.

Abstract Duchenne muscular dystrophy (DMD) is an X-linked recessive disease characterized by mutations in the dystrophin gene, causing motor and pulmonary function decline. Viltolarsen is indicated for patients with dystrophin gene mutations amenable to exon 53 skipping. Here, we report safety, motor function, and the first pulmonary function results from the open-label, phase II Galactic53 trial of viltolarsen (NCT04956289). Male participants aged ≥ 8 years with DMD received 80 mg/kg intravenous viltolarsen once weekly for 48 weeks. Results from participants receiving viltolarsen were compared with an external control cohort group-matched for multiple variables. All treatment-emergent adverse events were mild or moderate, 4 were considered treatment-related, and no participants discontinued. Participants receiving viltolarsen experienced clinically meaningful benefits in pulmonary function with higher percent predicted forced vital capacity and higher peak cough flow at Week 49 compared with the control cohort for both ambulatory and nonambulatory participants. Viltolarsen also stabilized upper limb motor function over the Treatment Period. These results support viltolarsen as an important part of the treatment armamentarium for both ambulatory as well as nonambulatory patients with DMD.

Abstract Background Wound healing complications are a major challenge following the extended lateral approach in calcaneal fractures. Soft-tissue microcirculation plays an important role via the delivery of oxygen, nutrients, and the regulation of a local milieu. The aim of this clinical study was to examine the effect of intraoperative pneumatic tourniquet application on skin and subcutaneous microcirculation, and its impact on wound healing progression. Methods Patients with calcaneal fractures were randomly assigned to two groups defined by a surgery conducted either with use or without use of a tourniquet. Blood flow (BF [AU]), tissue oxygen saturation (SO 2 [%]) and the relative amount of haemoglobin (rHb[AU]) were intraoperatively measured at two depths (2 and 8 mm) non-invasively by spectrophotometry (Micro-Lightguide O2C ® , LEA Medizintechnik, Giessen, Germany). Time points were before and after inflation of the pneumatic tourniquet and also at the end of surgery before deflation. A linear mixed model (LMM) was fitted for statistical analysis. Results Thirty-four patients (3 women and 31 men) with 37 calcaneal fractures were included. In 22 of them, the surgery was conducted with a tourniquet and in the other 15 without its use. A significant decrease of microcirculation, characterized by decreases in blood flow (p = 0.011) and tissue oxygenation (p = 0.023) was measured in 8 mm depth after inflating the tourniquet. However, these changes did not influence the time of postoperative wound healing. Conclusion The use of a pneumatic tourniquet reduces deep microcirculation without affecting postoperative wound healing. Trial registration The study was registered in www.ClinicalTrials.gov (NCT01264146).

Abstract Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal malignancies, presenting a persisting global health burden. Neutrophils have a double-edged role in tumor progression exhibiting both pro-tumor and anti-tumor functions. CD71, also known as transferrin receptor 1, performs a critical role in cellular iron uptake and is highly expressed on proliferating cells, and especially on activated immune cells. CD71 is known to be elevated in various types of solid cancers and is associated with poor prognosis, however, the expression of CD71 on neutrophils in PDAC and its potential clinical impact is still unknown. Therefore, we analyzed CD71 on circulating neutrophils in PDAC and clinical control patients and found a significant increased expression in PDAC patients. High expression of CD71 on neutrophils in PDAC patients was associated with reduced outcome compared to low expression. CD71 on neutrophils correlated positively with the levels of proinflammatory cytokines IL-6, IFN-γ, and growth factor ligands CD40-L, and BAFF in plasma of PDAC patients. Finally, we have demonstrated that high expression of CD71 on neutrophils was also associated with an increased expression of CD39 and CD25 on circulating T-cells. Based on our findings, we hypothesize that CD71 on neutrophils is associated with tumor progression in PDAC. Further studies are required to investigate the distinct functionality of CD71 expressing neutrophils and their potential clinical application.

Chronic lateral ankle instability is a relatively frequent consequence after acute ankle sprain. In case of unsuccessful conservative treatment, surgical therapy is recommended to prevent osteoarthritis of the ankle joint. To date, different surgical methods have evolved. Yet, it remains unclear which approach reveals the best results. We hypothesized that the modified Broström–Gould procedure with suture anchor ligament fixation leads to superior postoperative results compared to the Broström–Gould procedure or the periosteal flap technique.

Abstract Butyl octyl magnesium solutions are important raw materials in various chemical processes but suffer from their high reactivity with even traces of water, protic solvents or oxygen and an increased viscosity in hydrocarbon solution due to the formation of polymeric structures. N 1,N 2-diphenylacenaphthylene-1,2-diimines (BIANs) have already been identified as potential candidates to reduce the viscosity of alkyl magnesium solutions and this study provides a systematic insight into the dependence of this ability on the position and structures of substituents on the BIAN. Besides the various BIANs, ZnCl2 complexes and hydrogenated derivatives were characterized and tested for their ability to reduce the viscosity. HPLC-high resolution mass spectrometry, MALDI-ToF mass spectrometry, but most important FTIR and NMR experiments under inert conditions have been used to shine light on the interaction of the different BIAN derivatives with alkyl magnesium solutions. Hydrogenated BIANs, especially those with bulky alkyl groups in the ortho position(s) have been identified as the most promising candidates. An additional benefit of the hydrogenated species is that in contrast to BIANs and BIAN-Zn complexes they do not undergo permanent chemical modification and can be reused after extraction.

Abstract Preoperative identification of intracranial meningiomas with aggressive behaviour may help in choosing the optimal treatment strategy. Radiomics is emerging as a powerful diagnostic tool with potential applications in patient risk stratification. In this study, we aimed to compare the predictive value of conventional, semantic based and radiomic analyses to determine CNS WHO grade and early tumour relapse in intracranial meningiomas. We performed a single-centre retrospective analysis of intracranial meningiomas operated between 2007 and 2018. Recurrence within 5 years after Simpson Grade I-III resection was considered as early. Preoperative T1 CE MRI sequences were analysed conventionally by two radiologists. Additionally a semantic feature score based on systematic analysis of morphological characteristics was developed and a radiomic analysis were performed. For the radiomic model, tumour volume was extracted manually, 791 radiomic features were extracted. Eight feature selection algorithms and eight machine learning methods were used. Models were analysed using test and training datasets. In total, 226 patients were included. There were 21% CNS WHO grade 2 tumours, no CNS WHO grade 3 tumour, and 25 (11%) tumour recurrences were detected in total. In ROC analysis the best radiomic models demonstrated superior performance for determination of CNS WHO grade (AUC 0.930) and early recurrence (AUC 0.892) in comparison to the semantic feature score (AUC 0.74 and AUC 0.65) and conventional radiological analysis (AUC 0.65 and 0.54). The combination of human classifiers, semantic score and radiomic analysis did not markedly increase the model performance. Radiomic analysis is a promising tool for preoperative identification of aggressive and atypical intracranial meningiomas and could become a useful tool in the future.

Abstract Progressive gait impairment is common among aging adults. Remote phenotyping of gait during daily living has the potential to quantify gait alterations and evaluate the effects of interventions that may prevent disability in the aging population. Here, we developed ElderNet, a self-supervised learning model for gait detection from wrist-worn accelerometer data. Validation involved two diverse cohorts, including over 1000 participants without gait labels, as well as 83 participants with labeled data: older adults with Parkinson's disease, proximal femoral fracture, chronic obstructive pulmonary disease, congestive heart failure, and healthy adults. ElderNet presented high accuracy (96.43 ± 2.27), specificity (98.87 ± 2.15), recall (82.32 ± 11.37), precision (86.69 ± 17.61), and F1 score (82.92 ± 13.39). The suggested method yielded superior performance compared to two state-of-the-art gait detection algorithms, with improved accuracy and F1 score (p

Abstract To determine the diagnostic yield of cone beam computed tomography (CBCT) compared with 3 T magnetic resonance imaging (MRI) for the evaluation of subchondral insufficiency fractures of the knee. Consecutive patients with subchondral insufficiency fractures of the knee examined by 3 T MRI and CBCT of the femoral condyles were reviewed. Two experienced raters graded the lesion severity on 3 T MRI and CBCT images: grade 1: no signs of a subchondral bone lesion; grade 2: subchondral trabecular fracture or cystic changes, but without infraction of the subchondral bone plate; grade 3: collapse of the subchondral bone plate. Ratings were repeated after six weeks to determine reliability. In addition, the bone lesion size was measured as elliptical area (mm2) and compared between CBCT and T1-weighted MRI sequences. Among 30 patients included (43.3% women; mean age: 60.9 ± 12.8 years; body mass index (BMI) 29.0 ± 12.8 kg/m2), the medial femoral condyle was affected in 21/30 patients (70%). The grading of subchondral lesions between MRI and CBCT did not match in 12 cases (40%). Based on MRI images, an underestimation (i.e., undergrading) compared with CBCT was observed in nine cases (30%), whereas overgrading occurred in three cases (10%). Compared to CBCT, routine T1-weighted 3 T sequences significantly overestimated osseus defect zones in sagittal (84.7 ± 68.9 mm2 vs. 35.9 ± 38.2 mm2, p

At 3 severe infection cohort sites in Uganda, Orientia seropositivity was common. We identified 4 seroconversion cases and 1 PCR-positive case. These results provide serologic and molecular support for Orientia spp. circulating in sub-Saharan Africa, possibly expanding its endemic range. Orientia infections could cause severe illness and hospitalizations in this region.

Abstract To evaluate the prognostic value of biomarkers from peripheral blood obtained as routine laboratory assessment for overall survival in a cohort of stage III non-small cell lung cancer (NSCLC) patients treated with definitive radiochemotherapy at a high-volume cancer center. Seven blood biomarkers from 160 patients treated with definitive radiochemotherapy for stage III NSCLC were analyzed throughout the course treatment. Parameters were preselected using univariable and multivariable proportional hazards analysis and were assessed for internal validity using leave-one-out cross validation. Cross validated classifiers including biomarkers in addition to important clinical parameters were compared with classifiers containing the clinical parameters alone. An increased C-reactive protein (CRP) value in the final week of radiotherapy was found as a prognostic factor for overall survival, both as a continuous (HR 1.099 (1.038–1.164), p

Objectives We evaluated the ability of the assessment of regional wall motion abnormalities (RWMA) detected via transthoracic echocardiography to predict the presence of obstructive coronary artery disease (CAD) in patients presenting with acute chest pain to the emergency department.Design Prospective single-centre observational study.Setting Tertiary care university hospital emergency unit.Participants Patients presenting to the emergency department with acute chest pain suggestive of obstructive CAD.Primary outcome measure The primary endpoint was defined as the presence of obstructive CAD, requiring revascularisation therapy.Results Overall, 657 patients (age 58.1±18.0 years, 53% men) were included in our study. RWMA were detected in 76 patients (11.6%). RWMA were significantly more frequent in patients reaching the primary endpoint (26.2% vs 7.6%, p

Abstract Background Adherence to physiotherapeutic treatment and recommendations is crucial to achieving planned goals and desired health outcomes. This overview of systematic reviews synthesises the wide range of additional interventions and behaviour change techniques used in physiotherapy, exercise therapy and physical therapy to promote adherence and summarises the evidence of their efficacy. Methods Seven databases (PEDro, PubMed, Cochrane Library, Web of Science, Scopus, PsycINFO and CINAHL) were systematically searched with terms related to physiotherapy, motivation, behaviour change, adherence and efficacy (last searched on January 31, 2023). Only systematic reviews of randomised control trials with adults were included. The screening process and quality assessment with AMSTAR-2 were conducted independently by the two authors. The extracted data was synthesised narratively. In addition, four meta-analyses were pooled in a panoramic meta-analysis. Results Of 187 reviews identified in the search, 19 were included, comprising 205 unique trials. Four meta-analyses on the effects of booster sessions, behaviour change techniques, goal setting and motivational interventions showed a significantly small overall effect (SMD 0.24, 95% CI 0.13, 0.34) and no statistical heterogeneity (I 2 = 0%) in the panoramic meta-analysis. Narrative synthesis revealed substantial clinical and methodological diversity. In total, the certainty of evidence is low regarding the efficacy of the investigated interventions and techniques on adherence, due to various methodological flaws. Most of the RCTs that were included in the reviews analysed cognitive and behavioural interventions in patients with musculoskeletal diseases, indicating moderate evidence for the efficacy of some techniques, particularly, booster sessions, supervision and graded exercise. The reviews provided less evidence for the efficacy of educational and psychosocial interventions and partly inconsistent findings. Most of the available evidence refers to short to medium-term efficacy. The combination of a higher number of behaviour change techniques was more efficacious. Conclusions The overview of reviews synthesised various potentially efficacious techniques that may be combined for a holistic and patient-centred approach and may support tailoring complex interventions to the patient’s needs and dispositions. It also identifies various research gaps and calls for a more holistic approach to define and measure adherence in physiotherapy. Systematic review registration PROSPERO CRD42021267355.

Abstract T cells recirculate through tissues and lymphatic organs to scan for their cognate antigen. Radiation therapy provides site-specific cytotoxicity to kill cancer cells but also has the potential to eliminate the tumor-specific T cells in field. To dynamically study the effect of radiation on CD8 T cell recirculation, we used the Kaede mouse model to photoconvert tumor-infiltrating cells and monitor their movement out of the field of radiation. We demonstrate that radiation results in loss of CD8 T cell recirculation from the tumor to the lymph node and to distant sites. Using scRNASeq, we see decreased proliferating CD8 T cells in the tumor following radiation therapy resulting in a proportional enrichment in exhausted phenotypes. By contrast, 5 days following radiation increased recirculation of T cells from the tumor to the tumor draining lymph node corresponds with increased immunosurveillance of the treated tumor. These data demonstrate that tumor radiation therapy transiently impairs systemic T cell recirculation from the treatment site to the draining lymph node and distant untreated tumors. This may inform timing therapies to improve systemic T cell-mediated tumor immunity.

Abstract Using ferric chloride (FeCl3) to induce experimental superior sagittal sinus (SSS) thrombosis might interfere with magnetic resonance imaging (MRI)-assisted visualization and evaluation of the thrombus, the brain parenchyma, and the quality of the occlusion. The aim of this study was to investigate whether aluminum chloride (AlCl3)-induced thrombosis of the SSS has comparable properties to those of FeCl3 without causing artifacts in MRI. SSS thrombosis was induced in 14 male Wistar rats by exposure of the SSS and subsequent topical application of a filter paper strip soaked in AlCl3 (n = 7) or FeCl3 (n = 7) over a period of 15 min. The animals with AlCl3-induced SSS thrombosis showed a constant and complete occlusion with in histological analysis large thrombi. Blood flow measurements indicated a significant reduction on the first and seventh postoperative day compared to preoperative measurements. MRI enabled visualization and subsequent evaluation of the thrombus and the surrounding parenchyma. In comparison, FeCl3-induced SSS thrombosis could not be evaluated by MRI due to artifacts caused by the paramagnetic properties and increased susceptibility of FeCl3. The occluded sinus and the surrounding area appeared hypointense. The quality of SSS occlusion by AlCl3 was comparable to that of FeCl3. AlCl3 therefore represents a significant alternative substance in experimental SSS thrombosis ideally suited for studies using MRI.

Abstract Self-identification as a victim of violence may lead to increased negative emotions and stress and thus, may change both structure and function of the underlying neural network(s). In a trans-diagnostic sample of individuals who identified themselves as victims of violence and a matched control group with no prior exposure to violence, we employed a social exclusion paradigm, the Cyberball task, to stimulate the re-experience of stress. Participants were partially excluded in the ball-tossing game without prior knowledge. We analyzed group differences in brain activity and functional connectivity during exclusion versus inclusion in exclusion-related regions. The victim group showed increased anger and stress levels during all conditions. Activation patterns during the task did not differ between groups but an enhanced functional connectivity between the IFG and the right vmPFC distinguished victims from controls during exclusion. This effect was driven by aberrant connectivity in victims during inclusion rather than exclusion, indicating that victimization affects emotional responses and inclusion-related brain connectivity rather than exclusion-related brain activity or connectivity. Victims may respond differently to the social context itself. Enhanced negative emotions and connectivity deviations during social inclusion may depict altered social processing and may thus affect social interactions.

Purpose: To compare suprapubic access (SPA) and transurethral catheterization (TUC) in voiding cystourethrogram (VCUG). Methods: Retrospective single-center evaluation of 311 VCUG performed in male patients under 12 years of age. Two study groups were built based on the bladder access method. TUC was performed in 213 patients, whereas 98 received SPA. The groups were compared regarding the procedural switch rate, the complication rate, radiation parameters, the amount of contrast media applied and the examination quality. Complications were graded in minor (contrast leakage, premature termination of the examination) and major (fever, urinary tract infection, bladder perforation). Fluoroscopy time and radiation parameters were compared. Examination quality was assessed based on the satisfactory acquisition of fluoroscopic images using a four-point Likert scale. Results: In 9% of the SPA examinations a method switch to TUC was necessary. The minor complication rate was 1.9% for TUC and 35.7% for SPA (p < 0.001). The major complication rate was 0.9% for TUC and 2% for SPA (p > 0.05). Mean fluoroscopy time and radiation dose were significantly lower in TUC (TUC, 26 ± 19 s, 0.6 ± 1.2 µGy·m2; SPA, 38 ± 33 s, 1.7 ± 2.9 µGy·m2; p = 0.01/0.001). There was no significant difference regarding the amount of contrast media applied (TUC, 62 ± 40 mL; SPA, 66 ± 41 mL; p > 0.05) and the examination quality with full diagnostic quality achieved in 88% of TUC and 89% of SPA examinations (p > 0.05). Conclusions: As TUC provides significantly lower radiation exposure and less periprocedural complications, it should be the primary bladder access route for VCUG in pediatric male patients.

Abstract Cognitive impairment is the most frequent symptom reported in post-COVID-19 syndrome (PCS). Aetiology of cognitive impairment in PCS is still to be determined. Neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP) are increased in acute COVID-19. Their role as biomarkers in other neurological disorders is under debate. We analysed serum levels of NfL and GFAP as markers for neuronal and astrocytic damage in 53 patients presenting to a PCS Neurology outpatient clinic. Only individuals with self-reported cognitive complaints were included. In these individuals, cognitive complaints were further assessed by comprehensive neuropsychological assessment (NPA). Patients were categorized into subgroups of subjective cognitive decline, single domain impairment, or multi-domain impairment. Serum NfL was in normal range, however an increase of serum GFAP was detected in 4% of patients. Serum NfL and GFAP levels correlated with each other, even when adjusting for patient age (r = 0.347, p = 0.012). NPA showed deficits in 70%; 40% showing impairment in several tested domains. No significant differences were found between serum NfL- and GFAP-levels comparing patients with subjective cognitive decline, single domain impairment, or multi-domain impairment. Persistent neuronal or astrocytic damage did not correlate with cognitive impairment in PCS.

Introduction Colorectal cancer (CRC) survivors often struggle with side effects following treatment such as reduced quality of life, fatigue and psychological distress and need therefore efficient comprehensive interventions. The aim of this qualitative study was to explore CRC survivors’ expectations before the yoga intervention as well as their unique experiences beyond those reported with standard questionnaires.Methods Interpretative phenomenological approach was used in this qualitative study. Semi-structured interviews were conducted before and after a 10-week yoga program (90 min once a week, Hatha Yoga) with CRC survivors enrolled in a randomized controlled trial. Thematic analysis was used to uncover themes present in participants’ accounts.Results Nine patients participated in the interviews, mean interview duration was 27.49 min (SD = 7.71) before and 38.41 min (SD = 15.93) after the intervention. Our analysis identified following themes: (1) representations and expectations from the yoga intervention; (2) course structure and implementation; (3) perceptions and effects of the intervention; (4) differences between the study yoga intervention and other physical activities. The superordinate theme regarding effects of intervention included aspects of intervention at multiple levels such as emotional, physical, behavioral and spiritual.Conclusions This qualitative study provides valuable insight regarding CRC survivors’ expectations and experiences following a 10-week yoga intervention. While expectations varied from skepticism to specific symptom improvement, the majority of participants had a positive, open attitude towards yoga. Consistent with participants’ experiences, yoga may represent a promising intervention for CRC survivors if the groups’ specific concerns are taken into account.

Background COVID-19 remains a challenge to individual health and healthcare resources worldwide. Telemedical surveillance might minimise hospitalisation and direct patient–physician contacts. Yet, randomised clinical trials evaluating telemedical management of COVID-19 patients are lacking. Methods COVID-SMART is a randomised, open-label, controlled clinical trial investigating whether telemedicine reduces the primary end-point of hospitalisation or any unscheduled utilisation of an emergency medical service within 30 days of follow-up. Key secondary end-points included mortality and primary end-point components. We enrolled acutely infected SARS-CoV-2 patients suitable for outpatient care. All presented with ≥1 risk factor for an adverse COVID-19 course. Patients were randomised 1:1 into a control group receiving standard of care and an intervention group receiving smartphone-based assessment of oxygen saturation, heart rate and electrocardiogram, and telemedical counselling via a 24/7 emergency hotline. Results Of 607 enrolled patients (mean±sd age 46.7±13.5 years), 304 were randomised into the intervention and 303 into the control group. The primary end-point occurred in 6.9% (n=21) of the intervention and in 9.6% (n=29) of the control group (hazard ratio (HR) 0.72, 95% confidence interval (CI) 0.41–1.26; p=0.24). No deaths occurred during follow-up. Fewer intervention group participants utilised outpatient-based emergency medical services (HR 0.43, 95% CI 0.20–0.90; p=0.03). Conclusions COVID-SMART is the first randomised clinical trial assessing the benefit of telemedicine in an acute respiratory infectious disease. Whereas telemedical management did not reduce the primary end-point of hospitalisation, fewer intervention group patients used outpatient-based emergency services, suggesting a potential benefit for less-acutely infected individuals.

Background and purpose The associations of fundamental motor skills (FMS), health-related physical fitness (e.g., cardiorespiratory fitness, CRF), and moderate-vigorous physical activity (MVPA) have been demonstrated in Western children, but these associations have not yet been validated in a sample of Chinese children. The aims of this study, therefore, were to examine the association between FMS subdomains and MVPA in a sample of Chinese children and to evaluate whether this association is mediated by CRF. Methods A cross-sectional study consisting of 311 children aged 8–12 years (49.2% girls; mean age = 9.9 years) from Shanghai was conducted. FMS, CRF and MVPA were assessed using the Test of Gross Motor Development-3rd Edition, Progressive Aerobic Cardiovascular Endurance Run and ActiGraph GT3X accelerometers. Preacher & Hayes’s bootstrap method was used to test the mediating effects of CRF on the association between FMS and MVPA. Results CRF fully mediated the association between total FMS and MVPA in girls (indirect effects, b = 0.21, 95% CI [0.07–0.37]), while the mediation was only partial in boys (indirect effects, b = 0.12, 95% CI [0.01–0.26]). CRF fully mediated the association between locomotor skills and MVPA in girls (indirect effects, b = 0.27, 95% CI [0.09– 0.51]), whereas CRF partially mediated the association between object control skills and MVPA in boys (indirect effects, b = 0.15, 95% CI [0.18–0.35]). Conclusion In order to better design and implement sex-specific interventions aiming to increase MVPA, it is essential to consider FMS subdomains and CRF alongside the sex differences in the association between them.

Abstract Cholesterol deposition in intimal macrophages leads to foam cell formation and atherosclerosis. Reverse cholesterol transport (RCT), initiated by efflux of excess cholesterol from foam cells, counteracts atherosclerosis. However, targeting RCT by enhancing cholesterol efflux was so far accompanied by adverse hepatic lipogenesis. Here, we aimed to identify novel natural enhancers of macrophage cholesterol efflux suitable for the prevention of atherosclerosis. Plant extracts of an open-access library were screened for their capacity to increase cholesterol efflux in RAW264.7 macrophages trace-labeled with fluorescent BODIPY-cholesterol. Incremental functional validation of hits yielded two final extracts, elder (Sambucus nigra) and bitter orange (Citrus aurantium L.) that induced ATP binding cassette transporter A1 (ABCA1) expression and reduced cholesteryl ester accumulation in aggregated LDL-induced foam cells. Aqueous elder extracts were subsequently prepared in-house and both, flower and leaf extracts increased ABCA1 mRNA and protein expression in human THP-1 macrophages, while lipogenic gene expression in hepatocyte-derived cells was not induced. Chlorogenic acid isomers and the quercetin glycoside rutin were identified as the main polyphenols in elder extracts with putative biological action. In summary, elder flower and leaf extracts increase macrophage ABCA1 expression and reduce foam cell formation without adversely affecting hepatic lipogenesis.

Abstract Optical coherence tomography angiography (OCTA) enables three-dimensional reconstruction of the functional blood vessels in the retina. Therefore, it enables the quantification of 3D retinal vessel parameters such as surface area and vessel volume. In spite of the widespread use of OCTA, no representative volume-rendered vessel volume (VV) data are published to date. In this study, OCTA 3 × 3 mm macular cubes were processed with volume-rendering techniques to measure VV in 203 eyes from 107 healthy volunteers. Generalized linear models (GLM) were constructed to assess the impact of age, gender, visual acuity (VA), spherical equivalent (SE), and axial length (AL) on VV. Overall mean VV was 0.23 ± 0.05mm3. Age and axial length showed a negative correlation with VV. However, GLM model analysis found that AL exerted the most pronounced influence on VV. No statistically significant associations were identified between gender or between left and right eyes. This is the first study to assess 3D OCTA VV and its naturally occurring variations in a large series of healthy subjects. It offers novel insights into the characterization of normal retinal vascular anatomy in healthy individuals, contributing to a valuable reference for future research in this field.

Abstract Increasing dorsolateral prefrontal cortex (DLPFC) activity by anodal transcranial direct current stimulation (tDCS) enhances cognitive control and might reduce aggression. The Val158Met polymorphism within the catechol-O-methyltransferase gene (rs4680) plays a pivotal role in prefrontal dopamine signaling, displaying associations with aggressive behavior, and potentially influencing the effects of tDCS. In a double-blind, sham-controlled study, we investigated the influence of rs4680 on tDCS effects on aggression. While undergoing functional magnetic resonance imaging, 89 healthy male participants performed the Taylor aggression paradigm before and immediately after tDCS. Actively stimulated participants (n = 45) received anodal tDCS (1.5 mA) for 20 min targeting the right DLPFC. Carriers of the val-allele (val+; n = 46; active tDCS n = 23) were compared to met-allele homozygotes (val−; n = 43; active tDCS n = 22). Analysis revealed decreased aggressive behavior in the val− group following active tDCS (p

Abstract This study aimed to validate a wearable device’s walking speed estimation pipeline, considering complexity, speed, and walking bout duration. The goal was to provide recommendations on the use of wearable devices for real-world mobility analysis. Participants with Parkinson’s Disease, Multiple Sclerosis, Proximal Femoral Fracture, Chronic Obstructive Pulmonary Disease, Congestive Heart Failure, and healthy older adults (n = 97) were monitored in the laboratory and the real-world (2.5 h), using a lower back wearable device. Two walking speed estimation pipelines were validated across 4408/1298 (2.5 h/laboratory) detected walking bouts, compared to 4620/1365 bouts detected by a multi-sensor reference system. In the laboratory, the mean absolute error (MAE) and mean relative error (MRE) for walking speed estimation ranged from 0.06 to 0.12 m/s and − 2.1 to 14.4%, with ICCs (Intraclass correlation coefficients) between good (0.79) and excellent (0.91). Real-world MAE ranged from 0.09 to 0.13, MARE from 1.3 to 22.7%, with ICCs indicating moderate (0.57) to good (0.88) agreement. Lower errors were observed for cohorts without major gait impairments, less complex tasks, and longer walking bouts. The analytical pipelines demonstrated moderate to good accuracy in estimating walking speed. Accuracy depended on confounding factors, emphasizing the need for robust technical validation before clinical application. Trial registration: ISRCTN – 12246987.

Abstract Modern cementless short stems in total hip arthroplasty (THA) enable a precise reconstruction of the native pre-arthritic hip geometry. While gender differences have been reported for older generation straight hip stems, there are hardly reports regarding modern cementless short hip stems. Therefore, we aimed to evaluate the influence of gender differences in hip anatomy in cementless short stem THA. A total of 207 patients (109 females, 98 males) with unilateral THA and absence of contralateral joint space narrowing (Kellgren-Lawrence grade ≤ 2) were included. Acetabular height and offset as well as femoral height and offset were measured on pre- and 3-months-postoperative anteroposterior X-rays of the pelvis and compared to the contralateral hip. Additionally, implant position was evaluated on the postoperative radiograph. In male patients, the loss of acetabular offset was significantly greater than in females (p = 0.012), leading to a compensatory increase in femoral offset (p = 0.041). Femoral height discrepancy was significantly higher in females (p

Abstract Secretory immunoglobulin A (sIgA) in saliva is the most important immunoglobulin fighting pathogens in the respiratory tract and may thus play a role in preventing SARS-CoV-2 infections. To gain a better understanding of the plasticity in the mucosal antibody, we investigated the proactive change in secretion of salivary SARS-CoV-2-specific sIgA in 45 vaccinated and/or previously infected, generally healthy persons (18 to 35 years, 22 women). Participants were exposed to a disease video displaying humans with several respiratory symptoms typical for COVID-19 in realistic situations of increased contagion risk. The disease video triggered an increase in spike-specific sIgA, which was absent after a similar control video with healthy people. The increase further correlated inversely with revulsion and aversive feelings while watching sick people. In contrast, the receptor binding domain-specific sIgA did not increase after the disease video. This may indicate differential roles of the two salivary antibodies in response to predictors of airborne contagion. The observed plasticity of spike-specific salivary antibody release after visual simulation of enhanced contagion risk suggests a role in immune exclusion.

The Electro Cardio Gram (ECG) is a very valuable clinical tool to access the electric function of the heart. It provides insight into the different phases of the heart beat and various kinds of disorders which may affect them. In literature the impact of linear dependency between feature signals upon the classification outcome and how to reduce it have been largely investigated and discussed. This study puts a focus upon linear dependency between samples of imbalanced data sets, its relation to the observed over fitting with respect to majority classes and hot to reduce it. A set of 58 feature signals is used to train a several LDA classifier either discriminating 3 classes (Normal, Artefact, Arrhythmic) or 5 Classes (Normal, Artefact, Atrial and ventricular premature contractions and bundle branch blocks). The training data set is preprocessed using four sample reduction approaches and a nearest neighbour clustering method. In the case of 5 classes accuracies of 96.82% in the imbalanced case and 97.44% for the data preprocessed with the QR or SVD methods were obtained. For 3 classes curacies of 97.68% and 98.12% were achieved. With the nearest neighbour clustering method only accuracies of 96.00% for 5 classes and 97.37% for 3 classes could be achieved. The results clearly show that imbalanced ECG data does contain linear dependent samples. These cause a bias towards majority class which will be over fitted by the classifier. Sample reduction methods and algorithms which are not aware of the presence linear dependent samples like the nearest neighbour clustering approach even further increase this bias ore even worse destroy relevant information by merging samples which encode distinct aspects of the beat class, destroying relevant information.

Poliovirus infection causes paralysis in up to 1 in 200 infected persons. The use of safe and effective inactivated poliovirus vaccines and live attenuated oral poliovirus vaccines (OPVs) means that only two pockets of wildtype poliovirus type 1 remain, in Afghanistan and Pakistan. However, OPVs can revert to virulence, causing outbreaks of circulating vaccine-derived poliovirus (cVDPV). During 2020–2022, cVDPV type 2 (cVDPV2) was responsible for 97–99% of poliomyelitis cases, mainly in Africa. Between January and August 2022, cVDPV2 was detected in sewage samples in Israel, the United Kingdom and the United States of America, where a case of acute flaccid paralysis caused by cVDPV2 also occurred. The Pan American Health Organization has warned that Brazil, the Dominican Republic, Haiti and Peru are at very high risk for the reintroduction of poliovirus and an additional eight countries in Latin America are at high risk, following dropping vaccination rates (average 80% coverage in 2022). Sabin type 2 monovalent OPV has been used to control VDPV2 outbreaks, but its use could also lead to outbreaks. To address this issue, a more genetically stable, novel OPV2 (nOPV2) was developed against cVDPV2 and in 2020 was granted World Health Organization Emergency Use Listing. Rolling out a novel vaccine under the Emergency Use Listing in mass settings to contain outbreaks requires unique local regulatory and operational preparedness.

BackgroundWrist-worn inertial sensors are used in digital health for evaluating mobility in real-world environments. Preceding the estimation of spatiotemporal gait parameters within long-term recordings, gait detection is an important step to identify regions of interest where gait occurs, which requires robust algorithms due to the complexity of arm movements. While algorithms exist for other sensor positions, a comparative validation of algorithms applied to the wrist position on real-world data sets across different disease populations is missing. Furthermore, gait detection performance differences between the wrist and lower back position have not yet been explored but could yield valuable information regarding sensor position choice in clinical studies. ObjectiveThe aim of this study was to validate gait sequence (GS) detection algorithms developed for the wrist position against reference data acquired in a real-world context. In addition, this study aimed to compare the performance of algorithms applied to the wrist position to those applied to lower back–worn inertial sensors. MethodsParticipants with Parkinson disease, multiple sclerosis, proximal femoral fracture (hip fracture recovery), chronic obstructive pulmonary disease, and congestive heart failure and healthy older adults (N=83) were monitored for 2.5 hours in the real-world using inertial sensors on the wrist, lower back, and feet including pressure insoles and infrared distance sensors as reference. In total, 10 algorithms for wrist-based gait detection were validated against a multisensor reference system and compared to gait detection performance using lower back–worn inertial sensors. ResultsThe best-performing GS detection algorithm for the wrist showed a mean (per disease group) sensitivity ranging between 0.55 (SD 0.29) and 0.81 (SD 0.09) and a mean (per disease group) specificity ranging between 0.95 (SD 0.06) and 0.98 (SD 0.02). The mean relative absolute error of estimated walking time ranged between 8.9% (SD 7.1%) and 32.7% (SD 19.2%) per disease group for this algorithm as compared to the reference system. Gait detection performance from the best algorithm applied to the wrist inertial sensors was lower than for the best algorithms applied to the lower back, which yielded mean sensitivity between 0.71 (SD 0.12) and 0.91 (SD 0.04), mean specificity between 0.96 (SD 0.03) and 0.99 (SD 0.01), and a mean relative absolute error of estimated walking time between 6.3% (SD 5.4%) and 23.5% (SD 13%). Performance was lower in disease groups with major gait impairments (eg, patients recovering from hip fracture) and for patients using bilateral walking aids. ConclusionsAlgorithms applied to the wrist position can detect GSs with high performance in real-world environments. Those periods of interest in real-world recordings can facilitate gait parameter extraction and allow the quantification of gait duration distribution in everyday life. Our findings allow taking informed decisions on alternative positions for gait recording in clinical studies and public health. Trial RegistrationISRCTN Registry 12246987; https://www.isrctn.com/ISRCTN12246987 International Registered Report Identifier (IRRID)RR2-10.1136/bmjopen-2021-050785

The AUD2IT-algorithm is a tool to structure the data, which is collected during an emergency treatment. The goal is on the one hand to structure the documentation of the data and on the other hand to give a standardised data structure for the report during handover of an emergency patient. AUD2IT-algorithm was developed to provide residents a documentation aid, which helps to structure the medical reports without getting lost in unimportant details or forgetting important information. The sequence of anamnesis, clinical examination, considering a differential diagnosis, technical diagnostics, interpretation and therapy is rather an academic classification than a description of the real workflow. In a real setting, most of these steps take place simultaneously. Therefore, the application of the AUD2IT-algorithm should also be carried out according to the real processes. A big advantage of the AUD2IT-algorithm is that it can be used as a structure for the entire treatment process and also is entirely usable as a handover protocol within this process to make sure, that the existing state of knowledge is ensured at each point of a team-timeout. PR-E-(AUD2IT)-algorithm makes it possible to document a treatment process that, in principle, does not have to be limited to the field of emergency medicine. Also, in the outpatient treatment the PR-E-(AUD2IT)-algorithm could be used and further developed. One example could be the preparation and allocation of needed resources at the general practitioner. The algorithm is a standardised tool that can be used by healthcare professionals of any level of training. It gives the user a sense of security in their daily work.

Summary: Background: In cardiovascular magnetic resonance imaging parametric T1 mapping lacks universally valid reference values. This limits its extensive use in the clinical routine. The aim of this work was the introduction of our self-developed Magnetic Resonance Imaging Software for Standardization (MARISSA) as a post-hoc standardisation approach. Methods: Our standardisation approach minimises the bias of confounding parameters (CPs) on the base of regression models. 214 healthy subjects with 814 parametric T1 maps were used for training those models on the CPs: age, gender, scanner and sequence. The training dataset included both sex, eleven different scanners and eight different sequences. The regression model type and four other adjustable standardisation parameters were optimised among 240 tested settings to achieve the lowest coefficient of variation, as measure for the inter-subject variability, in the mean T1 value across the healthy test datasets (HTE, N = 40, 156 T1 maps). The HTE were then compared to 135 patients with left ventricular hypertrophy including hypertrophic cardiomyopathy (HCM, N = 112, 121 T1 maps) and amyloidosis (AMY, N = 24, 24 T1 maps) after applying the best performing standardisation pipeline (BPSP) to evaluate the diagnostic accuracy. Findings: The BPSP reduced the COV of the HTE from 12.47% to 5.81%. Sensitivity and specificity reached 95.83% / 91.67% between HTE and AMY, 71.90% / 72.44% between HTE and HCM, and 87.50% / 98.35% between HCM and AMY. Interpretation: Regarding the BPSP, MARISSA enabled the comparability of T1 maps independently of CPs while keeping the discrimination of healthy and patient groups as found in literature. Funding: This study was supported by the BMBF / DZHK.

Objectives Public access databases such as clinicaltrials.gov achieve dissemination of clinical trial design and aggregated study results. However, return of participant-level data is rarely done. A key barrier includes the proprietary ownership of data by the sponsor. Additionally, investigators may not have access to centralised data, and per International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) Good Clinical Practice, must maintain the confidentiality of participants. This study piloted an approach to return both individual and aggregate clinical trial data to parents of children participating in a series of open-label clinical trials.Setting and design A small biotech company obtained central ethics approval (centralised institutional review board [IRB], non-exempt). The study was advertised via parent advocacy groups. Parents of trial participants were offered the option to contact an employee (coordinator) within the company, requesting return of their child’s study results. Ethics approval covered participation in six countries. The study focused on the sequential clinical trials of vamorolone VBP15-002 (NCT02760264) and VBP15-003 (NCT02760277) (post-results).Interventions Contact initiated by the parent enabled the coordinator to obtain informed consent (and separate General Data Protection Regulations consent), with phone translation when needed. Using date of birth and study site location provided by the parent, the data manager reported the participant number to the coordinator. The coordinator retrieved and compiled data, along with an aggregate summary, which was mailed via a password protected and encrypted memory device to the parent. Prereturn and postreturn surveys were sent to consented parents (n=19; 40% of 48 total trial participants) and investigators.Results Prereturn surveys indicated a request for as much data as offered, in all formats offered. Postreturn survey showed high satisfaction with the process and data returned. Survey of the physician site investigators (n=10; 100% participation of investigators) voiced general satisfaction with the process, with some reservations.Conclusions This pilot study demonstrates an innovative, cost-effective, centralised and labour conservative approach to return of participant-level and aggregate data to participants in studies.

Abstract Short stems are associated with a significantly lower blood loss (BL) compared to straight stems in total hip arthroplasty (THA). Different types of stems differ in design, fixation and level of femoral neck osteotomy. Therefore, we sought to evaluate the difference regarding the perioperative BL between two short stems with different designs in direct anterior approach (DAA). A total of 187 THA performed by a single surgeon were analysed. 107 patients received a neck-resecting (Group A) and 80 patients a neck-sparing short stem (Group B). Blood counts of the day before surgery and of two days after surgery were evaluated. Total blood volume and BL were calculated. Additionally, duration of surgery was analysed. The perioperative BL was significantly lower in Group B (451.4 ± 188.4 ml) compared to Group A (546.6 ± 232.7 ml; p = 0.002). The postoperative haematocrit (31.6 ± 3.7% vs. 30.4 ± 4.4%; p = 0.049) and haemoglobin-level (11.0 ± 1.3 g/dL vs. 10.4 ± 1.5 g/dL; p = 0.002) were significantly higher in Group B. Duration of surgery was significantly shorter in Group B (62.0 ± 11.4 min vs. 72.6 ± 21.8 min; p

Abstract In the framework of the Laser Lightning Rod project, whose aim is to show that laser-induced filaments can guide lightning discharges over considerable distances, we study over a distance of 140 m the filaments created by a laser system with J-range pulses of 1 ps duration at 1 kHz repetition rate. We investigate the spatial evolution of the multiple filamentation regime using the fundamental beam at 1030 nm or using combination with the second and third harmonics. The measurements were made using both a collimated beam and a loosely focused beam.

Abstract Background With the first complete draft of a human genome, the Telomere-to-Telomere Consortium unlocked previously concealed genomic regions for genetic analyses. These regions harbour nearly 2000 potential novel genes with unknown function. In order to uncover candidate genes associated with human neurological pathologies, a comparative transcriptome study using the T2T-CHM13 and the GRCh38 genome assemblies was conducted on previously published datasets for eight distinct human neurological disorders. Results The analysis of differential expression in RNA sequencing data led to the identification of 336 novel candidate genes linked to human neurological disorders. Additionally, it was revealed that, on average, 3.6% of the differentially expressed genes detected with the GRCh38 assembly may represent potential false positives. Among the noteworthy findings, two novel genes were discovered, one encoding a pore-structured protein and the other a highly ordered β-strand-rich protein. These genes exhibited upregulation in multiple epilepsy datasets and hold promise as candidate genes potentially modulating the progression of the disease. Furthermore, an analysis of RNA derived from white matter lesions in multiple sclerosis patients indicated significant upregulation of 26 rRNA encoding genes. Additionally, putative pathology related genes were identified for Alzheimer’s disease, amyotrophic lateral sclerosis, glioblastoma, glioma, and conditions resulting from the m.3242 A > G mtDNA mutation. Conclusion The results presented here underline the potential of the T2T-CHM13 assembly in facilitating the discovery of candidate genes from transcriptome data in the context of human disorders. Moreover, the results demonstrate the value of remapping sequencing data to a superior genome assembly. Numerous potential pathology related genes, either as causative factors or related elements, have been unveiled, warranting further experimental validation.

Abstract Positron emission tomography with 68Gallium (68Ga) labeled inhibitors of fibroblast activation protein (68Ga-FAPI-PET) is a promising imaging technique for patients with recurrent pancreatic ductal adenocarcinomas (PDAC). To date, it is not clear if different acquisition timepoints for 68Ga-FAPI-PET may result in comparable imaging information and if repetitive 68Ga-FAPI-PET imaging may add diagnostic value to single timepoint acquisition for recurrent PDAC. Here we analyzed retrospectively early (20 min p.i.) and late (60 min p.i.) 68Ga-FAPI-PET imaging using FAPI-46 of 33 patients with possible recurrence of PDAC concerning detection rates and uptake over time of local recurrences, metastases, inflammatory lesions of the pancreas, cholestatic lesions of the liver and reactive tissue. 33 patients with histologically confirmed PDAC after complete or partial resection of the pancreas and possible recurrence were examined by 68Ga-FAPI-46-PET acquired 20- and 60-min post injection (p.i.) of the radiotracer. FAPI-positive lesions were classified as local recurrences, metastases, inflammatory lesions of the pancreas (ILP), cholestatic lesions of the liver and reactive tissue based on histology, PET- and CT-morphology and clinical information. Lesions were contoured, and standardized uptake values (SUVmax and SUVmean) and target-to-background ratios (TBR) were analyzed for both acquisition timepoints. In total, 152 FAPI-positive lesions (22 local relapses, 47 metastases, 26 inflammatory lesions of the pancreas, 28 reactive tissues, and 29 cholestatic lesions) were detected. Detection rates for the early and late acquisition of 68Ga-FAPI-46-PET were almost identical except cholestatic lesions, which showed a higher detection rate at early imaging. SUV parameters and TBRs of ILP significantly decreased over time. Cholestatic lesions showed a tendency towards decreasing uptake. All other types of lesions showed relatively stable uptake over time. Early and late acquisition of 68Ga-FAPI-PET results in comparable imaging information in patients with possible recurrence of PDAC. Two timepoint imaging offers additional diagnostic potential concerning differential diagnoses.

Abstract We sought to evaluate the rates and predictors of SARS-CoV-2 vaccination among members of a structurally-marginalized population of people who use drugs (PWUD) during a targeted, community-wide, vaccination campaign in Vancouver, Canada. Interviewer-administered data were collected from study participants between June 2021 and March 2022. Generalized estimating equation analysis was used to identify factors associated with SARS-CoV-2 vaccine uptake, ascertained through a province-wide vaccine registry. Among 223 PWUD, 107 (48.0%) reported receipt of at least two SARS-CoV-2 vaccine doses at baseline and this increased to 151 (67.7%) by the end of the study period. Using social media as a source of vaccine information was negatively associated with SARS-CoV-2 vaccine uptake (Adjusted odds ratio [AOR] 0.27, 95% confidence interval [CI] 0.09–0.81) and HIV seropositivity (AOR 2.68, 95% CI 1.12–6.39) and older age (AOR 1.27, 95% CI 1.07–1.51) were positively associated with SARS-CoV-2 vaccine uptake. These findings suggest that the targeted vaccination campaign in Vancouver may be an effective model to promote SARS-CoV-2 vaccination in other jurisdictions. However, using social media as a source of vaccine information likely reduced SARS-CoV-2 vaccine uptake in PWUD arguing for further efforts to promote accessible and evidence-based vaccine information among marginalized populations.

Abstract When a colloidal probe is forced through a viscoelastic fluid which is characterized by a long stress-relaxation time, the fluid is excited out of equilibrium. This is leading to a number of interesting effects including a non-trivial recoil of the probe when the driving force is removed. Here, we experimentally and theoretically investigate the transient recoil dynamics of non-spherical particles, i.e., colloidal dumbbells. In addition to a translational recoil of the dumbbells, we also find a pronounced angular reorientation which results from the relaxation of the surrounding fluid. Our findings are in good agreement with a Langevin description based on the symmetries of a director (dumbbell) as well as a microscopic bath-rod model. Remarkably, we find an instability with amplified fluctuations when the dumbbell is oriented perpendicular to the direction of driving. Our results demonstrate the complex behavior of non-spherical objects within a relaxing environment which are of immediate interest for the motion of externally but also self-driven asymmetric objects in viscoelastic fluids.

Abstract Collective self-organization of animal groups is a recurring phenomenon in nature which has attracted a lot of attention in natural and social sciences. To understand how collective motion can be achieved without the presence of an external control, social interactions have been considered which regulate the motion and orientation of neighbors relative to each other. Here, we want to understand the motivation and possible reasons behind the emergence of such interaction rules using an experimental model system of light-responsive active colloidal particles (APs). Via reinforcement learning (RL), the motion of particles is optimized regarding their foraging behavior in presence of randomly appearing food sources. Although RL maximizes the rewards of single APs, we observe the emergence of collective behaviors within the particle group. The advantage of such collective strategy in context of foraging is to compensate lack of local information which strongly increases the robustness of the resulting policy. Our results demonstrate that collective behavior may not only result on the optimization of behaviors on the group level but may also arise from maximizing the benefit of individuals. Apart from a better understanding of collective behaviors in natural systems, these results may also be useful in context of the design of autonomous robotic systems.

The electrocardiogram is a very valuable clinical tool which allows to retrieve information about the presence and location of arrhythmic foci as well as ischemic and scar tissue and disorder’s of the dedicated cardiac conduction system. In the presented study timing parameters computed by a delineating beat detector for identifying the P-Wave, QRS - complex and T-Wave are used to classify the individual beats. From a set of total 419 feature generated from these parameters 64 are used to train LDA classifier for discriminating 3 classes (Normal, Artifact, Arrhythmic) and 5 Classes (Normal, Artifact, Atrial and ventricular premature contractions and bundle branch blocks). Further it is investigated how the imbalance between normal beats and arrhythmic beats as well as the beats missed by the beat detector affect the classification results. In the case of 5 classes accuracies of 97.52 % in the imbalanced case and 96.38 r for the balanced data were obtained. For 3 classes accuracies of 97.76 % and 95.18 % were achieved. Considering in addition the beats missed by the detector the accuracies dropped to 96.68 %, and 95.54 % for 5 classes and 95.54 % and 96.92 % for 3 classes. These values are within the ranges for linear classifier reported in literature. This is quite promising for implementing a real-time classifier which exploits the parameters and values computed by the beat detector.

Abstract Biliary tract cancers are rare cancers with poor prognosis due to a lack of therapeutic options, especially after the failure of first-line systemic treatment. Targeted treatments for this clinical situation are promising and have entered clinical practice. We aimed to describe the overall survival of matched targeted treatment after first-line treatment in patients with biliary tract cancers in an Austrian real-world multicenter cohort. We performed a multicenter retrospective chart review of patients with biliary tract cancer between September 2015 and January 2022. Data, including comprehensive molecular characteristics—next generation sequencing (NGS) and immunohistochemistry (IHC), clinical history, surgical procedures, ablative treatments, patient history, and systemic chemotherapy, were extracted from the records of the participating institutions. Targeted treatment was matched according to the ESMO scale for the clinical actionability of molecular targets (ESCAT). We identified 159 patients with the available molecular characteristics. A total of 79 patients underwent second-line treatment. Of these, 36 patients received matched targeted treatment beyond the first-line and were compared with 43 patients treated with cytotoxic chemotherapy in terms of efficacy outcomes. For Tier I/II alterations, we observed a progression free survival ratio (PFStargeted/PFSpre-chemotherapy) of 1.86, p = 0.059. The overall survival for patients receiving at least two lines of systemic treatment significantly favored the targeted approach, with an overall survival of 22.3 months (95% CI 14.7–29.3) vs. 17.5 months (95% CI 1.7–19.8; p = 0.048). Our results underscore the value of targeted treatment approaches based on extended molecular characterization of biliary tract cancer to improve clinical outcomes.

A strategic priority of the World Health Organization’s Immunization Agenda 2030 is to increase vaccination coverage and equity through reaching “zero-dose” children. Through an ecological study, we sought to quantify the impact of the COVID-19 pandemic on the coverage of the pentavalent and the measles/rubella vaccines in Kenya, without implying causality. The monthly number of doses from January 2017 to August 2022 were obtained from the Kenya Health Information System for the pentavalent and the measles/rubella vaccines. Immediate (step) and long-term (ramp) changes following interruptions occurring during the period from March 2020 to December 2020 were assessed through an interrupted time series analysis using an autoregressive integrated moving average (ARIMA) model, accounting for seasonality. In December 2020, there was an immediate decrease of 8337, 12,212, and 20,848 in the number of doses for the first, second, and third dose of the pentavalent vaccine, respectively (statistically significant for the third dose only). This corresponded to a percentage relative difference of −21.6, −20.1, and −24.5, respectively, for three doses of pentavalent vaccines, while for measles/rubella vaccine it was −27.3 and −33.6, respectively, for the first and second dose. COVID-19 resulted in interruptions affecting routine immunization, but recovery occurred within four months.

Background: Several COVID-19 vaccines were developed and approved in China. Of these, the BIBB-CorV and CoronaVac inactivated whole-virion vaccines were widely distributed in China and developing countries. However, the performance of the two vaccines in the real world has not been summarized. Methods: A living systematic review based on findings from ongoing post-licensure studies was conducted, applying standardized algorithms. Articles published between 1 May 2020 and 31 May 2022 in English and Chinese were searched for in Medline, Embase, WanFang Data, medRxiv, bioRxiv, arXiv, SSRN, and Research Square, using SARS-CoV-2, COVID-19, and vaccine as the MeSH terms. Studies with estimates of safety, immunogenicity, and effectiveness from receiving the BIBB-CorV or CoronaVac vaccine that met the predefined screening criteria underwent a full-text review. The Joanna Briggs Institute’s Critical Appraisal Checklist and the Cochrane risk of bias were used for assessment of the quality. A random-effects meta-regression model was applied to identify the potential impact factors on the vaccines’ effectiveness. Results: In total, 32578 articles were identified, of these, 770 studies underwent a full-text review. Eventually, 213 studies were included. The pooled occurrence of solicited and unsolicited adverse events after any dose of either vaccine varied between 10% and 40%. The top five commonly reported rare adverse events were immunization stress-related responses (211 cases, 50.0%), cutaneous responses (43 cases, 10.2%), acute neurological syndrome (39 cases, 9.2%), anaphylaxis (17 cases, 4.0%), and acute stroke (16 cases, 3.8%). The majority (83.3%) recovered or were relieved within several days. The peak neutralization titers against the ancestral strain was found within 1 month after the completion of the primary series of either vaccine, with a GMT (geometric mean titer) of 43.7 (95% CI: 23.2–82.4), followed by a dramatic decrease within 3 months. At Month 12, the GMT was 4.1 (95% CI: 3.8–4.4). Homologous boosting could restore humoral immunity, while heterologous boosting elicited around sixfold higher neutralization titers in comparison with homologous boosting. The effectiveness of receiving either vaccine against death and severe disease was around 85% for both shortly after the primary series. At Month 12, the protection against death did not decline, while the protection against severe disease decreased to ~75%. Conclusions: Both the BIBP-CorV and CoronaVac inactivated vaccines are safe. Sustained vaccine effectiveness against death was determined 12 months after the primary series, although protection against severe disease decreased slightly over time. A booster dose could strengthen the waning effectiveness; however, the duration of the incremental effectiveness and the additional benefit provided by a heterologous booster need to be studied.

(1) Background: Meteorological factors seem to exert various effects on human health, influencing the occurrence of diseases such as thromboembolic events and strokes. Low atmospheric pressure in summer may be associated with an increased likelihood of ischemic stroke. The aim of this study was to investigate the potential impact of meteorological conditions on left atrial appendage (LAA) thrombus formation. (2) Methods: A total of 131 patients were included, diagnosed with a first instance of thrombus via 3D transesophageal echocardiography (TEE) between February 2009 and February 2019. Months with frequent thrombus diagnoses of at least 10 thrombi per month were categorized as frequent months (F-months), while months with fewer than 10 thrombus diagnoses per month were labelled as non-frequent months (N-months). The analysis focused on differences in meteorological parameters in two-week and four-week periods before the diagnosis. (3) Results: F-months were predominantly observed in spring and summer (April, May, June, and July), as well as in February and November. During F-months, a higher absolute temperature difference, lower relative humidity, longer daily sunshine duration, and greater wind speed maximum were observed in the two- and four-week periods rather than for N-months. In the two-week period, average temperatures, equivalent temperatures, and temperature maxima were also significantly higher during F-months than N-months. (4) Conclusion: Thrombi in the left atrial appendage are more prevalent during periods characterized by high absolute temperature differences, low relative humidity, and long daily sunshine duration.