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Well maintained cycleways will encourage more people to cycle, as the condition of cycleways is important for the safety, accessibility and riding comfort of cyclists. Despite that, only a few models used to describe the quality of service for cyclists take the surface condition into account. Objective measuring methods are needed to enable reliable and effective assessment of surface conditions, and measurable performance criteria related to the needs of cyclists should be developed. The purpose of this study has been to test the reliability and validity of using accelerometers in smartphones to assess the riding comfort on cycleways. A smartphone application converting three-dimensional accelerometer measurements into a single indicator for cycleways has been used to assess road surfaces in two field studies, in Sweden and Norway, respectively. Both studies assessed test sections of varying quality. To relate the measurements to subjective riding comfort assessments by cyclists, recruited cyclists collected quantitative data using the app, whilst also rating their perceived riding comfort by completing a survey. Measurements were also related to standard road surface condition indicators, generated from a road surface tester equipped with 19 laser sensors: international roughness index (IRI), mega- and macrotexture. The results show that it is possible to describe the unevenness of a cycleway using the technology present in smartphones. A software application can be used to collect and analyse data from the acceleration sensors in the phone, which can then be used to describe the riding comfort of cyclists. It is mainly the unevenness in the 50–1000 mm size-range that create the greatest discomfort for cyclists, and intermittent vibrations are perceived as more uncomfortable than more evenly distributed vibrations. Therefore, IRI is not a relevant measurement for describing the riding comfort of cyclists.

Abstract Sulfur mustard (SM) is a highly toxic chemical warfare agent. Exposure to SM results in various pathologies including skin lesions with subsequent impaired wound healing. To date, there are no effective treatments available. Here we discover a SM-triggered pathomechanism involving miR-497-5p and its target survivin which contributes to keratinocyte dysfunction. Transcriptome analysis using RNA-seq in normal human epidermal keratinocytes (NHEK) revealed that SM evoked differential expression of 1896 mRNAs and 25 miRNAs with many of these RNAs known to be involved in keratinocyte function and wound healing. We demonstrated that keratinocyte differentiation and proliferation were efficiently regulated by miRNAs induced in skin cells after exposure to SM. The inhibition of miR-497-5p counteracted SM-induced premature differentiation and stimulated proliferation of NHEK. In addition, we showed that microneedle-mediated transdermal application of lipid-nanoparticles containing miR-497-5p inhibitor restored survivin biosynthesis and cellular functionality upon exposure to SM using human skin biopsies. Our findings expand the current understanding of SM-associated molecular toxicology in keratinocytes and highlight miR-497-5p as feasible clinical target for specific skin therapy in SM-exposed patients and beyond.

Digital technologies have transformed medical care and education by providing rapid access to knowledge and advanced methods, such as augmented reality and haptic feedback. These technologies are improving the efficiency of healthcare professionals and the quality of medical education. Particularly in Germany, where a shortage of skilled workers and an aging population are increasing pressure on the healthcare system, digital methods can help to optimize workflows and improve training. The integration of haptic feedback in this context makes it possible to make virtual objects tangible, increasing immersion and ultimately learning success. The application presented, SkillsLab+, uses augmented reality and haptic feedback via a data glove to provide a digitized version of the analog SkillsLab medical training programme. SkillsLab+ was evaluated using standardized questionnaires (Igroup Presence Questionnaire, presence, and haptic questionnaires). In order to determine the learning outcomes of the students, an AB test was carried out comparing the final grades. At the same time, a subjective questionnaire was used to assess whether students felt better prepared for the exam. In this context, this article aims to evaluate the learning success and compare the results with the previous proof of concept study of 2022. The results of the comparison show an improvement in the responses to the SkillsLab+ questionnaire in 2023. The result of the examination also improved compared to the group without AR experience. This shows the improvement in application and learning with the help of augmented reality and haptic feedback. They were more confident, had better results, and felt better prepared for the exams.

Abstract Recent progress in image-based spatial RNA profiling enables to spatially resolve tens to hundreds of distinct RNA species with high spatial resolution. It presents new avenues for comprehending tissue organization. In this context, the ability to assign detected RNA transcripts to individual cells is crucial for downstream analyses, such as in-situ cell type calling. Yet, accurate cell segmentation can be challenging in tissue data, in particular in the absence of a high-quality membrane marker. To address this issue, we introduce ComSeg, a segmentation algorithm that operates directly on single RNA positions and that does not come with implicit or explicit priors on cell shape. ComSeg is applicable in complex tissues with arbitrary cell shapes. Through comprehensive evaluations on simulated and experimental datasets, we show that ComSeg outperforms existing state-of-the-art methods for in-situ single-cell RNA profiling and in-situ cell type calling. ComSeg is available as a documented and open source pip package at https://github.com/fish-quant/ComSeg .

Innate myeloid cells especially neutrophils and their extracellular traps are known to promote intravascular coagulation and thrombosis formation in infections and various other conditions. Innate myeloid cell dependent fibrin formation can support systemic immunity while its dysregulation enhances the severity of infectious diseases. Less is known about the immune mechanisms preventing dysregulation of fibrin homeostasis in infection. During experimental systemic infections local fibrin deposits in the liver microcirculation cause rapid arrest of CD4+ T cells. Arrested T helper cells mostly represent Th17 cells that partially originate from the small intestine. Intravascular fibrin deposits activate mouse and human CD4+ T cells which can be mediated by direct fibrin - CD4+ T cell interactions. Activated CD4+ T cells suppress fibrin deposition and microvascular thrombosis by directly counteracting coagulation activation by neutrophils and classical monocytes. T cell activation, which is initially triggered by IL- 12p40- and MHC-II dependent mechanisms, enhances intravascular fibrinolysis via LFA-1. Moreover, CD4+ T cells disfavor the association of the fibrinolysis inhibitor TAFI with fibrin whereby fibrin deposition is increased by TAFI in the absence but not presence of T cells. In human infections thrombosis development is inversely related to microvascular levels of CD4+ T cells. Thus, fibrin promotes LFA-1 dependent T helper cell activation in infections which drives a negative feedback cycle that rapidly restricts intravascular fibrin and thrombosis development.

IntroductionAtherosclerosis is a lipid-driven inflammatory disease of the arterial wall, and the underlying cause of the majority of cardiovascular diseases. Recent advances in high-parametric immunophenotyping of immune cells indicate that T cells constitute the major leukocyte population in the atherosclerotic plaque. The E3 ubiquitin ligase Casitas B-lymphoma proto-oncogene-B (CBL-B) is a critical intracellular regulator that sets the threshold for T cell activation, making CBL-B a potential therapeutic target to modulate inflammation in atherosclerosis. We previously demonstrated that complete knock-out of CBL-B aggravated atherosclerosis in Apoe-/- mice, which was attributed to increased macrophage recruitment and increased CD8+ T cell activation in the plaque.MethodsTo further study the T cell specific role of CBL-B in atherosclerosis, Apoe-/- CD4creCblbfl/fl (Cbl-bcKO) mice and Apoe-/-CD4WTCblbfl/fl littermates (Cbl-bfl/fl) were fed a high cholesterol diet for ten weeks.ResultsCbl-bcKO mice had smaller atherosclerotic lesions in the aortic arch and root compared to Cbl-bfl/fl, and a substantial increase in CD3+ T cells in the plaque. Collagen content in the plaque was decreased, while other plaque characteristics including plaque necrotic core, macrophage content, and smooth muscle cell content, remained unchanged. Mice lacking T cell CBL-B had a 1.4-fold increase in CD8+ T cells and a 1.8-fold increase in regulatory T cells in the spleen. Splenic CD4+ and CD8+ T cells had increased expression of C-X-C Motif Chemokine Receptor 3 (CXCR3) and interferon-γ (IFN-γ), indicating a T helper 1 (Th1)-like/effector CD8+ T cell-like phenotype.ConclusionIn conclusion, Cbl-bcKO mice have reduced atherosclerosis but show increased T cell accumulation in the plaque accompanied by systemic T cell activation.

Abstract Background Agonism at the receptor for the glucose-dependent insulinotropic polypeptide (GIPR) is a key component of the novel unimolecular GIPR:GLP-1R co-agonists, which are among the most promising drugs in clinical development for the treatment of obesity and type 2 diabetes. The therapeutic effect of chronic GIPR agonism to treat dyslipidemia and thus to reduce the cardiovascular disease risk independently of body weight loss has not been explored yet. Methods After 8 weeks on western diet, LDL receptor knockout (LDLR-/-) male mice were treated with daily subcutaneous injections of long-acting acylated GIP analog (acyl-GIP; 10nmol/kg body weight) for 28 days. Body weight, food intake, whole-body composition were monitored throughout the study. Fasting blood glucose and intraperitoneal glucose tolerance test (ipGTT) were determined on day 21 of the study. Circulating lipid levels, lipoprotein profiles and atherosclerotic lesion size was assessed at the end of the study. Acyl-GIP effects on fat depots were determined by histology and transcriptomics. Results Herein we found that treatment with acyl-GIP reduced dyslipidemia and atherogenesis in male LDLR-/- mice. Acyl-GIP administration resulted in smaller adipocytes within the inguinal fat depot and RNAseq analysis of the latter revealed that acyl-GIP may improve dyslipidemia by directly modulating lipid metabolism in this fat depot. Conclusions This study identified an unanticipated efficacy of chronic GIPR agonism to improve dyslipidemia and cardiovascular disease independently of body weight loss, indicating that treatment with acyl-GIP may be a novel approach to alleviate cardiometabolic disease.

Ilmenau is a relatively small town in a beautiful landscape, close to the centre of Germany. Since 1894 it has been the home of a Technical College which after World War II and through some permutations became today’s Technische Universität Ilmenau. For 70 years the university has contributed to Design Science. It is interesting to note that the fundamentals were developed in practice, at the Carl Zeiss company in Jena; it was only later that the new ideas were further developed for academic research and teaching in Ilmenau. The origins at Zeiss Jena still account for the main application area at Technische Universität Ilmenau today: Precision Engineering which, in addition to mechanical, has always included electric, electronic, control, software, and even optical components (“mechatronics” before the term was coined). This article – written by three (out of four in total) of the professors who were and are, respectively, in charge over almost 50 out of the 70 years – tells the story of Design Science in Ilmenau: background, beginnings, development, contributions to research, teaching, and transfer to industry. As Ilmenau was situated in the German Democratic Republic (“East Germany”) between 1949 and 1990, the story is not free of political and societal implications, some of them quite surprising.

Crosstalk between innate and adaptive immunity is pivotal for an efficient immune response and to maintain immune homeostasis under steady state conditions. As part of the innate immune system, type 2 innate lymphoid cells (ILC2s) have emerged as new important regulators of tissue homeostasis and repair by fine-tuning innate-adaptive immune cell crosstalk. ILC2s mediate either pro- or anti-inflammatory immune responses in a context dependent manner. Inflammation has proven to be a key driver of atherosclerosis, resembling the key underlying pathophysiology of cardiovascular disease (CVD). Notably, numerous studies point towards an atheroprotective role of ILC2s e.g., by mediating secretion of type-II cytokines (IL-5, IL-13, IL-9). Boosting these protective responses may be suitable for promising future therapy, although these protective cues are currently incompletely understood. Additionally, little is known about the mechanisms by which chemokine/chemokine receptor signaling shapes ILC2 functions in vascular inflammation and atherosclerosis. Hence, this review will focus on the latest findings regarding the protective and chemokine/chemokine receptor guided interplay between ILC2s and other immune cells like T and B cells, dendritic cells and macrophages in atherosclerosis. Further, we will elaborate on potential therapeutic implications which result or could be distilled from the dialogue of ILC2s with cells of the immune system in cardiovascular diseases.

Background: The fifth version of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) introduced the dissociative subtype of posttraumatic stress disorder (D-PTSD). To assess this subtype, the Dissociative Subtype of PTSD Scale (DSPS), a 15-item self-report measure to identify lifetime and current dissociative symptoms of D-PTSD, was developed. However, so far, the scale has only been validated in war veterans. Moreover, criterion validity and diagnostic utility have not been examined yet. Objective: We aimed to validate the DSPS in two samples of civilian trauma-exposed German-speaking participants. Methods: In Study 1, a pre-registered online study, participants with and without PTSD symptoms (N = 558) answered questionnaires about traumatic experiences, dissociation, PTSD, depression, generalized anxiety disorder, somatic symptom disorder, alcohol use disorder, absorption, and dissociative responding to trauma-related questionnaires. In Study 2, which used secondary data of a pre-registered clinical study, participants with a PTSD diagnosis (N = 71) answered questionnaires about traumatic experiences, dissociation, PTSD, depression, generalized anxiety disorder, somatic symptom disorder, and dissociative responding to standardized trauma exposure. Moreover, PTSD, D-PTSD, and other diagnoses were assessed with structured clinical interviews. Results: Analyses confirmed a three-factor structure as well as high internal consistency, and high convergent, discriminant, and criterion validity of the DSPS. Moreover, the scale was able to identify a latent D-PTSD group and individuals with D-PTSD diagnosis. Conclusions: The DSPS constitutes a reliable and valid tool to assess D-PTSD symptoms in clinical practice and research and thereby may contribute to a better understanding of these debilitating symptoms.

Abstract Radiation Induced Lung Injury (RILI) is one of the main limiting factors of thorax irradiation, which can induce acute pneumonitis as well as pulmonary fibrosis, the latter being a life-threatening condition. The order of cellular and molecular events in the progression towards fibrosis is key to the physiopathogenesis of the disease, yet their coordination in space and time remains largely unexplored. Here, we present an interactive murine single cell atlas of the lung response to irradiation, generated from C57BL6/J female mice. This tool opens the door for exploration of the spatio-temporal dynamics of the mechanisms that lead to radiation-induced pulmonary fibrosis. It depicts with unprecedented detail cell type-specific radiation-induced responses associated with either lung regeneration or the failure thereof. A better understanding of the mechanisms leading to lung fibrosis will help finding new therapeutic options that could improve patients’ quality of life.

The development and implementation of information systems strategy in multi-national corporations (MNCs) faces particular challenges—cultural differences and variations in work values and practices across different countries, numerous technology landscapes and legacy issues, language and accounting particularities, and differing business models. This article builds upon the existing literature and in-depth interviews with eighteen industry practitioners employed in six MNCs to construct an operational model to address these challenges. The research design is based on an inductive, qualitative approach that develops an initial conceptual framework—derived from the literature—into an operational model, which is then applied and refined in a case study company. The final model consists of change components and process phases. Six change components are identified that drive and underpin IS strategy—business strategy, systems projects, technology infrastructure, process change, skills and competencies, and costs and benefits. Five core process phases are recognized—review, align, engage, execute, and control. The model is based on the interaction between these two dimensions—change components and process phases—and an action list is also developed to support the application of the model, which contributes to the theory and practice of information systems deployment in MNCs.

Bombesin receptor-activated protein (BRAP) and its homologous protein in mice, which is encoded by bc004004 gene, were expressed abundantly in brain tissues with unknown functions. We treated bc004004-/- mice with chronic unpredictable mild stress (CUMS) to test whether those mice were more vulnerable to stress-related disorders. The results of forced swimming test, sucrose preference test, and open field test showed that after being treated with CUMS for 28 days or 35 days both bc004004-/- and bc004004+/+ mice exhibited behavioural changes and there was no significant difference between bc004004+/+ and bc004004-/-. However, behavioural changes were observed only in bc004004-/- mice after being exposed to CUMS for 21 days, but not in bc004004+/+ after 21-day CUMS exposure, indicating that lack of BRAP homologous protein may cause vulnerability to stress-related disorders in mice. In addition, bc004004-/- mice showed a reduction in recognition memory as revealed by novel object recognition test. Since memory changes and stress related behavioural changes are all closely related to the hippocampus function we further analyzed the changes of dendrites and synapses of hippocampal neurons as well as expression levels of some proteins closely related to synaptic function. bc004004-/- mice exhibited decreased dendritic lengths and increased amount of immature spines, as well as altered expression pattern of synaptic related proteins including GluN2A, synaptophysin and BDNF in the hippocampus. Those findings suggest that BRAP homologous protein may have a protective effect on the behavioural response to stress via regulating dendritic spine formation and synaptic plasticity in the hippocampus.

Abstract Background The management of chondral defects of the patellofemoral joint is debated, and definitive evidence is lacking. This study systematically updated and summarised the current literature on the surgical management of isolated chondral defects of the patellofemoral joint, discussing techniques, outcome, pitfalls, and new frontiers. Methods This systematic review was conducted according to the 2020 PRISMA statement. In August 2022, PubMed, Web of Science, Google Scholar, and Embase databases were accessed with no time constrain. All the clinical studies investigating the surgical management of chondral defects of the patellofemoral joint were retrieved. Articles which reported data on patients with advanced to severe osteoarthritis were not eligible. Only studies with a minimum 24 months follow-up were considered. Studies which mixed results of patellofemoral and tibiofemoral joints were not considered. Results Data from 10 studies (692 procedures) were retrieved. The mean follow-up was 46.9 ± 18.2 months. The mean age of the patients was 34.0 ± 6.1 years, and the mean BMI was 25.9 ± 0.8 kg/m2. The mean duration of symptoms before the index surgery was 81.0 ± 24.0 months. The mean defect size was 3.8 ± 0.8 cm2. All the PROMs improved from baseline to last follow-up: VAS 0–10 (P = 0.04), Tegner (P = 0.02), Lysholm (P = 0.03), and International Knee Documentation Committee (P = 0.03). The rate of hypertrophy was 5.6% (14 of 251), the rate of progression to total knee arthroplasty was 2.4% (2 of 83), the rate of revision was 16.9% (29 of 136), and the rate of failure was 13.0% (16 of 123). Conclusion Current surgical strategies may be effective to improve symptoms deriving from chondral defects of the patellofemoral joint. The limited and heterogeneous data included for analysis impact negatively the results of the present study. Further clinical studies are strongly required to define surgical indications and outcomes, and the most suitable technique.

Abstract During Autologous Matrix-Induced Chondrogenesis (AMIC), the membrane is often glued into the chondral defect. However, whether fibrin glue influences cells proliferation and migration remain unclear. This study evaluated the impact of fibrin glue addition to biologic membranes loaded with bone marrow-derived mesenchymal stem cells (B-MSCs). A porcine derived collagen membrane (Cartimaix, Matricel GmbH, Germany) was used. B-MSCs were harvested from three different unrelated donors. The membranes were embedded in mounting medium with DAPI (ABCAM, Cambridge, UK) and analysed at 1-, 2-, 3-, 4-, 6-, and at 8-week follow-up. The DAPI ties the DNA of the cell nucleus, emitting blue fluorescence. DAPI/nuclei signals were analysed with fluorescence microscopy at 100-fold magnification. The group without fibrin glue demonstrated greater migration of the B-MSCs within the membrane at week 4 (P

Abstract Background Corrective osteotomies of the upper extremities with patient-specific instruments (PSIs) are increasingly used. In this context, the concordance between planning and postoperative 3D radiographs as well as the association between 3D accuracy and clinical outcome has rarely been evaluated. In this pilot study, we aimed to investigate our clinical mid-term outcome and 3D accuracy as well as their possible correlation, including identifying aspects critical to reaching optimal correction results. Methods From October 2018 to January 2020, we used PSIs for 12 corrective osteotomies of the upper extremity in 11 bones of 8 patients (congenital or posttraumatic deformities in 2 elbows, 3 forearms, 3 distal radii). In follow-up examination (10–25 months postoperatively), patient satisfaction, grip strength, ROM, VAS, and DASH were evaluated. Three-dimensional radiological accuracy was determined with 3D-reconstructed postoperative CT scans. With the software tool “Part Comparison” of Mimics® Innovation Suite Software/Materialise, surface differences of pre-planned and postoperative 3D models were compared. Results Compared to the preoperative situation pain and function were better at follow-up: The average VAS score significantly decreased from 6.5 ± 4.1 cm preoperatively to 2.3 ± 2.6 cm at the follow-up time point (p = 0.008). The average DASH score significantly improved, from 48.4 ± 30.9 to 27.0 ± 25.2 (p = 0.015). In the part comparison analysis “planned vs postoperative comparison”, significantly more points in percent (= 3D accuracy) were in a −3 mm to 3 mm interval than in the “preoperative vs planned comparison” (87.3 ± 13.8% vs 48.9 ± 16.6%, p = 0.004). After surgery, the maximum deviation value over all cases was 4.5 ± 1.1 mm, and the minimum deviation value was − 4.5 ± 1.2 mm vs preoperatively 12.9 ± 6.2 mm (p = 0.004) and − 7.2 ± 2.1 mm (p = 0.02), respectively. Clinically, in all cases with higher accuracy (> 90%), an improvement of either DASH or VAS or both of > 60% to the preoperative values occurred. There was a significant correlation between accuracy (%) and ΔVAS (p = 0.004). There were no method-related complications. Conclusions Our data after PSI-based corrective osteotomy in complex deformities of the upper extremity in a limited number of cases indicate a positive correlation between 3D accuracy and clinical outcomes. Examination of 3D accuracy to analyse sources of error in the hole procedure from initial CT scan to end of surgery even in patients with not fully satisfactory clinical results is required for further development of the method to achieve optimal correction results with nearly 100% congruence between the planned and postoperative 3D bone position. Trial registration This retrospective study was registered in the Center for Translational & Clinical Research Aachen (CTC-A) with the number 20-514 on November 20, 2021

Amyloid self-assembly is linked to type 2 diabetes and Alzheimer’s disease. Here the authors designed constrained peptides which are nanomolar amyloid inhibitors of the key polypeptides IAPP and Aβ42 and act via supramolecular nanofiber co-assembly.

Learning personalization has proven its effectiveness in enhancing learner performance. Therefore, modern digital learning platforms have been increasingly depending on recommendation systems to offer learners personalized suggestions of learning materials. Learners can utilize those recommendations to acquire certain skills for the labor market or for their formal education. Personalization can be based on several factors, such as personal preference, social connections or learning context. In an educational environment, the learning context plays an important role in generating sound recommendations, which not only fulfill the preferences of the learner, but also correspond to the pedagogical goals of the learning process. This is because a learning context describes the actual situation of the learner at the moment of requesting a learning recommendation. It provides information about the learner’s current state of knowledge, goal orientation, motivation, needs, available time, and other factors that reflect their status and may influence how learning recommendations are perceived and utilized. Context-aware recommender systems have the potential to reflect the logic that a learning expert may follow in recommending materials to students with respect to their status and needs. During the last decade, several approaches have emerged in the literature to define the learning context and the factors that may capture it. Those approaches led to different definitions of contextualized learner-profiles. In this paper, we review the state-of-the-art approaches for defining a user’s learning-context. We provide an overview of the definitions available, as well as the different factors that are considered when defining a context. Moreover, we further investigate the links between those factors and their pedagogical foundations in learning theories. We aim to provide a comprehensive understanding of contextualized learning from both pedagogical and technical points of view. By combining those two viewpoints, we aim to bridge a gap between both domains, in terms of contextualizing learning recommendations.

Alzheimer`s disease (AD) is the most prevalent cause of dementia. It is often assumed that AD is caused by an aggregation of extracellular beta-amyloid and intracellular tau-protein, supported by a recent study showing reduced brain amyloid levels and reduced cognitive decline under treatment with a beta-amyloid-binding antibody. Confirmation of the importance of amyloid as a therapeutic target notwithstanding, the underlying causes of beta-amyloid aggregation in the human brain, however, remain to be elucidated. Multiple lines of evidence point towards an important role of infectious agents and/or inflammatory conditions in the etiology of AD. Various microorganisms have been detected in the cerebrospinal fluid and brains of AD-patients and have thus been hypothesized to be linked to the development of AD, including Porphyromonas gingivalis (PG) and Spirochaetes. Intriguingly, these microorganisms are also found in the oral cavity under normal physiological conditions, which is often affected by multiple pathologies like caries or tooth loss in AD patients. Oral cavity pathologies are mostly accompanied by a compositional shift in the community of oral microbiota, mainly affecting commensal microorganisms and referred to as ‘dysbiosis’. Oral dysbiosis seems to be at least partly mediated by key pathogens such as PG, and it is associated with a pro-inflammatory state that promotes the destruction of connective tissue in the mouth, possibly enabling the translocation of pathogenic microbiota from the oral cavity to the nervous system. It has therefore been hypothesized that dysbiosis of the oral microbiome may contribute to the development of AD. In this review, we discuss the infectious hypothesis of AD in the light of the oral microbiome and microbiome-host interactions, which may contribute to or even cause the development of AD. We discuss technical challenges relating to the detection of microorganisms in relevant body fluids and approaches for avoiding false-positives, and introduce the antibacterial protein lactoferrin as a potential link between the dysbiotic microbiome and the host inflammatory reaction.

The wide use of sulfuryl difluoride (SO2F2) for termite control in buildings, warehouses and shipping containers requires the implementation of suitable sensors for reliable detection. SO2F2 is highly toxic to humans and the environment, and moreover, it is a potent greenhouse gas. We developed two photoacoustic two-chamber sensors with the aim to detect two different concentration ranges, 0–1 vol.-% SO2F2 and 0–100 ppm SO2F2, so that different applications can be targeted: the sensor for high concentrations for the effective treatment of buildings, containers, etc., and the sensor for low concentrations as personal safety device. Photoacoustic detectors were designed, fabricated, and then filled with either pure SO2F2 or pure substituent gas, the refrigerant R227ea, to detect SO2F2. Absorption cells with optical path lengths of 50 mm and 1.6 m were built for both concentration ranges. The sensitivity to SO2F2 as well as cross-sensitivities to CO2 and H2O were measured. The results show that concentrations below 1 ppm SO2F2 can be reliably detected, and possible cross-sensitivities can be effectively compensated.

Type 2 diabetes mellitus (T2D) poses a significant global health challenge and demands effective self-management strategies, including continuous blood glucose monitoring (CGM) and lifestyle adaptations. While CGM offers real-time glucose level assessment, the quest for minimizing trauma and enhancing convenience has spurred the need to explore non-invasive alternatives for monitoring vital signs in patients with T2D. Objective: This systematic review is the first that explores the current literature and critically evaluates the use and reporting of non-invasive wearable devices for monitoring vital signs in patients with T2D. Methods: Employing the PRISMA and PICOS guidelines, we conducted a comprehensive search to incorporate evidence from relevant studies, focusing on randomized controlled trials (RCTs), systematic reviews, and meta-analyses published since 2017. Of the 437 publications identified, seven were selected based on predetermined criteria. Results: The seven studies included in this review used various sensing technologies, such as heart rate monitors, accelerometers, and other wearable devices. Primary health outcomes included blood pressure measurements, heart rate, body fat percentage, and cardiorespiratory endurance. Non-invasive wearable devices demonstrated potential for aiding T2D management, albeit with variations in efficacy across studies. Conclusions: Based on the low number of studies with higher evidence levels (i.e., RCTs) that we were able to find and the significant differences in design between these studies, we conclude that further evidence is required to validate the application, efficacy, and real-world impact of these wearable devices. Emphasizing transparency in bias reporting and conducting in-depth research is crucial for fully understanding the implications and benefits of wearable devices in T2D management.

Abstract Background Some authors secured the membrane during matrix-induced autologous chondrocyte implantation (mACI) with fibrin glue or did not use a formal fixation. The real impact of fibrin glue addition on chondrocytes migration and proliferation has not yet been clarified. This study evaluated the impact of fibrin glue on a chondrocyte loaded collagenic membrane. Methods A resorbable collagen I/III porcine derived membrane commonly employed in AMIC was used for all experiments. Chondrocytes from three difference donors were used. At 1-, 2-, 3-, 4-, 6-, and at 8-week the membranes were embedded in Mounting Medium with Dapi (ABCAM, Cambridge, UK). The Dapi contained in the mounting medium ties the DNA of the cell nucleus and emits a blue fluorescence. In this way, the spreading of the cells in the membrane can be easily monitored. The outcomes of interest were to evaluate (1) cell migration and (2) cell proliferation within the porous membrane layer. DAPI/nuclei signals were analysed with fluorescence microscope under a magnification of 100-fold. Results The no-fibrin group demonstrated greater migration of the cells within the membrane. Although migration resulted higher in the no-fibrin group at every follow-up, this difference was significant only at week 1 (P

An innovative laser based photoacoustic (PA) gas sensing concept with intrinsic miniaturization potential was developed and investigated for methane trace gas detection. An interband cascade laser (ICL) with an optical power of 8.5 mW targets a methane (CH4) absorption line feature around 3057.7 cm−1 (or 3270 nm). The ICL was focused into the sound port of a MEMS microphone, where the PA signal was generated and detected using a wavelength modulation concept (2f-WMS-PAS). The MEMS microphone was successfully implemented as an intrinsically miniaturized PA cell being gas sensing volume, acoustic resonator and sound transducer at once. Frequencies between 2 kHz and 100 kHz were investigated and used for methane detection. A sensitive and resonant methane detection at 41.8 kHz was investigated by concentration variations between 0 and 10 ppm CH4 in N2. A limit of detection (3σ-LOD) of 329 ppb was estimated. The long term stability of this sensor was investigated by the measurement of methane in ambient air. A noise equivalent concentration (NEC) of 14 ppb (parts per billion) at an average time of 10 s was estimated. This value corresponds to a normalized noise equivalent absorption (NNEA) of 2⋅10−8 W cm−1 Hz−1/2. Using the MEMS microphone directly as PA cell offers the possibility for an extremely miniaturized, highly sensitive and very cost-efficient photoacoustic trace gas sensor.

Three systemic biological systems, i.e., the nervous, the immune, and the cardiovascular systems, form a mutually responsive and forward-acting tissue network to regulate acute and chronic cardiovascular function in health and disease. Two sub-circuits within the cardiovascular system have been described, the artery brain circuit (ABC) and the heart brain circuit (HBC), forming a large cardiovascular brain circuit (CBC). Likewise, the nervous system consists of the peripheral nervous system and the central nervous system with their functional distinct sensory and effector arms. Moreover, the immune system with its constituents, i.e., the innate and the adaptive immune systems, interact with the CBC and the nervous system at multiple levels. As understanding the structure and inner workings of the CBC gains momentum, it becomes evident that further research into the CBC may lead to unprecedented classes of therapies to treat cardiovascular diseases as multiple new biologically active molecules are being discovered that likely affect cardiovascular disease progression. Here, we weigh the merits of integrating these recent observations in cardiovascular neurobiology into previous views of cardiovascular disease pathogeneses. These considerations lead us to propose the Neuroimmune Cardiovascular Circuit Hypothesis.